Thermal-distortion analysis of a spacecraft box truss in geostationary orbit

The Mission to Planet Earth enlists the use of a geostationary platform to support Earth science monitoring instruments. The strongback for a proposed geostationary platform is a deployable box truss that supports two large diameter passive microwave radiometer (PMR) and several other science instruments. A study was performed to estimate the north-south and east-west pointing errors at the mounting locations of the two PMRs due to on-orbit thermal distortions of the main truss. The baseline configuration indicated that the east-west pointing error greatly exceeded the required limits. Primary origins of the pointing errors were identified, and methods for their reduction were discussed. Thermal performance enhancements to the truss structure were modeled and analyzed, including state-of-the-art surface coatings and insulation techniques. Comparisons of the thermal enhancements to the baseline were performed. Results demonstrated that using a thermal enclosure insulating technique reduced external heat fluxes, and distributed those heat fluxes more evenly throughout the structure, sufficiently reducing the pointing error to satisfy pointing accuracy requirements for the PMR's

Predicting Clinical Response to Everolimus in ER+ Breast Cancers Using Machine-Learning

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and 23 patients treated with everolimus to develop and validate an integrative machine learning biomarker of mTOR inhibitor response. Our results show that the machine learning biomarker can successfully distinguish responders from non-responders and can be applied to identify patients that will most likely benefit from everolimus treatment

A conceptual design study for a two-dimensional, electronically scanned thinned array radiometer

A conceptual design for the Two-Dimensional, Electronically Steered Thinned Array Radiometer (ESTAR) is described. This instrument is a synthetic aperture microwave radiometer that operates in the L-band frequency range for the measurement of soil moisture and ocean salinity. Two auxiliary instruments, an 8-12 micron, scanning infrared radiometer and a 0.4-1.0 micron, charge coupled device (CCD) video camera, are included to provided data for sea surface temperature measurements and spatial registration of targets respectively. The science requirements were defined by Goddard Space Flight Center. Instrument and the spacecraft configurations are described for missions using the Pegasus and Taurus launch vehicles. The analyses and design trades described include: estimations of size, mass and power, instrument viewing coverage, mechanical design trades, structural and thermal analyses, data and communications performance assessments, and cost estimation

Seasonal pattern of apoplastic solute accumulation and loss of cell turgor during ripening of Vitis vinifera fruit under field conditions

Using a novel pressure membrane (PM) apparatus for the extraction of apoplastic fluid from field-grown grape (Vitis vinifera L.) berries, our hypothesis that significant apoplast solutes accumulate at the beginning of the ripening process (i.e. veraison), and that this accumulation might contribute to progressive berry softening due to a progressive loss of mesocarp cell turgor pressure (P) was tested. It was necessary to correct the solute potential (Ψs) of fluid collected with the PM for dilution due to the presence of a dead volume in the apparatus, but after correction, the Ψs obtained with the PM agreed with that obtained by low speed centrifugation. A clear decline in fruit apoplastic solute potential (ψSA) began approximately 10 d prior to fruit coloration, and it was found to be coincident with a decline in mesocarp cell P and fruit elasticity (E). By late in fruit development when berry growth ceased (90 d after anthesis), both apoplast and fruit Ψs reached almost –4 MPa. These results support the hypothesis that a decrease in ψSA is responsible for the observed loss in mesocarp cell P, and is the mechanistic cause of berry softening

The predictive role of symptoms in COVID-19 diagnostic models : A longitudinal insight

Acknowledgements 2019nCoV-302 Study Group Members: The NVX-CoV2373-2019nCoV-302 clinical trial was a collective group effort across multiple institutions and locations. Below is a list of sites and staff that significantly contributed to the implementation and conduct of the NVX-CoV2373-2019nCoV-302 clinical trial.Peer reviewe

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of NovavaxPeer reviewedPublisher PD

Safety and efficacy of the NVX-CoV2373 coronavirus disease 2019 vaccine at completion of the placebo-controlled phase of a randomized controlled trial

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods: Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. Clinical Trials Registration: EudraCT, 2020-004123-16

A role for the cell-wall protein silacidin in cell size of the diatom Thalassiosira pseudonana

Diatoms contribute 20% of global primary production and form the basis of many marine food webs. Although their species diversity correlates with broad diversity in cell size, there is also an intraspecific cell-size plasticity due to sexual reproduction and varying environmental conditions. However, despite the ecological significance of the diatom cell size for food-web structure and global biogeochemical cycles, our knowledge about genes underpinning the size of diatom cells remains elusive. Here, a combination of reverse genetics, experimental evolution and comparative RNA8 sequencing analyses enabled us to identify a previously unknown genetic control of cell size in the diatom Thalassiosira pseudonana. In particular, the targeted deregulation of the expression of the cell-wall protein silacidin caused a significant increase in valve diameter. Remarkably, the natural downregulation of the silacidin gene transcript due to experimental evolution under low temperature also correlated with cell-size increase. Our data give first evidence for a genetically controlled regulation of cell size in Thalassiosira pseudonana and possibly other centric diatoms as they also encode the silacidin gene in their genomes

The Formulated Microbicide RC-101 Was Safe and Antivirally Active Following Intravaginal Application in Pigtailed Macaques

Background: RC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported is active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, and is non-toxic and non-inflammatory in cervicovaginal cell culture. Herein, film-formulated RC-101 was assessed for its antiviral activity in vitro, safety in vivo, retention in the cervix and vagina, and ability to remain active against HIV-1 and SHIV after intravaginal application in macaques. Methodology/Principal Findings: RC-101 was formulated as a quick-dissolving film (2000 μg/film), retained complete activity in vitro as compared to unformulated peptide, and was applied intravaginally in six pigtailed macaques daily for four days. At one and four days following the final application, the presence of RC-101 was assessed in peripheral blood, cervicovaginal lavage, cytobrushed cervicovaginal cells, and biopsied cervical and vaginal tissues by quantitative western blots. One day following the last film application, cervical biopsies from RC-101-exposed and placebo-controlled macaques were collected and were subjected to challenge with RT-SHIV in an ex vivo organ culture model. RC-101 peptide was detected primarily in the cytobrush and biopsied cervical and vaginal tissues, with little to no peptide detected in lavage samples, suggesting that the peptide was associated with the cervicovaginal epithelia. RC-101 remained in the tissues and cytobrush samples up to four days post-application, yet was not detected in any sera or plasma samples. RC-101, extracted from cytobrushes obtained one day post-application, remained active against HIV-1 BaL. Importantly, cervical biopsies from RC-101-treated animals reduced RT-SHIV replication in ex vivo organ culture as compared to placebo-treated animals. Conclusions/Significance:Formulated RC-101 was stable in vivo and was retained in the mucosa. The presence of antivirally active RC-101 after five days in vivo suggests that RC-101 would be an important molecule to develop further as a topical microbicide to prevent HIV-1 transmission. © 2010 Cole et al