What Happens When a Country Has an Absolute Advantage in All Goods

The molecular surface of proteolytic enzymes has an important role in stability of the enzymatic activity in extraordinary environments Youhei Yamagata 1 , Hiroshi Maeda 1 , Tasuku Nakajima 1 and Eiji Ichishima 2 1 Laboratory of Molecular Enzymology, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Japan; 2 Department of Biotechnology, Faculty of Engineering, Soka University, Hachioji, Tokyo, Japan It is scientifically and industrially important 1 to clarify the stabilizing mechanism of proteases in extraordinary envi- ronments. We used subtilisins ALP I and Sendai as models to study the mechanism. Subtilisin ALP I is extremely sensitive to highly alkaline conditions, even though the enzyme is produced by alkalophilic Bacillus, whereas sub- tilisin Sendai from alkalophilic Bacillus is stable under conditions of high alkalinity. We constructed mutant subtilisin ALP I enzymes by mutating the amino acid residues specific for subtilisin ALP I to the residues at the corresponding positions of amino acid sequence alignment of alkaline subtilisin Sendai. We observed that the two mutations in the C-terminal region were most effective for improving stability against surfactants and heat as well as high alkalinity. We predicted that the mutated residues are located on the surface of the enzyme structures and, on the basis of three-dimensional modelling, that they are involved in stabilizing the conformation of the C-terminal region. As proteolytic enzymes frequently become inactive due to autocatalysis, stability of these enzymes in an extraordinary environment would depend on the confor- mational stability of the molecular surface concealing scissile peptide bonds. It appeared that the stabilization of the molecular surface structure was effective to improve the stability of the proteolytic enzymes. Keywords: alkalophilic alkaline resistance; Bacillus;mole- cular surface structure; serine protease; subtilisin. There have been several studies of the difference aspects of proteolytic enzymes and they have been used in various industrial fields. In particular, subtilisins, serine proteases from a variety of Bacillus species,aresomeofthemost investigated enzymes [1,2]. Subtilisins are classified into three groups, the neutral subtilisins, the alkaline subtilisins and Ôthe ALP I-typeÕ subtilisin (Fig. 1) [3]. The neutral subtilisins consist of the subtilisins from neutrophilic Bacillus such as subtilisin BPN¢ [4], Carlsberg [5], E [6], and NAT [7]. The alkaline subtilisin group contains the enzymes from alkalophilic Bacillus such as subtilisin YaB [8], no. 221 protease [9], Savinase [10], subtilisin Sendai (Sendai) [11]. Subtilisin ALP I (ALP I) from alkalophilic Bacillus NKS-21 [3] is only member of the ALP I-type subtilisins. ALP I is extremely sensitive to high alkaline conditions, even though the enzyme is produced by an alkalophilic Bacillus. On the other hand, Sendai from alkalophilic Bacillus sp. G-825-6, categorized as an alkaline subtilisin, is very stable under highly alkaline conditions. Maeda et al. reported that the inactivation of subtilisin ALP I at high alkalinity was caused by the instability of its molecular surface structure and autolysis in the N-terminal region and/or the C-terminal region [12,13]. We hypothesized that the divergence of the What Happens When a Country Has an Absolute Advantage in All Goods What Happens When a Country Has an Absolute Advantage in All Goods By: OpenStaxCollege What happens to the possibilities for trade if one country has an absolute advantage in everything? This is typical for high-income countries that often have well-educated workers, technologically advanced equipment, and the most up-to-date production processes These high-income countries can produce all products with fewer resources than a low-income country If the high-income country is more productive across the board, will there still be gains from trade? But good students of Ricardo understand that trade is about mutually beneficial exchange Even when one country has an absolute advantage in all products, trade can still benefit both sides This is because gains from trade come from specializing in one’s comparative advantage Production Possibilities and Comparative Advantage Consider the example of trade between the United States and Mexico described in [link] In this example, it takes four U.S workers to produce 1,000 pairs of shoes, but it takes five Mexican workers to so It takes one U.S worker to produce 1,000 refrigerators, but it takes four Mexican workers to so The United States has an absolute advantage in productivity with regard to both shoes and refrigerators; that is, it takes fewer workers in the United States than in Mexico to produce both a given number of shoes and a given number of refrigerators Resources Needed to Produce Shoes and Refrigerators Country Number of Workers needed to produce 1,000 units — Shoes Number of Workers needed to produce 1,000 units — Refrigerators United States workers worker Mexico workers workers 1/10 What Happens When a Country Has an Absolute Advantage in All Goods Absolute advantage simply compares the productivity of a worker between countries It answers the question, “How many inputs I need to produce shoes in Mexico?” Comparative advantage asks this same question slightly differently Instead of comparing how many workers it takes to produce a good, it asks, “How much am I giving up to produce this good in this country?” Another way of looking at this is that comparative advantage identifies the good for which the producer’s absolute advantage is relatively larger, or where the producer’s absolute productivity disadvantage is relatively smaller The United States can produce 1,000 shoes with four-fifths as many workers as Mexico (four versus five), but it can produce 1,000 refrigerators with only one-quarter as many workers (one versus four) So, the comparative advantage of the United States, where its absolute productivity advantage is relatively greatest, lies with refrigerators, and Mexico’s comparative advantage, where its absolute productivity disadvantage is least, is in the production of shoes Mutually Beneficial Trade with Comparative Advantage When nations increase production in their area of comparative advantage and trade with each other, both countries can benefit Again, the production possibility frontier is a useful tool to visualize this benefit Consider a situation where the United States and Mexico each have 40 workers For example, as [link] shows, if the United States divides its labor so that 40 workers are making shoes, then, since it takes four workers in the United States to make 1,000 shoes, a total of 10,000 shoes will be produced (If four workers can make 1,000 shoes, then 40 workers will make 10,000 shoes) If the 40 workers in the United States are making refrigerators, and each worker can produce 1,000 refrigerators, then a total of 40,000 refrigerators will be produced Production Possibilities before Trade with Complete Specialization Country Shoe Production — using 40 workers Refrigerator Production — using 40 workers United States 10,000 shoes or 40,000 refrigerators Mexico 8,000 shoes or 10,000 refrigerators As always, the slope of the production possibility frontier for each country is the opportunity cost of one refrigerator in terms of foregone shoe production–when labor is transferred from producing the latter to producing the former (see [link]) 2/10 What Happens When a Country Has an Absolute Advantage in All Goods Production Possibility Frontiers (a) With 40 workers, the United States can produce either 10,000 shoes and zero refrigerators or 40,000 refrigerators and zero shoes (b) With 40 workers, Mexico can produce a maximum of 8,000 shoes and zero refrigerators, or 10,000 refrigerators and zero shoes All other points on the production possibility line are possible combinations of the two goods that can be produced given current resources Point A on both graphs is where the countries start producing and consuming before trade Point B is where they end up after trade Let’s say that, in the situation before trade, each nation prefers to produce a combination of shoes and refrigerators that is shown at point A [link] shows the output of each good for each country and ...7.4. SCALE-FREE NETWORKS 181 systematically disabling hubs should quickly partition a network into sev- eral disjoint components, a highly undesirable situation. To illustrate these matters, Figure 7.12 shows what happens when we systematically remove vertices from a scale-free graph in comparison to re- moving the best-connected vertices from an ER random graph. We also show the effect of removing randomly selected vertices from a scale-free graph (which is very similar to randomly removing vertices from an ER graph). A scale-free network is thus seen to be sensitive to a targeted attack, but just as robust as an ER random graph in the case of a random attack. 1.0 0.8 0.6 0.4 0.2 0.2 0.4 0.6 0.8 1.0 Scale-free network Random network Scale-free network, randomremoval Fractionofremovedvertices Fractionoutsidegiantcluster Figure 7.12: The fraction of vertices outside the giant component when removing hubs from a scale-free graph, and those from an ER random graph. Related networks As we mentioned, the Barab ´ asi-Albert approach for constructing a scale- free graph has one important shortcoming when comparing it to real-world networks: its relatively low clustering coefficient. A better understanding of real-world phenomena should normally be reflected by better models and in this sense, a BA random graph is difficult to validate against many real-world data. Therefore, researchers have been seeking solutions for con- structing scale-free graphs that have a high clustering coefficient. As argued by Dorogovtsev et al. [2003], constructing such graphs is ac- tually quite simple. The trick is to make sure that there are many triangles. This can be achieved, for example, by adding an edge to a triple at each step of the growing process. (Recall that a triple was a subgraph with 3 vertices and 2 edges.) Holme and Kim [2002] provide a scheme that combines scale- freeness and at the same time allows to tune to what extent clustering is to be provided. Their algorithm proceeds as follows: A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2-2 phenotype with homogeneous structure I. H. Lai 1 , Kung-Yu Lin 1 , Mikael Larsson 2 , Ming Chi Yang 1 , Chuen-Huei Shiau 3 , Ming-Huei Liao 4 and Simon J. T. Mao 1,5 1 Institute of Biochemical Engineering, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan 2 Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden 3 Pingtung County Livestock Disease Control Center, Pingtung, Taiwan 4 Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan 5 Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan Haptoglobin (Hp) is an acute-phase protein (respon- sive to infection and inflammation) that is present in the plasma of all mammals [1–4]. A recent study has found that Hp also exists in lower vertebrates (bony fish) but not in frog and chicken [5]. The most fre- quently reported biological functions of the protein are to capture released hemoglobin during excessive hemo- lysis [6] and to scavenge free radicals during oxidative Keywords amino acid sequence; deer and human haptoglobin; monoclonal antibody; phenotype; purification Correspondence S. J. T. Mao, Institute of Biochemical Engineering, College of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30050, Taiwan Fax: +886 3 572 9288 Tel: +886 3 571 2121 ext. 56948 E-mail: mao1010@ms7.hinet.net Database The sequence corresponding to deer Hp is available in the DDBJ ⁄ EMBL ⁄ GenBank database under the accession number EF601928 (Received 21 November 2007, revised 20 December 2007, accepted 28 December 2007) doi:10.1111/j.1742-4658.2008.06267.x Similar to blood types, human plasma haptoglobin (Hp) is classified into three phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inherited from two alleles Hp 1 and Hp 2 (represented in bold), but only the Hp 1-1 phenotype is found in almost all animal species. The Hp 2-2 protein consists of complicated large polymers cross-linked by a2-b subunits or (a2-b) n (where n ‡ 3, up to 12 or more), and is associated with the risk of the development of diabetic, cardiovascular and inflam- matory diseases. In the present study, we found that deer plasma Hp mimics human Hp 2, containing a tandem repeat over the a-chain based on our cloned cDNA sequence. Interestingly, the isolated deer Hp is homogeneous and tetrameric, i.e. (a-b) 4 , although the locations of )SH groups (responsible for the formation of polymers) are exactly identical to that of human. Denaturation of deer Hp using 6 m urea under reduc- ing conditions (143 mm b-mercaptoethanol), followed by renaturation, sustained the formation of (a-b) 4 , suggesting that the Hp tetramers are not randomly assembled. Interestingly, an a-chain monoclonal antibody (W1), known to recognize both human and deer a-chains, only binds to intact human Hp polymers, but not to deer Hp tetramers. This implies that the epitope of the deer a-chain is no longer exposed on the surface when Hp tetramers are formed. We propose that steric hindrance plays a major role in determining the polymeric formation in human and deer polymers. Phylogenetic and immunochemical analyses revealed that BioMed Central Page 1 of 6 (page number not for citation purposes) Virology Journal Open Access Research Vaccinia virus A12L protein and its AG/A proteolysis play an important role in viral morphogenic transition Su Jung Yang † and Dennis E Hruby* † Address: Department of Microbiology, Oregon State University, Corvallis, Oregon 97331-3804, USA Email: Su Jung Yang - sujung.yangs@gmail.com; Dennis E Hruby* - hrubyd@oregonstate.edu * Corresponding author †Equal contributors Abstract Like the major vaccinia virus (VV) core protein precursors, p4b and p25K, the 25 kDa VV A12L late gene product (p17K) is proteolytically maturated at the conserved Ala-Gly-Ala motif. However, the association of the precursor and its cleavage product with the core of mature virion suggests that both of the A12L proteins may be required for virus assembly. Here, in order to test the requirement of the A12L protein and its proteolysis in viral replication, a conditional lethal mutant virus (vvtetOA12L) was constructed to regulate A12L expression by the presence or absence of an inducer, tetracycline. In the absence of tetracycline, replication of vvtetOA12L was inhibited by 80% and this inhibition could be overcome by transient expression of the wild-type copy of the A12L gene. In contrast, mutation of the AG/A site abrogated the ability of the transfected A12L gene to rescue, indicating that A12L proteolysis plays an important role in viral replication. Electron microscopy analysis of the A12L deficient virus demonstrated the aberrant virus particles, which were displayed by the AG/A site mutation. Thus, we concluded that the not only A12L protein but also its cleavage processing plays an essential role in virus morphogenic transition. Background Proteolytic processing in vaccinia virus (VV) plays an important role in morphogenic transitions during the virus replication cycle. To date, six VV-encoded, proteolyt- ically processed proteins have been reported. They are the gene products of A10L (p4a), A3L (p4b), L4R (p25K), A17L (p21K), G7L, and A12L (p17K) [1-6]. Extensive studies of these proteins have provided more specific mechanisms of VV proteolysis in terms of the transforma- tion of immature virions (IV) into intracellular mature vir- ions (IMV). One of the VV major core proteins, A10L has been shown to be essential in virus replication and its absence in virus assembly resulted in defective virus morphology such as IV-like particles, which lacked granular viral materials and consequently produced the irregular-shaped virus parti- cles [7]. These morphogenic defects suggested that A10L protein is required for the correct organization of the nucleocomplex within the IVs [7,8]. L4R, a DNA binding protein, plays an essential role in virus replication, being involved in an early stage of infection such as early tran- scription or unpackaging viral core and DNA [9,10]. The L4R-deficient virus produced virus particles with non- associated viroplasm and its surrounding viral mem- branes, suggesting its role in correct incorporation of viral DNA and cores with immature virus membrane. Published: 11 July 2007 Virology Journal 2007, 4:73 doi:10.1186/1743-422X-4-73 Received: 29 June 2007 Accepted: 11 July 2007 This article The Fear Factor Also by Colin Read GLOBAL FINANCIAL MELTDOWN: HOW WE CAN AVOID THE NEXT ECONOMIC CRISIS INTERNATIONAL TAXATION HANDBOOK: POLICY, PRACTICE, STANDARDS AND REGULATION (edited with G. Gregoriou) The Fear Factor What Happens When Fear Grips Wall Street Colin Read © Colin Read 2009 All rights reserved. No reproduction, copy or transmission of this publication may be made without written permission. No portion of this publication may be reproduced, copied or transmitted save with written permission or in accordance with the provisions of the Copyright, Designs and Patents Act 1988, or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, Saffron House, 6-10 Kirby Street, London EC1N 8TS. Any person who does any unauthorized act in relation to this publication may be liable to criminal prosecution and civil claims for damages. The author has asserted his right to be identified as the author of this work in accordance with the Copyright, Designs and Patents Act 1988. First published 2009 by PALGRAVE MACMILLAN Palgrave Macmillan in the UK is an imprint of Macmillan Publishers Limited, registered in England, company number 785998, of Houndmills, Basingstoke, Hampshire RG21 6XS. Palgrave Macmillan in the US is a division of St Martin’s Press LLC, 175 Fifth Avenue, New York, NY 10010. Palgrave Macmillan is the global academic imprint of the above companies and has companies and representatives throughout the world. Palgrave® and Macmillan® are registered trademarks in the United States, the United Kingdom, Europe and other countries. ISBN-13: 978–0–230–22846–7 hardback This book is printed on paper suitable for recycling and made from fully managed and sustained forest sources. Logging, pulping and manufacturing processes are expected to conform to the environmental regulations of the country of origin. A catalogue record for this book is available from the British Library. A catalog record for this book is available from the Library of Congress. 10 9 8 7 6 5 4 3 2 1 18 17 16 15 14 13 12 11 10 09 Printed and bound in Great Britain by CPI Antony Rowe, Chippenham and Eastbourne I dedicate this book to my fiancé and wonderful partner, Natalie, and my mother, Gail This page intentionally left blank vii Contents List of Figures ix Preface x About the Author xi Introduction 1 Part I The Nature of Risk 5 1 The Biology and Psychology of Fear 7 2 An Economic Definition of Fear and Risk 16 Part II The Supply and Demand of Loanable Funds 19 3 The Demand Side 21 4 The Supply Side 32 5 Balance of Capital 44 Part III Measurement of Risk 51 6 The Risk Premium – How Risk Affects Expected Returns 53 7 The Fear Premium 59 8 The Demographics of Risk and Fear 67 9 The Microeconomics of Risk Aversion 76 Part IV The Problems with Risk 83 10 Moral Hazard 85 11 Privatized Gains and Socialized Losses 93 12 Adverse Selection and Imperfect Information 105 13 Risk, Uncertainty, Fear, and Gambling 112 Part V Risk and the Market 119 14 Market Volatility and Returns 121 viii Contents 15 Fear, Panic, and Market Returns 126 16 The Fear Factor 132 Part VI A History of Panics 137 17 A Brief History of the Fear-Gripped Market 139 18 The Roaring Twenties and the Great Crash 151 19 The Depression-Gripped Economy 156 20 Along Comes Keynes 162 Part VII Coordination Failures 171 21 The Market for Lemmings, or A Tale of Two Cultures 173 22 The Role of Machines and Programmed Trading 179 23 The Ratings Agencies – More Perfect Information? 184 Part VIII Social Responsibility as an Antidote to Fear 189 24 Where Were the Regulators 191 25 Ethics and Social Responsibility 202 26 Wall Street, Main Street, and the Social Contract 207 Part IX Institutions That Ameliorate or Amplify Fear 213 27 The Media as an Antidote to Fear 215 28 Politics That Fan the Flames of Fear 221 29 Is There More to Fear than Fear Itself? 223 Part X Solutions to an Economic Quagmire 227 30 Economic Leadership as an Antidote ... cost in producing lumber Step In this example, absolute advantage is the same as comparative advantage Canada has the absolute and comparative advantage in lumber; Venezuela has the absolute and... Total 9,500 28,500 This numerical example illustrates the remarkable insight of comparative advantage: even when one country has an absolute advantage in all goods and another country has an absolute. .. how to calculate absolute and comparative advantage and the way to apply them to a country s production Calculating Absolute and Comparative Advantage In Canada a worker can produce 20 barrels