Replacement of Hydrochlorofluorocarbon (HCFC) -225 Solvent for Cleaning and Verification Sampling of NASA Propulsion Oxygen Systems Hardware, Ground Support Equipment, and Associated Test Systems

Since the 1990's, NASA's rocket propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have used hydrochlorofluorocarbon-225 (HCFC-225), a Class II ozone-depleting substance, to safety clean and verify the cleanliness of large scale propulsion oxygen systems and associated test facilities. In 2012 through 2014, test laboratories at MSFC, SSC, and Johnson Space Center-White Sands Test Facility collaborated to seek out, test, and qualify an environmentally preferred replacement for HCFC-225. Candidate solvents were selected, a test plan was developed, and the products were tested for materials compatibility, oxygen compatibility, cleaning effectiveness, and suitability for use in cleanliness verification and field cleaning operations. Honewell Soltice (TradeMark) Performance Fluid (trans-1-chloro-3,3, 3-trifluoropropene) was selected to replace HCFC-225 at NASA's MSFC and SSC rocket propulsion test facilities

CEBS—Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data

CEBS (Chemical Effects in Biological Systems) is an integrated public repository for toxicogenomics data, including the study design and timeline, clinical chemistry and histopathology findings and microarray and proteomics data. CEBS contains data derived from studies of chemicals and of genetic alterations, and is compatible with clinical and environmental studies. CEBS is designed to permit the user to query the data using the study conditions, the subject responses and then, having identified an appropriate set of subjects, to move to the microarray module of CEBS to carry out gene signature and pathway analysis. Scope of CEBS: CEBS currently holds 22 studies of rats, four studies of mice and one study of Caenorhabditis elegans. CEBS can also accommodate data from studies of human subjects. Toxicogenomics studies currently in CEBS comprise over 4000 microarray hybridizations, and 75 2D gel images annotated with protein identification performed by MALDI and MS/MS. CEBS contains raw microarray data collected in accordance with MIAME guidelines and provides tools for data selection, pre-processing and analysis resulting in annotated lists of genes of interest. Additionally, clinical chemistry and histopathology findings from over 1500 animals are included in CEBS. CEBS/BID: The BID (Biomedical Investigation Database) is another component of the CEBS system. BID is a relational database used to load and curate study data prior to export to CEBS, in addition to capturing and displaying novel data types such as PCR data, or additional fields of interest, including those defined by the HESI Toxicogenomics Committee (in preparation). BID has been shared with Health Canada and the US Environmental Protection Agency. CEBS is available at http://cebs.niehs.nih.gov. BID can be accessed via the user interface from https://dir-apps.niehs.nih.gov/arc/. Requests for a copy of BID and for depositing data into CEBS or BID are available at http://www.niehs.nih.gov/cebs-df/

When algorithms shape collective action: Social media and the dynamics of cloud protesting

How does the algorithmically mediated environment of social media restructure social action? This article combines social movement studies and science and technology studies to explore the role of social media in the organization, unfolding, and diffusion of contemporary protests. In particular, it examines how activists leverage the technical properties of social media to develop a joint narrative and a collective identity. To this end, it offers the notion of cloud protesting as a theoretical approach and framework for empirical analysis. Cloud protesting indicates a specific type of mobilization that is grounded on, modeled around, and enabled by social media platforms and mobile devices and the virtual universes they identify. The notion emphasizes both the productive mediation of social and mobile media and the importance of activists’ sense-making activities. It also acknowledges that social media set in motion a process that is sociotechnical in nature rather than merely sociological or communicative, and thus can be understood only by intersecting the material and the symbolic dimensions of contemporary digitally mediated collective action. The article shows how the specific materiality of social media intervenes in the actors’ meaning work by fostering four mechanisms—namely performance, interpellation, temporality, and reproducibility—which concur to create a "politics of visibility" that alters traditional identity dynamics. In addition, it exposes the connection between organizational patterns and the role of individuals, explaining how the politics of visibility is the result of a process that originates and ends within the individual—which ultimately creates individuals-in-the-group rather than groups

Influence of family and friend smoking on intentions to smoke and smoking-related attitudes and refusal self-efficacy among 9-10 year old children from deprived neighbourhoods: a cross-sectional study.

BACKGROUND: Smoking often starts in early adolescence and addiction can occur rapidly. For effective smoking prevention there is a need to identify at risk groups of preadolescent children and whether gender-specific intervention components are necessary. This study aimed to examine associations between mother, father, sibling and friend smoking and cognitive vulnerability to smoking among preadolescent children living in deprived neighbourhoods. METHODS: Cross-sectional data was collected from 9-10 year old children (n =1143; 50.7% girls; 85.6% White British) from 43 primary schools in Merseyside, England. Children completed a questionnaire that assessed their smoking-related behaviour, intentions, attitudes, and refusal self-efficacy, as well as parent, sibling and friend smoking. Data for boys and girls were analysed separately using multilevel linear and logistic regression models, adjusting for individual cognitions and school and deprivation level. RESULTS: Compared to girls, boys had lower non-smoking intentions (P = 0.02), refusal self-efficacy (P = 0.04) and were less likely to agree that smoking is 'definitely' bad for health (P < 0.01). Friend smoking was negatively associated with non-smoking intentions in girls (P < 0.01) and boys (P < 0.01), and with refusal self-efficacy in girls (P < 0.01). Sibling smoking was negatively associated with non-smoking intentions in girls (P < 0.01) but a positive association was found in boys (P = 0.02). Boys who had a smoking friend were less likely to 'definitely' believe that the smoke from other people's cigarettes is harmful (OR 0.57, 95% CI: 0.35 to 0.91, P = 0.02). Further, boys with a smoking friend (OR 0.38, 95% CI: 0.21 to 0.69, P < 0.01) or a smoking sibling (OR 0.45, 95% CI: 0.21 to 0.98) were less likely to 'definitely' believe that smoking is bad for health. CONCLUSION: This study indicates that sibling and friend smoking may represent important influences on 9-10 year old children's cognitive vulnerability toward smoking. Whilst some differential findings by gender were observed, these may not be sufficient to warrant separate prevention interventions. However, further research is needed

A comparison of machine learning algorithms for chemical toxicity classification using a simulated multi-scale data model

<p>Abstract</p> <p>Background</p> <p>Bioactivity profiling using high-throughput <it>in vitro </it>assays can reduce the cost and time required for toxicological screening of environmental chemicals and can also reduce the need for animal testing. Several public efforts are aimed at discovering patterns or classifiers in high-dimensional bioactivity space that predict tissue, organ or whole animal toxicological endpoints. Supervised machine learning is a powerful approach to discover combinatorial relationships in complex <it>in vitro/in vivo </it>datasets. We present a novel model to simulate complex chemical-toxicology data sets and use this model to evaluate the relative performance of different machine learning (ML) methods.</p> <p>Results</p> <p>The classification performance of Artificial Neural Networks (ANN), K-Nearest Neighbors (KNN), Linear Discriminant Analysis (LDA), Naïve Bayes (NB), Recursive Partitioning and Regression Trees (RPART), and Support Vector Machines (SVM) in the presence and absence of filter-based feature selection was analyzed using K-way cross-validation testing and independent validation on simulated <it>in vitro </it>assay data sets with varying levels of model complexity, number of irrelevant features and measurement noise. While the prediction accuracy of all ML methods decreased as non-causal (irrelevant) features were added, some ML methods performed better than others. In the limit of using a large number of features, ANN and SVM were always in the top performing set of methods while RPART and KNN (k = 5) were always in the poorest performing set. The addition of measurement noise and irrelevant features decreased the classification accuracy of all ML methods, with LDA suffering the greatest performance degradation. LDA performance is especially sensitive to the use of feature selection. Filter-based feature selection generally improved performance, most strikingly for LDA.</p> <p>Conclusion</p> <p>We have developed a novel simulation model to evaluate machine learning methods for the analysis of data sets in which in vitro bioassay data is being used to predict in vivo chemical toxicology. From our analysis, we can recommend that several ML methods, most notably SVM and ANN, are good candidates for use in real world applications in this area.</p

Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new <it>in vitro </it>model of NASH.</p> <p>Methods</p> <p>HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured.</p> <p>Results</p> <p>FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species.</p> <p>Conclusions</p> <p>The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH.</p

Stigma and Ebola survivorship in liberia: Results from a longitudinal cohort study

Background Survivors of the 2014–2016 West Africa Ebola epidemic have been reported to suffer high levels of stigmatization after return to their communities. We sought to characterize the stigma encountered by a cohort of Ebola survivors in Liberia over time. Methods Ebola-related stigma was assessed from June 2015 to August 2017 in 299 adolescent and adult Liberian Ebola Survivor Cohort participants at three month intervals using adapted HIV stigma scales scored from 0 to 10 according to the proportion of answers indicating stigmatization. Findings The median time from Ebola Virus Disease (EVD) to study entry was 393 days (IQR 336–492). Participants (43% female) had a median age of 31 (IQR 25–40) years. Mean self-reported stigma levels were greater at baseline (6.28 ± 0.15 [IQR: 4.38–8.75]) compared to the first post-baseline visit (0.60 ± 0.10 [IQR: 0–0]; p<0.0001). During follow-up, stigma levels were stable. Baseline stigma significantly increased during enrollment and following clusters of Ebola re-emergence in Liberia. Survivors encountered primarily enacted and perceived external stigma rather than internalized stigma. Conclusions Ebola-related stigma was prevalent among Liberian survivors more than a year after EVD recovery. Self-reported stigma was greater in the period before cohort enrollment; however, some degree of stigmatization persisted years after EVD. Transient rises in stigma were observed following episodic Ebola re-emergence of EVD in Liberia. During future EVD outbreaks, enhanced public health interventions designed to prevent and mitigate Ebola-related stigma that is enacted and external should be implemented to support survivor recovery and community re-integration

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in ⩾50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC50 values of 2–7 ng ml−1. MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: &lt;65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at &lt;65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients &gt;65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients