Nutritive value for yearling beef steers of pastures of orchardgrass-clover, fescue and midland bermudagrass alone or with fescue or legumes

Midland bermudagrass pastures consisting of Midland bermudagrass or Midland in combination with either tall fescue or legumes were compared to each other and to orchardgrass-clover or tall fescue pastures. The cage-and-strip method was used to determine forage consumption from the beginning of May until the beginning of September during 1975, 1976 and 1977. Yearling beef steers acquired from fall feeder calf sales and weighing an average of approximately 213 kg were used in a put-and-take grazing system. Tester steers were weighed at about 21-day intervals to determine rate of gain. All forage samples were assayed for total N and in vitro digestible dry matter (IVDDM). Estimated total digestible nutrients (ETDN) was calculated from IVDDM. Three years of forage composition and intake data were reduced to polynomial equations describing the regression of ETDN and crude protein (CP) content and the intake of ETDN and CP, on elapsed days of grazing. The regression equations were used to generate predicted percentages of ETDN and CP and consumption of ETDN and CP at monthly intervals beginning on May 1 and extending to September 1. The available forage of all the pastures decreased in ETDN content during the month of May with Mid + N and Mid + legumes forage exhibiting this decline throughout the grazing season. The %ETDN in available Mid + fescue, fescue and OG + clover changed little from June until pasture grazing was terminated. Available Mid + legumes was the only pasture forage to increase in %CP from the beginning of the season, while all other pastures decreased in %CP. However, the decline of %CP in available Mid + N, Mid + fescue, fescue and OG + clover ended during early summer and began to increase. Only the pastures containing Midland forage decreased in CP content in late summer. Consumed Mid + N, Mid + legumes. Mid + fescue and OG + clover forage decreased in ETDN content during May, with Mid + N and Mid + legumes continuing this trend throughout the season. Consumed Mid + fescue and OG + clover increased in %ETDN from July 1 until the animals were taken off. Fescue varied little in the ETDN content of consumed forage. The %CP in consumed Mid + N and Mid + legumes decreased at about the same rate from May 1 to September 1. Consumed Mid + fescue, fescue and OG + clover increased in %CP throughout May. The CP content of consumed Mid + fescue and OG + clover were decreasing at season\u27s end, while consumed fescue forage increased in %CP for the entire season. Animals grazing Mid + fescue and Mid + legumes decreased their DM consumption/day for the entire season with Mid + legumes being consumed at a higher level in the beginning. Only in late spring and late August was Mid + N consumed at a greater level than either of the other two Midland treatments. Fescue DM consumption decreased steadily from May 1 to August 1, while OG + clover forage consumption increased from mid-May until late June preceded by a dramatic decrease. Steer ETDN consumption/day decreased continuously from the beginning for all treatments except OG + clover which increased slowly from mid-May to mid-June followed by a significant decrease through July. Fescue pastures allowed steers to consume levels of CP that were comparable to Mid + legumes without as rapid a decline, while steers on OG + clover increased CP consumption steadily until July when consumption levels decreased drastically. Intake above maintenance data followed the same trends as consumption data. Steer ETDN consumption per unit metabolic weight (gm/day) decreased throughout the season for all treatments. Steers grazing Mid + legumes, Mid + fescue and fescue decreased their CP intake per unit metabolic weight by 25.3, 5 and 11.2 gm/day, respectively, over the course of the grazing season. Mid+N and OG + clover provided more CP consumption in late spring (16.4 gm/day) and early summer (17.8 gm/day, respectively) than any other time. ETDN composition of available forage appeared to be more related to ADO than did CP composition. ADC did not appear to be related to the composition of consumed forage except for Mid + N pastures that demonstrated a rapid decline in both variables. ADG seemed to be most closely related to the consumption of ETDN and less related to CP and DM consumption

Methane Post-Processing and Hydrogen Separation for Spacecraft Oxygen Loop Closure

State-of-the-art life support oxygen recovery technology on the International Space Station is based on the Sabatier reaction where only about half of the oxygen required for the crew is recovered from metabolic carbon dioxide (CO2). The Sabatier reaction produces water as the primary product and methane as a byproduct. Oxygen recovery is constrained by both the limited availability of reactant hydrogen from water electrolysis and Sabatier methane (CH4) being vented as a waste product resulting in a continuous loss of reactant hydrogen. Post-processing methane with the Plasma Pyrolysis Assembly (PPA) to recover this hydrogen has the potential to substantially increase oxygen recovery and thus dramatically reduce the logistical challenges associated with oxygen resupply. The PPA decomposes methane into predominantly hydrogen and acetylene. A purification system is necessary to purify hydrogen before it is recycled back to the Sabatier reactor. Testing and evaluation of acetylene removal systems and PPA system architectures are presented and discussed

Ke Ao: A Low-Cost 1U CubeSat for Aerospace Education and Research in Hawaii

The Ke Ao satellite is a low-cost 1U CubeSat designed and developed by an undergraduate team of engineering students at the University of Hawaii at Manoa (UHM) in collaboration with the Hawaii Space Flight Laboratory (HSFL). The primary goal of the mission is to take one or more pictures from space and automatically identify the Hawaiian Islands using Machine Learning Algorithms - this will demonstrate improved onboard operational autonomy in space. A secondary goal of this project is to promote Aerospace Education and Workforce training in Hawaii. The Ke Ao project was inspired by the Hiapo CubeSat initiative of the Hawaii Science and Technology Museum as a unique platform used to provide engaging meaningful hands-on STEM curriculum for Hawaii students K-12. The realization that low-cost flight hardware, in the order of ～$10k, is practically non-existent, and therefore the barrier to launch a flight-capable CubeSat is still high for small organizations and schools with low budgets. The Ke Ao project started in the Fall of 2019 with the Vertically Integrated Project (VIP) Aerospace Technologies with Electrical, Mechanical, and Computer Science Engineering Students at UH and continued to be facilitated under the Mechanical Engineering Senior Design Course within the College of Engineering throughout the year of 2020. The project was impacted by the global COVID-19 pandemic but this enabled the student team to improve on the design and simulations. Hiapo and Ke Ao also inspired the NASA Artemis CubeSat Kit project being developed at the HSFL. The Artemis CubeSat Kit will be used as an educational tool for teaching aerospace and distribution in the public domain. The development of these three CubeSats allowed for synergistic development and multipurpose designs and gave the students a wide breadth of design experiences. This paper will expand on the design and development for the main objectives for Ke Ao (1) take one or more pictures of the Hawaiian Islands from space; (2) cost shall be no more than$10,000 with built parts; and (3) launch-ready via the NASA CSLI application and requirements. To address these objectives Ke Ao uses spaceflight capable but low-cost hardware flown in previous CubeSat missions and consists of seven primary subsystems: Attitude Determination and Control System, Communications, Electrical Power Systems, On-Board Computer and Flight Software, Payload, Structure and Mechanisms, and Thermal Control Systems. Ke Ao will use onboard magnetic torquers to control the attitude of the payload and take pictures of the Hawaiian Islands. The data will be transmitted to the HSFL ground stations in Hawaii and through the SatNOGS ground station network across the World. Ke Ao’s mission and primary goals are in line with the 2018 NASA Strategic Plan’s Strategic Objective 3.3 to Inspire and Engage the Public in Aeronautics, Space, and Science and contribute to the Nation’s science literacy

NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Cappelli et al. reported that Nitric Oxide Synthase 1 Adaptor Protein is a co-regulated transcript of the TAR DNA-binding protein 43 kDa, reduced in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients with TAR DNA-binding protein 43 kDa pathology. Overall, their results highlight Nitric Oxide Synthase 1 Adaptor Protein as a novel druggable disease-relevant gene in TAR DNA-binding protein 43 kDa-related proteinopathies.Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.MethodsBuilding on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.ResultsA gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10–39; OR = 4.73, p = 2 × 10–10; OR = 2.3, p = 7.49 × 10–9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10–7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10–16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10–6).ConclusionsIn a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers