709 research outputs found

    Synthesis and acylation of some thieno- and benzo[1,2]diazepines

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    Noise and performance of propellers for light aircraft : final report

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    July 1980Project Manager: G. P. Succi ; Contributors: E.E. Larrabee, P.D. [i.e. P. B.] Dunbeck, D.H. Munro, J.A. Zimmer; Principal Investigators: K.U. Ingard, J.L. KerrebrockIncludes bibliographical references (pages 22-23)Final report. February 24, 1978 to July 31, 1980Introduction and Summary: The project "Noise and Performance of Propellers for Light Aircraft," Contract #NASl-15154 between NASA Langley and MIT, has now been completed, and the main results obtained are summarized in this report and its appendices. The primary practical objective of the study was to explore the possibility of reducing the noise from a general aviation type propeller without altering significantly its aerodynamic performance or the engine characteristics. After an extensive study of this question, involving aerodynamic and acoustic theory, design, construction and wind tunnel testing of model propellers, design and manufacturing of full scale propellers and, finally, flight tests, we are pleased to report that for one of the propellers tested an overall reduction of 4.8 dBA as measured in a flight test was achieved.The theory deals with aerodynamics and acoustics of lightly loaded propellers with subsonic tip speeds and includes studies of the effects of sweeping the blades, altering the radial load distribution, and changing the number of blades. These studies lead to new insight into the general problem of sound generation from moving bodies. Of particular value are the algorithms, which are well suited for computer coding. The wind tunnel tests involved three propellers, 1/4 scale, including a replica of a fixed pitch propeller used on a 150 HP single engine airplane. The other two propellers were designed to have the peak radial load distribution shifted inboard. The acoustic wind tunnel which was used in these tests enabled measurement not only of the radiated sound field but also the thrust and torque of the propeller. In addition, the load distribution was determined indirectly from wake surveys.Sound pressure signatures were obtained at different locations and speeds (up to a tip Mach number of 0.75) and compared with theoretical predictions in which only the shape and motion of the propeller were needed as input parameters; no empirical adjustments were made. Agreement to within a few percent was obtained throughout except in the presence of a transonic "buzz" instability which was encountered within a narrow speed range. On the basis of the theoretical analysis and its verification in the model tests, a two-bladed fixed pitch propeller was designed for a 150 HP single engine airplane. Flight tests with this propeller indicated about the same performance as the production propeller for that airplane, but the maximum sound level during a full power flyover at 1000 feet was found to be 4.8 dBA lower. A second propeller, with three blades and fixed pitch, was designed for the Ohio State University 180 HP single engine airplane.Flight tests of this propeller have not yet been made at this time.NASA Contract NAS1-1515

    Nrf2 regulates mass accrual and the antioxidant endogenous response in bone differently depending on the sex and age

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    Accumulation of reactive oxygen species (ROS) is an important pathogenic mechanism underling the loss of bone mass and strength with aging and other conditions leading to osteoporosis. The transcription factor erythroid 2-related factor2 (Nrf2) plays a central role in activating the cellular response to ROS. Here, we examined the endogenous response of bone regulated by Nrf2, and its relationship with bone mass and architecture in the male and female murine skeleton. Young (3 month-old) and old (15 month-old) Nrf2 knockout (KO) mice of either sex exhibited the expected reduction in Nrf2 mRNA expression compared to wild type (WT) littermates. Nrf2 deletion did not lead to compensatory increase in Nrf1 or Nrf3, other members of this transcription factor family; and instead, Nrf1 expression was lower in KO mice. Compared to the respective WT littermate controls, female KO mice, young and old, exhibited lower expression of both detoxifying and antioxidant enzymes; young male KO mice, displayed lower expression of detoxifying enzymes but not antioxidant enzymes; and old male KO mice showed no differences in either detoxifying or antioxidant enzymes. Moreover, old male WT mice exhibited lower Nrf2 levels, and consequently lower expression of both detoxifying and antioxidant enzymes, compared to old female WT mice. These endogenous antioxidant responses lead to delayed rate of bone acquisition in female KO mice and higher bone acquisition in male KO mice as quantified by DXA and μCT, demonstrating that Nrf2 is required for full bone accrual in the female skeleton but unnecessary and even detrimental in the male skeleton. Therefore, Nrf2 regulates the antioxidant endogenous response and bone accrual differently depending on sex and age. These findings suggest that therapeutic interventions that target Nrf2 could be developed to enhance the endogenous antioxidant response in a sex- and age-selective manner

    Incentive-based approaches to sustainable fisheries

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    The failures of traditional target-species management have led many to propose an ecosystem approach to fisheries to promote sustainability. The ecosystem approach is necessary, especially to account for fishery-ecosystem interactions, but by itself is not sufficient to address two important factors contributing to unsustainable fisheries — inappropriate incentives bearing on fishers, and the ineffective governance that frequently exists in commercial, developed fisheries managed primarily by total harvest limits and input-controls. We contend that much greater emphasis must be placed on fisher motivation when managing fisheries. Using evidence from more than a dozen ‘natural experiments’ in commercial fisheries, we argue that incentive-based approaches that better specify community, individual harvest, or territorial rights and also price ecosystem services — coupled with public research, monitoring and effective oversight — promote sustainable fisheries.incentives, sustainability, rights, fisheries management

    Incentive-based approaches to sustainable fisheries (now replaced by EEN0508)

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    Using examples from more than a dozen fisheries, we highlight the failures of ‘command control’ management and show that approaches that empower fishers with the incentives and the mandate to be co-custodians of the marine environment can promote sustainability. Evidence is provided that where harvesters share well-defined management responsibilities over fish, and experience both the pain of overexploitation and the gains from conservation, they are much more likely to protect fish stocks and habitat. The key insight is that to maintain marine ecosystems for present and future generations, fishing incentives must be compatible with long-term goals of sustainability.incentives, sustainability, rights, fisheries management

    Age-dependent loss of cohesion protection in human oocytes

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    Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate that SGO2 preserves sister chromatid cohesion in meiosis by protecting a ‘‘cohesin bridge’’ between sister chromatids. In human oocytes, SGO2 localizes to both sub-centromere cups and the pericentromeric bridge, which spans the sister chromatid junction. SGO2 normally colocalizes with cohesin; however, in meiosis II oocytes from older women, SGO2 is frequently lost from the pericentromeric bridge and sister chromatid cohesion is weakened. MPS1 and BUB1 kinase activities maintain SGO2 at sub-centromeres and the pericentromeric bridge. Removal of SGO2 throughout meiosis I by MPS1 inhibition reduces cohesion protection, increasing the incidence of single chromatids at meiosis II. Therefore, SGO2 deficiency in human oocytes can exacerbate the effects of maternal age by rendering residual cohesin at pericentromeres vulnerable to loss in anaphase I. Our data show that impaired SGO2 localization weakens cohesion integrity and may contribute to the increased incidence of aneuploidy observed in human oocytes with advanced maternal age

    Structural insights into TAZ2 domain-mediated CBP/p300 recruitment by transactivation domain 1 of the lymphopoietic transcription factor E2A.

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    The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding protein P300 (p300). This interaction is necessary for B-cell maturation and oncogenesis by E2A-PBX1 and occurs through conserved ϕ-x-x-ϕ-ϕ motifs (with ϕ denoting a hydrophobic amino acid) in AD1 and AD2. However, disruption of this interaction via mutation of the KIX domain in CBP/p300 does not completely abrogate binding of E2A and E2APBX1. Here, we determined that E2A-AD1 and E2A-AD2 also interact with the TAZ2 domain of CBP/p300. Characterization of the TAZ2:E2AAD1(1-37) complex indicated that E2A-AD1 adopts an α-helical structure and uses its ϕ-x-x-ϕ-ϕ motif to bind TAZ2. While this region overlapped with the KIX recognition region, key KIX-interacting E2A-AD1 residues were exposed, suggesting that E2A-AD1 could simultaneously bind both the KIX and TAZ2 domains. However, we did not detect a ternary complex involving E2A-AD1, KIX, and TAZ2 and found that E2A containing both intact AD1 and AD2 is required to bind to CBP/p300. Our findings highlight the structural plasticity and promiscuity of E2A-AD1 and suggest that E2A binds both the TAZ2 and KIX domains of CBP/p300 through AD1 and AD2

    Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

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    Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer\u27s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults

    Rationale and Methods for a Multicenter Clinical Trial Assessing Exercise and Intensive Vascular Risk Reduction in Preventing Dementia (rrAD Study)

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    Alzheimer\u27s Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of four intervention group for two years: usual care, Intensive Reduction of Vascular Risk factors (IRVR) with blood pressure and cholesterol reduction, exercise training (EX), and IRVR+EX. Neurocognitive function is measured at baseline, 6, 12, 18, and 24 months; brain MRIs are obtained at baseline and 24 months. We hypothesize that both IRVR and EX will improve global cognitive function, while IRVR+EX will provide a greater benefit than either IRVR or EX alone. We also hypothesize that IRVR and EX will slow brain atrophy, improve brain structural and functional connectivity, and improve brain perfusion. Finally, we will explore the mechanisms by which study interventions impact neurocognition and brain. If rrAD interventions are shown to be safe, practical, and successful, our study will have a significant impact on reducing the risks of AD in older adults. NCT Registration: NCT02913664

    Skeletal Protection and Promotion of Microbiome Diversity by Dietary Boosting of the Endogenous Antioxidant Response

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    There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (α-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (β-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex.Fil: Sato, Amy Y.. University of Arkansas for Medical Sciences; Estados Unidos. Indiana University. School of Medicine; Estados UnidosFil: Pellegrini, Gretel Gisela. Indiana University. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Cregor, Meloney. University of Arkansas for Medical Sciences; Estados Unidos. Indiana University. School of Medicine; Estados UnidosFil: McAndrews, Kevin. Indiana University. School of Medicine; Estados UnidosFil: Choi, Roy B. Indiana University. School of Medicine; Estados UnidosFil: Maiz, Maria. Purdue University; Estados UnidosFil: Johnson, Olivia. Indiana University. School of Medicine; Estados UnidosFil: McCabe, Linda D.. Purdue University; Estados UnidosFil: McCabe, George P.. Purdue University; Estados UnidosFil: Ferruzzi, Mario G.. North Carolina State University; Estados UnidosFil: Lila, Mary Ann. North Carolina State University; Estados UnidosFil: Peacock, Munro. Indiana University. School of Medicine; Estados UnidosFil: Burr, David B.. Indiana University. School of Medicine; Estados UnidosFil: Nakatsu, Cindy H.. Purdue University; Estados UnidosFil: Weaver, Connie M.. Purdue University; Estados UnidosFil: Bellido, Teresita. University of Arkansas for Medical Sciences; Estados Unidos. Indiana University. School of Medicine; Estados Unido
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