A Correlation of Spectral Lag Evolution with Prompt Optical Emission in GRBs?

We report on observations of correlated behavior between the prompt gamma-ray and optical emission from GRB 080319B, which (i) strongly suggest that they occurred within the same astrophysical source region and (ii) indicate that their respective radiation mechanisms were most likely dynamically coupled. Our preliminary results, based upon a new cross-correlation function (CCF) methodology for determining the time-resolved spectral lag, are summarized as follows. First, the evolution in the arrival offset of prompt gamma-ray photon counts between Swift-BAT 15-25 keV and 50-100 keV energy bands (intrinsic gamma-ray spectral lag) appears to be anti-correlated with the arrival offset between prompt 15-350 keV gamma-rays and the optical emission observed by TORTORA (extrinsic optical/gamma-ray spectral lag), thus effectively partitioning the burst into two main episodes at ~T+28+/-2 sec. Second, prompt optical emission is nested within intervals of (a) trivial intrinsic gamma-ray spectral lag (~T+12+-2 and ~T+50+/-2 sec) with (b) discontinuities in the hard to soft evolution of the photon index for a power law fit to 15-150 keV Swift-BAT data (~T+8+/-2 and ~T+48+/-1 sec), both of which coincide with the rise (~T+10+/-1 sec) and decline (~T+50+/-1 sec) of prompt optical emission. This potential discovery, robust across heuristic permutations of BAT energy channels and varying temporal bin resolution, provides the first observational evidence for an implicit connection between spectral lag and the dynamics of shocks in the context of canonical fireball phenomenology.Comment: 5 pages. Adapted from a contribution to the Proceedings of the 2008 Nanjing GRB Conference. Edited by Y. F. Huang, Z. G. Dai and B. Zhan

FAP-1 Association with Fas (Apo-1) Inhibits Fas Expression on the Cell Surface

As revealed by intracellular pools of nonactive Fas (Apo-1), export of Fas to the cell surface is often impaired in human tumors, thereby inactivating Fas ligand-mediated apoptosis. Here, we demonstrate that association with Fas-associated phosphatase 1 (FAP-1) attenuates Fas export to the cell surface. Forced expression of FAP-1 reduces cell surface Fas levels and increases the intracellular pool of Fas within the cytoskeleton network. Conversely, expression of dominant-negative forms of FAP-1, or inhibition of FAP-1 expression by short interfering RNA, efficiently up-regulates surface expression of Fas. Inhibition of Fas surface expression by FAP-1 depends on its association with the C terminus of Fas. Mutation within amino acid 275 results in decreased association with FAP-1 and greater export of Fas to the cell surface in melanomas, normal fibroblasts, or Fas null cells. Identifying the role of FAP-1 in binding to, and consequently inhibition of, Fas export to the cell surface provides novel insight into the mechanism underlying the regulation of Fas trafficking, which is commonly impaired in advanced tumors with FAP-1 overexpression

Cholesterol- and actin-centered view of the plasma membrane: updating the Singer–Nicolson fluid mosaic model to commemorate its 50th anniversary

Two very polarized views exist for understanding the cellular plasma membrane (PM). For some, it is the simple fluid described by the original Singer–Nicolson fluid mosaic model. For others, due to the presence of thousands of molecular species that extensively interact with each other, the PM forms various clusters and domains that are constantly changing and therefore, no simple rules exist that can explain the structure and molecular dynamics of the PM. In this article, we propose that viewing the PM from its two predominant components, cholesterol and actin filaments, provides an excellent and transparent perspective of PM organization, dynamics, and mechanisms for its functions. We focus on the actin-induced membrane compartmentalization and lipid raft domains coexisting in the PM and how they interact with each other to perform PM functions. This view provides an important update of the fluid mosaic model

Applicability of open rainfall data to event-scale urban rainfall-runoff modelling

Rainfall-runoff simulations in urban environments require meteorological input data with high temporal and spatial resolutions. The availability of precipitation data is constantly increasing due to the shift towards more open data sharing. However, the applicability of such data for urban runoff assessments is often unknown. Here, the feasibility of Finnish Meteorological Institute's open rain gauge and open weather radar data as input sources was studied by conducting Storm Water Management Model simulations at a very small (33.5 ha) urban catchment in Helsinki, Finland. In addition to the open data sources, data were also available from two research gauges, one of them located on-site, and from a research radar. The results confirmed the importance of local precipitation measurements for urban rainfall-runoff simulations, implying the suitability of open gauge data to be largely dictated by the gauge's distance from the catchment. Performance of open radar data with 5 min and 1 km' resolution was acceptable in terms of runoff reproduction, albeit peak flows were constantly and flow volumes often underestimated. Gauge adjustment and advection interpolation were found to improve the quality of the radar data, and at least gauge adjustment should be performed when open radar data are used. Finally, utilizing dual-polarization capabilities of radars has a potential to improve rainfall estimates for high intensity storms although more research is still needed. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Super-long single-molecule tracking reveals dynamic-anchorage-induced integrin function

Single-fluorescent-molecule imaging tracking (SMT) is becoming an important tool to study living cells. However, photobleaching and photoblinking (hereafter referred to as photobleaching/photoblinking) of the probe molecules strongly hamper SMT studies of living cells, making it difficult to observe in vivo molecular events and to evaluate their lifetimes (e.g., off rates). The methods used to suppress photobleaching/photoblinking in vitro are difficult to apply to living cells because of their toxicities. Here using 13 organic fluorophores we found that, by combining low concentrations of dissolved oxygen with a reducing-plus-oxidizing system, photobleaching/photoblinking could be strongly suppressed with only minor effects on cells, which enabled SMT for as long as 12,000 frames (~7 min at video rate, as compared to the general 10-s-order durations) with ~22-nm single-molecule localization precisions. SMT of integrins revealed that they underwent temporary (<80-s) immobilizations within the focal adhesion region, which were responsible for the mechanical linkage of the actin cytoskeleton to the extracellular matrix

Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon

Objectives The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. Methods In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. Results At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm3 lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. Conclusions Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy succes

Epigenetic Activation of a Subset of mRNAs by eIF4E Explains Its Effects on Cell Proliferation

BACKGROUND: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5′ cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. METHODOLOGY/PRINCIPAL FINDINGS: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum-mediated apoptosis. CONCLUSIONS/SIGNIFICANCE: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs