The Mass of the Convective Zone in FGK Main Sequence Stars and the Effect of Accreted Planetary Material on Apparent Metallicity Determinations

The mass of the outer convective zone in FGK main sequence stars decreases dramatically with stellar mass. Therefore, any contamination of a star's atmosphere by accreted planetary material should affect hotter stars much more than cool stars. If recent suggestions that high metal abundances in stars with planets are caused by planetesimal accretion are correct, then metallicity enhancements in earlier-type stars with planets should be very pronounced. No such trend is seen, however.Comment: Submitted ApJ Letters March 26th; accepted April 30th. 12 pages, 2 figure

The Social and Cultural Context of Coping with Sickle Cell Disease: I. A Review of Biomedical and Psychosocial Issues

Sickle cell disease (SCD) is widely conceived in the United States as a group of blood disorders that principally affect African Americans. Although pain is its principal feature, strokes, lung problems, sepsis, anxiety, depression, impaired social functioning, and maladjustment at work are frequent concomitants. This article selectively reviews biomedical and psychosocial aspects of SCD related to pain assessment, medical treatment, genetic counseling, education, and employment. The strongest support exists for claims of social deficits among adolescents and depression and work-related problems among adults. The social context of SCD, including issues related to socioeconomic status (SES), urbanicity, ethnicity, cultural values, and racial stigmatization, are important to include in empirical assessments and theoretical analyses of the effects of SCD on children and their families. The adverse psychosocial functioning often described as an effect of SCD might indeed be a consequence of these factors acting alone or in concert with the strains of SCD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67048/2/10.1177_0095798499025003002.pd

Ultraintense X-Ray Induced Ionization, Dissociation, and Frustrated Absorption in Molecular Nitrogen

Sequential multiple photoionization of the prototypical molecule N_2 is studied with femtosecond time resolution using the Linac Coherent Light Source (LCLS). A detailed picture of intense x-ray induced ionization and dissociation dynamics is revealed, including a molecular mechanism of frustrated absorption that suppresses the formation of high charge states at short pulse durations. The inverse scaling of the average target charge state with x-ray peak brightness has possible implications for single-pulse imaging applications

Imaging Molecular Structure through Femtosecond Photoelectron Diffraction on Aligned and Oriented Gas-Phase Molecules

This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray Free-Electron Laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C8H5F) and dissociating, laseraligned 1,4-dibromobenzene (C6H4Br2) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.Comment: 24 pages, 10 figures, Faraday Discussions 17

The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Induces Tumor Regression in a Genetically Engineered Mouse Model of PIK3CA Wild-Type Colorectal Cancer

To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC).PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM) model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC(50) = 9.0-14.3 nM). Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01) vs. a 43% decrease (p = 0.008) in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003), no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013).These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC

Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer

PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. Keywords: PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cance

Risk-shifting Through Issuer Liability and Corporate Monitoring

This article explores how issuer liability re-allocates fraud risk and how risk allocation may reduce the incidence of fraud. In the US, the apparent absence of individual liability of officeholders and insufficient monitoring by insurers under-mine the potential deterrent effect of securities litigation. The underlying reasons why both mechanisms remain ineffective are collective action problems under the prevailing dispersed ownership structure, which eliminates the incentives to moni-tor set by issuer liability. This article suggests that issuer liability could potentially have a stronger deterrent effect when it shifts risk to individuals or entities holding a larger financial stake. Thus, it would enlist large shareholders in monitoring in much of Europe. The same risk-shifting effect also has implications for the debate about the relationship between securities litigation and creditor interests. Credi-tors’ claims should not be given precedence over claims of defrauded investors (e.g., because of the capital maintenance principle), since bearing some of the fraud risk will more strongly incentivise large creditors, such as banks, to monitor the firm in jurisdictions where corporate debt is relatively concentrated