bluuebunny/crossref_metadata_2025 huggingface dataset:
Technological Progress, Investment, and Full-Employment Growth
Authors: Cragg J. G.
Published: June 2006

Technological progress and investment are considered generally to be among the crucial determinants of economic growth; both have been prominent accompaniments of experienced growth. It seems likely that they are closely related, and a way of seeing this relationship is desirable. This paper seeks to develop a theoretical framework to help examine their roles in the growth of output, to show how they influence the paths which output and other economic variables trace out through time and to lead towards a more general theory of growth. However, no such general theory is developed. Many factors relevant to the course of economic growth are not considered, especially those concerned with what would happen if the economy moved away from full employment. Consequently, the analysis is not intended to be immediately relevant to actual conditions, but merely to throw some light on the relationships between technological progress and investment.

The analysis is related closely to the work of Nicolas Kaldor. However, the model contains a more flexible treatment of the effects of technological progress and the willingness to invest, in order that we may be better able to examine, in a less rigid framework, the effects of past courses of investment and technological progress on present developments in the economy. The variables of the model consist of a few aggregates expressed in real terms and we shall not be concerned with the method of their measurement.
The Canadian Consumer Price Index
Authors: Asimakopulos A.
Published: June 2006

The periodic revision of the weights for an index provides an opportunity to review and modify the concepts and procedures used and also to give information about them. The latest revision of the Canadian Consumer Price Index (CPI) has made some use of this opportunity to change procedures, but the explanation of the index leaves much to be desired. This is unfortunate because the published material describing the procedures used in the construction of the Canadian CPI is very limited. In the Preface of an earlier publication, “a more technical reference paper as well as other explanations of the index” were announced for later release. These explanations have not appeared, and the publication under review, with its extensive quotations from the earlier publication, is not a suitable substitute.
Time Series Analysis by Electronic Computers: A Report on Some Recent Applications at the Dominion Bureau of Statistics
Authors: Crozier R. B. , Darcovich W.
Published: June 2006

Economists and statisticians are gradually amassing new knowledge of economic processes and enlarging the range of data which provide the underpinnings of their craft. Since the end of the Second World War, a number of new statistical tools have been developed for measuring the performance of the economy, and a good deal of new quantitative information on the structure and behaviour of the economic system has been collected. Among these new tools have been developments in the field of social accounting, and new and improved techniques for isolating and studying fluctuations in the business cycle. It is with the latter question that this paper is concerned-the decomposition of time series into their trend-cycle, seasonal, and residual elements. While the work in this field in Canada in the early 1950's was initially focused on measuring cyclical fluctuations in the quarterly national accounts, it has long since evolved a full-fledged life of its own, and a general programme of time series analysis has been under way at the Dominion Bureau of Statistics since 1955. The recent application of electronic computers to the problem is rapidly transforming the entire field.

The present paper has a three-fold aim: to review the rationale of time series analysis; to give an account of the background and status of the work at the Dominion Bureau of Statistics; and to provide a brief outline of the electronic computer programme now in use in this area.
An Ombudsman Scheme for Canada
Authors: Rowat Donald C.
Published: June 2006

There has been considerable discussion recently in the English-speaking world about the office of Ombudsman, or complaints commissioner, in the Nordic countries. The present paper first explains the need for the office, and shows how it meets this need. We then deal with arguments that have been raised against transplanting the institution to other countries, consider some problems regarding its functions and powers, and finally discuss the specific problem of its application to Canada.

Briefly stated, the argument for the Ombudsman scheme derives from the fact that all democratic countries in the twentieth century have experienced a shift from the laissez-faire to the positive state. The accompanying tremendous growth in the range and complexity of government activities has brought with it the need to grant increasing powers of discretion to the executive side of government; and as Dicey has warned us, “Wherever there is discretion, there is room for arbitrariness.” It is quite possible nowadays for a citizen's rights to be accidentally crushed by the vast juggernaut of the government's administrative machine. In this age of the welfare state, thousands of administrative decisions are made each year by governments or their agencies, many of them by lowly officials; and if some of these decisions are arbitrary or unjustified, there is no easy way for the ordinary citizen to gain redress.
The Protestant Ethic as a General Precondition for Economic Development
Authors: Hansen Niles M.
Published: June 2006

Problems of economic development have inevitably stimulated interest in human motivation as it pertains to economic action. In this regard, frequent allusion has been made to Max Weber's The Protestant Ethic and the Spirit of Capitalism. This paper argues that understanding of Weber's thesis concerning both the Protestant ethic and capitalism has been frequently erroneous or incomplete, and that when his thought concerning the metaphysical foundations of economic rationality is seen in an adequate context its implications for economic motivation and development problems are more important than has been generally acknowledged. More specifically, the present analysis holds that Weber's basic ideas concerning the practical economic effects of the economic actor's value orientation are valid within the framework of any given economic system.

