The Soft Gluon Emission Process in the Color-Octet Model for Heavy Quarkonium Production

The Color-Octet Model has been used successfully to analyze many problems in heavy quarkonium production. We examine some of the conceptual and practical problems of the soft gluon emission process in the Color-Octet Model. We use a potential model to describe the initial and final states in the soft gluon emission process, as the emission occurs at a late stage after the production of the heavy quark pair. It is found in this model that the soft gluon M1 transition, 1S0(8)->3S1(1), dominates over the E1 transition, 3PJ(8)->3S1(1), for J/psi and psi' production. Such a dominance may help resolve the questions of isotropic polarization and color-octet matrix element universality in the Color-Octet Model.Comment: 26 pages, in LaTe

Toll-Like Receptor 2 Signaling Protects Mice from Tumor Development in a Mouse Model of Colitis-Induced Cancer

Inflammatory bowel disease (IBD) is a disorder of chronic inflammation with increased susceptibility to colorectal cancer. The etiology of IBD is unclear but thought to result from a dysregulated adaptive and innate immune response to microbial products in a genetically susceptible host. Toll-like receptor (TLR) signaling induced by intestinal commensal bacteria plays a crucial role in maintaining intestinal homeostasis, innate immunity and the enhancement of intestinal epithelial cell (IEC) integrity. However, the role of TLR2 in the development of colorectal cancer has not been studied. We utilized the AOM-DSS model for colitis-associated colorectal cancer (CAC) in wild type (WT) and TLR2−/− mice. Colons harvested from WT and TLR2−/− mice were used for histopathology, immunohistochemistry, immunofluorescence and cytokine analysis. Mice deficient in TLR2 developed significantly more and larger colorectal tumors than their WT controls. We provide evidence that colonic epithelium of TLR2−/− mice have altered immune responses and dysregulated proliferation under steady-state conditions and during colitis, which lead to inflammatory growth signals and predisposition to accelerated neoplastic growth. At the earliest time-points assessed, TLR2−/− colons exhibited a significant increase in aberrant crypt foci (ACF), resulting in tumors that developed earlier and grew larger. In addition, the intestinal microenvironment revealed significantly higher levels of IL-6 and IL-17A concomitant with increased phospho-STAT3 within ACF. These observations indicate that in colitis, TLR2 plays a protective role against the development of CAC

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Gradient microfluidics enables rapid bacterial growth inhibition testing

Bacterial growth inhibition tests have become a standard measure of the adverse effects of inhibitors for a wide range of applications, such as toxicity testing in the medical and environmental sciences. However, conventional well-plate formats for these tests are laborious and provide limited information (often being restricted to an end-point assay). In this study, we have developed a microfluidic system that enables fast quantification of the effect of an inhibitor on bacteria growth and survival, within a single experiment. This format offers a unique combination of advantages, including long-term continuous flow culture, generation of concentration gradients, and single cell morphology tracking. Using Escherichia coli and the inhibitor amoxicillin as one model system, we show excellent agreement between an on-chip single cell-based assay and conventional methods to obtain quantitative measures of antibiotic inhibition (for example, minimum inhibition concentration). Furthermore, we show that our methods can provide additional information, over and above that of the standard well-plate assay, including kinetic information on growth inhibition and measurements of bacterial morphological dynamics over a wide range of inhibitor concentrations. Finally, using a second model system, we show that this chip-based systems does not require the bacteria to be labeled and is well suited for the study of naturally occurring species. We illustrate this using Nitrosomonas europaea, an environmentally important bacteria, and show that the chip system can lead to a significant reduction in the period required for growth and inhibition measurements (<4 days, compared to weeks in a culture flask)

Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays

In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool

Circulating 25-Hydroxyvitamin D and the Risk of Rarer Cancers: Design and Methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations

Efficient ancestry and mutation simulation with msprime 1.0

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement