The 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. Some businesses simply fabricate their financials while others invent fake companies to inflate their asset’s value and profitability. Both situations are attempts to increase their earnings as much as possible for top executives own interests. The two most well-known and fairly recent instances of major accounting scandals include Enron and WorldCom. How did Enron, once one of the five largest audit and accountancy partnerships in the world, and WorldCom, once the United States’ second largest long distance telephone company, both end in bankruptcy just one year after the other? By exploring the history, scandal, and aftermath of Enron and WorldCom, comparing the two business’ malpractice, understanding the ethical issues involved, considering the historical context of the scandal which includes the Sarbanes-Oxley Act of 2002, and my opinion regarding the effect, it will become clear how these once successful businesses ended with criminal charges. 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   |  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. The profession of accounting has become a mockery due to the accounting scandals that took place all over the world in theRead MoreEssay on The Consequences of Bad Business Decisions1304 Words   |  6 Pagespractices. Once respected businesses like Enron, WorldCom, and Arthur Anderson have been found deceiving there customers, stockholders, and employees. C.E.O.s try to achieve the American dream and pursue capitalism to its fullest potential. In doing so, business leaders have lost their values and ethics, and make bad business decisions. The downfalls of a company are the consequence of C.E.O.s bad decisions. According to Marjaana Kopperi business ethics, can simply be defined in terms of socialRead MoreThe Sarbanes Oxley Act Of 20021133 Words   |  5 Pagesinto customers, the Securities and Exchange Committee proposed and implemented a new law. This policy was put in place to regulate the accounting practices and to make them more honest. Titled the Sarbanes-Oxley Act of 2002 (enacted just after the WorldCom scandal), basically set rules and regulations in place that included (but not limited too): a Public Company Accounting Oversight Board to provide independent justification and to oversee the accounting department; Auditor Independence to limit theRead MoreEnron Questionable Transactions Essay765 Words   |  4 PagesEnron Questionable Transactions Question 1 The question which segment of its operations got Enron into difficulties is simple to answer, everything. Almost every all segments of their operation were improper. First of all, they practice unethical and dishonest practices which victimized workers, consumers, taxpayers and stockholders. Enron created partnerships within their own organization which led to them creating new financial instruments, called SPE’s (special purpose entities) which wasRead MoreThe Sarbanes Oxley Act Of 20021015 Words   |  5 PagesThe Sarbanes-Oxley Act of 2002, also known as the SOX Act, is enacted on July 30, 2002 by Congress as a result of some major accounting frauds such as Enron and WorldCom. The main objective of this act is to recover the investors’ trust in the stock market, and to prevent and detect corporate accounting fraud. I will discuss the background of Sarbanes-Oxley Act, and why it became necessary in the first section of this paper. The second section will be the actà ¢â‚¬â„¢s regulations for the management, externalRead MoreFraud : The Perfect Fraud Storm1420 Words   |  6 PagesFinancial Statement Fraud Option #2 The perfect fraud storm occurred between the years 2000 and 2002 involving two of the largest energy and telecom corporations in the United States: Enron and WorldCom. It was determined that both organizations fraudulently overstated assets, created assets from expenses or overstated revenues, costing investors billions of dollars and resulting in both organizations declaring bankruptcy (Albrecht, Albrecht, Albrecht Zimbelman, 2012). Nine factors contributedRead MoreA Case Of Accounting Fraud1555 Words   |  7 PagesAnother major case of accounting fraud driven by the desire to build and protect one’s personal financial condition is the WorldCom debacle. Bernie Ebbers had to show continually growing net worth in order to avoid margin calls on his own WorldCom stock that he had pledged to secure loans. When WorldCom, the telecommunications giant, failed and was put into bankruptcy, the U.S. witnessed the largest accounting frauds in history. Former CEO, Bernie Ebbers, was convicted of orchestrating this accountingRead MoreThe Sarbanes Oxley ( Sox ) Act Of 20021617 Words   |  7 Pagesbrief historical summary of SOX will be presented, including the events leading up to its passage. The key ethical components of SOX will be identified and explained. The social responsibility implications of the mandatory publication of corporate ethics will be assessed. One of the main criticisms of SOX has been its implementation costs, and this specific criticism will be addressed in regards to smaller organizations. Finally, potential improvements to the SOX legislation will be explored, basedRead MoreThe Enron and Worldcom Scandals875 Words   |  4 PagesE. Boos – Week 2 – Assignment February 17, 2013 The Enron and WoldCom Scandals ENRON 1. The segment of Enron’s operations that got them into difficulties had several parts. They published misleading financial reports. They could not meet their bridge financing commitment with Barclay Bank because outside investors were not found. Because of this, they restated activities of JEDI and Chewco SPEs so they could be retroactively consolidated into Enron’s accounts. The SPEsRead MoreThe, Greed, And Hubris Of Action1236 Words   |  5 Pagescorrupts absolutely†. There were three specific corporate scandals that led to failed confidence in the financial sector and the subsequent legislation known as Sarbanes-Oxley Act of 2002 which attempted to address this malfeasance: Enron, WorldCom, and Arthur Andersen. Enron Notably, the most widely recognized scandal of all time because it led to a systemic lack of trust in corporations and the financial markets in general. Enron’s fraud was twofold; it included complex financial maneuvering through

