bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Differences in Fos Protein Expression in the Neonatal Rat Brain
Authors: Olesen K. M. , Auger A. P.
Published: April 2005

Sex differences in the brain and behaviour are mostly a result of transient increases in testosterone during the perinatal period. Testosterone influences brain development primarily through aromatization to oestradiol and subsequent binding to oestrogen receptors. Although some studies report that steroid hormones regulate the expression of the inducible transcription factor, Fos, in developing brain, it is not known if there is a sex difference in Fos expression. Changes in Fos protein can be used as an indicator of neuronal/genomic activity. Thus, it provides a useful tool to identify brain regions responding directly or indirectly to steroid hormones. In a first experiment, we examined Fos protein expression in the developing male and female rat brain using western immunoblotting. Dissections were taken from male and female rat pups on the day of birth (postnatal day 0; PN 0), PN1, PN5, PN11 or PN20. Although there was no difference on PN 0, males expressed significantly greater levels of Fos protein on PN1, PN5 and PN20. In a second experiment, we localized the sex difference in Fos protein expression using immunocytochemistry. We found that males expressed significantly higher levels of Fos within a variety of brain regions. These data indicate a sex difference in Fos protein expression during brain development, suggesting a potential role for Fos in differentiating male from female rat brain.
Colour stability of low fusing porcelains: an in vitro study
Authors: ERTAN A. A. , ŞAHIN E.
Published: April 2005

summary  Developing porcelain manufacturing technology provides lower fusing porcelains to avoid thermal stresses in metal substructure, particularly for titanium and gold alloys. So far, aesthetic properties of low fusing ceramics have not been well documented. The purpose of this study was, therefore, to estimate the long‐term colour stability of low fusing ceramics by using an accelerated aging procedure. Four different ceramics (Vita Omega 900, Vita Titankeramik, Ceramco Finesse, Ceramco II) were used. Porcelain samples 11 ± 0·5 mm in diameter and 1·4 ± 0·2 mm in thickness were prepared in three commonly used shades to provide 10 samples of each group. The samples were fired in accordance with the recommendations of the manufacturers. CIE Lab readings were recorded with a spectrophotometer prior to experiments and after a 100 h accelerated aging. The results revealed that only Ceramco Finesse porcelain had a colour change (ΔE > 1) that is noticeable by human eye. When the shades of porcelains were compared, C3 had greater colour change compared with A3 and B3 shades (P < 0·05).
Pre‐collisional high pressure metamorphism and nappe tectonics at active continental margins: a numerical simulation
Authors: Stöckhert Bernhard , Gerya Taras V.
Published: April 2005

The evolution of a subduction channel and orogenic wedge is simulated in 2D for an active continental margin, with P‐T paths being displayed for selected markers. In our simulation, subduction erosion affects the active margin and a structural pattern develops within a few tens of millions of years, with four zones from the trench into the forearc: (i) an accretionary complex of low grade metamorphic sedimentary material, (ii) a wedge of nappes with alternating upper and lower crustal provenance, and minor interleaving of oceanic or hydrated mantle material, (iii) a megascale melange composed of high pressure (HP) and ultra‐high pressure (UHP) metamorphic rocks extruded from the subduction channel, and (iv) the upward tilted frontal part of the remaining lid. The P–T paths and time scales correspond to those typically recorded in orogenic belts. The simulation shows that HP/UHP metamorphism of continental crust does not necessarily indicate collision, but that the material can be derived from the active margin by subduction erosion and extruded from the subduction channel beneath the forearc during ongoing subduction.
New record of Bathonian–Callovian calcareous nannofossils in the eastern Karakoram block: a possible clue to understanding the dextral offset along the Karakoram Fault
Authors: Upadhyay Rajeev , Rai Jyotsana , Sinha Anshu K
Published: April 2005

We report the first record of Bathonian–Callovian calcareous nannofossils from a marine sedimentary sequence of the eastern Karakoram block, in northern India. The calcareous mudstones and packstones, occasionally bearing red chert nodules, yielded calcareous nanofossils and Middle Jurassic Choffatia furcula ammonoids. Middle to Upper Jurassic nannofossil assemblage is dominated by representatives of the genus Watznaueria. The occurrence of Ansulasphaera helvetica whose range is Upper Bathonian–Upper Callovian, indicates a correlation with nannofossil zones NJ12–13. The occurrence of Cyclagelosphaera wiedmannii further infer an Upper Bathonian–Callovian age. These specimens show affinities with those found in a similar sedimentary formation exposed in north Karakoram. This suggests the existence of a narrow and elongated sedimentary basin, oriented in a NW–SE direction, at a latitude of c. 25°–30°N. At that time, the Karakoram block was situated near the already welded Qiangtang block of Asia. The northern and eastern Karakoram blocks were connected during Middle Jurassic. The activity and dextral offset of the Karakoram fault separated the Jurassic sedimentary formations of the northern and eastern Karakoram blocks by c. 150 km.
Functional and compositional comparison of two activated sludge communities remediating coking effluent
Authors: Manefield Mike , Griffiths Robert I. , Leigh Mary Beth , Fisher Ray , Whiteley Andrew S.
Published: April 2005

The success of engineered microbiological systems is evident in the global application of activated sludge communities to remediate coking effluent. However, there is a lack of understanding of the microbiology underlying treatment efficiency and stability. In this study, two functionally distinct activated sludge pools, treating the same effluent and operating under the same conditions, were examined to establish a relationship between overall diversity and/or functional diversity with respect to process stability. Molecular profiling, sequencing and RNA‐based stable isotope probing were used to examine the bacterial diversity, general composition and functional composition of the most abundant members of the two communities. The inferior process stability in one of the pools could not be explained by reduced total bacterial diversity or evenness. RNA‐based stable isotope probing revealed that both pools harboured an abundant phenol‐degrading Acidovorax species, and that the pool of inferior stability accommodated an additional closely related phenol‐degrading Acidovorax species at high abundance. These results are discussed in the context of deterministic and stochastic models of microbial community assembly.
Retrieval of nearly complete 16S rRNA gene sequences from environmental DNA following 16S rRNA‐based community fingerprinting
Authors: Höfle Manfred G. , Flavier Sébastien , Christen Richard , Bötel Julia , Labrenz Matthias , Brettar Ingrid
Published: April 2005

16S rRNA‐based fingerprinting techniques allow rapid analyses of overall bacterial community structure but suffer from a lack of phylogenetic information hitherto retrievable from the short 16S rRNA gene sequences obtained from excised bands. An approach is presented that allows nearly complete 16S rRNA gene sequences to be retrieved for abundant components of the bacterial community as obtained by the community fingerprint, i.e. those reflected by major fingerprint bands. This was achieved by designing a pair of highly specific primers derived from the sequence of an excised band. Combined with universal 16S rRNA primers, these specific primers were applied directly to environmental DNA serving as template. This procedure allowed the generation of a nearly complete 16S rRNA gene sequence of the target taxon by specific polymerase chain reaction (PCR) followed by cycle sequencing down to a relative abundance of at least 1.5% of the environmental DNA. The procedure was exemplified for an epsilonproteobacterium related to Thiomicrospira denitrificans occurring in the central Baltic Sea. This approach is based only on PCR without any cloning step involved. It allows focussing on specific target taxa and is thus rather efficient. This approach should be applicable in general to 16S rRNA or 16S rRNA gene‐based fingerprinting techniques and their respective environmental DNA.
Early development of delinquency within divorced families: evaluating a randomized preventive intervention trial
Authors: DeGarmo David S. , Forgatch Marion S.
Published: April 2005

This paper reports on an experimental test of coercion theory early onset model of delinquency. Results are from the Oregon Divorce Study‐II, a randomized preventive intervention trial with a sample of 238 recently separated mothers and their sons in early elementary school. The objective was to experimentally manipulate parenting variables hypothesized to influence development of delinquent behaviors. Multiple‐method assessment spanned 36 months. Because the intervention focused on parent training, we expected that any intervention effects on changes in child outcomes would be mediated by hypothesized intervening mechanisms. Linear growth models showed significantly greater reduction in boys’ delinquency and deviant peer affiliation in the experimental group relative to the controls. Subsequent models using no method overlap in constructs demonstrated that the intervention effect on delinquency operated through growth in parenting and reduction in deviant peer affiliation.
Ancient plant DNA: review and prospects
Authors: Gugerli Felix , Parducci Laura , Petit Rémy J.
Published: April 2005

Ancient DNA has received much attention since the mid‐1980s, when the first sequence of an extinct animal species was recovered from a museum specimen. Since then, the majority of ancient DNA studies have focused predominantly on animal species, while studies in plant palaeogenetics have been rather limited, with the notable exception of cultivated species found in archaeological sites. Here, we outline the recent developments in the analysis of plant ancient DNA. We emphasize the trend from species identification to population‐level investigation and highlight the potential and the difficulties in this field, related to DNA preservation and to risks of contamination. Further efforts towards the analysis of ancient DNA from the abundant store of fossil plant remains should provide new research opportunities in palaeoecology and phylogeography. In particular, intraspecific variation should be considered not only in cultivated plants but also in wild taxa if palaeogenetics is to become a fully emancipated field of plant research.
AN INTEGRATED SYSTEM OF SOCIAL ACCOUNTS FOR AN ECONOMY OF THE YUGOSLAV TYPE
Authors: Horvat Branko
Published: April 2005

The system of social accounts described in this article is based on the following five principles:

(1) Producers of goods and services are working organizations which represent groups of people or individuals organized for the purpose of earning a living by producing goods and services that satisfy individual or collective needs. Business, government, profit and nonprofit, corporate and unincorporated working organizations are treated in a uniform way.

(2) Since the behaviors of the market and non‐market sectors differ considerably, these two sectors are consistently separated throughout the accounting system.

(3) There are four basic activities: (a) production, (b) consumption, (c) investment, and (d) income redistribution. These call for four separate accounts: (a) Working Organizations, (b) Households, (c) Community, including government and certain non‐government institutions, and (d) Accumulation. The fifth account, Rest of the World, serves for balancing purposes.

(4) The same classifications of transactions are used for activities and institutions, making possible complete matching of social product and financial flows accounts.

(5) The system strives to achieve the maximum analytical flexibility. Some of its possibilities are visible from the classification of industries: A. Market (Material) Sector: 1. Agriculture, II. Forestry, III. Mining and Manufacturing, IV. Construction, V. Transportation, VI. Trade and Catering, VII. Handicrafts; B. Non‐Market (Non‐Material) Sector: VIII. Housing and Communal Economy, IX. Education, Culture, and Social Welfare, X. Public Services Social Organizations (Political, Religious, etc.), Finance and Insurance, Public Administration and Judiciary, National Defence. Sector A corresponds to the material definition of social product. Sectors A + B correspond to the SNA definition. Sectors A + B minus Industry × reflects the welfare definition. Further, Industries I‐IV produce goods, V‐VII market services, VIII and IX non‐market services with welfare content, X intermediate nonmarket services, V‐X all services.
INCOME, CONSUMPTION AND SAVING IN URBAN AND RURAL INDIA*
Authors: Choudhury Uma Datta Roy
Published: April 2005

The main purpose of the study is to determine the savings potential of urban and rural households in India and in the process determine the possible savings and consumption functions separately for urban and rural areas.

Four different possible functions have been used for determining the savings behaviour of the households both at the aggregate level and at the per capita level. The rural households, according to the results, have an extremely low rate of saving with income elasticity of saving of less than unity. For the urban households on the other hand, the income elasticity of saving is high enough to suggest the possibilities of considerably high savings potential.

To understand the consumption behaviour of these households, the long‐run and the short‐run marginal propensities to consume and the marginal propensities to consume out of‘permanent’ or ‘normal’ income and ‘transitory’ income have been worked out. For the urban sector none of these give encouraging enough results and the analysis has been extended to examine whether other factors like prices and household assets are of any significance. Whereas for the rural sector, Milton Friedman's theory of ‘permanent’ or ‘normal’ income is somewhat substantiated, other factors like ‘transitory’ income, prices and assets appear to inthence urban consumption behaviour though no single one of them substantially enough. A negligible effect of ‘permanent’ income on urban consumption behaviour is, on the other hand, very clearly suggested by the results.

Household consumption and savings have next been projected using the above results to determine the possible levels for the next three years. The results suggest that the rate of domestic savings likely to be achieved by the end of the Third Five Year Plan (1965–66) falls short of the targets laid down.
FOREIGN MANPOWER IN THE U.S. SCIENCES
Authors: Grunel Herbert G.
Published: April 2005

Because of the recent public concern over the brain drain, this study attempts to measure the U.S. gain of highly skilled manpower. The paper discusses the serious short‐comings of the data on gross immigration of scientists and engineers provided by the U.S. immigration authorities as a measure of true U.S. gains. In a case study of Swedish scientists and engineers it was found, for example, that whereas the U.S. data showed a gain of 106 Swedish scientists and engineers over a number of years, the net figure was only 26 after adjustment for remigration and the application of the proper OECD education criteria.

The paper then reports the findings of a statistical study which uses the stock data on U.S. scientists in the National Register of Scientific and Technical Personnel to estimate the number of foreign born in this stock and analyse their characteristics with respect to age, educational attainment, and employment preferences.

It was found that nearly 7 percent of all U.S. scientists are of foreign origin (foreign born and foreign secondary education), whereas 11.5 percent of all scientists with a Ph.D. are of foreign origin. The percentage among Ph.D. holders is highest in meteorology (22.3), followed by linguistics (18.7), physics (17.1) and statistics (14.6).

The greatest percentage of scientists comes from Canada (10.4 per thousand), followed by Germany (8.3 per thousand) and the United Kingdom (6.7 per thousand). However, after adjustment of these data for the different sizes of the total foreign born population from each country in the U.S., it turns out that by this measure the greatest shares of scientists are supplied by the Japanese, followed by the Austrian‐Swiss, Benelux and Canadians.

The analysis of the age composition of all foreign born reveals that in the age groups that were 20–29, 45–54, and 65 and over in 1964 foreigners represent a smaller than average share, probably reflecting war casualties and education completed at a later age. Germans and Austrians are heavily concentrated in the group 55–64 years old in 1964, suggesting that a great share of scientists from these countries may have been victims of a brain push.
REAL INCOME LEVELS IN LATIN AMERICA
Authors: Braithwaite Stanley N.
Published: April 2005

The measurement and inter‐spatial comparison of Latin American real income levels calls for techniques which depart substantially from the conventional procedure of applying such official or free market exchange rates as happen to prevail in any given period. The reasons are varied, the main ones being that in an area such as Latin America prices are notoriously volatile, their structure differs radically from that encountered in other parts of the world, and the exchange rate system is characterized by frequent and usually irregular revisions, while in certain countries a multiple exchange rate system applies and no single factor is available for conversion purposes. In addition, there exists the problem common to all developing countries that the rates to a large extent reflect the exchange value of a limited number of export commodities vis‐à‐vis a wide range of imported goods and in no way typify the internal‐external price relationship for the bulk of production which by its nature fails to enter into international trading transactions.

