Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (<200 nm) was greater than large EVs (≥200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs

Comparison of Mixing Characteristics for Several Fuel Injectors at Mach 8, 12, and 15 Hypervelocity Flow Conditions

CFD analysis is presented of the mixing characteristics and performance of three fuel injectors at flight Mach numbers of 8, 12, and 15. The Reynolds-averaged simulations (RAS) were carried out using the VULCAN-CFD solver. The high Mach number flow conditions match those of the experiments conducted as a part of the Enhanced Injection and Mixing Project (EIMP) at the NASA Langley Research Center. The EIMP aims to investigate scramjet fuel injection and mixing physics, improve the understanding of underlying physical processes, and develop enhancement strategies relevant to flight Mach numbers greater than 8. The injectors include a fuel placement device, a strut, and a fluidic vortical mixer, a ramp. These fuel injectors accomplish the necessary task of distributing and mixing fuel into the supersonic cross-flow, albeit via different strategies. For comparison, a flush-wall injector is also included. This type of injector generally represents the simplest method of introducing fuel into a scramjet combustor. The three injectors represent the baseline configurations of the EIMP experiments. The mixing parameters of interest, such as mixing efficiency and total pressure recovery, are computed from the RAS and compared for the three flight conditions and injector configurations. In addition to mixing efficiency and total pressure recovery, the combustion efficiency and thrust potential are also computed for the reacting simulations. Plotting the total pressure recovery and thrust potential as a function of mixing efficiency provides added insight into critical aspects of combustor performance as the flight condition and injector type are varied

Hormonal contraceptive methods and risk of HIV acquisition in women : a systematic review of epidemiological evidence

Peer reviewedPublisher PD

VLBI Images of 49 Radio Supernovae in Arp 220

We have used a Very Long Baseline Interferometry (VLBI) array at 18cm wavelength to image the nucleus of the luminous IR galaxy Arp 220 at ~1 pc linear resolution, and with very high sensitivity. The resulting map has an rms of 5.5 microJy/beam, and careful image analysis results in 49 confirmed point sources ranging in flux density from 1.2 mJy down to ~60 microJy. Comparison with high sensitivity data from 12 months earlier reveals at least four new sources. The favored interpretation of these sources is that they are radio supernovae, and if all new supernovae are detectable at this sensitivity, a resulting estimate of the supernova rate in the Arp 220 system is 4 +/- 2 per year. The implied star formation rate is sufficient to power the entire observed far-infrared luminosity of the galaxy. The two nuclei of Arp 220 exhibit striking similarities in their radio properties, though the western nucleus is more compact, and appears to be ~3 times more luminous than the eastern nucleus. There are also some puzzling differences, and differential free-free absorption, synchrotron aging and expansion losses may all be playing a role. Comparison with the nearby starburst galaxy M82 supports the hypothesis that the activity in Arp 220 is essentially a scaled-up version of that in M82.Comment: 24 pages, 3 figures, 1 table. Accepted for publication in Ap.

Factors Associated With Sustained Use of Long-Lasting Insecticide-Treated Nets Following a Reduction in Malaria Transmission in Southern Zambia

Understanding factors influencing sustained use of long-lasting insecticide-treated nets (LLIN) in areas of declining malaria transmission is critical to sustaining control and may facilitate elimination. From 2008 to 2013, 655 households in Choma District, Zambia, were randomly selected and residents were administered a questionnaire and malaria rapid diagnostic test. Mosquitoes were collected concurrently by light trap. In a multilevel model, children and adolescents of 5-17 years of age were 55% less likely to sleep under LLIN than adults (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.35, 0.58). LLIN use was 80% higher during the rainy season (OR = 1.8; CI = 1.5, 2.2) and residents of households with three or more nets were over twice as likely to use a LLIN (OR = 2.1; CI = 1.4, 3.1). For every increase in 0.5 km from the nearest health center, the odds of LLIN use decreased 9% (OR = 0.9; CI = 0.88, 0.98). In a second multilevel model, the odds of LLIN use were more than twice high if more than five mosquitoes (anopheline and culicine) were captured in the house compared with households with no mosquitoes captured (OR = 2.1; CI = 1.1, 3.9). LLIN use can be sustained in low-transmission settings with continued education and distributions, and may be partially driven by the presence of nuisance mosquitoes

A CD4+ T cell antagonist epitope down-regulates activating signaling proteins, up-regulates inhibitory signaling proteins and abrogates HIV-specific T cell function

BACKGROUND: CD4(+) T cells are critically important in HIV infection, being both the primary cells infected by HIV and likely playing a direct or indirect role in helping control virus replication. Key areas of interest in HIV vaccine research are mechanisms of viral escape from the immune response. Interestingly, in HIV infection it has been shown that peptide sequence variation can reduce CD4(+) T cell responses to the virus, and small changes to peptide sequences can transform agonist peptides into antagonist peptides. RESULTS: We describe, at a molecular level, the consequences of antagonism of HIV p24-specific CD4(+) T cells. Antagonist peptide exposure in the presence of agonist peptide caused a global suppression of agonist-induced gene expression and signaling molecule phosphorylation. In addition to down-regulation of factors associated with T cell activation, a smaller subset of genes associated with negative regulation of cell activation was up-regulated, including KFL-2, SOCS-1, and SPDEY9P. Finally, antagonist peptide in the absence of agonist peptide also delivered a negative signal to T cells. CONCLUSIONS: Small changes in p24-specific peptides can result in T cell antagonism and reductions of both T cell receptor signaling and activation. These changes are at least in part mediated by a dominant negative signal delivered by antagonist peptide, as evidenced by up-regulation of negative regulatory genes in the presence of agonist plus antagonist stimulation. Antagonism can have dramatic effects on CD4(+) T cell function and presents a potential obstacle to HIV vaccine development

Shuttle Gaseous Hydrogen Venting Risk from Flow Control Valve Failure

This paper describes a series of studies to assess the potential risk associated with the failure of one of three gaseous hydrogen flow control valves in the orbiter's main propulsion system during the launch of Shuttle Endeavour (STS-126) in November 2008. The studies focused on critical issues associated with the possibility of combustion resulting from release of gaseous hydrogen from the external tank into the atmosphere during assent. The Shuttle Program currently assumes hydrogen venting from the external tank will result in a critical failure. The current effort was conducted to increase understanding of the risk associated with venting hydrogen given the flow control valve failure scenarios being considered in the Integrated In-Flight Anomaly Investigation being conducted by NASA

Coherent Control of Ballistic Photocurrents in Multilayer Epitaxial Graphene Using Quantum Interference

International audienceWe report generation of ballistic electric currents in unbiased epitaxial graphene at 300 K via quantum interference between phase-controlled cross-polarized fundamental and second harmonic 220 fs pulses. The transient currents are detected via the emitted terahertz radiation. Because of graphene's special structure symmetry, the injected current direction can be well controlled by the polarization of the pump beam in epitaxial graphene. This all optical injection of current provides not only a noncontact way of injecting directional current in graphene but also new insight into optical and transport process in epitaxial graphene

Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p&lt;0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR&lt;0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p&lt;0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p&lt;0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies