2,082 research outputs found

    Institute Brief: Support through Mentorship: Accessible Supervision of Employees with Intellectual and Developmental Disabilities

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    Effective supervision of employees with intellectual or developmental disabilities can be challenging for businesses that may not have experience in hiring people with diverse support requirements. This is largely due to the relatively low participation rates of people with disabilities in the workforce. This is, thankfully, changing as more businesses are seeing the value of diversifying their workforce, which includes hiring people with diverse cognitive abilities like people with intellectual or developmental disabilities

    Tools for Inclusion: The Power of Friendship

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    Friendship is important for all of us! This includes people with and without disabilities. People often feel better and happier when they have friends. As part of a research project about the choices people with disabilities make about work, we interviewed 16 people with intellectual or developmental disabilities (IDD). These people also chose family members and professional staff people for us to interview. We asked them how they made decisions about working and making friends

    Marker-based estimates reveal significant non-additive effects in clonally propagated cassava (Manihot esculenta): implications for the prediction of total genetic value and the selection of varieties

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    Open Access JournalIn clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of non-additive genetic variation for key traits in a breeding population of cassava from sub-Saharan Africa using additive and non-additive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction of additive compared to total (additive plus non-additive) genetic value. We confirmed previous findings based on diallel populations, that non-additive genetic variation is significant, especially for yield traits. Further, we show that we total genetic value correlated more strongly to observed phenotypes than did additive value, although this is constrained by low broad-sense heritability and is not beneficial for traits with already high heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species

    Chaperone Mediated Protective Protein Aggregation and Spatial Quality Control

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    The accumulation of amyloid-like aggregates is a characteristic of protein conformational disorders such as Huntington Disease, but whether amyloid-like aggregation is causative or a cytoprotective mechanism remains unclear. Molecular chaperones act as the front line of defense against proteotoxicity, as they protect cells by partitioning misfolded proteins towards refolding, degradation, or assembly into large benign aggregates. Herein, a yeast model of proteotoxicity was utilized to study cellular mechanisms for protective aggregation. Ectopic expression of polyglutamine (polyQ) expanded Huntingtin (Htt103Q) is toxic in yeast, and targeting it to the nucleus enhances toxicity while decreasing SDS-resistant aggregation. I utilized this nuclear Htt103Q as the substrate for a high copy toxicity suppressor screen in yeast which identified Sti1 as a molecule that promotes protective aggregation of Htt103Q. The Hsp70 co-chaperone Sti1 regulates spatial quality control of amyloid-like proteins as it induces formation of perinuclear foci containing SDS-resistant material. Accumulation of distinct perinuclear foci correlates with suppression of toxicity and increased complex formation with the Hsp70/Hsp40 chaperone machinery. Endogenous Sti1 appears to be a crucial player in a chaperone-facilitated protective aggregation pathway, because deletion of Sti1 enhances Htt103Q toxicity while decreasing aggregation. In addition to Sti1, the screen produced a group of polyQ-rich proteins, Nab3, Pop2 and Cbk1, as high-copy suppressors of Htt103Q toxicity. PolyQ proteins play different roles in Htt103Q toxicity, either to a detrimental outcome where a Q-rich protein is titrated away from its normal function, or beneficially via interactions that promote protective aggregation. Over-expression of Nab3 appears to suppress Htt103Q toxicity by replacing a functional pool of Nab3 that was lost to aberrant polyQ interaction. Over-expression of Pop2 and Cbk1each suppresses toxicity and promotes aggregation of Htt103Q in a slightly different way, but neither can carry out this function in the absence of Sti1. Therefore, Pop2 and Cbk1 act upstream of Sti1 in pathway which promotes protective aggregation of amyloid-like assemblies. These proteins alter the cellular outcome of proteotoxic insult caused by Htt103Q by modulating spatial quality control.Doctor of Philosoph

    The urban and economic impacts of mega-events: mechanisms of change in global games

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    Mega-events are global affairs with profound effects across a variety of scales, and are the focus of a large and growing body of academic inquiry. This special section in Sports in Society centers on the urban and economic impacts of mega-events on the societies that host them, offering an examination of individual cases and emerging patterns. The authors explore different dimensions of the recent mega-event expe- rience from around the world, proposing novel ways of theorizing these outsized expressions of transnational sport, politics, commerce, and culture. Combined, these contributions unpack how socio-economic and cultural contexts shape the organization of events and impact hosts in variegated and contingent ways in the Global North, South, and East. This introduction offers a brief overview of the landscape of the existing research before summarizing each contribution and placing them in context within the broader literature. All told, the articles in this special section explore how the Olympics, the FIFA Men’s World Cup and the Commonwealth Games deploy different mechanisms to transform urban space, and offer innovative means of understanding what mega- events can do to the people and places that host them

    Aeronautics Research Mission Directorate Integrated Systems Research Program (ISRP) and UAS Integration in the NAS Project

