Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of Human Papillomavirus Type 16 Neutralization by L2 Cross-Neutralizing and L1 Type-Specific Antibodies

ABSTRACT Pseudovirions of human papillomavirus type 16 (HPV16), the principal etiologic agent in 50% of cervical cancers, were used as a model system to investigate the cell surface interactions involved in the exposure of the broadly cross-neutralizing papillomavirus L2 epitopes. These neutralizing epitopes were exposed only after cell surface binding and a subsequent change in capsid conformation that permitted cleavage by the cellular protease furin at a specific highly conserved site in L2 that is immediately upstream of the cross-neutralizing epitopes. Unexpectedly, binding of L2 antibodies led to the release of the capsid/antibody complexes from the cell surface and their accumulation on the extracellular matrix. Study of the dynamics of exposure of the L2 epitopes further revealed that representatives of the apparently dominant class of L1-specific neutralizing antibodies induced by virus-like particle vaccination prevent infection, not by preventing cell surface binding but rather by preventing the conformation change involved in exposure of the L2 neutralizing epitope. These findings suggest a dynamic model of virion-cell surface interactions that has implications for both evolution of viral serotypes and the efficacy of current and future HPV vaccines.
Systematic Reviews and Meta- and Pooled Analyses A Pooled Analysis of Extremely Low-Frequency Magnetic Fields and Childhood Brain Tumors

Pooled analyses may provide etiologic insight about associations between exposure and disease. In contrast to childhood leukemia, no pooled analyses of childhood brain tumors and exposure to extremely low-frequency magnetic fields (ELF-MFs) have been conducted. The authors carried out a pooled analysis based on primary data (1960–2001) from 10 studies of ELF-MF exposure and childhood brain tumors to assess whether the combined results, adjusted for potential confounding, indicated an association. The odds ratios for childhood brain tumors in ELF-MF exposure categories of 0.1–<0.2 lT, 0.2–<0.4 lT, and 0.4 lT were 0.95 (95% confidence interval: 0.65, 1.41), 0.70 (95% CI: 0.40, 1.22), and 1.14 (95% CI: 0.61, 2.13), respectively, in comparison with exposure of <0.1 lT. Other analyses employing alternate cutpoints, further adjustment for confounders, exclusion of particular studies, stratification by type of measurement or type of residence, and a nonparametric estimate of the exposure-response relation did not reveal consistent evidence of increased childhood brain tumor risk associated with ELF-MF exposure. These results provide little evidence for an association between ELF-MF exposure and childhood brain tumors.
Did Tectonic Activity Stimulate Oligo–Miocene Speciation in the Indo-West Pacific?

Abstract Analyses of molecular phylogenies of three unrelated tropical marine gastropod genera, Turbo, Echinolittorina, and Conus, reveal an increase in the rate of cladogenesis of some Indo-West Pacific (IWP) clades beginning in the Late Oligocene or Early Miocene between 23.7 and 21.0 million years ago. In all three genera, clades with an increased rate of diversification reach a maximum of diversity, in terms of species richness, in the central IWP. Congruence in both the geographical location and the narrow interval of timing suggests a common cause. The collision of the Australia and New Guinea plate with the southeast extremity of the Eurasian plate approximately 25 Mya resulted in geological changes to the central IWP, including an increase in shallow-water areas and length of coastline, and the creation of a mosaic of distinct habitats. This was followed by a period of rapid diversification of zooxanthellate corals between 20 and 25 Mya. The findings reported here provide the first molecular evidence from multiple groups that part of the present-day diversity of shallow-water gastropods in the IWP arose from a rapid pulse of speciation when new habitats became available in the Late Oligocene to Early Miocene. After the new habitats were filled, the rate of speciation likely decreased and this combined with high levels of extinction (in some groups), resulted in a slow down in the rate of diversification in the genera examined.
Recurring exon deletions in the haptoglobin ( HP ) gene associate with lower blood cholesterol levels

Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels. Abstract Two exons of the human haptoglobin (HP) gene exhibit copy number variation that affects HP multimerization and underlies one of the first protein polymorphisms identified in humans. The evolutionary origins and medical significance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from the recurring reversion of an ancient hominin-specific duplication of these exons. Though this polymorphism has been largely invisible to genome-wide genetic studies to date, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We show that these deletions, and a SNP that affects HP expression, are the likely drivers of the strong but complex association of cholesterol levels to SNPs near HP. Recurring exonic deletions in the haptoglobin gene likely enhance human health by lowering cholesterol levels in the blood.
Knowledge audit for References and Customer Services Unit at UNITEN library

