bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Y‐chromosomal Heritage of the Azores Islands Population
Authors: Pacheco P. R. , Branco C. C. , Cabral R. , Costa S. , Araújo A. L. , Peixoto B. R. , Mendonça P. , Mota‐Vieira L. 
Published: November 2005

SummaryThe Azores, a Portuguese archipelago located in the north Atlantic Ocean, had no native population when the Portuguese first arrived in the 15th century. The islands were populated mainly by the Portuguese, but Jews, Moorish prisoners, African slaves, Flemish, French and Spaniards also contributed to the initial settlement. To understand the paternal origins and diversity of the extant Azorean population, we typed genomic DNA samples from 172 individuals using a combination of 10 Y‐biallelic markers (YAP, SRY‐1532, SRY‐2627, 92R7, M9, sY81, Tat, SRY‐8299, 12f2 and LLY22g) and the following Y‐chromosomal STR systems: DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. We identified nine different haplogroups, most of which are frequent in Europe. Haplogroup J* is the second most frequent in the Azores (13.4%), but it is modestly represented in mainland Portugal (6.8%). The other non‐European haplogroups, N3 and E3a, which are prevalent in Asia and sub‐Saharan Africa, respectively, have been found in the Azores (0.6% and 1.2%, respectively) but not in mainland Portugal. Microsatellite data indicate that the mean gene diversity (D) value for all the loci analysed in our sample set is 0.590, while haplotype diversity is 0.9994. Taken together, our analysis suggests that the current paternal pool of the Azorean population is, to a great extent, of Portuguese descent with significant contributions from people with other genetic backgrounds.
Spinal Muscular Atrophy Carrier Screening by Multiplex Polymerase Chain Reaction using Dried Blood Spot on Filter Paper
Authors: Majumdar R. , Rehana Z. , Jumah M. Al , Fetaini N. 
Published: November 2005

SummarySpinal muscular atrophy (SMA) is a common, often fetal, autosomal recessively inherited disease leading to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. The SMA‐determining gene, called the survival of motor neuron gene (SMN), is present on 5q13 in two nearly identical copies, telomeric SMN (SMN1) and centromeric SMN (SMN2). It has been established that SMA is caused by mutations in SMN1 whereas homozygous deletion of SMN2 has apparently no pathological consequences. The aim of this study is to develop an easy and inexpensive method for the isolation of high‐quality template DNA from blood samples for SMA carrier screening by multiplex polymerase chain reaction. We have developed a protocol that optimizes detection of the SMN1 copy number in the human genome, producing a specific and sensitive assay using DNA extracted from a dried blood spot on IsoCode™ paper.
A Method for Pooling Alleles from Different Genotyping Experiments
Authors: Aulchenko Y. S. , Bertoli‐Avella A. M. , Van Duijn C. M. 
Published: November 2005

SummarySingle tandem repeat (STR) polymorphisms are widely used in linkage and association studies. One of the drawbacks of using these markers is that genetic data coming from different experiments cannot be easily pooled together, because both allele length and binning distance may change. As large studies with multiple series of subjects sequentially included become more and more common, there is an increasing interest in pooling the genetic data obtained in different experiments. Correct reconstruction of allelic correspondences between genotyping experiments is particularly crucial for association‐oriented studies, such as candidate gene studies and genome‐wide association studies in isolated populations.Here, we suggest a maximum‐likelihood framework to find the best correspondence between alleles typed in different genotyping experiments. We also address the issue of goodness‐of‐fit and robustness. We perform a study simulating results obtained in a genome scan using 787 STR markers. The simulations show that the suggested method yields good results with respect to the error rate, even if the sizes of the samples to be pooled are as low as 10 subjects (3% errors), though only 9% of alleles pass our tests. As sample sizes increase to 250 subjects the proportion of alleles pooled reaches 96% with an error rate of <0.1%.
Generating Genetic Risk Scores from Intermediate Phenotypes for Use in Association Studies of Clinically Significant Endpoints
Authors: Horne B. D. , Anderson J. L. , Carlquist J. F. , Muhlestein J. B. , Renlund D. G. , Bair T. L. , Pearson R. R. , Camp N. J. 
Published: November 2005

