bluuebunny/crossref_metadata_2025 huggingface dataset:
Slavery, Atlantic Trade and the British Economy, 1660–1800
Authors: Morgan Kenneth
Published: December 2009

This book considers the impact of slavery and Atlantic trade on British economic development in the generations between the restoration of the Stuart monarchy and the era of the Younger Pitt. During this period Britain's trade became 'Americanised' and industrialisation began to occur in the domestic economy. The slave trade and the broader patterns of Atlantic commerce contributed important dimensions of British economic growth although they were more significant for their indirect, qualitative contribution than for direct quantitative gains. Kenneth Morgan investigates five key areas within the topic that have been subject to historical debate: the profits of the slave trade; slavery, capital accumulation and British economic development; exports and transatlantic markets; the role of business institutions; and the contribution of Atlantic trade to the growth of British ports. This stimulating and accessible book provides essential reading for students of slavery and the slave trade, and British economic history.
Perspectives on Modern German Economic History and Policy
Authors: Borchardt Knut
Published: December 2009

This collection of essays covers themes central to German economic history while considering their interaction with other historical phenomena. Among the essays Borchardt considers Germany's late start as an industrial nation, the West-East developmental gradient, key patterns of long-term economic development, and unusual changes in the phenomena of business cycles. The collection also contains the essays which have become the subject of so-called 'Borchardt controversies', in which hypotheses are presented on the economic causes of the collapse of the parliamentary regime by 1929–30, at the very end of the 'crisis before the crisis'. He also explains why there were no alternatives to the economic policies of the slump, and in particular why there was no 'miracle weapon' against Hitler's seizure of power. These are among the most original and stimulating contributions of recent years to the economic history of modern Germany and will be of interest to anyone who ponders deeply the meaning of history.
Thrillers
Authors: Rubin Martin
Published: December 2009

The thriller is perhaps the most popular and widespread movie genre - and the most difficult to define. Thrillers can contain gangsters or ghosts, space helmets or fedoras. They charge our familiar world with a spirit of exotic, old-fashioned adventure. They give us pleasure by making us uncomfortable - on the edge of our seats.Thrillers provides a comprehensive treatment of this genre, from silent serials to stalker films, from Alfred Hitchcock to Quentin Tarantino, from The Great Train Robbery to L.A. Confidential. This accessible, wide-ranging volume is designed to appeal to students and general filmgoers alike, and shows how this visceral, double-faced film genre has aroused our intense sensations throughout decades of American cinema.
Minority Rights, Majority Rule
Authors: Binder Sarah A.
Published: December 2009

Minority Rights, Majority Rule seeks to explain a phenomenon evident to most observers of the US Congress. In the House of Representatives, majority parties rule and minorities are seldom able to influence national policy making. In the Senate, minorities quite often call the shots, empowered by the filibuster to frustrate the majority. Why did the two chambers develop such distinctive legislative styles? Conventional wisdom suggests that differences in the size and workload of the House and Senate led the two chambers to develop very different rules of procedure. Sarah Binder offers an alternative, partisan theory to explain the creation and suppression of minority rights, showing that contests between partisan coalitions have throughout congressional history altered the distribution of procedural rights. Most importantly, new majorities inherit procedural choices made in the past. This institutional dynamic has fuelled the power of partisan majorities in the House but stopped them in their tracks in the Senate.
Rethinking World History
Authors: Hodgson Marshall G. S.
Published: December 2009

Is the history of the modern world the history of Europe writ large? Or is it possible to situate the history of modernity as a world historical process apart from its origins in Western Europe? In this posthumous collection of essays, Marshall G. S. Hodgson challenges adherents of both Eurocentrism and multiculturalism to rethink the place of Europe in world history. He argues that the line that connects Ancient Greeks to the Renaissance to modern times is an optical illusion, and that a global and Asia-centred history can better locate the European experience in the shared histories of humanity. Hodgson then shifts the historical focus and in a parallel move seeks to locate the history of Islamic civilisation in a world historical framework. In so doing he concludes that there is but one history - global history - and that all partial or privileged accounts must necessarily be resituated in a world historical context. The book also includes an introduction by the editor, Edmund Burke, contextualising Hodgson's work in world history and Islamic history.
Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies
Authors: Arguin Hélène , Sánchez Marina , Bray George A. , Lovejoy Jennifer C. , Peters John C. , Jandacek Ronald J. , Chaput Jean-Philippe , Tremblay Angelo
Published: December 2009

