bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing the substrate specificity of the dengue virus type 2 NS3 serine protease by using internally quenched fluorescent peptides
Authors: Niyomrattanakit Pornwaratt , Yahorava Sviatlana , Mutule Ilze , Mutulis Felikss , Petrovska Ramona , Prusis Peteris , Katzenmeier Gerd , Wikberg Jarl E. S. 
Published: June 2006

The NS3 (dengue virus non-structural protein 3) serine protease of dengue virus is an essential component for virus maturation, thus representing an attractive target for the development of antiviral drugs directed at the inhibition of polyprotein processing. In the present study, we have investigated determinants of substrate specificity of the dengue virus NS3 protease by using internally quenched fluorogenic peptides containing Abz (o-aminobenzoic acid; synonymous to anthranilic acid) and 3-nitrotyrosine (nY) representing both native and chimaeric polyprotein cleavage site sequences. By using this combinatorial approach, we were able to describe the substrate preferences and determinants of specificity for the dengue virus NS2B(H)–NS3pro protease. Kinetic parameters (kcat/Km) for the hydrolysis of peptide substrates with systematic truncations at the prime and non-prime side revealed a length preference for peptides spanning the P4–P3′ residues, and the peptide Abz-RRRRSAGnY-amide based on the dengue virus capsid protein processing site was discovered as a novel and efficient substrate of the NS3 protease (kcat/Km=11087 M−1·s−1). Thus, while having confirmed the exclusive preference of the NS3 protease for basic residues at the P1 and P2 positions, we have also shown that the presence of basic amino acids at the P3 and P4 positions is a major specificity-determining feature of the dengue virus NS3 protease. Investigation of the substrate peptide Abz-KKQRAGVLnY-amide based on the NS2B/NS3 polyprotein cleavage site demonstrated an unexpected high degree of cleavage efficiency. Chimaeric peptides with combinations of prime and non-prime sequences spanning the P4–P4′ positions of all five native polyprotein cleavage sites revealed a preponderant effect of non-prime side residues on the Km values, whereas variations at the prime side sequences had higher impact on kcat.
Robust estimation of the false discovery rate
Authors: Pounds Stan , Cheng Cheng 
Published: June 2006

AbstractMotivation: Presently available methods that use p-values to estimate or control the false discovery rate (FDR) implicitly assume that p-values are continuously distributed and based on two-sided tests. Therefore, it is difficult to reliably estimate the FDR when p-values are discrete or based on one-sided tests.Results: A simple and robust method to estimate the FDR is proposed. The proposed method does not rely on implicit assumptions that tests are two-sided or yield continuously distributed p-values. The proposed method is proven to be conservative and have desirable large-sample properties. In addition, the proposed method was among the best performers across a series of ‘real data simulations’ comparing the performance of five currently available methods.Availability: Libraries of S-plus and R routines to implement the method are freely available fromContact: stanley.pounds@stjude.orgSupplementary information: Supplementary data are avilable at Bioinformatics online.
Women and Money: Lessons from Senegal
Authors: Guérin Isabelle 
Published: June 2006

AbstractThis article examines the complexity and diversity of women's informal financial practices using data from surveys conducted in Senegal. It suggests that these practices are at the centre of a constant dialectic between short‐term and long‐term horizons, between the requirements of daily survival and the demands of community solidarity, and between personal aspirations and collective constraints. These practices also clearly illustrate a desire among the women in Senegal to impose a form of financial self‐discipline, and to create situations that will oblige them to earn income. The socio‐economic diversity among these entrepreneurs is also underscored. Informal financial arrangements are both a product and producer of gender inequalities and inequalities among women, as reflected in the research. This has direct policy implications, especially for microfinance products. If they are to be effective, microfinance services must develop beyond a standard, one‐size fits all model and become more innovative and adaptable to the diverse demands of women. They must be combined with complementary measures that challenge the systemic causes of inequality. Microfinance programmes should draw on informal financial arrangements while challenging their tendency to perpetuate inequality.
A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis
Authors: AZZAROLI F. , COLECCHI A. , LODATO F. , TRERÈ D. , BACCHI REGGIANI M. L. , FESTI D. , PRATI G. M. , ACCOGLI E. , CASANOVA S. , DERENZINI M. , RODA E. , MAZZELLA G. 
Published: June 2006

SummaryBackgroundIncidence of hepatocellular carcinoma in hepatitis C virus‐related cirrhosis is 4% per year. Although cost‐effective, current screening could be improved.AimTo develop a statistical model including non‐invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma.MethodsOne hundred and fifty‐eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 ± 1.44 months.ResultsFifty‐six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (≤25%), 65 had hepatitis C virus‐related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus‐related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), γ‐globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographyc pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index.ConclusionsThe model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.
Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests)
Authors: LEWIS N. R. , SCOTT B. B. 
Published: June 2006

SummaryBackgroundWith the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive features.AimTo compare the sensitivities and specificities of the endomysial antibody and the tissue transglutaminase antibody tests.MethodsUsing electronic databases a search was made for relevant papers using the terms tissue transglutaminase and endomysial antibody.ResultsBoth the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. Human recombinant tissue transglutaminase performs much better than guinea pig tissue transglutaminase. Review of studies comparing endomysial antibody with human recombinant tissue transglutaminase antibody shows that endomysial antibody more often has a higher specificity and human recombinant tissue transglutaminase antibody more often has a higher sensitivity.ConclusionThe human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding coeliac disease in symptomatic individuals with a low pretest probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of practical and financial advantages. If the pretest probability is >25%, biopsy is preferred as the post‐test probability of coeliac disease with a negative test is still >2%.
Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents
Authors: Kaur G , Tirkey N , Bharrhan S , Chanana V , Rishi P , Chopra K 
Published: June 2006

SummaryThe present study is aimed at investigating the effect of curcumin (CMN) in salvaging endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rodents. Hepatotoxicity was induced by administering lipopolysaccharide (LPS) in a single dose of 1 mg/kg intraperitoneally to the animals, which were being treated with CMN daily for 7 days. Liver enzymes serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin and total protein were estimated in serum. Oxidative stress in liver tissue homogenates was estimated by measuring thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content and superoxide dismutase (SOD) activity. Serum and tissue nitrite was estimated using Greiss reagent and served as an indicator of NO production. A separate set of experiments was performed to estimate the effect of CMN on cytokine levels in mouse serum after LPS challenge. LPS induced a marked hepatic dysfunction evident by rise in serum levels of ALT, AST, ALP and total bilirubin (P &lt; 0·05). TBARS levels were significantly increased, whereas GSH and SOD levels decreased in the liver homogenates of LPS-challenged rats. CMN administration attenuated these effects of LPS successfully. Further CMN treatment also regressed various structural changes induced by LPS in the livers of rats and decreased the levels of tumour necrosis factor-α and interleukin-6 in mouse plasma. In conclusion, these findings suggest that CMN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO, oxygen free radicals and cytokines.
Cognitive performance in Rett syndrome girls: a pilot study using eyetracking technology
Authors: Baptista P. M. , Mercadante M. T. , Macedo E. C. , Schwartzman J. S. 
Published: June 2006

AbstractBackground  Rett syndrome (RS) is a pervasive developmental disorder with cognitive and neuromotor impairments (including loss of handiness and loss of communicative skills).Objective  To verify whether girls with RS use their gaze intentionally, by observing their performance in three cognitive tasks: (1) verbal instruction condition (look at picture X), (2) recognition and matching of pictures (look at the one that is the same), and (3) categorization of pictures (look at the one that is similar).Method  Seven girls diagnosed with RS according to DSM‐IV criteria were studied. Eyegaze® technology was used to record the girls’ eye movements’ responses to visual stimulation.Results  The comparison of fixation time on the alternatives revealed a higher percentage (62.4%) of correct alternatives (χ2 = 76.31; P = 0.000). Of the seven children assessed, only one did not present predominance of fixations on the correct alternatives in any one of the tasks. One did well in all tasks. Six responded correctly to all verbal instructions.Conclusion  The rate of correct answers suggests that there is measurable and intentional gaze in RS girls and it can be used as a path to explore their cognitive performance.
Characteristics of Rat CD4+CD25+ T Cells and Their Ability to Prevent Not Only Diabetes But Also Insulitis in an Adoptive Transfer Model in BB Rats
Authors: Holm T. L. , Lundsgaard D. , Markholst H. 
Published: June 2006

AbstractHuman and mouse CD4+CD25+ T cells have been intensively studied through the last decade. However, little is known about this subset in other species. This study describes the phenotype of rat CD4+CD25+ Foxp3+ T cells and the site in which they exert regulation in a transfer‐induced autoimmune diabetes model. Several proteins and mRNAs are up‐regulated in unstimulated rat CD4+CD25+ T cells compared with CD4+CD25– T cells, including Foxp3, Lag‐3, CD80, interleukin 10 (IL‐10) and CTLA‐4. To investigate CD4+CD25+ T cells in vivo, we transferred three million diabetogenic T cells either alone or in combination with two million CD4+CD25+ T cells to 30‐day‐old BB rats. The pancreas and the pancreatic lymph nodes were examined as two potential regulatory sites. Time‐course analysis of pancreatic histology following diabetogenic T‐cell transfers revealed insulitis from about 14 days after transfer. By contrast, rats receiving both diabetogenic T cells and CD4+CD25+ T cells had no insulitis at any time. Moreover, the frequency of diabetogenic T cells in the pancreatic lymph nodes 2 days after transfer was significantly reduced in rats receiving both subsets. These data indicate that the primary site of T‐cell regulation is in the draining lymph nodes and not the pancreas in our model.
Dawsonite, alumohydrocalcite, nordstrandite and gorceixite in Permian marine strata of the Sydney Basin, Australia
Authors: GOLDBERY R. , LOUGHNAN F. C. 
Published: June 2006

ABSTRACTDawsonite, alumohydrocalcite, nordstrandite, gorceixite and calcite are associated in marine strata of the Permian Shoalhaven Group of the Sydney Basin, south‐eastern Australia. The assemblages were apparently of late syngenetic or epigenetic development and resulted from two interrelated processes: (a) precipitation from solutions rich in sodium, aluminate and carbonate ions and (b) reaction of these solutions with earlier‐formed minerals leading to the development of complete and partial pseudomorphs. Although the evidence is inconclusive, the host rocks were probably the source of the ions.
The first description of an oesophageal candidosis by Bernhard von Langenbeck in 1839
Authors: Knoke M. , Bernhardt H. 
Published: June 2006

SummaryIn November 1839 the young university lecturer Bernhard (von) Langenbeck (1810–1887) published the first description of a fungus as aetiological agent of an oro‐pharyngeal and oesophageal candidosis. We present his in English translated paper entitled ‘Finding of fungi on the mucous membrane of the gullet of a typhoid fever corpse’ (Germ.) in ‘Neue Notizen aus dem Gebiete der Natur‐ und Heilkunde’ (Froriep). There are interesting particulars in Langenbeck's description and discussion. The publication happened at the same time as that by Johann Lukas Schoenlein about fungi as the cause of the favus lesions. In this time Langenbeck lived at Göttingen. Later he went to Kiel and Berlin and became one of the most prominent surgeons of the 19th century. He sponsored the founding of the German Surgical Society, the Berlin Medical Society and the ‘Archiv für Klinische Chirurgie’. In 1864 he was ennobled. Some of his assistants were Th. Billroth, R.U. Kroenlein, F. von Esmarch, and F. Trendelenburg.
Enzymatic activities of Alternaria alternata allergenic extracts and its major allergen (Alt a 1)
Authors: Sáenz‐de‐Santamaría Miriam , Guisantes Jorge A. , Martínez Jorge 
Published: June 2006

SummarySeveral allergens from Alternaria alternata have been isolated allowing some of them to be identified and characterised. Despite the fact that the major allergen of A. alternata (Alt a 1) has been extensively produced by recombinant technology, its biological activity still remains unknown. In the present study, extracts from culture filtrates were used to evaluate the intra‐specific variability of the enzymes and also as a source for isolating and purifying native Alt a 1. This was purified by affinity chromatography using antibody anti‐recombinant Alt a 1 (produced in Escherichia coli). Enzyme activities were analysed by the API‐ZYM System screening method. Results demonstrated the high variability of enzyme activities among the different strains. Only activities corresponding to phosphatases, esterases and β‐glucosidase were expressed by 100% of the strains. Both native and recombinant Alt a 1 showed phosphatase and esterase activities, suggesting that the glucidic moiety of this allergen does not significantly affect its enzyme activity.
Histoplasmosis: a review for clinicians from non‐endemic areas
Authors: Joseph Wheat L. 
Published: June 2006

SummaryHistoplasmosis is an important systemic mycosis in the Americas, Asia, and Africa. Increasingly cases are recognised in nonendemic areas. Proper management requires recognition of the clinical syndromes caused by Histoplasma capsulatum infection, familiarity with the uses and limitations of the diagnostic tests, an understanding of the indications for treatment and role of specific antifungal agents. This review will address these issues with the goal of providing physicians in non‐endemic areas sufficient information to suspect, diagnose, and treat patients with histoplasmosis.
Clinical and experimental evaluation of a new chromogenic medium (OCCA®, Oxoid) for direct identification of Candida albicans, C. tropicalis and C. krusei
Authors: Baixench M. T. , Taillandier A. , Paugam A. 
Published: June 2006

SummaryOxoid Chromogenic Candida Agar (OCCA®) is a new commercial ready‐to‐use medium that contains chromogenic substrates for rapid detection and specific identification of Candida albicans, C. tropicalis and C. krusei. We evaluated the performance of this medium with 364 clinical specimens and 31 subcultures, and examined its ability to support the growth of small inocula of six reference strains. CHROMagar Candida was used as the reference medium. OCCA permitted the growth of most important yeasts, and readily discriminated among Candida spp. in clinical specimens, including mixed cultures.
In vitro tests indicate that certain varieties of oats may be harmful to patients with coeliac disease
Authors: Silano Marco , Dessì Mariarita , De Vincenzi Massimo , Cornell Hugh 
Published: June 2006

AbstractBackground:  The presence of oats in gluten‐free diet is controversial. The aim of this work is to evaluate if different varieties of oats exert different toxicity in coeliac disease.Methods:  Three varieties of oats were tested by two in vitro assay based on the known ability of peptic‐tryptic digests of coeliac‐active proteins to agglutinate K562 cells and to disrupt lysosomes, respectively.Results:  Avenins from the Italian variety Astra and the Australian variety Mortlook were much more active than the Australian variety Lampton. Gliadin, digested in the same way, certainly displayed more activity than all three avenins, but rice (var. Roma) did not have measurable activity.Conclusions:  The results indicate that some varieties of oats may be potentially harmful to individuals with coeliac disease and therefore should be excluded from the gluten‐free diet required to maintain good health in coeliac disease. It is important to realize that constant, small amounts of active proteins in the diet, such as certain avenins, may prevent complete recovery of the intestinal mucosa in this disease.
Online data collection in academic research: advantages and limitations
Authors: Lefever Samúel , Dal Michael , Matthíasdóttir Ásrún 
Published: June 2006

AbstractOnline data collection in academic research might be replacing paper‐and‐pencil surveys or questionnaires in the near future. This paper discusses the advantages and limitations of online data collection, with particular reference to the conduct of two qualitative studies involving upper secondary school teachers and students in Iceland in 2002. Email was used for contacting the participants to ask them to visit a designated website in order to complete the questionnaire. Some problems arose with the use of an online web‐based programme for data collection. Among them were the unreliability of the email address lists and the lack of willingness, particularly among students, to participate. The paper concludes that while online surveys can access large and geographically distributed populations and achieve quick returns, they may no longer be as universally appealing as was once believed. Reaching the population sample remains a problem in online as well as in traditional data collection.
Research apprenticeships: A report on a model graduate programme in instructional systems
Authors: Carr‐Chellman Alison A. , Gursoy Husra , Almeida Luis , Beabout Brian 
Published: June 2006

AbstractGraduate programmes in instructional design/educational technology are, by their nature, continuously being updated and improved. As a most recent iteration of the ever‐evolving graduate experience, an experimental programme at Pennsylvania State University’s Instructional Systems programme takes as its centerpiece a research apprenticeship in which graduate students work directly with their advisors in research teams as part of a credit‐bearing coursework. This paper reports the results of an evaluation to examine the uses and the effectiveness of the research apprenticeship from both faculty and staff perspectives. The findings indicate that the course enjoyed a great degree of flexibility and allowed faculty to integrate a number of different approaches and activities into this course and to account for extensive mentoring of graduate students through the credit‐bearing apprenticeship. Students indicated that the course gave them much more equitable access to mentoring for publications and presentations and opportunities to engage in scholarly activities throughout their apprenticeship. Suggestions for programmes seeking to employ an apprenticeship approach were drawn along with future research directions.
Pulling Structured Inequality into Higher Education: the Impact of Part‐Time Working on English University Students
Authors: Humphrey Robin 
Published: June 2006

AbstractThis paper explores the social and academic effects of term‐time working on undergraduate students at an English university. Data initially collected via a survey of student social relationships were enhanced by the inclusion of end‐of‐year academic performance. Various inferential statistical techniques were used to identify these effects. Path analysis was employed to disentangle significant variables and to show that term‐time working had direct and significant effects on the two factors shown to be affected most significantly by term‐time working: end‐of‐year average grade and participation in university societies. A major finding was that almost all students who worked came from state schools rather than from independent privately financed schools. The findings are discussed within the context of the recent history of funding policy regarding higher education in England. A key conclusion is that structured inequality, an inherent feature of a divided secondary education system, is being pulled firmly into higher education.