SummaryWhile previous results of genetic association studies for common, complex diseases (eg., coronary artery disease, CAD) have been disappointing, examination of multiple related genes within a physiologic pathway may provide improved resolution. This paper describes a method of calculating a genetic risk score (GRS) for a clinical endpoint by integrating data from many candidate genes and multiple intermediate phenotypes (IPs). First, the association of all single nucleotide polymorphisms (SNPs) to an IP is determined and regression β‐coefficients are used to calculate an IP‐specific GRS for each individual, repeating this analysis for every IP. Next, the IPs are assessed by a second regression as predictors of the clinical endpoint. Each IP's individual GRS is then weighted by the regression β‐coefficients from the second step, creating a single, composite GRS. As an example, 3,172 patients undergoing coronary angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway. Although these data provide only a preliminary example, the GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not. These results illustrate the potential of the GRS methodology for multigenic risk evaluation and suggest that such approaches deserve further examination in common, complex diseases such as CAD.
Institutional Breakdown? An Exploratory Taxonomy of Australian University Failure
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Authors: Murray David , Dollery Brian 
Published: November 2005

Abstract
Australian higher education has undergone radical change aimed at transforming universities into commercial enterprises less dependent on public funding. Despite some significant successes, including dramatic increases in the numbers of domestic and international students, decreased Commonwealth subsidies, and more private sector finance, there are ominous indications that institutional failure is endemic, especially financial accountability. Drawing on various theories of institutional failure, this paper attempts to examine the causes of the current crisis. A fourfold taxonomy of Australian university failure is developed that identifies governance failure, accountability failure, quality failure, and information failure as the primary sources of tertiary education institutional breakdown.
Making Sense of Organizational Failure: The Marconi Debacle
Authors: Kam Jacqueline 
Published: November 2005

Abstract
Organizational failure is usually explained with linear causality, attributed to either environmental change or managerial behavior. This paper attempts to capture the dynamic interplays of human actions in changing environments, taking into account both the environmental and behavioral factors. The breath‐taking debacle of Marconi, a British telecommunications equipment supplier, is examined, revealing the complexities and interrelatedness of the environmental change and human actions, and the consequences for organizational performance. This research is intended to develop thinking about organizational failure, to broaden perspectives currently framed by conventional boundaries, and to encourage a new approach in making sense of failure. Failure may seem obvious and its understanding simple; in fact, failure is an elusive concept and the simplicity commonly attached to its understanding is dangerously deceptive.
Global Landscapes: A Speculative Assessment of Emerging Organizational Structures within the International Wine Industry
Authors: Aylward David 
Published: November 2005

Abstract
As a rapidly evolving sector the international wine industry represents an interesting subject for analysis. Over the past two centuries the industry has experienced a number of major innovations and direction changes. The organizational shifts involved in these changes have been profound. From a monopolization of wine culture through the nineteenth and much of the twentieth century by Europeans, to the emergence of New World operators and their democratic influence, the international wine industry now stands at the edge of another major paradigm shift. This paper traces the industry’s historical changes and speculates on the implications of such issues as global production, distribution, technology transfer, branding and the escalation of mergers and alliances. It argues that with the increasing global tendency of the industry, ‘New’ and ‘Old World’ distinctions may blur and disappear. Furthermore, as the wine landscape continues to evolve, we may well see a new set of rules, where the emergence of localized branding, an enhanced role for small to medium enterprises and the decline of national industries results in an irrevocable reconfiguration of the industry.
No significant effect of acute moderate alcohol intake on leptin levels in healthy male volunteers
Authors: Dammann Gerhard , Dierkes Jutta , Graf Marc , Wiesbeck Gerhard , Pridzun Lutz , Schulte Tilman , Westphal Sabine , Luley Claus , Allen John , Wurst Friedrich 
Published: November 2005

AbstractAs, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake in healthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29?3.75 years, body mass index (BMI) 24.3?3.5, leptin at baseline 3.3?3.1ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day 1 of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mg/ml. A placebo‐controlled double‐blind trial was performed. Leptin levels of blood samples were taken at baseline (t1), before ethanol intake (t2), when blood alcohol had reached its maximum (t3) and the morning after (t4). The oral dose of ethanol administered was 0.6g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t1) (rs=0.85, p <0.0001) and follow‐up (t4) (rs=0.768, p<0.0001). (b) Leptin levels for the placebo and the alcohol‐consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann‐Whitney U‐test (p=0.669, p=1.0 and p=0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t1 and t4 were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.
Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?
Authors: Egli Mark 
Published: November 2005