Knowledge management has become a common phrase in many service-oriented or business-oriented and government or privately owned organizations. Consequently, libraries have followed suit in deploying knowledge management for the many benefits being realized by these organizations. In this paper, we consider the appropriateness of a mixed-method approach, which include both quantitative and qualitative techniques of collecting data to reinforce the fact that library reference and customer service trends are changing. The paper proves and acknowledges that knowledge audit is an approach for assessing the viability of knowledge sources for reference librarians in academic institutions. Our subject for this study is the Reference and Customer Services Unit (RSCU) of Universiti Tenaga Nasional (UNITEN). A knowledge map for the unit is conceived to show the locations of knowledge within the unit.
Diagnostic Imaging of Canine Hepatobiliary Affections: A Review

Hepatic disease is often treatable and has a predictable prognosis when a definitive diagnosis is made. The aim of clinicopathological evaluation of hepatobiliary affections is to identify and characterize hepatic damage and dysfunction, identify possible primary causes of secondary liver disease, differentiate causes of icterus, evaluate potential anaesthetic risks, assess prognosis and response to xenobiotics, and monitor response to therapy. This paper describes the different diagnostic methods and imaging techniques employed in diagnosis of hepatobiliary affections in dogs. Besides reviewing the significant clinical manifestations and imaging structural abnormalities in diagnostic approach to different hepatic affections, it also depicts radiographic, ultrasonographic, and wherever applicable, the laparoscopic characterization of different hepatic affections and target lesions encountered in clinical cases presented in the Teaching Veterinary Clinical Complex, COVAS, Palampur in the year 2007-2008.
A Survey of Dynamic Analysis and Test Generation for JavaScript

JavaScript has become one of the most prevalent programming languages. Unfortunately, some of the unique properties that contribute to this popularity also make JavaScript programs prone to errors and difficult for program analyses to reason about. These properties include the highly dynamic nature of the language, a set of unusual language features, a lack of encapsulation mechanisms, and the “no crash” philosophy. This article surveys dynamic program analysis and test generation techniques for JavaScript targeted at improving the correctness, reliability, performance, security, and privacy of JavaScript-based software.
Long‐term magnetic resonance imaging of stem cells in neonatal ischemic injury

Quantitative magnetic resonance imaging (MRI) can serially and noninvasively assess the degree of injury in rat pup models of hypoxic ischemic injury (HII). It can also noninvasively monitor stem cell migration following iron oxide prelabeling. Reports have shown that neural stem cells (NSCs) may help mediate neuroprotection or stimulate neuroreparative responses in adult and neonatal models of ischemic injury. We investigated the ability of high‐field MRI to monitor and noninvasively quantify the migration, proliferation, and location of iron oxide–labeled NSCs over very long time periods (58 weeks) in real time while contemporaneously correlating this activity with the evolving severity and extent of neural damage.
Administration of intravenous immunoglobulins for prophylaxis or treatment of infection in preterm infants: meta-analyses.

AIMS--To determine the effectiveness of intravenous immunoglobulin administration to premature infants in the prevention and/or treatment of bacterial infection. METHODS--Computer searches of MEDLINE, EMBASE, SCISEARCH and Oxford Database of Perinatal Trials were made. Two independent researchers applied inclusion criteria of: randomised controlled trial; premature and/or low birthweight infant; use of intravenous immunoglobulin; and infection or mortality. Nineteen of 44 identified studies fulfilled these criteria. Study quality was assessed and information on study population, intervention, and outcomes were collected. RESULTS--Studies were divided into prophylaxis or treatment; results were tabulated for infection, sepsis, and death from all causes. For 17 studies of prophylaxis (n = 5245), the relative risk and confidence interval were, for proved infection 0.81, 0.67-0.97; for sepsis 0.87, 0.66-1.13; for death from all causes 0.85, 0.64-1.14. Some outcome results were heterogeneous. Two treatment studies showed no reduction in mortality when combined. CONCLUSIONS--Routine administration of intravenous immunoglobulin to preterm infants is not recommended.
Ex Vivo Priming of Endothelial Progenitor Cells With SDF-1 Before Transplantation Could Increase Their Proangiogenic Potential

Objectives—As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis. Methods and Results—EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface α4 and αM integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti–intercellular adhesion molecule1 (ICAM-1) and anti–vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500s−1. Conclusions—SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.
Coordinate Analysis of Murine Immune Cell Surface Markers and Intracellular Phosphoproteins by Flow Cytometry1

Recently, phosphospecific flow cytometry has emerged as a powerful tool to analyze intracellular signaling events in complex populations of cells because of its ability to simultaneously discriminate cell types based on surface marker expression and measure levels of intracellular phosphoproteins. This has provided novel insights into the cell- and pathway-specific nature of immune signaling. However, we and others have found that the fixation and permeabilization steps necessary for phosphoprotein analysis often negatively affect the resolution of cell types based on surface marker analysis and light scatter characteristics. Therefore, we performed a comprehensive profile of >35 different murine surface marker Abs to understand the effects of fixation and permeabilization on surface Ag staining. Fortuitously, ∼80% of the Abs tested resolved cell populations of interest, although with decreased separation between positive and negative populations and at very different titers than those used on live cells. The other 20% showed either complete loss of separation between populations or loss of intermediately staining populations. We were able to rescue staining of several of these Ags by performing staining after fixation, but before permeabilization, although with limited fluorophore choices. Scatter characteristics of lymphocytes were well retained, but changed dramatically for monocyte and neutrophil populations. These results compile a comprehensive resource for researchers interested in applying phosphospecific flow cytometry to complex populations of cells while outlining steps necessary to successfully apply new surface marker Abs to this platform.
Clinical analysis of 21-gene relapse score test in hormone receptor-positive early-stage breast cancer

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2− early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot. com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2–47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.
Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients

Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory disorder, primarily affecting the gastrointestinal tract. Genetic and functional studies have highlighted a key role for innate immunity in its pathogenesis. Profound systemic defects in innate immunity and acute inflammation are understood to result in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes. Macrophages, key orchestrators of acute inflammation, are likely to play an important role in the initial impaired innate immune response. Monocyte‐derived macrophages from CD patients stimulated with Escherichia coli were shown to release attenuated levels of tumour necrosis factor and interferon‐γ with normal secretion of interleukin‐8 (IL‐8), IL‐10 and IL‐6. In controls, the secretion of these cytokines was strongly positively correlated, which was not seen with CD macrophages. The transcriptomes of CD and control macrophages were examined in an attempt to understand the molecular basis of this defect. There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under‐expressed in subgroups of CD patients. The most common of these was optineurin (OPTN) which was under‐expressed in approximately 10% of the CD patients. Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with small interfering RNA knockdown in THP‐1 cells. Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.
X-ray crystal structure and solution fluorescence characterization of Mg.2'(3')-O-(N-methylanthraniloyl) nucleotides bound to the Dictyostelium discoideum myosin motor domain.

Mant (2'(3')-O-(N-methylanthraniloyl)) labeled nucleotides have proven to be useful tools in the study of the kinetic mechanism of the myosin ATPase by fluorescence spectroscopy. The sensitivity of the mant fluorophore to its local environment also makes it suitable to investigate the exposure of bound nucleotides to solvent from collisional quenching measurements. Here we present the crystal structure of mant-ADP and beryllium fluoride complexed with Dictyostelium discoideum myosin motor domain (S1dC) at 1.9 A resolution. We complement the structural approach with an investigation of the accessibility of the mant moiety to solvent using acrylamide quenching of fluorescence emission. In contrast to rabbit skeletal myosin subfragment 1, where the mant group is protected from acrylamide (Ksv=0.2 M-1), the fluorophore is relatively exposed when bound to Dictyostelium myosin motor domain (Ksv= 1.4 M-1). Differences between the Dictyostelium structure and that of vertebrate skeletal subfragment 1, in the region of the nucleotide binding pocket, are proposed as an explanation for the differences observed in the solvent accessibility of complexed mant-nucleotides. We conclude that protection of the mant group from acrylamide quenching does not report on overall closure of the nucleotide binding pocket but reflects more local structural changes.
Functional Structure of Spontaneous Sleep Slow Oscillation Activity in Humans

Background During non-rapid eye movement (NREM) sleep synchronous neural oscillations between neural silence (down state) and neural activity (up state) occur. Sleep Slow Oscillations (SSOs) events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. Methodology/Principal Findings We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. Conclusions/Significance This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.
Conditions of the Anode Spot Formation in a Vacuum Arc

A critical analysis of available experimental data and models of an anode spot formation shows their insufficiency for developing a clear-cut physical model of anode processes in a high-current vacuum arc. Based on new results of studying an anode medium- and low-pressure arc region, a qualitative physical model of an anode spot formation in a vacuum arc is proposed. The main idea of the model is that a change of the sign of the anode voltage drop (from negative to positive) is a necessary condition for an anode spot formation. Experimental data are qualitatively discussed from the point of view of the proposed model.
Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study.

OBJECTIVE To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.