Large Angle Transient Dynamics (LATDYN) user's manual

A computer code for modeling the large angle transient dynamics (LATDYN) of structures was developed to investigate techniques for analyzing flexible deformation and control/structure interaction problems associated with large angular motions of spacecraft. This type of analysis is beyond the routine capability of conventional analytical tools without simplifying assumptions. In some instances, the motion may be sufficiently slow and the spacecraft (or component) sufficiently rigid to simplify analyses of dynamics and controls by making pseudo-static and/or rigid body assumptions. The LATDYN introduces a new approach to the problem by combining finite element structural analysis, multi-body dynamics, and control system analysis in a single tool. It includes a type of finite element that can deform and rotate through large angles at the same time, and which can be connected to other finite elements either rigidly or through mechanical joints. The LATDYN also provides symbolic capabilities for modeling control systems which are interfaced directly with the finite element structural model. Thus, the nonlinear equations representing the structural model are integrated along with the equations representing sensors, processing, and controls as a coupled system

Tracking the evolution of alternatively spliced exons within the Dscam family

BACKGROUND: The Dscam gene in the fruit fly, Drosophila melanogaster, contains twenty-four exons, four of which are composed of tandem arrays that each undergo mutually exclusive alternative splicing (4, 6, 9 and 17), potentially generating 38,016 protein isoforms. This degree of transcript diversity has not been found in mammalian homologs of Dscam. We examined the molecular evolution of exons within this gene family to locate the point of divergence for this alternative splicing pattern. RESULTS: Using the fruit fly Dscam exons 4, 6, 9 and 17 as seed sequences, we iteratively searched sixteen genomes for homologs, and then performed phylogenetic analyses of the resulting sequences to examine their evolutionary history. We found homologs in the nematode, arthropod and vertebrate genomes, including homologs in several vertebrates where Dscam had not been previously annotated. Among these, only the arthropods contain homologs arranged in tandem arrays indicative of mutually exclusive splicing. We found no homologs to these exons within the Arabidopsis, yeast, tunicate or sea urchin genomes but homologs to several constitutive exons from fly Dscam were present within tunicate and sea urchin. Comparing the rate of turnover within the tandem arrays of the insect taxa (fruit fly, mosquito and honeybee), we found the variants within exons 4 and 17 are well conserved in number and spatial arrangement despite 248–283 million years of divergence. In contrast, the variants within exons 6 and 9 have undergone considerable turnover since these taxa diverged, as indicated by deeply branching taxon-specific lineages. CONCLUSION: Our results suggest that at least one Dscam exon array may be an ancient duplication that predates the divergence of deuterostomes from protostomes but that there is no evidence for the presence of arrays in the common ancestor of vertebrates. The different patterns of conservation and turnover among the Dscam exon arrays provide a striking example of how a gene can evolve in a modular fashion rather than as a single unit

Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (FHP) were compared to 15 young men without a family history of alcoholism (FHN). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148 ± 36 mg/kg/hr, compared to FHN subjects, 124 ± 18 mg/kg/hr, p=.01. However, FHN subjects increased their rate of metabolism by 10 ± 27 percent compared to a decrease of -15 ± 24 percent in FHP subjects, p =.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, p=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence

Adolescent THC Usage in Virginia: Post-Legalization Challenges and Strategies for Schools

Recreational marijuana was legalized for anyone over the age of 21 in Virginia in 2021. This research and policy brief explores evidence of the impact of such legalization on Tetrahydrocannabinol (THC) usage in PK-12 aged youth, including smoking, vaping, edibles, and dabbing. It addresses the following questions: 1) What are the recent trends in marijuana usage among PK-12 aged youth? 2) What are the impacts of THC usage in schools, particularly after legalization? 3) How can schools and school systems effectively respond to THC usage? 4) What are relevant federal, state, and school division policies that guide responses to youth THC usage in the MERC region? It concludes with a series of key takeaways and recommendations for curbing THC usage in schools

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Far-IR/Submillimeter Spectroscopic Cosmological Surveys: Predictions of Infrared Line Luminosity Functions for z<4 Galaxies

Star formation and accretion onto supermassive black holes in the nuclei of galaxies are the two most energetic processes in the Universe, producing the bulk of the observed emission throughout its history. We simulated the luminosity functions of star-forming and active galaxies for spectral lines that are thought to be good spectroscopic tracers of either phenomenon, as a function of redshift. We focused on the infrared (IR) and sub-millimeter domains, where the effects of dust obscuration are minimal. Using three different and independent theoretical models for galaxy formation and evolution, constrained by multi-wavelength luminosity functions, we computed the number of star-forming and active galaxies per IR luminosity and redshift bin. We converted the continuum luminosity counts into spectral line counts using relationships that we calibrated on mid- and far-IR spectroscopic surveys of galaxies in the local universe. Our results demonstrate that future facilities optimized for survey-mode observations, i.e., the Space Infrared Telescope for Cosmology and Astrophysics (SPICA) and the Cerro Chajnantor Atacama Telescope (CCAT), will be able to observe thousands of z>1 galaxies in key fine-structure lines, e.g., [SiII], [OI], [OIII], [CII], in a half-square-degree survey, with one hour integration time per field of view. Fainter lines such as [OIV], [NeV] and H_2 (0-0)S1 will be observed in several tens of bright galaxies at 1<z<2, while diagnostic diagrams of active-nucleus vs star-formation activity will be feasible even for normal z~1 galaxies. We discuss the new parameter space that these future telescopes will cover and that strongly motivate their construction.Comment: Accepted for publication in The Astrophysical Journal on 20/10/2011, 17 pages, 13 figure

Quantitative trait loci associated with longevity of lettuce seeds under conventional and controlled deterioration storage conditions

Lettuce (Lactuca sativa L.) seeds have poor shelf life and exhibit thermoinhibition (fail to germinate) above ∼25°C. Seed priming (controlled hydration followed by drying) alleviates thermoinhibition by increasing the maximum germination temperature, but reduces lettuce seed longevity. Controlled deterioration (CD) or accelerated ageing storage conditions (i.e. elevated temperature and relative humidity) are used to study seed longevity and to predict potential seed lifetimes under conventional storage conditions. Seeds produced in 2002 and 2006 of a recombinant inbred line (RIL) population derived from a cross between L. sativa cv. Salinas×L. serriola accession UC96US23 were utilized to identify quantitative trait loci (QTLs) associated with seed longevity under CD and conventional storage conditions. Multiple longevity-associated QTLs were identified under both conventional and CD storage conditions for control (non-primed) and primed seeds. However, seed longevity was poorly correlated between the two storage conditions, suggesting that deterioration processes under CD conditions are not predictive of ageing in conventional storage conditions. Additionally, the same QTLs were not identified when RIL populations were grown in different years, indicating that lettuce seed longevity is strongly affected by production environment. Nonetheless, a major QTL on chromosome 4 [Seed longevity 4.1 (Slg4.1)] was responsible for almost 23% of the phenotypic variation in viability of the conventionally stored control seeds of the 2006 RIL population, with improved longevity conferred by the Salinas allele. QTL analyses may enable identification of mechanisms responsible for the sensitivity of primed seeds to CD conditions and breeding for improved seed longevity

Return of non-ACMG recommended incidental genetic findings to pediatric patients: Considerations and opportunities from experiences in genomic sequencing

BACKGROUND: The uptake of exome/genome sequencing has introduced unexpected testing results (incidental findings) that have become a major challenge for both testing laboratories and providers. While the American College of Medical Genetics and Genomics has outlined guidelines for laboratory management of clinically actionable secondary findings, debate remains as to whether incidental findings should be returned to patients, especially those representing pediatric populations. METHODS: The Sequencing Analysis and Diagnostic Yield working group in the Clinical Sequencing Evidence-Generating Research Consortium has collected a cohort of pediatric patients found to harbor a genomic sequencing-identified non-ACMG-recommended incidental finding. The incidental variants were not thought to be associated with the indication for testing and were disclosed to patients and families. RESULTS: In total, 23 non-ACMG-recommended incidental findings were identified in 21 pediatric patients included in the study. These findings span four different research studies/laboratories and demonstrate differences in incidental finding return rate across study sites. We summarize specific cases to highlight core considerations that surround identification and return of incidental findings (uncertainty of disease onset, disease severity, age of onset, clinical actionability, and personal utility), and suggest that interpretation of incidental findings in pediatric patients can be difficult given evolving phenotypes. Furthermore, return of incidental findings can benefit patients and providers, but do present challenges. CONCLUSIONS: While there may be considerable benefit to return of incidental genetic findings, these findings can be burdensome to providers and present risk to patients. It is important that laboratories conducting genomic testing establish internal guidelines in anticipation of detection. Moreover, cross-laboratory guidelines may aid in reducing the potential for policy heterogeneity across laboratories as it relates to incidental finding detection and return. However, future discussion is required to determine whether cohesive guidelines or policy statements are warranted

Inequalities in vaccination coverage for young females whose parents are informal caregivers

The effects of caregiver strain and stress on preventive health service utilization among adult family members are well-established, but the effects of informal caregiving on children of caregivers are unknown. We aimed to assess whether inequalities in vaccination coverage (specifically human papillomavirus [HPV] and influenza) exist for females aged 9 to 17 years whose parents are informal caregivers (i.e., care providers for family members or others who are not functionally independent) compared with females whose parents are not informal caregivers. Data from the 2009 Behavioral Risk Factor Surveillance System were analyzed using Poisson regression with robust variance to estimate overall and subgroup-specific HPV and influenza vaccination prevalence ratios (PRs) and corresponding 95% confidence limits (CL) comparing females whose parents were informal caregivers with females whose parents were not informal caregivers. Our unweighted study populations comprised 1645 and 1279 females aged 9 to 17 years for the HPV and influenza vaccination analyses, respectively. Overall, both HPV and influenza vaccination coverage were lower among females whose parents were informal caregivers (HPV: PR = 0.72, 95% CL: 0.53, 0.97; Influenza: PR = 0.89, 95% CL: 0.66, 1.2). Our results suggest consistently lower HPV and influenza vaccination coverage for young females whose parents are informal caregivers. Our study provides new evidence about the potential implications of caregiving on the utilization of preventive health services among children of caregivers