AbstractEvaluating medications in animal laboratory paradigms can reveal whether the compound is effective in an established alcoholism model, at clinically relevant doses and exposure conditions, when administered orally (or transdermally) and without serious limiting side effects. Positive outcomes constitute a possible discovery for relevance to alcoholism and, under favorable marketing conditions, encourage further development. Medication testing using animal models of alcoholism might also guide clinical testing by discriminating clinically effective from clinically ineffective compounds. This ability rests on whether there are tests or, more reasonably, batteries of tests having this discriminative ability. The present paper examines this possibility. Effects of naltrexone and acamprosate in animal paradigms which model behavioral aspects of alcoholism are reviewed and compared with the effects of compounds which have limited effects in alcoholics. It is not clear at present whether any single paradigm or combination of paradigms differentiates clinically effective from clinically limited compounds. Steps are suggested to improve the use of preclinical laboratory tests to predict which compounds are likely to be effective medications for reducing drinking and sustaining abstinence in human alcoholics.
Methylone and mCPP, two new drugs of abuse?
Authors: Bossong M. , Van Dijk J. , Niesink R. 
Published: November 2005

AbstractRecently, two new ecstasy‐like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4‐methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called ‘Explosion’. mCPP (meta‐chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4‐methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.
Enhanced prolactin levels in opium smokers
Authors: Moshtaghi‐Kashanian Ghollam‐Reza , Esmaeeli Farzaneh , Dabiri Shahriar 
Published: November 2005

AbstractIn Iran, opium is smoked for pleasure or as a medication by some people. It is a complex mixture of 40 different alkaloids, including morphine and codeine along with many impurities. Although it is well established that opioids or tobacco affect many physiological functions in humans, to our knowledge there has been no specific study looking at these effects in opium smokers. To assess that, we investigated the circulating levels of prolactin, TSH, LH, FSH and testosterone in male opium smokers who also smoke cigarettes (n =23, aged 28.4?4.1 years), and comparing this with the corresponding values for nicotine abusers (n =12, 15–25 cigarettes/day) or a healthy control group (n =20) of the same age. Our results showed that 86.96% of the opium‐dependent and 41.67 % of the nicotine‐dependent group displayed high prolactin values (p)
Opioid plasma concentrations in methadone‐and buprenorphine‐maintained patients
Authors: Jagsch Reinhold , Gombas Wolfgang , Schindler Shird‐Dieter , Eder Harald , Moody David , Fischer Gabriele 
Published: November 2005

AbstractThis is the first trial to compare the relationship of opioid plasma concentrations in methadone‐versus buprenorphine‐maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2mg or 8mg tablets; maximum daily dose: 8mg) or oral methadone (racemic R‐/S‐methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra‐individual variation was much higher for buprenorphine (p < 0.0001), while the concentration‐to‐dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine‐maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine‐maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration‐to‐dose ratios or intra‐individual variation.
On the improvement of the metrological properties of manganin sensors
Authors: Rostocki Aleksander J , Urbański Michał K , Wiśniewski Roland , Wilczyńska Teresa 
Published: November 2005

The paper presents the recent progress made in the accuracy improvement of the manganin pressure sensors at the Warsaw University of Technology (WUT) and at the Institute of Nuclear Energy. The efforts of the authors were concentrated on three problems:(1) The improvement of the temperature characteristics by the design of a manganin sensor with the temperature compensation achieved by the application of two manganin coils with two different temperature characteristics;(2) The improvement of the calibration process by- (a) using a high pressure deadweight piston gauge (with the correction of effective area versus pressure dependence, built at WUT),- (b) measurements of the manganin resistance as a function of the temperature and of the pressure using a precise multimeter and- (c) application of statistical methods for long series of measurements.(3) The modification of the thermal characteristic by implantation of bismuth and krypton ions.
Complexities and uncertainties of neuronal network function
Authors: Parker David 
Published: November 2005

The nervous system generates behaviours through the activity in groups of neurons assembled into networks. Understanding these networks is thus essential to our understanding of nervous system function.Understanding a network requires information on its component cells, their interactions and their functional properties. Few networks come close to providing complete information on these aspects. However, even if complete information were available it would still only provide limited insight into network function. This is because the functional and structural properties of a network are not fixed but are plastic and can change over time. The number of interacting network components, their (variable) functional properties, and various plasticity mechanisms endows networks with considerable flexibility, but these features inevitably complicate network analyses.This review will initially discuss the general approaches and problems of network analyses. It will then examine the success of these analyses in a model spinal cord locomotor network in the lamprey, to determine to what extent in this relatively simple vertebrate system it is possible to claim detailed understanding of network function and plasticity.
Shelf‐margin clinoforms and prediction of deepwater sands
Authors: Johannessen Erik P. , Steel Ron J. 
Published: November 2005