The aim of these studies was to evaluate the potential of some nutritional approaches to prevent or reduce the body load of organochlorines (OC) in humans. Study 1 compared plasma OC concentrations between vegans and omnivores while study 2 verified if the dietary fat substitute olestra could prevent the increase in OC concentrations that is generally observed in response to a weight-reducing programme. In study 1, nine vegans and fifteen omnivores were recruited and the concentrations of twenty-six OC (β-hexachlorocyclohexane (β-HCH),p,p′-dichlorodiphenyldichloroethane (p,p′-DDE),p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT), hexachlorobenzene, mirex, aldrin, α-chlordane, γ-chlordane, oxychlordane,cis-nonachlor,trans-nonachlor, polychlorinated biphenyl (PCB) nos. 28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor 1260) were determined. In study 2, the concentrations of these twenty-six OC were measured before and after weight loss over 3 months in thirty-seven obese men assigned to one of the following treatments: standard group (33 % fat diet;n13), fat-reduced group (25 % fat diet;n14) or fat-substituted group (1/3 of dietary lipids substituted by olestra;n10). In study 1, plasma concentrations of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were significantly lower in vegans compared with omnivores. In study 2, β-HCH was the only OC which decreased in the fat-substituted group while increasing in the other two groups (P = 0·045). In conclusion, there was a trend toward lesser contamination in vegans than in omnivores, and olestra had a favourable influence on β-HCH but did not prevent plasma hyperconcentration of the other OC during ongoing weight loss.
Effect of postprandial modulation of glucose availability: short- and long-term analysis
Authors: Nazare Julie-Anne , de Rougemont Alexis , Normand Sylvie , Sauvinet Valérie , Sothier Monique , Vinoy Sophie , Désage Michel , Laville Martine
Published: December 2009

Low glycaemic index (LGI) foods have been proposed as potential means to decrease postprandial glucose excursions and thus to improve diabetes management. We modulated glucose availability of cereal products and thus their glycaemic index to study the metabolic effect of LGI foods on daylong glucose control acutely and in the long term following a 5-week GI intervention diet in free-living subjects. In this randomised, parallel trial, two groups of nineteen overweight subjects followed an ad libitum 5-week intervention diet in which usual starch was replaced by either LGI or high GI (HGI) starch. During the exploration days (days 1 and 36), subjects ate their assigned 13C-labelled test breakfast (LGI or HGI), and total and exogenous glucose kinetics (using stable isotopes), postprandial concentrations of glucose, insulin, lipid profile and nutrient oxidation were assessed after the test breakfast and a standardised lunch. At day 1, LGI breakfast significantly decreased post-breakfast glycaemic response with a parallel decrease in exogenous and total glucose appearance (P < 0·05). Post-lunch and post-breakfast glycaemic responses were positively correlated (r 0·79, P < 0·0001). Following the 5-week diet, difference between the groups in terms of glucose kinetics and response was maintained (no significant interaction group × time) but tended to decrease over time for the post-breakfast glycaemic response. Post-lunch and post-breakfast glycaemic responses remained positively correlated (r 0·47, P = 0·004). Modulation of postprandial glucose availability at breakfast decreased plasma exogenous glucose appearance and improved glucose control at the subsequent lunch. After 5 weeks, these effects were maintained in healthy subjects but remained to be confirmed in the longer term.
“There Is a Spirit in that Image”: Mass-Produced Jesus Pictures and Protestant-Pentecostal Animation in Ghana
Authors: Meyer Birgit
Published: December 2009

In southern Ghana, where I have been conducting research on the genesis of popular Christianity for almost twenty years, Christian imagery is everywhere. The Ghanaian state re-adopted a democratic constitution in 1992, and this was followed by a liberalization and commercialization of mass media, which in turn facilitated the spread of Pentecostalism in the public sphere (see De Witte 2008; Gifford 2004; Meyer 2004a). Within this process, Christian pictures have become ubiquitous. Pentecostal-charismatic churches assert their public presence and power via television, radio, posters, and stickers, and there has also emerged a new public culture rife with Christian imagery. This visual and aural expansion of Christianity and its particular aesthetic severely challenges what is being called African Traditional religion, and clashes with initiatives developed by the state and intellectuals to secure a national heritage.
Evaluation of different approaches for the estimation of daily yield from single milk testing scheme in cattle
Authors: Jenko Janez , Perpar Tomaž , Gorjanc Gregor , Babnik Drago
Published: December 2009

Three models for the estimation of milk, fat and protein daily yield (DY) based on a.m. (AM) or p.m. (PM) milkings were compared. A total of 518 766 test-day records from 5078 dairy cattle farms obtained between March 2004 and April 2008 were analysed. The DY model was a linear model with DY as a dependent variable. In the PYR model and the DYR model, partial yield ratios (AM:DY and PM:DY) and daily yield ratios (DY:AM and DY:PM), respectively, were used as a dependent variable in the first step. In the second step, DY was estimated as a partial yield divided (PYR model) or multiplied (DYR model) by the estimated yield ratio from the first step. Models included the effect of partial yield (only in the DY model), milking interval, stage (month) of lactation and parity. Analysis of variance indicated that partial yield was the most important source of variation for the DY model whereas milking interval had the biggest effect in the PYR model and the DYR model. Differences in accuracy (correlation between the true and the estimated DY) between the models were negligible. On the other hand, models differed in the amount of bias (average error). The DYR model on average overestimated DY by 0·13 kg, 0·01 kg and 0·01 kg for milk, fat and protein, respectively. For the other two models the overall bias was almost zero. However, the DY model overestimated low and underestimated high DY owing to the well known regression property. The DYR model progressively overestimated high DY. These problems were not observed with the PYR model which seemed to be the best model. In this paper a relatively old topic was analysed and discussed from a new point of view, where the estimation of DY is based on modelling biologically more stable partial yield ratios rather than yield values from a.m. or p.m. milking.
Manifold Grace in John Cassian and Prosper of Aquitaine
Authors: Hwang Alexander Y.
Published: December 2009

This article is about John Cassian and Prosper of Aquitaine's understanding of grace and free will as put forward during the initial phase of the Western Church's struggle to define the doctrine of grace in the wake of the Pelagian controversy. Although both figured prominently in this struggle, both Cassian and Prosper's later understandings of grace and free will, which appreciated the diverse expressions of grace, failed to have any influence on the terms of the debate set forth in the Pelagian controversy. The history of the debate on grace and free will followed the mutually exclusive model in which salvation was the result of either grace or free will. Cassian and Prosper, who both offered an alternative to the mutually exclusive model, have not been fully recognised for their innovative views.
Introduction
Authors: Hamilton William Douglas
Published: December 2009

In its main features this History may be described as a continuation of “The Customes of London,” by Richard Arnold, from which the earlier portion, i.e. as far as the 11th year of Henry VIII., is a mere plagiarism. After that date the Chronicle becomes original, and contains much valuable information. From internal evidence it would appear to be the work of a scholar, and to have been written contemporaneously, the events being jotted down from day to day as they occurred. The characteristic of City Chronicles is maintained throughout by the adoption of the civic year, marking the term of office of each Lord Mayor instead of the regnal year of the sovereign, thus causing an apparent confusion in the chronology. This form was probably adopted by our author as he found it already employed by Richard Arnold, whose reign of Henry VII.
Estimating reservoir sedimentation rates at large spatial and temporal scales: A case study of California
Authors: Minear J. Toby , Kondolf G. Matt
Published: December 2009

Previous reservoir sedimentation models have ignored two key factors for large spatial and temporal modeling of multiple reservoirs: trapping by upstream dams and decreasing sediment trapping as reservoirs fill. We developed a spreadsheet‐based model that incorporates both factors. Using California as a case study, we used measured sedimentation rates to estimate sediment yields for distinct geomorphic regions and applied those rates to unmeasured reservoirs by region. Statewide reservoirs have likely filled with 2.1 billion m3 of sediment to date, decreasing total reservoir capacity by 4.5%. About 200 reservoirs have likely lost more than half their initial capacity to sedimentation.
Revisiting sites of the South Pole Queen Maud Land Traverses in East Antarctica: Accumulation data from shallow firn cores
Authors: Anschütz H. , Müller K. , Isaksson E. , McConnell J. R. , Fischer H. , Miller H. , Albert M. , Winther J.‐G.
Published: December 2009

Ground‐based accumulation measurements are scarce on the high East Antarctic plateau, but highly necessary for model validation and the interpretation of satellite data for the determination of Antarctic mass balance. Here, we present accumulation results obtained from four shallow firn cores drilled in the Antarctic summer season 2007/2008. The cores were drilled along the first leg of the Norwegian‐US IPY traverse through East Antarctica, visiting sites like Plateau Station and Pole of Relative Inaccessibility that have been covered by the South Pole Queen Maud Land Traverses (SPQMLT) in the 1960s. Accumulation has been determined from volcanic chronology established from the conductivity records measured by dielectric profiling (DEP). The Tambora 1815/unknown 1809 double peak is clearly visible in the conductivity data and serves as a reliable time marker. Accumulation rates averaged over the period 1815–2007 are in the range of 16 to 32 kg m−2 a−1, somewhat lower than expected from the SPQMLT data. The spatial pattern is mainly influenced by elevation and continentality. Three of the firn cores show a decrease of more than 20% in accumulation for the time period 1815–2007 in relation to accumulation rates during the period 1641–1815. The spatial representativity of the firn cores is assessed by ground‐penetrating radar, showing a rather smoothly layered pattern around the drill sites. Validation of the DEP results is utilized by comparison with chemistry data, proving the validity of the DEP method for dating firn cores. The results help understanding the status of the East Antarctic ice sheet and will be important for e.g. future model‐derived estimates of the mass balance of Antarctica.
Generalization of the multirate basis for time convolution to unequal forward and reverse rates and connection to reactions with memory
Authors: Ginn Timothy R.
Published: December 2009

The convolution form used to express mass transfer between mobile and immobile aqueous domains, and often associated with multirate mass transfer representations of matrix diffusion processes, is generalized to the case of unequal forward and reverse rates for each of the multiple rates of the multirate mass transfer and is shown to represent also linear but non‐Markovian reactions that kinetically partition mass between mobile and immobile phases with rate of return to mobile phase dependent on contiguous time spent in the immobile phase. In the case where a multirate model refers to multiple sites with distributed mobilization or release rates but single‐valued immobilization rate, an equivalent formulation is found using single‐site mobilization‐immobilization with non‐Markovian mobilization rate dependent on contiguous time spent immobilized.
Anthropometric Measures and Risk of Epithelial Ovarian Cancer: Results From the Nurses' Health Study
Authors: Kotsopoulos Joanne , Baer Heather J. , Tworoger Shelley S.
Published: December 2009

Epidemiologic evaluations of the relationship between anthropometry and ovarian cancer risk have not been conclusive. Using data collected from two large cohorts, the Nurses' Health Study (NHS) and NHSII, we prospectively evaluated the association between waist and hip circumference, the waist‐to‐hip ratio (WHR), and BMI with risk of epithelial ovarian cancer. Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976 (NHS) and 1989 (NHSII). For the WHR and BMI analyses, 333 and 862 confirmed cases were identified, respectively, through 1 June 2006 (NHS) and 1 June 2005 (NHSII). WHR and waist circumference were not associated with risk (P‐trend = 0.63 and 0.65, respectively). There was evidence for a decreased risk with increasing hip circumference among postmenopausal women (P‐trend = 0.03), but a suggestive positive association among premenopausal women (P‐trend = 0.04) (P‐interaction = 0.01). The hazard ratios (HRs) comparing the highest vs. lowest quintile of hip circumference among pre‐ and postmenopausal women were 1.54 (95% confidence interval (CI) = 0.45–5.23) and 0.66 (95%CI = 0.37–1.16), respectively. BMI was not clearly associated with risk in pre‐ or postmenopausal women. Results from this large prospective study suggest that hip circumference could be a possible risk factor for premenopausal ovarian cancer, but may reduce risk of postmenopausal ovarian cancer. The differential effect of hip circumference based on menopausal status requires further confirmation.
Evaluation of Left Ventricular Synchronicity in Hypertensive Patients With Overweight or Obesity
Authors: Li Shao‐Hua , Tan Hong‐Wei , Wang Zhi‐Hao , Zhang Yun , Zhong Ming , Zhang Wei
Published: December 2009

The left ventricular synchronicity in hypertensive patients with overweight or obesity has not been well elucidated. This study was designed to evaluate the left ventricular synchronicity in these patients. Tissue Doppler imaging was performed in 126 hypertensive patients and 25 control subjects. The hypertensive patients were divided into three groups according to BMI: normal weight group (BMI <25 kg/m2, n = 32, H‐NW group), overweight group (BMI 25–29.9 kg/m2, n = 64, H‐OW group), and obese group (BMI ≥30 kg/m2, n = 30, H‐OB group). Left ventricular systolic and diastolic synchronicity were determined by measuring the maximal differences in time to peak myocardial systolic contraction (Ts‐diff) and early diastolic relaxation (Te‐diff) between any two of the left ventricular segments and the standard deviation of time to peak myocardial systolic contraction (Ts‐SD) and early diastolic relaxation (Te‐SD) of all 12 segments. Compared with the control group, the indexes of synchronicity including Ts‐diff, Ts‐SD, Te‐diff, and Te‐SD were significantly prolonged in the hypertensive patients. Furthermore, although the indexes of blood pressure had no difference among the hypertensive groups, the impaired systolic and diastolic synchronicity including Ts‐diff, Ts‐SD, and Te‐SD was obviously aggravated with the increasing BMI. Stepwise multivariate analysis revealed BMI as an independent predictor of Ts‐SD and Te‐SD. Therefore, the impairment of left ventricular synchronicity was aggravated with increasing BMI in hypertensive patients. Overweight and obesity may be important factors to impact the left ventricular synchronicity.
Reducing Portion Size Reduces Food Intake and Plate Waste
Authors: Freedman Marjorie R. , Brochado Carolina
Published: December 2009

As portion size (PS) increases, so does food intake. The effect of decreasing PS on food intake in a nonlaboratory setting is unknown. This 5‐week study sought to determine whether decreasing PS resulted in decreased intake of the same food, and if so, at what point further PS reductions might lack benefit. It also assessed effects of PS reduction on food production and waste in a university all‐you‐can‐eat dining facility (DF). Subjects were primarily freshmen who regularly ate lunch at the DF, and self‐selected French fries (FF) presented in individual paper bags, portioned originally at 88 g, and decreased ∼15 g/week for 3 weeks. Diners were covertly observed choosing one or more bags. Total FF production and plate waste (PW) were determined daily. Decreasing PS resulted in significant decreases in consumption per diner (P < 0.05) and PW (P < 0.05), and nonsignificant decreases in total FF consumption and production. PS was positively correlated with consumption per diner (r = 0.897, P = 0.001) and PW (r = 0.852, P = 0.001), but inversely correlated with number of diners choosing ≥2 bags (r = −0.809, P = 0.003). Total FF production was positively correlated with PW (r = 0.728, P = 0.011). This study shows that reducing PS of a particular item in an all‐you‐can‐eat environment results in reduced intake of that food for most individuals, and that reducing PS reduces PW and food production.
Showing the Essential Science Structure of a Scientific Domain and its Evolution
Authors: Vargas-Quesada Benjamin , de Moya-Anegón Félix , Chinchilla-Rodríguez Zaida , González-Molina Antonio
Published: December 2009

Category cocitation and its representation through social networks is proving to be a very adequate technique for the visualization and analysis of great scientific domains. Its combination with pathfinder networks using pruning values r = ∞ and q=n–1 makes manifest the essence of research in the domain represented, or what we might call the ‘most salient structure’. The possible loss of structural information, caused by aggressive pruning in peripheral areas of the networks, is overcome by creating heliocentric maps for each category. The depictions obtained with this procedure become tools of great usefulness in view of their capacity to reveal the evolution of a given scientific domain over time, to show differences and similarities between different domains, and to suggest possible new lines for development. This article presents the scientogram of the United States for the year 2002, identifying its essential structure. We also show the scientograms of China for the years 1990 and 2002, in order to study its particular national evolution. Finally, we try to detect patterns and tendencies in the three scientograms that would allow one to predict or flag the evolution of a scientific domain.
Measurement of mass, density, and volume during the cell cycle of yeast
Authors: Bryan Andrea K. , Goranov Alexi , Amon Angelika , Manalis Scott R.
Published: December 2009

