Simultaneous release of a hydroxy-methylglutaryl coenzyme A reductase inhibitor and a glycoprotein IIb/IIIa antagonist from a thermoresponsive NiPAAm/NtBAAm copolymer system.

While deployment of intracoronary stents has been shown to reduce restenosis, stenting can also damage the endothelial was eluted during this period. Xemilofiban release was measured in terms of its ability to inhibit platelet adhesion, using a microfluidic system. To investigate the influence of location and hydrophobicity on elution of bioactivity, three separate systems were employed. While elution of anti-adhesive activity from the system containing xemilofiban-loaded matrices was more dramatic in the short term, a more sustained level of inhibition was achieved when xemilofiban had been incorporated into microgels. All samples investigated for anti-adhesive activity also decreased human coronary artery smooth muscle cell proliferation. Therefore xemilofiban has potential as an agent for preventing in-stent thrombosis. Our study has demonstrated the feasibility of using this novel matrix/microgel system to regulate simultaneous release of both agents in bioactive concentratio

Influence of nutrients and currents on the genomic composition of microbes across an upwelling mosaic

Metagenomic data sets were generated from samples collected along a coastal to open ocean transect between Southern California Bight and California Current waters during a seasonal upwelling event, providing an opportunity to examine the impact of episodic pulses of cold nutrient-rich water into surface ocean microbial communities. The data set consists of ∼5.8 million predicted proteins across seven sites, from three different size classes: 0.1–0.8, 0.8–3.0 and 3.0–200.0 μm. Taxonomic and metabolic analyses suggest that sequences from the 0.1–0.8 μm size class correlated with their position along the upwelling mosaic. However, taxonomic profiles of bacteria from the larger size classes (0.8–200 μm) were less constrained by habitat and characterized by an increase in Cyanobacteria, Bacteroidetes, Flavobacteria and double-stranded DNA viral sequences. Functional annotation of transmembrane proteins indicate that sites comprised of organisms with small genomes have an enrichment of transporters with substrate specificities for amino acids, iron and cadmium, whereas organisms with larger genomes have a higher percentage of transporters for ammonium and potassium. Eukaryotic-type glutamine synthetase (GS) II proteins were identified and taxonomically classified as viral, most closely related to the GSII in Mimivirus, suggesting that marine Mimivirus-like particles may have played a role in the transfer of GSII gene functions. Additionally, a Planctomycete bloom was sampled from one upwelling site providing a rare opportunity to assess the genomic composition of a marine Planctomycete population. The significant correlations observed between genomic properties, community structure and nutrient availability provide insights into habitat-driven dynamics among oligotrophic versus upwelled marine waters adjoining each other spatially

Landsat 9 Thermal Infrared Sensor 2 Architecture and Design

The Thermal Infrared Sensor 2 (TIRS-2) will fly aboard the Landsat 9 spacecraft and leverages the Thermal Infrared Sensor (TIRS) design currently flying on Landsat 8. TIRS-2 will provide similar science data as TIRS, but is not a buildto-print rebuild due to changes in requirements and improvements in absolute accuracy. The heritage TIRS design has been modified to reduce the influence of stray light and to add redundancy for higher reliability over a longer mission life. The TIRS-2 development context differs from the TIRS scenario, adding to the changes. The TIRS-2 team has also learned some lessons along the way

The development of a HAMstring InjuRy (HAMIR) index to mitigate injury risk through innovative imaging, biomechanics, and data analytics : Protocol for an observational cohort study

Background The etiology of hamstring strain injury (HSI) in American football is multi-factorial and understanding these risk factors is paramount to developing predictive models and guiding prevention and rehabilitation strategies. Many player-games are lost due to the lack of a clear understanding of risk factors and the absence of effective methods to minimize re-injury. This paper describes the protocol that will be followed to develop the HAMstring InjuRy (HAMIR) index risk prediction models for HSI and re-injury based on morphological, architectural, biomechanical and clinical factors in National Collegiate Athletic Association Division I collegiate football players. Methods A 3-year, prospective study will be conducted involving collegiate football student-athletes at four institutions. Enrolled participants will complete preseason assessments of eccentric hamstring strength, on-field sprinting biomechanics and muscle–tendon volumes using magnetic-resonance imaging (MRI). Athletic trainers will monitor injuries and exposure for the duration of the study. Participants who sustain an HSI will undergo a clinical assessment at the time of injury along with MRI examinations. Following completion of structured rehabilitation and return to unrestricted sport participation, clinical assessments, MRI examinations and sprinting biomechanics will be repeated. Injury recurrence will be monitored through a 6-month follow-up period. HAMIR index prediction models for index HSI injury and re-injury will be constructed. Discussion The most appropriate strategies for reducing risk of HSI are likely multi-factorial and depend on risk factors unique to each athlete. This study will be the largest-of-its-kind (1200 player-years) to gather detailed information on index and recurrent HSI, and will be the first study to simultaneously investigate the effect of morphological, biomechanical and clinical variables on risk of HSI in collegiate football athletes. The quantitative HAMIR index will be formulated to identify an athlete’s propensity for HSI, and more importantly, identify targets for injury mitigation, thereby reducing the global burden of HSI in high-level American football players. Trial Registration The trial is prospectively registered on ClinicalTrials.gov (NCT05343052; April 22, 2022)

Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells

INTRODUCTION: Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. METHODS: The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. RESULTS: Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. CONCLUSION: By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Landsat 9 TIRS-2 Architecture and Design

No abstract availabl

Landsat 9 TIRS-2 Architecture and Design

TIRS-2 will fly on the LandSat 9. Like TIRS on Landsat 8, TIRS-2 will produce radiometrically calibrated, geo-located thermal image data. USGS is responsible for operational code. TIRS-2 image data will have the same performance characteristics as that of TIRS on Landsat 8 except better in some cases