ABSTRACTEarly Eocene successions from Spitsbergen and offshore Ireland, showing well‐developed shelf‐margin clinoforms and a variety of deepwater sands, are used to develop models to predict the presence or absence of turbidite sands in clinoform strata without significant slope disturbance/ponding by salt or mud diapers. The studied clinoforms formed in front of narrow to moderate width (10–60 km) shelves and have slopes, 2–4°, that are typical of accreting shelf margins. The clinoforms are evaluated in terms of both shelf‐transiting sediment‐delivery systems and the resultant partitioning of the sand and mud budget along their different segments. Although this sediment‐budget partitioning is controlled by sediment type and flux, shelf width and gradient, process regime on the shelf and relative sea‐level behaviour, the most tell‐tale or predictive signs in the stratigraphic record appear to be (1) sediment‐delivery system type, (2) degree of shelf‐edge channelling and (3) character of shelf‐edge trajectory through time. The clinoform data sets from the Porcupine Basin (wells and 3‐D seismic) and from the Central Basin on Spitsbergen (outcrops) suggest that river‐dominated deltas are the most efficient delivery systems for dispersing sand into deep water beyond the shelf‐slope break. In addition, low‐angle or flat, channelled shelf‐edge trajectories associate with co‐eval deepwater slope and basin‐floor sands, whereas rising trajectories tend to associate with muddy slopes and basin floors. Characteristic features of the shelf‐edge, slope and basin‐floor segments of clinoforms for these trajectory types are documented. Seismic lines along the slope to basin‐floor transects tend to show apparent up‐dip sandstone pinchouts, but most of these are likely to be simply sidelap features. Dip lines aligned along the axes of sandy fairways show that stratigraphic traps are unlikely, unless slope channels become mud‐filled or are structurally partitioned. Another feature that is prominent in the data sets examined is the lack of slope onlap. During the relative rise of sea level back up to the shelf, the clinoform slopes are generally mud‐prone and they are characteristically aggradational.
Discrete‐element modelling of detachment folding
Authors: Hardy Stuart , Finch Emma 
Published: November 2005

ABSTRACTA two‐dimensional, discrete‐element modelling technique is used to investigate the initiation and growth of detachment folds in sedimentary rocks above a weak décollement level. The model depicts the sedimentary rocks as an assemblage of spheres that obey Newton's equations of motion and that interact with elastic forces under the influence of gravity. Faulting or fracturing between neighbouring elements is represented by a transition from repulsive–attractive forces to solely repulsive forces. The sedimentary sequence is mechanically heterogeneous, consisting of intercalated layers of markedly different strengths and thicknesses. The interlayering of weak and strong layers within the sedimentary rocks promotes the localization of flexural flow deformation within the weak layers. Even with simple displacement boundary conditions, and straightforward interlayering of weak and strong layers, the structural geometries that develop are complex, with a combination of box, lift‐off and disharmonic detachment fold styles forming above the décollement. In detail, it is found that the modelled folds grow by both limb rotation and limb lengthening. The combination of these two mechanisms results in uplift patterns above the folds that are difficult, or misleading, to interpret in terms of simple kinematic models. Comparison of modelling results with natural examples and with kinematic models highlights the complexities of structural interpretation in such settings.
Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma
Authors: Yasui Hiroshi , Hideshima Teru , Richardson Paul G. , Anderson Kenneth C. 
Published: November 2005

SummaryMultiple myeloma (MM) remains largely incurable despite conventional and high‐dose therapies, and novel biologically based treatment approaches are urgently required. Recent studies demonstrate that various growth factors including interleukin (IL)‐6, insulin‐like growth factor (IGF)‐1, vascular endothelial growth factor (VEGF), the tumour necrosis factor (TNF) family proteins, Wnt, and Notch family members play an important role in MM pathogenesis, and mediate tumour cell proliferation, drug resistance and migration in the bone marrow (BM) milieu. Targeting growth factors, therefore, represents a promising therapeutic strategy in MM. Novel agents inhibiting growth factor signalling cascades can target ligands, receptors, and/or downstream signalling cascade proteins in MM cells and the BM microenvironment. Combinations of these novel agents with conventional therapies may not only enhance cytotoxicity, but also avoid drug resistance and thereby improve patient outcome in MM.