tag:blogger.com,1999:blog-14815237963553213072024-03-13T14:27:05.804-07:00Write an essay on democracyFinancial Crisis 2008 Essay Topicsdebracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.comBlogger37125tag:blogger.com,1999:blog-1481523796355321307.post-9702591127940827882020-09-03T23:13:00.001-07:002020-09-03T23:13:13.361-07:00Analysis for Proton EssayPolitical In the event that we are going to beware of the high selling costs of the national vehicles of Malaysia in light of high creation expenses and absence of merchant effectiveness, there is a major chance that the neighborhood market will be administered by imported vehicles. Subsequently, there will be increment in the quantity of the vehicles out and about and there will be an overabundance of trade-in vehicles in the market, since individuals will in general exchange their vehicles for less expensive and imported brands (Frost and Sullivan 2002). Then again, the issue with respect to the earth is essential since it is considered as one of the most discussion about themes on the planet. The ecological guideline in Malaysia can be followed back during the expansionism of British which presented the natural gauges about the mineral and farming assets to Europe. Monetary Essentially the issue of worldwide monetary emergency, which influenced the nearby budgetary status of the nation .therefore, the administration of the nation is anticipating a moderate financial development for the nation, which can influence the purchasing conduct of the clients. Furthermore,it had expanded the opposition, which will affect the presentation of Proton. In any case, the exhibition of the car business will be kept up and overseen because of the colossal absolute work power. Social The developing populace in the nation is one of the components which can influence the car business. This will give a more noteworthy number of business sectors. Besides, the proportion of vehicle proprietorship in the nation is to some degree high or aggregate of 1:5, which connotes that individuals are thinking about vehicles as significant things in their lives. Moreover, individuals will likewise set on expensive things or buyers are required to put off purchasing distinctive engine vehicles due to the business advertise vulnerability on account of the worldwide and nearby budgetary crisis.Another factor to consider is the developing information and worry of the individuals with respect to various natural issues. Moreover, the effect of the picture to the steadfastness of the client is likewise another factor. Mechanical Innovation is considered as one of the most significant factor in the car business. Because of the expanding rivalry, the advancement in innovation is developing and influencing the presentation and position of every single organization in the car business. It is additionally imperative to think about the development of innovation, along with the development and limit of assembling, which influence the advancement procedure of any organization. The protected innovation is likewise significant factor, since it is considered as an indication of credibility and uniqueness. Because of the various advancements, fundamentally the assistance of PC and the Internet, the potential for development and improvement is expanding. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-14458086440321297422020-08-25T13:29:00.001-07:002020-08-25T13:29:05.268-07:00The Impact Of Tourism In The Construction Industry EssayThe Impact Of Tourism In The Construction Industry - Essay Example This sort of improvement is presently under the scanner and appearances different weights and difficulties like ecological guidelines, land-use arranging and conventions, neighborhood financial powers and different prerequisites. Under this circumstance, it presents a decent defense to survey and examine the effects and ramifications of advanced the travel industry on the development segment. A cautious glance at any vacationer goal uncovers the repetitive connection among the travel industry and the development business, both capacitating and encouraging one another. Distinguishing this connection, Riera (1999) and Apostolopoulos et.al. (2001) communicated that mass the travel industry and convenience development are between woven, housing and inns need vacationer to endure and work together and the travel industry too needs great settlement office for pulling in voyagers (Riera A., 1999; Apostolopoulos et.al., 2001). In this way, the current pattern is agreeable to extraordinary goals and excursion or second home, a home away from the home which is likewise a speculation home for a few. The development of the travel industry is consistently welcome as it has the capability of offering numerous advantages (WWF, 2001; UNEP/CI, 2003; WITC, 2005)- monetary chances, socio-social trades and incorporation, global relationship building and numerous other related points of interest. For any visitor goal or detect, the development of the travel industry suggests extra deluge of voyagers which thus calls for development of extra housing/summer homes and the travel industry foundations. Under this circumstance, the travel industry development implies more voyagers, more requests for facilities and foundations and thusly more development exercises. Looking it the other way, great foundations and housing can likewise add to the genuine estimation of a goal and draw in individuals encouraging the travel industry all the while. In this manner, there is by all accounts a straight forward interrelation among the travel industry and the development business (Apostolopoulos et.al., 200 1). Notwithstanding, this interrelation or reliance isn't as basic as it sounds. The travel industry is naturally a movement obliged by reality and development also is intensely subject to space or topographical zone and land-use arrangement (Hall, 2005). Space has impediments and along these lines, the travel industry and the development business can't continue developing or growing unpredictably and constantly or disaster will be imminent, the real factors of room limitations and the conceivable negative natural results make certain to drive this industry into the annihilation. Development identified with the travel industry improvement (inns, air terminals, streets, and getaway homes) makes the best negative effect the environment and all the more so when the goal is wealthy in biodiversity like the Mediterranean area. Loss of biodiversity and beautiful scenes as of now influences various traveler goals all through the Mediterranean and regularly, these misfortunes or negative effects are far more noteworthy than the positive results or the related estimations of the travel industry (Paris Chris, 2006). In this manner, adjusting the debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-63575957826530731842020-08-22T21:03:00.001-07:002020-08-22T21:03:19.455-07:00PharmaCare essayThe twenty-first century has seen pharmaceutical organizations develop in remarkable size and quality. Because of the uncommon development the bigger pharmaceutical organizations have picked up influence and force in the physician recommended sedate industry, however they need advancement to market and they look for approaches to enable the business to keep on expanding its benefits. The pharmaceutical business was once morally solid and was a significant player in the advancement of human wellbeing. Be that as it may, extra time with the absence of advancement pharmaceutical organizations are turning into an exploitative market that abuses patients, specialists and any other individual it can to expand its profitability.With eyes just on productivity this can make a danger for patients in light of the fact that there is inadequate trying of the medications before the medications hitting the American market. In this exploration paper we will cover the numerous aspects of PharmaCare, Coleria, and Wellco and the medication AD23 symptoms, and its assembling in a ruined country with the low wages and perilous working conditions. Which will all be secured all through this report. Promoting and Advertising The Food and Drug Administration loosened up the guidelines with respect to the need to publicize the symptoms of physician recommended medicates in 1997.à (FDA)The loosened up guideline takes into consideration direct-to-buyer promoting and this change the showcasing systems. There is currently a flood of pharmaceutical promoting utilizing infomercials. Gary Humphreys illuminates us in his article, ââ¬Å"Direct-to-Consumer Advertising Under Fireâ⬠, that pharmaceutical organizations ââ¬Å"spent just shy of $5 billion a year ago aloneâ⬠(576) on this sort of promoting. The infomercials by one way or another cause purchasers to accept that there is a requirement for them to have the medication and subsequently make an expansion in its sales.Because buyer s want to assume responsibility for their wellbeing they are currently going in the doctorââ¬â¢s office and educating the doctorââ¬â¢s concerning the infomercial and the medication that they might want to attempt. In any case, purchasers don't know that they physician recommended medicate organizations are not required to share the entirety of the reactions of the medications and it might cause genuine medical issues when shoppers can request sedates by name. As per the Centers for Disease Control and Prevention physician recommended medicate misuse isn't a plague. The high utilization of physician recommended drugs has prompted a reduction use in illicit drugs.In the United States it is normal for Medical Doctors to get an attempt to close the deal from a medication organization with respect to their professionally prescribed medications and feature its numerous advantages too. This is target advertising in which medication organizations are focusing on those in the clinical field and those that are destined to offer the item to a buyer and thusly this will prompt an expansion in sedate deals. This training prompts addresses identified with clinical morals in the business. Licensed innovation Protection The laws and guidelines have reinforced the protected innovation insurance of marked drugs.One of the essential explanations behind the Intellectual Property Protection was to get the pharmaceutical world reasoning and give motivations for the individuals who are being inventive. Items can be fixed for a predefined time allotment on the off chance that they have a patent; this means it disposes of any immediate rivalry which thus permits the designer to set the cost of the medication and commonly they are charging as much as possible. The creator is attempting to recover all cash spent on the making of the medication while additionally making a strong profit.The Intellectual Property Protection have expanded patent existence of roughly 50 percent of all medications from 1980 to introduce which adds to professionally prescribed medication spending. A 1998 Congressional Budget Office (CBO) study indicated that fabricates will in general present new marked medications at premium costs, and afterward raise these costs. The examination found that significantly after comparable marked items enter the market, tranquilize organizations regularly keep on expanding the cost. The moral issue is on the grounds that when the patent is protracted it defers the passage of more affordable conventional drugs.And thus the marked medications overwhelm the market and the expense is passed down to the purchaser. Guidelines and Product Safety The Federal Food, Drug Administration is answerable for building up the Code of Federal Regulations which plots the standards and guidelines overseeing pharmaceuticals. The principles are partitioned into areas and incorporate direction dependent on sedate classifications. Because of every individual having changin g responses to pharmaceutical items not every single reaction are identified during clinical testing.The Federal Food, Drug Administration is answerable for offering the data to purchasers. In any case, it appears to be somewhat exploitative on the grounds that the huge pharmaceutical organizations don't need to share all of reaction data that may help buyers in settling on its decision on whether to attempt an item or to not attempt an item. Through different surveyââ¬â¢s it was found that customers are under the sentiment that pharmaceutical organizations need to have improved inner controls to guarantee their consistence with regulations.Due to doctors and pharmaceutical organizations cooperating and are subject to each other there should be controls set up that would have an unprejudiced perspective on the guidelines. The legislature should keep presenting new guidelines that will helper in observing the connections. Direct-To ââ¬Consumer Marketing Direct to customer is a t ype of promoting that business sectors straightforwardly to shoppers bypassing the wholesaler. In the mid 1980ââ¬â¢s pharmaceutical organizations gave data about physician endorsed medications to specialists and pharmacists.The Federal Drug Administration (FDA) permitted print promotions to run and the pharmaceutical organizations had extraordinary achievement and were then allowed to start running ad on TV. Right now over $5 billion is spent yearly to introduce this ad to the American open through direct promoting print advertisements, transmission, and on the web. There is an issue with this is the FDA doesn't deliberately screen these advertisements and the notice may really be deluding and the American open may not know that the promotion didn't pass the FDA check.The Office of Prescription Drug Promotion (OPDP) is required to make a move against advertisements that damage the law and are required to make a move alongside imparting data to purchasers and representatives in th e human services industry. Professionally prescribed medication promotions brief almost 33% of Americans to get some information about a publicized medication, and 82% of the individuals who ask say their doctors suggested a medicine. The discoveries in a national overview by USA TODAY, the Kaiser Family Foundation and the Harvard School of Public Health come as medication publicizing hit a record $4. 8 billion out of 2006, up from $2.6 billion in 2002.ââ¬Å"Our overview shows why the medication organizations every one of these promotions: They work,â⬠says Drew Altman, leader of the Kaiser Foundation. ââ¬Å"Many individuals get drugs they in any case wouldn't. While there's a discussion about whether that is something beneficial for patients, it costs the nation more. â⬠Among individuals who mentioned a medication, 44% said doctors gave the one they got some information about, while somewhat the greater part said specialists recommended an alternate medication. Some of the time, specialists did both. At the point when copy answers were evacuated, the survey discovered 82% of patients got some kind of prescription.à (USA Today)I would make the contention against Direct-to-Consumer showcasing in spite of the fact that it is by all accounts is working and returning the decisions to the consumersââ¬â¢ hands. My contention against the direct-to-buyer ad is basically in light of the fact that shoppers are not being given all the essential insights concerning an item. Medication producers are overlooking the rules that apply to purchaser training and are featuring just a couple on the many reactions. Shoppers regularly won't mull over doctorââ¬â¢s proposals additionally in light of the fact that they visit their PCP bearing in mind the end goal of picking up indistinguishable outcomes from what was appeared in the advertising ad.The numerous infomercials appear to support male improvements medications, for example, Cialis and Viagra which can bef uddle youngsters on the off chance that they, see the infomercial. It ought to be the obligation of doctors to decide the correct meds for their patients. Intensifying Pharmacy Regulators Generally, state sheets of drug store will keep on having essential duty regarding the everyday oversight of state-authorized drug stores that compound medications as per the states of segment 503A of the FDCA, in spite of the fact that FDA holds some authority over their operations.For model, the contaminated or misbranding of medications exacerbated under area 503A, or bogus or misdirecting explanations in the naming or promoting of such medications, may bring about infringement of Federal law. Firms that register with FDA as ââ¬Å"outsourcing facilitiesâ⬠under segment 503B will be managed by FDA and investigated by FDA as indicated by a hazard based calendar. (FDA) In the PharmaCare situation ought to have authorized the Prescription Drug User Fee Act (PDUFA) of 1992 prior. As indicated b y Forbes magazine, to tackle this issue, Congress sanctioned the Prescription Drug User Fee Act (PDUFA) of 1992.PDUFA gave a component whereby charges were exacted on pharmaceutical organizations for each new medication application (NDA) documented. The incomes from these ââ¬Å"user feesâ⬠were utilized to recruit 600 new medication commentators and care staff. These new clinical officials, physicists, pharmacologists, and different specialists were entrusted with freeing the overabundance from NDAs anticipating endorsement. Therefore, the FDA had the option to lessen audit times of NDAs to a year for standard NDAs and to a half year for need applications that included critical advances over existing treatment.As an aftereffect of PDUFA,à the timing of U. S. sedate endorsements started to reflect that of the remainder of the world. (Forbes) If the Act was set up the pha debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-59106101650507575742020-08-22T04:39:00.001-07:002020-08-22T04:39:15.080-07:00Real life research Coursework Example | Topics and Well Written Essays - 250 words - 1Genuine research - Coursework Example 2. A significant bit of leeway of mail board investigate is that the expense is low particularly since mass postage is modest. There is additionally no questioner predisposition and the respondents can reply whenever the timing is ideal. Besides, mail overviews might be long so a lot of data can be gotten. A significant disadvantage of this sort of research is that the reviews can be returned following a while; consequently, a reason for delay in the examination. There is a low reaction rate with this sort of review. This sort of research isn't appropriate if the issues in the review need explanation, for example, exceptionally specialized themes. I think NFO utilized a mail board since it is less expensive. Since NFO has a lot of specialists as of now, they didn't need to assemble another gathering for the examination. This implies less exertion and cost on their part. In addition, NFO can arrive at a bigger populace with this sort of review since it doesn't require individual debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-74145973287609918402020-08-21T18:45:00.001-07:002020-08-21T18:45:31.196-07:00Business Structure Legal Responsibilities â⬠Myassignmenthelp.ComQuestion: Talk About The Business Structure Legal Responsibilities? Answer: Presentation: The accompanying report will in general build a business structure based on its legitimate duties and liabilities. The picked business for this case is eatery that would be confined inside the normal lawful strategies. I work in a café that serves neighborhood individuals with multi-cooking styles. The business is a little one with not in excess of ten representatives. The café is at risk to offer best support to the clients along these lines guaranteeing best strategic approaches. Solidness in business disposition would help creating steady structure of business methodology. Legitimate consistence is exceptionally required since a large portion of the business techniques are profoundly good with its relationship with the outer components. So as to approve the business, the café should agree to food and refreshment industry guidelines of Australia. This would enable the business to stay away from obstacles as far as lawful thought and guarantee best strategic policies (Friend and Kohn 2014). Acceptance Manual for Workplace: At AgedCare we set the goal to help and help the customers in understanding the social job and estimation of theirs. This With compelling and enterprising colleagues we convict the issues and the battles of the matured populaces of the nation by giving them best administrations in order to guarantee their future security. We esteem our customers who have been seen to have been denied of taking an interest in dynamic social exhibitions (Blanpain and Bisom-Rapp 2014). Outline of Corporate Organization: Following structure is followed with adequacy: The corporate structure has been framed with adequacy in an alternate strategy. Indeed, it has the conceivable outcomes of the creation of the whole case relating to the whole comprehension of the issues. Truly, this has been taken in to certain thought relating to the compelling industry understandin While organizing the HACCP report, followings can be taken into certain thought: Log Cleaning Schedule Great Receive Form Providers Contact Cook/Heat/Service temp. log The accompanying working structures can be put in manual treatment of the whole workforce: Work Safe Information Medical aid Information Clearing Procedure Set of accepted rules Uniform Requirement The previously mentioned thought can be organized with the assistance of fundamental comprehension of the whole case relating to the theoretical comprehension of how the administration and business rules and guidelines are considered with vitality. For example, work safe data, emergency treatment data, departure strategies are to be set and reported relying upon th circumstance of the episodes. Work environment wellbeing and security is an imperative concern and commitment for the whole comprehension of the works. In actuality, this has been taken into certain thought relating to the compelling models of the issues. As this has been taken into the essential thought for the whole case the majority of the auxiliary arrangements are to be brought into a typical recognition. These are to be taken care of physically as this are not anticipated at the appropriate time of time. Hazard Penalties: The organization will be forcing hazard punishments if any sort of error or carelessness is found in the thought of hazard factors in working hour. In actuality this has been taken into certain thought relating to the essential comprehension of the whole case relating to the whole comprehension of the whole methodology. Following is the structure of punishment of breaking WHS rules and guidelines of NSW: Recognition of the punishment relating to the hazard factors must be taken into certain thought with the viable change as far as making an idea of the specific thought. Three unique classifications have been found- Position of the offense of breaking the standards must be taken into certain thought with the powerful consistence of the law. The guidelines and guidelines set over the span of the work must be taken into certain thought. Penetrating of specific guidelines and guidelines would fall under specific punishments that would force important activities against a specific representative. End: Legitimate consistence should be determined as it helps an association creates it reasonable business approaches with best practices. Such strategic policies would acquire the achievement viability. References: Blanpain, R. what's more, Bisom-Rapp, S., 2014.Global Workplace: International and Comparative Employment Law Cases and Materials. Wolters Kluwer Law Business. Business.qld.gov.au. (2017).Penalties for breaks to work wellbeing and security law | Business Queensland. [online] Available at: https://www.business.qld.gov.au/running-business/whs/whs-laws/punishments [Accessed 12 Aug. 2017]. Companion, M.A. what's more, Kohn, J.P., 2014.Fundamentals of word related security and wellbeing. Bernan Press. Reese, C.D., 2015.Occupational wellbeing and security the executives: a down to earth approach. CRC press. Taris, T.W. what's more, Kompier, M.A., 2014. Circumstances and logical results: Optimizing the plans of longitudinal examinations in word related wellbeing brain science. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-55910298943295047772020-08-04T08:33:00.001-07:002020-08-04T08:33:03.593-07:00Genetic Causes of Borderline Personality DisorderGenetic Causes of Borderline Personality Disorder BPD Print Genetic Causes of Borderline Personality Disorder By Kristalyn Salters-Pedneault, PhD Kristalyn Salters-Pedneault, PhD, is a clinical psychologist and associate professor of psychology at Eastern Connecticut State University. Learn about our editorial policy Kristalyn Salters-Pedneault, PhD Updated on September 20, 2019 Mixmike/Getty Images More in BPD Diagnosis Treatment Living With BPD Related Conditions Are you wondering about the genetic causes of borderline personality disorder? Youre not alone. Many people wonder why they or a loved one has borderline personality disorder (BPD). Unfortunately, there are no easy answers, but research is getting closer to understanding the causes of BPD. Genetics or Environmental Causes Studies of BPD in families show that first-degree relatives â" meaning siblings, children, or parents â" of people treated for BPD are ten times more likely to have been treated for BPD themselves than the relatives of people with schizophrenia or bipolar disorder. However, while this suggests that BPD runs in families, studies of this type do not tell us exactly how much of BPD is due to genetics. Thats because first-degree relatives share not just genes, but also environments in most situations. For example, siblings may be raised together by the same parents. This means that these studies may reflect, in part, any environmental causes of BPD as well. Twin Studies Show Genetics Play a Large Role in BPD A more direct, though still imperfect, way to study the influence of genes on BPD is to examine rates of BPD among identical versus fraternal twins. Identical twins have the exact same genetic makeup whereas fraternal twins only have similar genetic makeup, just like two regular siblings. There have been a few twin studies of BPD, which have shown that 42 to 69 percent of the variance in BPD is caused by genetics. This means that 58 to 31 percent of the variance in BPD is caused by other factors, such as the environment. This suggests that BPD is fairly strongly related to genetic causes. Yet, most likely an interaction of genes and environment leads to BPD in most people with the disorder. What the Genetic Factor Means What does this mean for you? If you have BPD, it means that it is not your fault. You probably have a genetic predisposition to develop the disorder. Perhaps you have also experienced a few of the environmental events that seem to be linked to BPD in some cases, such as being abused as a child or losing a loved one. You do not have BPD because you are âweakâ or âcanât handle things.â There is a reason why you experience the symptoms you do. If you have a first-degree relative with BPD, it means that you may have an increased chance of developing the disorder yourself. However, this by no means guarantees that you will develop BPD. In fact, chances are likely that you will not. Why Treatment Is Essential If youre concerned that youre showing signs of BPD, its important to get treatment early. This will reduce any risk factors and help alleviate your symptoms. Speak to your doctor about your symptoms, testing for a proper diagnosis, and treatment options. Borderline Personality Disorder Discussion Guide Get our printable guide to help you ask the right questions at your next doctors appointment. Download PDF If you are a parent and you have BPD, you may be concerned about whether your kids will have BPD too. While it is a possibility, know that even though genes are important, they are not the sole cause of BPD. There may be ways to ensure the environment you provide for your kids reduces their risk. Part of that is ensuring that you get treatment and that you stick with the treatment plan you and your doctor decide on. Psychotherapy may also be an option to help you learn effective parenting skills. The 9 Best Online Therapy Programs debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-92228330089663805352020-06-22T07:08:00.001-07:002020-06-22T07:08:02.361-07:00Best Practices for Network Security Coursework - 1925 WordsBest Practices for Network Security (Coursework Sample) Content: Best Practices for Network SecurityNameInstitutionDateBest Practices for Network SecurityIntroductionIT security teams are faced with rapid mutating threats at all the possible entries from mobile to cloud and from the perimeter to the desktop. Network security management has become more complex and challenging because of the evolving threat and changes in security and network architecture. In order to protect your computer network, network security teams have to have a better understanding of network fundamentals. Once the essential elements to computer network security are covered, best practices can be implemented to minimize the risk of unauthorized access from attackers (Manshaei, Quanyan, Alpcan, BaÃâ¦Ã
¸ar Hubaux, 2013).ÃâSecurity teams must also support external and internal compliance mandates, optimize performance, enable new services, support the possibility to efficiently troubleshoot on demand, and ensure availability with no room for error. The w hole of that is too much to balance in the management of network security. A sound understanding of network best practices will allow individuals and corporations to secure their computer infrastructure better from potential hackers (Manshaei, Quanyan, Alpcan, BaÃâ¦Ã
¸ar Hubaux, 2013). This paper seeks to address the fundamentals of network security and some best practices on how to deter and counter network attacks on their networks.The greatest threat to network security and computer systems originate from humans, through ignorant or malicious actions. The goal of malicious actions is to attack. For example, one may seek to disrupt the normal operations of the business, thus deny data production and availability. Due to these network security possibilities, there have been numerous researches on the best practices for network security and how to safeguard the business operations from malicious actions. The following are among the best practices for network security that have been highlighted in most studies (Dey, Lahiri Zhang, 2012).Designing a Macro View for the Network SecurityEvery organization requires a holistic view of their computer network. With hosts and devices of disparate vendor, security personnel require a comprehensive, normalized view of the network including: access rules, routing rules, VPN, NAT; assets such as asset classifications and groupings; and hosts such as services, all product versions, patches, and vulnerabilities. Where security personnel have a comprehensive view of the network, they can view network hosts, classifications, configurations, and other pertinent information (Dey, Lahiri Zhang, 2012).A network model or map is both a useful diagnostic and visualization tool that provides analysis only possible when the considering the general view. For example, compliance and security personnel can use this macro view to monitoring the manner in which data would move from one point to another on the network. It also illustrat es the missing information such as access control list, hosts, data, and more. It is also possible to conduct sophisticated analytics accurately and quickly without disrupting a live network in a model-based environment. Access path analysis can also help in validating changes, and is able to troubleshoot connectivity and outages issues, improving security processes and enhancing visibility (Chenoweth, Minch Tabor, 2010).Having a Micro View of the daily Device ManagementWhile the macro view is required to monitor the way all network pieces fit together, network teams must also be in a position to capture details for a specific device, access policies, information access rules, and configuration compliance. Such information need to be considered within the broader network framework. The information can include context such as routing, zones or segments, switches, routers, firewalls, and intrusion prevention systems. Information need to be offered in a digestible fashion. The compone nts of the network that impact the device originate from different vendors, creating data of various vendor languages that have to be correlated, deciphered, and optimized to enable network teams to streamline sets of rule (Chenoweth, Minch Tabor, 2010). For example, network teams have to be in a position to view access policy violations and limit or block access by applications.Weekly or even daily device reviews on the network can be attained with a mutual process. Less frequent device configuration review risks network compliance and security. Automating policy compliance can also help in ensuring consistency and compliance, and preserves resources of information technology. Ideally, a modeling tool of any network that allows administrators to have a macro view should also permit security teams to drill down into a micro view of every device. It provides information on users, vulnerabilities, applications, and more through a micro view. It also allows security teams to view the wider network and then focus in on specific devices for security management (Gupta Zhdanov, 2012).Attack simulation for context-aware risk assessmentMerely acknowledging the vulnerabilities of the network and their criticality is inadequate for understanding the actual risk level to the organization. Attacks, today, often incorporate numerous stages that cross many different zones of the network. An isolated view of any of these stages could be innocuous. Technology of attack simulation automatically looks at the holistic network, known vulnerabilities, threats, and business assets. It also identifies any possibility in case the conditions are combined. Simulation of attacks, additionally, evaluates potential options to limit or block an attack, providing intelligence for decision support. The key to assessing what threats and vulnerabilities pose most risk lie on the understanding of the likelihood of an attack and its impact on valuable targets (Ailin, 2014).Through attack simula tion technology, administrators can look at asset criticality, network context, existing security controls, and business metrics when determining the impact of a potential attack. For example, when an asset runs a crucial application to maintain the business and needs continuous availability, a medium-level vulnerability threatening to disable the same asset might be a high-level risk to the business in question. The impact of deploying a specific security control is, therefore, necessary to consider. Maintaining IPS on active mode continually can impact the performance of the network. Tools of attack simulation allow administrators to target the use of their IPS protection, maximizing performance, activating vital signatures, and prioritizing vulnerabilities (Gupta Zhdanov, 2012).Secure change managementThere is a need for a secure change management process, once a network is in compliance, in order to maintain continuous compliance and validate that there is no introduction of ri sk on the part of the planned changes. Secure change management incorporates assessment of risk in a standardized, orchestrated process. It also flags changes outside the structure, troubleshoots where necessary, and enables the security teams to reconcile flagged changes (Security of the Internet and the Known Unknowns, 2012).In addition, secure change management verifies that there was an implementation of the changes just as intended, highlights unapproved changes and recognizes unintended implications of the changes. For example, a process of change management can flag when a firewall change opens access to risky services, when a network change exposes vulnerabilities, or when there is unauthorized access path to an internal zone from a partner. In order to maintain network security, the impact of the proposed change can be determined by the change management process before implementing the change (Security of the Internet and the Known Unknowns, 2012).Implementing these best pr actices for the management of network security can reduce the risk across the network. With adequate visibility on both device and network level, incredible amounts of data are transformed into intelligence, which deciphers complicated network security transactions into actionable, manageable information. With such an insight, attack simulation can prioritize vulnerabilities and eliminate the vectors of the attack that are most crucial to the business, and protect the data and services of the organizations. Nevertheless, change management can optimize and regulate processes of security to reduce the management of security workload and improve security (Ahmad, Sahib Azuwa, 2014).Besides the above-discussed practices for network security, network administrators have been advised to observe guidelines in all their operations in order to prevent security threats and vulnerabilities. Some of the basic guidelines that any business, organization can follow to address security concerns inc lude the following: * Encrypting data: organizations need to encrypt all file systems, stored data, and across the wire transfers. Encryption helps to protect sensitive data and prevent data loss to equipment loss or theft (Ahmad, Sahib Azuwa, 2014). * Implement auditing and DLP: organizations need to use file auditing and data loss prevention to alert, monitor, block, and identify the flow of data out of and into the network. * Using digital certificates to sign all company sites: all certificates need to be saved to hardware devices such as load balancers or routers and not on web servers. These certificates should be obtained from only trusted authorities. * Implement a removable media policy: organizations should limit the use of external hard disks, USB drives, external DVD writers, thumb drives, and any other writeable media. Such devices promote breaches to security leav... debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-71454141065957644192020-05-23T04:29:00.001-07:002020-05-23T04:29:03.891-07:00Comparing Othello and Canterbury Tales Essay - 1160 Words Comparing Othello and Canterbury Tales The use of manipulation and misleading for personal gain has proved to be successful for many people throughout history. Famous poet, Geoffrey Chaucer, and famous play writer, William Shakespeare, illustrate characters who possess these manipulating qualities in their personalities. Geoffrey Chaucerââ¬â¢s Pardoner, from The Canterbury Tales, and William Shakespeareââ¬â¢s Iago, from Othello, are good examples deceiving characters. These literary figures manipulating techniques are very effective on the other characters in Chaucerââ¬â¢s and Shakespeareââ¬â¢s works. Iagoââ¬â¢s main motivation for his manipulation is his hatred of the main character, Othello. Iagos reasons for his hatred ofâ⬠¦show more contentâ⬠¦Othello must feel that same horrible jealousy that Iago feels. Iago has a very effective way with words. When Desdemona, Iago, and Iagos wife, Emilia, arrive in Cyprus, Cassio welcomes Emilia with a kiss, then says to Iago, ââ¬Å"Let it not gall your patience, good Iago, That I extend my manners. ââ¬ËTis my breeding That gives me this bold show of courtesyâ⬠(2.1.97-99). Cassio is making a big point of what a charmer he is, but Iago shoots him down by saying, ââ¬Å"Sir, would she give you so much of her lips as of her tongue she oft bestows on me, you would have enoughâ⬠(2.1.100-102). Hes saying that if Emilia kissed Cassio as much as she nags Iago, Cassio would have more than enough kissing. This apparently casual devaluation of Emilia and her kisses is a deception; a little later we learn that Iago is intensely jealous and suspects Cassio of having an affair with Emilia. Also, Iago convinces Cassio that the best way to get his job back is to appeal to Desdemona, then sends him off. Alone on stage, Iago asks us why we think hes a villain, since his advice to Cassio is free and honest, and after all he is called ââ¬Å"honest Iago.â⬠Answering his own question, he comments, ââ¬Å"When devils will the blackest sins put on, They do suggest at first with heavenly shows, as I do now.â⬠(2.3.351-353). Iago knows that he is a devilish hypocrite, but he seems to beShow MoreRelated Contradictions in Chaucers The Canterbury Tales Essay3897 Words à |à 16 PagesContradictions in Chaucers The Canterbury Tales There is no question that contradictory values make up a major component of The Canterbury Tales. Fate vs. Fortuna, knowledge vs. experience and love vs. hate all embody Chaucers famous work. These contrasting themes are an integral part of the complexity and sophistication of the book, as they provide for an ironic dichotomy to the creative plot development and undermine the superficial assumptions that might be made. The combination of completelyRead MoreStudy Guide Literary Terms7657 Words à |à 31 Pagesthe pursuit of justice is no virtue. Barry Goldwater *Brutus: Not that I loved Caesar less, but that I loved Rome more. Shakespeare, Julius Caesar 14. Anecdote A very short tale told by a character in a literary work. In Chaucers Canterbury Tales, The Millers Tale and The Carpenters Tale are examples a short account of a particular incident or event of an interesting or amusing nature, often biographical 15. antagonist- A person or force which opposes the protagonist debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-65565376092306063352020-05-18T12:40:00.001-07:002020-05-18T12:40:09.728-07:00Quality Improvement or Patient Safetychange Initiative in Your Department - Free Essay Example Sample details Pages: 9 Words: 2564 Downloads: 1 Date added: 2019/10/10 Did you like this example? Patient safety refers to how health care institutions and hospitals protect patients from possible injuries, medical errors, infections and accidents (Aiken et al, 2012). It is the responsibility of hospitals and health care facilities to ensure that their patients are protected and safe while they are being attended to.à The patient safety greatly impacts the recovery process. If a patient suffers recovery will take longer, sometimes even life can be lost. Donââ¬â¢t waste time! Our writers will create an original "Quality Improvement or Patient Safetychange Initiative in Your Department" essay for you Create order For example, if medical error results to air embolism (air bubble in the blood), the patient is likely to have a stroke or even lose his or her life. The air bubbles interfere with the blood flow through the body hence the stroke (Murray et al., 2013). In the United States, it is approximated that 440,000 people lose their lives due to medical errors, 1 out of 25 patients gets an infection, 1 out 4 Medicare suffers injuries or harm when gets admitted and over 1000 patients are likely to die due to preventable medical errors(Makary $ Daniel, 2016).à This figure is very high and should worry the stakeholders in the health care provision. Whereas there no hospital or health facility that is totally immune from potential dangers, safety measures can be put in place to protect the patients. For instance, having a strong team of health care providers can minimize the rate of infections. In addition, the strong team can come up with measures to prevent possible mistakes and medical errors that might occur in the process.à This can be done by having an efficient and clear means of communication among the staff, patient and the patientsââ¬â¢ family. An inefficient team in the hospital is an open risk to patients. These disturbing figures form the basis of this project which aims at creating a safer environment both the medical staff and the patients. According to the study by Coetze et al (2013) the patientsââ¬â¢ safety is closely tied to the medical staffsââ¬â¢ welfare.à Studies have shown that fatigue in nurses have a negative impact on the safety of the patients. Yoder (2014) found out that fatigue increases chances of having medical errors such wrong diagnosis Aims These are what should be accomplished at the end of the project. Patients record zero harm while receiving care There is improved an improvement in access to health care services. Improved patient experience with the care givers. Minimize hospital readmissions The above aims will be achieved by using the road maps below. Aim 1: Patients record zero harm while receiving care a) Minimizing negative effects The health care givers must ensure there is compliance with the Reduction of Adverse Drug Events or Medical Reconciliation i.e. the medication administered to the patient should be the same as those prescribed by the care giver. b) Minimizing harm via reducing prevalence and cases of Healthcare Acquired Infections This will be done by ensuring there is compliance Informed care bundles and strategies in the management of MRSA, VRE, C-Diff, surgical site prevention of infections, and hand hygiene. To determine whether there has been an improvement, Hospital Standard Mortality Ration (HSMR) should be below 100 by the end of the next financial year (2018/19) at the strategic level. At both, the unit and program level, Medical Reconciliation, VTE, VRE, Infection on the surgical area are among the factors that will be considered. Aim 2: There is improved an improvement in access to health care services a) Improvement in the flow of patient from admission to discharge. This will be done by adopting a spread solution that will be piloted with the Emergency Department, b) Minimize the waiting time for planned surgical process Process related to waiting strategies like the hip and Knees are enhanced c) Improving the care given to the chronic patients i.e. those with Diabetes and Congestive Heart Failure (CHF). This will be done by the implementation of evidence based population care models. To establish where there has been improvement, at the strategic level the average time taken in ER is expected to reduce by at least 10% at the end of the financial year 2018/19. At program and Unit level, process indicators will be used in monitoring the flow of patients. In addition, the time it takes to replace knee and hip will also be considered. Aim 3: Improved patient experience with the care givers. a) Design a care and service system that gives more room for the patients and their families to voice their concerns. This will be done by creating an advisory to the manager together with the network programs for specific departments with the hospital. b) Enhancing how the hospital collects and analyze the patientsââ¬â¢ feedback. This will be done through an improved rigorous process of information collection of feedback from the patients. The information will then be shared among the staff and the physicians. Secondly, the hospital will have to fully fledged and efficient customer service department with qualified personnel. c) Providing patients with information they require in a simple and understandable form. The improvement will be examined by evaluating if there is an increase in the result of the picker questions. The question asks the patients and their families to give an overall rating of the quality of the service they received from the hospital. An improvement of at least 10% is expected at the end of the financial year 2018/19. At the program and unit level, surveys that focus on the score of Emergency Department will be conducted.à The surveys will seek to establish the general satisfaction with the care provided by the department including pain management. Aim 4: Minimize hospital readmissions a) Improved transition in the line of continuum care. This will be achieved by enhancing admission needs after hospital with focus on friendly referral hospitals, patient and family communication, fool up after discharge from the hospital, coordination with community health care givers among other external partners. This is intended to improve planning of the discharge and information transfer especially where a patient is referred to a ââ¬Ësenior hospitalââ¬â¢. b) Improved care of patients with chronic conditions like diabetes and Congestive Heart Failure. This will be achieved through the implementation of evidence based population care model like the inpatient-outpatient components for such conditions. The set standards must be adhered to. The assessment at the strategic level will be done by assessing the rise in the number of the enrollment of the CHF and COPD.à à The number is expected to rise by 25% for patients with high risk at the end of the financial year 2018/19. The care transition should be implemented by the end of the same year. At the program and unit level, indicators will be the readmission in a span of 30 days for the picked volumes of CMGs and measure of the vital long-term conditions. Plan Implementation The implementation of this quality improvement plan will involve all the stakeholders involved in the health care provision. The stakeholders include the policy makers, the hospital management of the hospital, the patients and the patientsââ¬â¢ family. Most of the approaches and methods of quality improvement being used today were developed in other industries that are not related to health care provision. However, they have adopted by the health care industry nearly for 30 years now. Unfortunately, the approaches and methods have not been fully embedded into the health despite being adopted nearly 30 years ago. This, in turn, has resulted in lack of a complete evidence based analysis of their effectiveness.à All the staffs are expected to adhere to the proposed implementation plan. The implementation of this plan is expected to spread across the financial year 2018/19. Assessment will be done after every quarter to establish if there is any progress being made. The progress refers to the improvement in the quality of service being provided to the patients. In establishing this improvement, we will use the PDSA cycle i.e. the Plan-Do- Study-Act. PDSA was first developed by Dermin in 1982 and gives a four model for a continuous implementation of the improvement of patient safety improvement initiatives. The model can be used in the following instance: When a new quality improvement plan is being started. When there is a redesign or an improvement on the existing healthcare service When data collection and analysis plans are being developed to help in improving the service delivery. Today management is no longer an art but a science where management decisions are driven and influenced by the available data. Cost-effects implementing patient safety initiatives. For an effective implementation of the proposed patient safety initiative and changes, the hospital management will incur extra cost in leadership training for the staff especially the team leaders. Secondly, the management will have to additional health care staff to cover for the possible shortage to reduce the work load. All the staff will also be trained on the importance of having a team work. The implementation process will be under the leadership of the PDSA select team. Lack of funds and uncooperative members of staff are likely to be the major challenges in the implementation process. There is a likelihood of resistance for change at first. Training and employment of new additional staff might also be costly to the hospital management. Compensation for the Executives and other staff Performance-based compensation helps in driving accountability during the implementation of the quality improvement. It links the compensation to the achievement of the set target. There will only be compensation if the target is achieved. The executives and the staffs are thus motivated to ensure the set target is achieved. In addition, it enables the hospital to have a consistency in the performance incentives application and transparency in the whole process.à The table below provides a guideline how the compensation will be done.