Lower frequency of TLR9 variant associated with protection from breast cancer among African Americans

IntroductionToll-like receptor 9 (TLR9) is an innate immune system DNA-receptor that regulates tumor invasion and immunity in vitro. Low tumor TLR9 expression has been associated with poor survival in Caucasian patients with triple negative breast cancer (TNBC). African American (AA) patients with TNBC have worse prognosis than Caucasians but whether this is due to differences in tumor biology remains controversial. We studied the prognostic significance of tumor Toll like receptor-9 (TLR9) protein expression among African American (AA) triple negative breast cancer (TNBC) patients. Germline TLR9 variants in European Americans (EAs) and AAs were investigated, to determine their contribution to AA breast cancer risk.MethodsTLR9 expression was studied with immunohistochemistry in archival tumors. Exome Variant Server and The Cancer Genome Atlas were used to determine the genetic variation in the general EA and AA populations, and AA breast cancer cases. Minor allele frequencies (MAFs) were compared between EAs (n = 4300), AAs (n = 2203), and/or AA breast cancer cases (n = 131).ResultsThirty-two TLR9 variants had a statistically significant MAF difference between general EAs and AAs. Twenty-one of them affect a CpG site. Rs352140, a variant previously associated with protection from breast cancer, is more common in EAs than AAs (p = 2.20E-16). EAs had more synonymous alleles, while AAs had more rare coding alleles. Similar analyses comparing AA breast cancer cases with AA controls did not reveal any variant class differences; however, three previously unreported TLR9 variants were associated with late onset breast cancer. Although not statistically significant, rs352140 was observed less frequently in AA cases compared to controls. Tumor TLR9 protein expression was not associated with prognosis.ConclusionsTumor TLR9 expression is not associated with prognosis in AA TNBC. Significant differences were detected in TLR9 variant MAFs between EAs and AAs. They may affect TLR9 expression and function. Rs352140, which may protect from breast cancer, is 1.6 X more common among EAs. These findings call for a detailed analysis of the contribution of TLR9 to breast cancer pathophysiology and health disparities

Design, recruitment, and retention of African-American smokers in a pharmacokinetic study

<p>Abstract</p> <p>Background</p> <p>African-Americans remain underrepresented in clinical research despite experiencing a higher burden of disease compared to all other ethnic groups in the United States. The purpose of this article is to describe the study design and discuss strategies used to recruit and retain African-American smokers in a pharmacokinetic study.</p> <p>Methods</p> <p>The parent study was designed to evaluate the differences in the steady-state concentrations of bupropion and its three principal metabolites between African-American menthol and non-menthol cigarette smokers. Study participation consisted of four visits at a General Clinical Research Center (GCRC) over six weeks. After meeting telephone eligibility requirements, phone-eligible participants underwent additional screening during the first two GCRC visits. The last two visits (pharmacokinetic study phase) required repeated blood draws using an intravenous catheter over the course of 12 hours.</p> <p>Results</p> <p>Five hundred and fifteen African-American smokers completed telephone screening; 187 were phone-eligible and 92 were scheduled for the first GCRC visit. Of the 81 who attended the first visit, 48 individuals were enrolled in the pharmacokinetic study, and a total of 40 individuals completed the study (83% retention rate).</p> <p>Conclusions</p> <p>Although recruitment of African-American smokers into a non-treatment, pharmacokinetic study poses challenges, retention is feasible. The results provide valuable information for investigators embarking on non-treatment laboratory-based studies among minority populations.</p

CP Violation and Dark Matter

A brief review is given of the effects of CP violation on the direct detection of neutralinos in dark matter detectors. We first summarize the current developments using the cancellation mechanism which allows for the existence of large CP violating phases consistent with experimental limits on the electron and on the neutron electric dipole moments in a broad class of SUSY, string and D brane models. We then discuss their effects on the scattering of neutralinos from quarks and on the event rates. It is found that while CP effects on the event rates can be enormous such effects are reduced significantly with the imposition of the EDM constraints. However, even with the inclusion of the EDM constraints the effects are still very significant and should be included in a precision prediction of event rates in any SUSY, string or D brane model.Comment: Based on an invited talk at the conference "Sources and Detection of Dark Matter in the Universe", at Marina del Rey, CA, Feb. 23-25, 2000; 12 pages, Latex including 2 figure

Aquatic parasite cultures and their applications

In this era of unprecedented growth in aquaculture and trade, aquatic parasite cultures are essential to better understand emerging diseases and their implications for human and animal health. Yet culturing parasites presents multiple challenges, arising from their complex, often multihost life cycles, multiple developmental stages, variable generation times and reproductive modes. Furthermore, the essential environmental requirements of most parasites remain enigmatic. Despite these inherent difficulties, in vivo and in vitro cultures are being developed for a small but growing number of aquatic pathogens. Expanding this resource will facilitate diagnostic capabilities and treatment trials, thus supporting the growth of sustainable aquatic commodities and communities

Effects of Asian air pollution transport and photochemistry on carbon monoxide variability and ozone production in subtropical coastal south China

Author name used in this publication: K. S. LamAuthor name used in this publication: Y. S. Li2002-2003 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Treatment of Residential Complexes’ Wastewater using Environmentally Friendly Technology

Residential complexes discharge huge quantities of wastewater, which has a negative impact on nearby water bodies. Moreover, the treatment of this type of wastewater requires a large area, which could be a challenge as construction sites are normally limited in size. Different technologies have been used for the treatment of residential complexes’ wastewater (RCWW). Compared to the conventional wastewater treatments methods, sequencing batch reactors (SBRs) are lower cost and have smaller area requirements and sludge bulking rarely occurs. A considerable number of researchers have been optimising SBR operating conditions to gain a better removal efficiency of undesired wastewater pollutants. However, many researchers have reported bad, slow or incomplete particle settling. This study examines the impact of organic loading rate (OLR) on the effluent quality and sludge settling performance in a sequencing batch reactor. Four SBR reactors were used in this study; the working volume of each one is 5l. The reactors were operated under different glucose concentrations (750, 1000, 1250 and 1500 mg/l), constant aeration, 1.0 l/min, ±20 Cº temperature and 6 h cycle time. Each cycle of the SBR operation included Fill (30 minutes), React (240 minutes), Settle (30 minutes), Draw (30 minutes) and Idle (30 minutes). Influent and effluent samples were analysed for COD, NH3-N, NO3-N and NO2-N. In addition, the sludge volume index (SVI) and a morphological study were used to study the sludge characteristics. The SVI and morphological study results showed a direct relationship between the glucose concentration and sludge settling behaviour. The results obtained from this study, which operated for 120 days, showed that the sequencing batch reactor could biodegrade up to 93.2%, 95.2%, 94.9% and 96.5% for COD, NH3-N, NO3-N and NO2-N respectively with glucose concentration between 750 and 1250 mg/l, and a steady sludge settling performance occurred during that range

Towards high-speed optical quantum memories

Quantum memories, capable of controllably storing and releasing a photon, are a crucial component for quantum computers and quantum communications. So far, quantum memories have operated with bandwidths that limit data rates to MHz. Here we report the coherent storage and retrieval of sub-nanosecond low intensity light pulses with spectral bandwidths exceeding 1 GHz in cesium vapor. The novel memory interaction takes place via a far off-resonant two-photon transition in which the memory bandwidth is dynamically generated by a strong control field. This allows for an increase in data rates by a factor of almost 1000 compared to existing quantum memories. The memory works with a total efficiency of 15% and its coherence is demonstrated by directly interfering the stored and retrieved pulses. Coherence times in hot atomic vapors are on the order of microsecond - the expected storage time limit for this memory.Comment: 13 pages, 5 figure

Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines