239 research outputs found

    Lunar hand tools

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    Tools useful for operations and maintenance tasks on the lunar surface were determined and designed. Primary constraints are the lunar environment, the astronaut's space suit and the strength limits of the astronaut on the moon. A multipurpose rotary motion tool and a collapsible tool carrier were designed. For the rotary tool, a brushless motor and controls were specified, a material for the housing was chosen, bearings and lubrication were recommended and a planetary reduction gear attachment was designed. The tool carrier was designed primarily for ease of access to the tools and fasteners. A material was selected and structural analysis was performed on the carrier. Recommendations were made about the limitations of human performance and about possible attachments to the torque driver

    Wellness and Multiple Sclerosis: The National MS Society Establishes a Wellness Research Working Group and Research Priorities

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    Background: People with multiple sclerosis (MS) have identified “wellness” and associated behaviors as a high priority based on “social media listening” undertaken by the National MS Society (i.e. the Society). Objective: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. Method: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. Results: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society’s Wellness Research Working Group. Conclusion: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences

    Gonadotropin-releasing hormone analogs during chemotherapy for preservation of ovarian function and fertility in premenopausal early breast cancer patients: a systematic review and meta-analysis of individual patient-level data

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    Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient\u2013level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P, .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer

    A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation

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    SummaryCalcium/calmodulin (Ca2+/CaM)-dependent protein kinase II (CaMKII) couples increases in cellular Ca2+ to fundamental responses in excitable cells. CaMKII was identified over 20 years ago by activation dependence on Ca2+/CaM, but recent evidence shows that CaMKII activity is also enhanced by pro-oxidant conditions. Here we show that oxidation of paired regulatory domain methionine residues sustains CaMKII activity in the absence of Ca2+/CaM. CaMKII is activated by angiotensin II (AngII)-induced oxidation, leading to apoptosis in cardiomyocytes both in vitro and in vivo. CaMKII oxidation is reversed by methionine sulfoxide reductase A (MsrA), and MsrA−/− mice show exaggerated CaMKII oxidation and myocardial apoptosis, impaired cardiac function, and increased mortality after myocardial infarction. Our data demonstrate a dynamic mechanism for CaMKII activation by oxidation and highlight the critical importance of oxidation-dependent CaMKII activation to AngII and ischemic myocardial apoptosis

    The Power of Play: A Pediatric Role in Enhancing Development in Young Children

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    Children need to develop a variety of skill sets to optimize their development and manage toxic stress. Research demonstrates that developmentally appropriate play with parents and peers is a singular opportunity to promote the social-emotional, cognitive, language, and self-regulation skills that build executive function and a prosocial brain. Furthermore, play supports the formation of the safe, stable, and nurturing relationships with all caregivers that children need to thrive

    Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Priscu, J. C., Kalin, J., Winans, J., Campbell, T., Siegfried, M. R., Skidmore, M., Dore, J. E., Leventer, A., Harwood, D. M., Duling, D., Zook, R., Burnett, J., Gibson, D., Krula, E., Mironov, A., McManis, J., Roberts, G., Rosenheim, B. E., Christner, B. C., Kasic, K., Fricker, H. A., Lyons, W. B., Barker, J., Bowling, M., Collins, B., Davis, C., Gagnon, A., Gardner, C., Gustafson, C., Kim, O-S., Li, W., Michaud, A., Patterson, M. O., Tranter, M., Ryan Venturelli, R., Trista Vick-Majors, T., & Elsworth, C. Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations. Annals of Glaciology, 62(85–86), (2021): 340–352, https://doi.org/10.1017/aog.2021.10.The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 ÎŒm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.This material is based upon work supported by the US National Science Foundation, Section for Antarctic Sciences, Antarctic Integrated System Science program as part of the interdisciplinary (Subglacial Antarctic Lakes Scientific Access (SALSA): Integrated study of carbon cycling in hydrologically-active subglacial environments) project (NSF-OPP 1543537, 1543396, 1543405, 1543453 and 1543441). Ok-Sun Kim was funded by the Korean Polar Research Institute. We are particularly thankful to the SALSA traverse personnel for crucial technical and logistical support. The United States Antarctic Program enabled our fieldwork; the New York Air National Guard and Kenn Borek Air provided air support; UNAVCO provided geodetic instrument support. Hot water drilling activities, including repair and upgrade modifications of the WISSARD hot water drill system, for the SALSA project were supported by a subaward from the Ice Drilling Program of Dartmouth College (NSF-PLR 1327315) to the University of Nebraska-Lincoln. J. Lawrence assisted with manuscript preparation. Finally, we are grateful to C. Dean, the SALSA Project Manager, and R. Ricards, SALSA Project Coordinator at McMurdo Station, for their organizational skills, and B. Huber of Lamont-Doherty Earth Observatory for providing the SBE39 PT sensors and the Nortek Aquadopp current meter and assisting with interpretation of the data. B. Huber also provided helpful input on programing and calibrating the SBE19PlusV2 6112 CTD

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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