Titration 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 [â€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 3†² :5†²-monophosphate (cyclic AMP) [I], its mediation through complex protein kinases [2,3] and the mechanism of the activation of these enzymes [4–61 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 3†²: 5†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 – 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. – 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 â€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 â€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 â€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 â€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 â€Å"C in 2. 5 ml Krebs-Ringer-bicarbonate buffer (0, 95 °/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 – + + + + – :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 – 20 mM Tris extract pellet 48 218 9. 5 26 extract pellet 45 242 pmo1/100 mg wet tissue – 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 50-60 °/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 â€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-‘) l / f r e e cyclic A M P (nM-‘) 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 – 0 ) ; 60nM ( – ) 0 0 ; SO (A-A); 100 nM ( –) #-. , a t 0 â€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 â€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 â€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 â€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 â€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 â€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 â€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 â€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 â€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 â€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 â€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 20 °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 – Total binding capacities of the proteins could thus be measured by incubating the extracts first with 100 nM unlabelled cyclic AMP a t 0 â€Å"C and carrying on the exchange reaction in the presence of 1 pM cyclic I13H]AMP at 20 â€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 â€Å"C) and exchange (20 â€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 â€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 â€Å"C for 2 h and then at 20 â€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 â€Å"free† 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 â€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 â€Å"C. After 2 h, the temperature was raised to 20 â€Å"C and completion ofthe exchange measured after 1-2 h further incubation. Fig. 5 shows that a t 0 â€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 â€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 â€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 â€Å"C; maximal binding capacities were determined in the same extracts a t 20 â€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 – – – + + + + + + 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 50 °/, 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-‘) 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 . . â€Å". Lett. 15,’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

Critical Appraisal of Epidemiological Study †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. Conclusion Thus, it can be concluded that the study helped to establish the benefits of regular physical activity and dietary control among the target population. The intervention showed significant improvements among obese, schizophrenia inpatients that were treated with clozapine. However, a strong health monitoring and lifestyle modifications are required to observe the long term effect of the interventions. References Amiaz, R., Rubinstein, K., Czerniak, E., Karni, Y., Weiser, M. (2016). A diet and fitness program similarly affects weight reduction in schizophrenia patients treated with typical or atypical medications.Pharmacopsychiatry,26(03), 112-116. Arcopinto, M., Isgaard, J., Marra, A. M., Formisano, P., Bossone, E., Vriz, O., ... Cittadini, A. (2014). IGF-1 predicts survival in chronic heart failure. Insights from the TOS CA.(Trattamento Ormonale Nello Scompenso CArdiaco) registry.International journal of cardiology,176(3), 1006-1008. Dipasquale, S., Pariante, C. M., Dazzan, P., Aguglia, E., McGuire, P., Mondelli, V. (2013). The dietary pattern of patients with schizophrenia: a systematic review.Journal of psychiatric research,47(2), 197-207. Gressier, F., Porcelli, S., Calati, R., Serretti, A. (2016). Pharmacogenetics of clozapine response and induced weight gain: a comprehensive review and meta-analysis.European Neuropsychopharmacology,26(2), 163-185. Kim, E. J., Lim, S. Y., Lee, H. J., Lee, J. Y., Choi, S., Kim, S. Y., ... Kim, S. W. (2017). Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with schizophrenia and the development of dietary guidelines for schizophrenia.Nutrition Research,45, 10-18. Lau, S. L., Muir, C., Assur, Y., Beach, R., Tran, B., Bartrop, R., ... Caetano, D. (2016). Predicting weight gain in patients treated with clozapine: the role of sex, body mass index, and smoking.Journal of clinical psychopharmacology,36(2), 120-124. Leutwyler, H., Hubbard, E. M., Jeste, D. V., Miller, B., Vinogradov, S. (2014). Associations of schizophrenia symptoms and neurocognition with physical activity in older adults with schizophrenia.Biological research for nursing,16(1), 23-30. Manu, P., Dima, L., Shulman, M., Vancampfort, D., De Hert, M., Correll, C. U. (2015). Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management.Acta Psychiatrica Scandinavica,132(2), 97-108. McLean, D., Thara, R., John, S., Barrett, R., Loa, P., McGrath, J., Mowry, B. (2014). DSM-IV criterion A schizophrenia symptoms across ethnically different populations: evidence for differing psychotic symptom content or structural organization?.Culture, Medicine, and Psychiatry,38(3), 408-426. McNamee, L., Mead, G., MacGillivray, S., Lawrie, S. M. (2013). Schizophrenia, poor physical health and physical activity: evidence-based interventions are required to reduce major health inequalities. Mizuno, Y., Suzuki, T., Nakagawa, A., Yoshida, K., Mimura, M., Fleischhacker, W. W., Uchida, H. (2014). Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis.Schizophrenia bulletin,40(6), 1385-1403. Nuzzo, R. (2014). Statistical errors.Nature,506(7487), 150. Olfson, M., Gerhard, T., Crystal, S., Stroup, T. S. (2016). Clozapine for schizophrenia: state variation in evidence-based practice.Psychiatric Services,67(2), 152-152. Rosenbaum, S., Tiedemann, A., Sherrington, C., Curtis, J., Ward, P. B. (2014). Physical activity interventions for people with mental illness: a systematic review and meta-analysis. Sagy, R., Weizman, A., Katz, N. (2014). Pharmacological and behavioral management of some often-overlooked clozapine-induced side effects.International clinical psychopharmacology,29(6), 313-317. Samara, M. T., Leucht, S. (2016). Use of Clozapine in SchizophreniaReply.JAMA psychiatry,73(10), 1098-1099. Thompson, P. D., Arena, R., Riebe, D., Pescatello, L. S. (2013). ACSMs new preparticipation health screening recommendations from ACSMs guidelines for exercise testing and prescription.Current sports medicine reports,12(4), 215-217. Troncoso, R., Ibarra, C., Vicencio, J. M., Jaimovich, E., Lavandero, S. (2014). New insights into IGF-1 signaling in the heart.Trends in Endocrinology Metabolism,25(3), 128-137. Vancampfort, D., De Hert, M., Stubbs, B., Ward, P. B., Rosenbaum, S., Soundy, A., Probst, M. (2015). Negative symptoms are associated with lower autonomous motivation towards physical activity in people with schizophrenia.Comprehensive psychiatry,56, 128-132. Wu, M. K., Wang, C. K., Bai, Y. M., Huang, C. Y., Lee, S. D. (2007). Outcomes of obese, clozapine-treated inpatients with schizophrenia placed on a six-month diet and physical activity program.Psychiatric services,58(4), 544-550.

The Dissolution Of The Manasteries Essay Research free essay sample

The Dissolution Of The Manasteries Essay, Research Paper Background to the Dissolution The Dissolution of the Monasteries and the events which followed, were all brought approximately as a direct consequence of the interruption with Rome. The ground for the interruption, lies merely in Henry? s defeat at his inability to procure a divorce signifier his married woman Catherine of Aragon, and a approval from the Pope for his new matrimony to Anne Boleyn, although arguably, there was a demand for reformation within the church. Prior to the interruption with Rome, the church was rife with pluralism, barratry ( one of the Catholic Pope? s chief weaknesss ) and breaches of the vows of celibacy. It is hence clear that there were jobs with the English church prior to the interruption, but although it was unpopular, many people including Henry remained Catholic: ? A house Catholic, he was acute to hold apostolic blessing, and the more improbable this became, the more he was forced to oppugn the Pope? s legal power in England? [ 2 ] To carry through a interruption, Henry needed some sort of justification, and he would besides hold to guarantee that in implementing the interruption itself, he was non seen as back uping unorthodoxy and the Protestant reformation in peculiar. We will write a custom essay sample on The Dissolution Of The Manasteries Essay Research or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page With the assistance of adviser Thomas Cromwell, Henry aims to ordain the interruption with Rome utilizing codified authorization ; that of the male monarch, Godheads and parks moving through parliament. ? A sequence of genuinely radical Acts of the Apostless of parliament now cut the bonds? religious, legal, fiscal? which linked the English church and province to Rome? [ 3 ] There were several chief landmarks in the interruption with Rome, the first of which was the act in restraint of entreaties. This was a justification and definition of royal domination, and was grafted by Thomas Cromwell. It was the act of domination in 1534 nevertheless, that would turn out to be Henrys greatest measure frontward in the interruption. It confirmed Henry? s headship of the church and explicitly reserved the Crown the rights to the organizing and jurisdictional powers once held by the Papacy. By this, the Crown would command the right O specify the church? s instructions and doctrinal determinations, finally ensuing in the ruin of the monasteries. As a consequence of Henry? s force per unit area on the English clergy in his efforts to convert the Pope to allow a divorce, the disintegration of the monasteries became an of import and necessary undertaking. By taking the Pope? s most loyal protagonists from England, Henry was badly restricting his power. In 1533, in position of Anne Boleyn? s impending gestation, Thomas Cranmer, an archbishop, declared Henry? s matrimony to Catherine shut-in, ( ? the male monarch must halt life in this wickedness with this adult female who is non his married woman? [ 4 ] ) and married him to Anne Boleyn. ? The Act of Supremacy? so, established Henry as caput of the Church of England, and marked the terminal of the Pope? s influence in his kingdom. Threatened by the Pope with exclusion, if he did non take Catherine back, all hopes of rapprochement with Rome were passed. Henry? s reformation was traveling quickly.When H VIII foremost initiated the disintegration of the Monasteries, he was confronting unfavorable judgment from assorted sides. It must be understood that in make up ones minding the cogency of Henry? s claims for the disintegration, there are two sides to the statement. Protestant supp orters of Henry? s actions, argue that after the 1530? s, all the monasteries were corrupt and a topographic point where evildoers lived in a luxury paid for by others. The grounds for cloistered life they claimed, were based on a prevarication created by the Papacy, to beef up its ain place: In order to decrease the clip a individual spends in purgatory when they die, money must be donated to the church in order to salvage their psyche. As a consequence of these false and morally corrupt claims on behalf of the Papacy, Protestants argued that the monasteries deserved to be dissolved, as the money they survived upon was gained under false pretensions. Another factor that supports Henry? s statement for the disintegration, were the consequences found from the? heroism Ben Sira? . Within this, it was discovered that on norm, one one-fourth of a cloistered houses wealth went to the caput of the house, normally an absentee leader, populating their life as a state gentleman, free signifier duty. Disclosures such as this evidently angered the populace, but whether or non Henry was angered in the same manner, or simply saw these factors as farther support for his claims to fade out the monasteries is problematic. It is true that there was a certain component of corruptness nowadays, with immorality, sexual perversion and homosexual patterns all being admitted to by 100s of monastics. But certainly, all these factors point to a demand for reform instead than disintegration. The above grounds entirely does non show a clear image of the existent state of affairs of the monasteries in England, that is certain. It is now known that merely 10 per centum of the cloistered houses in England were capable to corruptness, and that the bulk followed their cloistered ideals and manner of life unfailingly, greatly supported by the populace, and hence laying waste to Henry? s claims that the monasteries were no longer regarded as topographic points of worship, but of wickedness, animal and detestable. Monasteries by and large functioned good, and there is an air of lip service about these claims, if we consider that Thomas Cromwell himself gained wealth at the monasteries # 8217 ; expense wherever possible. Cromwell accepted assorted? gifts? from the smaller cloistered houses, in return for back uping their entreaties against the new statute law? s, an act which he neither intended to transport out nor brood upon. It is clear so that following his promise to the King to do him and the Crown wealthy and moneymaking one time more, Cromwell decided that the closing of the monasteries was where he would accomplish this proposed wealth. By lawfully shuting the monasteries, this? larceny? would do the King affluent beyond his wildest dreams. If we consider so, that Henry? s motivations were about wholly based on his want for wealth, and without which his proposed disintegration would neer hold taken topographic point, the cogency of his claims is slightly decreased. Henry VIII? s grounds for he disintegration of the monasteries hence, were non at all justified in the manner he had claimed. He sought merely wealth, and it is this desire to derive control and achieve the wealths that came with it which motivated Henry. His greed and the falseness of his many claims against the monasteries succeeds in uncovering his existent wants, and nullifies any old statements based on his spiritual concerns for the disintegration.

franciso de zurbaran essays

franciso de zurbaran essays The Annunciation: A Painting by Francisco de Zurbaran Works of art can best be appreciated when the elements of design, the principles of design, and the iconography of the work are observed and understood. The Annunciation, a painting by the Spanish artist Francisco de Zurbaran, is a work of art that incorporates both the elements and principles of design. The iconography of the painting is of great importance as well as its aesthetic quality. The ability to create a picture of The Annunciation in ones mind is a key factor in understanding the analysis of the work. Francisco de Zurbaran approaches the painting with a naturalistic style. The painting features a room in which a woman like angel is seen at the left kneeling on the ground before the Virgin Mary. The figure of Mary is placed between a chair and a small wooden table draped with a green cloth. Mary disregards an open Bible on the table, as she appears solemn while staring at the floor. Floating above the two main figures in the upper left side of the painting are cherubs resting on a bed of clouds. They happily gaze down at Mary with eyes from Heaven. The Annunciation uses elements of design to create a visually pleasing picture. The visual elements consist of light, color, texture, shape, and line. The use of light is one of the most evident elements in this painting. The source of light is not directly visible in the painting, but appears as a radiant angelic host floating above the two main figures. Light emphasizes the fair skin of the Angel and Mary as they both look down towards a shadowy floor. Light also reflects the open Bible on the table suggesting emphasis on the holiness of Mary. The rest of the room remains eerily dark and dull. Color is used to draw attention to important characters and objects in the painting. The red of Marys shirt emphasizes her place as the main figure. A bright, yellow cloud floating above t...

Sense and Sensibility Quotes

Sense and Sensibility Quotes Jane Austen published Sense and Sensibility in 1811- it was her first published novel. Shes also famous for Pride and Prejudice, Mansfield Park, and a number of other novels in the Romantic Period of English Literature. Here are some quotes from Sense and Sensibility. They gave themselves up wholly to their sorrow, seeking increase of wretchedness in every reflection that could afford it, and resolved against ever admitting consolation in future.- Sense and Sensibility, Ch. 1People always live forever when there is an annuity to be paid them.- Sense and Sensibility, Ch. 2An annuity is a very serious business.- Sense and Sensibility, Ch. 2He was not handsome, and his manners required intimacy to make them pleasing. He was too diffident to do justice to himself; but when his natural shyness was overcome, his behaviour gave every indication of an open, affectionate heart.- Sense and Sensibility, Ch. 3On every formal visit a child ought to be of the party, by way of provision for discourse.- Sense and Sensibility, Ch. 6In hastily forming and giving his opinion of other people, in sacrificing general politeness to the enjoyment of undivided attention where his heart is engaged, and in slighting too easily the forms of worldly propriety, he displayed a want of caution which Elinor could not approve.- Sense and Sensibility, Ch. 10 Sense will always have attractions for me.- Sense and Sensibility, Ch. 10When he was present she had no eyes for anyone else. Everything he did was right. Everything he said was clever. If their evenings at the Park were concluded with cards, he cheated himself and all the rest of the party to get her a good hand. If dancing formed the amusement of the night, they were partners for half the time; and when obliged to separate for a couple of dances, were careful to stand together, and scarcely spoke a word to anybody else. Such conduct made them, of course, most exceedingly laughed at; but ridicule could not shame, and seemed hardly to provoke them.- Sense and Sensibility, Ch. 11There is something so amiable in the prejudices of a young mind, that one is sorry to see them give way to the reception of more general opinions.- Sense and Sensibility, Ch. 11When the romantic refinements of a young mind are obliged to give way, how frequently are they succeeded by such opinions as are but t oo common and too dangerous!- Sense and Sensibility, Ch. 11 It is not time or opportunity that is to determine intimacy it is disposition alone. Seven years would be insufficient to make some people acquainted with each other, and seven days are more than enough for others.- Sense and Sensibility, Ch. 12The pleasantness of an employment does not always evince its propriety.- Sense and Sensibility, Ch. 13At my time of life opinions are tolerably fixed. It is not likely that I should now see or hear anything to change them.- Sense and Sensibility, Ch. 17A fond mother ... in pursuit of praise for her children, the most rapacious of human beings, is likewise the most credulous; her demands are exorbitant; but she will swallow anything.- Sense and Sensibility, Ch. 21It was impossible for her to say what she did not feel, however trivial the occasion; and upon Elinor therefore the whole task of telling lies when politeness required it, always fell.- Sense and Sensibility, Ch. 21She was stronger alone; and her own good sense so well supported her, t hat her firmness was as unshaken, her appearance of cheerfulness as invariable, as, with regrets so poignant and so fresh, it was possible for them to be.-  Sense and Sensibility, Ch. 23 Death ... a melancholy and shocking extremity.-  Sense and Sensibility, Ch. 24I wish with all my soul his wife may plague his heart out.-  Sense and Sensibility, Ch. 30When a young man, be he who he will, comes and makes love to a pretty girl, and promises marriage, he has no business to fly off from his word, only because he grows poor, and a richer girl is ready to have him. Why  dont  he, in such a case, sell his horses, let his house, turn off his servants, and make a thorough reform at once.-  Sense and Sensibility, Ch. 30Nothing in the way of pleasure can ever be given up by the young men of this age.-  Sense and Sensibility, Ch. 30Elinor had not needed ... to be assured of the injustice to which her sister was often led in her opinion of others, by the irritable refinement of her own mind, and the too great importance placed by her on the delicacies of a strong sensibility and the graces of a polished manner. Like half the rest of the world, if more than half there be that are clever and good, Marianne, with excellent abilities and an excellent disposition, was neither reasonable nor candid. She expected from other people the same opinions and feelings as her own, and she judged of their motives by the immediate effect of their actions on herself.-  Sense and Sensibility, Ch. 31 A man who has nothing to do with his own time has no conscience in his intrusion on that of others.-  Sense and Sensibility, Ch. 31Life could do nothing for her, beyond giving time for a better preparation for death; and that was given.-  Sense and Sensibility, Ch. 31She felt the loss of Willoughbys character yet more heavily than she had felt the loss of his heart.-  Sense and Sensibility, Ch. 32A person and face, of strong, natural, sterling insignificance, though adorned in the first style of fashion.-  Sense and Sensibility, Ch. 33There was a kind of cold-hearted selfishness on both sides, which mutually attracted them; and they sympathized with each other in an insipid propriety of  demeanour, and a general want of understanding.-  Sense and Sensibility, Ch. 34Elinor was to be the  comfor/ter  of others in her own distresses, no less than in theirs.-  Sense and Sensibility, Ch. 37The world had made him extravagant and vain - extravagance and vanity had made him cold-hearted and selfish. Vanity, while seeking its own guilty triumph at the expense of another, had involved him in a real attachment, which extravagance, or at least its offspring necessity, had required  to be  sacrificed. Each faulty propensity in leading him to  evil,  had led him likewise to punishment.-  Sense and Sensibility, Ch. 44 His own enjoyment, or his own ease, was, in every particular, his ruling principle.-  Sense and Sensibility, Ch. 47Elinor now found the difference between the expectation of an unpleasant event, however certain the mind may be told to consider it, and certainty itself. She now found that, in spite of herself, she had always admitted a hope, while Edward remained single, that something would occur to prevent his marrying Lucy; that some resolution of his own, some mediation of friends, or some more eligible opportunity of establishment for the lady, would arise to assist the happiness of all. But he was now married; and  she condemned her heart for the lurking flattery which so much heightened the pain of the intelligence.-  Sense and Sensibility, Ch. 48

Leadership Plan Addendum Research Paper Example | Topics and Well Written Essays - 2000 words

Leadership Plan Addendum - Research Paper Example Leaders have to go through different stages of learning which will help to avoid the errors that one may encounter in the initial stages when one takes up leadership position. This paper will develop a greater understanding of risk issues that will have an impact on Simcenter, Inc. and their leadership styles. SimCenter, Inc. is one the nation’s leading pilot training facilities in the United States and is privately owned by the George Family from its headquarters in Miami, Florida. SimCenter has been providing flight training instructions for over ten years and has built is reputation on providing the airline industry well trained and highly experienced pilots. Air carriers seek pilots trained by SimCenter both nationally and internationally because of their professionalism. Although SimCenter has primarily been a training center for commercial carriers that have large aircraft such as Airbus300 series, Boeing 737s, and Boeing 757s; it is uniquely positioned to profit from both current pilot shortages and hiring requirements of National and International carriers by leasing pilots and creating a charter airline to the Bahamas. This new venture is based on Porter’s Value Chain Theory, which explains the need of producers to provide products and services at the same level of customer demands (Value Chain, 2005). Value chain of any organization reflects its history, the strategy and the approach to implementing the strategy, and the economics of the activities. The purpose of a value chain is to create a process or product that would generate profits. According to Porter, adding value is a strategic means to achieve profit and competitive advantage. Traditionally different business functions perceived and created value differently. Under Porter’s model profitability and market control can be maintained if an organization controls all aspects of the buying experience including supplies,

Reading Assignment Example | Topics and Well Written Essays - 250 words - 4

Reading - Assignment Example The creative solution on how to defeat cramming is to review lessons constantly even just for few minutes. But reviewing itself can sometimes be boring or taxing so the creative solution to this consistent to Higgins approach is to make it fun to defeat boredom. How can we make studying fun? We have actually made it several times by doing a group study that is like a picnic. Studying suddenly transforms to a small picnic, hanging out or chill event where we learn while we are having fun. Yes the pranks and the jokes and the crazy stories are still there but the important thing is that everybody reviewed their lesson without even knowing it. The Creative Problem Solving (CPS) here is to make studying fun so that we are engaged in it early and thus avoid the problem. The convergent thinking or the single correct solution here in the problem is to review long before the exam. The divergent thinking is creative approach to the solution which is to make it fun by doing group studies where we could also hang out while

Factors afecting enzyme activity Essay Example for Free

Factors afecting enzyme activity Essay Below is a table of result which I obtained when conducting these experiments. Time (s) Amount of gas given off using 1cm3 of liver suspension and 1cm3 of hydrogen peroxide (cm3) 0. 0 Amount of gas given off using 2cm3 of liver suspension and 3cm3 of hydrogen peroxide(cm3)   Amount of gas given off using 1cm3 of liver suspension and 3cm3 of hydrogen peroxide(cm3) 0 Amount of gas given off using 1cm3 of liver suspension and 4cm3 of hydrogen peroxide(cm3). Amount of gas given off using 1cm3 of liver suspension and 5cm3 of hydrogen peroxide(cm3)   Amount of gas given off using 0. 5cm3 of liver suspension and 5cm3 of hydrogen peroxide(cm3) 0By looking at these results I can see that the best ratio I have tested so far is the ratio of 10:1 (5cm3 hydrogen peroxide to 0. 5 cm3 liver suspension) as it gives me a good spread of results and does not happen so quickly that I cannot take results from it. I obtained a 1cm3 syringe with which I could accurately measure to the nearest 0. 02 cm3 I used 0. 2cm3 of liver suspension and 5cm3 of hydrogen peroxide my results are in the table below. Time (s): 0. 0   Amount of gas given off using 0. 2cm3 of liver suspension and 1cm3 of hydrogen peroxide (cm3his ratio gave me good results which I can easily analyse so I have decided to use this ratio in my final experiment. I will use the concentrations 0%, 2%, 4%, 6%, 8% and 10% of liver suspension in my experiments as these should give me sensible results. Also, after conducting these experiments I have decided to use a 1cm3 syringe as this will give me accurate results and I have decided to use a gas cylinder rather than a measuring cylinder to collect gas as this is more accurate and easy to read. Fair testing In order to ensure that my results are reliable and accurate I will endeavour to make sure that there is only one variable in all of my experiments. Given that I only wish to test one variable I will make sure that I control all other variables that could affect the amount of gas produced in my experiments. Factors that could affect the results of my experiments are temperature, pH, apparatus