à It should be noted that the compensation is tied to the achievement of the set target. Part B:à Change Management Theory Change management (CM) refers to the ââ¬Å"all approaches used to prepare and support individuals, teams, and organizationâ⬠(Hayes, 2014) while making change within the organization. Additionally, it includes the change in use of resources, process in business, allocation of budget or any other change that has a significant influence on the operation of the organization or company (Bratton Gold, 2012). Under Organization Change Management (OCM), we looked into the organization as a whole and what ought to be changed. In contrast, change management only refers to people and how they are affected by transition during the change within the organization. There are six change management theories according to Hills, Jones Schilling (2014). The Classical theory put emphasis on structure and things like division of labor, the command its direction are considered.à The scientific method puts emphasis on the efficiency, productivity, time and maximum utilization of space. The bureaucratic system has a strong emphasis on the authority and the rules of the organization. Under this system, the employees are expected to strictly adhere to the rules and regulations of the organization as they are with no flexibility. Junior officers are required to get approval from their seniors before undertaking some responsibilities no matter how simple they might be. This system is very common with the government institutions. The Human Relation Management system is one that focuses on the human factors within the organization or company. The human factors include things such as motivation (both as individual and at group level.à The contingency theory mainly aims at first establishing the problem then a solution is created through management. The final theory is the system management theory. This theory mainly focuses on the interdependency and the complexity of the system. This is done through combining and analyzing all the components to determine their impact on the general productivity of the organization or company. The most important factors to consider while selecting the type of change includes: goal and strategies, system measurement, the sequence of the steps and finally the implementation of the desired organization changes. John Fisher and John Kotter have come up with models that can be used to evaluate and enhance the implementation process of the change in the organization.à In this section discusses the John M. Fisherââ¬â¢s Change Model. This model is appropriate since it promotes corporation among the staff during the implementation process. Fisher uses a Transition model to explain how people react to any change as discussed by McDowell et al (2013). Ideally, people are generally resistant to change since they prefer being in their current situation.à Fisher theory is based on the study that was done by Elisabeth Kubler-Ross. In the study, Elisabeth identified the stages of grief. From that study, Fisher identified eight stages that include; Anxiety, Happiness, Fear, Threat, Guilt, Depression, Gradual Acceptance and Moving Forward.à Different people have different speed of moving through the levels. The speed is influenced by different factors like an individualââ¬â¢s temperamental, prior experiences among others. The key areas that this model focuses on include the resistance to change in the early stage and working with people through change. à à à à à à à à à à à à à à à Initial Resistance to change Generally, people have negative reaction to change during the early stages since the change causes disruption in their operation. Another reason why people are most likely to have a negative reaction is the uncertainty that comes with the change. It is even worse when one has a bad experience with change. One might have lost his or her job in before due to changes that were adopted by that organization or company. Such experience causes fear to the individuals and influences their perception about change in general. Such individuals are likely to be reluctant in adopting the proposed changes. However, this can be overcome by having an efficient and timely communication to the staff that will be affected. Good communication makes them understand the need to have change and its benefits to them. In this case, the nurses and other physicians will be informed on why the Patient Safety Initiative Change is important to them. Benefits such having a reduced readmission rate of patients, reduced infection among others are beneficial to them since they will result in reduced work load. Reduced workload means there will be no fatigue.à In addition, the improvement in the quality of healthcare delivery will build their reputation as professionals thus building their resume. With effective communication, the fear will go away hence making them eager to adopt the proposed changes. Similarly, the training is likely to a motivating factor since it provides them with an opportunity for self-growth. However, the process should not be rushed as it can end up producing the exact opposite of the desired result. People must be given time to overcome fear without being rushed through the process.à T here should only be a movement to the action when the whole team is ready for it. Working with people through the change process During the implementation process, there is a possibility of some of the staff remaining stuck in the past system by constantly denying that change is actually taking place. In order for the process to be successful, the whole team should move as a unit. It is thus necessary to involve every member of the team through the whole process. In the implementation of the Patient Safety Change Initiative, the PDSA select team will consist of the departmental heads of all the departments in the hospital. This creates a sense of inclusivity as all the staffs will feel represented. The head of departments will also be expected to communicate to their members on the progress and need for the change. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-24262372988933478242020-05-11T16:19:00.001-07:002020-05-11T16:19:01.977-07:00Wuthering Heights Quotes Wuthering Heights is a famous work of Gothic fiction by Emily Brontà «. It is a tale of all-consuming romantic passion. Here are a few key quotes from Wuthering Heights. Quotes The intense horror of nightmare came over me: I tried to draw back my arm, but the hand clung to it, and a most melancholy voice sobbed, Let me inââ¬âlet me in! Who are you? I asked, struggling, meanwhile, to disengage myself. Catherine Linton, it replied, shiveringly (why did I think of LINTON? I had read EARNSHAW twenty times for Linton) - Im come home: Id lost my way on the moor! As it spoke, I discerned, obscurely, a childs face looking through the window.(Nelly and Catherine, Ch. 3) Terror made me cruel; and finding it useless to attempt shaking the creature off, I pulled its wrist on to the broken pane, and rubbed it to and fro till the blood ran down and soaked the bedclothes.(Nelly, Ch. 3) I cannot love thee; thou rt worse than thy brother. Go, say thy prayers, child, and ask Gods pardon. I doubt thy mother and I must rue that we ever reared thee!(Mr. Earnshaw, Ch. 5) Im trying to settle how I shall pay Hindley back. I dont care how long I wait, if I can only do it at last. I hope he will not die before I do!(Heathcliff, Ch. 7) They DO live more in earnest, more in themselves, and less in surface, change, and frivolous external things. I could fancy a love for life here almost possible; and I was a fixed unbeliever in any love of a years standing.(Nelly, Ch. 8) ...he had ceased to express his fondness for her in words, and recoiled with angry suspicion from her girlish caresses, as if conscious there could be no gratification in lavishing such marks of affection on him.(Nelly, Ch. 8) Doubtless Catherine marked the difference between her friends, as one came in and the other went out. The contrast resembled what you see in exchanging a bleak, hilly, coal country for a beautiful fertile valley; and his voice and greeting were as opposite as his aspect.(Nelly, Ch. 8) It would degrade me to marry Heathcliff now; so he shall never know how I love him: and that, not because hes handsome, Nelly, but because hes more myself than I am. Whatever our souls are made of, his and mine are the same; and Lintons is as different as a moonbeam from lightning, or frost from fire.(Catherine, Ch. 9) If all else perished, and HE remained, I should still continue to be; and if all else remained, and he were annihilated, the universe would turn to a mighty stranger: I should not seem a part of it.(Catherine, Ch. 9) Nelly, I am Heathcliff! Hes always, always in my mind: not as a pleasure, any more than I am always a pleasure to myself, but as my own being.(Catherine, Ch. 9) I seek no revenge on you...Thats not the plan. The tyrant grinds down his slaves and they dont turn against him; they crush those beneath them. You are welcome to torture me to death for your amusement, only allow me to amuse myself a little in the same style, and refrain from insult as much as you are able. Having levelled my palace, dont erect a hovel and complacently admire your own charity in giving me that for a home. If I imagined you really wished me to marry Isabel, Id cut my throat!(Heathcliff, Ch. 11) Well, if I cannot keep Heathcliff for my friend if Edgar will be mean and jealous, Ill try to break their hearts by breaking my own. That will be a prompt way of finishing all, when I am pushed to extremity!(Mrs. Linton, Ch. 11) It is not in him to be loved like me: how can she love in him what he has not?(Heathcliffe, Ch. 14) THAT is how Im loved! Well, never mind. That is not MY Heathcliff. I shall love mine yet; and take him with me: hes in my soul.(Mrs. Linton, Ch. 15) Kiss me again; and dont let me see your eyes! I forgive what you have done to me. I love MY murderer but YOURS! How can I?(Heathcliffe, Ch. 15) And I pray one prayerââ¬âI repeat it till my tongue stiffensââ¬âCatherine Earnshaw, may you not rest as long as I am living; you said I killed youââ¬âhaunt me, then! The murdered DO haunt their murderers, I believe. I know that ghosts HAVE wandered on earth. Be with me alwaysââ¬âtake any formââ¬âdrive me mad! only DO not leave me in this abyss, where I cannot find you! Oh, God! it is unutterable! I CANNOT live without my life! I CANNOT live without my soul!(Heathcliffe, Ch. 16) Ill be very kind to him, you neednt fear...Only nobody else must be kind to him: Im jealous of monopolising his affection.(Heathcliffe, Ch. 20) Besides, hes MINE, and I want the triumph of seeing MY descendant fairly lord of their estates; my child hiring their children to till their fathers lands for wages. That is the sole consideration which can make me endure the whelp: I despise him for himself, and hate him for the memories he revives! But that consideration is sufficient: hes as safe with me, and shall be tended as carefully as your master tends his own.(Heathcliffe, Ch. 20) But theres this difference; one is gold put to the use of pavingstones, and the other is tin polished to ape a service of silver.(Heathcliffe, Ch. 21) He wanted all to lie in an ecstasy of peace; I wanted all to sparkle and dance in a glorious jubilee. I said his heaven would be only half alive; and he said mine would be drunk: I said I should fall asleep in his; and he said he could not breathe in mine, and began to grow very snappish.(Catherine, Ch. 24) Hell never let his friends be at ease, and hell never be at ease himself!(Catherine, Ch. 24) Catherines face was just like the landscapeââ¬âshadows and sunshine flitting over it in rapid succession; but the shadows rested longer, and the sunshine was more transient.(Nelly, Ch. 27) Im glad, for I shall be master of the Grange after him. Catherine always spoke of it as her house. It isnt hers! Its mine: papa says everything she has is mine. All her nice books are mine; she offered to give me them, and pretty birds, and her pony Minny, if I would get the key of her room, and let her out; but I told her she had nothing to give, they were all, all mine.(Linton, Ch. 28) You have left me so long to struggle against death, alone, that I feel and see only death! I feel like death!(Catherine, Ch. 30) I have lost the faculty of enjoying their destruction, and I am too idle to destroy for nothing.(Heathcliffe, Ch. 33) Last night, I was on the threshold of hell. To-day, I am within sight of my heaven. I have my eyes on it: hardly three feet to sever me!(Heathcliffe, Ch. 34) debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-39272178440992274882020-05-06T20:43:00.001-07:002020-05-06T20:43:36.080-07:00Essay about Animal Testing - 605 Words Animals have long sense been a part of human life. The dog for example is thought to have been the first animal to be domesticated by humans, sometime around 13,000ââ¬â10,000 B.C., from wolves. It is not known for sure how humans gained the trust of the Canines but in any event they did, and soon found dogs to be reliable companions. Animals have aided us any many ways, from offering protection and companionship. They should be respected and loved for loyalty; however it has been a very common practice to test household items, cosmetics and pharmaceutical products on animals for a very long time. Countless of innocent creatures are killed, or live a maimed life thanks to the endeavors of human scientist who use them to further there research.â⬠¦show more contentâ⬠¦He is known as the father of vivisection. ââ¬Å"Vivisection means the cutting up of a living animal, and historically referred only to experiments that involved the dissection of live animals.â⬠(AllSands, History Of Animal Testing) In 1859, Charles Darwin wanted to better understand how the human body functioned; therefore he used animals, who are much like humans to further his studies through many forms of experimentation. Recently animal testing has turned into a highly controversial and intense topic. The nature of the test and the effect on the animal which is being tested is what causes the debates. For example, very few would find animal testing wrong when testing animal food. It would be seen as a taste test, however using an animal to test a cosmetic for skin rashes, and hair loss is seen in a different view. People who are for animal testing states that it help researches to discover drugs and treatment that can aid humans. Researchers claim that animal experimentation is a must in order to help us as human being. They say that many medical advances have come from animal testing. There have been advances in cancer treatment and even HIV. Because of this, it is said that animals are vital for improving human health. Another argument that supports the testing of animals is that it actually helps scientist to known for sure if the drugs or cosmetic they want to sell to the public is safe. Since the products are tested on the animals ahead of time,Show MoreRelatedAnimal Testing678 Words à |à 3 Pages Animal testing is a controversial topic in todayââ¬â¢s society, much more than it was 100ââ¬â¢s of years ago. Testing on animals was practiced long ago, and is still practiced today. Greek writings about vivisection [the dissection of a live organism] can be found dated as early as 500 BC. At that time, in Ancient Rome and Alexandria, and later in Greece, vivisection was originally practiced on human criminals, but prohibitions on the mutilation of the human body soon arose. This caused a reliance on animalsRead MoreTesting On Animals : The Dangers Of Animal Testing1375 Words à |à 6 Pagesnumber of animals that undergo constant suffering in the name of human vanity. Animal testing was originally introduced in the early 20th century and is still prominent today. It is morally unacceptable to experiment on animals for human purposes. The procedures used in animal testing are cruel and inhumane, nor are they the most reliable source of data; resulting in many mishaps. Moreover , with the perpetual advancements in technology, there are several alternative methods making animal testing unnecessaryRead MoreHuman Testing : The Benefits Of Animal Testing802 Words à |à 4 PagesAnimal testing has helped us for years discover cures for sickness in humans and sometimes even animals. But as long as they test the animals humanely, animals can be tortured with pain from the testing. However many efforts are being made to reduce the testing to a minimum. Scientists know that without the tests they wouldnââ¬â¢t know how to check the safety of new drugs. If there was no animal testing scientists would have probably resulted into something very unacceptable, human testing. And scientistsRead MoreThe Cruelty of Animal Testing1644 Words à |à 7 PagesAnimal testing is a completely unnecessary act of cruelty and should not be allowed for various reasons. It is superfluous for innocent animals to undergo chemical testing of any sort, not only do they suffer, but there are other more humane alternatives to test products. Many people who are in favor of animal testing do not know of these safer more humane alternatives. Many methods have been developed to help stop animal testing, and improve the health system of all human beings. A significantRead MoreThe Importance Of Animal Testing1240 Words à |à 5 Pages Animal testing has long played a part in the science of testing, and it still plays a very important role in the medical world. Testing on animals in order to create a cure for AIDS is one thing, but testing on animals for human vanity is another. Animal testing is used to test the safety of a product. It has kept some very unsafe substances out of the cosmetic world. However, in this day in age, animal testing is not the only way to test the safety of a product. Animal testing in cosmetics hasRead MoreEssay on Animal Testing1383 Words à |à 6 Pagesand Behavior Animal testing is not a problem in todayââ¬â¢s society because it is beneficial to humans. It seems unethical to put animals through such pain and torture, but if we stopped it completely there would be a large amount of human lives lost. How could this be? The further advancements in medical and technological science is inevitable. Therefore, if the testing must be done to learn more about the brain and body, which spe cies (animals or man) seems expendable for such testing. The real questionRead MoreThe Negatives of Animal Testing1027 Words à |à 5 Pageshave been tested on animals; from lipstick and shampoo to dish soap and foot powder. Even the white ink on an MM has been tested on animals. To some, this statement may be alarming and even disturbing ââ¬â to others it may not mean much at all. Either way, the debate over animal testing has gained much popularity in recent decades. Animal testing has been done since at least 500 BC; even Aristotle experimented on animals for scientific reasoning. Around 200 AD, dissecting animals in public was actuallyRead More Animal Testing Essay710 Words à |à 3 Pagesanimal testing ââ¬Å"Beauty without crueltyâ⬠is the outcry that can be heard from animal right activists around the world. The FDA does not require companies to perform tests on animals but if the cosmetic product contains chemicals that can be seen as toxins, testing becomes a necessity. There are currently thirteen safety tests that are performed on animals. Anti-testing activists deem these unnecessary and consider them to be cruel. ââ¬Å"Fourteen million animals are used currently in the U.SRead MoreThe Rights Of Animal Testing2041 Words à |à 9 Pagesrights of all animals with further argument or debates, do humans have the right to use animals on medical testing and lab use? There are several issues that can be placed in this argument this research will acknowledge four important topics in the rights of animal testing. Is it right to use animals for testing? Is it right to compare animal DNA to human DNA in these animal experiments? Is it right to use real animals instead of computers to generate results? Is it right to state animals are beingRead MoreThe Efficiency Of Animal Testing1394 Words à |à 6 PagesEfficiency of Animal Testing For many years, the primary way to make advances in biomedical science was through experimentation on animals, also known as vivisection. This method involves using different species of animals in experiments and developmental procedures to determine toxicity, dosing, and effectiveness of test drugs before proceeding to human clinical trials. However; the use of animals in testing laboratories is becoming less common due to improved alternative options. Animal experimentation debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-15438489785834353712020-05-06T11:30:00.001-07:002020-05-06T11:30:13.496-07:00Global Environmental Issues Free Essays Global Problems ââ¬â The Environment Over time, the Earthââ¬â¢s environment has become more and more damaged and deteriorated. Because of this, it is increasingly difficult for both the animal kingdom and the human population to inhabit certain regions of the globe as desired. There are many different issues that can factor into environmental harm. We will write a custom essay sample on Global Environmental Issues or any similar topic only for you Order Now Some examples of these issues are deforestation, desertification, climate change, and pollution. A more general term used to identify these types of issues is Environmental Problems. Deforestation is a massive clearing of the Earthââ¬â¢s forests. Each year, strips of forest equivalent to the size of Panama are cut down and cleared. If these mass clearings continue at the rate they have been, all of the rain forests across the globe could cease to exist within one century. One major cause of deforestation is agriculture. When farmers need more room to plant crops, or more space to graze their livestock, they cut acres of forests down to accommodate themselves. Sometimes, small farmers clear away trees in the forest to feed their families. They do this through a process often referred to as ââ¬Å"slash and burnâ⬠agriculture. One country affected by deforestation is Brazil. Farmers often use the slash and burn agriculture method to clear away trees in the Amazon rain forest. After space is made, farmers are only able to settle for one to two years. This is because the rain forestââ¬â¢s soil does not have enough nutrients to keep the crops growing. When crops are no longer able to grow in the area, farmers move on, leaving what used to be acres upon acres of trees to be nothing but a dry and empty piece of land. Desertification is the decaying of the Earthââ¬â¢s dryland ecosystems. It is also the advancement of sand dunes on land. Each year, close to 30 million acres are lost to desertification and drought, thatââ¬â¢s about 56 acres per minute. One major cause of desertification is human interaction/humans overusing the land. Examples of how humans overuse land to the point of degradation are farming, mining, over grazing livestock, and clear-cutting. One area that is majorly affected by desertification is sub-Saharan Africa. An estimated 70% of the drylands in Africa used for agricultural purposes are being swept away by desertification. This is severely tragic for the people of sub-Saharan Africa because everything they depend on comes from their immediate surroundings. Therefore, if their farmlands are no longer useful, their food source is no longer existent. How to cite Global Environmental Issues, Essay examples Global Environmental Issues Free Essays Environmental issues are a major problem in our world, and all people need to recognize the need for our social obligations. The effect of humans on our planet has increased significantly over the years. Not only is the population constantly growing, there is ââ¬Å"new technical power to dig deeper, cut faster, build larger, and traverse more quickly great distances in automobiles, trucks, and planesâ⬠(Brown, 2001). We will write a custom essay sample on Global Environmental Issues or any similar topic only for you Order Now Severe environmental issues have appeared throughout the world as a result. It is very important that environmentalists work to educate everyone so that they can learn how to make the most effective ethical decisions in order to preserve nature. There are ethical and social obligations that the world needs to consider when it comes to environmental issues. People do not have respect for nature because they think they are superior, but everyone should learn how to live in harmony with nature and the environment. It is critical that we learn how to preserve our world in which we live. Climate change and global warming, gas emissions, population growth, and energy security are just a few of the many areas of environmental issues that we need to address in our world. All of these areas could have disastrous global consequences, and everyone should learn how to make the best decisions to try to protect the environment. ââ¬Å"The climate is changing. The earth is warming up, and there is now overwhelming scientific consensus that it is happening, and human-induced. With global warming on the increase and species and their habitats on the decrease, chances for ecosystems to adapt naturally are diminishing. Many are agreed that climate change may be one of the greatest threats facing the planetâ⬠(Anup, 2009). Global warming and climate change can be best described as an increase in average global temperatures. The increases in ââ¬Å"greenhouse gasesâ⬠such as carbon dioxide created by human activities are one of the main causes contributing to the increase of global temperatures (Anup, 2009). Many people do not understand exactly the meaning of greenhouse gases. ââ¬Å"The meaning of the greenhouse effect can be defined in these following steps: ? Energy from the sun drives the earthââ¬â¢s weather and climate, and heats the earthââ¬â¢s surface; ? In turn, the earth radiates energy back into space; ?Some atmospheric gases including water vapor, carbon dioxide, and other gases trap some of the outgoing energy, retaining heat somewhat like the glass panels of a greenhouse; ? These gases are therefore known as greenhouse gases; ?The greenhouse effect is the rise in temperature on Earth as certain gases in the atmosphere trap energy (Anup, 2009). â⬠Here is an illustration showing the increased levels of gases that affect