Replication of Epstein-Barr Virus Primary Infection in Human Tonsil Tissue Explants

Epstein-Barr virus (EBV) may cause a variety of virus-associated diseases, but no antiviral agents have yet been developed against this virus. Animal models are thus indispensable for the pathological analysis of EBV-related infections and the elucidation of therapeutic methods. To establish a model system for the study of EBV infection, we tested the ability of B95–8 virus and recombinant EBV expressing enhanced green fluorescent protein (EGFP) to replicate in human lymphoid tissue. Human tonsil tissues that had been surgically removed during routine tonsillectomy were sectioned into small blocks and placed on top of collagen sponge gels in culture medium at the air-interface, then a cell-free viral suspension was directly applied to the top of each tissue block. Increasing levels of EBV DNA in culture medium were observed after 12–15 days through 24 days post-infection in tissue models infected with B95–8 and EGFP-EBV. Expression levels of eight EBV-associated genes in cells collected from culture medium were increased during culture. EBV-encoded small RNA-positive cells were detected in the interfollicular areas in paraffin-embedded sections. Flow cytometric analyses revealed that most EGFP+ cells were CD3− CD56− CD19+ HLA-DR+, and represented both naïve (immunoglobulin D+) and memory (CD27+) B cells. Moreover, EBV replication in this model was suppressed by acyclovir treatment in a dose-dependent manner. These data suggest that this model has potential for use in the pathological analysis of local tissues at the time of primary infection, as well as for screening novel antiviral agents

Cosmogenic production of 37Ar in the context of the LUX-ZEPLIN experiment

We estimate the amount of 37Ar produced in natural xenon via cosmic ray-induced spallation, an inevitable consequence of the transportation and storage of xenon on the Earth's surface. We then calculate the resulting 37Ar concentration in a 10-tonne payload~(similar to that of the LUX-ZEPLIN experiment) assuming a representative schedule of xenon purification, storage and delivery to the underground facility. Using the spallation model by Silberberg and Tsao, the sea level production rate of 37Ar in natural xenon is estimated to be 0.024~atoms/kg/day. Assuming the xenon is successively purified to remove radioactive contaminants in 1-tonne batches at a rate of 1~tonne/month, the average 37Ar activity after 10~tonnes are purified and transported underground is 0.058--0.090~μBq/kg, depending on the degree of argon removal during above-ground purification. Such cosmogenic 37Ar will appear as a noticeable background in the early science data, while decaying with a 35~day half-life. This newly-noticed production mechanism of 37Ar should be considered when planning for future liquid xenon-based experiments

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Sub-volcanic intrusions and the link to global climatic and environmental changes:

Most of the Large Igneous Provinces (LIPs) formed during the last 260 million years are associated with climatic changes, oceanic anoxia, or extinctions in marine and terrestrial environments. Current hypotheses involve (1) degassing of carbon from either oceans or shallow sea-bed reservoirs, (2) degassing from flood basalts, or from (3) sedimentary basins heavily intruded by LIP-related sills. These hypotheses are based on detailed geological and geochemical studies from LIPSs or relevant proxy data sequences. Here we present new data on gas generation and degassing from a LIP, based on the LA1/68 borehole north of the Ladybrand area in the Karoo Basin, South Africa