The first two sections attempt to clarify Weber's thought concerning the nature of the Protestant ethic and its relation to capitalism. The remainder of the article deals with the contemporary significance of Weber's insight for economic development in Soviet Russia and in the newly-developing countries.
Investment Policy for Economic Development: Some Lessons of the Communist Experience
Authors: Fallenbuchl Z. M.
Published: June 2006

Communist experience in the field of investment policy for economic development is particularly instructive in connection with such problems as the determination of the rate of investment which results in the highest possible rate of growth; balanced versus unbalanced development; and the role of the rate of interest in the efficient allocation of investment funds. Our purpose is to examine this experience in relation to the first of the above problems. Since the three problems overlap, however, the paper relates to some extent to the other two.

It is suggested that the investment experience of Communist countries is relevant for developing countries in general. Although the results of various policies have been conditioned by the specific institutional framework of the Communist countries, they seem to depend also on the logic of the process of economic growth and of the basic economic problem of allocating scarce resources. Communist economists have been forced to admit that some aspects of economic development are as difficult under socialism as they are under capitalism, although until recently this fact was consistently denied. It is also possible, as has been suggested by Professor T. Haavelmo, that the process of economic growth can be seen most clearly when it is studied in a centrally planned economy, where major complications of a market economy are absent. Moreover, some features of the Communist system reflect the leaders' desire to achieve fast economic growth, and such measures as a high rate of forced saving and a large volume of public investment may be found in any country trying to accelerate its development.
Canadian Anti-Combines Administration, 1952–1960
Authors: Rosenbluth G. , Thorburn H. G.
Published: June 2006

Important changes were made in the Combines Investigation Act in 1952, and again in 1960; the intervening period provides a suitable unit for the study of operations under the Act. We shall try to account for the changes that were made in 1952 and for the manner in which the Act was administered thereafter, in terms of some basic propositions about the process of government in Canada, which are well known though perhaps not universally accepted. We conclude with a brief discussion of the 1960 revision of the Act.

Canadian governments of both parties must try to avoid policies that will antagonize large blocks of voters. They must also steer clear of policies that will lose them the support of substantial business interests, not only because they depend on business groups for campaign funds, but also because the environment in which government operates is influenced, in a great variety of ways, by the actions and attitudes of the major business groups. Many policy decisions, particularly in non-economic fields, do not involve a conflict between these two objectives. Where there is a conflict, the policy decisions that emerge represent a compromise.
Financial Alternatives to International Commodity Stabilization
Authors: Swerling Boris C.
Published: June 2006

Modern societies apply certain concepts of the “social minimum” in sustaining domestic groups whose incomes are either cyclically or chronically depressed. Presumably, postwar programs of international foreign aid reflect an extension of this attitude. The first major effort in that direction, the European Recovery Program, was brilliantly successful in providing the base upon which Europe built its impressive economic performance of the past dozen years. The very success of the Marshall Plan, however, leads to a certain impatience with the comparatively unsatisfactory results of the more recent aid efforts—those directed towards accelerating economic growth in the less developed countries (LDC's). At the very time when the United States Congress is becoming increasingly disenchanted with foreign aid, the rising political power of the LDC's in the various agencies of the United Nations has been adding to the external pressures for an enlarged aid effort, as evidenced by the United Nations Conference on Trade and Development held in Geneva from March to June this year.

The newer focus of foreign aid raises particularly difficult problems both of diagnosis and of prescription. On the one hand, disturbances arising from cyclical instability within individual LDC's are often compounded by those associated with structural maladjustment, and it is by no means an easy task to distinguish between these separate sources of trouble. On the other hand, because primary commodities loom so large in the export trade of the LDC's, the industrial countries can be led (by a combination of good intentions and political blackmail) to accept, in the name of foreign aid, commodity policies that are ill-conceived and self-defeating. It is just as important to resist the implementation of unwise policies as it is to develop new institutional devices appropriate to current circumstances.
The Short-Run Effects of Instalment Credit Control
Authors: Chiang Alpha C.
Published: June 2006

In an earlier paper, I presented an analysis of the intermediate-run effects of instalment credit control, that is, the effects prevailing after the new credit terms have fully replaced the old ones. Although brief reference was made there to the effects of control in the short run, that is, in the time periods immediately following the change in credit terms, yet several interesting questions regarding the short run had to be ignored because of the scope of that paper. One may ask, for example: Does the down-payment effect tend to grow or diminish in strength from one period to the next during the transition from old credit terms to new ones? What about the maturity effect? Do these effects change with time, if at all, at a steady rate? In one direction only, or with reversals)? And how will different types of consumer reaction to new credit terms, as reflected in the amount of credit purchases, modify the down-payment and maturity effects, especially when there is perversity? These questions are important because for purposes of credit control policy, the short-run effects are in many cases more relevant than the intermediate-run effects. The present paper seeks to answer these questions.

As the questions themselves suggest, the following discussion will be principally concerned with the delineation of the time paths of effects of credit term changes. In this sense, then, the paper pertains to the realm of “dynamics,” in contrast to the comparative-statics orientation of the earlier article. As in the earlier paper, I shall assume (a) a constant rate of growth of credit purchases before control, (b) uniform down-payment and maturity terms on all credit purchases, (c) straight-line amortization of all instalment debts, and (d) the absence of secondary effects. But instead of assuming that new credit terms will always result in a new (fixed) rate of growth of instalment purchases, I shall also consider several other types of consumer reaction. Finally, to make the analysis more general, the concept “marginal propensity to cut outlays for down payments” will be introduced, to supplement the “marginal propensity to cut outlays for instalments” used in the other paper.
The Two Themes of Canadian Federalism
Authors: Smiley Donald V.
Published: June 2006

Canadian federal experience has centred around two major themes. The first relates to cultural dualism, the desire and ability of French- and English-speaking Canadians to survive as such and to use the governmental institutions which they respectively dominate in order to ensure this outcome. The second involves public action to meet the material expectations of individuals and groups living within an economy where burdens and benefits have been determined largely by the economic policies of successive federal administrations. Those who have concerned themselves with Canadian federalism have usually believed, explicitly or implicitly, that either the cultural or the economic problem was the major challenge which the federal system faced. Thus there are two versions of what our constitutional arrangements are all about, and these are most strikingly illustrated by the divergent perspectives of the Rowell-Sirois and Tremblay Commission. The former was almost exclusively concerned with the reallocation of revenues, revenue sources, and functional responsibilities between the two levels of government and did not deal in any explicit way with the impact of existing or proposed arrangements on the survival of the two cultures. To the Tremblay Commission the great theme of our constitutional history since Confederation is the attempt of English-speaking Canada to subvert the original federal compact and the resistance of these attempts by French Canadians; its Report does deal in great detail with economic issues but its basic argument is that the essential and permanent value of Canadian federalism is to make possible the survival of the two cultural groups.
Canadian Automotive Protection: Content Provisions, The Bladen Plan, And Recent Tariff Changes
Authors: Wonnacott Paul
Published: June 2006

In the past several years, a Royal Commission has reported on the automotive industry and a number of changes have been made in tariffs on automobiles and parts. Although the changes of late 1962 and late 1963 differed in detail from the recommendations of Dean Bladen in his Royal Commission report, they introduced in an alternative form the major innovation recommended by the report, namely, export incentives. By encouraging exports, and particularly exports of parts, the government hoped to stimulate Canadian employment, improve the current account balance, and contribute to the efficiency of the Canadian industry by making possible longer production runs.

Issues of great complexity were introduced by both the Bladen recommendations and the recent changes. Evaluation of their probable effects is made doubly difficult because of the previously existing system of import duties compounded with Canadian content requirements. Nevertheless, it is important that a detailed study be made of recent innovations, particularly as the three-year limit on the changes of late 1963 has made it clear that there will be a major review of policy in the near future. American objections to the innovations, and the possibility of retaliation, have further increased the importance of an evaluation.
La Transformation Du Parti Liberal Quebecois
Authors: Comeau Paul-Andre
Published: June 2006

La science politique n'a pas encore réussi à élaborer de grands ensembles théoriques. A vrai dire, les politicologues doivent se contenter de quelques généralisations, assimilables tout au plus à des hypothèses de travail d'une nature bien particulière, de typologies destinées à faciliter le dépouillement des données politiques. Signalons à la volée, les multiples typologies des régimes politiques, les essais de classification de « l'homme politique » et les théories des « élites ». Toutefois, devant la nécessité de développer et de multiplier démarches et recherches en vue d'échaffauder un début de théorie, il nous paraît intéressant, utile peut-être, de tenter de découvrir la dynamique qui agite et soutient les divers éléments d'une telle typologie.

Ainsi, la typologie des partis politiques, mise au point par Maurice Duverger. Le juriste français a regroupé autour de deux principaux pôles les divers types de partis politiques que connaît le monde contemporain. Les « partis de notables », groupes restreints composés de personnalités en vue dans un milieu et dont l'objectif unique se définit par l'organisation des campagnes électorales, se dressent contre les « partis de masse », créés par les mouvements socialistes européens et destinés à rallier tous les sympathisants d'une même cause politique, de façon permanente. Bien sûr, Duverger reconnaît la possibilité de multiples variantes, sur un continuum reliant ces deux pôles extrêmes.
A Contradiction in Hobbes' Analysis of Sovereignty
Authors: Williamson Colwyn
Published: June 2006

In this article, I argue that there is a fundamental contradiction in Hobbes' political theory: the contradiction is between the method (which may be called “realism”) used in the deduction of the commonwealth and sovereign, and the sovereign's alleged obligation to obey the laws of nature. In order to explain how the contradiction arises, I begin by giving a brief account of the laws of nature in Hobbes, and the way in which he deduces the necessity for a sovereign. I then discuss a number of possible ways of avoiding the contradiction, and find them all unsatisfactory. Finally, I propose a solution to the problem. This solution involves some criticisms of Professor C. B. Macpherson's analysis of Hobbes, and also has some bearing on the relationship of the thought of Marx to more orthodox political theory.