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    Program Goal: Conduct research at an integrated system-level on promising concepts and technologies and explore, assess, or demonstrate the benefits in a relevant environment.Criteria for selection of projects for Integrated Systems Research: a) Technology has attained enough maturity in the foundational research program that they merit more in-depth evaluation at an integrated system level in a relevant environment. b) Technologies which systems analysis indicates have the most potential for contributing to the simultaneous attainment of goals. c) Technologies identified through stakeholder input as having potential for simultaneous attainment of goals. d) Research not being done by other government agencies and appropriate for NASA to conduct. e) Budget augmentation. Environmentally Responsible Aviation (ERA) Project Explore and assess new vehicle concepts and enabling technologies through system-level experimentation to simultaneously reduce fuel burn, noise, and emissions Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project Contribute capabilities that reduce technical barriers related to the safety and operational challenges associated with enabling routine UAS access to the NAS Innovative Concepts for Green Aviation (ICGA) Project Spur innovation by offering research opportunities to the broader aeronautics community through peer-reviewed proposals, with a focus on making aviation more eco-friendly. Establish incentive prizes similar to the Centennial Challenges and sponsor innovation demonstrations of selected technologies that show promise of reducing aviation s impact on the environmen

    Genomic prediction and quantitative trait locus discovery in a cassava training population constructed from multiple breeding stages

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    Open Access Article; Published online: 11 Dec 2019Assembly of a training population (TP) is an important component of effective genomic selection‐based breeding programs. In this study, we examined the power of diverse germplasm assembled from two cassava (Manihot esculenta Crantz) breeding programs in Tanzania at different breeding stages to predict traits and discover quantitative trait loci (QTL). This is the first genomic selection and genome‐wide association study (GWAS) on Tanzanian cassava data. We detected QTL associated with cassava mosaic disease (CMD) resistance on chromosomes 12 and 16; QTL conferring resistance to cassava brown streak disease (CBSD) on chromosomes 9 and 11; and QTL on chromosomes 2, 3, 8, and 10 associated with resistance to CBSD for root necrosis. We detected a QTL on chromosome 4 and two QTL on chromosome 12 conferring dual resistance to CMD and CBSD. The use of clones in the same stage to construct TPs provided higher trait prediction accuracy than TPs with a mixture of clones from multiple breeding stages. Moreover, clones in the early breeding stage provided more reliable trait prediction accuracy and are better candidates for constructing a TP. Although larger TP sizes have been associated with improved accuracy, in this study, adding clones from Kibaha to those from Ukiriguru and vice versa did not improve the prediction accuracy of either population. Including the Ugandan TP in either population did not improve trait prediction accuracy. This study applied genomic prediction to understand the implications of constructing TP from clones at different breeding stages pooled from different locations on trait accuracy

    NASA Integrated Systems Research with an Environmental Focus

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    This slide presentation reviews the Integrated Systems Research Program (ISRP) with a focus on the work being done on reduction of environmental impact from aeronautics. The focus of the ISRP is to Conduct research at an integrated system-level on promising concepts and technologies and explore, assess, or demonstrate the benefits in a relevant environment. The presentation reviews the criteria for an ISRP project, and discusses the Environmentally Responsible Aviation (ERA) project, and the technical challenges

    Genome editing of HBG1 and HBG2 to induce fetal hemoglobin

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    Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress gamma-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and beta-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rgamma-/-/KitW41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies

    Classical and MgII-selected Damped Lyman-alpha Absorbers: impact on Omega_HI at z<1.7

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    The Damped Lyman-alpha systems (DLAs), seen in absorption in the spectrum of quasars, are believed to contain a large fraction of the neutral gas in the Universe. Paradoxically, these systems are more difficult to observe at z_abs<1.7, since they are rare and their HI feature then falls in UV spectra. Rao & Turnshek (2000) pioneered a method based on MgII-selected DLAs, that is absorbers discovered thanks to our knowledge of their MgII feature in optical spectra. We use new observations undertaken at the TNG as well as a careful literature & archival search to build samples of low redshift absorbers classified according to the technique used for their discovery. We successfully recover N(HI) and equivalent widths of FeII 2600, MgII 2796, MgII 2803 and MgII 2852 for a sample of 36 absorbers, 21 of which are MgII-selected. We find that the MgII-selected sample contains a marginally larger fraction of absorbers with log N(HI)>21.0 than seen otherwise at low redshift. If confirmed, this property will in turn affect estimates of Omega_HI which is dominated by the highest HI column densities. We find that log N(HI) does not correlate significantly with metal equivalent widths. Similarly, we find no evidence that gravitational lensing, the fraction of associated systems or redshift evolution affect the absorber samples in a different way. We conclude that the hint of discrepancies in N(HI) distributions most likely arises from small number statistics. Therefore, further observations are required to better clarify the impact of this discrepancy on estimates of Omega_HI at low redshift.Comment: 13 pages, 8 figures. Accepted for publication in MNRA
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