Resting respiratory tract dendritic cells preferentially stimulate T helper cell Type 2(Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the “default” T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2–3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-γ by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing– associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor α or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli

Long-Term X-ray Variability in GX 354-0

We report for the first time the detection of long-term X-ray variability in the bright bulge source GX 354-0 (=4U 1728-34) observed with the All Sky Monitor (ASM) on board the Rossi X-Ray Timing Explorer (RXTE). The 2-year RXTE ASM database reveals significant power at ~72 days. Similar behaviour was seen in the 6-year Ariel 5 ASM database, but at a period of ~63 days. The timescales and light curves resemble the ~78 days modulation seen in Cyg X-2 and we therefore interpret this modulation in GX 354-0 as a super-orbital effect.Comment: 9 pages, 3 figures, accepted for publication in New Astronom

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM‐85

Objectives Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways. Here, we aimed to provide proof of concept for a novel solution to reduce the burden and potential long-term sequelae of severe early-life respiratory viral infection through maternal oral treatment during pregnancy with OM-85, already in widespread human clinical use. Methods In this study, we performed flow cytometry and targeted gene expression (RT-qPCR) analysis on lungs from neonatal offspring whose mothers received oral OM-85 treatment during pregnancy. We next determined whether neonatal offspring from OM-85 treated mothers demonstrate enhanced protection against lethal lower respiratory infection with mouse-adapted rhinovirus (vMC0), and associated lung immune changes. Results Offspring from mothers treated with OM-85 during pregnancy display accelerated postnatal seeding of lung myeloid populations demonstrating upregulation of function-associated markers. Offspring from OM-85 mothers additionally exhibit enhanced expression of TLR4/7 and the IL-1β/NLRP3 inflammasome complex within the lung. These treatment effects were associated with enhanced capacity to clear an otherwise lethal respiratory viral infection during the neonatal period, with concomitant regulation of viral-induced IFN response intensity. Conclusion These results demonstrate that maternal OM-85 treatment protects offspring against lethal neonatal respiratory viral infection by accelerating development of innate immune mechanisms crucial for maintenance of local immune homeostasis in the face of pathogen challenge

Using Flow Specifications of Parameterized Cache Coherence Protocols for Verifying Deadlock Freedom

We consider the problem of verifying deadlock freedom for symmetric cache coherence protocols. In particular, we focus on a specific form of deadlock which is useful for the cache coherence protocol domain and consistent with the internal definition of deadlock in the Murphi model checker: we refer to this deadlock as a system- wide deadlock (s-deadlock). In s-deadlock, the entire system gets blocked and is unable to make any transition. Cache coherence protocols consist of N symmetric cache agents, where N is an unbounded parameter; thus the verification of s-deadlock freedom is naturally a parameterized verification problem. Parametrized verification techniques work by using sound abstractions to reduce the unbounded model to a bounded model. Efficient abstractions which work well for industrial scale protocols typically bound the model by replacing the state of most of the agents by an abstract environment, while keeping just one or two agents as is. However, leveraging such efficient abstractions becomes a challenge for s-deadlock: a violation of s-deadlock is a state in which the transitions of all of the unbounded number of agents cannot occur and so a simple abstraction like the one above will not preserve this violation. In this work we address this challenge by presenting a technique which leverages high-level information about the protocols, in the form of message sequence dia- grams referred to as flows, for constructing invariants that are collectively stronger than s-deadlock. Efficient abstractions can be constructed to verify these invariants. We successfully verify the German and Flash protocols using our technique

Real-time monitoring of the silicidation process of tungsten filaments at high temperature used as catalysers for silane decomposition

The scope of this work is the systematic study of the silicidation process affecting tungsten filaments at high temperature (1900ºC) used for silane decomposition in the hot-wire chemical vapour deposition technique (HWCVD). The correlation between the electrical resistance evolution of the filaments, Rfil(t), and the different stages of the their silicidation process is exposed. Said stages correspond to: the rapid formation of two WSi2 fronts at the cold ends of the filaments and their further propagation towards the middle of the filaments; and, regarding the hot central portion of the filaments: a initial stage of silicon dissolution into the tungsten bulk, with a random duration for as-manufactured filaments, followed by the inhomogeneous nucleation of W5Si3 (which is later replaced by WSi2) and its further growth towards the filaments core. An electrical model is used to obtain real-time information about the current status of the filaments silicidation process by simply monitoring their Rfil(t) evolution during the HWCVD process. It is shown that implementing an annealing pre-treatment to the filaments leads to a clearly repetitive trend in the monitored Rfil(t) signatures. The influence of hydrogen dilution of silane on the filaments silicidation process is also discussed

Emoções, “stress”, ansiedade e “coping": estudo qualitativo com treinadores de nível internacional

A influência dos fatores e processos psicológicos no desempenho desportivo dos atletas está, de uma forma geral, amplamente demonstrada; todavia, poucas investigações procuraram estudar esta relação nos treinadores. Neste sentido, empregando uma entrevista semi-estruturada, a presente investigação procurou, junto de seis treinadores de elite com idades compreendidas entre os 55 e os 63 anos (M = 59 ± 3,03) de diversas modalidades, identificar as características/competências psicológicas mais importantes para o sucesso desportivo, as principais fontes de “stress” e ansiedade experienciadas e as estratégias de “coping” a que recorriam em situações estressantes e/ou problemáticas, adicionalmente, pretendeu explorar o papel de outras emoções no seu desempenho. Os resultados revelaram que: 1) a motivação era uma das competências/características psicológicas percepcionadas pelos treinadores como mais importantes para o sucesso; 2) as principais fontes de “stress” estavam relacionadas com preocupações com o desempenho dos atletas, sendo comuns a diferentes modalidades; 3) os treinadores recorriam a diversas estratégias de “coping” em simultâneo, geralmente adaptativas; e 4) para além da ansiedade, outras emoções, positivas e negativas, pareciam influenciar o desempenho dos treinadores.Fundação para a Ciência e Tecnologia (FCT

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types