In De Corpore Politico, Hobbes says that the laws of nature are “the dictates of natural reason … moral laws, because they concern the manners and conversation of men, one towards another; so are they also divine laws in respect of the author thereof. …” The laws of nature, then, can be seen in three ways: as rational, as moral, and as divine. It is because he says that they are both moral laws and dictates of reason, in that reason dictates on the basis of certain facts, that Hobbes is said to be guilty of the naturalistic fallacy, of attempting to deduce values from facts. And he calls them divine in order to emphasize that they cannot, according to his own account of law, properly be called laws at all except they be commands, in this case the commands of God. “And forasmuch as law, to speak properly, is a command, and these dictates, as they proceed from nature, are not commands, they are not therefore called laws, in respect of nature, but in respect of the author of nature, God Almighty.” Hobbes gives various explanations of just why the laws are moral, and all of them are unsatisfactory in one way or another. In the above passage he says that they are moral because they concern the manners and conversation of men, one towards another; but not everything which concerns the manners and conversation of men is moral.
Taxpayer Participation under the Registered Retirement Savings Program
Authors: Schoeplein Robert N.
Published: June 2006

The Registered Retirement Savings Plan, adopted in 1957, afforded Canadian taxpayers a new deduction from assessable income under the individual income tax. Qualified participants in this program may reduce current tax liabilities by their contributions to personal retirement savings accounts. This tax-inducement scheme was somewhat unusual, and “representative” taxpayer response would therefore occur only after a time lapse for individual evaluation of program advantages. Sufficient time has now expired, however, to permit a study of program performance.

Taxpayer response should be judged by reference to program objectives. Parliamentary discussions indicate that the measure had two objectives. The first was to restore an element of fairness, or uniform treatment, to the taxation of retirement funds. The second was to reinforce the social policy of fostering retirement saving in the private sector. The particular construction of the retirement saving scheme and the consequent taxpaper response seem, however, to have led to a failure to achieve either objective.

Taxpayer participation in 1962 is analysed in this article. Registered retirement savings deductions in that year were declared on only 1.49 per cent of all taxable returns filed by individuals under 65 years of age. Few taxpayers, then, utilize this deduction, and those who do are concentrated in the higher income classes.
The Roots of French-Canadian Discontent
Authors: Kwavnick D.
Published: June 2006

It is possible that the current “crisis” in French-English relations in Canada has been helped to its present pitch through a simple lack of understanding of the roots of French-Canadian discontent on the part of English Canadians, rather than as the result of a clash between irreconcilable ends. Two of the most common manifestations of this lack of understanding are to be seen in the lines of argument so often employed by English Canadians in discussing constitutional questions. The first has a long and honourable history, going back at least as far as 1887. Moreover, it enjoys the distinction of having seen active service down through the years on both sides in the various English-French and Dominion-provincial disputes.

The error in question is that of basing constitutional arguments upon an interpretation of the intentions of the Fathers of Confederation. This basis of argument has been invoked by both the compact theorists, among the upholders of provincial rights, and the “Judicial Committee ruined our Constitution” school among the centralists. (This word is used in a non-pejorative sense, although it seems to have acquired pejorative overtones in recent years.) The Fathers of Confederation were practical politicians attempting to deal with the practical political problems of the mid-nineteenth century, and it was with reference to these problems and to the contemporary value systems of the various communities of British North America that they conceived the series of compromises embodied in the British North America Act. To credit the Confederation settlement of a century ago with eternal validity is to credit the Fathers with a prescience which they simply did not possess.
Michigan and Ontario Legislators: Perspectives on the Federal System
Authors: Heubel E. J.
Published: June 2006

In analysing the American and Canadian federal systems it is possible to stress the trends common to both systems or, alternately, to emphasize the differences that distinguish the Canadian from the American experience with federal institutions. Both political systems have persisted with recognizable federal features even while substantial nationalizing developments have occurred in the economies and cultures of the two nations. One leading authority characterizes the kind of federalism that results as “co-operative” in contrast to the older “classical” variety. Others, while noting common trends, stress the greater degree of resistance to centralization found in Canada by use of such labels as “pluralistic federalism,” “double-image federalism,” and “peri-pheralized federalism.” While briefs can be made for affixing one or another label to a system, it seems more useful at this stage to study some of the array of differences between the Canadian and American federal systems. One way to get a rough measure of differences and similarities is to pose a set of questions on federalism to comparable groups of Canadians and Americans. These questions can be designed to determine the respective orientations to their federal systems and their opinions on various provincial (state)-federal problems. In this study the questions were put to members of the Ontario Legislative Assembly and the Michigan Senate.
On the Economic Implications of the Yield Ceiling on Government-Insured Mortgages
Authors: Smith Lawrence B.
Published: June 2006

Policy makers have recently devoted a great deal of attention to the interest rate ceiling on bank loans, one of the two main impediments to the free flow of funds within the Canadian capital markets. The other major impediment, the interest rate ceiling on government-insured mortgages, has largely been ignored despite the pronounced impact it has upon the allocation of funds, and the recommendation of the Royal Commission on Banking and Finance that it be abolished. Recent instability in the residential construction sector has, however, once again focused attention upon this ceiling and raised the question of its desirability. The purpose of this paper is to correct a major misconception concerning the impact of this ceiling and to point out some of the other major implications of an interest rate maximum on governmentinsured mortgages.
Housing Demand in Canada, 1947 to 1962: Some Preliminary Experimentation
Authors: Oksanen Ernest H.
Published: June 2006

The paucity of econometric analyses of the demand for consumer durables stands in sharp contrast to the number of studies involving the demand for non-durables, and for agricultural commodities in particular. The neglect of durables undoubtedly reflects in part the greater difficulty of obtaining the necessary data, especially data on stocks, and in part the heterogeneity of most durables, such as houses or automobiles. Econometric analysis in the post-war period has also been centred around the construction of large-scale macro-economic models. Until rather recently, however, such models were relatively highly aggregated, and seldom involved examination of particular durables markets by themselves. Moreover, where an equation for the housing market has been included, it has often been a hybrid of supply and demand forces, intended to serve in a “forecasting” role, presumably in the hope that appreciable structural change would not occur during the forecast period.

The present study will, it is hoped, cast some light on the controversy generated in the United States over the size of demand elasticities for housing with respect to income. The results of the econometric techniques employed here may also assist in evaluating the appropriateness of alternative estimating techniques for the study of demand for durables.

An econometric analysis of the demand for housing immediately raises two questions. First, is it a flow or a stock demand that is to be analysed? Here it is the demand for a long-run equilibrium stock, the “desired stock” of housing, that is the focus of concern.
A Reformulation of the Keynesian System
Authors: Steigmann A. J.
Published: June 2006

The Keynesian faith in the effectiveness of fiscal policy consists in the belief that there is a positive rate of change of national income with respect to autonomous expenditure. This in turn stems from the belief that the marginal efficiency schedule is downward-sloping. This dependence can be seen from a simple formulation of the Keynesian system. Letting Y be national income, E1 investment expenditure, E2 autonomous expenditure, r the marginal efficiency of capital, i the interest rate, and M the stock of money:

The dependent variables are Y, E1, r, and i. The derivative dY/dE2, evaluated from (1)–(4),is the expression:

The addition of dE1/dt to the right side of (3) yields a differential-equation system whose solution is stable only if the denominator of this expression is positive. It follows that dY/dE2, the rate of change of national income with respect to autonomous expenditure, is opposite in sign to ∂η/∂E1, the slope of the marginal efficiency schedule.
Leptin (
ob
gene) of the South African clawed frog
Xenopus laevis
Authors: Crespi Erica J. , Denver Robert J.
Published: June 2006

Leptin, the protein product of the
obese
(
ob
) gene, is a type-I cytokine hormone secreted by fat that is integral to food intake regulation and influences almost every physiological system in juvenile and adult mammals. Since the identification of leptin in the mouse in 1994, biologists have searched for orthologous genes in other species with limited success. In this article, we report the identification and functional characterization of leptin and leptin receptor (LR) in
Xenopus
. Despite low amino acid sequence similarity to mammalian leptins (≈35%) the frog protein has a nearly identical predicted tertiary structure and can activate the frog and mouse LRs
in vitro
. We showed that recombinant frog leptin (rxLeptin) is a potent anorexigen in frogs, as it is in mammals, but this response does not develop until midprometamorphosis. However, during early prometamorphosis, exogenous rxLeptin induced growth and development of the hind limb, where LR mRNA is expressed. The rxLeptin also stimulated cell proliferation in cultured hind limbs from early prometamorphic tadpoles, as measured by [
3
H]thymidine uptake. These findings are evidence that leptin can influence limb growth and differentiation during early development. Furthermore, the isolation and characterization of leptin and its receptor in a nonamniote provides an essential foundation for elucidating the structural and functional evolution of this important hormone.
Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient
Authors: Rousseau François , Gauchat Jean-François , McLeod James G. , Chevalier Sylvie , Guillet Catherine , Guilhot Florence , Cognet Isabelle , Froger Josy , Hahn Angelika F. , Knappskog Per M. , Gascan Hugues , Boman Helge
Published: June 2006

Ciliary neurotrophic factor (CNTF) receptor controls a pathway supporting the differentiation and survival of a wide range of neural cell types during development and in adulthood. Cardiotrophin-like cytokine (CLC)–cytokine-like factor 1 (CLF) composite cytokine is a second ligand for the CNTF α-component receptor (CNTFRα). This composite cytokine is built on the structural model of IL-12, with a complex formed by a four-helix bundle type I cytokine, CLC (also referred to asCLCF1), bound to a soluble receptor subunit, CLF (also known asCRLF1). We have reported mutations in the chaperone soluble receptor CLF, causing cold-induced sweating syndrome (CISS). In this study, we studied theCLC-mutated alleles in a patient suffering from a similar disease. This patient was compound heterozygous for two differentCLCmutations. The first allele was inactivated by a stop codon at position 107 (Y107X). In the second allele, a R197L mutation in the CLC-predicted binding site to the CNTFRα was detected. Functional analysis of the mutated protein revealed an incapacity for R197L CLC to bind to CNTFRα and activate the subsequent signaling events. Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRα.
Rab3 GTPase-activating protein regulates synaptic transmission and plasticity through the inactivation of Rab3
Authors: Sakane Ayuko , Manabe Shinji , Ishizaki Hiroyoshi , Tanaka-Okamoto Miki , Kiyokage Emi , Toida Kazunori , Yoshida Takayuki , Miyoshi Jun , Kamiya Haruyuki , Takai Yoshimi , Sasaki Takuya
Published: June 2006

Rab3A small G protein is a member of the Rab family and is most abundant in the brain, where it is localized on synaptic vesicles. Evidence is accumulating that Rab3A plays a key role in neurotransmitter release and synaptic plasticity. Rab3A cycles between the GDP-bound inactive and GTP-bound active forms, and this change in activity is associated with the trafficking cycle of synaptic vesicles at nerve terminals. Rab3 GTPase-activating protein (GAP) stimulates the GTPase activity of Rab3A and is expected to determine the timing of the dissociation of Rab3A from synaptic vesicles, which may be coupled with synaptic vesicle exocytosis. Rab3 GAP consists of two subunits: the catalytic subunit p130 and the noncatalytic subunit p150. Recently, mutations in p130 were found to cause Warburg Micro syndrome with severe mental retardation. Here, we generated p130-deficient mice and found that the GTP-bound form of Rab3A accumulated in the brain. Loss of p130 in mice resulted in inhibition of Ca
2+
-dependent glutamate release from cerebrocortical synaptosomes and altered short-term plasticity in the hippocampal CA1 region. Thus, Rab3 GAP regulates synaptic transmission and plasticity by limiting the amount of the GTP-bound form of Rab3A.
A comparison of intestinal lymphatic transport and systemic bioavailability of saquinavir from three lipid-based formulations in the anaesthetised rat model
Authors: Griffin Brendan T , O'Driscoll Caitriona M
Published: June 2006

Saquinavir is a lipophilic, poorly water-soluble HIV protease inhibitor that undergoes extensive first-pass metabolism and exhibits poor oral bioavailability. Redirection of the absorption pathway of anti-HIV compounds from the portal blood to the HIV-rich intestinal lymphatics may enhance therapeutic efficacy and reduce the extent of the first-pass effect. This study investigates the potential of targeted intestinal lymphatic transport of saquinavir via a lipid formulation approach. Three formulations containing oleic acid were examined: cremophor-oleic acid mixed micelles, d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS)-oleic acid mixed micelles and an oleic acid microemulsion. The mesenteric lymph duct cannulated anaesthetised rat model was employed. Plasma and lymph samples were analysed by HPLC. Lymph triglyceride was measured using an enzymatic colorimetric technique. The extent of lymphatic transport from the lipid vehicles was 0.025-0.05% of the dose administered. The microemulsion produced higher and more prolonged mesenteric lymph concentrations than the micellar formulations. A strong correlation existed between the concentration of saquinavir in intestinal lymph and lymph triglyceride levels. The systemic bioavailability was estimated to be 8.5% and 4.8% for the cremophor mixed micelle and the microemulsion, respectively. The cremophor mixed micelles produced higher bioavailability than TPGS mixed micelles, implying that the nature of the surfactant can influence the distribution of drug between lymph and plasma.
Oxidative stress parameters in different systemic rheumatic diseases
Authors: Firuzi Omidreza , Fuksa Leoš , Spadaro Chiara , Boušovà Iva , Riccieri Valeria , Spadaro Antonio , Petrucci Rita , Marrosu Giancarlo , Saso Luciano
Published: June 2006

The involvement of oxidative stress in the pathogenesis of rheumatic disorders, such as systemic sclerosis (SSc) and chronic polyarthritides, has been suggested yet not thoroughly verified experimentally. We analysed 4 plasmatic parameters of oxidative stress in patients with SSc (n = 17), psoriatic arthritis (PsA) (n = 10) and rheumatoid arthritis (RA) (n = 9) compared with healthy subjects (n = 22). The biomarkers were: total antioxidant capacity (TAC) measured by ferric reducing antioxidant power (FRAP) method, hydroperoxides determined by ferrous ion oxidation in presence of xylenol orange (FOX) method and sulfhydryl and carbonyl groups assessed by spectrophotometric assays. The results showed significantly increased hydroperoxides in SSc, PsA and RA (3.97 ± 2.25, 4.87 ± 2.18 and 5.13 ± 2.36 μmol L−1, respectively) compared with the control group, (2.31 ± 1.40 μmol L−1; P < 0.05). Sulfhydryls were significantly lower in SSc (0.466 ± 0.081 mmol L −1), PsA (0.477 ± 0.059 mmol L−1) and RA (0.439 ± 0.065 mmol L−1) compared with the control group) (0.547 ± 0.066 mmolL−1; P < 0.05). TAC in all three diseases showed no difference in comparison with controls. Carbonyls were significantly higher in RA than in the control group (32.1 ± 42 vs 2.21 ± 1.0 nmol (mg protein)−1; P < 0.05). The obtained data indicate augmented free radical-mediated injury in these rheumatic diseases and suggest a role for the use of antioxidants in mediated prevention and treatment of these pathologies.
A tetravalent RGD ligand for integrin-mediated cell adhesion
Authors: Watson N , Duncan G , Annan W S , van der Walle C F
Published: June 2006

Monovalent RGD (arginine-glycine-aspartic acid) peptides or polymers furnished with RGD in random distributions are employed as cell-scaffolds and gene delivery vehicles. However, integrin binding to RGD is dependent on the spatial distribution (clustering) of the ligand and intrinsic integrin affinity via conformational changes (avidity). Here we have designed and expressed a polypeptide consisting of a tetrameric coiled coil and spacer facilitating polyvalent (clustered) display of integrin ligands; the RGD motif was used as proof of principle. Size-exclusion chromatography and circular dichroism showed that the polypeptide self assembled as a tetramer in solution with a defined secondary structure. Cell adhesion to surfaces coated with the polypeptide was up to 3-fold greater than that for (monovalent) RGDS peptide at equivalent concentrations. Moreover, the polypeptide in solution at concentrations ≥1μM inhibited cell adhesion to fibronectin-coated surfaces, while RGDS peptide in solution at concentrations up to 500μM did not. These cell data demonstrate that the polypeptide bound integrin receptors in a polyvalent manner. The polypeptide will therefore be of use in the engineering of tissue-culture scaffolds with increased cell adhesion activity, or to targeted gene delivery vehicles, and could incorporate protein ligands in place of the RGD motif.
Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's disease
Authors: Ren Yuhao , Houghton Peter , Hider Robert C
Published: June 2006

The centipede Scolopendra subspinipes mutilans L. Koch (‘Wugong’), the beetle Mylabris phalerata Pallas (‘Ban mao’) and the earthworm Pheretima aspergillum Chen (‘DiLong’) have a reputation in traditional Chinese medicine for reducing symptoms of central nervous system decline, including memory loss. A series of extracts of all three organisms was tested for acetylcholinesterase (AChE) inhibition and copper ion binding effects, the latter likely to reduce oxidative damage caused by excess copper. The beetle and centipede chloroform extracts showed the strongest AChE inhibitory effects (30.6% inhibition at 105 μg mL−1 and 32.3% inhibition at 167 μg mL−1, respectively) and, in the case of the centipede, this was traced to the unsaturated fatty acids present using bioassay-guided fractionation. Cantharidin from the beetle was shown to have AChE activity (31% inhibition at 1 μM, 0.196μg mL−1), making it a major contributor to the activity of the beetle extract. The earthworm showed no AChE inhibitory activity. Since unsaturated fatty acids have not been previously reported to have AChE inhibitory activity, a series of related compounds was tested to determine structure-activity relationships. It was found that activity existed where there was a chain length of more than 16 C atoms with at least one unsaturated bond in the chain. The carboxylic acid group was also necessary for activity. The fatty acids present in the centipede also showed the ability to bind copper ions when tested using a novel thin layer chromatography method designed to detect copper-binding compounds. The activities reported give some support to the use of the beetle and centipede in traditional Chinese medicine for improving cognitive function.
The Report of the Duff Commission
Authors: McDougall John L.
Published: June 2006

This report naturally falls into two separate and almost completely unrelated parts. The final chapter, “Proposals and Remedies”, is wholly admirable. For the judgments expressed in it the writer has the greatest respect. The first four chapters are another matter. They contain some useful information, a great deal of banal comment on facts already known, some statements which are plainly false, and others which, while not altogether wrong, are likely to give a wholly distorted impression of the facts which they are supposed to report. It is the purpose of this article to cite some of these statements, to give the facts which they are supposed to summarize, to show that these facts were brought to the attention of the Commission, and thus to prove that this condemnation is justified.

All of the statements to which exception is taken are, with one exception, concerned with the relative operating efficiency of the Canadian National and Canadian Pacific Railways. (The exception charges, by implication, the Canadian National with extravagance in branch-line construction costs.) The form of railway operating accounts has been worked out in the very greatest detail by the Interstate Commerce Commission of the United States. They are designed to show the costs of performing particular functions, maintenance of way and structures, maintenance of equipment, conducting transportation, etc. Every general rate case and many of the cases involving rates on particular commodities have turned on the question of costs, and on the significance of such factors as density of traffic and length of haul in causing variations in unit costs.
Canadian Defence Policy
Authors: Stacey C. P.
Published: June 2006

The brief period since 1935 has produced in the attitude of the Canadian Government and people towards national armaments and defence policy a change so sudden and striking as to merit the name of revolution. Observers who in the quite recent past had remarked the obstinate refusal of Ministry, Parliament, and public to pay the slightest attention to the apparatus of defence, have been astonished during the past three years by the energy with which the present Government (headed by a statesman who in three previous terms in office had shown no special interest in this phase of the national life) has attacked the problems of military policy, and by the vigour with which the Canadian electorate has fallen to discussing them.

Students of the past, of course, are aware that Canada is merely running true to form. Her history is marked by an alternation of long periods when the national defences are utterly neglected with short violent interludes, arising out of sudden foreign complications, when the country awakes to the inadequacy of those defences and tries to make up for earlier inactivity by measures taken in the teeth of the crisis. In the light of this record, it is not surprising that a desperately perilous international situation has now forced the Dominion into one more military stock-taking. Nevertheless, the episode is arresting; and its possible ultimate implications for all Canadians are of such necessary interest that it may be worth while to record here the things that have been done, and to assess, in however imperfect and conjectural a fashion, the ideas that lie behind the new departures and the policies which they are designed to serve.
Some Aspects of Canadian Statistics of Merchandising
Authors: Marshall H.
Published: June 2006

A first attempt at a census of distribution, designated the “Census of Trading Establishments”, was made in Canada during the years 1921-4 in connection with the Population Census of 1921. Names and addresses of merchandising concerns were collected on a special schedule by the regular census enumerators and were subsequently checked with local directories, gazetteers, and other sources of information. A questionnaire was then sent by post to each address. Pressure of work in connection with the compilation of the Population Census rendered it impossible to distribute the questionnaire until 1924. By that date many of the addresses were obsolete. Moreover, owing to the necessity, during the economic stringency of 1924-5, of reducing staff to a minimum, it was not possible to have a proper follow-up after delinquent returns, either by mail or supplementary investigation in the field; consequently the census was incomplete. Returns were obtained from 66,814 establishments as compared with 138,143 in 1931. These were classified as retail, wholesale, or wholesale-retail. There were 60,181 retail, 3,782 wholesale, and 2,851 wholesale-retail stores. The questions asked included value of sales, value of purchases, salaries and wages, number of employees by sex, expenses, and capital investment. Thirtynine classifications by kind of business were used. It is probable that approximately 60 per cent of the value of retail trade was covered, but the wholesale coverage was much smaller, the proportion of wholesalers proper being much greater than that of other types. Probably less than one-third of the value of wholesale trade was included. In spite of the shortcomings of this 1924 census, it did give some idea of the importance and operating results of “trading establishments” in the general economy and paved the way for a more comprehensive census.
Some Notes on the Distributive Trades in Canada
Authors: Reynolds Lloyd G.
Published: June 2006

The past few decades have witnessed a steady growth in the importance of marketing activity in the Canadian economy and rapid alterations in marketing methods. These developments have posed new problems of economic efficiency and of public policy. The rapid multiplication of retail stores, for example, has raised the question whether there are not too many stores to permit of the greatest efficiency of each, and whether high over-head costs due to “excess capacity” is not a more serious problem in this field than in manufacturing industry. The rise of large distributors has presented the issue whether their buying and selling policies are not so oppressive as to call for legislation to protect the independent merchant, the manufacturer, and the wage-earner. Discussion of these issues has been for the most part cursory. Few attempts have been made to apply to them the methods of economic analysis which have been used in the study of manufacturing and other industries. It is essential, however, that such attempts should be made. The price of a finished good to consumers does not depend merely upon the manufacturer's price-policy, but upon a succession of price-determinations made in a series of markets, running from the farmer or miner at one end of the chain to the final purchaser at the other. Monopoly elements in any one of these markets may affect the final price quite as much as that monopolistic competition among manufacturers to which so much attention has recently been devoted. It is therefore necessary to study commodity distribution, not as an isolated, descriptive, and barely respectable “subject”, but as an integral part of the theory of prices.