133 research outputs found

    Teacher's Action Plan for "Shuttle External Tank and Solid Rocket Booster Math"

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    My name is Mike Prince and I was one of eleven Brevard County teachers selected by United Space Alliance, LLC (USA), to work at the Kennedy Space Center (KSQ along side USA & NASA engineers during the Summer of 2007. Attached is a summary of my experience

    Needs assessment to strengthen capacity in water and sanitation research in Africa:experiences of the African SNOWS consortium

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    Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project

    Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial

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    Abstract: Porosity, one of the important quality attributes of pharmaceutical tablets, directly affects the mechanical properties, the mass transport and hence tablet disintegration, dissolution and ultimately the bioavailability of an orally administered drug. The ability to accurately and quickly monitor the porosity of tablets during manufacture or during the manufacturing process will enable a greater assurance of product quality. This tutorial systematically outlines the steps involved in the terahertz-based measurement method that can be used to quantify the porosity of a tablet within seconds in a non-destructive and non-invasive manner. The terahertz-based porosity measurement can be performed using one of the three main methods, which are (i) the zero-porosity approximation (ZPA); (ii) the traditional Bruggeman effective medium approximation (TB-EMA); and (iii) the anisotropic Bruggeman effective medium approximation (AB-EMA). By using a set of batches of flat-faced and biconvex tablets as a case study, the three main methods are compared and contrasted. Overall, frequency-domain signal processing coupled with the AB-EMA method was found to be most suitable approach in terms of accuracy and robustness when predicting the porosity of tablets over a range of complexities and geometries. This tutorial aims to concisely outline all the necessary steps, precautions and unique advantages associated with the terahertz-based porosity measurement method

    Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands

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    Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 æ from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules’ effects on Hsp90 enzymatic, conformational, cochaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary

    Causes of nursing home placement for older people with dementia: a systematic review and meta-analysis

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    Background: Up to half of people with dementia in high income countries live in nursing homes and more than two-thirds of care home residents have dementia. Fewer than half of these residents report good quality of life and most older people are anxious about the prospect of moving into a nursing home. Robust evidence is needed as to the causes of admission to nursing homes, particularly where these risk factors are modifiable. Methods: We conducted a systematic literature search to identify controlled comparison studies in which the primary outcome was admission to nursing home of older adults with dementia. Identified studies were assessed for validity and 26 (17 cohort and 9 case-control) were included. Qualitative and quantitative analyses were conducted, including meta-analysis of 15 studies. Results: Poorer cognition and behavioral and psychological symptoms of dementia (BPSD) were consistently associated with an increased risk of nursing home admission and most of our meta-analyses demonstrated impairments in activities of daily living as a significant risk. The effects of community support services were unclear, with both high and low levels of service use leading to nursing home placement. There was an association between caregiver burden and risk of institutionalization, but findings with regard to caregiver depression varied, as did physical health associations, with some studies showing an increased risk of nursing home placement following hip fracture, reduced mobility, and multiple comorbidities. Conclusion: We recommend focusing on cognitive enhancement strategies, assessment and management of BPSD, and carer education and support to delay nursing home placement

    Crop Updates - 2003 Lupins

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    This session covers twenty one papers from different authors LUPIN ISSUES AND R & D DIRECTIONS Mark Sweetingham, Department of Agriculture ACKNOWLEDGEMENTS VARIETIES AND BREEDING New lupin line for release – WALAN2141, Bevan J, Buirchell, Mark Sweetingham, Geoff Thomas, Amelia McLarty, Harmohinder Dhammu and CVT and Lupin Breeding teams, Department of Agriculture Lupin variety trial, Martin Harries and Wayne Parker, Department of Agriculture Herbicide tolerance of new lupins, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture YELLOW AND ALBUS LUPINS Selection for high lupin yield under terminal drought, Jairo A. Palta1&2, Neil C. Turner1&2 Bob French2&3 and Bevan Buirchell2&3 , 1CSIRO Plant Industry, Floreat, WA, 2CLIMA, University of Western Australia, Crawley, WA, 3Department of Agriculture Outcrossing and isolation distance in yellow lupins, Kedar Adhikari, Bevan Buirchell and Katia Stefanova, Department of Agriculture Development of aphid tolerant yellow lupins in Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Françoise Berlandier, Department of Agriculture ESTABLISHMENT Development of anthracnose resistant albus lupins for Western Australia, Kedar Adhikari, Bevan Buirchell, Mark Sweetingham and Geoff Thomas, Department of Agriculture Lupin sowing methods for improved yields, Glen Riethmuller, Department of Agriculture Moisture delving = more reliable lupin establishment, Paul Blackwell and Wayne Parker, Department of Agriculture Effect of time of sewing, plant density and row orientation on lupins at various row spacings, Geoff Fosbery, Farm Focus Consultants, Bill Crabtree, Crabtree Consulting and Tracy Gilham, WANTFA Influence of row spacing on water stress and water use of lupins, Bob French and Laurie Wahlsten, Department of Agriculture AGRONOMY Effect on lupin protein and yield from variety, planting time and seed rate, Pierre Fievez, Pierre Fievez and Associates Lupin row cropping: herbicides to band, shield design and economics, Mike Collins, WANTFA and John Holmes, 4 Farmers Harvest options for narrow leaf lupins, Martin Harries and Dirranie Kirby, Department of Agriculture NUTRITION Additional nutrients on lupin yield and protein, Pierre Fievez, Pierre Fievez and Associates Demonstrating the effect of phosphorous placement on yields of narrow leaf lupin and yellow lupin on high phosphorus retention soils, Martin Harries and Wayne Parker, Department of Agriculture PESTS AND DISEASES How far are anthracnose spores spread by rain splash? Geoff Thomas, Mark Sweetingham and Ken Adcock, Department of Agriculture Height of cereal stubble affects spread of lupin anthracnose, Geoff Thomas, Bill MacLeod and Ken Adcock, Department of Agriculture Controlling non-necrotic strains of bean yellow mosaic virus in lupins by cultural methods, Roger Jones and Rohan Prince, Department of Agriculture, and Centre for Legumes in Mediterranean Agriculture MARKET DEVELOPMENT Australian sweet lupin – is it the next human health food? Stuart Johnson, Deakin University; Ramon Hall, ARC SPIRT PhD Scholar; Madeleine Ball, University of Tasmania; Sofia Sipsas and David Petterson; Department of Agriculture CONTACT DETAILS FOR PRINCIPAL AUTHOR

    Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

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    10.2139/ssrn.15462511-2

    Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency

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    BACKGROUND: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. OBJECTIVE: We explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. METHODS: Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type vs. mutant LIG4 were performed in LIG4 knock-out Jurkat T cells and DNA damage tolerance was subsequently assessed. RESULTS: A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naïve CD4+^{+} T cells and low TCR-Vα7.2+^{+} T cells, while T/B-cell receptor repertoires showed only mild alterations. Cohort screening identified two other non-related patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. CONCLUSION: We provide evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency
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