2,779 research outputs found
Performance Qualification Test of the ISS Water Processor Assembly (WPA) Expendables
The Water Processor Assembly (WPA) for use on the International Space Station (ISS) includes various technologies for the treatment of waste water. These technologies include filtration, ion exchange, adsorption, catalytic oxidation, and iodination. The WPA hardware implementing portions of these technologies, including the Particulate Filter, Multifiltration Bed, Ion Exchange Bed, and Microbial Check Valve, was recently qualified for chemical performance at the Marshall Space Flight Center. Waste water representing the quality of that produced on the ISS was generated by test subjects and processed by the WPA. Water quality analysis and instrumentation data was acquired throughout the test to monitor hardware performance. This paper documents operation of the test and the assessment of the hardware performance
Gaussian Process Modelling for Improved Resolution in Faraday Depth Reconstruction
The incomplete sampling of data in complex polarization measurements from
radio telescopes negatively affects both the rotation measure (RM) transfer
function and the Faraday depth spectra derived from these data. Such gaps in
polarization data are mostly caused by flagging of radio frequency interference
and their effects worsen as the percentage of missing data increases. In this
paper we present a novel method for inferring missing polarization data based
on Gaussian processes (GPs). Gaussian processes are stochastic processes that
enable us to encode prior knowledge in our models. They also provide a
comprehensive way of incorporating and quantifying uncertainties in regression
modelling. In addition to providing non-parametric model estimates for missing
values, we also demonstrate that Gaussian process modelling can be used for
recovering rotation measure values directly from complex polarization data, and
that inferring missing polarization data using this probabilistic method
improves the resolution of reconstructed Faraday depth spectra.Comment: 16 pages, 10 figures, submitted to MNRA
Analysis of whole exome sequencing with cardiometabolic traits using family-based linkage and association in the IRAS Family Study
Family-based methods are a potentially powerful tool to identify trait-defining genetic variants in extended families, particularly when used to complement conventional association analysis. We utilized two-point linkage analysis and single variant association analysis to evaluate whole exome sequencing (WES) data from 1,205 Hispanic Americans (78 families) from the Insulin Resistance Atherosclerosis Family Study. WES identified 211,612 variants above the minor allele frequency threshold of ≥0.005. These variants were tested for linkage and/or association with 50 cardiometabolic traits after quality control checks. Two-point linkage analysis yielded 10,580,600 LOD scores with 1,148 LOD scores ≥3, 183 LOD scores ≥4, and 29 LOD scores ≥5. The maximal novel LOD score was 5.50 for rs2289043:T\u3eC, in UNC5C with subcutaneous adipose tissue volume. Association analysis identified 13 variants attaining genome-wide significance (pT in APOA5, and triglyceride levels (p=3.67×10-10). Overall, there was a 5.2-fold increase in the number of informative variants detected by WES compared to exome chip analysis in this population, nearly 30% of which were novel variants relative to dbSNP build 138. Thus, integration of results from two-point linkage and single-variant association analysis from WES data enabled identification of novel signals potentially contributing to cardiometabolic traits
Targeted online liquid chromatography electron capture dissociation mass spectrometry for the localization of sites of in vivo phosphorylation in human Sprouty2
We demonstrate a strategy employing collision-induced dissociation for phosphopeptide discovery, followed by targeted electron capture dissociation (ECD) for site localization. The high mass accuracy and low background noise of the ECD mass spectra allow facile sequencing of coeluting isobaric phosphopeptides, with up to two isobaric phosphopeptides sequenced from a single mass spectrum. In contrast to the previously described neutral loss of dependent ECD method, targeted ECD allows analysis of both phosphotyrosine peptides and lower abundance phosphopeptides. The approach was applied to phosphorylation analysis of human Sprouty2, a regulator of receptor tyrosine kinase signaling. Fifteen sites of phosphorylation were identified, 11 of which are novel
Exome Sequencing Identifies Genetic Variants Associated with Circulating Lipid Levels in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study (IRASFS)
Genome-wide association studies have identified numerous variants associated with lipid levels; yet, the majority are located in non-coding regions with unclear mechanisms. In the Insulin Resistance Atherosclerosis Family Study (IRASFS), heritability estimates suggest a strong genetic basis: low-density lipoprotein (LDL, h2 = 0.50), high-density lipoprotein (HDL, h2 = 0.57), total cholesterol (TC, h2 = 0.53), and triglyceride (TG, h2 = 0.42) levels. Exome sequencing of 1,205 Mexican Americans (90 pedigrees) from the IRASFS identified 548,889 variants and association and linkage analyses with lipid levels were performed. One genome-wide significant signal was detected in APOA5 with TG (rs651821, PTG = 3.67 × 10−10, LODTG = 2.36, MAF = 14.2%). In addition, two correlated SNPs (r2 = 1.0) rs189547099 (PTG = 6.31 × 10−08, LODTG = 3.13, MAF = 0.50%) and chr4:157997598 (PTG = 6.31 × 10−08, LODTG = 3.13, MAF = 0.50%) reached exome-wide significance (P \u3c 9.11 × 10−08). rs189547099 is an intronic SNP in FNIP2 and SNP chr4:157997598 is intronic in GLRB. Linkage analysis revealed 46 SNPs with a LOD \u3e 3 with the strongest signal at rs1141070 (LODLDL = 4.30, PLDL = 0.33, MAF = 21.6%) in DFFB. A total of 53 nominally associated variants (P \u3c 5.00 × 10−05, MAF ≥ 1.0%) were selected for replication in six Mexican-American cohorts (N = 3,280). The strongest signal observed was a synonymous variant (rs1160983, PLDL = 4.44 × 10−17, MAF = 2.7%) in TOMM40. Beyond primary findings, previously reported lipid loci were fine-mapped using exome sequencing in IRASFS. These results support that exome sequencing complements and extends insights into the genetics of lipid levels
Immunometabolic Signatures Predict Risk of Progression to Active Tuberculosis and Disease Outcome
Fibrotic idiopathic interstitial lung disease: the molecular and cellular key players.
Interstitial lung disease (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma culminating into inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies, can be di-vided into two groups: ILDs that have a known cause and those where the cause is unknown clas-sified as Idiopathic Interstitial Pneumonia (IIPs). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), Acute interstitial pneumonia (AIP), Desquamative Interstitial Pneumonia (DIP), Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review our aim is to de-scribe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung disease without known cause, would contribute to give a more accurate diagnosis to the patients, that would translate in a more effective treatment decision
The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.
In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies
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Loss of CD103+ DCs and Mucosal IL-17+ and IL-22+ Lymphocytes is Associated with Mucosal Damage in SIV Infection
HIV/SIV disease progression is associated with multifocal damage to the GI tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of IL-17-producing lymphocytes, cells that microarray analysis showed express genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ DCs after SIV infection which associated with loss of IL-17 and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and co-culture of CD103+ DCs and naïve T-cells led to increased IL17A and RORc expression in differentiating T-cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis
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