We use Chandra data to map the gas temperature in the central region of the merging cluster A2142. The cluster is markedly nonisothermal; it appears that the central cooling flow has been disturbed but not destroyed by a merger. The X-ray image exhibits two sharp, bow-shaped, shock-like surface brightness edges or gas density discontinuities. However, temperature and pressure profiles across these edges indicate that these are not shock fronts. The pressure is reasonably continuous across these edges, while the entropy jumps in the opposite sense to that in a shock (i.e. the denser side of the edge has lower temperature, and hence lower entropy). Most plausibly, these edges delineate the dense subcluster cores that have survived a merger and ram pressure stripping by the surrounding shock-heated gas.

We present multiband photometry of 185 type-Ia supernovae (SNe Ia), with over 11,500 observations. These were acquired between 2001 and 2008 at the F. L. Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics (CfA). This sample contains the largest number of homogeneously observed and reduced nearby SNe Ia (z 0.08) published to date. It more than doubles the nearby sample, bringing SN Ia cosmology to the point where systematic uncertainties dominate. Our natural system photometry has a precision of 0.02 mag in BV RI r i and 0.04 mag in U for points brighter than 17.5 mag. We also estimate a systematic uncertainty of 0.03 mag in our SN Ia standard system BV RI r i photometry and 0.07 mag for U. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars, where available for the same SN, reveal agreement at the level of a few hundredths mag in most cases. We find that 1991bg-like SNe Ia are sufficiently distinct from other SNe Ia in their color and light-curve-shape/ luminosity relation that they should be treated separately in light-curve/distance fitter training samples. The CfA3 sample will contribute to the development of better light-curve/distance fitters, particularly in the few dozen cases where near-infrared photometry has been obtained and, together, can help disentangle host-galaxy reddening from intrinsic supernova color, reducing the systematic uncertainty in SN Ia distances due to dust.

Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ dysfunction, age, genetics) and extrinsic (e.g., drug-drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision-making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool.

We present 1210 Johnson/Cousins B, V , R, and I photometric observations of 22 recent Type Ia supernovae (SNe Ia) : SNe 1993ac, 1993ae, 1994M, 1994S, 1994T, 1994Q, 1994ae, 1995D, 1995E, 1995al, 1995ac, 1995ak, 1995bd, 1996C, 1996X, 1996Z, 1996ab, 1996ai, 1996bk, 1996bl, 1996bo, and 1996bv. Most of the photometry was obtained at the Fred Lawrence Whipple Observatory of the HarvardSmithsonian Center for Astrophysics in a cooperative observing plan aimed at improving the database for SNe Ia. The redshifts of the sample range from cz \ 1200 to 37,000 km s~1 with a mean of cz \ 7000 km s~1.

The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells including biosynthesis, cell signaling, and oxidative protection. Herein, we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux, that selectively and potently targets the amino acid transporter ASCT2 (SLC1A5). Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated cancer cell growth and proliferation, increased cell death, and increased oxidative stress, which collectively, contributed to anti-tumor responses in vitro and in vivo. Representing a new class of targeted therapy, this is the first study to demonstrate the utility of a pharmacological inhibitor of glutamine transport in oncology, laying a framework for paradigm-shifting therapies targeting cancer cell metabolism.