The effects of discreteness of galactic cosmic rays sources

Most studies of GeV Galactic Cosmic Rays (GCR) nuclei assume a steady state/continuous distribution for the sources of cosmic rays, but this distribution is actually discrete in time and in space. The current progress in our understanding of cosmic ray physics (acceleration, propagation), the required consistency in explaining several GCRs manifestation (nuclei, $\gamma$,...) as well as the precision of present and future space missions (e.g. INTEGRAL, AMS, AGILE, GLAST) point towards the necessity to go beyond this approximation. A steady state semi-analytical model that describes well many nuclei data has been developed in the past years based on this approximation, as well as others. We wish to extend it to a time dependent version, including discrete sources. As a first step, the validity of several approximations of the model we use are checked to validate the approach: i) the effect of the radial variation of the interstellar gas density is inspected and ii) the effect of a specific modeling for the galactic wind (linear vs constant) is discussed. In a second step, the approximation of using continuous sources in space is considered. This is completed by a study of time discreteness through the time-dependent version of the propagation equation. A new analytical solution of this equation for instantaneous point-like sources, including the effect of escape, galactic wind and spallation, is presented. Application of time and space discretness to definite propagation conditions and realistic distributions of sources will be presented in a future paper.Comment: final version, 8 figures, accepted in ApJ. A misprint in fig 8 labels has been correcte

The spin dependence of high energy proton scattering

Motivated by the need for an absolute polarimeter to determine the beam polarization for the forthcoming RHIC spin program, we study the spin dependence of the proton-proton elastic scattering amplitudes at high energy and small momentum transfer.We examine experimental evidence for the existence of an asymptotic part of the helicity-flip amplitude phi_5 which is not negligible relative to the largely imaginary average non-flip amplitude phi_+. We discuss theoretical estimates of r_5, essentially the ratio of phi_5 to phi_+, based upon extrapolation of low and medium energy Regge phenomenological results to high energies, models based on a hybrid of perturbative QCD and non-relativistic quark models, and models based on eikonalization techniques. We also apply the model-independent methods of analyticity and unitarity.The preponderence of evidence at available energy indicates that r_5 is small, probably less than 10%. The best available experimental limit comes from Fermilab E704:those data indicate that |r_5|<15%. These bounds are important because rigorous methods allow much larger values. In contradiction to a widely-held prejudice that r_5 decreases with energy, general principles allow it to grow as fast as ln(s) asymptotically, and some models show an even faster growth in the RHIC range. One needs a more precise measurement of r_5 or to bound it to be smaller than 5% in order to use the classical Coulomb-nuclear interference technique for RHIC polarimetry. As part of this study, we demonstrate the surprising result that proton-proton elastic scattering is self-analysing, in the sense that all the helicity amplitudes can, in principle, be determined experimentally at small momentum transfer without a knowledge of the magnitude of the beam and target polarization

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF

Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

The authors describe a new approach to studying cellular lipid profiles and propose a compensatory mechanism that may help maintain the normal membrane function of adipocytes in the context of obesity

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme