Structure–properties relationships in fibre drawing of bioactive phosphate glasses

New bioactive phosphate glasses suitable for continuous fibre production are investigated in this work. The structure of both bulk and fibres from Na2O–CaO–MgO–P2O5 glasses has been studied by means of Raman and 31P and 23Na nuclear magnetic resonance spectroscopies, and the structural results have been correlated with the mechanical properties of the fibres and the dissolution rate of the bulk glasses. It has been observed that the mechanical properties of the phosphate glass fibres are influenced by the glass network connectivity, while the dissolution rates are governed by the Qi speciation of the PO4 units. As seen in previous studies, molar volume seems to play an important role in the fragility behaviour of phosphate glasses. Here, a lower molar volume resulting from the increase in the oxygen packing density hinders the cooperative flow of the PO4 units throughout the glass network and, therefore, causes a reduction in the kinetic fragility

The Alternative Splice Variant of Protein Tyrosine Kinase 6 Negatively Regulates Growth and Enhances PTK6-Mediated Inhibition of β-Catenin

Protein tyrosine kinase 6 (PTK6), also called breast tumor kinase (BRK), is expressed in epithelial cells of various tissues including the prostate. Previously it was shown that PTK6 is localized to epithelial cell nuclei in normal prostate, but becomes cytoplasmic in human prostate tumors. PTK6 is also primarily cytoplasmic in the PC3 prostate adenocarcinoma cell line. Sequencing revealed expression of wild type full-length PTK6 transcripts in addition to an alternative transcript lacking exon 2 in PC3 cells. The alternative transcript encodes a 134 amino acid protein, referred to here as ALT-PTK6, which shares the first 77 amino acid residues including the SH3 domain with full length PTK6. RT-PCR was used to show that ALT-PTK6 is coexpressed with full length PTK6 in established human prostate and colon cell lines, as well as in primary cell lines derived from human prostate tissue and tumors. Although interaction between full-length PTK6 and ALT-PTK6 was not detected, ALT-PTK6 associates with the known PTK6 substrates Sam68 and β-catenin in GST pull-down assays. Coexpression of PTK6 and ALT-PTK6 led to suppression of PTK6 activity and reduced association of PTK6 with tyrosine phosphorylated proteins. While ALT-PTK6 alone did not influence β-catenin/TCF transcriptional activity in a luciferase reporter assay, it enhanced PTK6-mediated inhibition of β-catenin/TCF transcription by promoting PTK6 nuclear functions. Ectopic expression of ALT-PTK6 led to reduced expression of the β-catenin/TCF targets Cyclin D1 and c-Myc in PC3 cells. Expression of tetracycline-inducible ALT-PTK6 blocked the proliferation and colony formation of PC3 cells. Our findings suggest that ALT-PTK6 is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization. Fully understanding functions of ALT-PTK6 and its impact on PTK6 signaling will be critical for development of therapeutic strategies that target PTK6 in cancer

The Islamic Law in the Historical Study

Dalam kajian tentang sejarah awal Islam dan agama di dunia Barat, Islam dipandang sebagai agama \u27\u27dalam sejarab". Melaiui pandangan ini, para sarjana mempelajari sejarah awal Islam, di antaranya, dengan menggunakan meiode analisa kritik terbadap sumber-sumber sejarah termasuk kepusiakaan selain Islam dijadikan sebagai sumber dan bukti sejarah. Sejak itu pula hukum Islam dikaji melaiui pendekatan yang sama. Melaiui pendekatan ini diyakini bahwa hukum Islam mengandung tradisi-tradisi keagamaan khususnya di wilayab limur dekat yang ada sebeium Islam, dan dipandang sebagai suatu perkembangan yang berkelanjutan. Sebagaimana hasii kajian daripada Patricia Crone dan Gordon D. Newby menunjukkan bahwa di antara tradisi-tradisi keagamaan dimaksud, saiah satunya, adalab hukum Yahudi. Crone memberikan contoh qasama khususnya yang ada pada mazhab Maiiki dan mengktaim bahwa qasama dimaksud merupakan salah satu tradisi hukum yang ada pada orang-orang Yahudi. Sedangkan Newby memberikan contoh tentang penentuan orang band sebagai laki-iaki atau sebagai perempuan dalam hubungannya dengan pembagian kewarisan yang ada pada catatan \u27Amirb. Zarib di daiam sirah Ibnu Ishaq, dan mengktaim juga bahwa catatan tersebut berasai dari hukum Yahudi. Sebaliknya, pendekatan ini merupakan salah satu pendekatan yang ada dalam kajian hukum Islam dan sangat baik dipakai untuk mencari keseimhangan dan menunjukkan bahwa walaupun terdapat kesamaan antara hukum Islam dengan hukum-hukum yang lain, proses sejarab perkembangan hukum Islam itu sendiri sangat berbeda dan mempunyai karakteryang khusu

Residential exposure to motor vehicle emissions and the risk of wheezing among 7-8 year-old schoolchildren: a city-wide cross-sectional study in Nicosia, Cyprus

<p>Abstract</p> <p>Background</p> <p>Several studies have reported associations between respiratory outcomes in children and a range of self-reported, administrative or geographical indicators of traffic pollution. First-time investigation into the frequency of asthmatic symptoms among 7-8 year-old Cypriot children in 1999-2000 showed increased prevalence in the capital Nicosia compared to other areas. Geographical differences on an island the size of Cyprus may reflect environmental and/or lifestyle factors. This study investigates the relationship between self-reported symptoms and residential exposure to motor vehicle emissions among Nicosia schoolchildren.</p> <p>Methods</p> <p>The addresses of children in the metropolitan area of Nicosia who participated in the original survey (N = 1,735) were geo-coded and the level of exposure of each child was assessed using distance- and emission-based indicators (i.e. estimated levels of particulate matter and nitrogen oxides emissions due to motor vehicles on main roads around the residence). Odds ratios of wheezing and asthma diagnosis in relation to levels of exposure were estimated in logistic regression models adjusting for person-based factors, co-morbidity and intra-school clustering.</p> <p>Results</p> <p>We found an increased risk of wheezing at distances less than 50 m from a main road and/or only among those experiencing the highest levels of exposure. The strongest effect estimates were observed when exposure was defined in terms of the cumulative burden at all roads around the residence. Adjusted odds ratios for current wheezing were 2.33 (95% CI 1.27, 4.30) amongst the quartile of participants exposed to the highest levels of PM at all roads 50 m of their residence and 2.14 (95% CI 1.05, 4.35) for NOx, with no effect at intermediate levels of exposure. While the direction of effect was apparent at longer distances, differences were generally not statistically significant.</p> <p>Conclusions</p> <p>Children experiencing the highest burden of emissions in Nicosia seem to be at a higher risk of reporting asthmatic symptoms. Due to the small number of children residing at close proximity to main roads and lack of evidence of risk at intermediate levels of exposure or longer distances, the observed pattern alone does not explain the generally higher prevalence observed in urban Nicosia compared to other areas.</p

The Statistics of Bulk Segregant Analysis Using Next Generation Sequencing

We describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard statistic, and takes into account variation in allele frequency estimates due to sampling of segregants to form bulks as well as variation introduced during the sequencing of bulks. Using simulation, we explore the impact of key experimental variables such as bulk size and sequencing coverage on the ability to detect QTLs. Counterintuitively, we find that relatively large bulks maximize the power to detect QTLs even though this implies weaker selection and less extreme allele frequency differences. Our simulation studies suggest that with large bulks and sufficient sequencing depth, the methods we propose can be used to detect even weak effect QTLs and we demonstrate the utility of this framework by application to a BSA experiment in the budding yeast Saccharomyces cerevisiae

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Exposure to Moderate Air Pollution during Late Pregnancy and Cord Blood Cytokine Secretion in Healthy Neonates

Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown. In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM₁₀), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders. Mean (95%-CI) PM₁₀ exposure for the last 7 days of pregnancy was 18.3 (10.3-38.4 µg/m³). PM₁₀ exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found. Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort

Phylogenetic and Preliminary Phenotypic Analysis of Yeast PAQR Receptors: Potential Antifungal Targets

Proteins belonging to the Progestin and AdipoQ Receptor (PAQR) superfamily of membrane bound receptors are ubiquitously found in fungi. Nearly, all fungi possess two evolutionarily distinct paralogs of PAQR protein, which we have called the PQRA and PQRB subtypes. In the model fungus Saccharomyces cerevisiae, these subtypes are represented by the Izh2p and Izh3p proteins, respectively. S. cerevisiae also possesses two additional PQRA-type receptors called Izh1p and Izh4p that are restricted to other species within the “Saccharomyces complex”. Izh2p has been the subject of several recent investigations and is of particular interest because it regulates fungal growth in response to proteins produced by plants and, as such, represents a new paradigm for interspecies communication. We demonstrate that IZH2 and IZH3 gene dosage affects resistance to polyene antifungal drugs. Moreover, we provide additional evidence that Izh2p and Izh3p negatively regulate fungal filamentation. These data suggest that agonists of these receptors might make antifungal therapeutics, either by inhibiting fungal development or by sensitizing fungi to the toxic effects of current antifungal therapies. This is particularly relevant for pathogenic fungi such as Candida glabrata that are closely related to S. cerevisiae and contain the same complement of PAQR receptors

An Improved, Bias-Reduced Probabilistic Functional Gene Network of Baker's Yeast, Saccharomyces cerevisiae

Background: Probabilistic functional gene networks are powerful theoretical frameworks for integrating heterogeneous functional genomics and proteomics data into objective models of cellular systems. Such networks provide syntheses of millions of discrete experimental observations, spanning DNA microarray experiments, physical protein interactions, genetic interactions, and comparative genomics; the resulting networks can then be easily applied to generate testable hypotheses regarding specific gene functions and associations. Methodology/Principal Findings: We report a significantly improved version (v. 2) of a probabilistic functional gene network [1] of the baker's yeast, Saccharomyces cerevisiae. We describe our optimization methods and illustrate their effects in three major areas: the reduction of functional bias in network training reference sets, the application of a probabilistic model for calculating confidences in pair-wise protein physical or genetic interactions, and the introduction of simple thresholds that eliminate many false positive mRNA co-expression relationships. Using the network, we predict and experimentally verify the function of the yeast RNA binding protein Puf6 in 60S ribosomal subunit biogenesis. Conclusions/Significance: YeastNet v. 2, constructed using these optimizations together with additional data, shows significant reduction in bias and improvements in precision and recall, in total covering 102,803 linkages among 5,483 yeast proteins (95% of the validated proteome). YeastNet is available from http://www.yeastnet.org.This work was supported by grants from the N.S.F. (IIS-0325116, EIA-0219061), N.I.H. (GM06779-01,GM076536-01), Welch (F-1515), and a Packard Fellowship (EMM). These agencies were not involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.Cellular and Molecular Biolog

Spatial analysis of air pollution and childhood asthma in Hamilton, Canada: comparing exposure methods in sensitive subgroups

<p>Abstract</p> <p>Background</p> <p>Variations in air pollution exposure within a community may be associated with asthma prevalence. However, studies conducted to date have produced inconsistent results, possibly due to errors in measurement of the exposures.</p> <p>Methods</p> <p>A standardized asthma survey was administered to children in grades one and eight in Hamilton, Canada, in 1994–95 (N ~1467). Exposure to air pollution was estimated in four ways: (1) distance from roadways; (2) interpolated surfaces for ozone, sulfur dioxide, particulate matter and nitrous oxides from seven to nine governmental monitoring stations; (3) a kriged nitrogen dioxide (NO₂) surface based on a network of 100 passive NO₂monitors; and (4) a land use regression (LUR) model derived from the same monitoring network. Logistic regressions were used to test associations between asthma and air pollution, controlling for variables including neighbourhood income, dwelling value, state of housing, a deprivation index and smoking.</p> <p>Results</p> <p>There were no significant associations between any of the exposure estimates and asthma in the whole population, but large effects were detected the subgroup of children without hayfever (predominately in girls). The most robust effects were observed for the association of asthma without hayfever and NO₂LUR OR = 1.86 (95%CI, 1.59–2.16) in all girls and OR = 2.98 (95%CI, 0.98–9.06) for older girls, over an interquartile range increase and controlling for confounders.</p> <p>Conclusion</p> <p>Our findings indicate that traffic-related pollutants, such as NO₂, are associated with asthma without overt evidence of other atopic disorders among female children living in a medium-sized Canadian city. The effects were sensitive to the method of exposure estimation. More refined exposure models produced the most robust associations.</p