everyone on our planet. Gas emissions can be a huge problem that we are facing in todayââ¬â¢s world. Human industrialization processes are growing at a very rapid pace. Carbon dioxide is the most significant of the greenhouse gases although it is not the strongest one (Anup, 2009). Most of the industrialized nations are responsible for the carbon dioxide emissions that can cause so much damage. The more underdeveloped countries do not contribute as much to this problem. Global warming affects us in more ways than we realize. Global warming will possibly lead to the following situations: rapid global heating, dramatic increase in greenhouse gas emissions, ozone loss, warming of the oceans, permafrost thawing, oceanic changes, massive extinction of species, and sudden collapse of biological and ecological systems may occur (Anup, 2009). The over population of the planet is also a concern for environmental ethics. The increased population helps to increase the amount of greenhouse gases, but it mainly contributes to the consumption of our worldââ¬â¢s natural resources. The more advanced countries like the United States use so many resources. Our people waste so much more than they help to conserve. ââ¬Å"Energy security is a growing concern for rich and emerging nations alike. The past drive for fossil fuel energy has led to wars, overthrow of democratically elected leaders, and puppet governments and dictatorships. â⬠There are many concerns and fears which include oil and other fossil fuel depletion, reliance on foreign sources of energy, energy demands rising from advancing developing countries such as China and India, economic efficiency versus population growth debate, and renewable and other alternative energy sources. Shah, 2009). Many people are scared that we are wasting too much of our fossil fuels. They think that if we keep going at our current rate, we will quickly use up all of our fossil fuels. People need to try to consider all of the facts so that we can make good ethical decisions. It would be very wise to invest in alternatives to fossil fuels. In the present and future, we need to work on preser ving as much as we possibly can. Currently, we are trying to find alternative fuel sources instead of using all of our oil. That is just one example of ethical decisions that we are committing to. If everyone was informed about all of the dangers so that they could better understand the issues we are facing, they might possibly make better ethical decisions in their daily lives. Concluding, everyone in our world needs to wake up and notice what is going on around them. If we want our children to have a safe place to live in this world, we need to start doing everything that we can in order to protect and preserve it. It is our moral and social obligations to make ethical decisions because our decisions affect everyone around us. Climate change and global warming, gas emissions, population growth, and energy security are just a few of the things that we need to worry about. It is our responsibility to educate ourselves on these issues so that we can implement better and safer processes to use. Working together, we can help to come up with new ideas and slow down our destruction of our environment and homes. References Anup, S. (2009, December 30). Climate Change and Global Warming. Retrieved January 17, 2010, from Global Issues: http://www. globalissues. org/issue/178/climate-change-and-global-warming Brennan, A. , Lo, Y. -S. (n. d. ). Environmental Ethics. Retrieved January 15, 2009, from The Stanford Encyclopedia of Philosophy (Winter 2009 Edition): http://plato. stanford. edu/archives/win2009/entries/ethics-environmental Brown, D. A. (2001). The Ethical Dimensions of Global Environmental Issues. Retrieved January 21, 2010, from American Academy of Arts Sciences: http://www. amacad. org/publications/fall2001/brown. aspx Ruggiero, V. R. (2008). Thinking Critically About Ethical Issues, (7th Edition). New York: McGraw-Hill. Shah, A. (2009, Novemeber 20). Energy Security. Retrieved January 16, 2010, from Global Issues: http://www. globalissues. org/artical/595/energy-security How to cite Global Environmental Issues, Papers debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-18072214820781470262020-05-06T03:53:00.001-07:002020-05-06T03:53:18.873-07:00Underworld by Symphony X free essay sample Ah yes we are back into prog territory. Symphony X is back here to be mentioned here. Symphony X is a progressive power metal band that have been around since the early 90s with albums like Divine Wings of Tragedy, Dantes Inferno and their self titled debut in the classic line up. Since albums like The Odyssey and Paradise Lost they have begun to break out much more in the metal community and have been highly respected since then and have become more mainstream with a bit of a heavier touch. Underworld is a loose concept album that pays homage to alot of their older material(The Odyssey and prior) and still have twinges of their newer albums Paradise Lost and Iconoclast withheld and is the main sound youll hear. Also Russell Allens voice is a bit cleaner here then in the previous two. While it may seem a bit simple when compared to, well, their old material, you can probably blame it on his occupation with Adrenaline Mob but that can benefit in some cases and the music is still good. We will write a custom essay sample on Underworld by Symphony X or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page From the singles Nevermore and Without You, to the epic gems To Hell and Back and Swansong, this album can be considered golden. It has a certain charm to it that is more or less unique to the other ones, but then again, every album has had a different charm to them so it really shouldnt be nothing special. But it is, if nothing else, it shows what this band can do and that they can try new things with sound or concept or both. Its whats to be expected of them and they still got it even after 20 years, try to name a band that has their old charm consistently in every one of their releases. I thought so, very few can do that, at least from my point of view, and try new things almost everytime. Ok Im gushing, lets move on. I mentioned that they have homages in this album, well, they managed to reference The Divine Wings of Tragedy in the Overture I believe, though its quite hard to notice and you got to listen closely for these references, including the one I mentioned. This has somet hing for every Symphony X fan, the ones that wanted current Symphony X have the heavyness and semi-simplicity of Paradise Lost and Iconoclast. Those that want old Symphony X have got Russells vocals, the small references and easter eggs, if you will, and songs like Without You(one of the singles). I love this album and I would be surprised if it doesnt end up on my end of year list. I give this a 9/10. I am the Grim Reaper, signing off. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-61721765049702494832020-04-30T21:23:00.001-07:002020-04-30T21:23:02.220-07:00The 1960s Happenings, Causes, And Effects Essays - The 1960s: Happenings, Causes, and Effects Many social changes that were addressed in the 1960s are still the issues being confronted today. the '60s was a decade of social and political upheaval. in spite of all the turmoil, there were some positive results: the civil rights revolution, john f. Kennedy's bold vision of a new frontier, and the breathtaking advances in space, helped bring about progress and prosperity. however, much was negative: student and anti-war protest movements, political assassinations, and ghetto riots excited american people and resulted in lack of respect for authority and the law. The decade began under the shadow of the cold war with the soviet union, which was aggravated by the u-2 incident, the berlin wall, and the cuban missile crisis, along with the space race with the ussr. The decade ended under the shadow of the viet nam war, which deeply divided americans and their allies and damaged the country's self-confidence and sense of purpose. Even if you weren't alive during the '60s, you know what they meant when they said, "tune in, turn on, drop out." you know why the nation celebrates Martin luther king, jr.'s birthday. all of the social issues are reflected in today's society: the civil rights movement, the student movement, space exploration, the sexual revolution, the environment, medicine and health, and fun and fashion. The Civil Rights Movement The momentum of the previous decade's civil rights gains led by rev. Martin luther king, jr. carried over into the 1960s. but for most blacks, the tangible results were minimal. only a minuscule percentage of black children actually attended integrated schools, and in the south, "jim crow" practices barred blacks from jobs and public places. New groups and goals were formed, new tactics devised, to push forward for full equality. as often as not, white resistance resulted in violence. this violence spilled across tv screens nationwide. the average, neutral american, after seeing his/her tv screen, turned into a civil rights supporter. Black unity and white support continued to grow. in 1962, with the first large-scale public protest against racial discrimination, rev. Martin luther king, jr. Gave a dramatic and inspirational speech in washington, d.c. After a long march of thousands to the capital. the possibility of riot and bloodshed was always there, but the marchers took that chance so that they could accept the responsibilities of first class citizens. "the negro," King said in this speech, "lives on a lonely island of poverty in the midst of a vast ocean of material prosperity and finds himself an exile in his own land." King continued stolidly: "it would be fatal for the nation to overlook the urgency of the moment and to underestimate the determination of the negro. this sweltering summer of the negro's legitimate discontent will not pass until there is an invigorating autumn of freedom and equality." when King came to the end of his prepared text, he swept right on into an exhibition of impromptu oratory that was catching, dramatic, and inspirational. "I have a dream," King cried out. the crowd began cheering, but king, never pausing, brought silence as he continued, "i have a dream that one day on the red hills of georgia the sons of former slaves and the sons of former slaveowners will be able to sit down together at the table of brotherhood." "I have a dream," he went on, relentlessly shouting down the thunderous swell of applause, "that even the state of mississippi, a state sweltering with people's injustices, sweltering with the heat of oppression, will be transformed into an oasis of freedom and justice. i have dream," cried King for the last time, "that my four little children will one day live in a nation where they will not be judged by the color of their skin but by the content of their character." Everyone agreed the march was a success and they wanted action now! but, now! remained a long way off. president kennedy was never able to mobilize sufficient support to pass a civil rights bill with teeth over the opposition of segregationist southern members of congress. but after his assassination, president johnson, drawing on the kennedy legacy and on the press coverage of civil rights marches and protests, succeeded where kennedy had failed. However, by the summer of 1964, the black revolution had created its own crisis of disappointed expectations. rioting by urban blacks was to be a feature of every "long, hot, summer" of the mid-1960s. In 1965, King and other black leaders wanted to push debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-31046114691468394072020-03-21T13:07:00.001-07:002020-03-21T13:07:03.644-07:00Free Essays on Construction EquipmentKomatsu is one of the worldââ¬â¢s largest manufacturers of construction machines. In this paper I will discuss five different categories and a total of twenty different machines that Komatsu produces. I will include, articulated dump truck, backhoe loaders, crawler carriers, crawler dozers and motor graders. Articulated Dump Truck The articulated dump truck is a six-wheeled dump truck that is equipped with a fully hydraulic articulated steering system. This allows the truck to pivot between the cab and the body of the truck. The Komatsu HM400-1 articulated dump truck is one example. This truck is used to haul up to 29 cubic yards of material over the roughest of terrains. It is especially useful in mining operations to haul the product away. The HM400-1 has many user-friendly features, which include a wide, spacious cab that allows the operator work in a comfortable environment. The cab can also be tilted rearward to provide easy service to the engine. It is equipped with a turbocharged high performance and environmentally friendly Komatsu SAA6D140E-3 engine that meets North American EPA tier 2 emission regulations for 2001. It is a six cylinder, 444 horsepower, water-cooled 4-cycle engine with 1,508 foot-pounds of torque. The transmission is a fully automatic, countershaft type, with six speeds forward and two reverses. It has an electronic shift control with automatic clutch modulation in all gears. This truck can reach a maximum speed of 36.4 mile per hour. The axles are full time all wheel drive. They also come with 100% differential lock in all three axles with a gear ratio of 3.417:1. The hydro pneumatic suspension system of the HM400-1 ensures a comfortable ride even over rough terrain. The rear suspension is a combination hydro pneumatic and rubber suspension system. The steering system is the most unique feature on all articulated dump trucks. The HM400-1 uses an articulated type, fully hydraulic power steering syste... Free Essays on Construction Equipment Free Essays on Construction Equipment Komatsu is one of the worldââ¬â¢s largest manufacturers of construction machines. In this paper I will discuss five different categories and a total of twenty different machines that Komatsu produces. I will include, articulated dump truck, backhoe loaders, crawler carriers, crawler dozers and motor graders. Articulated Dump Truck The articulated dump truck is a six-wheeled dump truck that is equipped with a fully hydraulic articulated steering system. This allows the truck to pivot between the cab and the body of the truck. The Komatsu HM400-1 articulated dump truck is one example. This truck is used to haul up to 29 cubic yards of material over the roughest of terrains. It is especially useful in mining operations to haul the product away. The HM400-1 has many user-friendly features, which include a wide, spacious cab that allows the operator work in a comfortable environment. The cab can also be tilted rearward to provide easy service to the engine. It is equipped with a turbocharged high performance and environmentally friendly Komatsu SAA6D140E-3 engine that meets North American EPA tier 2 emission regulations for 2001. It is a six cylinder, 444 horsepower, water-cooled 4-cycle engine with 1,508 foot-pounds of torque. The transmission is a fully automatic, countershaft type, with six speeds forward and two reverses. It has an electronic shift control with automatic clutch modulation in all gears. This truck can reach a maximum speed of 36.4 mile per hour. The axles are full time all wheel drive. They also come with 100% differential lock in all three axles with a gear ratio of 3.417:1. The hydro pneumatic suspension system of the HM400-1 ensures a comfortable ride even over rough terrain. The rear suspension is a combination hydro pneumatic and rubber suspension system. The steering system is the most unique feature on all articulated dump trucks. The HM400-1 uses an articulated type, fully hydraulic power steering syste... debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-23592805326971863102020-03-05T03:34:00.001-08:002020-03-05T03:34:02.708-08:00Sten Gun in World War IISten Gun in World War II The Sten submachine gun was a weapon developed for use by British and Commonwealth forces during World War II. It takes its name from the last names of its designers, Major Reginald V. Shepherd and Harold J. Turpin, and Enfield. Intended to be simple to build, the Sten was employed across all theaters of the conflict and was retained by many militaries for several decades after the war. The Sten also saw extensive use by resistance groups in Europe during the conflict and its easy to construct design permitted some to produce their own variations. Development During the early days of World War II, the British Army purchased large numbers of Thompson submachine guns from the United States under Lend-Lease. As American factories were operating at peacetime levels, they were unable to meet the British demand for the weapon. Following their defeat on the Continent and the Dunkirk Evacuation, the British Army found itself short on weapons with which to defend Britain. As sufficient numbers of Thompsons were unavailable, efforts moved forward to design a new submachine gun that could be built simply and cheaply. This new project was led by Major Reginald V. Shepherd, OBE of The Royal Arsenal, Woolwich, and Harold John Turpin of the Design Department of the Royal Small Arms Factory, Enfield. Drawing inspiration from the Royal Navys Lanchester submachine gun and the German MP40, the two men created the STEN. The weapons name was formed by using Shepherd and Turpins initials and combining them with EN for Enfield. The action for their new submachine gun was a blowback open bolt in which the movement of the bolt loaded and fired the round as well as re-cocked the weapon. Design Problems Due to the need to quickly manufacture the Sten, construction consisted of a variety of simple stamped parts and minimal welding. Some variants of the Sten could be produced in as few as five hours and contained only 47 parts. An austere weapon, the Sten consisted of a metal barrel with a metal loop or tube for a stock. Ammunition was contained in a 32-round magazine which extended horizontally from the gun. In an effort facilitate use of captured 9 mm German ammunition, the Stens magazine was a direct copy of one used by the MP40. This proved problematic as the German design utilized a double column, single feed system that led to frequent jamming. Further contributing to this issue was the long slot along the side of the Sten for the cocking knob which also allowed debris to enter the firing mechanism. Due to the speed of the weapons design and construction it contained only basic safety features. The lack of these led to the Sten having a high rate of accidental discharge when hit or dropped. Efforts were made in later variants to correct this problem and install additional safeties. Sten Gun Cartridge: 9 x 19mm ParabellumCapacity: 32-round detachable box magazineMuzzle Velocity: 1,198 ft./sec.Weight: approx. 7.1 lbs.Length: 29.9 in.Barrel Length: 7.7 in.Rate of Fire: 500-600 rounds per minuteSights: Fixed peep rear, post frontAction: Blowback-operated, open bolt Variants The Sten Mk I entered service in 1941 and possessed a flash hider, refined finish, and wooden foregrip and stock. Approximately 100,000 were produced before factories switched to the simpler Mk II. This type saw the elimination of the flash hider and hand grip, while possessing a removable barrel and shorter barrel sleeve. A rough weapon, over 2 million Sten Mk IIs were built making it the most numerous type. As the threat of invasion eased and production pressure relaxed, the Sten was upgraded and built to a higher quality. While the Mk III saw mechanical upgrades, the Mk V proved to be the definitive wartime model. Woman worker poses with finished Sten submachinegun, 1942. Library and Archives Canada Essentially a Mk II built to a higher quality, the Mk V included a wooden pistol grip, foregrip (some models), and stock as well as a bayonet mount. The weapons sights were also upgraded and its overall manufacture proved more reliable. A variant with an integral suppressor, dubbed the Mk VIS, was also built at the request of the Special Operation Executive. On par with the German MP40 and U.S. M3, the Sten suffered the same problem as its peers in that its use of 9 mm pistol ammunition severely restricted accuracy and limited its effective range to approximately 100 yards. An Effective Weapon Despite its issues, the Sten proved an effective weapon in the field as it dramatically increased the short-range firepower of any infantry unit. Its simplistic design also allowed it to fire without lubrication which reduced maintenance as well as made it ideal for campaigns in desert regions where oil could attract sand. Used extensively by British Commonwealth forces in Northern Africa and Northwest Europe, the Sten became one of the iconic British infantry weapons of the conflict. Both loved and hated by troops in the field, it earned the nicknames Stench Gun and Plumbers Nightmare. American officer and French partisan with a Sten crouch behind an auto during a street fight in a French city, 1944. National Archives and Records Administration The Stens basic construction and ease of repair made it ideal for use with Resistance forces in Europe. Thousands of Stens were dropped to Resistance units across occupied Europe. In some nations, such as Norway, Denmark, and Poland, domestic production of Stens began in clandestine workshops. In the final days of World War II, Germany adapted a modified version of the Sten, the MP 3008, for use with its Volkssturm militias. Following the war, the Sten was retained by the British Army until the 1960s when it was fully replaced by the Sterling SMG. Other Users Produced in large numbers, the Sten saw use around the world after World War II. The type was fielded by both sides of the 1948 Arab-Israeli War. Due to its simple construction, it was one of the few weapons that could be produced domestically by Israel at that time. The Sten was also fielded by both the Nationalists and Communists during the Chinese Civil War. One of the last large-scale combat uses of the Sten occurred during the 1971 Indo-Pakistani War. On a more notorious note, a Sten was used in the assassination of Indian Prime Minister Indira Gandhi in 1984. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-17281420377788783102020-02-17T18:59:00.001-08:002020-02-17T18:59:03.235-08:00Business Decision Making Essay Example | Topics and Well Written Essays - 1000 wordsBusiness Decision Making - Essay Example It has done extensive market analysis and has been able to put measures of probability on the happening of each of the outcomes. However, these are subjective estimates as there is no past data to rely on. What decision the management of MPL finally takes depends a lot on whether they are risk-averse, risk-neutral or risk-loving. That would decide whether they opt for Maximax, Maximin or Minimax course of action (Jones 2004). Effectiveness of Decision Making Structure Decision making by a business organization is largely dependent on the structure of the decision making body. In a sole proprietorship organization, all decisions are taken by a single person. Hence, the entire decision making process is fast without any time consuming meetings and exchange of opinions. But, such decisions could also be incorrect at times as there are usually no inputs from other people. However, in organizations that have more than one owner, decision making is done through interactions between managin g partners and quite obviously decision making takes a far longer time than it takes in single owner scenarios. But, one must realize that though it is more time consuming, any decision making process that involves more than one person is better than a single person taking decisions. This is simply because while such decisions are taken, several, often differing, perspectives are considered and this aids in arriving at a more balanced decision (Cyert and March 1992). In case of MPL the decision making process is fairly inclusive and democratic in nature. Other than Lee Corbusier and Frank Lloyd, managers of three separate divisions meet once every month to discuss company strategy, market trends and receive departmental reports. This allows managers to micromanage their individual... The author begins with the description of the decision-making model of the company. The author thinks that decision-making by a business organization is largely dependent on the structure of the decision-making body. In a sole proprietorship organization, all decisions are taken by a single person. Hence, the entire decision-making process is fast without any time-consuming meetings and exchange of opinions. But, such decisions could also be incorrect at times as there are usually no inputs from other people. However, in organizations that have more than one owner, decision making is done through interactions between managing partners and quite obviously decision making takes a far longer time than it takes in single owner scenarios. But, one must realize that though it is more time consuming, any decision-making process that involves more than one person is better than a single person taking decisions. This is simply because while such decisions are taken, several, often differing, perspectives are considered and this aids in arriving at a more balanced decision (Cyert and March 1992). In the case of MPL, the decision-making process is fairly inclusive and democratic in nature. Other than Lee Corbusier and Frank Lloyd, managers of three separate divisions meet once every month to discuss company strategy, market trends and receive departmental reports. This allows managers to micromanage their individual departments while corporate decisions are taken by the management team. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-34320133211593621642020-02-03T11:50:00.001-08:002020-02-03T11:50:02.375-08:00The Use of Multi-word Units (MWU) Essay Example | Topics and Well Written Essays - 750 wordsThe Use of Multi-word Units (MWU) - Essay Example I will employ key sequence analysis to reveal the significantly overused or underused MWUs by Taiwanese learners. In addition, this analysis will explore the extent to which use of MWUs developed over time. Time in consideration is the one-year intercultural exposure of Taiwanese with their British peers. The aim is to analyze the MWUs used by Taiwanese students to examine their approximation to those sequences used by native speakers of English. Previous section proved that use of MWUs is often linked to particular conditions of use. It also established three central functions of communication could be achieved: social interaction, necessary topics, and discourse devices (see Biber et al., 2004; Nattinger & DeCarrico, 1992; Schmitt & Carter, 2004; Wray & Perkins, 2000). Nevertheless, it is evident that the use of MWUs in different communication modes is different with reference to the functional types, as shown in Table 12 and Figure 1. Concerning MWUs for social interaction, they are extremely common across different datasets. In this study, large amount of conventionalized language is typically attached to them for different speech acts in social interaction. For instance thanks for the to express politeness, it would be to comply with a request, I canââ¬â¢t wait to express personal intension, would you like to provide an offer and an amount of other related usage. Moreover, an increase of the use of MWUs for social interaction can be observed in online communication (BATICC-O) to face-to-face interaction (BATICC-F), occupying approximately 38%, and 54% of the top 50 MWUs respectively. It is likely that the young learners focused more on social interaction when they meet face-to-face. On the other hand, in online communication they focus on number of topics related to the two different languages, cultures and countries. About MWUs serving the function of necessary topics, it can be seen from Table 12 that overall they are particularly common in online debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-30352856180259773102020-01-26T08:14:00.001-08:002020-01-26T08:14:05.392-08:00The Uses And Misuses Of Derivatives Finance EssayThe Uses And Misuses Of Derivatives Finance Essay Hedge funds are pools of investment that invest in almost any opportunity in any market where they foresee impressive gains at reduced risk. Hedging refers to implementing strategies that manage or protect against an identified risk exposure. They take leveraged positions in publically traded equity, debt, foreign exchange and derivatives. The primary aim of most hedge funds is to reduce volatility and risk while attempting to preserve capital and deliver positive returns under all market conditions (Friedland., 2008). Derivatives provide institutions the opportunity to break financial risks into smaller components and then to buy or sell those components to manage risk. Hedge funds hold a number of assets; they use derivatives to protect against the adverse price movement of these assets. Hedge funds play more of the role of speculators than of hedgers. They use derivatives when buying and selling assets and by putting long-short positions, they seek to hedge themselves against broad market moves while profiting from changes in the relative value of the instruments they go long or short. Hedge funds offer a variety of unique strategies to utilize when investing in hedge funds, these are called hedging techniques. These include Market Neutral Strategies, Event Drive / Special Situations Strategies, Long Short, Global Macro, Sector and Country, Dynamic Strategies, Funds of Funds, Funds of Funds of Funds etc. (http://www.global-derivatives.com) Market Neutral Strategies are used in Market Neutral Funds. They tend to take positions which offset each other through both a long and short position simultaneously to reduce their risk exposure. These strategies include Long Short and Convertible Arbitrage. Long-Short methodology attempts to reduce market risk by taking both long and short positions in the market. This can be done by taking a long position in undervalued assed and a short position in overvalued ones. In these funds, it is anticipated that the undervalued assets will increase in value than any losses incurred from the overvalued assets, or vice versa. Convertible arbitrage is a relatively more complex strategy. In this convertible securities such as convertible bonds which can be converted into normal shares or bonds are bought, to take advantage of any price discrepancies between the convertible security and that of the exchangeable underlying. A position can be taken for buying convertible security or selling the underlying asset to realise any difference in prices. (http://www.global-derivatives.com) Event Driven / Special Situations Strategies intend to make profit from events related to particular companies. Event Driven funds take a bet that something in the future will happen which will affect the company and its assets in a particular way. These funds include Distressed Securities and Merger/ Risk Arbitrage; these securities include debt and equity of companies undergoing reorganization or bankruptcy, it is hoped that companies will recover and increase in value. These securities have very low value and can be given to the management of a company during the restructuring process. Merger/Risk Arbitrage funds tend to analyze companies which are potential takeover or merger targets by taking two positions. An example of it would be to buy the stocks of a company that is being acquired with hope that its prices will rise and to sell stocks of the company that is acquiring, in anticipation that its value might fall. (http://www.global-derivatives.com) Long Short is another strategy which includes buying and selling a security based on the sentiments in the market or of a company. It includes short selling, long, and growth fund. Short selling occurs when a person anticipates that the price will fall in future and sells a stock which it does not possess, through borrowing. If the price really falls in future, they buy the lot from the market at a lower price and return it to the one they borrowed from earlier at lower price, thus making a profit. Long is another strategy in hedge funds, it is a fixed income instrument that benefits from the rise in the price of the held asset. They often utilize leveraged positions to maximize returns. Global Macro is an economics based strategy which intends to benefit from shifts in global economic conditions such as inflation, interest rates and other macro-economic factors; a common example of it is the use of interest rate derivatives for speculative purposes, they give profit from economic movements within particular countries. Sector and Country strategies include sector funds and emerging markets. Sector funds are hedge funds that specialize within a particular industry for example technology, textile etc. these investments consist of long or short positions in stock, debt, or even derivatives on the stocks. Emerging markets include funds that emphasize on emerging markets with less-developed economies and aim to profit from market growth which influence the securities positively. Securities in these hedge funds include sovereign debt or corporate securities with the anticipation that their prices will rise with economic growth. Dynamic strategies include elements such as market timings and opportunistic. Strategy of market timing involves the right timing of the market. It includes making profit based on the correct timing of investments across markets by moving between various asset classes depending upon the view of the manager regarding the market environment. Opportunistic strategy involves switching across asset classes, they use a number of strategies mentioned above depending upon the managers discretion, and the reason for switching strategies is to make the most profit. (http://www.global-derivatives.com) Funds of funds is the strategy of hedge funds to invest in other hedge funds in order to diversify the risk and exposure. The success of these funds depends upon the managers way of handling the funds rather than the performance of the actual investments. Funds of funds of funds or F3s is a new concept to hedge the risk exposure in terms of investments by reducing the volatility of the funds itself. They are good for high risk-averse investors willing to invest in the hedge funds industry. (http://www.global-derivatives.com) Amaranth Advisors LLC (Amaranth) Formation and Background Amaranth comprises of Amaranth LLC and Amaranth Advisors LLC. It was founded by Nick Maounis (Maounis) in 2000 as a multi-strategy hedge fund with a special focus on convertible arbitrage (selling (short) equity stocks and at the same time buying (long) convertibles of the same company creating a delta neutral portfolio), with its headquarter in Greenwich, Connecticut and with approximately $600 million in capital. Maounis experience was in managing a number of various arbitrage accounts in the US, Japan, Europe and Canada. The aim was to make profits from the small discrepancies in prices of stocks and bonds, through its structure of three principal funds Amaranth Partners LLC, Amaranth Capital Partners LLC, and Amaranth International Limited and the 27 investment professionals. It sought to employ a group of arbitrage trading strategies particularly featuring convertible bonds, stocks of merging companies and utilities. However, Over the years, the trading activity of Amaranth ex panded into merger arbitrage (making a riskless profit by purchasing individual stocks of two merging companies and selling them together), leveraged loans (loans given/extended to individuals or companies that already have large debts on their books), blank-check companies (developing companies) ,volatility trading arbitrage (buying or selling an option on an underlying instrument and selling or buying a varying percentage of the underlying instrument this to gain from the difference between the implied volatility of an option and forecasted future probable volatility of the corresponding underlying instrument), long/short equity, and energy trading. (ICMR, 2010) Strategy As noted above, at the time of formations and throughout its term, the firm emphasized that it was a multi-strategy hedge fund, but as it could be noted in the aftermaths that most of the firms investments and losses were in natural gas derivatives. Amaranths basic strategy comprised of trading in the Natural Gas market; the firm took a long position in winters, with hope that the prices will rise, especially when the demand for natural gas exceeds the supply and storage capacity due to the cold season. Its winter months were November, December, January, February and March. Amaranth used to take a short position in summers when it anticipated that the prices will fall. Part of its strategy also included taking short position in April and long position in March. Moreover, another strategy was to purchase call options on winter months and put options on non-winter months. Amaranth used to bet that natural gas prices will rise, and the spreads in March and April prices will rise as well. Nature of Natural Gas Market By nature, the natural gas market is very risky and volatile. Majorly because there is a commercial need for the commodity. This situation creates a need for an institution to control its supply and storage. In America, there has been inadequate storage capacity of natural gas for peak the winter season demand. Therefore the price of natural gas is higher in winters; firstly due high demand and secondly due to increase the incentives to store natural gas. These factors raise the prices of winter natural gas contracts to an all time high level. Apart from that, the market of natural gas is also volatile because the natural gas production in America is lower than the rise in the demand for natural gas. U.S. Natural Gas markets are shielded from the global energy factors because a very small amount of US natural gas need are met by imports of Liquid Natural Gas (LNG). Commodities trades require less margin money (collateral) than other markets. On the main exchanges, trades post 10 percent of their positions value, whereas in the stock market, 50 percent is common. (Davis, Sender, Zuckerman, 2006). After gaining credit from banks, it is very easy for commodity hedge funds to get highly leveraged quickly. Traders of natural gas have a number of options. The largest exchange for trading natural gas is the NYMEX (New York Mercantile Exchange) which has standardized futures contracts up to few delivery months up to 5 years that are traded on the exchange. Traders can also use ICE (Intercontinental Exchange) which is an over-the-counter market for trading natural gas futures contracts. There has been a lot of debate if hedge funds have an impact on energy trading. According to Gary Gensler (a former Goldman Sachs banker and treasury department official and chairman of the Commodity Futures and Trading Commission (CFTC) the chief regulator for energy futures energy trading said I believe that excessive speculation in commodity futures can cause sudden or unreasonable fluctuations or unwarranted changes in commodity prices,. He also expressed his opinion that the rapid growth of commodity index funds and increased hedge fund allocation to commodity assets contributed to the bubble in commodity prices. (Delamaide, Jan 11, 2010) Performance The founders original expertise was in convertible bonds (Till, 2006). The firm later specialized in leveraged loans, blank-check companies and in energy trading. Till June 30th 2006, energy trades accounted for about half of the funds capital and generated about 75% of their profits. (Till, 2006) In 2002 Amaranth started trading with JP Morgan Chase, in energy commodity trading. The winters of 2003 were exceptionally cold and lasted till February, this raised the prices of natural gas manifolds, and this in turn gave huge profits to Amaranth due to its long position in winters. By 2004-5 Amaranth shifted most of its investments into energy trading. The company used to make huge profits from placing spread trades and placing bullish bets on energy in 2005. In the same year America was severely hit by Hurricane Katrina, which adversely impacted it natural gas and oil production and refining capacity. This raised the price of natural gas and Amaranth reaped huge profits out of it. The accounts of Amaranth LLC showed robust performance by the company since its inception. The compound annual return for the period September 2000-November 2005 according to media reports was 14.72 net of all costs. (Gupta Kazemi) The chart below shows Amaranths returns till May 2005. The chart compares the Amaranths returns against CISDM Equal Weighted Hedge Fund Index and CISDM Convertible Arbitrage Index. Amaranth had gained a noteworthy position in May 2005, in CISDM Equal Weighted Hedge Fund Index. The chart show the volatility Amaranth was facing in May 2005, this volatility had brought high returns in the past but things then started taking the turn towards the wrong side. Amaranths returns; source: (Gupta Kazemi) NYMEX (New York Mercantile Exchange) noticed Amaranths considerable open interest of 51% in Aug 2006 in September natural gas futures contract, which would expire at the end of the month. NYMEX (New York Mercantile Exchange) brought its concerns into notice to Amaranth. Amaranth not only reduced their September but also Octobers positions, as per the directions of NYMEX (New York Mercantile Exchange). Alongside Amaranth increased their positions in October and September positions under ICE contracts, thus escalating their overall positions in natural gas. (Gupta Kazemi) According to US Securities and Exchange Commission filings, investors in Amaranths funds included a number of Wall Street banks including Morgan Stanley, Credit Suisse Group and Deutsche Bank AG. (Burton Leising, 2006) Amaranth was marketing energy and commodities fund to open in December 2006 of about $5 billion. The fund was to be managed by Hunter and Jeff Baired, co-head of Amaranths Global energy and commodities business. But unfortunately the events that followed didnt allow it to happen. (Burton Leising, 2006) Collapse and Beyond Amaranth used to bet that natural gas prices will rise, and the spreads in March and April prices will rise as well. However in 2006, so did not happen and gas prices began to decline due to rising inventories leaving Amaranth on the wrong side of the market trend and consequently reducing its portfolio value of $9.2 billion by less than half. Headed by Brian Hunter, it seemed that Amaranth had not anticipated the rise in the natural gas storage capacity, and the weather pattern bringing a warmer winter. It was in a weeks time that Amaranth lost 65% of its $9.2 billion assets. On September 14 alone, the fund lost $681 million from its natural gas exposure. On September 20th 2006, Amaranth sold its entire energy trading portfolio in a flurry to J.P. Morgan Chase and Citadel Investment Group. It did so at significant discounts to the portfolios then mark-to-market value. (Till, 2006) At the time of liquidation of Amaranth, the spread on gas future declined. The spread on positions held by Amaranth were $2.85 in late August, but after the liquidation had reached below $0.75. (MORGENSON ANDERSON, September 20, 2006). This indicates the lower price expectations in both the bid and ask price for every $1 invested in Amaranths holdings. When Amaranth Advisors LLC announced that it had suffered losses just as big as LTCMs, markets did not respond for Amaranth the way as they did for LTCM (Long Term Capital Management). New York Fed did not hold summit meeting for a bailout plan; but JP. Morgan Co. and Merrill Lynch Co started selling off Amaranths portfolio of natural gas futures. The co-founder of Energy Hedge Fund Centre (which tracks 520 energy funds) said, There is not systematic risk. The market can absorb this. (Mufson, 2006). The reasons for such a reaction were that, firstly Amaranth (although was doing rash trading) but borrowed less heavily and had less leverage than LTCM (Long Term Capital Management); secondly its positions were smaller and focused in natural gas futures. LTCM s failure threatened the stability of banks, whereas Amaranths failure only hurt imprudent investors in the natural gas market who hadnt done any research before investing. Amaranths co-founder and chief executive, Nicholas Maounis, said in his letter to investors that the fund was aggressively reducing our natural gas exposure to meet payments to creditors. The said that there was large scale fluctuations in the value of the fund, which was up sharply in August, would be down 35 percent for the year after the sell-off. Later Maounis said that the conditions in the natural gas market deteriorated and market liquidity dried up so quickly that the fund was unable to unwind its energy positions. He said it became clear that we couldnt trade out of it. Amaranth had no choice but to sell its positions at a huge loss because the fund was faced with margin calls and couldnt borrow anymore because of the liquidity problem that emerged once news of its losses hit the market. Maounis apologized to the institutional investors, pension funds and wealthy individuals who lost money as a result of the bad trades. He said We feel bad about losing our money. We feel even worse about losing your money. (CBC-News, 2006) Officially at Amaranth desperately tried to sell the fund to Citigroup. But despite the extensive talks and negotiations, Citigroup decided to walk away from making any deal. (Taulli, Sep 29th 2006 ) On July 25, 2007, the Commodity Futures Trading Commission (CFTC) charged Amaranth and head energy trader Brian Hunter with Attempted Manipulation of the Price of Natural Gas Futures including making false statements to the New York Mercantile Exchange (NYMEX). The Federal Energy Regulatory Commission has also charged Amaranth and its traders with market manipulation. Amaranth filed a lawsuit against JP Morgan claiming US$ 1 billion in damages, on the grounds that the bank interfered in the companys work to make a deal with Goldman Sachs and Citadel Investments. The Federal Energy Regulatory Commission (FERC) later announced a settlement with Amaranths defendants. However Commodity Futures Trading Commission (CFTC) did not withdraw its charges on Amaranth and on August 12, 2009, the federal court ordered Amaranth to pay a $7.5 million civil monetary penalty. The court also enjoins Amaranth from violating the anti-manipulation provisions of the Commodity Exchange Act. (Release, 2009) Amaranth then sued Touradji and his employees (Touradji Capital Management LP), by filing a complaint on September 18, 2006 in New York Supreme court in Manhattan, seeking at least $350 million for claims including breach of contract and misappropriation of trade secrets. Amaranth says that Touradji Capital Management LP breached two contracts agreed to in September 2006 regarding the transfer and purchase of Amaranths base-metals portfolio. According to the official documents, Touradji Capital Management LP used the information to recover profits obtained by defendants through improper trading practices and misuse of plaintiffs propriety and confidential information. Maounis, through a spokesman, refused to comment on the Touradji Capital Management LP suit (Chanjaroen, 2006). However in September 2009, Amaranth withdrew the summon it filed against Touradji Capital Management. Neither of the parties made a payment of any kind due to the withdrawal of notice. After the fall of Amaranth, Goldman Sachs was quick to come into action, and struck a deal to take over hedge fund manager of Amaranth Advisor LLCs lease at Greenwich America. Goldman occupied about 124,000 square feet at the property, which had served at Amaranths headquarters before the company was wound up in September. Amaranths lease was to expire in at the end of 2015 and had a rate of about $35 per square foot. (Ambroz, April 10, 2007) Internal control or Management of Amaranth Maouniss original expertise was in convertible bonds. In mid 2004 Maounis hired Brian Hunter (Hunter) an energy trader who was working for Deutshe Bank energy trading desk. Calgary-based Hunter was Amaranths head energy trader, who was given a free hand to trade the commodity market, due to his past experience of taking huge positions and making huge profits in the natural gas market. Maounis was impressed that Hunters made hundreds of millions of dollars (around 1 billion) for the firm in 2005 after Hurricane Katrina sent natural gas prices soaring, made the 32-year-old Canadian a co-head of commodities trading. Maounis let Hunter increase the size of his natural gas positions so that they became more than half of the entire firms exposure. This was against Amaranths claim of maintaining a multi-strategy fund. Before Hunters arrival, all commodities positions made up about 20 percent of Amaranths portfolio with natural gas having roughly 7 percent share. Amaranths partners had a confidence built on past success and they thought that they had a fool-proof strategy (taking long position in winters and short in summers); the company had reaped huge profits in 2002-2005 from this strategy. Amaranths website said moving nimbly and effectively within an ever-changing investment landscape and said that its employees possess fearlessness with respect to complexity, learning, as well as invention, and continuously strive for perfection. Maounis, said he had chosen the companys name, which means unfading in Greek. According to the wall street journal, Brian Hunters had so much success in trading natural gas futures, or bets, on the future prices of the commodity, that Amaranth allowed him to work from his home in Calgary, where he drove a Ferrari in summer and a Bentley in winters. (Hedge fund: a gamble too far, 2006, September 20). Analysts estimate that in order to fund his positions, Hunter was borrowing $8 for every $1 of Amaranths own funds. When the bet went in his favour, he could pay back the debt and keep the rest of the profit for Amaranth. As the bets started to go against him September 2006, his borrowing amplified his losses. (Hedge fund: a gamble too far, 2006, September 20). It is commonly believed that hedge funds improve the efficiency of the financial markets by introducing liquidity and innovation (Hedge fund: a gamble too far, 2006, September 20). However Amaranths collapse shows that the hedge fund managers earn for their lavish salaries only and not for the investors who have put up their earnings and savings in their funds. Operational risk is the risk associated with the internal management of the company and the probability of making wrong decisions that might harm the performance of the firm. Amaranth seemed to be suffering highly from operational risk. Hunters had a target of making $2 billion for the year at the end of August 2006. Analysts comment of such a target that Hunters must have had an unconsciously large position for this market, One of the biggest players in the energy markets, such as Goldman Sachs Group, would take up positions less than a tenth as big as Hunters, traders said. Hunter was involved in rash trading in the market as his positions were often twice as big as the next biggest. It is also said that in Amaranth, there was an exclusive risk manager for every trading book, who sat with the risk takers on the trading desk. (http://www.icmrindia.org/casestudies/catalogue/Finance/Collapse-Amaranth%20Advisors-Case%20Studies.htm#Risk_Management)The risk managers were well qualified and had advance degrees. Paul Touradji, founder and managing partner of Touradji Capital Management, said was obvious about risk control and not about commodities. Touradji admitted that he exited the natural gas market for a year because Amaranth had entered the market, comparing its presence with that of well-financed poker player sitting down with poorer players and making big bets. I cant think of a right counterstrategy other than to say, I am going to be at the bar until youre done, Touradji said. (http://www.hedgefundintelligence.com/Event.aspx?ProductID=7035ElementID=4983, 2006) Problems Diversification is the key element of all investment portfolios. It reduces the unsystematic risk of instability in any part of the economy. Amaranth specialized in the natural gas industry