An active nutation damper for spacecraft

An active nutation damping device, consisting of an angular accelerometer, a dc-motor-driven flywheel, and associated electronics, developed for spacecraft use is described. This damping system was used on the LAGEOS spacecraft to control nutation buildup during the long coast period (approximately 75 minutes) after the third stage separation. The damper package was evaluated and proven on a three-axis gas-bearing simulator that duplicated the LAGEOS spacecraft critical flight dynamics. In addition, a failure analysis of the damper assembly was performed. Performance of the damper during the LAGEOS flight has confirmed the preflight evaluation and analysis

MOS field-effect-transistor technology

Metal oxide semiconductor field effect transistor circuit development and laminated electronic packaging for computer storage device

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells

CARD 11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKC theta/beta-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKC theta/beta-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells. Through mass spectrometry-based proteomics analysis, we identified multiple constitutive and inducible CARD11 phosphorylation sites in T cells. We demonstrated that a single TCR- or BCR-inducible phosphorylation on Ser 893 in the carboxyl terminus of CARD1 1 prevented the activation of the transcription factor NF-kappa B, the kinase JNK, and the protease MALT1. Moreover, CARD11 Ser(893) phosphorylation sensitized BCR-addicted lymphoma cells to toxicity induced by Bruton's tyrosine kinase (BTK) inhibitors. Phosphorylation of Ser 893 in CARD11 by PKCO controlled the strength of CARD11 scaffolding by impairing the formation of the CBM complex. Thus, PKCO simultaneously catalyzes both stimulatory and inhibitory CARD11 phosphorylation events, which shape the strength of CARD11 signaling in lymphocytes

MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells

The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor kappa B (NF-kappa B) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1 alpha as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-kappa B signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-kappa B activation in lymphocytes and survival of lymphoma cells

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Advancing dendrochronological studies of fire in the United States

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Dendroecology is the science that dates tree rings to their exact calendar year of formation to study processes that influence forest ecology (e.g., Speer 2010 [1], Amoroso et al., 2017 [2]). Reconstruction of past fire regimes is a core application of dendroecology, linking fire history to population dynamics and climate effects on tree growth and survivorship. Since the early 20th century when dendrochronologists recognized that tree rings retained fire scars (e.g., Figure 1), and hence a record of past fires, they have conducted studies worldwide to reconstruct [2] the historical range and variability of fire regimes (e.g., frequency, severity, seasonality, spatial extent), [3] the influence of fire regimes on forest structure and ecosystem dynamics, and [4] the top-down (e.g., climate) and bottom-up (e.g., fuels, topography) drivers of fire that operate at a range of temporal and spatial scales. As in other scientific fields, continued application of dendrochronological techniques to study fires has shaped new trajectories for the science. Here we highlight some important current directions in the United States (US) and call on our international colleagues to continue the conversation with perspectives from other countries

Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703

Using Routinely Collected Administrative Data in Public Health Research: Geocoding Alcohol Outlet Data

We describe our process of geocoding alcohol outlets to create a national longitudinal exposure dataset for Wales, United Kingdom from 2006 to 2011. We investigated variation in the availability of data items and the quality of alcohol outlet addresses held within unitary authorities. We used a standard geocoding method augmented with a manual matching procedure to achieve a fully spatially referenced dataset. We found higher quality addresses are held for outlets based in urban areas, resulting in the automatic geocoding of 68 % of urban outlets, compared to 48 % in rural areas. Missing postcodes and a lack of address structure contributed to a lower geocoding proportion. An urban rural bias was removed with the development of a manual matching procedure. Only one-half of the unitary authorities provided data on on/off sales and opening times, which are important availability factors. The resulting outlet dataset is suitable for contributing to the evidence-base of alcohol availability and alcohol-related harm. Local government should be encouraged to use standardised data fields, including addresses, to enable accurate geocoding of alcohol outlets and facilitate research that aims to prevent alcohol-related harm. Standardising data collection would enable efficient secondary data reuse using record linkage techniques, allowing the retrospective creation and evaluation of population-based natural experiments to provide evidence for policy and practice

Is concern about young people's anti-social behaviour associated with poor health? cross-sectional evidence from residents of deprived urban neighbourhoods

<p><b>Background:</b> Young people in disadvantaged neighbourhoods are often the focus of concerns about anti-social behaviour (ASB). There is inconsistent evidence to support the hypothesis that perceptions of ASB (PASB) are associated with poor health. We ask whether perceptions of young people's ASB are associated with poor health; and whether health, demographic and (psycho)social characteristics can help explain why PASB varies within disadvantaged neighbourhoods (Glasgow, UK).</p> <p><b>Methods:</b> Regression analysis of survey data exploring associations between perceiving teenagers hanging around to be a serious neighbourhood problem and SF-12v2 mental and physical health scores (higher = better), including adjustment for demographic characteristics. Further analysis explored associations with self-reported measures of health service use, psychosocial characteristics of homes and neighbourhoods and social contacts.</p> <p><b>Results:</b> 6008 adults participated (50% response) and 22% (n = 1,332) said teenagers were a serious neighbourhood problem (the most frequently reported local problem). Demographic characteristics associated with perceiving serious teenager problems included regular health service use, age (inverse relationship), financial problems and living with children. Lower SF-12v2 physical health scores were associated with perceiving teenager problems after adjustment for demographic variables (OR 0.98; 95%CI 0.97,0.99; p = < 0.001), whilst adjusted findings for mental health scores were less conclusive (OR 0.99; 95%CI 0.98,1.00; p = 0.103). Further analysis suggested that perceiving teenager problems was more strongly associated with a number of self-reported psychosocial factors: e.g. lacking social support, < weekly family contacts, poor neighbourhood safety, low trust in neighbours, neighbourhood perceived to be a barrier to self-esteem, and neighbourhood decline.</p> <p><b>Conclusions:</b> Given the evidence we found of weak and small associations between PASB and health, we caution against assuming that tackling concern about teenagers' ASB will lead to substantial public health gains in disadvantaged areas. Although the findings do not present a compelling case for making PASB a public health priority, it is still important to address concerns about young people's ASB. Reasons for doing so may include improving social cohesion, reducing fear and isolation, and improving the general quality of people's lives - particularly in neighbourhoods burdened by multiple disadvantages. Future research should evaluate interventions that attempt to reduce PASB in disadvantaged areas. Findings from this study could help inform the targeting of such interventions.</p&gt