1,799 research outputs found

    Activated Protective Fabric

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    Disclosed are fibrous activated materials that can remove and/or deactivate potentially dangerous airborne agents from a gas or air stream. Disclosed materials are multi-layer materials that include a fibrous nonwoven interceptor layer and an active layer immediately adjacent the interceptor layer. The interceptor layer is a fibrous membrane of very low basis weight and defines a relatively low porosity, and the active layer describes geometries, chemistries, etc. that can entrap and/or decontaminate compounds contained in an airstream passing through the material. Disclosed materials can be utilized in forming protective garments, face masks, and the like

    Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial

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    BACKGROUND: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. METHODS: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. CONCLUSION: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events

    Association of protein function-altering variants with cardiometabolic traits:the strong heart study

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    Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencing of American Indians. We tested the association of each SNV/indel with 35 cardiometabolic traits. Among 1206 variants (average minor allele count = 20, range of 1 to 1064), similar to 43% were not present in publicly available repositories. We identified seven SNV-trait significant associations including a missense SNV at ABCA10 (rs779392624, p= 8 x 10(-9)) associated with fasting triglycerides, which gene product is involved in macrophage lipid homeostasis. Among non-diabetic individuals, missense SNVs at four genes were associated with fasting insulin adjusted for BMI (PHIL, chr6:79,650,711, p= 2.1 x 10(-6); TRPM3, rs760461668, p= 5 x10(-8); SPTY2D1, rs756851199, p= 1.6 x 10(-8); and TSPO, rs566547284, p= 2.4 x 10(-6)). PHIL encoded protein is involved in pancreatic beta-cell proliferation and survival, and TRPM3 protein mediates calcium signaling in pancreatic beta-cells in response to glucose. A genetic risk score combining increasing insulin risk alleles of these four genes was associated with 53% (95% confidence interval 1.09, 2.15) increased odds of incident diabetes and 83% (95% confidence interval 1.35, 2.48) increased odds of impaired fasting glucose at follow-up. Our study uncovered novel gene-trait associations through the study of protein-coding variants and demonstrates the advantages of association screenings targeting diverse and high-risk populations to study variants absent in publicly available repositories

    Dynamin I phosphorylation by GSK3 controls activity-dependent bulk endocytosis of synaptic vesicles.

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    Glycogen synthase kinase 3 (GSK3) is a critical enzyme in neuronal physiology; however, it is not yet known whether it has any specific role in presynaptic function. We found that GSK3 phosphorylates a residue on the large GTPase dynamin I (Ser-774) both in vitro and in primary rat neuronal cultures. This was dependent on prior phosphorylation of Ser-778 by cyclin-dependent kinase 5. Using both acute inhibition with pharmacological antagonists and silencing of expression with short hairpin RNA, we found that GSK3 was specifically required for activity-dependent bulk endocytosis (ADBE) but not clathrin-mediated endocytosis. Moreover we found that the specific phosphorylation of Ser-774 on dynamin I by GSK3 was both necessary and sufficient for ADBE. These results demonstrate a presynaptic role for GSK3 and they indicate that a protein kinase signaling cascade prepares synaptic vesicles for retrieval during elevated neuronal activity

    The differential effects of ecstasy/polydrug use on executive components: shifting, inhibition, updating and access to semantic memory

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    Rationale/Objectives Recent theoretical models suggest that the central executive may not be a unified structure. The present study explored the nature of central executive deficits in ecstasy users. Methods In study 1, 27 ecstasy users and 34 non-users were assessed using tasks to tap memory updating (computation span; letter updating) and access to long-term memory (a semantic fluency test and the Chicago Word Fluency Test). In study 2, 51 ecstasy users and 42 non-users completed tasks that assess mental set switching (number/letter and plus/minus) and inhibition (random letter generation). Results MANOVA revealed that ecstasy users performed worse on both tasks used to assess memory updating and on tasks to assess access to long-term memory (C- and S-letter fluency). However, notwithstanding the significant ecstasy group-related effects, indices of cocaine and cannabis use were also significantly correlated with most of the executive measures. Unexpectedly, in study 2, ecstasy users performed significantly better on the inhibition task, producing more letters than non-users. No group differences were observed on the switching tasks. Correlations between indices of ecstasy use and number of letters produced were significant. Conclusions The present study provides further support for ecstasy/polydrug-related deficits in memory updating and in access to long-term memory. The surplus evident on the inhibition task should be treated with some caution, as this was limited to a single measure and has not been supported by our previous work

    T-cell Receptor (TCR)-Peptide Specificity Overrides Affinity-enhancing TCR-Major Histocompatibility Complex Interactions

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    Ī±Ī² T-cell receptors (TCRs) engage antigens using complementarity-determining region (CDR) loops that are either germ line-encoded (CDR1 and CDR2) or somatically rearranged (CDR3). TCR ligands compose a presentation platform (major histocompatibility complex (MHC)) and a variable antigenic component consisting of a short ā€œforeignā€ peptide. The sequence of events when the TCR engages its peptide-MHC (pMHC) ligand remains unclear. Some studies suggest that the germ line elements of the TCR engage the MHC prior to peptide scanning, but this order of binding is difficult to reconcile with some TCR-pMHC structures. Here, we used TCRs that exhibited enhanced pMHC binding as a result of mutations in either CDR2 and/or CDR3 loops, that bound to the MHC or peptide, respectively, to dissect the roles of these loops in stabilizing TCR-pMHC interactions. Our data show that TCR-peptide interactions play a strongly dominant energetic role providing a binding mode that is both temporally and energetically complementary with a system requiring positive selection by self-pMHC in the thymus and rapid recognition of non-self-pMHC in the periphery
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