so much that it failed to realise that if it took any incorrect venture at any point in time, it would not have to face severe consequences. This is counted as a factor of poor risk management. One of the biggest issues with hedge funds is that there is lack of transparency for investors and they have no idea as to what the fund is doing with their money. Most hedge funds make money with the performance fees that are generated when the fund achieves larger gains; the bigger the gains the larger the fees for the hedge funds. If the funds stays still or falls, the performance fee is exactly the same. This type of fee structure can force hedge fund traders to implement exceedingly risky strategies. Much of the blame for what happened to Amaranth is being put on Brian Hunters, although he had a strategy, experience and understanding in the natural gas market; which worked well with various weather shocks, but the fund manager failed to take into account the rise in storage capacity of natural gas. The arrival of a relatively warm winter did not raise the demand of natural gas as much as in the previous years. These factors did not increase the price of natural gas as much, thus creating problems for Amaranth which has a long position. Amaranth was operating on a high leverage. As told earlier, Amaranth was operating on an 8:1 of debt to equity ratio. This amplified the credit problems for Amaranth because once it started facing liquidity problems; it ran out of cash to maintain its cash flows. After its collapse but before liquidating, Amaranth placed restrictions on its investors to withdraw holdings of cash. That is, they were allowed to withdraw for certain number of days but were required to submit the amount before the end of the term because inability to do so resulted in a penalty. Investors were not allowed their savings beyond 7.5% of their savings. (MORGENSON ANDERSON, September 20, 2006). The bankruptcy of funds causes damage to a number of individuals and companies that have their stake with them. In the Case of Amaranth, Morgan Stanley, invested $126 million, or about 5 percent, of its $2.3 billion funds of hedge funds in Amaranth. Even New York Fed Governor Timothy F. Geithner warned that hedge fund failures could hurt market participants other than those investors and lenders who have chosen to do business directly with those funds. (Mufson, 2006). This is because the instability created in the market (because of the bankruptcy of the company and the loss of a lot of people) can result in a systemic risk, which influences other sectors as well. It is commonly said that Amaranths systems did not measure risks correctly and did not take steps that would reduce the risk. The risk models that were employed by hedge funds use historic data, but the natural gas markets in 2006 were more volatile than any other year since 2001, making models less useful. A managing director of Lyster Watson Co, an advisory firm that invests in hedge funds for clients but not with Amaranth said, It was a total failure of risk control to put your entire business at risk and not seem to know it. They were more leveraged than they realised. (Davis, Sender, Zuckerman, 2006). Lessons to be learnt Derivatives as we know are risky sources of investments, and there a number of lessons that one can learn from the incident of Amaranth. Before making an investment (esp. in sector fund) it is important to analyze the performance of the sector relating to the profits and losses, during the past few years. A monthly sector analysis reveals that a -24% monthly loss is normal and the monthly volatility of the energy strategies was around 12% (Till, 2006), therefore due consideration should be made by investors before investing in such an industry. The second factor that fund managers should consider is of marketability or liquidity, which is the ease with which the contracts can be sold into the market again. The exchange traded futures market of natural gas contracts is way smaller than the over-the-counter natural gas positions. This should put the question in investors minds that in case the market of natural gas declines so how will they sell their contracts and liquidate their position. The strategy of Amaranth did not include an exit strategy. The following case of MotherRock also proves this point. Before the fall of Amaranth, on August 2, 2006 MotherRock, a natural-gas-oriented hedge fund had announced that it was shutting down, its losses had reached up to $300 million; it had made a wrong short position and was therefore forced to liquidate due to mounting losses. This should have sent alarming bell to the investors in Amaranth to secure their position in the market and they make sure that the dont face liquidity risk in near future (liquidity risk explained later). All successful investors have an exit strategy as part of their main strategy; liquidity is one of the four core factors to consider when investing in the market, these factors are risk, return, liquidity and maturity. Liquidity risk includes the risk that liabilities cannot be met when they fall due and can only be met at an uneconomic price. This risk can be accounted for by widening the bid/offer spread. An institution might lose liquidity if its credit ratings fall, it experiences sudden unexpected cash outflows or some other event that causes the counterparties to avoid trading with or lending to the institution. A firm can also be exposed to liquidity risk if markets on which it depends are subject to loss of liquidity. Liquidity risk tends to compound other risks. If a trading organization has a position in an illiquid asset, its limited ability to liquidate that position at short notice will compound its market risk. Suppose a firm has offsetting cash flows with two different parties on a given day. If the counterparty that owes it a payment defaults, the firm will have to raise cash from other sources to make its payment. Should it be unable to make its payment, it will default too. Here liquidity risk is compounding credit risk. A position can be hedged against market risk, through diversification of the portfolio by including assets with different unsystemic risks, but still has liquidity risk. Amaranths investments were high-risk funds that lacked liquidity due to the nature of the natural gas futures market. They did not have any counter party to take their position under a week, when they needed it most. One reason that can explain this liquidity problem is that the counter parties had already locked their position in the forward contracts relating to production or storage. It seemed that due to their past experience, of success in assuming long position in winters and short position in summers, Amaranth failed to anticipate the liquidity risk they were getting into by being unable to find a counter party. (Till, 2006). This was the job of the funds risks managers to employ scenario analysis based on this past events. Taking all the factors mentioned above proves that Amaranth was taking immense risk with respect to liquidity. Amaranth was giving the natural gas comodity market a service by providing liquidity to the participants who cou debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-77156646559312426132020-01-18T04:38:00.001-08:002020-01-18T04:38:02.359-08:00Sociology Evaluation of MethodOne good aspect that my method had was that it allowed me to collect very in depth data, people were able to open up to me as it was unstructured interviews, I did have a problem with this though, as I didn't have prepared questions it was hard to compare my participants points of views afterwards and by talking so in depth about a sensitive subject like divorce things could get out of hand, one of my participants even began to cry as she became very emotional. The location to do my interviews in were varied, some were good and some were bad, one of them I had to do in my room and privacy was hard to come by. In my opinion my results are unreliable, but I believe that when talking to people about something as private as this, results will always be this as people feel awkward and don't want a stranger, or somebody from outside of the family to know their business. The participants I believe were the correct ones to interview and had enough experience and met with my criteria, the problem which I found though was that I hadn't interviewed enough; I only interviewed one of each that I wanted. I.e. ONE married couple, ONE cohabiting couple etc. If I had interviewed more people my results would have been more representative, I hadn't thought of this until after. The sampling method I used I thought was appropriate; people knew that they could confide in me and no problems arose with this. If I were to repeat this project I would defiantly change my method, I would do structured interviews as I believe that for my content and analysis it would be a lot easier to compare and that it is also possible to get in depth data this way. I would also interview more people. Evaluation of findings In relation of my first aim, to find out whether divorce on the increase is really seen as a negative aspect of today's society I found that people do take divorce less seriously than before but they don't give it less importance, I know this because nearly all of the couples I interviewed seemed slightly scared of divorce but would mostly consider it, I have found that, on contrary to my beliefs people don't rush into marriages and just get divorced when they find that marriage isn't what they expected, couples nowadays tend to cohabit first so that when they do get divorced they know it is the right thing to do, and the only way out. They cohabit to test their relationship, in order to avoid divorce. Some couples do not marry because of the threat of divorce. I found that people who are more religious see divorce as a problem. I also found that people feel divorce can affect mental health, respondents stated that divorce is not good for your health. The reasons given for the rise of divorce including the fact that marriages are now based of love rather than expectations and the changing role of women. In relation to my second aim, to find out the main reason for more divorces I found that most people believe that it is due to women having more independence, less sexism. This was the one and only thing that all my participants had in common. My findings were similar to previous studies in this area such as Robert Chester who found that nuclear families would never stop existing; he found that families would just change their forms. By having divorces this is what happens, children don't just stop having one of their parents, they still have both, the way in which families tend to be perceived just changes, cohabiting couples are on the up and so is divorce. People see divorce as something negative and positive at the same time, it affects you in both ways and people realise this, they also know that divorce can give them a second start in life when most of their hope is gone. What was interesting about my project was that I was able to research on something that causes hundreds and thousands of people heartbreak and depression everyday but is also seen as normal, I learnt a lot from doing this project, I used to think that people were just careless and got married and divorced as if it doesn't mean a thing, I've found that this is not the case, although more people are getting divorced it doesn't mean that more people are getting married, people stand up for themselves more nowadays, and despite my previous beliefs people DO see divorce as a problem, but also as something positive. By doing this project I have learnt a lot. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-70135953825947494062020-01-10T01:01:00.001-08:002020-01-10T01:01:04.133-08:00The Secret of Homework That No One Is DiscussingThe Secret of Homework That No One Is Discussing Ideas, Formulas and Shortcuts for Homework Prior to beginning an assignment, determine how long it should take to finish the assignment. When you're prepared to start homework, it's smart to specify a time limit, ideally with a warning bell. So take some time to speak to your child and see whether you're able to understand their resistance to homework assignments. The info they need to finish their homework is simply a modem away. The Upside to Homework For instance, you might simply check your son's or daughter's desk and the printer to make certain no assignments are getting left behind. Each teacher is extraordinarily trained and can help with just about any subject, employing a number of methods. Some educationists of the opinion that homework shouldn't be given to students. Setting homework does not have any true value unless the teacher has a normal review approach. Rumors, Lies and Homework Fortunately, not everybod y agrees. If you're behind on your homework, particularly if you've missed a good deal of sick days, communicating with your teachers is essential! These tips should help to make homework time less stressful for you as well as your parents! In any case, you don't need to know all the answers. The Nuiances of Homework You don't need to be concerned about whether your spouse is on the edge of asking you for a divorce. In a couple of cases both parents are deployed at precisely the same moment. A parent on deployment could be gone for around a year at one time. Figure out if your kid can turn in homework the very same way for each class. If you suspect your kid is getting excessive homework because of the teacher's poor classroom performance. Homework Frustration-If your son or daughter is having difficulty with any subject and they've attended all classes, it's imperative to talk to the teacher. Some children take part in scouting. The Homework Chronicles If a twenty minute assignment isn't further along after an hour, there is something which you child isn't receiving. The perfect purpose is to establish a workable time frame your family members can live with. A wholesome snack shouldn't be the extent of a complete meal. In case the kid is doing the homework immediately following the close of the school day, have a wholesome snack available. Alice finds them confusing since they ask riddles to which there is not any answer and pretend there is no room for her whereas there is. After a time you'll have developed the practice of getting your homework done at the very same time and place. Based on your children's independence, you might want to be sitting at the table too, or simply walking past the room periodically. The kitchen table isn't only for dinner, anymore. The Basics of Homework Learning is an excellent privilege which shouldn't be marred by parents who don't need to manage homework. School homework is the exact last thing they would like to do. Practice homework would be assignments like math issues, chemical equations or flashcards that offer additional practice in a particular skill. Keep in mind, homework folders are ONLY for completed homework that's prepared to be turned in! Clean up after you're finished with your homework. In the end one ought to define homework. Just keep in mind that homework is for your son or daughter, not you. The objective is to make learning fun. Some of us will feel dissatisfied with you, and you'll feel frustrated once you give up doing certain things you want. Children that are easily distracted may discover the excitement and stimulus of their bedroom toys too tricky to ignore. Finding out how to craft professional emails is a skill you are able to take with you in the so-called real world. Find out the length of time the teacher expects homework to take and receive the teacher's buy in to quit working after a set period of time. You may be taken aback at how frequently students obtain their professor's name wrong. You are going to want to speak with your teacher when possible. Teachers are starting to question the wo rth of homework increasingly more. What the In-Crowd Won't Tell You About Homework Just like any program with children, you might want to adapt or change a few things to fit the demands of your program. You must know your priorities. If your kid is turning school work projects which are suspiciously well written, well you know what's going on. A child with bad memory, attention, and focus is going to have a challenging time taking down assignments, bringing home the appropriate books, and keeping an eye on deadlines. Let your kid's teachers know about the strategies you're using and request ideas for working with each other to help your son or daughter make progress. Many adults never learn to manage their priorities and have a tough time keeping a great balance in their lives. Have your son or daughter use their learning experience to finish every one of the assignments. At CollegeAmerica, our instructors understand the value of prioritizing time and setting goals as a component of the academic practice. It is crucial to set a routine for your little one. Figure out where the difficulty lies and what your little one can do in order to boost understanding. So the next time that you want to complain about your children's teacher sending all of that darn homework home, thank them for giving you the opportunity to have unparalleled influence in your youngster's life. If your child absolutely hates doing their homework, take some time to try to understand just what the issue is. debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-42759112726326532602020-01-01T21:25:00.001-08:002020-01-01T21:25:02.623-08:00The, The Greatest Threat Of Public Confidence - 1950 Words Jimmy Rizzo Mr. Kotlewski Period 3 13 January 2017 The Latter Amendments Essay Draft As Ruth Bader Ginsburg once said, ââ¬Å"The greatest threat to public confidence in elections in this case is the prospect of enforcing a purposefully discriminatory law, one that likely imposes an unconstitutional poll tax and risks denying the right to vote to hundreds of thousands of eligible votersâ⬠(Ruth Bader Ginsburg Quote). To elaborate, the Twenty Fourth Amendment forbids any government from making voters pay poll tax, money, or a fee to vote in any election. This opens up the right to vote to many more American citizens of any ethnicity or gender. To justify, a poll tax was a tax that was simply just paid for living in a taxed area, but became veryâ⬠¦show more contentâ⬠¦Toombs was known for his unfair practices to the African races, and usually if a white person could not afford to pay their poll tax, he was also known to ââ¬Å"buy their voteâ⬠and pay the tax for them. Months after the Civil War ended, some Constitutio nal amendments were passed helping black rights and giving them the freedom to vote. Southerners were afraid of all this new political power towards the Negroes, so they did whatever they could to limit that power, and made it nearly impossible for Negroes to vote with the new laws they passed. With the Ku Klux Klan being formed and more discriminatory acts to interfere with black voting rights, it was not until the civil rights movements of the 1950ââ¬â¢s and 1960ââ¬â¢s until the amendment was finally brought up, almost a century later. During the Ku Klux Klan era, southerners passed laws to limit the power of African Americans, otherwise known as black codes. They did whatever they could to limit the blackââ¬â¢s freedom, even with such small things like requiring them to use a different water fountain or, even bigger, forcing them to pay an unreasonable poll tax to vote. With the rise of civil rights acts though, it became harder and harder to limit their power, and in t he middle of 1962 when Congress proposed the amendment to require no fee to vote, southerners knew that this was more of the beginning of racial movements and equal rights to all.Show MoreRelatedInterned or Imprisoned1358 Words à |à 5 Pagesbusinesses. 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Most of the consumer s concerns are the price, and the brand of theRead MoreDigital Fraud Common Forms and Preventative Measures Essays1627 Words à |à 7 PagesIntroduction ââ¬Å"Whoever commits a fraud is guilty not only of the particular injury to him who he deceives, but of the diminution of that confidence which constitutes not only the ease but the existence of societyâ⬠-Samuel Johnson In our ever changing world, technological advances over the past twenty years have paved the way for and deepened our reliance on the digital and computerized lifestyle; electronic mailing, online social networking, computer gaming, e-book reading, mobile phoning, etc debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-83170364493299535262019-12-24T17:11:00.001-08:002019-12-24T17:11:02.379-08:00The Ethics Of Enron And Worldcom - 1821 Words The desire for money, power, and praise can lead some top executives to participate in unethical behavior to satisfy these needs. 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Enron Corporation was an American energy and service company based in Houston, Texas. In 1985, Kenneth Lay merged two natural gas pipeline companies, InterNorth and Houston Natural Gas to form Enron. This new company eventually had 36,000 miles of pipe stretching across the United States and into Canada, making it the second largest pipeline network in the United States. By 1992, Enron became theShow MoreRelatedEnron and Worldcom Case Study1225 Words à |à 5 PagesEnron and WorldCom Case Study This report is based on the demise of Enron Corporation and WorldCom. Both the firms are demised due to the ethical lapses. These ethical lapses come into existence when managements of the firm, uses unethical practices to accomplish the goals of the firm. Maintaining financial and accounting standards in the business practices are necessary. 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Enronââ¬â¢s fraud was twofold; it included complex financial maneuvering through debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-84062447135514233272019-12-16T13:41:00.001-08:002019-12-16T13:41:05.269-08:00Titration Journal Free Essays E r J. Biochem. 40,177-185 (1973) u. We will write a custom essay sample on Titration Journal or any similar topic only for you Order Now Intracellular Titration of Cyclic AMP Bound to Receptor Proteins and Correlation with Cyclic-AMP Levels in the Surviving Rat Diaphragm Lien DO KHAC,Simone HARBON Hubert J. CLAUSER and lnstitut de Biochimie, Universit6 de Paris-Sud, Orsay (Received April 9/July 17, 1973) Extracts prepared from rat diaphragms incubated with or without theophylline and/or epinephrine have been tested for their total cyclic AMP content and for their ability to bind exogenously added cyclic [ââ¬Å"]AMP. Less cyclic [3H]AMP can be bound inthe extracts after theophylline and/or epinephrine treatment indicating that the rise in cyclic AMP level was accompanied by a n increase in the quantity of cyclic AMP bound intracellularly to the cyclic AMP-dependent protein kinases. Maximum cyclic AMP binding capacities, as measured by total cyclic AMP exchanges, were however identical in all cases. Accurate estimations of intracellular binding of cyclic AMP have been correlated with the level of cyclic AMP in the tissue : the reaction seems to obey simple saturation kinetics, a n apparent intracellular K d for cyclic AMP has been evaluated as 330 nM. The findings are consistent either with a real difference in the intracellular binding constant as compared to that measured in vitro (28 nM) or with the fact that the cyclic nucleotide in the cell may not all be available for the kinase protein receptors. They also suggest that the method described may prove useful for studying any possible intracellular control beyond the step of cyclic AMP synthesis. Regulation of cellular metabolism by adenosine 3â⬠² :5â⬠²-monophosphate (cyclic AMP) [I], its mediation through complex protein kinases [2,3] and the mechanism of the activation of these enzymes [4ââ¬â61 have been well documented within the past years in the eukaryotic cell. Activation has been demonstrated to occur according to Equation (1) through a n interaction of cyclic AMP with the regulatory subunit (R) of the enzyme, leading to a dissociation of this subunit from the catalytic subunit (C) which is thus activated. RC cyclic AMP + R cyclic AMP C . (1) + + However completely satisfactory correlations between the levels of intracellular cyclic AMP and its ultimate metabolic effects have been in many cases difficult to obtain. Striking examples for this situation are to be found in the results of Craig et al. [7] in rat diaphragm, of Stull and Mayer [8] in rabbit skeletal muscle concerning the regulation of phosphorylase activation, of Schaeffer et al. [9] and Miller et al. [lo] concerning regulation of glycogen metabolism in adrenalectomized rats, and of Harbon and Clauser [Ill This work is dedicated to Professor E. Lederer for his 65 th anniversary. Abbreviations. Cyclic AMP; adenosine 3â⬠²: 5â⬠²-monophosphate. in the rat uterus stimulated by prostaglandin El or E,. I n all these cases, cyclic AMP levels may be elevated without eliciting the expected metabolic responses. Two hypotheses have been formulated to explain these obvious discrepancies, either a decrease in the activation of the enzymes mediating cyclic AMP action within the cell, or a compartmentalization of the intracellular nucleotide. Hence it seems necessary to measure directly the degree to which the first step of the activation sequence (Equation 1)reflects the apparent intracellular cyclic AMP concentrations. This might be achieved by establishing in intact cells or tissues, correlations between the levels of intracellular cyclic AMP under welldefined physiological conditions, the extent to which it is bound to the specific receptor protein and the extent to which the complex protein kinases are in the active state. Satisfactory correlations between cyclic AMP levels and protein kinase activation have been recently established in various tissues by Corbin et al. [I21 and Soderling et al. [13]. The present work was to investigate if correlations could also be obtained between intracellular cyclic AMP levels and the amounts of intracellular cyclic AMP bound to receptor protein (R cyclic AMP) in the surviving rat diaphragm incubated with or without theophylline and epinephrine. The results reported demonstrate that ââ¬â E r J. Biochem. 40 (1973) u. 178 Intracellular Titration of Cyclic AMP-Receptor Protein Binding precise titrations of endogenous cyclic AMP bound versus cyclic AMP present in the intact tissue may be obtained. An apparent Kd value for the intracehlar cyclic AMP binding is observed which differs widely from the K d of the same binding established in vitro [14-161. This method may prove to be useful for studying the modification of cyclic AMP binding under conditions where the formation and breakdown of cyclic AMP does not seem to be affected. A preliminary report of these results has been presented [17]. MATERIALS AND METHODS Cylic AMP was obtained from P L Biochemicals Inc. , theophylline and Tris from Merck (Darmstadt), Na,ATP 4 H,O, L-epinephrine bitartrate from Calbiochem. Cellulose ester membrane filters (HA 0. 45 pm, 24 mm) were purchased from Millipore Corp. All reagents used were products of Prolabo (reagent grade). Cyclic [3H]AMP was a product of New England Nuclear Inc. , specific activity 24 Ci/ mmol. Animals were Wistar rats weighing about 200 to 300 g and fasted 24 h before the experiments. Tissue homogenizations were performed with an Ultra Turrax homogenizer. ââ¬â The reaction mixture for the binding assay contained in a final volume of 250 p1, 20 mM TrisHC1 buffer pH 7. 5, 10 mM MgCI,, 6. 7 mM theophylline and cyclic [3H]AMP a t various concentrations as indicated. The reaction was initiated by the addition of a n aliquot of diaphragm extracts equivalent to 70- 150 pg protein. Method B. I n this case, cyclic [3H]AMPwas added to the homogenizing medium a t saturating concentrations up to 0. 2 p M a t 0 ââ¬Å"C, centrifugation was carried out immediately and cyclic [3H]AMP bound measured directly on the extract. Cyclic [3H]AMP bound to the proteins, under either condition, was determined after different incubation times at 0 ââ¬Å"C: the reaction mixtures were then diluted to 3 m l with cold buffer (20mM TrisHC1, 10mM MgCl,, pH 7. 5) and passed through cellulose acetate Millipore filters (0. 45 pm). The filters were washed with 25ml of the same buffer, dried and counted in i 0 ml scintillation fluid, in a Packard Tri-Carb liquid scintillation spectrometer. Results were expressed as pmol cyclic AMP bound/mg protein ; the concentration of endogenous unlabelled cyclic AMP has been always taken into account for the estimation of the specific activity of cyclic [3H]AMP present in the incubation medium. Incubation Procedures The animals were killed by decapitation. The diaphragms were rapidly removed, freed from connective tissue, cut to small pieces, pooled and divided into equal parts. 200-250 mg tissue were preincubated in 2. ml Krebs-Ringer-bicarbonate buffer pH 7. 4, gas phase (95O/, O,, 5O//, CO,) for 30 min a t 37 ââ¬Å"C, in the absence or presence of 10 mM theophylline. Incubations were then performed in the absence or presence of epinephrine (5 pM) for varying periods of time. Extraction of the Tissue Standard Binding Assays for Cyclic A M P Two methods have been deviced to extract the tissue and estimate the binding of exogenous cyclic [3H]AMP to the extracted proteins, both slightly modified from the method defined by Walton and Garren [15]. Method A . The tissue was homogenized a t 0 ââ¬Å"C in 3 ml of one of the following solutions: 20 mM TrisHCl buffer pH 7. or 20 mM sodium acetate pH 7. 5 or 4 mM EDTA pH 6. 0. Theophylline (10 mM) was always present in the various homogenizing media in order to minimize any degradation of cyclio AMP by phosphodiesterase present in diaphragm extracts. A first centrifugation was carried out for 5 min a t 3000 x g , followed by a second one a t 50000 x g for 30min. The supernatants will be referred to as Tris extract, acetate extract and EDTA extract. Assay for Cyclic-AMP Levels For cyclic AMP assay, the tissue was homogenized in 3 ml cold 7 trichloroacetic acid and centrifuged for 30 min a t 50000 xg. After addition of 0. 1 ml N HC1, the supernatants were extracted 7-8 times with twice their volume of cold ether and evaporated to dryness. Total levels of cyclic AMP in the tissue trichloroacetic acid extract were determined according to Gilman using a protein b a s e and the heatstable inhibitor prepared from rabbit skeletal muscle [161. I n some instances, cyclic AMP content was also evaluated in the Tris and acetate extracts. Proteins were precipitated by trichloroacetic acid and extracts processed as described above. Proteins in the extracts were determined according to Lowry et al. 18] using bovine serum albumin as a standard. RESULTS AXD DISCUSSION Total Cyclic-AMP Levels in Rat Diaphragm. Effects of Epinephrine and Theophylline In order to study the cyclic AMP binding capacity of rat diaphragm proteins and its possible rnodification under the influence of epinephrine, it seemed necessary to test the first effect of the catecholamine, viz. the rise in the tissue cyclic AMP lev el under our experimental conditions. Em. J. Biochem. 40 (1973) L. Do Khac, S. Harbon, and H. J. Clauser Table 1. Total cyclic A H P levels in trichloroacetic acid extracts of rat diaphragm. Effect of epinephrine and theophylline R a t diaphragms (200-250 mg) were preincubated for 30 rnin a t 37 ââ¬Å"C in 2. 5 ml Krebs-Ringer-bicarbonate buffer (0, 95à °/0-C0, 50/0) in the absence or presence of 10mM theophylline, Incubation was then performed for 5 rnin with or without 5 pM epinephrine. The tissue was then homogenized in 7O/, trichloroacetic acid for cyclic AMP assay as described under Methods. Levels of cyclic AMP were expressed as pmol cyclic AMP/100mg wet tissue and as pmol cyclic AMP/mg soluble protein (as estimated by the Lowry procedure in the Tris extract. Values are means f S. E. M. of 5 different experiments Incubation condit,ions Total cyclic AMP TheoDhvlline EDineDhrine pmo1/100 mg pmol/mg wet tissue soluble protein 41 f 8. 0 20. 5 f 4. 7 104 1. 1 52 0. 47 93 f 4. 5 46 2 350 f 21 170 f 10. 7 179 Table 3. Distribution of cyclic [3H]AMP-bindingfractions i n different hom. ogenutes from rat diaplwagms incubated with or without epinephrine Preincubation and incubation conditions as described in Table 2. Tissues were homogenized in 3 ml 20mM TrisHCI, p H 7. 5, 4 mM EDTA or 20 mM sodium acetate pH 7. and centrifuged for 5 rnin at 3000 x g, the supernatants were centrifuged once more at 500OOxg for 30 min yielding extract 1 and pellet 1. The sediment of the first centrifugation was resuspended in 1. 5 ml of the corresponding buffer and centrifuged at 500OOxg for 30 min giving extract 2 and pellet 2. Binding activity for cyclic rSH]AMP was measured in each fraction as described in the text under method A and was expressed as pmol cyclic AMP bound/l00 mg wet tissue Fraction Cyclic AMP bound in EDTA Acetate Tris extract extract, extract, 5 yM noepinoepino epinephrine nephrine nephrine ââ¬â + + + + ââ¬â :Lhrine pmo1/100 mg wet tissue Extract 1 Extract 2 Pellet 1 Pellet 2 15. 70 1. 47 0. 76 1. 49 14. 90 1. 54 0. 83 1. 50 15. 30 1. 35 0. 80 1. 10 9. 40 0. 80 0. 44 0. 39 Table 2. Cyclic A M P levels in different extracts obtained from epinephrine-treated and untreated rat diaphragms Preincubation with 10 mM theophylline and incubation conditions in the absence or presence of 5 pM epinephrine as in Table 1. Diaphragms were homogenized in three different solutions: cold 7O/, trichloroacetic acid, Tris-HC1 pH 7. 5 or acetate p H 7. 5 as described under methods. Centrifugation was carried out for 30 rnin at 50000 x g. Soluble Tris extract, acetate extract and their corresponding sediments were deproteinized by 7 o/o trichloroacetic acid before cyclic AMP assay Incubation with epinephrine None 5wM Total cyclic AMP in Trichloroacetic 20 mM acetate acid extract pellet 57 280 ââ¬â 20 mM Tris extract pellet 48 218 9. 5 26 extract pellet 45 242 pmo1/100 mg wet tissue ââ¬â 8. 5 8. 3 As shown in Table 1, epinephrine (5 pM) in the absence of theophylline increases (by a factor of 2. 5) the total cyclic AMP content of rat diaphragm extracted by trichloroacetic acid. Theophylline alone (10 mM) had a stimulating effect, double; when both compounds were used together, the rise in cyclic AMP levels was 8- t o 9-fold, reaching 350pmol cyclic AMP/100 mg wet tissue. When cyclic AMP was assayed in either acetate or Tris extracts after deproteinization with trichloroacetic acid the values obtained were identical t o those found when the diaphragms were directly extracted with trichloroacetic acid ; hence almost none of the cyclic nucleotide in these extracts was associatcd with membrane-bound fractions (Table 2). Eur. J. Biochem. 0 (1973) Location of Cyclic AMP-Binding Fractions Table 3 shows the distribution of cyclic AMP binding activity in various fractions of three rat diaphragm homogenates measured by method A : in all cases more than goo/, of this activity was recovered in the 50000 x g supernatant, almost no cyclic AMP binding occurred in the pellets. Preincubation of the diaphragm with epinephrine did not modify the percentage distribution of the radioactive nucleotide between the supernatants and the pellets, hence subsequent experiments have been performed on the soluble extracts. On the other hand, in the case of epinephrine-treated diaphragms, less exogenous labelled cyclic AMP (about 50-60à °/0) was bound to the various fractions, indicating a decrease in the binding capacity of the extract as compared to the untreated diaphragm. Dilution by endogenous cyclic AMP cannot explain the effect of epinephrine, since allowance was made for this parameter (see Methods) ; the phenomenon was consistently reproducible and will be further substantiated and discussed below. The binding capacities of the various extracts for cyclic E3H]AMP have also been verified in the absence of any free endogenous cyclic AMP after removal of the latter by filtration through Sephadex G 50 (1x 37 cm) columns, previously equilibrated with 20 mM Tris-HC1 buffer, pH 7. 5 a t 4 ââ¬Å"C. I n these experiments, the detail of which w l not be reported in i l the present manuscript, the effect of epinephrine was still observed, when binding was measured on the main protein peak emerging with the void volume of the columns. When the corrections outlined in the 180 Intracellular Titration of Cyclic AMP-Receptor Protein Binding Z A 0. 51 / 0 20 40 60 Time ( m i n ) l / f r e e cyclic AMP (nM-ââ¬Ë) l / f r e e cyclic A M P (nM-ââ¬Ë) Fig. 1. The time wurse and cyclic-AMP-concentration dependence of cyclic A M P binding in rat-diaphragm extracts (method A ) . (A) Diaphragms were incubated for 30 min in the presence of 10 mM theophylline and extracted with Tris HCI buffer (meth od A). Cyclic AMP binding was estimated in the presence of various concentrations of cyclic E3H]AMP: 20nM ( 0 ââ¬â 0 ) ; 60nM ( ââ¬â ) 0 0 ; SO (A-A); 100 nM ( ââ¬â) #-. , a t 0 ââ¬Å"C. The react,ion mixtures contained in a final volume of 2. 5 ml, 20 mM Tris-HC1 buffer, pH 7. , 10 mM MgCI,, 6. 5 mM theophylline. The reaction was initiated by the addition of 930 pg protein. At the indicated times, aliquots were pipetted, immediately diluted with cold 30 mM Tris-HC1buffer pH 7. 5,lO mM MgCl, and passed on the Millipore filters. Filters were washed with the same buffer, dried and counted. Binding activity is expressed as pmol cyclic AMP bound/mg protein. (B) Data obtained from similar experiments where binding for cyclic AMP was performed a t 0 ââ¬Å"C, for 1 h, in the presence of cyclic [aHIAMP ranging from 12 nM to 110 I. Double-reciprocal plot, according to Klotz [25] Fig. 2. Cyclic-AMP-Concentration dependence of cyclic A M P binding in rat-diaphragm extracts (method B ) . Binding assays were carried out as described under method B. Various concentrations of cyclic [3H]AMP ranging from 12nM to 200 nM were added directly to the homogenizing medium for preparing extracts from epinephrine treated (A-A) and untreated (0-0) rat diaphragms. Aliquot,s of the extracts were filtered through Millipore filters, dried and counted. Double-reciprocal plot, according to Klotz [25] present paper were applied to these figures, the results were essentially identical to those obtained with the unfiltered extracts. Specificity. Kinetics and Concentration Dependence of Exogenous Cyclic-AMP Binding in the Extracts Specificity of cyclic AMP binding has been assessed by dilution experiments of cyclic [3H]AMP (100 nM) with unlabelled nucleotides (adenine, AMP, ATP, cyclic AMP) a t molar concentrations equalling up t o 100 times cyclic [3H]AMP concentrations. I n no case, except with unlabelled cyclic AMP, the amount of radioactive material bound to proteins by either method A or B was significantly reduced (the details of these experiments are not reported). When various concentrations of cyclic [3H]AMP were added to diaphragm extracts (after homogenization and centrifugation) and the binding reaction (method A) carried out for different incubation times at 0 ââ¬Å"C (Fig. I), it appears that saturation was obtained at a concentration of 80 nM for the cyclic nucleotide which essentially coincides with previously published data [14-161 and that binding equilibrium was reached a t p H 7. 5 and 0 ââ¬Å"C after less than 60 min incubation. It has also been verified that with the protein concentration used (70-150 pg in 250 pl) binding of cyclic AMP was directly proportional to the amount of added proteins. From a reciprocal plot of cyclic AMP binding versus cyclic AMP concentration (inset of Fig. I), an apparent Kd of 33 nM can be calculated. When similar experiments were performed by adding various concentrations of cyclic [3H]AMP into the homogenizing medium (method B) and using diaphragms which have been incubated in the presence and absence of epinephrine, the double-reciprocal plots of Fig. 2 were obtained. The apparent Kd values calculated with this method (45 nM) are in the same range as with method A. I n addition this figure shows that epinephrine treatment of the diaphragms does not modify this Kd but decreases the amount of exogenous cyclic AMP which can be bound to the extract proteins. By comparing exogenous cyclic AMP binding values obtained with methods A and B, it appears (Table 4) that when cyclic [3H]AMPwas added to the Eur. J. Biochem. 40 (1973) L. Do Khac, S. Harbon, and H. J. Clauser Table 4. Comparison of exogenous binding of cyclic [SII]AMP to diaphragm extracts by method A or method B. Rat diaphragms were incubated with theophylline in the absence or presancc of 5 p M epinephrine. Extracts in Tris-HC1 were prepared as described under method A for subsequent binding of cyclic [3H]AMP (100 nM), 1 h, a t 0 ââ¬Å"C. A second series of extracts were prepared in the same way but in the prescnce of 100 nM cyclic [3H]ABIP in the homogenizing medium (method R); binding of cyclic [3H]AMP was measured in a n aliquot immediately after centrifugation at 0 ââ¬Å"C (about 1 h after the end of incubation). Values are expressed as pmol bound cyclic AMP/mg protein. Numerals within brackets indicate number of experiments Method Cvclic A P bound with M 5 pM epinephrine no epinephrine pmol/mg protein 4 f 0. 22 (9) 4. 80 5 0. 2 (5) 181 6 t e . ;? 4 Q Q E A B 2 f 0. 13 (9) 3 f 0. 19 (5) 0 I I I 30 60 90 * Time (rnin) homogenization medium (extract B) higher binding values were obtained both with epinephrine-treated and untreated diaphragms, than with method A. This demonstrates that some additional binding of endogenous cyclic AMP occurred during the homogenization and fractionati on procedures, which tends to decrease the amount of unoccupied binding sites available for exogenous cyclic [3H]AMP. Hence method B has been currently used to measure exogenous cyclic AMP binding, since the values obtained with this method seem to reflect intracellular conditions more accurately. Fig. 3. Time course of cyclic [3H]AMP binding in extracts from rat diaphragms incubated in the absence or presence of theophylline orland epinephrine. Half rat diaphragms were preincubated in the absence (m, A ) or in the presence ( 0 , 0 ) of 10 m31 theophylline for 30 min at 37 ââ¬Å"C. Epinephrine (5 pM) was added ( A , 0 )and incubation continued for 5min. Tissue was homogenized in 1. 5 ml Tris-HC1 buffer containing 200 nnf cyclic [3H]AMP and centrifuged at 5000xg for 10 min at 0 ââ¬Å"C. Binding of cyclic [3H]AMP was measured in aliquots of the supernatant at the times indicated, through Millipore filtration, t = 0 corresponds to the onset of the extraction. Results are expressed as pmol cyclic AMP bound/ mg protein (without correction for cyclic AMP exchange) Effect of Theophylline and Epinephrine Treatment on the Binding of Exogenous Cyclic [3H]AMP by Diaphragm Extracts Fig. 3 shows the results of a typical experiment in which diaphragms have been incubated in the absence or presence of theophylline and epinephrine. Homogenization has been performed according to method B, the centrifugation time of the homogenate kept to a inimum (10 min), and the binding capacity for cyclic [3H]AMP determined a t different times. As may have been expected, this cyclic [3H]AMP binding (which measures the residual binding capacities of the extracts) was, in the course of the whole titration period, inversely related t o the amount of endogenous cyclic AMP present in the relevant ext racts (see Table 1). Hence the agents which increase the intracellular cyclic AMP level appear to decrease the amount of binding sites available for exogenous cyclic [3H]AMP, probably through an increase of endogenous cyclic AMP binding to the receptors. I n order to titrate endogenous binding of cyclic AMP accurately, experiments were designed to estiEm. J. Biochem. 40 (1973) mate the total binding capacities of the extracts through complete exchange of endogenously bound cyclic AMP with cyclic [3H]AMP, and also to estimate the actual amount of exchange occurring in the extracts between endogenous bound unlabelled cyclic AMP and exogenous cyclic [3H]AMP during the titration period. A precise knowledge of these two parameters is required for the determination of the binding sites occupied by endogenous cyclic AMP at the moment where the tissues are homogenized. Cyclic-AM P Exchange and Determination of Maximal Binding Capacities Total cyclic AMP exchange has been measured under the conditions defined by Wilchek et al. [19] for parotid gland and skeletal muscle : extracts from both treated and untreated diaphragms were f i s t incubated at 0 ââ¬Å"C with cyclic [3H]AMP (100 nM) under binding conditions of method A and then allowed t o exchange with 1 pM unlabelled cyclic AMP at 20 ââ¬Å"C in the presence of 100p. M ATP and 10mM MgCl,. Fig. 4 shows that almost complete exchange of the bound labelled nucleotide occurred within 30 min, 182 Intracellular Titration of Cyclic AMP-Receptor Protein Binding 0 10 20 30 40 50 60 Time (min) 70 80 90 Fig. 4. Exchange of bound cyclic [SHIAMP. Extracts were prepared from epinephrine-treated ( + o ) and untreated (0-0) rat diaphragms. Binding of cyclic [3H]AMP was carried out a t 0 ââ¬Å"C in a volume of 2. 5 ml with 500 pg proteins, and 100 nM cyclic r3H]AMP in Tris-HC1 buffer, MgCl, and theophylline a t the concentrations described for the standard binding assay. After 1-h incubation, 1 pM unlabelled cyclic AMP and 100 pM ATP were added and the mixture allowed to stand at 20à °C. At the different times indicated in the figure, aliquots corresponding t o 50 pg protein were pipetted, rapidly diluted with 20 mM Tris-HC1 buffer, 2. 5 mM MgC1, p H 7 5 and filtered through Millipore filters. The filters . were washed with the same buffer, dried and counted. Results are expressed as pmol/mg protein 0 30 60 90 120 Time (rnin) 180 240 ââ¬â Total binding capacities of the proteins could thus be measured by incubating the extracts first with 100 nM unlabelled cyclic AMP a t 0 ââ¬Å"C and carrying on the exchange reaction in the presence of 1 pM cyclic I13H]AMP at 20 ââ¬Å"C for 1-2 h ; the values obtained averaged 8. -9. 5 pmol cyclic [3H]AMP/mg soluble protein, both with epinephrine-treated and untreated diaphragms. These results were confirmed by direct assay of bound cyclic AMP: the extracts have been fully saturated with unlabelled 1pM cyclic AMP and filtered as described. After washing the Millipore filters, bound cyclic AMP was extracted by cold 7 O/, trichl oroacetic acid and the cyclic nucleotide was directly assayed according to Gilman [16]. The average value was 9. 8 f 0. 4 pmol cyclic AMP bound per mg protein, which is of the same order of magnitude as the amount of bound cyclic [3H]AMP calculated above. Previously published data are in close agreement with these values. Walton and GarFen [15] reported maximal binding capacities of 9. 8 pmol/mg protein for adrenal extracts, whereas Gilman [l6] found a total binding of 12pmol/mg protein in muscle extracts. The values for maximal cyclic AMP binding are very low as compared t o the total endogenous cyclic AMP present in the extract (46 pmol/mg protein with the theophylline-treated diaphragm and 170 pmol/mg protein with the epinephrine theophylline-treated diaphragm). It must be added that the binding proteins, saturated with cyclic AMP or not, were almost completely retained on the Millipore filters, and that endogenous cyclic AMP, not Fig. 5. T i m e course of cyclic A M P exchange under binding (0 ââ¬Å"C) and exchange (20 ââ¬Å"C} conditions. Extracts were prepared from epinephrine treated (0,A ) and untreated ( 0 , A) r a t diaphragms. Binding of cyclic AMP was performed as described in Fig. 2 in the presence of 100 nM cyclic AMP for 60 min at 0 ââ¬Å"C. A t the end of the binding reaction 1 pM cyclic [3H]AMP was added t. the different extracts, in the absence (A, A ) or presence ( 0 , 0 ) of l00p. M ATP. The reaction mixtures were maintained a t 0 ââ¬Å"C for 2 h and then at 20 ââ¬Å"C (arrow) for 2 more hours. At the different times indicated on the figure, aliquots corresponding t o 70 pg protein were pipetted and treated as in Fig. 4. Results are expressed as cyclic rH]AMP bound in pmol/mg protein. bound to these fractions, was quant itatively recovered in the Millipore filtrates after trichloroacetic acid extraction. The extent t o which this ââ¬Å"freeâ⬠cyclic AMP may or not be bound to other proteins is presently not known. Cyclic-AMP Exchange under Binding Conditions The extent of cyclic AMP exchange under binding conditions (0 ââ¬Å"C, 1 h, 100 nM cyclic AMP) must be controlled if corrections for simultaneous exchange have to be applied t o binding data: extracts of rat diaphragms treated with theophylline and theophylline epinephrine were first saturated with 1 O O n M unlabelled cyclic AMP (binding conditions) and then exchanged with 1 pM cyclic [3H]AMP but a t 0 ââ¬Å"C. After 2 h, the temperature was raised to 20 ââ¬Å"C and completion ofthe exchange measured after 1-2 h further incubation. Fig. 5 shows that a t 0 ââ¬Å"C, within 1h incubation time, which are the conditions described above for the binding assay, about 200/, of total sites were exchangeable. Under these conditions, ATP and Mg ions slightly increase the exchange velocity. I n addition, this figure confirms that a t 20 ââ¬Å"C total exchange capacities were identical for epinephrine-treated and untreated diaphragms ; hence initial + + Em. J. Biochem. 40 (1973) L. Do Khac, S. Harbon, and H. J. Clauser 183 Table 5. Relationship between intracellular cyclic A M P levels and cyclic A M P binding in extracts from diaphragm incubated under various conditions Diaphragms were incubated with or without 10 mM theophylline for 30 min at 37 ââ¬Å"C, 5 pM epinephrine was added where indicated and incubation continued for varying times. From each incubation, half a diaphragm was extracted by trichloroacetic acid for cyclic AMP estimation. The other half was homogenized with Tris-HC1buffer lOOnM cyclic [3H]AMP(method B) for exogenous cyclic AMP binding after 1 h a t 0 ââ¬Å"C; maximal binding capacities were determined in the same extracts a t 20 ââ¬Å"C in the presence of 1 pM cyclic [3H]AMP under conditions described for cyclic A P exchange. R. esults are expressed as pmol cyclic AMP/mg M protein. Endogenous binding values were calculated as the difference between maximal binding capacities ( A )and exogenousbinding ( B ) and corrected for the 200/, exchange + Incubation conditions Theophylline 10 mM Epinephrine 5t*M Time Cyclic AMP Total level Maximal binding Exogenous capacity binding (a) (b) Endogenous binding (a-b) corrected min pmol/mg protein ââ¬â ââ¬â ââ¬â + + + + + + 0 2 10 30 5 5 20. 5 52 43 38 46 170 f 4. 7 0. 47 f2 f 10. 7 9. 6 f 0. 9 9. 4 f 0. 1 9. 20 9. 40 8. 9 5 0. 73 8. 9 0. 85 5. 35 f0. 40 4. 50 f 0. 133 4. 40 4. 70 4. 46 f 0. 20 2. 7 f0. 224 5. 31 6. 13 6 5. 5 5. 53 7. 77 differences in residual binding capacities reflect variations in the degree of saturation of the receptor proteins by endogenous cyclic AMP, rather than modifications of their maximal binding capacity. 1 Titration o Endogenous Cyclic-AMP Binding in Rat f Diaphragm. Effects of Theophylline and Epinephrine Since total bindin g capacities of the receptor proteins in the extracts and the amount of exogenous cyclic [3H]AMP bound by these extracts after homogenization may be estimated, it appears possible to calculate endogenous cyclic AMP bound in the intact organs, correcting for a 2001, exchange during the titration period. Table 5 summarizes the results of a series of experiments where diaphragms have been incubated under conditions which modify endogenous levels of cyclic AMP :in every case, half of the diaphragm was extracted with cold trichloroacetic acid (see Methods) for the assay of intracellular cyclic AMP levels: the second half was extracted according to method B for the estimation of exogenous cyclic [3H]AMP binding and of total cyclic AMP binding capacities. The endogenous cyclic AMP bound was calculated from the latter experimental data. This table definitely establishes that the average values obtained for the intracellular binding of endogenous cyclic AMP in the intact organ seem to correlate with its cyclic AMP levels. A reciprocal plot of intracellular binding versus intracellular cyclic AMP concentrations (Fig. 6) shows that this correlation fits simple saturation kinetics very accurately. I n the unstimulated diaphragm (no theophylline nor epinephrine added to the incubation medium) about 50à °/, of the available binding sites are occupied by endogenous cyclic AMP; this Eur. J. Biochem. 