Discovery of a supernova associated with GRB 031203: SMARTS Optical-Infrared Lightcurves from 0.2 to 92 days

Optical and infrared monitoring of the afterglow site of gamma-ray burst (GRB) 031203 has revealed a brightening source embedded in the host galaxy, which we attribute to the presence of a supernova (SN) related to the GRB ("SN 031203"). We present details of the discovery and evolution of SN 031203 from 0.2 to 92 days after the GRB, derived from SMARTS consortium photometry in I and J bands. A template type Ic lightcurve, constructed from SN 1998bw photometry, is consistent with the peak brightness of SN 031203 although the lightcurves are not identical. Differential astrometry reveals that the SN, and hence the GRB, occurred less than 300 h_71^-1 pc (3-sigma) from the apparent galaxy center. The peak of the supernova is brighter than the optical afterglow suggesting that this source is intermediate between a strong GRB and a supernova.Comment: 11 pages, 3 figures, submitted to ApJ Letter

Role of Dicer Enzyme in the Regulation of Store Operated Calcium Entry (SOCE) in CD4+ T Cells

Background/Aims: Activation of T cell receptors (TCRs) in CD4+ T cells leads to a cascade of signalling reactions including increase of intracellular calcium (Ca2+) levels with subsequent Ca2+ dependent stimulation of gene expression, proliferation, cell motility and cytokine release. The increase of cytosolic Ca2+ results from intracellular Ca2+ release with subsequent activation of store-operated Ca2+ entry (SOCE). Previous studies suggested miRNAs are required for the development and functions of CD4+ T cells. An enzyme called Dicer is required during the process of manufacturing mature miRNAs from the precursor miRNAs. In this study, we explored whether loss of Dicer in CD4+ T cells affects SOCE and thus Ca2+ dependent regulation of cellular functions. Methods: We tested the expression of Orai1 by q-RT-PCR and flow cytometry. Further, we measured SOCE by an inverted phase-contrast microscope with the Incident-light fluorescence illumination system using Fura-2. Intracellular Ca2+ was also measured by flow cytometry using Ca2+ sensitive dye Fluo-4. Results: We found that in Dicer deficient (DicerΔ/Δ) mice Orai1 was downregulated at mRNA and protein level in CD4+ T cells. Further, SOCE was significantly smaller in DicerΔ/Δ CD4+ T cells than in CD4+ T cells isolated from wild-type (Dicerfl/fl) mice. Conclusion: Our data suggest that miRNAs are required for adequate Ca2+ entry into CD4+ T cells and thus triggering of Ca2+ sensitive immune functions

Ab Initio Liquid Hydrogen Muon Cooling Simulations with ELMS in ICOOL

This paper presents new theoretical results on the passage of muons through liquid hydrogen which have been confirmed in a recent experiment. These are used to demonstrate that muon bunches may be compressed by ionisation cooling more effectively than suggested by previous calculations. Muon cooling depends on the differential cross section for energy loss and scattering of muons. We have calculated this cross section for liquid H2 from first principles and atomic data, avoiding traditional assumptions. Thence, 2-D probability maps of energy loss and scattering in mm-scale thicknesses are derived by folding, and stored in a database. Large first-order correlations between energy loss and scattering are found for H2, which are absent in other simulations. This code is named ELMS, Energy Loss & Multiple Scattering. Single particle trajectories may then be tracked by Monte Carlo sampling from this database on a scale of 1 mm or less. This processor has been inserted into the cooling code ICOOL. Significant improvements in 6-D muon cooling are predicted compared with previous predictions based on GEANT. This is examined in various geometries. The large correlation effect is found to have only a small effect on cooling. The experimental scattering observed for liquid H2 in the MUSCAT experiment has recently been reported to be in good agreement with the ELMS prediction, but in poor agreement with GEANT simulation.Comment: 6 pages, 3 figure

Pamela: development of the RF system for a non-relativistic non-scaling FFAG

The PAMELA project(Particle Accelerator For MEdical Applications) currently consists of the design of a particle therapy facility. The project, which is in the design phase, contains Non-Scaling FFAG, particle accelerator capable of rapid beam acceleration, giving a pulse repetition rate of 1kHz, far beyond that of a conventional synchrotron. To realise the repetition rate, a key component of the accelerator is the rf accelerating system. The combination of a high energy gain per turn and a high repetition rate is a significant challenge. In this paper, options for the rf system of the proton ring and the status of development are presented

MicroRNAs control the apoptotic threshold in primed Pluripotent stem cells through regulation of BIM

Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death

P17-04. Targeting HIV peptides to human dendritic cells via CD40 elicits expansion of multi-epitope polyfunctional CD4+ and CD8+ T cells in HIV patients

International audiencen.

GRB 050408: An Atypical Gamma-Ray Burst as a Probe of an Atypical Galactic Environment

The bright GRB 050408 was localized by HETE-II near local midnight, enabling an impressive ground-based followup effort as well as space-based followup from Swift. The Swift data from the X-Ray Telescope (XRT) and our own optical photometry and spectrum of the afterglow provide the cornerstone for our analysis. Under the traditional assumption that the visible waveband was above the peak synchrotron frequency and below the cooling frequency, the optical photometry from 0.03 to 5.03 days show an afterglow decay corresponding to an electron energy index of p_lc = 2.05 +/- 0.04, without a jet break as suggested by others. A break is seen in the X-ray data at early times (at ~12600 sec after the GRB). The spectral slope of the optical spectrum is consistent with p_lc assuming a host-galaxy extinction of A_V = 1.18 mag. The optical-NIR broadband spectrum is also consistent with p = 2.05, but prefers A_V = 0.57 mag. The X-ray afterglow shows a break at 1.26 x 10^4 sec, which may be the result of a refreshed shock. This burst stands out in that the optical and X-ray data suggest a large H I column density of N_HI ~ 10^22 cm^-2; it is very likely a damped Lyman alpha system and so the faintness of the host galaxy (M_V > -18 mag) is noteworthy. Moreover, we detect extraordinarily strong Ti II absorption lines with a column density through the GRB host that exceeds the largest values observed for the Milky Way by an order of magnitude. Furthermore, the Ti II equivalent width is in the top 1% of Mg II absorption-selected QSOs. This suggests that the large-scale environment of GRB 050408 has significantly lower Ti depletion than the Milky Way and a large velocity width (delta v > 200 km/s).Comment: ApJ submitte

MicroRNAs regulate Ca2+ homeostasis in murine embryonic stem cells

MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs due to the deletion of Dicer, which encodes an RNase that is essential for the synthesis of miRNAs. One pathway that stood out was Ca2+ signaling. Interestingly, we found that Dicer-/- ESCs had no difference in basal cytoplasmic Ca2+ levels but were hyperresponsive when Ca2+ import into the endoplasmic reticulum (ER) was blocked by thapsigargin. Remarkably, the increased Ca2+ response to thapsigargin in ESCs resulted in almost no increase in apoptosis and no differences in stress response pathways, despite the importance of miRNAs in the stress response of other cell types. The increased Ca2+ response in Dicer-/- ESCs was also observed during purinergic receptor activation, demonstrating a physiological role for the miRNA regulation of Ca2+ signaling pathways. In examining the mechanism of increased Ca2+ responsiveness to thapsigargin, neither store-operated Ca2+ entry nor Ca2+ clearance mechanisms from the cytoplasm appeared to be involved. Rather, it appeared to involve an increase in the expression of one isoform of the IP3 receptors (Itpr2). miRNA regulation of Itpr2 expression primarily appeared to be indirect, with transcriptional regulation playing a major role. Therefore, the miRNA regulation of Itpr2 expression offers a unique mechanism to regulate Ca2+ signaling pathways in the physiology of pluripotent stem cells

A Cost-Effective Design for a Neutrino Factory

There have been active efforts in the U.S., Europe, and Japan on the design of a Neutrino Factory. This type of facility produces intense beams of neutrinos from the decay of muons in a high energy storage ring. In the U.S., a second detailed Feasibility Study (FS2) for a Neutrino Factory was completed in 2001. Since that report was published, new ideas in bunching, cooling and acceleration of muon beams have been developed. We have incorporated these ideas into a new facility design, which we designate as Study 2B (ST2B), that should lead to significant cost savings over the FS2 design.Comment: 46 pages, 38 figures; to be submitted to Physical Review Special Topics: Accelerators and Beam

How was it for you? Experiences of participatory design in the UK health service

Improving co-design methods implies that we need to understand those methods, paying attention to not only the effect of method choices on design outcomes, but also how methods affect the people involved in co-design. In this article, we explore participants' experiences from a year-long participatory health service design project to develop ‘Better Outpatient Services for Older People’. The project followed a defined method called experience-based design (EBD), which represented the state of the art in participatory service design within the UK National Health Service. A sample of participants in the project took part in semi-structured interviews reflecting on their involvement in and their feelings about the project. Our findings suggest that the EBD method that we employed was successful in establishing positive working relationships among the different groups of stakeholders (staff, patients, carers, advocates and design researchers), although conflicts remained throughout the project. Participants' experiences highlighted issues of wider relevance in such participatory design: cost versus benefit, sense of project momentum, locus of control, and assumptions about how change takes place in a complex environment. We propose tactics for dealing with these issues that inform the future development of techniques in user-centred healthcare design