The Structure of Costs in the Long Run

On the molecular basis of the recognition of angiotensin II (AII) NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab131 Andreas G. Tzakos 1 , Alexandre M. J. J. Bonvin 2 , Anasstasios Troganis 3 , Paul Cordopatis 4 , Mario L. Amzel 5 , Ioannis P. Gerothanassis 1 and Nico A. J. van Nuland 2 1 Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, GR-45110, Greece, 2 Bijvoet Center for Biomolecular Research, Department of NMR Spectroscopy, Utrecht, the Netherlands; 3 Department of Biological Applications and Technologies, University of Ioannina, Greece; 4 Department of Pharmacy, University of Patras, Greece; 5 Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA The high-resolution 3D structure of the octapeptide hor- mone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using high- resolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 ± 0.23 A ˚ . AII adopts a fairly compact folded structure, with its C-terminus and N-ter- minus approaching to within  7.2 A ˚ of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science 257, 502–507] provides important quantitative information on two common structural fea- tures: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asx- turn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4–7 in the solution structure of AII are required by a mean value of 0.76 ± 0.03 A ˚ for structure alignment and  1.27 ± 0.02 A ˚ for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological ÔnucleusÕ conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor–antigen recognition and binding. Keywords: angiotensin II; monoclonal antibody; NMR; peptide structure; VIb turn. Angiotensin II (AII), the main effector octapeptide hor- mone (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8) of the renin–angiotesin system [1], exerts a variety of actions on different target organs via specific receptors designated AT 1 and AT 2 [2,3]. Most of the known physiological effects of AII have been attributed to AT 1 , e.g. vasoconstriction, aldosterone release, renal The Structure of Costs in the Long Run The Structure of Costs in the Long Run By: OpenStaxCollege The long run is the period of time when all costs are variable The long run depends on the specifics of the firm in question—it is not a precise period of time If you have a oneyear lease on your factory, then the long run is any period longer than a year, since after a year you are no longer bound by the lease No costs are fixed in the long run A firm can build new factories and purchase new machinery, or it can close existing facilities In planning for the long run, the firm will compare alternative production technologies (or processes) In this context, technology refers to all alternative methods of combining inputs to produce outputs It does not refer to a specific new invention like the tablet computer The firm will search for the production technology that allows it to produce the desired level of output at the lowest cost After all, lower costs lead to higher profits—at least if total revenues remain unchanged Moreover, each firm must fear that if it does not seek out the lowest-cost methods of production, then it may lose sales to competitor firms that find a way to produce and sell for less Choice of Production Technology Many tasks can be performed with a range of combinations of labor and physical capital For example, a firm can have human beings answering phones and taking messages, or it can invest in an automated voicemail system A firm can hire file clerks and secretaries to manage a system of paper folders and file cabinets, or it can invest in a computerized recordkeeping system that will require fewer employees A firm can hire workers to push supplies around a factory on rolling carts, it can invest in motorized vehicles, or it can invest in robots that carry materials without a driver Firms often face a choice between buying a many small machines, which need a worker to run each one, or buying one larger and more expensive machine, which requires only one or two workers to operate it In short, physical capital and labor can often substitute for each other Consider the example of a private firm that is hired by local governments to clean up public parks Three different combinations of labor and physical capital for cleaning up 1/15 The Structure of Costs in the Long Run a single average-sized park appear in [link] The first production technology is heavy on workers and light on machines, while the next two technologies substitute machines for workers Since all three of these production methods produce the same thing—one cleaned-up park—a profit-seeking firm will choose the production technology that is least expensive, given the prices of labor and machines Three Ways to Clean a Park Production technology 10 workers machines Production technology workers machines Production technology 3 workers machines Production technology uses the most labor and least machinery, while production technology uses the least labor and the most machinery [link] outlines three examples of how the total cost will change with each production technology as the cost of labor changes As the cost of labor rises from example A to B to C, the firm will choose to substitute away from labor and use more machinery Total Cost with Rising Labor Costs Example A: Workers cost $40, machines cost $80 Labor Cost Machine Cost Total Cost Cost of technology 10 × $40 = $400 × $80 = $160 $560 Cost of technology × $40 = $280 × $80 = $320 $600 Cost of technology 3 × $40 = $120 × $80 = $560 $680 Labor Cost Machine Cost Total Cost Cost of technology 10 × $55 = $550 × $80 = $160 $710 Cost of technology × $55 = $385 × $80 = $320 $705 Example B: Workers cost $55, machines cost $80 2/15 The Structure of Costs in the Long Run × $55 = $165 × $80 = $560 $725 Labor Cost Machine Cost Total Cost Cost of technology 10 × $90 = $900 × $80 = $160 $1,600 Cost of technology × $90 = $630 × $80 = $320 $950 Cost of technology 3 × $90 = $270 × $80 = $560 $830 Cost of technology Example C: Workers cost $90, machines cost $80 Example A shows the firm’s cost calculation when wages are $40 and machines costs are $80 In this case, technology is the low-cost production technology In example B, wages rise to $55, while the cost of machines does not change, in which case technology is the low-cost production technology If wages keep rising up to $90, while the cost of machines remains unchanged, then technology clearly becomes the low-cost form of production, as shown in example C This example shows that as an input becomes more expensive (in this case, the labor input), firms will attempt to conserve on using that input and will instead shift to other inputs that are relatively less expensive This pattern helps to explain why the demand curve for labor (or any input) slopes down; that is, as labor becomes relatively more expensive, profit-seeking firms will seek to substitute the use of other inputs When a multinational employer like Coca-Cola or McDonald’s sets up ...[...]... and how they invest their savings Economists also study how people interact with one another For instance, they examine how the multitude of buyers and sellers of a good together determine the price at which the good is sold and the quantity that is sold Finally, economists analyze forces and trends that affect the economy as a whole, including the growth in average income, the fraction of the population... Policy Influences Aggregate Demand 474 The Theory of Liquidity Preference 475 The Downward Slope of the Aggregate-Demand Curve 477 FYI Interest Rates in the Long Run and the Short Run 478 Changes in the Money Supply 479 The Role of Interest-Rate Targets in Fed Policy 481 IN THE NEWS The FOMC Explains Itself 482 CASE STUDY Why the Fed Watches the Stock Market (and Vice Versa) 482 How Fiscal Policy Influences... Expectations 501 The Long- Run Phillips Curve 501 The Meaning of “Natural” 503 Reconciling Theory and Evidence 504 The Short -Run Phillips Curve 505 The Natural Experiment for the Natural-Rate Hypothesis 506 Shifts in the Phillips Curve: The Role of Supply Shocks 508 IN THE NEWS Will Stagflation Return? 511 The Cost of Reducing Inflation 512 The Sacrifice Ratio 512 Rational Expectations and the Possibility... 225 The Consumer Price Index 226 How the Consumer Price Index Is Calculated 226 Problems in Measuring the Cost of Living 228 FYI What Is In the CPI’s Basket? 229 IN THE NEWS Accounting for Quality Change 230 The GDP Deflator versus the Consumer Price Index 232 Correcting Economic Variables for the Effects of Inflation 233 Dollar Figures from Different Times 234 Indexation 234 Real and Nominal Interest... 13 SAVING, INVESTMENT, AND THE FINANCIAL SYSTEM 271 Financial Institutions in the U.S Economy 272 Financial Markets 272 Financial Intermediaries 274 FYI Key Numbers for Stock Watchers 275 Summing Up 276 PART V THE REAL ECONOMY IN THE LONG RUN 243 CHAPTER 12 PRODUCTION AND GROWTH 245 Economic Growth around the World 246 FYI A Picture Is Worth a Thousand Statistics 248 FYI Are You Richer Than the Richest... “preview of coming attractions.” HOW PEOPLE MAKE DECISIONS There is no mystery to what an economy is Whether we are talking about the economy of Los Angeles, the United States, or the whole world, an economy is just a group of people dealing with one another as they go about their lives Because the behavior of an economy reflects the behavior of the individuals who make up the economy, we begin our study... Benefits of International Trade 186 IN THE NEWS Should the Winners from Free Trade Compensate the Losers? 187 The Arguments for Restricting Trade 188 The Jobs Argument 188 IN THE NEWS Offshore van Gils et al. Cost Effectiveness and Resource Allocation 2010, 8:15 http://www.resource-allocation.com/content/8/1/15 Open Access REVIEW © 2010 van Gils et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Review The scope of costs in alcohol studies: Cost-of-illness studies differ from economic evaluations Paul F van Gils* †1 , Heleen H Hamberg-van Reenen †2 , Matthijs van den Berg †2 , Luqman Tariq †1 and G Ardine de Wit †1,3 Abstract Background: Alcohol abuse results in problems on various levels in society. In terms of health, alcohol abuse is not only an important risk factor for chronic disease, but it is also related to injuries. Social harms which can be related to drinking include interpersonal problems, work problems, violent and other crimes. The scope of societal costs related to alcohol abuse in principle should be the same for both economic evaluations and cost-of-illness studies. In general, economic evaluations report a small part of all societal costs. To determine the cost- effectiveness of an intervention it is necessary that all costs and benefits are included. The purpose of this study is to describe and quantify the difference in societal costs incorporated in economic evaluations and cost-of-illness studies on alcohol abuse. Method: To investigate the economic costs attributable to alcohol in cost-of-illness studies we used the results of a recent systematic review (June 2009). We performed a PubMed search to identify economic evaluations on alcohol interventions. Only economic evaluations in which two or more interventions were compared from a societal perspective were included. The proportion of health care costs and the proportion of societal costs were estimated in both type of studies. Results: The proportion of healthcare costs in cost-of-illness studies was 17% and the proportion of societal costs 83%. In economic evaluations, the proportion of healthcare costs was 57%, and the proportion of societal costs was 43%. Conclusions: The costs included in economic evaluations performed from a societal perspective do not correspond with those included in cost-of-illness studies. Economic evaluations on alcohol abuse underreport true societal cost of alcohol abuse. When considering implementation of alcohol abuse interventions, policy makers should take into account that economic evaluations from the societal perspective might underestimate the total effects and costs of interventions. Introduction Alcohol abuse results in problems on various levels in society. In terms of health, alcohol abuse is not only an important risk factor for chronic disease, but it is also related to unintentional and intentional injuries [1-3]. On the social level the WHO Expert Committee on Problems Related to Alcohol Consumption reported that social harms which can be related to drinking include interper- sonal problems, work problems, violent and other crimes [2]. From the economic point of view, the estimated tangi- ble costs of alcohol in the European Union were €125 bil- lion in 2003, including €59 billion worth of lost productivity through absenteeism, unemployment and lost working years due to premature death [4]. Another study reported that the weighted average costs in four high-income countries (France, USA, Scotland and Can- ada) were 1.4% of the gross domestic product [3]. To reduce the negative effect of alcohol abuse it is nec- essary for countries to develop an alcohol policy and implement prevention programs. An alcohol policy can be defined as a set of measures in a jurisdiction or society aimed at minimizing the health and social problems from alcohol consumption [2]. The alcohol abuse prevention * Correspondence: paul.van.gils@rivm.nl 1 INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. 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Further reproduction prohibited without permission. An Examination of the Long-run Market Reaction to the Announcement of Dividend Omissions and Reductions A Thesis Submitted to the Faculty of Drexel University by Yi Liu in partial fulfillment o f the requirements for the degree of Doctor o f Philosophy June 2003 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number 3086406 Copyright 2003 by Liu, Yi All rights reserved. UMI* UMI Microform 3086406 Copyright 2003 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor. Ml 48106>1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. © Copyright 2003 Yi Liu. All Rights Reserved. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Drexel University O ffice o f Research and Graduate Studies Thesis Approval Form (For Masters and Doctoral Students) Hagerty Library will bond a copy of this form with each copy of your thesis/dissertation. This thesis, entitled / \ r \ yyin.r'ti-eyC -31 through day +180 relative to the WSJ announcement date. For sub-sample comparisons, the statistical significance of the difference between the average abnormal common stock returns is tested using the parametric r-test, assuming unequal variances. The null hypothesis tested is that the difference is equal to zero. The results are identical assuming equal variances. *■*, " , and * denote significance at the 1,5 and 10 percent levels, respectively, in a two-tailed test Difference Decrease in risk Increase in risk between Lower half Upper half Lower half Upper half (1) and (1) (2) (3) (4) (4) -14.70 -4.215 -10.28 -11.35 /-pep --..aiiv Average abnormal return (%) -15.56 -4.41*** -4.00*** -6.31*** -4.16*** -0.95 weiehte?index weighted index '*slatistic Number 0f observations 278 369 369 278 -18.20 -4.249 Average abnormal return (%) -14.87 -10.83 -10.62 Size r-statistic -3.18*** -2.52** -3.30*** -2.78*** -0.70 369 278 278 369 Number of observations -16.46 -3.37 -8.99 -1.730 Average abnormal return (%) -10.72 -2.40** -4.54*** -2.46** ■0.30 Size and industry r-statistic -0.78 369 278 278 369 Number of observations -12.00 -7.01 -7.524 -9.45 Size and nrior Average abnormal return (%) -14.54 -2.66*** -2.66*** -1.87* -1.93* -1.13 nerformance f*statistic 369 369 278 278 Number of observations -4.66 -8.43 -9.53 -5.761 Industry and nrior AveragC aboonnal rc*ura -15.29 -3.07*** -2.00** -1.31 -2.38** -0.90 performance statistic U J l U l H l d l lW THE LONG-RUN RELATIONSHIPS AND SHORT-TERM LINKAGES IN INTERNATIONAL SECURITIZED REAL ESTATE MARKETS CHEN ZHIWEI NATIONAL UNIVERSITY OF SINGAPORE 2007 THE LONG-RUN RELATIONSHIPS AND SHORT-TERM LINKAGES IN INTERNATIONAL SECURITIZED REAL ESTATE MARKETS CHEN ZHIWEI (B.Econ, Tsinghua University of China) A THESIS SUBMITTED FOR THE DEGREE OF MASTER OF SCIENCE DEPARTMENT OF REAL ESTATE NATIONAL UNIVERSITY OF SINGAPORE 2007 Acknowledgement I would like to express my sincerest gratitude to all those who gave me the possibility to complete this thesis. I would like to thank my supervisor, Associate Professor Liow Kim Hiang, for his stimulating suggestions, continuous guidance and constructive ideas helped me in all the time of research for and writing of this thesis. Without his suggestions, encouragement and great supervision, I could not complete my study and finish this research work. I would also like to thank A/P Fu Yuming, A/P Ong Seow Eng, A/P Sing Tien Foo, A/P Tu Yong, A/P Ho Kim Hin, David, A/P Zhu Jieming and other professors who have helped me in my research and coursework in various ways. I am also grateful to the Department of Real Estate, National University of Singapore, for giving me the opportunity and research scholarship to finish my graduate study. Besides, I wish to thank the entire SDE family for providing a loving environment for me. Mr. Zhu Haihong, Mr. Sun Liang, Mr. Wang Jingliang, Ms. Huang Yingying, Ms. Deng Leiting, Ms. Dong Zhi, Mr. Li Lin, Mr. Zhou Dingding, Mr. Wu Jianfeng, Mr. Qin Bo, and Mr. You Wenpei, deserve special mention. I wish to thank all my friends and colleagues for their selfless assistance and companionship during my study in the program. Their generous help and great friendship make all this a memorable time for me. Lastly, and most importantly, I wish to thank my parents, Chen Yuanchun and Lin Ruiqin. They bore me, raised me, supported me, taught me, and loved me. To them I dedicate this thesis. I Table of Contents Acknowledgement ..................................................................................... I Table of Contents ..................................................................................... II Summary ................................................................................................ IV Chapter 1 1.1 1.2 1.3 1.4 1.5 Introduction ......................................................................... 1 Background and Conceptual Framework ..................................................................1 Research Objective and Expected Contribution........................................................5 Research Data ...............................................................................................................6 Research Methodology .................................................................................................7 Organization .................................................................................................................9 Chapter 2 Literature Review .............................................................. 12 2.1 Introduction ...................................................................................................................12 2.2 International Diversification: Concept and Earlier Studies ......................................12 2.3 Structural Breaks and Long-run Relationships ..........................................................17 2.3.1 Concept and Background ..................................................................................17 2.3.2 Methodology of Testing Structural Breaks .......................................................19 2.3.3 Empirical Evidence ............................................................................................21 2.4 The Heteroskedasticity and Short-term Linkages ......................................................29 2.4.1 Concept and Background ................................................. ... article about the complexity of the belief that banks can be “too-big-to-fail.” 7/15 The Structure of Costs in the Long Run The Size and Number of Firms in an Industry The shape of the long- run average... close to the bottom of the long- run average cost curve? 14/15 The Structure of Costs in the Long Run Critical Thinking Questions It is clear that businesses operate in the short run, but they ever... factory 3/15 The Structure of Costs in the Long Run [link] illustrates the idea of economies of scale, showing the average cost of producing an alarm clock falling as the quantity of output rises