P-Wave Charmonium Production in B-Meson Decays

We calculate the decay rates of $B$ mesons into P-wave charmonium states using new factorization formulas that are valid to leading order in the relative velocity of the charmed quark and antiquark and to all orders in the running coupling constant of QCD. We express the production rates for all four P states in terms of two nonperturbative parameters, the derivative of the wavefunction at the origin and another parameter related to the probability for a charmed-quark-antiquark pair in a color-octet S-wave state to radiate a soft gluon and form a P-wave bound state. Using existing data on $B$ meson decays into $\chi_{c1}$ to estimate the color-octet parameter, we find that the color-octet mechanism may account for a significant fraction of the $\chi_{c1}$ production rate and that $B$ mesons should decay into $\chi_{c2}$ at a similar rate.Comment: 14 page

Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man

Block bond-order potential as a convergent moments-based method

The theory of a novel bond-order potential, which is based on the block Lanczos algorithm, is presented within an orthogonal tight-binding representation. The block scheme handles automatically the very different character of sigma and pi bonds by introducing block elements, which produces rapid convergence of the energies and forces within insulators, semiconductors, metals, and molecules. The method gives the first convergent results for vacancies in semiconductors using a moments-based method with a low number of moments. Our use of the Lanczos basis simplifies the calculations of the band energy and forces, which allows the application of the method to the molecular dynamics simulations of large systems. As an illustration of this convergent O(N) method we apply the block bond-order potential to the large scale simulation of the deformation of a carbon nanotube.Comment: revtex, 43 pages, 11 figures, submitted to Phys. Rev.

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Insulin-Like Growth Factor Levels During Pregnancy in the Cow are Affected by Protein Supplementation in the Maternal Diet

To determine if dietary protein supplementation in early pregnancy alters total circulating insulinlike growth factor (IGF) levels, genetically similar heifers were fed diets containing different levels of protein in the first and second trimesters of gestation. The groups were: low/low (L/L), fed a diet containing 7% crude protein (CP) per kg/DM (low protein) in the first and second trimesters; high/high (H/H), fed a diet containing 14% CP per kg/DM (high protein) in the first and second trimesters; low/high (L/H), fed low protein in the first trimester and high in the second trimester and vice versa for the high/low (H/L) group. At day 62 of gestation, there was a significant difference (

BotSwindler: Tamper Resistant Injection of Believable Decoys in VM-Based Hosts for Crimeware Detection

We introduce BotSwindler, a bait injection system designed to delude and detect crimeware by forcing it to reveal during the exploitation of monitored information. The implementation of BotSwindler relies upon an out-of-host software agent that drives user-like interactions in a virtual machine, seeking to convince malware residing within the guest OS that it has captured legitimate credentials. To aid in the accuracy and realism of the simulations, we propose a low overhead approach, called virtual machine verification, for verifying whether the guest OS is in one of a predefined set of states. We present results from experiments with real credential-collecting malware that demonstrate the injection of monitored financial bait for detecting compromises. Additionally, using a computational analysis and a user study, we illustrate the believability of the simulations and we demonstrate that they are sufficiently human-like. Finally, we provide results from performance measurements to show our approach does not impose a performance burden

Cosmic Microwave Background Anisotropies from Scaling Seeds: Global Defect Models

We investigate the global texture model of structure formation in cosmogonies with non-zero cosmological constant for different values of the Hubble parameter. We find that the absence of significant acoustic peaks and little power on large scales are robust predictions of these models. However, from a careful comparison with data we conclude that at present we cannot safely reject the model on the grounds of present CMB data. Exclusion by means of galaxy correlation data requires assumptions on biasing and statistics. New, very stringent constraints come from peculiar velocities. Investigating the large-N limit, we argue that our main conclusions apply to all global O(N) models of structure formation.Comment: LaTeX file with RevTex, 27 pages, 23 eps figs., submitted to Phys. Rev. D. A version with higher quality images can be found at http://mykonos.unige.ch/~kunz/download/lam.tar.gz for the LaTeX archive and at http://mykonos.unige.ch/~kunz/download/lam.ps.gz for the compiled PostScript fil

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

Introduction Early diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe. Methods We analysed HIV test data from Zimbabwe's nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV-positive test after at least one HIV-negative test in the programme. We used logistic regression to analyse test positivity over three time-periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time-periods. Results During the 10-year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV-negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2). Conclusions Test positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

Introduction Early diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe. Methods We analysed HIV test data from Zimbabwe's nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV-positive test after at least one HIV-negative test in the programme. We used logistic regression to analyse test positivity over three time-periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time-periods. Results During the 10-year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV-negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2). Conclusions Test positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance