Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV

The inclusive cross section for production of isolated photons has been measured in \pbarp collisions at $\sqrt{s} = 630$ GeV with the \D0 detector at the Fermilab Tevatron Collider. The photons span a transverse energy ($E_T$) range from 7-49 GeV and have pseudorapidity $|\eta| < 2.5$. This measurement is combined with to previous \D0 result at $\sqrt{s} = 1800$ GeV to form a ratio of the cross sections. Comparison of next-to-leading order QCD with the measured cross section at 630 GeV and ratio of cross sections show satisfactory agreement in most of the $E_T$ range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001

Syndecan 4 Is Involved in Mediating HCV Entry through Interaction with Lipoviral Particle-Associated Apolipoprotein E

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV infection represents a major health problem. HCV associates with host lipoproteins forming host/viral hybrid complexes termed lipoviral particles. Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may likewise mediate HCV entry. We sought to define the functional regions of apoE with an aim to identify critical apoE binding partners involved in HCV infection. Using adenoviral vectors and siRNA to modulate apoE expression we show a direct correlation of apoE expression and HCV infectivity, whereas no correlation exists with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE revealed key residues that are critical for mediating HCV infection. Furthermore, a novel synthetic peptide that mimics apoE's HSPG-BD directly and competitively inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1 and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish infection. Targeting apoE-SDC interactions could be an alternative strategy for blocking HCV entry, a critical step in maintaining chronic HCV infection

Characterization and Whole Genome Analysis of Human Papillomavirus Type 16 E1-1374^63nt Variants

Background. The variation of the most common Human papillomavirus (HPV) type found in cervical cancer, the HPV16, has been extensively investigated in almost all viral genes. The E1 gene variation, however, has been rarely studied. The main objective of the present investigation was to analyze the variability of the E6 and E1 genes, focusing on the recently identified E1-1374^63nt variant. Methodology/Principal Findings. Variation within the E6 of 786 HPV16 positive cervical samples was analyzed using high-resolution melting, while the E1-1374^63nt duplication was assayed by PCR. Both techniques were supplemented with sequencing. The E1-1374^63nt duplication was linked with the E-G350 and the E-C109/G350 variants. In comparison to the referent HPV16, the E1-1374^63nt E-G350 variant was significantly associated with lower grade cervical lesions (p=0.029), while the E1-1374^63nt E-C109/G350 variant was equally distributed between high and low grade lesions. The E1-1374^63nt variants were phylogenetically closest to E-G350 variant lineage (A2 sub-lineage based on full genome classification). The major differences between E1-1374^63nt variants were within the LCR and the E6 region. On the other hand, changes within the E1 region were the major differences from the A2 sub-lineage, which has been historically but inconclusively associated with high grade cervical disease. Thus, the shared variations cannot explain the particular association of the E1-1374^63nt variant with lower grade cervical lesions. Conclusions/Significance. The E1 region has been thus far considered to be well conserved among all HPVs and therefore uninteresting for variability studies. However, this study shows that the variations within the E1 region could possibly affect cervical disease, since the E1-1374^63nt E-G350 variant is significantly associated with lower grade cervical lesions, in comparison to the A1 and A2 sub-lineage variants. Furthermore, it appears that the silent variation 109T&gt;C of the E-C109/G350 variant might have a significant role in the viral life cycle and warrants further study

The orphan germinant receptor protein GerXAO (but not GerX3b) is essential for L-alanine induced germination in Clostridium botulinum Group II

Clostridium botulinum is an anaerobic spore forming bacterium that produces the potent botulinum neurotoxin that causes a severe and fatal neuro-paralytic disease of humans and animals (botulism). C. botulinum Group II is a psychrotrophic saccharolytic bacterium that forms spores of moderate heat resistance and is a particular hazard in minimally heated chilled foods. Spore germination is a fundamental process that allows the spore to transition to a vegetative cell and typically involves a germinant receptor (GR) that responds to environmental signals. Analysis of C. botulinum Group II genomes shows they contain a single GR cluster (gerX3b), and an additional single gerA subunit (gerXAO). Spores of C. botulinum Group II strain Eklund 17B germinated in response to the addition of L-alanine, but did not germinate following the addition of exogenous Ca2+-DPA. Insertional inactivation experiments in this strain unexpectedly revealed that the orphan GR GerXAO is essential for L-alanine stimulated germination. GerX3bA and GerX3bC affected the germination rate but were unable to induce germination in the absence of GerXAO. No role could be identified for GerX3bB. This is the first study to identify the functional germination receptor of C. botulinum Group II

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Evaluation of Stepping Stones as a tool for changing knowledge, attitudes and behaviours associated with gender, relationships and HIV risk in Karnataka, India

<p>Abstract</p> <p>Background</p> <p>Stepping Stones training aims to help individuals explore sexual relationships and recognize gender inequalities, the structural drivers of the HIV epidemic, in order to understand risk behaviours and to seek solutions to factors that increase HIV vulnerability. Despite earlier studies suggesting the success of Stepping Stones, little data exist to show diffusion to trainees' social networks or the wider community.</p> <p>Methods</p> <p>A mixed-methods evaluation of this approach was undertaken using in-depth interviews of trainees and friends, and polling booth surveys in 20 villages where Stepping Stones training took place and in another 20 villages with no Stepping Stones intervention.</p> <p>Results</p> <p>The interview respondents and their friends reported significant changes in their relationships after training, and benefit from discussion of gender, sexuality, condom use and HIV vulnerability issues. However, though diffusion of this knowledge at the level of personal contacts was strong, the evaluation revealed that diffusion to the community level was limited.</p> <p>Conclusions</p> <p>The qualitative part of this study reflects other studies in different settings, in that SS participants gained immensely from the training. Wider behaviour change is a challenging goal that many programmes fail to attain, with most interventions too limited in scope and intensity to produce larger community effects. This may have contributed to the fact that we observed few differences between interventions and non-intervention villages in this study. However, it is also possible that we had excessive expectations of individual change at the community level, and that it might have been more appropriate to have had broader community level rather than individual behavioural change indicators. We suggest that SS could be enhanced by efforts to better engage existing community opinion leaders, to empower and train participants as community change agents, and to support the development of village-level action plans that combat sexual stereotyping and risky behaviours that lead to unhealthy sexual relationships.</p

New resampling method for evaluating stability of clusters

<p>Abstract</p> <p>Background</p> <p>Hierarchical clustering is a widely applied tool in the analysis of microarray gene expression data. The assessment of cluster stability is a major challenge in clustering procedures. Statistical methods are required to distinguish between real and random clusters. Several methods for assessing cluster stability have been published, including resampling methods such as the bootstrap.</p> <p>We propose a new resampling method based on continuous weights to assess the stability of clusters in hierarchical clustering. While in bootstrapping approximately one third of the original items is lost, continuous weights avoid zero elements and instead allow non integer diagonal elements, which leads to retention of the full dimensionality of space, i.e. each variable of the original data set is represented in the resampling sample.</p> <p>Results</p> <p>Comparison of continuous weights and bootstrapping using real datasets and simulation studies reveals the advantage of continuous weights especially when the dataset has only few observations, few differentially expressed genes and the fold change of differentially expressed genes is low.</p> <p>Conclusion</p> <p>We recommend the use of continuous weights in small as well as in large datasets, because according to our results they produce at least the same results as conventional bootstrapping and in some cases they surpass it.</p

Effect of collaborative depression treatment on risk for diabetes: A 9-year follow-up of the IMPACT randomized controlled trial

Considerable epidemiologic evidence and plausible biobehavioral mechanisms suggest that depression is an independent risk factor for diabetes. Moreover, reducing the elevated diabetes risk of depressed individuals is imperative given that both conditions are leading causes of death and disability. However, because no prior study has examined clinical diabetes outcomes among depressed patients at risk for diabetes, the question of whether depression treatment prevents or delays diabetes onset remains unanswered. Accordingly, we examined the effect of a 12-month collaborative care program for late-life depression on 9-year diabetes incidence among depressed, older adults initially free of diabetes. Participants were 119 primary care patients [M (SD) age: 67.2 (6.9) years, 41% African American] with a depressive disorder but without diabetes enrolled at the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. Incident diabetes cases were defined as diabetes diagnoses, positive laboratory values, or diabetes medication prescription, and were identified using electronic medical record and Medicare/Medicaid data. Surprisingly, the rate of incident diabetes in the collaborative care group was 37% (22/59) versus 28% (17/60) in the usual care group. Even though the collaborative care group exhibited greater reductions in depressive symptom severity (p = .024), unadjusted (HR = 1.29, 95% CI: 0.69-2.43, p = .428) and adjusted (HR = 1.18, 95% CI: 0.61-2.29, p = .616) Cox proportional hazards models indicated that the risk of incident diabetes did not differ between the treatment groups. Our novel preliminary findings raise the possibility that depression treatment alone may be insufficient to reduce the excess diabetes risk of depressed, older adults

Transcriptional Profiling of Non-Small Cell Lung Cancer Cells with Activating EGFR Somatic Mutations

Activating somatic mutations in epidermal growth factor receptor (EGFR) confer unique biologic features to non-small cell lung cancer (NSCLC) cells, but the transcriptional mediators of EGFR in this subgroup of NSCLC have not been fully elucidated.Here we used genetic and pharmacologic approaches to elucidate the transcriptomes of NSCLC cell lines. We transcriptionally profiled a panel of EGFR-mutant and -wild-type NSCLC cell lines cultured in the presence or absence of an EGFR tyrosine kinase inhibitor. Hierarchical analysis revealed that the cell lines segregated on the basis of EGFR mutational status (mutant versus wild-type), and expression signatures were identified by supervised analysis that distinguished the cell lines based on mutational status (wild-type versus mutant) and type of mutation (L858R versus Delta746-750). Using an EGFR mutation-specific expression signature as a probe, we mined the gene expression profiles of two independent cohorts of NSCLC patients and found the signature in a subset. EGFR tyrosine kinase inhibitor treatment regulated the expression of multiple genes, and pharmacologic inhibition of the protein products of two of them (PTGS2 and EphA2) inhibited anchorage-independent growth in EGFR-mutant NSCLC cells.We have elucidated genes not previously associated with EGFR-mutant NSCLC, two of which enhanced the clonogenicity of these cells, distinguishing these mediators from others previously shown to maintain cell survival. These findings have potential clinical relevance given the availability of pharmacologic tools to inhibit the protein products of these genes

Anomaly Mediation and Cosmology

We consider an extension of the MSSM wherein anomaly mediation is the source of supersymmetry breaking, and the tachyonic slepton problem is solved by a gauged U(1) symmetry, which is broken at high energies in a manner preserving supersymmetry, thereby also facilitating the see-saw mechanism for neutrino masses and a natural source for the Higgs mu-term. We show that these favourable outcomes can occur both in the presence and the absence of a large Fayet-Iliopoulos (FI) D-term associated with the new U(1). We explore the cosmological consequences of the model, showing that it naturally produces a period of hybrid inflation, terminating in the production of cosmic strings. In spite of the presence of a U(1) (even with an FI term), inflation is effected by the F-term, with a D-flat tree potential (the FI term, if present, being cancelled by non-zero squark and slepton fields). Calculating the 1-loop corrections to the inflaton potential, we estimate the constraints on the parameters of the model from Cosmic Microwave Background data. We will see that a consequence of these constraints is that the Higgs mu-term necessarily small. We briefly discuss the mechanisms for baryogenesis via conventional leptogenesis, the out-of-equilibrium production of neutrinos from the cosmic strings, or the Affleck-Dine mechanism. Cosmic string decays also boost the relic density of dark matter above the low value normally obtained in AMSB scenarios.Comment: 34 pages. Revised to incorporate discussion of the case when the Fayet-Ilipoulos term is absen