Cell growth comprises changes in both mass and volume—two processes that are distinct, yet coordinated through the cell cycle. Understanding this relationship requires a means for measuring each of the cell’s three basic physical parameters: mass, volume, and the ratio of the two, density. The suspended microchannel resonator weighs single cells with a precision in mass of 0.1% for yeast. Here we use the suspended microchannel resonator with a Coulter counter to measure the mass, volume, and density of budding yeast cells through the cell cycle. We observe that cell density increases prior to bud formation at the G1/S transition, which is consistent with previous measurements using density gradient centrifugation. To investigate the origin of this density increase, we monitor relative density changes of growing yeast cells. We find that the density increase requires energy, function of the protein synthesis regulator target of rapamycin, passage through START (commitment to cell division), and an intact actin cytoskeleton. Although we focus on basic cell cycle questions in yeast, our techniques are suitable for most nonadherent cells and subcellular particles to characterize cell growth in a variety of applications.
Interplay between ER Exit Code and Domain Conformation in CFTR Misprocessing and Rescue
Authors: Roy Gargi , Chalfin Elaine M. , Saxena Anita , Wang Xiaodong
Published: December 2009

Multiple mutations in cystic fibrosis transmembrane conductance regulator (CFTR) impair its exit from the endoplasmic reticulum (ER). We compared two processing mutants: ΔF508 and the ER exit code mutant DAA. Although both have severe kinetic processing defect, DAA but not ΔF508 has substantial accumulation in its mature form, leading to higher level of processing at the steady state. DAA has much less profound conformational abnormalities. It has lower Hsp70 association and higher post-ER stability than ΔF508. The ER exit code is necessary for ΔF508 residual export and rescue. R555K, a mutation that rescues ΔF508 misprocessing, improves Sec24 association and enhances its post-ER stability. Using in situ limited proteolysis, we demonstrated a clear change in trypsin sensitivity in ΔF508 NBD1, which is reversed, together with that of other domains, by low temperature, R555K or both. We observed a conversion of the proteolytic pattern of DAA from the one resembling ΔF508 to the one similar to wild-type CFTR during its maturation. Low temperature and R555K are additive in improving ΔF508 conformational maturation and processing. Our data reveal a dual contribution of ER exit code and domain conformation to CFTR misprocessing and underscore the importance of conformational repair in effective rescue of ΔF508.
Regulation of tRNA Bidirectional Nuclear-Cytoplasmic Trafficking inSaccharomyces cerevisiae
Authors: Murthi Athulaprabha , Shaheen Hussam H. , Huang Hsiao-Yun , Preston Melanie A. , Lai Tsung-Po , Phizicky Eric M. , Hopper Anita K.
Published: December 2009

tRNAs in yeast and vertebrate cells move bidirectionally and reversibly between the nucleus and the cytoplasm. We investigated roles of members of the β-importin family in tRNA subcellular dynamics. Retrograde import of tRNA into the nucleus is dependent, directly or indirectly, upon Mtr10. tRNA nuclear export utilizes at least two members of the β-importin family. The β-importins involved in nuclear export have shared and exclusive functions. Los1 functions in both the tRNA primary export and the tRNA reexport processes. Msn5 is unable to export tRNAs in the primary round of export if the tRNAs are encoded by intron-containing genes, and for these tRNAs Msn5 functions primarily in their reexport to the cytoplasm. The data support a model in which tRNA retrograde import to the nucleus is a constitutive process; in contrast, reexport of the imported tRNAs back to the cytoplasm is regulated by the availability of nutrients to cells and by tRNA aminoacylation in the nucleus. Finally, we implicate Tef1, the yeast orthologue of translation elongation factor eEF1A, in the tRNA reexport process and show that its subcellular distribution between the nucleus and cytoplasm is dependent upon Mtr10 and Msn5.
DCDB: Drug combination database
Authors: Liu Yanbin , Hu Bin , Fu Chengxin , Chen Xin
Published: December 2009

Summary: Rapid advances in pharmaceutical sciences have brought ever-increasing interests in combined therapies for better clinical efficacy and safety, especially in cases of complicated and refractory diseases. Innovative experimental technologies and theoretical frameworks are being actively developed for multicomponent drug research. In this work, we present the Drug Combination Database, with aims to facilitate analyses of known drug combinations, to summarize patterns of beneficial drug interactions, and to provide a basis for theoretical modeling and simulation of such drug interactions. Its current version (1.0) collected 499 approved or investigational drug combinations, including 40 unsuccessful drug combinations, involving 485 individual drugs, from >6000 references.

Availability:  http://www.cls.zju.edu.cn/dcdb/.

Contact:  xinchen@zju.edu.cn

Supplementary information:  Supplementary data are available at the database website and Bioinformatics online.
BRAT: bisulfite-treated reads analysis tool
Authors: Harris Elena Y. , Ponts Nadia , Levchuk Aleksandr , Roch Karine Le , Lonardi Stefano
Published: December 2009

Summary: We present a new, accurate and efficient tool for mapping short reads obtained from the Illumina Genome Analyzer following sodium bisulfite conversion. Our tool, BRAT, supports single and paired-end reads and handles input files containing reads and mates of different lengths. BRAT is faster, maps more unique paired-end reads and has higher accuracy than existing programs. The software package includes tools to end-trim low-quality bases of the reads and to report nucleotide counts for mapped reads on the reference genome.

Availability: The source code is freely available for download at http://compbio.cs.ucr.edu/brat/ and is distributed as Open Source software under the GPLv3.0.

Contact:  elenah@cs.ucr.edu
Eyes are on us, but nobody cares: are eye cues relevant for strong reciprocity?
Authors: Fehr Ernst , Schneider Frédéric
Published: December 2009

Strong reciprocity is characterized by the willingness to altruistically reward cooperative acts and to altruistically punish norm-violating, defecting behaviours. Recent evidence suggests that subtle reputation cues, such as eyes staring at subjects during their choices, may enhance prosocial behaviour. Thus, in principle, strong reciprocity could also be affected by eye cues. We investigate the impact of eye cues on trustees' altruistic behaviour in a trust game and find zero effect. Neither the subjects who are classified as prosocial nor the subjects who are classified as selfish respond to these cues. In sharp contrast to the irrelevance of subtle reputation cues for strong reciprocity, we find a large effect of explicit, pecuniary reputation incentives on the trustees' prosociality. Trustees who can acquire a good reputation that benefits them in future interactions honour trust much more than trustees who cannot build a good reputation. These results cast doubt on hypotheses suggesting that strong reciprocity is easily malleable by implicit reputation cues not backed by explicit reputation incentives.
Sexual conflict and the gender load: correlated evolution between population fitness and sexual dimorphism in seed beetles
Authors: Arnqvist Göran , Tuda Midori
Published: December 2009

Although males and females share much of the same genome, selection is often distinct in the two sexes. Sexually antagonistic loci will in theory cause a gender load in populations, because sex-specific selection on a given trait in one sex will compromise the adaptive evolution of the same trait in the other sex. However, it is currently not clear whether such intralocus sexual conflict (ISC) represents a transient evolutionary state, where conflict is rapidly resolved by the evolution of sexual dimorphism (SD), or whether it is a more chronic impediment to adaptation. All else being equal, ISC should manifest itself as correlated evolution between population fitness and SD in traits expressed in both sexes. However, comparative tests of this prediction are problematic and have been unfeasible. Here, we assess the effects of ISC by comparing fitness and SD across distinct laboratory populations of seed beetles that should be well adapted to a shared environment. We show that SD in juvenile development time, a key life-history trait with a history of sexually antagonistic selection in this model system, is positively related to fitness. This effect is due to a correlated evolution between population fitness and development time that is positive in females but negative in males. Loosening the genetic bind between the sexes has evidently allowed the sexes to approach their distinct adaptive peaks.
Expression Quantitative Trait Loci Analysis of Two Genes Encoding Rubisco Activase in Soybean
Authors: Yin Zhitong , Meng Fanfan , Song Haina , Wang Xiaolin , Xu Xiaoming , Yu Deyue
Published: December 2009

Rubisco activase (RCA) catalyzes the activation of Rubisco in vivo and plays a crucial role in photosynthesis. However, until now, little was known about the molecular genetics of RCA in soybean (Glycine max), one of the most important legume crops. Here, we cloned and characterized two genes encoding the longer α -isoform and the shorter β -isoform of soybean RCA (GmRCA α and GmRCA β, respectively). The two corresponding cDNAs are divergent in both the translated and 3 ′ untranslated regions. Analysis of genomic DNA sequences suggested that the corresponding mRNAs are transcripts of two different genes and not the products of a single alternatively splicing pre-mRNA. Two additional possible α -form RCA-encoding genes, GmRCA03 and GmRCA14, and one additional β -form RCA-encoding gene, GmRCA11, were also isolated. To examine the function and modulation of RCA genes in soybean, we determined the expression levels of GmRCA α and GmRCA β, Rubisco initial activity, photosynthetic rate, and seed yield in 184 soybean recombinant inbred lines. Correlation of gene expression levels with three other traits indicates that RCA genes could play an important role in regulating soybean photosynthetic capacity and seed yield. Expression quantitative trait loci mapping revealed four trans-expression quantitative trait loci for GmRCA α and GmRCA β. These results could provide a new approach for the modulation of RCA genes to improve photosynthetic rate and plant growth in soybean and other plants.
CD4+CD25+regulatory T cells in autoimmune arthritis
Authors: Oh Soyoung , Rankin Andrew L. , Caton Andrew J.
Published: December 2009

Summary: CD4+CD25+regulatory T (Treg) cells can play a critical role in the prevention of autoimmunity, as evidenced by the cataclysmic autoimmune disease that develops in mice and humans lacking the key transcription factor forkhead box protein 3 (Foxp3). At present, however, how and whether Treg cells participate in the development of rheumatoid arthritis (RA), which has both systemic manifestations and a joint‐targeted pathology that characterizes the disease, remains unclear. In this review, we describe work that has been carried out aimed at determining the role of Treg cells in disease development in RA patients and in mouse models of inflammatory arthritis. We also describe studies in a new model of spontaneous autoimmune arthritis (TS1 × HACII mice), in which disease is caused by CD4+T cells recognizing a neo‐self‐antigen expressed by systemically distributed antigen‐presenting cells. We show that TS1 × HACII mice develop arthritis despite the presence of CD4+CD25+Foxp3+Treg cells that recognize this target autoantigen, and we outline steps in the development of arthritis at which Treg cells might potentially act, or fail to act, in the development of inflammatory arthritis.
Genetics and genomics of ankylosing spondylitis
Authors: Thomas Gethin P. , Brown Matthew A.
Published: December 2009

Summary:  Ankylosing spondylitis (AS) is a common, highly heritable arthropathy, the pathogenesis of which is poorly understood. The mechanism by which the main gene for the disease, HLA‐B27, leads to AS is unknown. Genetic and genomic studies have demonstrated involvement of the interleukin‐23 (IL‐23) signaling pathway in AS, a finding which has stimulated much new research into the disease and has led to therapeutic trials. Several other genes and genetic regions, including further major histocompatibility complex (MHC) and non‐MHC loci, have been shown to be involved in the disease, but it is not clear yet how they actually induce the condition. These findings have shown that there is a strong genetic overlap between AS and Crohn’s disease in particular, although there are also major differences in the genes involved in the two conditions, presumably explaining their different presentations. Genomic and proteomic studies are in an early phase but have potential both as diagnostic/prognostic tools and as a further hypothesis‐free tool to investigate AS pathogenesis. Given the slow progress in studying the mechanism of association of HLA‐B27 with AS, these may prove to be more fruitful approaches to investigating the pathogenesis of the disease.
Role of HLA class II genes in susceptibility/resistance to inflammatory arthritis: studies with humanized mice
Authors: Taneja Veena , David Chella S.
Published: December 2009

Summary:  Predisposition to develop rheumatoid arthritis (RA) has been associated with certain human leukocyte antigen (HLA) class II molecules, although the mechanism is still unknown. Various experimental animal models of inflammatory arthritis have been studied to address the role of major histocompatibility complex (MHC) genes in pathogenesis. We have generated transgenic mice expressing HLA class II molecules (DR and DQ) lacking complete endogenous class II molecules to study the interactions involved between class II molecules (DQ and DR) and to define the immunologic mechanisms in inflammatory arthritis. The HLA transgene can positively select CD4+ T cells expressing various Vβ T‐cell receptors, and a peripheral tolerance is maintained to transgenic HLA molecules. The expression of HLA molecules on various cells in these mice is similar to that known in humans. In this review, we describe collagen‐induced arthritis as a model for human inflammatory arthritis using these transgenic mice. The transgenic mice carrying RA‐susceptible haplotype develop gender‐biased inflammatory arthritis with clinical and histopathological similarities to RA. Our studies show that polymorphism of HLA class II genes determine the predisposition to rheumatoid/inflammatory arthritis and the epistatic interactions between HLA‐DQ and HLA‐DR molecules dictate the severity, progression, and modulation of the disease.
Variation in gene expression ofAndropogon gerardiiin response to altered environmental conditions associated with climate change
Authors: Travers Steven E. , Tang Zhongwen , Caragea Doina , Garrett Karen A. , Hulbert Scott H. , Leach Jan E. , Bai Jianfa , Saleh Amgad , Knapp Alan K. , Fay Philip A. , Nippert Jesse , Schnable Patrick S. , Smith Melinda D.
Published: December 2009

1. If we are to understand the mechanisms underlying species responses to climate change in natural systems, studies are needed that focus on responses of non‐model species under field conditions. We measured transcriptional profiles of individuals ofAndropogon gerardii, a C4grass native to North American grasslands, in a field experiment in which both temperature and precipitation were manipulated to simulate key aspects of forecasted climate change.

2. By using microarrays developed for a closely related model species,Zea mays, we were able to compare the relative influence of warming versus altered soil moisture availability on expression levels of over 7000 genes, identify responsive functional groups of genes and correlate changes in gene transcription with physiological responses.

3. We observed more statistically significant shifts in transcription levels of genes in response to thermal stress than in response to water stress. We also identified candidate genes that demonstrated transcription levels closely associated with physiological variables, in particular chlorophyll fluorescence.

4.Synthesis. These results suggest that an ecologically important species responds differently to different environmental aspects of forecast climate change. These translational changes have the potential to influence phenotypic characters and ultimately adaptive responses.
One‐Stop Stereology: the estimation of 3D parameters using Isotropic Rulers
Authors: REED M.G. , HOWARD C.V. , DE YANÉS G. STAATS
Published: December 2009

The stereological estimation of second‐order descriptors of spatial architecture appears to be inherently more time‐consuming and labour‐intensive than the estimation of first‐order quantities (total quantities or ratios). Therefore, far fewer researchers tend to make use of second‐order approaches in their stereological research projects. In this paper, we use a tutorial approach to illustrate how a desire for practical simplicity has provided us with a data collection method that can be used to simultaneously estimate both first‐order and second‐order properties of the microstructure of a defined anatomical feature of an organ. The approach does not rely on new results from theory, but nevertheless allows either isotropic uniform random or vertical uniform random sections to be used to make estimates of a comprehensive list of 10 microstructural parameters using relationships that are well known in the literature. The probe used in all cases is an isotropically distributed Ruler and the data collection protocol is easy to learn and apply. We illustrate the method on brain tissue but emphasize that the approach can also be applied to non‐biological material.
Buffalo (Bubalus bubalis) Embryonic Stem Cell‐Like Cells and Preimplantation Embryos Exhibit Comparable Expression of Pluripotency‐Related Antigens
Authors: Anand T , Kumar D , Singh MK , Shah RA , Chauhan MS , Manik RS , Singla SK , Palta P
Published: December 2009

Contents

In this study, inner cell mass (ICM) cells were isolated fromin vitroproduced buffalo blastocysts and were cultured on mitomycin‐C treated buffalo foetal fibroblast feeder layer for producing embryonic stem (ES) cells. Among different sources (hatched vs expanded blastocysts) or methods (enzymatic vs mechanical), mechanical isolation of ICM from hatched blastocysts resulted in the highest primary colony formation rate and the maximum passage number up to which ES cells survived. Putative ES cells expressed alkaline phosphatase and exhibited a normal karyotype up to passage 7. Putative ES cells and embryos at 2‐ to 4‐cell, 8‐ to 16‐cell, morula and blastocyst stages strongly expressed stage‐specific embryonic antigen (SSEA)‐4 but lacked expressions of SSEA‐1 and SSEA‐3. Putative ES cells also expressed tumour rejection antigen (TRA)‐1‐60, TRA‐1‐81 and Oct4. Whereas in all early embryonic stages, TRA‐1‐60 was observed only in the periplasmic space, and TRA‐1‐81 expression was observed as small spots at a few places inside the embryos, both these markers were expressed by ICM. Oct4 expression, which was observed at all the embryonic stages and also in the trophectoderm, was the strongest in the ICM. Buffalo putative ES cells possess a unique pluripotency‐related surface antigen phenotype, which resembles that of the ICM.
Social Rights, Civil Rights, and Health Reform in Canada
Authors: BHATIA VANDNA
Published: December 2009

This article challenges the conventional wisdom that health programs have been largely insulated from welfare state retrenchment. Health care entitlements have in fact been transformed and diminished, albeit in more subtle ways. Employing rhetorical discursive constructions about the nature of social rights, and capitalizing on passive policy drift, reformists have succeeded in altering the right to health care away from a set of collective obligations and toward the competing claims of individuals. As a result, public health insurance programs are abandoning universalistic principles in favor of a narrower conception of rights that is consistent with and supportive of increased privatization of health care financing. Discursive constructions aimed at persuading target audiences to change their ideas aid and abet systemic and institutional factors, making policy changes seem both necessary and inevitable. Using the case of Canada, I contend that such changes are a form of retrenchment.
The Unnatural Coupling: Food and Global Finance
Authors: GHOSH JAYATI
Published: December 2009

The dramatic rise and fall of world food prices in 2007–8 was largely a result of speculative activity in global commodity markets, enabled by financial deregulation measures in the United States and elsewhere. Despite the recent fall in agricultural prices in world trade, the food crisis has been exacerbated in many developing countries where food prices remain high and even continue to increase. The financial crisis also directly operates to increase food insecurity by imposing constraints on fiscal policies and food imports in balance‐of‐payments constrained developing countries, causing exchange rate devaluation through capital flight and adversely affecting employment, thereby reducing the ability of vulnerable groups to purchase food.
The intermediate conductance Ca2+‐activated K+ channel inhibitor TRAM‐34 stimulates proliferation of breast cancer cells via activation of oestrogen receptors
Authors: Roy JW , Cowley EA , Blay J , Linsdell P
Published: December 2009

Background and purpose:  K+ channels play a role in the proliferation of cancer cells. We have investigated the effects of specific K+ channel inhibitors on basal and oestrogen‐stimulated proliferation of breast cancer cells.

Experimental approach:  Using the mammary adenocarcinoma cell line MCF‐7 we assayed cell proliferation by radiolabelled thymidine incorporation in the absence or presence of various K+ channel inhibitors with or without 17β‐oestradiol.

Key results:  Inhibitors of Kv10.1 and KCa3.1 K+ channels suppressed basal proliferation of MCF‐7 cells, but not oestrogen‐stimulated proliferation. TRAM‐34, a specific inhibitor of KCa3.1 channels increased or decreased cell proliferation depending on the concentration. At intermediate concentrations (3–10 µM) TRAM‐34 increased cell proliferation, whereas at higher concentrations (20–100 µM) TRAM‐34 decreased cell proliferation. The enhancement of cell proliferation caused by TRAM‐34 was blocked by the oestrogen receptor antagonists ICI182,780 and tamoxifen. TRAM‐34 also increased progesterone receptor mRNA expression, decreased oestrogen receptor‐α mRNA expression and reduced the binding of radiolabelled oestrogen to MCF‐7 oestrogen receptor, in each case mimicking the effects of 17β‐oestradiol.

Conclusions and implications:  Our results demonstrate that K+ channels Kv10.1 and KCa3.1 play a role in basal, but not oestrogen‐stimulated MCF‐7 cell proliferation. TRAM‐34, as well as inhibiting KCa3.1, directly interacts with the oestrogen receptor and mimics the effects of 17β‐oestradiol on MCF‐7 cell proliferation and gene modulation. Our finding that TRAM‐34 is able to activate the oestrogen receptor suggests a novel action of this supposedly specific K+ channel inhibitor and raises concerns of interpretation in its use.