Gamma-Ray Bursts in Circumstellar Shells: A Possible Explanation for Flares

It is now generally accepted that long-duration gamma ray bursts (GRBs) are due to the collapse of massive rotating stars. The precise collapse process itself, however, is not yet fully understood. Strong winds, outbursts, and intense ionizing UV radiation from single stars or strongly interacting binaries are expected to destroy the molecular cloud cores that give birth to them and create highly complex circumburst environments for the explosion. Such environments might imprint features on GRB light curves that uniquely identify the nature of the progenitor and its collapse. We have performed numerical simulations of realistic environments for a variety of long-duration GRB progenitors with ZEUS-MP, and have developed an analytical method for calculating GRB light curves in these profiles. Though a full, three-dimensional, relativistic magnetohydrodynamical computational model is required to precisely describe the light curve from a GRB in complex environments, our method can provide a qualitative understanding of these phenomena. We find that, in the context of the standard afterglow model, massive shells around GRBs produce strong signatures in their light curves, and that this can distinguish them from those occurring in uniform media or steady winds. These features can constrain the mass of the shell and the properties of the wind before and after the ejection. Moreover, the interaction of the GRB with the circumburst shell is seen to produce features that are consistent with observed X-ray flares that are often attributed to delayed energy injection by the central engine. Our algorithm for computing light curves is also applicable to GRBs in a variety of environments such as those in high-redshift cosmological halos or protogalaxies, both of which will soon be targets of future surveys such as JANUS or Lobster.Comment: 12 pages, 5 figures, Accepted by Ap

Radiation Hydrodynamical Instabilities in Cosmological and Galactic Ionization Fronts

Ionization fronts, the sharp radiation fronts behind which H/He ionizing photons from massive stars and galaxies propagate through space, were ubiquitous in the universe from its earliest times. The cosmic dark ages ended with the formation of the first primeval stars and galaxies a few hundred Myr after the Big Bang. Numerical simulations suggest that stars in this era were very massive, 25 - 500 solar masses, with H II regions of up to 30,000 light-years in diameter. We present three-dimensional radiation hydrodynamical calculations that reveal that the I-fronts of the first stars and galaxies were prone to violent instabilities, enhancing the escape of UV photons into the early intergalactic medium (IGM) and forming clumpy media in which supernovae later exploded. The enrichment of such clumps with metals by the first supernovae may have led to the prompt formation of a second generation of low-mass stars, profoundly transforming the nature of the first protogalaxies. Cosmological radiation hydrodynamics is unique because ionizing photons coupled strongly to both gas flows and primordial chemistry at early epochs, introducing a hierarchy of disparate characteristic timescales whose relative magnitudes can vary greatly throughout a given calculation. We describe the adaptive multistep integration scheme we have developed for the self-consistent transport of both cosmological and galactic ionization fronts.Comment: 6 pages, 4 figures, accepted for proceedings of HEDLA2010, Caltech, March 15 - 18, 201

"I'm a bit concerned" - early actions and psychological constructions in a child protection helpline

This article analyzes early actions in 50 calls reporting cases of abuse to a national child protection helpline in the UK (the National Society for the Prevention of Cruelty to Children Helpline, NSPCC). It focuses on the early turns in the caller's reason for call, in particular, a class of constructions in which the caller describes himself or herself as "concerned about x" (or similar). Analysis of the corpus of calls suggests concern constructions are canonical early elements of the reason-for-call sequence. Concern constructions (a) are oriented to a pre-move in the caller's reason for call, (b) project the unpacking of concerns in a way oriented to the NSPCCs institutional role, (c) attend to epistemological asymmetries between caller and call taker and remove the requirement for disaffiliative next actions such as asking for the basis of claims, (d) provide a way for the Child Protection Officer to take abuse claims seriously while not presupposing their truth, and (e) display an appropriate caller stance. These observations are supported by an analysis of deviant cases. The broader implications of this study for the relation between psychology, interaction, and institutions are discussed

Level of understanding of co-trimoxazole use among HIV infected, recurrent pulmonary tuberculosis suspects at a national referral tuberculosis clinic in Kampala, Uganda: a qualitative analysis.

Background: Co-trimoxazole use is the standard of care for preventing Pneumocystis jirovecii pneumonia in sub-Saharan Africa but implementation remains slow. Co-trimoxazole is self- administered with uncertain adherence. Knowledge of co-trimoxazole use among HIV infected persons is unknown.Objectives: To assess knowledge, attitudes and practices of co-trimoxazole use among HIV infected adults evaluated for recurrent PTB in Kampala, Uganda.Methods: A qualitative study utilizing 5 focus group discussions among 30 HIV infected PTB suspects at the national referral tuberculosis treatment centre in Kampala.Results: Males and females had similar median ages. 80% were currently on co-trimoxazole and 50% of participants were on HAART. Majority of participants defined co-trimoxazole as an analgesic. Few noted co-trimoxazole was a drug to treat cough and chest pain. However, few responses revealed that co-trimoxazole prevents opportunistic diseases among PLHIV. Most of participants believed HAART and anti-TB drugs work as co-trimoxazole thus it should not be taken together with them. This belief may lead to increased risk of opportunistic infections, morbidity and mortality.Conclusions: We revealed gaps in understanding of co-trimoxazole use among study participants. We therefore recommend that more facts about co-trimoxazle as prophylaxis against P. jirovecii, bacterial and diarrheal pathogens should be incorporated in VCT fact sheets.Key words: Recurrent tuberculosis; HIV; Co-trimoxazole use; Chemoprophylaxis; Adherenc

AGI-134: a fully synthetic alpha-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models

Background: Treatments that generate T cell-mediated immunity to a patient\u27s unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galalpha1-3Galbeta1-4GlcNAc (alpha-Gal) in situ leading to opsonization with pre-existing natural anti-alpha-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity. Methods: Various immunological effects of coating tumor cells with alpha-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (alpha1,3GT(-/-)) mice. CDC and phagocytosis data were analyzed by one-way ANOVA, ADCC results by paired t-test, distal tumor growth by Mantel-Cox test, C5a data by Mann-Whitney test, and single tumor regression by repeated measures analysis. Results: In vitro, alpha-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8alpha+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in alpha1,3GT(-/-) mice, intratumoral AGI-134 administration leads to primary tumor regression and has a robust abscopal effect, i.e., it protects from the development of distal, uninjected lesions. Combinations of AGI-134 and anti-PD-1 antibody shows a synergistic benefit in protection from secondary tumor growth. Conclusions: We have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment

The First Stars

We review recent theoretical results on the formation of the first stars in the universe, and emphasize related open questions. In particular, we discuss the initial conditions for Population III star formation, as given by variants of the cold dark matter cosmology. Numerical simulations have investigated the collapse and the fragmentation of metal-free gas, showing that the first stars were predominantly very massive. The exact determination of the stellar masses, and the precise form of the primordial initial mass function, is still hampered by our limited understanding of the accretion physics and the protostellar feedback effects. We address the importance of heavy elements in bringing about the transition from an early star formation mode dominated by massive stars, to the familiar mode dominated by low mass stars, at later times. We show how complementary observations, both at high redshifts and in our local cosmic neighborhood, can be utilized to probe the first epoch of star formation.Comment: 38 pages, 10 figures, draft version for 2004 Annual Reviews of Astronomy and Astrophysics, high-resolution version available at http://cfa-www.harvard.edu/~vbromm

Indoor Inertial Waypoint Navigation for the Blind

Indoor navigation technology is needed to support seamless mobility for the visually impaired. This paper describes the construction and evaluation of an inertial dead reckoning navigation system that provides real-time auditory guidance along mapped routes. Inertial dead reckoning is a navigation technique coupling step counting together with heading estimation to compute changes in position at each step. The research described here outlines the development and evaluation of a novel navigation system that utilizes information from the mapped route to limit the problematic error accumulation inherent in traditional dead reckoning approaches. The prototype system consists of a wireless inertial sensor unit, placed at the users’ hip, which streams readings to a smartphone processing a navigation algorithm. Pilot human trials were conducted assessing system efficacy by studying route-following performance with blind and sighted subjects using the navigation system with real-time guidance, versus offline verbal directions