and substances. To maintain a constant temperature throughout all my experiments I will conduct all of my experiments with the side arm boiling tube in an electronically heated water bath set at a temperature of 30i C. I have chosen this temperature as it is higher than room temperature so this will not affect it and it is not at a temperature high enough to denature the enzymes. To control pH I will add a pH buffer to the liver suspension buffering the pH at seven. I have chosen seven as it is neutral and therefore should not affect my experiments. I will also test the pH of the liver suspension at the start of each experiment using universal indicator if the paper turns light green I will know the pH is seven. To ensure that my apparatus is in working order I will ensure that I assemble the apparatus well and double check that all connections are well made and are therefore as air tight as possible. This will mean that any all gas produced goes into the gas cylinder and does not escape the apparatus so that my results are accurate. Given that all substance concentration that I will ask for will be mixed by the school biology department I cannot be sure exactly what is in them so unfortunately I will have to trust that all the substances I use are what they should be. Before using any of my substances I will stir them for ten seconds using a glass rod, this is to ensure that there is an even distribution of liver in my suspension so my results are accurate. Also, I will always use the same concentration of 10 vols hydrogen peroxide. Another factor which could affect my results is human error. When I am conducting my experiments it is possible that I could inaccurately measure my substances and I could start the stop clock at the wrong time. To accurately measure all of my substances I have chosen the most accurate apparatus to measure them with. I will measure as closely as is possible with the human eye measuring my liver suspension accurate to the nearest 0. 01cm3 and my hydrogen peroxide to the nearest 0. 1cm3. Also, when injecting my hydrogen peroxide I will inject it as quickly as possible so the full amount is in the boiling tube as soon as possible. I will start the stop clock at the very moment I inject the hydrogen peroxide so my results are accurate. Safety When conducting my experiments it is vital that I take the utmost care to be safe in the laboratory. I will wear safety glasses to protect my eyes as well as tucking my tie into my shirt to avoid it coming into contact with any apparatus or substances. Also, when dealing with hydrogen peroxide I will only remove the stopper from the bottle when I need to use it, I will extract it with a syringe and replace the stopper immediately. I will do this as hydrogen peroxide is highly dangerous and can cause the spontaneous combustion of clothing if applied in high concentrations. Also I will take great care when handling glass equipment and will ensure that all apparatus is properly clamped in place before beginning my experiments. I will be aware of others around me, tidying my apparatus away so it does not pose a danger to others. Also, I will wash my hands after conducting my experiments so as not to leave any dangerous substances on my hands which may be ingested if I put my hands near my mouth. MethodApparatus   A water bath   A trough A side arm boiling tube   A test tube rack   A gas cylinder   A stopwatch   A clamp and retort stand   1x 1cmi syringe   1x 5cmi syringe   A bung with a space for a syringe. Thermometer Diagram Procedure Before conducting any experiments I will ensure that the gas cylinder is full of water with no air bubbles by filling it then placing my thumb over it whilst submersing it in the trough. I will also ensure that the water bath is at a temperature of 30i C. After collecting the listed apparatus I will set it up as in the diagram above. I will then remove the bung and collect a liver suspension. I will begin with a concentration of 2% then proceed to use 4%, 6%, 8% and 10% as well as a control of distilled water. I will firstly take a sample of the solution in a test tube and universal indicator solution to it to in order to monitor the pH of the suspension. I will not add a buffer to control the pH as the chemicals in the buffer could interfere with the reaction and alter my results. I will measure out 0. 2cm3 of the suspension using a 1 cm3 syringe being as accurate as is possible with the naked eye when measuring. I will inject this suspension into the side arm boiling tube and replace the bung. I will then use the 5cm3 syringe to measure out 5cm3 of hydrogen peroxide. I will place the syringe into the bung and ensure that all my apparatus is air tight. I will then quickly inject all of the hydrogen peroxide into the boiling tube whilst simultaneously starting the stop clock. I will then record the amount of gas collected in the gas cylinder at ten second intervals for a period of two minutes. I will then repeat each experiment three times for each concentration of liver. I will record all my results on the table below. After collecting my results I will go on to test a different liver concentration until I have three sets of data for five different concentrations as well as a control. I will then tabulate these results and use the average results for each experiment to plot a graph of my results allowing me to analyse them easily. Taking the average of three experiments for each suspension will give me more reliable results as it will reduce the affect of anomalous results. Also, to ensure that all my tests are fair I will endeavour to use exactly the same conditions for each experiment by maintaining a constant temperature and by measuring all substances as accurately as is possible. I will also ensure that my apparatus is set up in exactly the same way for each experiment. When conducting my experiments I will consider all factors which I discussed in the fair testing section of this project making my results as reliable and accurate as possible. Observations On the next page is a table showing my results for the experiments described in my plan. I will go on to analyse these results in the analysis section. Analysis On the next page is a graph showing volume of gas produced against time for the six concentrations of liver suspension I used in my experiments. Although the graph of my results that I produced may at first appear not to agree with my predicted graph it does in fact indicate that my hypothesis was true. The lines on my graph are in the same positions as I predicted apart from the control graph which was higher than I expected. The lines did not flatten out as I predicted however, I believe this is due to the fact that I used a short time scale and the graphs would have flattened out had I used a longer time scale. I did not use a longer time scale as it would have been pointless given that I am investigating the rate of reaction of several different liver concentrations rather than the rate of reaction changing over time in one concentration of liver. On the whole I am happy with my graphs and I think they verify my hypothesis. My graph for the reaction rate of the 2% liver concentration followed this pattern well. Initially there was a dramatic increase in the amount of gas released. After the first ten seconds this slowed significantly, the amount of gas released still increased but it increased much more slowly and steadily. This was because the catalase broke down the hydrogen peroxide into water and oxygen slowly and steadily. The reason for the graph continuously going up slowly throughout the entire two minute period was because there was little catalase compared to hydrogen peroxide meaning that even by the end of the two minutes there was still a lot of hydrogen peroxide which had not been decomposed and so the enzymes were still working at the same rate. I think that if I had let the experiment continue for a longer time period the gradient of the graph would have flattened to zero as all of the hydrogen peroxide would have been decomposed. My line is approximately straight showing me that the reaction rate was roughly the same throughout the experiment however, the gradient is steepest at approximately sixty seconds meaning that the rate was highest here. In order to compare the rates of reaction of all my graphs I will need to calculate the rate of reaction for each graph. I will do this by dividing the amount of oxygen produced by the time taken to produce it. This will give me a rate in cmi of oxygen per second (cmi /s). I have chosen to take the rates of reaction from the points on the graphs after thirty seconds. Although it may seem that the maximum rate is at ten seconds and so I should take this rate I think this is due to the hydrogen peroxide I injected displacing air in the apparatus. I have chosen thirty seconds as I think this is sufficient time for the experiment to have settled after the initial burst of gas and it is not too late that some of the reactions had begun to slow down. The rate of reaction at thirty seconds for the 2% concentration suspension is as follows: 3. 83cmi 30s =0. 13cmi /s (2dp) I chose to take my rates to two decimal places as this is accurate enough for me to analyse my rate graph well and it is not so accurate that it would be difficult to plot on a graph. My graph for the rate of reaction of the 4% concentration liver suspension further supports my hypothesis. It has the same initial increase in gas from when I injected the hydrogen peroxide, it then continues to slope upwards but not as fast as before. As I predicted the 4% graph slopes up at a higher gradient than the 2% solution graph. This can be seen by simply looking at the graph. As predicted the gradient of each line is higher than the one that preceded it. This is because as the concentration of the suspension increases there is more catalase to break down the hydrogen peroxide into its component parts. I will now proceed to compare the gradients and rates of reaction for each concentration. On this graph the gradient of the line and the rate of reaction are the same thing as gradient=change in Y Change in X And rate of reaction=amount of gas produced (change in Y axis) Time (change in x axis) Below is a table showing the rates of reaction for each of my concentrations of catalase including the control experiment of 0% catalase. As before I will take the gradient of the line after thirty seconds. concentration of liver suspension amount of gas produced (cmi ) time (s) rate of reaction (cmi /s). On the next page is a graph of my results, I have plotted concentration of liver suspension against rate of reaction, this will better show my results and will help to verify my hypothesis. As you can see from the graph there is clearly a relationship of proportionality between the rate of reaction and the concentration of liver suspension as I predicted in my hypothesis. I have added a best-fit line to my graph to better show this trend. As I predicted the line is slopes upwards showing that as the concentration of liver suspension increases the rate of reaction increases, this is due to the fact that there was more catalase to collide with the hydrogen peroxide in the higher concentrations. One problem with these results is that my control experiment seems to have a rate of reaction however, this is simply due to the initial burst of gas at the start of the experiment when the hydrogen peroxide that I injected displaced air in my apparatus. Although this effectively means that all of my results are wrong I can still draw sensible conclusions from my graphs as every one of my results had the same displacement of air so when comparing my results this in fact has no effect. If there had been no displacement of air in my apparatus I think this line would have been straight and through the origin showing that rate of reaction and concentration of liver suspension are directly proportional. I will not attempt to subtract the gas displaced by the hydrogen peroxide from my results as this could further magnify any inaccuracies in my experiments and I do not need to in order to draw reliable conclusions from my graph. The conclusion I have come to by looking at my graphs is that my hypothesis was correct. I think that as the concentration of the liver suspension increases so does the rate of reaction proportionally.