Downregulation of HLA Class I Renders Inflammatory Neutrophils More Susceptible to NK Cell-Induced Apoptosis

Neutrophils are potent effector cells and contain a battery of harmful substances and degrading enzymes. A silent neutrophil death, i.e., apoptosis, is therefore of importance to avoid damage to the surrounding tissue and to enable termination of the acute inflammatory process. There is a pile of evidence supporting the role for pro-inflammatory cytokines in extending the life-span of neutrophils, but relatively few studies have been devoted to mechanisms actively driving apoptosis induction in neutrophils. We have previously demonstrated that natural killer (NK) cells can promote apoptosis in healthy neutrophils. In this study, we set out to investigate how neutrophil sensitivity to NK cell-mediated cytotoxicity is regulated under inflammatory conditions. Using in vitro-activated neutrophils and a human skin chamber model that allowed collection of in vivo-transmigrated neutrophils, we performed a comprehensive characterization of neutrophil expression of ligands to NK cell receptors. These studies revealed a dramatic downregulation of HLA class I molecules in inflammatory neutrophils, which was associated with an enhanced susceptibility to NK cell cytotoxicity. Collectively, our data shed light on the complex regulation of interactions between NK cells and neutrophils during an inflammatory response and provide further support for a role of NK cells in the resolution phase of inflammation

Monitoring of water content in a porous reservoir by seismic data: A 3D simulation study

A potential framework to estimate the amount of water stored in a porous storage reservoir from seismic data is neural networks. In this study, the water storage reservoir system is modeled as a coupled poroviscoelastic-viscoelastic medium, and the underlying wave propagation problem is solved using a three-dimensional discontinuous Galerkin method coupled with an Adams-Bashforth time stepping scheme. The wave problem solver is used to generate databases for the neural network-based machine learning model to estimate the water content. In the numerical examples, we investigate a deconvolution-based approach to normalize the effect from the source wavelet in addition to the network's tolerance for noise levels. We also apply the SHapley Additive exPlanations method to obtain greater insight into which part of the input data contributes the most to the water content estimation. The numerical results demonstrate the capacity of the fully connected neural network to estimate the amount of water stored in the porous storage reservoir

Changes in physical activity by context and residential greenness among recent retirees : Longitudinal GPS and accelerometer study

This study examined the changes in accelerometer-measured physical activity by GPS-measured contexts among Finnish retirees (n = 45 (537 measurement days)) participating in a physical activity intervention. We also assessed whether residential greenness, measured with Normalized Difference Vegetation Index, moderated the changes. Moderate-to-vigorous physical activity (MVPA) increased at home by 7 min/day, (P < 0.001) and during active travel by 5 min/day (P = 0.03). The participants with the highest vs. lowest greenness had 25 min/ day greater increase in MVPA over the follow-up (P for Time*Greenness interaction = 0.04). In conclusion, retirees participating in the intervention increased their MVPA both at home and in active travel, and more so if they lived in a greener area.Peer reviewe

Multifrequency Observations of the Gamma-Ray Blazar 3C 279 in Low-State during Integral AO-1

We report first results of a multifrequency campaign from radio to hard X-ray energies of the prominent gamma-ray blazar 3C 279 during the first year of the INTEGRAL mission. The variable blazar was found at a low activity level, but was detected by all participating instruments. Subsequently a multifrequency spectrum could be compiled. The individual measurements as well as the compiled multifrequency spectrum are presented. In addition, this 2003 broadband spectrum is compared to one measured in 1999 during a high activity period of 3C 279.Comment: 4 pages including 6 figures, to appear in: 'Proc. of the 5th INTEGRAL Workshop', ESA SP-552, in pres

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration

Zearalenone production and growth in drinking water inoculated with Fusarium graminearum

Production of the mycotoxin zearalenone (ZEN) was examined in drinking water inoculated with Fusarium graminearum. The strain employed was isolated from a US water distribution system. ZEN was purified with an immunoaffinity column and quantified by high-performance liquid chromatography (HPLC) with fluorescence detection. The extracellular yield of ZEN was 15.0 ng l−1. Visual growth was observed. Ergosterol was also indicative of growth and an average of 6.2 μg l−1 was obtained. Other compounds were also detected although remain unidentified. There is no equivalent information available. More work is required on metabolite expression in water as mycotoxins have consequences for human and animal health. The levels detected in this study were low. Water needs to be accepted as a potential source as it attracts high quality demands in terms of purity.Fundação para a Ciência e a Tecnologia (FCT

Estimation of groundwater storage from seismic data using deep learning

We investigate the feasibility of the use of convolutional neural networks to estimate the amount of groundwater stored in the aquifer and delineate water-table level from active-source seismic data. The seismic data to train and test the neural networks are obtained by solving wave propagation in a coupled poroviscoelastic-elastic media. A discontinuous Galerkin method is used to model wave propagation whereas a deep convolutional neural network is used for the parameter estimation problem. In the numerical experiment, the primary unknowns, the amount of stored groundwater and water-table level, are estimated, while the remaining parameters, assumed to be of less of interest, are successfully marginalized in the convolutional neural networks-based solution

Multiwavelength Observations of the Blazar Mrk 421 in December 2002 and January 2003

We report on a multiwavelength campaign on the TeV gamma-ray blazar Markarian (Mrk) 421 performed during December 2002 and January 2003. These target of opportunity observations were initiated by the detection of X-ray and TeV gamma-ray flares with the All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer (RXTE) and the 10 m Whipple gamma-ray telescope.The campaign included observational coverage in the radio (University of Michigan Radio Astronomy Observatory), optical (Boltwood, La Palma KVA 0.6m, WIYN 0.9m), X-ray (RXTE pointed telescopes), and TeV gamma-ray (Whipple and HEGRA) bands. At TeV energies, the observations revealed several flares at intermediate flux levels, peaking between 1 and 1.5 times the flux from the Crab Nebula. While the time averaged spectrum can be fitted with a single power law of photon index Gamma =2.8, we find some evidence for spectral variability. Confirming earlier results, the campaign reveals a rather loose correlation between the X-ray and TeV gamma-ray fluxes. In one case, a very strong X-ray flare is not accompanied by a comparable TeV gamma-ray flare. Although the source flux was variable in the optical and radio bands, the sparse sampling of the optical and radio light curves does not allow us to study the correlation properties in detail. We present a simple analysis of the data with a synchrotron-self Compton model, emphasizing that models with very high Doppler factors and low magnetic fields can describe the data.Comment: Accepted for publication in the Astrophysical Journa

The WEBT Campaign on the Blazar 3C279 in 2006

The quasar 3C279 was the target of an extensive multiwavelength monitoring campaign from January through April 2006, including an optical-IR-radio monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration. In this paper we focus on the results of the WEBT campaign. The source exhibited substantial variability of optical flux and spectral shape, with a characteristic time scale of a few days. The variability patterns throughout the optical BVRI bands were very closely correlated with each other. In intriguing contrast to other (in particular, BL Lac type) blazars, we find a lag of shorter- behind longer-wavelength variability throughout the RVB ranges, with a time delay increasing with increasing frequency. Spectral hardening during flares appears delayed with respect to a rising optical flux. This, in combination with the very steep IR-optical continuum spectral index of ~ 1.5 - 2.0, may indicate a highly oblique magnetic field configuration near the base of the jet. An alternative explanation through a slow (time scale of several days) acceleration mechanism would require an unusually low magnetic field of < 0.2 G, about an order of magnitude lower than inferred from previous analyses of simultaneous SEDs of 3C279 and other FSRQs with similar properties.Comment: Accepted for publication in Ap