The author has endeavoured to circumvent these difficulties by adopting the often‐discussed “purchasing power parity” approach whereby national accounts data are converted into a common monetary denominator (in this case, the U.S. dollar) expressed in “real” or quantitative terms which as far as possible eliminate inter‐spatial price differences. Results are presented and analyzed, first for the base year 1960, and then for the period 1955–1964 at the level of main expenditure sectors as well as for the total gross domestic product.

To the extent that available statistics permitted, results for Latin American countries are also related to the United States and certain countries in Western Europe, a main objective being to determine the approximate dimension of the incomes “gap” and to ascertain whether this is increasing, decreasing or remaining very much unchanged in size.
ESTIMATION OF CES PRODUCTION FUNCTIONS WITH NEUTRAL TECHNICAL CHANGE FOR INDUSTRIAL SECTORS IN THE FEDERAL REPUBLIC OF GERMANY 1958–1968
Authors: Frohn Joachim
Published: April 2005

This paper discusses the estimation of the CES Production Function with Hicks‐neutral technical change, and gives the results of an empirical study based on time series data (quarterly values) for sixteen industrial sectors in the Federal Republic of Germany (including West‐Berlin), 1958–1968. The validity of the basic assumptions of the production model used in this investigation—neutrality of technical change and perfect competition—is tested by estimation of alternative specifications of the equations of this model. For this purpose two different methods of estimation were used.
REFLECTIONS ON NATIONAL ACCOUNTING
Authors: Geary R. C.
Published: April 2005

This article consists of a description and critical analysis of two important works on national accounting which have appeared fairly recently—see footnotes 1 and 2. There are fundamental differences between the systems of accounts proposed in these two works, the author tending to prefer the Ruggles system. While full of admiration for the thoroughness and other qualities of the new SNA, the author finds the system it proposes over‐elaborate as a programme for national statistical offices. In his view decision as to which is the “best” system is still wide open, despite the acceptance of the new SNA by the UN Statistical Commission. In the article there is bare mention of a new (1972) book Economic Accounts and Their Uses by J. W. Kendrick which the author has since read. All three works help in determining the best practical system of accounts. It is hoped that this article (in its small way) will also make a contribution

The subject of national accounts at constant prices is not dealt with at all in any of the three works despite the fact that it has received considerable attention at various meetings of IARIW. Accounts at constant prices and their concomitant price indexes are more important in these days of the curse of inflation than are accounts at current prices. Of course the new SNA deals with items at constant prices but the author finds the treatment rather inadequate.

It is satisfactory that the new SNA provides for input‐output but the author agrees with the Ruggles view that the textual treatment in SNA is somewhat incomplete.

The article gives the author's views on many other topics relevent to national accounting (which encompass all economic statistics!) including price index number making, inaccuracies in data, delays in availability of so‐called “current” statistics, and treatment of financial intermediaries.
RETURNS TO SCALE IN RETAIL TRADE*
Authors: Ofer Gur
Published: April 2005

This paper attempts to estimate genuine scale effects in retail trade from a cross section of retail stores in Israel. This is done by estimating a simple production function for several retail branches and employing the faithful old direct Cobb‐Douglas structure with value added as output and labor and capital inputs. And indeed despite the well‐known peculiarities of the retail industry, a cross section estimation produces “normal” production‐function estimates with reasonable input elasticities. The estimates also identify marked increasing returns‐to‐scale parameters, higher in food and lower in branches less affected by consumer participation and geographical dispersion. These increasing returns may explain a good part of the increase in sales per unit of inputs observed in time series.
DATA REVISIONS AND FORECASTING ACCURACY: AN ECONOMETRIC ANALYSIS BASED ON PRELIMINARY AND REVISED NATIONAL ACCOUNTING ESTIMATES*
Authors: Denton Frank T. , Oksanen Ernest H.
Published: April 2005

This paper entails an investigation of the effects of data revisions on forecasting accuracy, through use of preliminary and revised national accounting data compiled by the United Nations. A small model was estimated for each of fourteen countries and ex post“forecasts” generated for each country and each year of the period 1957–1964, using first preliminary and then revised data.

A prior analysis of the data revisions indicated a strong and widespread tendency for the preliminary estimates to understate both levels and year‐to‐year changes. This is consistent with the findings of other studies.

Two sets of forecasts obtained from the reduced form of the model were considered in relation to “actual” levels and changes, obtained from the revised data, and also in relation to each other. A strong downward bias was observed in the forecasts of levels based on preliminary data, and a weaker one in the forecasts of changes. The forecast discrepancies for different variables were found to be significantly correlated.

The results suggest that a tendency toward understatement in preliminary data may account in part for the general tendency toward understatement in forecasts noted in other studies.
THE CONCENTRATION OF PERSONAL WEALTH IN AMERICA, 1969
Authors: Smith James D.
Published: April 2005

This essay focuses on the problems of estimating the share of America's personal wealth in the hands of affluent individuals by a technique known as the estate multiplier method. Rather than exploring these problems in an empirical vacuum, we first present some results from the most recent estimates of the distribution of U.S. personal wealth.1 The estimates—for the year 1969—are then used as a basis for gauging the sensitivity of estate multiplier estimates to variations in approach.

Section I presents new empirical findings dealing with the asset holdings of top wealth‐holders and the super rich, and with the shares of specific assets owned by them. Also presented is information about the sex and marital status of the super rich.

Section II discusses various technical aspects of the estate multiplier as applied to federal estate tax returns. The main concern is with the weighting process, but attention is paid to the fact that estate tax returns filed in a given year are not for decedents who died in that year or any single year, and to the problems of adjusting the face value of life insurance to cash surrender value.
ECONOMIC GROWTH AND SOCIAL DEVELOPMENT: A STATISTICAL INVESTIGATION*
Authors: King Mervyn A.
Published: April 2005

Some writers have emphasised the adverse environmental and social effects of economic growth, while others have claimed that countries with higher levels of social well‐being also tend to enjoy higher levels of per capita output. The aim of this study is to see what statistical light can be thrown on these issues by collating and comparing seventeen different social indicators for twenty countries in two bench‐mark years, 1951 and 1969.

Two methods of analysing data are employed. First, all the countries are ranked for each indicator in turn for a particular year. Each country is then given a score ranging from 1 to 20 for each indicator, and the scores aggregated over the indicators to obtain an overall ranking score for every country. Secondly, the data are subjected to a principal components analysis to examine the correlation between the indicators. The first principal component is a potential candidate for use as a social index number. Changes in these social variables are then related to the rate of economic growth, and no evidence is found of a negative correlation between economic growth and social development. On the contrary, the results suggest a positive correlation between the two, although the strength of this relationship may be diminishing. It is not claimed that the results are in any sense the most preferred test of the form of the relationship between economic growth and social welfare, which must be a matter for subjective evaluation; rather they are seen as a contribution to the body of empirical evidence on this subject.
THE ACCOUNTING TREATMENT OF HUMAN INVESTMENT AND CAPITAL
Authors: Kendrick John W.
Published: April 2005

Defining investment as outlays that increase income‐ and output‐producing capacity, the author presents estimates of human investment in the United States 1929–69, comprising rearing costs, education, training, health, safety and mobility outlays. He develops an economic accounting framework to accommodate human investments and research and development in national and sector capital accounts, with appropriate adjustments to the current accounts to provide consistency. The associated balance sheets and wealth statements are also developed.

The wealth and corresponding income estimates are used to compute rates of return on human, non‐human, and total capital. In the business economy the average net rate of return on total capital was 10.6 percent in 1969, compared with 10.0 percent in 1929. The average and marginal rates of return on human capital were generally somewhat higher than on non‐human capital throughout the period.
POSTSCHOOL LEARNING AND HUMAN RESOURCE ACCOUNTING
Authors: Bowman Mary Jean
Published: April 2005

The central concern of this paper is with the treatment of human resources in dynamic applications of capital and growth accounting. Despite many advances, national accounting conventions still give biased profiles of the economy, but the time is ripe for experimentation with measures that can correct those biases and provide a more adequate base for assessment of long‐term economic performance and prospects.

In the first section, the logic and feasibility of forward and backward measures of formation of human capital in the simplest case (of full‐time schooling) is examined in parallel with physical capital. In a dynamic economy, which is rarely if ever in equilibrium, these approaches complement each other; they are poor substitutes. In section two a number of conceptual and measurement issues are considered with particular reference to human‐capital investment periods and the treatment of appreciation, depreciation and obsolescence of human versus physical capital. Here special attention is given to the extended periods of investments in human resources, which overlap with realization of returns, and to the processes and agencies through which postschool investments are made. The last section presents a brief statement concerning asymmetries in disequilibrium biases with respect to the formation of human relative to physical capital. Drawing upon section 1 with regard to forward and backward measures and section 2 with regard to the critical importance of postschool learning, new possibilities in contributions of national accounting to a dynamic analysis of economic development are suggested.
THE CHARACTERIZATION OF GOODS AND SERVICES: AN ALTERNATIVE APPROACH
Authors: Gadrey Jean
Published: April 2005

The definitions of goods and services have been debated among economists for more than two centuries. This article seeks to consider the definitions currently used from a critical perspective and to offer a new general definition of services that is compatible with the existence of several demand rationales.
Correlation between conformational stability of the ternary enzyme–substrate complex and domain closure of 3‐phosphoglycerate kinase
Authors: Varga Andrea , Flachner Beáta , Gráczer Éva , Osváth Szabolcs , Szilágyi Andrea N. , Vas Mária
Published: April 2005

3‐Phosphoglycerate kinase (PGK) is a typical two‐domain hinge‐bending enzyme with a well‐structured interdomain region. The mechanism of domain–domain interaction and its regulation by substrate binding is not yet fully understood. Here the existence of strong cooperativity between the two domains was demonstrated by following heat transitions of pig muscle and yeast PGKs using differential scanning microcalorimetry and fluorimetry. Two mutants of yeast PGK containing a single tryptophan fluorophore either in the N‐ or in the C‐terminal domain were also studied. The coincidence of the calorimetric and fluorimetric heat transitions in all cases indicated simultaneous, highly cooperative unfolding of the two domains. This cooperativity is preserved in the presence of substrates: 3‐phosphoglycerate bound to the N domain or the nucleotide (MgADP, MgATP) bound to the C domain increased the structural stability of the whole molecule. A structural explanation of domain–domain interaction is suggested by analysis of the atomic contacts in 12 different PGK crystal structures. Well‐defined backbone and side‐chain H bonds, and hydrophobic and electrostatic interactions between side chains of conserved residues are proposed to be responsible for domain–domain communication. Upon binding of each substrate newly formed molecular contacts are identified that firstly explain the order of the increased heat stability in the various binary complexes, and secondly describe the possible route of transmission of the substrate‐induced conformational effects from one domain to the other. The largest stability is characteristic of the native ternary complex and is abolished in the case of a chemically modified inactive form of PGK, the domain closure of which was previously shown to be prevented [Sinev MA, Razgulyaev OI, Vas M, Timchenko AA & Ptitsyn OB (1989) Eur J Biochem180, 61–66]. Thus, conformational stability correlates with domain closure that requires simultaneous binding of both substrates.
A novel hyperthermostable 5′‐deoxy‐5′‐methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus
Authors: Cacciapuoti Giovanna , Forte Sabrina , Moretti Maria Angela , Brio Assunta , Zappia Vincenzo , Porcelli Marina
Published: April 2005

We report herein the first molecular characterization of 5′‐deoxy‐5′‐methylthio‐adenosine phosphorylase II from Sulfolobus solfataricus (SsMTAPII). The isolated gene of SsMTAPII was overexpressed in Escherichia coli BL21. Purified recombinant SsMTAPII is a homohexamer of 180 kDa with an extremely low Km (0.7 µm) for 5′‐deoxy‐5′‐methylthioadenosine. The enzyme is highly thermophilic with an optimum temperature of 120 °C and extremely thermostable with an apparent Tm of 112 °C that increases in the presence of substrates. The enzyme is characterized by high kinetic stability and remarkable SDS resistance and is also resistant to guanidinium chloride‐induced unfolding with a transition midpoint of 3.3 m after 22‐h incubation. Limited proteolysis experiments indicated that the only one proteolytic cleavage site is localized in the C‐terminal region and that the C‐terminal peptide is necessary for the integrity of the active site. Moreover, the binding of 5′‐deoxy‐5′‐methylthioadenosine induces a conformational transition that protected the enzyme against protease inactivation. By site‐directed mutagenesis we demonstrated that Cys259, Cys261 and Cys262 play an important role in the enzyme stability since the mutants C259S/C261S and C262S show thermophilicity and thermostability features significantly lower than those of the wild‐type enzyme. In order to get insight into the physiological role of SsMTAPII a comparative kinetic analysis with the homologous 5′‐deoxy‐5′‐methylthioadenosine phosphorylase from Sulfolobus solfataricus (SsMTAP) was carried out. Finally, the alignment of the protein sequence of SsMTAPII with those of SsMTAP and human 5′‐deoxy‐5′‐methylthioadenosine phosphorylase (hMTAP) shows several key residue changes that may account why SsMTAPII, unlike hMTAP, is able to recognize adenosine as substrate.
Differential effects of histone deacetylase inhibitors on phorbol ester‐ and TGF‐β1 induced murine tissue inhibitor of metalloproteinases‐1 gene expression
Authors: Young David A. , Billingham Olivia , Sampieri Clara L. , Edwards Dylan R. , Clark Ian M.
Published: April 2005

Expression of the tissue inhibitor of metalloproteinases‐1 (Timp‐1) gene can be induced by either phorbol myristate acetate (PMA) or transforming growth factor β1 (TGF‐β1), although the signalling pathways involved are not clearly defined. Canonically, histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) or sodium butyrate (NaB) increase total cellular histone acetylation and activate expression of susceptible genes. Remarkably, PMA and TGF‐β1 stimulation of Timp‐1 show a differential response to TSA or NaB. TSA or NaB potentiate PMA‐induced Timp‐1 expression but repress TGF‐β1‐induced Timp‐1 expression. The repression of TGF‐β1‐induced Timp‐1 by TSA was maximal at 5 ng·mL−1, while for the superinduction of PMA‐induced Timp‐1 expression, the maximal dose is > 500 ng·mL−1 TSA. A further HDACi, valproic acid, did not block TGF‐β1‐induced Timp‐1 expression, demonstrating that different HDACs impact on the induction of Timp‐1. For either PMA or TGF‐β1 to induce Timp‐1 expression, new protein synthesis is required, and the induction of AP‐1 factors closely precedes that of Timp‐1. The effects of the HDACi can be reiterated in transient transfection using Timp‐1 promoter constructs. Mutation or deletion of the AP‐1 motif (−59/−53) in the Timp‐1 promoter diminishes PMA‐induction of reporter constructs, however, the further addition of TSA still superinduces the reporter. In c‐Jun–/– cells, PMA still stimulates Timp‐1 expression, but TSA superinduction is lost. Transfection of a series of Timp‐1 promoter constructs identified three regions through which TSA superinduces PMA‐induced Timp‐1 and we have demonstrated specific protein binding to two of these regions which contain either an avian erythroblastosis virus E26 (v‐ets) oncogene homologue (Ets) or Sp1 binding motif.
Structures of Phanerochaete chrysosporium Cel7D in complex with product and inhibitors
Authors: Ubhayasekera Wimal , Muñoz Inés G. , Vasella Andrea , Ståhlberg Jerry , Mowbray Sherry L.
Published: April 2005

The cellobiohydrolase Pc_Cel7D is the major cellulase produced by the white‐rot fungus Phanerochaete chrysosporium, constituting ≈10% of the total secreted protein in liquid culture on cellulose. The enzyme is classified into family 7 of the glycoside hydrolases and, like other family members, catalyses cellulose hydrolysis with net retention of the anomeric carbon configuration. Previous work described the apo structure of the enzyme. Here we investigate the binding of the product, cellobiose, and several inhibitors, i.e. lactose, cellobioimidazole, Tris/HCl, calcium and a thio‐linked substrate analogue, methyl 4‐S‐β‐cellobiosyl‐4‐thio‐β‐cellobioside (GG‐S‐GG). The three disaccharides bind in the glucosyl‐binding subsites +1 and +2, close to the exit of the cellulose‐binding tunnel/cleft. Pc_Cel7D binds to lactose more strongly than cellobiose, while the opposite is true for the homologous Trichoderma reesei cellobiohydrolase Tr_Cel7A. Although both sugars bind Pc_Cel7D in a similar fashion, the different preferences can be explained by varying interactions with nearby loops. Cellobioimidazole is bound at a slightly different position, displaced ≈2 Å toward the catalytic centre. Thus the Pc_Cel7D complexes provide evidence for two binding modes of the reducing‐end cellobiosyl moiety; this conclusion is confirmed by comparison with other available structures. The combined results suggest that hydrolysis of the glycosyl‐enzyme intermediate may not require the prior release of the cellobiose product from the enzyme. Further, the structure obtained in the presence of both GG‐S‐GG and cellobiose revealed electron density for Tris at the catalytic centre. Inhibition experiments confirm that both Tris and calcium are effective inhibitors at the conditions used for crystallization.
Poly(ADP‐ribose) polymerase‐1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts
Authors: Parsons Jason L. , Dianova Irina I. , Allinson Sarah L. , Dianov Grigory L.
Published: April 2005

Base excision repair (BER), a major pathway for the removal of simple lesions in DNA, requires the co‐ordinated action of several repair and ancillary proteins, the impairment of which can lead to genetic instability. We here address the role of poly(ADP‐ribose) polymerase‐1 (PARP‐1) in BER. Using an in vitro cross‐linking assay, we reveal that PARP‐1 is always involved in repair of a uracil‐containing oligonucleotide and that it binds to the damaged DNA during the early stages of repair. Inhibition of PARP‐1 poly(ADP‐ribosyl)ation by 3‐aminobenzamide blocks dissociation of PARP‐1 from damaged DNA and prevents further repair. We find that excessive poly(ADP‐ribosyl)ation occurs when repair intermediates containing single‐strand breaks are in excess of the repair capacity of the cell extract, suggesting that repeated binding of PARP‐1 to the nicked DNA occurs. We also find increased sensitivity of repair intermediates to nuclease cleavage in PARP‐deficient mouse fibroblasts and after depletion of PARP‐1 from HeLa whole cell extracts. Our data support the model in which PARP‐1 binding to DNA single‐strand breaks or repair intermediates plays a protective role when repair is limited.
The structural comparison of the bacterial PepX and human DPP‐IV reveals sites for the design of inhibitors of PepX activity
Authors: Rigolet Pascal , Xi Xu Guang , Rety Stephane , Chich Jean‐François
Published: April 2005

X‐prolyl dipeptidyl aminopeptidases (X‐PDAP) are enzymes catalysing the release of dipeptides from the amino termini of polypeptides containing a proline or an alanine at the penultimate position. Involved in various mammalian regulation processes, as well as in chronic human diseases, they have been proposed to play a role in pathogenicity for Streptococci. We compared the structure of X‐PDAP from Lactococcus lactis (PepX) with its human counterpart DPP‐IV. Despite very different overall folds, the residues most implicated for X‐PDAP activity are conserved in the same positions and orientations in both enzymes, thus defining a structural signature for the X‐PDAP specificity that crosses the species frontiers of evolution. Starting from this observation, we tested some inhibitors of DPP‐IV on PepX activity, for which no specific inhibitor is known. We thus found that PepX was highly sensitive to valine‐pyrrolidide with a KI of 9.3 µm, close to that reported in DPP‐IV inhibition. We finally used the structure of PepX from L. lactis as a template for computer‐based homology modeling of PepX from the pathogenic Streptococcus gordonii. Docking simulations of valine‐pyrrolidide into the active site of PepX led to the identification of key residues for a rational drug design against PepX from Streptococci. These results could have applications in human health giving new perspectives to the struggle against pathogens.
RETHINKING RISK MANAGEMENT
Authors: Stulz René M.
Published: April 2005

This paper presents a theory of corporate risk management that attempts to go beyond the “variance‐minimization” model that dominates most academic discussions of the subject. It argues that the primary goal of risk management is not to dampen swings in corporate cash flows or value, but rather to provide protection against the possibility of costly lower‐tail outcomes–situations that would cause financial distress or make a company unable to carry out its investment strategy. (In the jargon of finance specialists, risk management can be viewed as the purchase of well‐out‐of‐the‐money put options designed to limit downside risk.)

By eliminating downside risk and reducing the expected costs of financial trouble, risk management can also help a company to achieve both its optimal capital structure and its optimal ownership structure. For, besides increasing corporate debt capacity, the reduction of downside risk also encourages larger equity stakes for managers by shielding their investments from “uncontrollables.”

The paper also departs from standard finance theory in suggesting that some companies may have a comparative advantage in bearing certain financial market risks–an advantage that derives from information acquired through their normal business activities. Although such specialized information may lead some companies to take speculative positions in commodities or currencies, it is more likely to encourage “selective” hedging, a practice in which the risk manager's “view” of future price movements influences the percentage of the exposure that is hedged.

But, to the extent that such view‐taking becomes an accepted part of a company's risk management program, it is important to evaluate managers' bets on a risk‐adjusted basis and relative to the market. If risk managers want to behave like money managers, they should be evaluated like money managers.
A PRACTICAL APPROACH TO CALCULATING COSTS OF EQUITY FOR INVESTMENTS IN EMERGING MARKETS
Authors: Godfrey Stephen , Espinosa Ramon
Published: April 2005

While most financial economists argue that multinational corporations (MNCs) should use discount rates that reflect only “systematic” or “covariance” risks when evaluating offshore projects, the managers of most MNCs do not appear to follow this prescription of the CAPM. Instead they favor use of discount rates that reflect the “total risk” of emerging‐market investments (as evidenced, for example, by the comments of the executives in the Roundtable discussion that immediately precedes this article).

The authors defend this practice by noting that emerging countries are generally in the midst of profound economic and political transformations; and, although an MNC's shareholders may be willing to accept considerably lower rates of return on emerging‐markets projects because of the expected portfolio diversification benefits, the managements of MNCs are likely to find that using higher discount rates for emerging‐markets investments does a better job of accomplishing what a capital budgeting system is supposed to do—namely, to send strategic planners clear signals of the full extent of project risks and to set high standards of profitability for overseas operating managers.

After describing the “total‐risk” focus of corporate planners, the authors present a “practical model” for calculating discount rates for emerging countries that incorporates two dimensions of risk: (1) credit quality, which is intended to capture political or “sovereign” risks; and (2) business volatility, which reflects primarily the commercial risks of operating in a given country. Credit‐quality risk is measured by the credit spread (over U.S. Treasuries) of a country's sovereign debt denominated in dollars or other reserve currency. Business volatility is captured by an additional risk premium that reflects the volatility of the local stock market relative to the volatility of the domestic (U.S.) market. And, because these two sources of risk are not completely independent, the authors propose a downward adjustment to compensate for any “double counting” inherent in the method.
SOME NEW EVIDENCE ON WHY COMPANIES USE CONVERTIBLE BONDS
Authors: Jen Frank C. , Choi Dosoung , Lee Seong‐Hyo
Published: April 2005

The popular argument for convertibles holds that they provide issuers with “cheap” debt and allow them to sell equity at a premium over current value. Objecting to the “free lunch” implied by such an argument, financial economists have offered other explanations that show how the combination of debt and equity built into convertibles can serve to reduce information and agency costs faced by companies and their investors.

In this article, the authors use the results of their recent study to reconcile the two positions. Following Jeremy Stein's view of convertibles as “backdoor equity,” the authors argue that convertible bond financing is an attractive alternative for companies that have large growth potential but find both conventional debt and equity financing very costly. Such companies are often deterred from funding their capital investments with straight public bonds by their high risk, relatively short track records, and high expected costs of financial distress. At the same time, the information “asymmetry” between management and outside investors can make equity very expensive in such cases. In layman's terms, management may feel that the company's share price does not accurately reflect its growth prospects, or be concerned that the mere announcement of a new equity offering will cause the share price to fall sharply.

To the extent the stock market is persuaded that management's choice of convertibles is based on this combination of promising growth prospects with limited financing options, it is likely to respond more favorably to the announcement of a new convertible offering. The authors furnish evidence in support of this argument by reporting that the market reacts less negatively to those convertible issuers with higher post‐issue capital expenditures and higher market‐to‐book ratios, but with lower credit ratings and higher (post‐offering) debt‐equity ratios.