40 (1973) -0. 002 I 0. 002 l/Free cyclic AMP (nM-ââ¬Ë) 0 0. 004 . Fig. 6. Reciprocal plot of intracellular cyclic A M P levels and cyclic A M P binding in rat-diaphragm extracts. Data arc obtained from experiments performed as described in Table 5 and replotted according t o the Klotz equation. The intercept on the y axis yields a n estimate of the number of binding sites and the x intercept provides a n estimation of the in tracellular apparent dissociation constant. Statistical analysis of the data were performed according to Cleland [26] using a Wang electronic calculator alue increases to almost goo/,, when the diaphragms have been fully stimulated with both theophylline and epinephrine. Various treatments with one of the agonists alone cause endogenous bindings ranging between these two extreme values. The apparent Kd value for intracellular binding according to this plot was estimated to 330 nM f 50, as compared to the apparent Kd (33-45 nM) when binding was assayed in the extracts (Fig. l and 2). Hence a difference of about one order of magnitude appears to obtain between the Kd values calculated within the cell and the 84 Intracellular Titration of Cyclic AMP-Receptor Protein Binding same constant measured with diaphragm homogenates. The double-reciprocal plot may also be used to calculate the intracellular maximal binding capacities, from its intercept with the ordinate axis. A value of 8. 9 pm ol/mg protein was found which coincides with the values measured in the extracts by total cyclic [3H]AMP exchange. This discrepancy between the intracellular Kd and the Kd measured in vitro in a variety of tissue extracts including diaphragm may a t first sight seem surprising. It has however repeatedly been pointed out that cyclic AMP concentration even in the unstimulated cell was far in excess of the concentration which should result in almost maximal stimulation of protein kinases and compartmentalization of the nucleotide within the cell has usually been postulated to explain this contradiction [8,9,20]. The present work shows that despite these high intracellular concentrations of cyclic AMP, protein kinases could indeed not be fully activated, since under the same conditions, the receptor proteins appear not to be fully saturated with cyclic AMP. Concluding Remarks As might have been expected from Equation (1) (if this reaction truly reflects intracellular conditions) a rise in cyclic AMP should be paralleled by an increase in the amount of cyclic AMP bound to receptor protein in the cell. The results reported show this indeed to be the case in the isolated rat diaphragm: when this tissue is stimulated by various agents which increase the level of cyclic AMP the amount of protein receptors endogenously saturated by cyclic AMP (R cyclic AMP) rises, as indicated in our experiments by a decrease in their ability to bind exogenously added cyclic [3H]AMP after tissue extraction. Maximal binding capacities for cyclic AMP do not seem to be affected under any circumstance. A parallel approach t o the study of this problem has been undertaken by Corbin et al. [12] and Soderling et al. [13] who investigated in adipose tissue under various stimulatory conditions, the state of activation of the catalytic subunit (C) by assaying the cyclic AMP dependence of the protein kinase in tissues extracts. These authors demonstrated that under well-defined xperimental conditions, there was a quantitative relationship between the intracellular level of cyclic AMP and the amount of the active C unit which could be separated from the complex protein kinase RC. However in their experiments high concentrations of NaCl had to be added to the extracts, since in its absence R and C tended to reassociate almost immediately, indicating that cyclic AMP is no longer bound to its receptor protein (R). The situation in various other tissue xtracts has been found to be analogous, except wit h skeletal muscle, where preliminary results obtained by the authors led them to suggest that the protein kinase subunits do not readily reassociate. This seems also to be the case for the diaphragm, since under the conditions of the present work, it has been possible to titrate for R * cyclic AMP in the crude extracts even in the absence of high salt concentrations : acccurate estimations of intracelM a r binding of cyclic AMP have been obtained and correlated with the absolute amounts of the nucleotide present in the stimulated and unstimulated cell. The binding seems t o obey simple saturation kinetics but the apparent Kd of this binding is about10 times higher as compared with the crude extracts. These results may be explained by cyclic AMP compartmentalization within the cell ; in this case, however, the simple saturation kinetics would indicate that the various pools of the cyclic nucleotide attain equilibrium very rapidly. Or else, if cyclic AMP within the cell is not compartmentalized, and if the reaction described by Equation (1) may be applied, without any modification, to intracellular equilibria, a decrease in the apparent Kd could be merely a consequence of the dilution (about 10-fold) of the protein components during extraction of the tissue, while cyclic AMP concentrations are maintained by the addition of exogenous cyclic [3H]AMP. However these two hypotheses are certainly oversimplified, since they do not take into account factors like the intracellular concentration of the heat-stable kinase inhibitor [21,22], ATP or Mg2+ [19,23], which are known to affect cyclic AMP binding either in crude extracts or with purified protein kinase preparations. It seems impossible to decide at present which of these interpretations is most likely to reflect true intracellular conditions. It is noteworthy that the apparent Kd estimated is close to the intracehlar cyclic AMP concentration of the nstimulated tissue, a fact which should account for maximal sensitivity of the regulatory mechanisms under physiological conditions. Hormonal controls at the level of cyclic AMP-receptor protein interaction have hitherto never been described; the data reported above provide a suitable means for investigating such problems. The authors are very much indebted to Mrs Ginette Delarbre for her excellent technical assistance and to Mrs Marie -ThBrBse Crosnier for preparing the manuscript. The present work has been performed thanks to two official grants of the C. N. R. S. Paris, France: ERA No 33 and ATP No 429. 914), to a grant obtained from the D. G. R. S. T. (No 72. 7. 0135), to a generous contribution of the Fondation pour la Recherche Mf? dicale Franpise and to a participation of the CEA (Saclay, France) in the purchase of radioactive compounds. The work has been performed as a partial fulfillment of a thesis (Doctorat Bs-Sciences) submitted by L. D. -K. Eur. J. Biochem. 40 (1973) L. Do Khac, S. Harbon, and H. J. Clauser REFERENCES 1. Robison, G. A. , Butcher, R. W. Sutherland, E. W. (1968) Ann. Rev. Biochem. 37, 149-174. 2. Walsh, D. A. , Perkins, J. P. Krebs, E. G. (1968) J. Biol. Chem. 243, 3763-3765. 3. Kuo, J. F. Greengard, P. (1969) Proc. Nut. Acad. Xci. U . S. A. 64, 1349-1355. 4. Reimann, E. M. , Brostrom, C. O. , Corbin, J. D. , King, C. A. Krebs, E. G. (1971) Biochem. Biophys. Res. Commun. 42, 187-194. 5. Tao, M, Salas, M. L. Lipmann, F. (1970) Proc. Nut. Acad. Sci. U . S. A. 67, 408-414. 6. Gill, G. N. Garren, L. D. (1970)Biochem. Biophys. Res. Commun. 39, 335-343. 7. Craig, J. W. , Rall, T. W. Larner, J. (1969) Biochim. Biophys. Acta, 177, 213-219. 8. Stuil, J. Mayer, S. E. (1971) J. Biol. Chem. 246, 5716-5723. 9. Schaeffer, L. D. , Chenoweth, M. Dunn, A. (1969) Biochim. Biophys. Acta, 192, 292-303. 10. Miller, T. B. , Exton, J. H. Park, C. R. (1971) J. Biol. Chem. 246, 3672-3678. 11. Harbon, S. Clauser, H. (1971) Biochem. Biophys. Res. Commun. 44, 1496-1503. 12. Corbin, J. D. , Soderling, T. R. Park, C. R. (1973) J. Biol. Chem. 248. 1813-1821. 185 13. Soderling, T. R. , Corbin, J. D. Park, C. R. (1973) J. Biol. Chem. 248, 1822-1829. 14. Gill, G. N. Garren, L. D. (1969) Proc. Nut. A d . Sci. U. 8. A. 63, 512-519. 5. Walton, G. M. Garren, L. D. (1970) Biochemistry, 9, 4223-4229. 16. Gilman, A. G. (1970) Proc. Nut. Acad. Sci. U. 8. A. 67, 305-3 12. 17. Do Khac, L. , Harbon, S. Clauser, H. (1973) Ninth Int. Congr. Biochem. p. 354. 18. Lowry, 0. H. , Rosebrough, N. J. , Farr, A. L. Randall, R. J. (1954) J. Biol. Chem. 193, 265-275. 19. Wilchek, M. , Salomon, Y. , Lowe, M. Selinzer, Z. (1971)Biochem. Biophys. Res. Commun. 45,1177-1184. 20. Chambaut. A. M. , Lerav, F. Hanoune, J. (1971)PEBS . . ââ¬Å". Lett. 15,ââ¬â¢328-334. Walsh, D. A. , Ashby, C. D. , Gonzalez, C. , Calkines, D. 21. Fisher. E. H. Krebs. E. G. (1971)J. Biol. Chem. 246, i977-1985. 22. Ashby, C. D. Walsh, D. A. (1973) J. Biol. Chem. 248, 1255-1261. 23. Haddox. M. K. , Newton, N. E. , Hartler, D. K. Goldberg, N. D. (1972) Biochem. Biophys. Res. Commun. 47,-653-661. 24. Klotz, I. M. (195 3)in The Proteins (Neurath, H. Bailey, K. , eds) p. 772, Academic Press, New York. 25. Cleland, W. W. (1967) Advan. Enzymol. 29, 1. , L. Do Khac, S. Harbon and H. J. Clauser, Institut de Biochimie, Universit6 de Paris-Sud, BLtiment 432, F-91405 Orsay, France Eur. J. Biochem. 40 (1973) How to cite Titration Journal, Papers debracarter1987http://www.blogger.com/profile/00685511868320575980noreply@blogger.com0tag:blogger.com,1999:blog-1481523796355321307.post-63372584603222320092019-12-08T10:25:00.001-08:002019-12-08T10:25:05.389-08:00Critical Appraisal of Epidemiological Study â⬠MyAssignmenthelp.com Question: Discuss about the Critical Appraisal of Epidemiological Study. Answer: Introduction Schizophrenia is a serious mental disorder that interferes with the ability of a person to think, make decisions, manage emotions and relate to others. It manifests commonly in the form of hallucinations or delusions. Cognitive issues such as, disorganized thinking, struggling to remember things and lack of insight (anosognosia) are often observed. Clozapine is one of the most commonly used atypical antipsychotics to treat schizophrenia (Leutwyler et al., 2014). It leads to a decrease in suicidal ideation. However, there are some serious side effects associated with its administration. One such effect is weight gain (Gressier et al., 2016). People under this medication report significant weight gain. This drug-induced weight gain is identified as a major risk factor for disorders that can increase morbidity and mortality rates of schizophrenic patients (Sagy, Weizman Katz, 2014). This report aims to critically appraise a study that was conducted to evaluate the effects of physical a ctivity and diet control on obese schizophrenic patients, under clozapine treatment (Wu et al., 2007). The paper focuses on a randomized, controlled study that was conducted to evaluate the effects of regular physical activity and continuous dietary control, for six months, on obese patients who were suffering from schizophrenia. These patients were being administered clozapine to reduce their mental disorder. The study tried to establish an association between clozapine use and weight gain among schizophrenia patients. It assessed biochemical and anthropometric parameters such as, triglyceride, serum glucose, insulin, cholesterol, prolactin, cortisol, and growth hormones for three months and six months. The study was a novel research as no other study had been conducted prior to this research that investigated the effects of dietary control among the target population, who were under clozapine medication (Wu et al., 2007). The study recruited 753 hospitalized patients who had been diagnosed with DSM-IV schizophrenia (McLean et al., 2014). The age of the participants ranged between 18-65 years. Respondents who were under administration of 300mg oral clozapine per day, for at least one year and had a BMI higher than 27 kg/m2 were included in the study. A registered dietitian implemented dietary control among the respondents and restricted the caloric intake to 1,600-1,800 kcal per day for men and 1,300-1,500 kcal per day for women. Minimum dietary requirements for men and women were 1,500 kcal and 1,200 kcal per day respectively (Dipasquale et al., 2013). The types of foods consumed by the participants were assessed, which included an evaluation of the vegetable, fruits, sugar free drinks and, artificial sweeteners (Kim et al., 2017). The calorie intake was measured. A minimum of 30 minutes of moderate intensity physical activity like brisk walking is recommended for people belonging to all age groups for most days of the week. The intervention involved performing physical activities for six months, three days a week. The patients were made to take part in activities that involved 1.62 km level walking for 40 minutes and walking up and down the stairs for 20 minutes, under supervision (231 steps upstairs and 330 steps downstairs). The speed and distance of these activities were maintained at a constant level, throughout the intervention period. The participants were encouraged to complete them in an hour. The guidelines proposed by the American College of Sports Medicine were used to estimate the rate of energy expenditure per week (Thompson et al., 2013). The effects of the interventions were assessed by anthropogenic measurements, which included measuring the body fat percentage, weight, height, hip and waist circumference and BMI (Lau et al., 2016). Serum glucose, insulin, cholesterol, cortisol, triglyceride and prolactin levels were measured by ELISA tests. On comparing the result values of the sample and control group using ANCOVA and SPSS software version 10.0, no significant difference was observed among the two groups at baseline. No significant changes in body fat percentages were observed between men and women or during the 3 month and 6 month intervention period. However, significant reduction (p0.05) was observed in body weight, waist circumference in the study group, after 3 months. Waist circumference showed significant reduction after 6 months. Metabolic analysis and ELISA failed to show any reduction at baseline or during the 3 month intervention period. However, triglyceride levels were significantly lower in the control group after 6 months (p0.05). A high IGF-1 to IGFBP-3 molar ratio was observed in the study group than the control group, after 6 months. The study found out that physical activity and dietary are responsible for normalizing metabolic abnormalities, attenuating neuroleptic side effects and minimizing hormonal changes. However, the researchers found presence of low motivation among psychiatric patients for weight reduction, in absence of supervision (Vancampfort et al., 2015). They also proposed that it is difficult to suppress appetite for a long period of time. Therefore, they suggested that long-term adherence to such lifestyle modification programs are necessary for putting these interventions to practice. Bias and Confounding variables Randomised control studies are generally less susceptible to sample bias, when compared to other study designs that assess the effect of several therapeutic interventions. The study avoided bias on the basis of baseline prognostic variables. Randomisation ensured that the treatment groups were balanced and as similar as possible. This was supported by the fact that all 53 participants selected from 753 hospitalised patients had a DSM-IV schilzophrenia diagnosis, were 18-65 years of age, had BMI higher than 27 kg/m2 and was under the medication of 300 mg oral clozapine intake for more than a year. No patients were included in the study if they were found to suffer from organ failure, abnormal ambulatory functions, and severe mental retardation or presented vented walking. Neither of the sample or control group included patients who were under medication of antipsychotics apart from clozapine. Moreover, bias due to presence of confounding variables was also removed by performing the two way mixed designs ANCOVA. This eliminated the influence of any external factors on the measured outcomes. The results obtained were therefore least likely to get affected. However, one major bias associated with the study was the recruitment of participants from inpatient settings. The rates of compliance to the 6 month intervention and the success rate of the study would have been different if the sample was selected from outpatient settings. Thus, it can be stated that the randomized controlled study did not remove bias with respect to selection of participants from a larger population. Chance variations are inherent errors in predictive statistical models. They are defined as the difference between actual and predicted values of the variable being investigated. Similar to other epidemiological studies, this research also included participants from a larger population. There was a chance of the small sample differing from the wider patient population (Nuzzo, 2014). To show that the difference in results between the sample and the control group reflected a real difference in the parent population, a statistical test was performed. The p Causal association between exposure and outcome The primary goal of most epidemiological studies is assessment of a particular disease cause. However, owing to the concept that most epidemiological studies are based on observation, rather than experiment, several possible explanations are considered before drawing inference for any cause and effect relationship. Causal relationships are more likely to demonstrate a stronger association between the cause and outcome in a particular study. Plausibiity establishes the cause-effect relationship between a biological factor and an adverse health outcome or effect. In this research study, a relationship was established between use of clozapine and weight gain among patients with schizophrenia. The study was built on the basis of several scientific researches that proposed that clozapine and olanzapine induced mean weight gain among patients who were under administration of these drugs for more than 6 months (Samara, Leucht, 2016). The research was based on other findings that such incre ase in mean weight, induced by the action of antipsychotics like clozapine often leads to noncompliance (Olfson et al., 2016). This results in treatment discontinuation and relapse of psychotic symptoms. Furthermore, scientific evidences suggest that weight control is effective in reducing health risks among schizophrenia patients who are overweight. The presence of existing biological research on the use of clozapine among such patients and their subsequent weight gain explains the association of interest of this research. Demonstrating the plausibility of causal relationships is complex since a particular health outcome is the result of balance and interplay between different factors. The study showed consistency with other findings, which indicated that schizophrenia patients who were treated with clozapine, reported a gain in weight (McNamee et al., 2013). These patients also demonstrated an increase in body fat deposits and BMI. A marked increase in the waist-to-hip ratio and central adiposity was reported by other studies. These outcomes were consistent with the findings of the current epidemiological research (Rosenbaum et al., 2014). Moreover, the results are also consistent with other studies that indicate a loss in weight among inpatients who took clozapine. The study also showed agreement with several other findings in the low levels of IGFBP-3 and high IGF-1 to IGFBP-3 molar ratio after six months of intervention. These results were consistent with research that displayed a reduction in IGFBP-3 levels with exercise. The special mechanism illustrated in the study focused on the effect of IGF-1 on the cardiovascular system. IGF-1 is a peptide hormone predominantly produced by the liver, in response to pituitary growth hormone. Several studies have elaborated on the role of low levels of IGF-1 in increasing the likelihood for cardiovascular diseases (Arcopinto et al., 2014). Low levels have been shown to promote atherosclerosis and stroke. This in turn increases the mortality rates. An increase in the level of IGF-1 in macrophages works to removed the plaques from clogged arteries and prevents the incidence of cardiovascular diseases (Troncoso et al., 2014). This study therefore elaborated on the fact that IGFBP-3 (insulin-like growth factorbinding protein-3) is the most abundant protein that carries the maximum amount of IGFs that circulate in the bloodstream. The study performed an ELISA test to investigate the molar ratio of IGF-1 to IGFBP-3, to determine the risk of cardiovascular diseases among the participants taken from inpatient settings, who were under clozapine treatment for schizophrenia. Although, previous studies did not investigate the role of IGF-1, IGFBP-3 and growth hormones among schizophrenic patients, this research illustrated the effects of long term clozapine therapy on the factors. Appraising external validity External validity measures the validity of the inferences obtained from the particular study to wider population. A research study is considered to be externally valid if the relevant results can be extrapolated to a larger population with similar characteristic features. The population, setting, interventions and treatment outcomes of this study can be applied to the source population of schizophrenia patients who adhered to clozapine medication. The interventions followed in this study could therefore be followed in the source population. The effects of dietary control and physical exercise could be applied to monitor the health effects of obese inpatients with schizophrenia, who were subjected to clozapine drugs (Mizuno et al., 2014). However, the external validity cannot be completely established before the interventions are applied to outpatient settings. Participants belonging to outpatient settings have a less likelihood of showing adherence to the interventions and following a strict dietary and exercise regime. The results of the intervention on such participants are therefore most likely to get altered. Such patients would show less success rate of the proposed intervention. Furthermore, other metabolic effects of the interventions were not diagnosed before the 6 month period. Therefore, before being applied to a larger population, the study parameters should be tested on outpatients and the secondary metabolic effects of the lifestyle modifications should be measured. Quality of the study The discussions prove that the study was successful in measuring the effects of physical activity and dietary control on the 53 participants, randomly distributed in the sample and control group. It effectively demonstrated the benefits of a 3 month and 6 month intervention that consisted of regular physical activity and integrated dietary control on obese patients, who suffered from schizophrenia and were subjected to clozapine treatment. The interventions were successful in showing significant reduction in body fat percentage, BMI and waist and hip circumference (Amiaz et al., 2016). In addition, the study effectively measured the insulin, triglyceride, cortisol, serum glucose, prolactin, IGF-1 and IGF-3 levels and their molar ratio among the participating patients. The results showed significant improvement in their metabolic profiles. In contrast, negligible or no improvement in the control group results for anthropometric measurements established the fact that the interventions were effective in managing weight gain in the sample. It can also be suggested that the study was of a good quality owing to the fact that the dietary control intervention was applied on the participants by following dietary guidelines. Approximately 200-300 fewer kilocalories were present in the diet of the participants during the 6 month intervention period and they were made to spend 600-750 kcal more energy per week by regular physical activity. The study chose these levels for calorie consumption or energy expenditure to minimize occurrence of adverse effects due to diet changes. These adverse events could be manifested in the form of emotional and mental instability among inpatients that were given fewer calories. Moreover, the study was of a good quality in selecting physical activities that were suitable for the patients. The activities chosen were uncomplicated and did not pose any danger. Furthermore, it utilized the role of efficient health professionals to evaluate and ensure the proper application of the weight management t echniques among the patients. A minimum body weight reduction by 5% to 10% produces significant health benefits among the patients (Manu et al., 2015). The results showed that there was a significant reduction in for obese patients with schizophrenia who are taking clozapine, the intervention resulted in body weight (5.4%), BMI (5.4%), hip circumference (3.3 cm) and waist circumference (3.3 cm) after the 6 month intervention period. The research was effective in lowering BMI and improving other outcome measures by the end of the intervention period. A reduction was observed in some of the parameters just after 3 months of intervention, while others showed significant changes in results after 6 months. These discussion state that the research considered appropriate intervention strategies to evaluate the intended outcomes. Moreover, the study focused on regular monitoring the anthropometric measurements, dietary behavior and physical activity of the sample group, by the ward staff and the investigators. At the end of the 6 month period, none of the participants displayed worsened conditions. Female patients with schizophrenia under clozapine medications are likely to get affected with cardiovascular diseases. The findings provided evidence for low IGFB-3 levels after the 6 month intervention but, failed to show any alteration of the levels of IGF-1. Therefore, it can be stated that the exercise intensity used in the intervention was inadequate to create changes in the levels of the growth hormone. 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