Problems Associated with Making Mechanical Measurements on Water–Ice at Quasistatic and Dynamic Strain Rates

Abstract: Space penetrators are a potential method of inserting instrumentation onto ice-covered bodies in the solar system. Part of a study to see whether this is feasible involves numerically simulating impact of the penetrator into ice at impact velocities of a few 100 m/s. In order to do this accurately, it is necessary to have a constitutive model for water ice that is valid at the strain rates and temperatures relevant to impact in the Outer Solar System. This paper reports certain issues and difficulties that arose during a study to obtain this data

Characterization of Cre recombinase models for the study of adipose tissue

The study of adipose tissue in vivo has been significantly advanced through the use of genetic mouse models. While the aP2-CreBI and aP2-CreSalk lines have been widely used to target adipose tissue, the specificity of these lines for adipocytes has recently been questioned. Here we characterize Cre recombinase activity in multiple cell populations of the major adipose tissue depots of these and other Cre lines using the membrane-Tomato/membrane-GFP (mT/mG) dual fluorescent reporter. We find that the aP2-CreBI and aP2-CreSalk lines lack specificity for adipocytes within adipose tissue, and that the aP2-CreBI line does not efficiently target adipocytes in white adipose depots. Alternatively, the Adiponectin-CreERT line shows high efficiency and specificity for adipocytes, while the PdgfRα-CreERUCL and PdgfRα-CreERJHU lines do not efficiently target adipocyte precursor cells in the major adipose depots. Instead, we show that the PdgfRα-Cre line is preferable for studies targeting adipocyte precursor cells in vivo

Dose-response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trial

Objective: To investigate whether a dose-response relationship existed between exercise and subjective sleep quality in postmenopausal women. This objective represents a post hoc assessment that was not previously considered. Design: Parallel-group randomised controlled trial. Setting: Clinical exercise physiology laboratory in Dallas, Texas. Participants: 437 sedentary or overweight/obese postmenopausal women. Intervention: Participants were randomised to one of four treatments, each of 6 months of duration: a non-exercise control treatment (n=92) or one of three dosages of moderate-intensity exercise (50% of VO2peak), designed to meet 50% (n=151), 100% (n=99) or 150% (n=95) of the National Institutes of Health Consensus Development Panel physical activity recommendations. Exercise dosages were structured to elicit energy expenditures of 4, 8 or 12 kilocalories per kilogram of body weight per week (KKW), respectively. Analyses were intent to treat. Primary outcome measures: Continuous scores and odds of having significant sleep disturbance, as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale. Outcome assessors were blinded to participate radomisation assignment. Results: Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group (control: -2.09 (95% CI -4.58 to 0.40), 4 KKW: -3.93 (-5.87 to -1.99), 8 KKW: -4.06 (-6.45 to -1.67), 12 KKW: -6.22 (-8.68 to -3.77); p=0.04), with a significant dose-response trend observed (p=0.02). Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control (4 KKW: OR 0.37 (95% CI 0.19 to 0.73), 8 KKW: 0.36 (0.17 to 0.77), 12 KKW: 0.34 (0.16 to 0.72)). The magnitude of weight loss did not differ between treatment conditions. Improvements in sleep quality were not related to changes in body weight, resting parasympathetic control or cardiorespiratory fitness. Conclusion: Exercise training induced significant improvement in subjective sleep quality in postmenopausal women, with even a low dose of exercise resulting in greatly reduced odds of having significant sleep disturbance

Using automated voice messages linked to telephone counselling to increase post-menstrual regulation contraceptive uptake and continuation in Bangladesh: study protocol for a randomised controlled trial.

BACKGROUND: Adoption of modern contraceptive methods after menstrual regulation (MR) is thought to reduce subsequent unwanted pregnancy and abortion. Long-acting reversible contraceptives (LARCs) are highly effective at reducing unintended pregnancy, but uptake in Bangladesh is low. Providing information on the most effective methods of contraception increases uptake of more effective methods. This protocol describes a randomised controlled trial of an intervention delivered by mobile phone designed to support post-MR contraceptive use in Bangladesh. METHODS: This is a multi-site single blind individual randomised controlled trial. At least 960 women undergoing MR procedures at selected facilities will be recruited after their procedure by female research assistants. Women will be randomised into the control or intervention group with a 1:1 ratio. All participants will receive usual clinic care, including contraceptive counselling and the telephone number of a non-toll-free call centre which provides counselling on MR and contraception. During the 4 months after their MR procedure, intervention participants will be sent 11 recorded interactive voice messages to their mobile phone about contraception with a focus on their chosen method and LARCs. Each message allows the participant to connect directly to the call centre. The intervention is free to the user. The control group will receive no messages delivered by mobile phone. All participants will be asked to complete an in-person questionnaire at recruitment and follow-up questionnaires by telephone at 2 weeks, 4 months and 12 months after their MR. The primary outcome for the trial will be self-reported LARC use 4 months post-MR. Secondary outcomes include LARC use at 2 weeks and 12 months post-MR, use of any effective modern contraceptive method at 2 weeks, 4 months and 12 months post-MR, and contraceptive discontinuation, contraceptive method switching, pregnancy, subsequent MR and experience of violence during the 12 month study period. DISCUSSION: Mobile phones offer a low-cost mechanism for providing individualised support to women with contraception outside of the clinic setting. This study will provide information on the effects of such an intervention among MR clients in Bangladesh. TRIAL REGISTRATION: Trial registered with clinicaltrials.gov Registration number: NCT02579785 Date of registration: 16th October 2015

Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.

We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level

Coastal Ocean Processes : a science prospectus

CoOP (Coastal Ocean Processes) is an organization meant to study major interdisciplinary scientific problems in the coastal ocean. Its goal is "to obtain a new level of quantitative understanding of the processes that dominate the transformations, transport and fates of biologically, chemically and geologically important matter on the continental margin". Central to obtaining this understanding will be advances in observing and modeling the cross-shelf component of transport. More specific objectives are to understand 1) cross-margin exchanges, 2) air sea exchanges, 3) benthic-pelagic exchanges, 4) terrestrial inputs and 5) biological and chemical transformations within the water column. CoOP research will be carried out primarly through a series of process-oriented field studies, each involving about two years of measurements. Each of these field studies is to be initiated and defined through a community workshop. In addition to the process studies, CoOP will also involve modeling, long time series, exploratory studies, remote sensing, technological innovation, data archiving and communications. A CoOP pilot study has been approved for funding by the National Science Foundation, and funding will begin in 1992. The CoOP science effort is thus already underway.Funding was provided by the National Science Foundation under Grant No. OCE-9108993

The First International Mini-Symposium on Methionine Restriction and Lifespan

It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met) ingestion by rats extends lifespan (Orentreich et al., 1993). Since then, several studies have replicated the effects of dietary methionine restricted (MR) in delaying age-related diseases (Richie et al., 1994; Miller et al., 2005; Ables et al., 2012; Sanchez-Roman and Barja, 2013). We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY, September 2013. The goals were (1) to gather researchers with an interest in MR and lifespan, (2) to exchange knowledge, (3) to generate ideas for future investigations, and (4) to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH), and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones, and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g., the naked mole rat, Brandt's bat, and Drosophila, in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies (Figure 3)

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease