389 research outputs found
The Mobility Enterprise - Improving Auto Productivity
The Mobility Enterprise is a particular version of a shared vehicle fleet, aimed at solving the problem of low automobile productivity. The automobile consumes a large portion of Americaâs transportation energy supply. It also operates much of the time with unused capacity: vacant seats and empty cargo space. Since programs to fill those vacant seats âride sharing and high occupancy vehicle incentives âhave fallen so far short of their objectives, a new approach is warranted. The enterpriseâs central concept is matching vehicle attributes to travel needs. Generally, a household purchases vehicles for those few trips that require a large capacity, rather than for the majority of trips (usually to work) that have minimal vehicular needs. If a household could tailor its âimmediate accessâ fleet to these frequent trips and still retain reasonable access to larger-capacity special purpose vehicles (SPVâs), considerable economies could be achieved. The household is relieved of owning seldom-used excess capacity, and automobile productivity and efficiency are greatly improved. Having easy access to a shared fleet of SPVâs also affords a household an increase in the quality and economy of its travel experiences. This paper describes a research project recently begun at Purdue that involves a comprehensive investigation of the Mobility Enterprise concept. Questions of institutional barriers, consumer response, and organization and management are discussed here as keys to the fate of the enterprise in the transportation climate of the foreseeable future
Harvest and Nitrogen Management of Three Perennial Grasses as Biomass Feedstock in Subarctic Alaska
High energy costs in high-latitude regions have generated interest in the feasibility of bioenergy cropping. The goal of this study was to determine the N response and best harvest regime for biomass production of three perennial, cool-season grass speciesâtufted hairgrass (Deschampsia caespitosa (L.) P. Beauv.), slender wheatgrass (Elymus trachyÂcaulus (Link) Gould ex Shinners), and smooth bromegrass (Bromus inermis Leyss)âat two locations in central Alaska. Maximum dry matter yields were 11.3 Mg ha-1 for smooth bromegrass, 8.1 Mg ha-1 for tufted hairgrass, and 8.0 Mg ha-1 for slender wheatgrass, but yields varied greatly among years. We found a linear N response in most cases, with highest yields at the 100 kg N ha-1 application rate. Yields for the double-harvest regime usually did not vary significantly from those of the fall harvest, but spring harvest sometimes reduced yields dramatically. Biomass in the spring harvest was usually dry enough not to require additional drying for storage. Results of this study indicate it may be possible to produce grass biomass yields high enough for use as bioenergy feedstocks in central Alaska, but questions remain about the best management practices and the economics of growing bioenergy crops in Alaska.Les coĂ»ts Ă©levĂ©s de lâĂ©nergie en haute latitude incitent les gens Ă se pencher sur la faisabilitĂ© dâentreprendre des cultures bioĂ©nergĂ©tiques. Lâobjectif de cette Ă©tude consistait Ă dĂ©terminer la rĂ©ponse Ă lâazote et le meilleur rĂ©gime dâexploitation pour la bioproduction de trois espĂšces de graminĂ©es vivaces en saison fraĂźche, soit la deschampsie cespiteuse (Deschampsia caespitosa (L.) P. Beauv.), lâĂ©lyme Ă chaumes rudes (Elymus trachycaulus (Link) Gould ex Shinners) et le brome inerme (Bromus inermis Leyss), Ă deux endroits du centre de lâAlaska. Le rendement maximum de matiĂšre sĂšche Ă©tait de 11,3 tm ha-1 dans le cas du brome inerme, de 8,1 tm ha-1 dans le cas de la deschampsie cespiteuse et de 8,0 tm ha-1 dans le cas de lâĂ©lyme Ă chaumes rudes, bien que les rendements aient connu dâimportantes variations dâune annĂ©e Ă lâautre. Nous avons trouvĂ© une rĂ©ponse linĂ©aire Ă lâazote dans la plupart des cas, les rendements les plus Ă©levĂ©s Ă©tant ceux de la dose dâapplication de 100 kg N ha-1. Le rendement du rĂ©gime Ă double rĂ©colte ne variait gĂ©nĂ©ralement pas beaucoup du rĂ©gime Ă rĂ©colte dâautomne, bien que les rĂ©coltes du printemps donnaient parfois un rendement considĂ©rablement rĂ©duit. De maniĂšre gĂ©nĂ©rale, la biomasse de la rĂ©colte du printemps Ă©tait suffisamment sĂšche pour ne pas avoir besoin dâĂȘtre assĂ©chĂ©e davantage avant dâĂȘtre stockĂ©e. Les rĂ©sultats de cette Ă©tude indiquent quâil peut ĂȘtre possible de produire des rendements en biomasse suffisamment Ă©levĂ©s Ă partir de graminĂ©es pour ĂȘtre utilisĂ©s comme charge bioĂ©nergĂ©tique dans le centre de lâAlaska, mais cela dit, il y a toujours lieu de rĂ©pondre aux questions portant sur les pratiques de gestion exemplaires et le caractĂšre Ă©conomique des productions bioĂ©nerÂgĂ©tiques en Alaska
Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2
AbstractThe yeast UBC9 gene encodes a protein with homology to the E2 ubiquitin-conjugating enzymes that mediate the attachment of ubiquitin to substrate proteins [1]. Depletion of Ubc9p arrests cells in G2 or early M phase and stabilizes B-type cyclins [1]. p18Ubc9, the Xenopus homolog of Ubc9p, associates specifically with p88RanGAP1 and p340RanBP2[2]. Ran-binding protein 2 (p340RanBP2) is a nuclear pore protein [3,4], and p88RanGAP1 is a modified form of RanGAP1, a GTPase-activating protein for the small GTPase Ran [2]. It has recently been shown that mammalian RanGAP1 can be conjugated with SUMO-1, a small ubiquitin-related modifier [5â7], and that SUMO-1 conjugation promotes RanGAP1's interaction with RanBP2 [2,5,6]. Here we show that p18Ubc9 acts as an E2-like enzyme for SUMO-1 conjugation, but not for ubiquitin conjugation. This suggests that the SUMO-1 conjugation pathway is biochemically similar to the ubiquitin conjugation pathway but uses a distinct set of enzymes and regulatory mechanisms. We also show that p18Ubc9 interacts specifically with the internal repeat domain of RanBP2, which is a substrate for SUMO-1 conjugation in Xenopus egg extracts
Sonic Booms in Atmospheric Turbulence (SonicBAT): The Influence of Turbulence on Shaped Sonic Booms
The objectives of the Sonic Booms in Atmospheric Turbulence (SonicBAT) Program were to develop and validate, via research flight experiments under a range of realistic atmospheric conditions, one numeric turbulence model research code and one classic turbulence model research code using traditional N-wave booms in the presence of atmospheric turbulence, and to apply these models to assess the effects of turbulence on the levels of shaped sonic booms predicted from low boom aircraft designs. The SonicBAT program has successfully investigated sonic boom turbulence effects through the execution of flight experiments at two NASA centers, Armstrong Flight Research Center (AFRC) and Kennedy Space Center (KSC), collecting a comprehensive set of acoustic and atmospheric turbulence data that were used to validate the numeric and classic turbulence models developed. The validated codes were incorporated into the PCBoom sonic boom prediction software and used to estimate the effect of turbulence on the levels of shaped sonic booms associated with several low boom aircraft designs. The SonicBAT program was a four year effort that consisted of turbulence model development and refinement throughout the entire period as well as extensive flight test planning that culminated with the two research flight tests being conducted in the second and third years of the program. The SonicBAT team, led by Wyle, includes partners from the Pennsylvania State University, Lockheed Martin, Gulfstream Aerospace, Boeing, Eagle Aeronautics, Technical & Business Systems, and the Laboratory of Fluid Mechanics and Acoustics (France). A number of collaborators, including the Japan Aerospace Exploration Agency, also participated by supporting the experiments with human and equipment resources at their own expense. Three NASA centers, AFRC, Langley Research Center (LaRC), and KSC were essential to the planning and conduct of the experiments. The experiments involved precision flight of either an F-18A or F-18B executing steady, level passes at supersonic airspeeds in a turbulent atmosphere to create sonic boom signatures that had been distorted by turbulence. The flights spanned a range of atmospheric turbulence conditions at NASA Armstrong and Kennedy in order to provide a variety of conditions for code validations. The SonicBAT experiments at both sites were designed to capture simultaneous F-18A or F-18B onboard flight instrumentation data, high fidelity ground based and airborne acoustic data, surface and upper air meteorological data, and additional meteorological data from ultrasonic anemometers and SODARs to determine the local atmospheric turbulence and boundary layer height
Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics
The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed âtrained immunity.â An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to âbend the pandemic curve,â averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease
Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline
Background: As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. Objective: Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. Methods: We measured tibia and patella lead using K-X-ray fluorescence (1991â1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993â1998 and 1995â2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n = 358). Results: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele compared with men with only wild-type alleles (p interaction = 0.03), such that a 15 ÎŒg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (p-trend = 0.008). Results for patella lead were similar. Conclusion: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose
Brief Report: Using Individualized Orienting Cues to Facilitate First-Word Acquisition in Non-Responders with Autism
Though considerable progress has been made in developing techniques for improving the acquisition of expressive verbal communication in children with autism, research has documented that 10â25% still fail to develop speech. One possible technique that could be significant in facilitating responding for this nonverbal subgroup of children is the use of orienting cues. Using a multiple baseline design, this study examined whether individualized orienting cues could be identified, and whether their presentation would result in verbal expressive words. The results suggest that using individualized orienting cues can increase correct responding to verbal models as well as subsequent word use. Theoretical and applied implications of orienting cues as they relate to individualized programming for children with autism are discussed
Developing decision support tools incorporating personalised predictions of likely visual benefit versus harm for cataract surgery:research programme
Background
Surgery for established cataract is highly cost-effective and uncontroversial, yet uncertainty remains for individuals about when to proceed and when to delay surgery during the earlier stages of cataract.
Objective
We aimed to improve decision-making for cataract surgery through the development of evidence-based clinical tools that provide general information and personalised risk/benefit information.
Design
We used a mixed methodology consisting of four work packages. Work package 1 involved the development and psychometric validation of a brief, patient self-reported measure of visual difficulty from cataract and its relief from surgery, named Cataract Patient-Reported Outcome Measure, five items (Cat-PROM5). Work package 2 involved the review and refinement of risk models for adverse surgical events (posterior capsule rupture and visual acuity loss related to cataract surgery). Work package 3 involved the development of prediction models for the Cat-PROM5-based self-reported outcomes from a cohort study of 1500 patients; assessment of the validity of preference-based health economic indices for cataract surgery and the calibration of these to Cat-PROM5; assessment of patientsâ and health-care professionalsâ views on riskâbenefit presentation formats, the perceived usefulness of Cat-PROM5, the value of personalised riskâbenefit information, high-value information items and shared decision-making; development of cataract decision aid frequently asked questions, incorporation of personalised estimates of risks and benefits; and development of a cataract decision quality measure to assess the quality of decision-making. Work package 4 involved a mixed-methods feasibility study for a fully powered randomised controlled trial of the use of the cataract decision aid and a qualitative study of discordant or mismatching perceptions of outcome between patients and health-care professionals.
Setting
Four English NHS recruitment centres were involved: Bristol (lead centre), Brighton, Gloucestershire and Torbay. Multicentre NHS cataract surgery data were obtained from the National Ophthalmology Database.
Participants
Work package 1 â participants (nâ=â822) were from all four centres. Work package 2 â electronic medical record data were taken from the National Ophthalmology Database (final set >â1M operations). Work package 3 â cohort study participants were from Bristol (nâ=â1200) and Gloucestershire (nâ=â300); qualitative and development work was undertaken with patients and health-care professionals from all four centres. Work package 4 â Bristol, Brighton and Torbay participated in the recruitment of patients (nâ=â42) for the feasibility trial and recruitment of health-care professionals for the qualitative elements.
Interventions
For the feasibility trial, the intervention was the use of the cataract decision aid, incorporating frequently asked questions and personalised estimations of both adverse outcomes and self-reported benefit.
Main outcome measures
There was a range of quantitative and qualitative outcome measures: questionnaire psychometric performance metrics, risk indicators of adverse surgical events and visual outcome, predictors of self-reported outcome following cataract surgery, patient and health-care practitioner views, health economic calibration measures and randomised controlled trial feasibility measures.
Data sources
The data sources were patient self-reported questionnaire responses, study clinical data collection forms, recorded interviews with patients and health-care professionals, and anonymised National Ophthalmology Database data.
Results
Work package 1 â Cat-PROM5 was developed and validated with excellent to good psychometric properties (Rasch reliability 0.9, intraclass correlation repeatability 0.9, unidimensionality with residual eigenvalues â€â1.5) and excellent responsiveness to surgical intervention (Cohen delta â1.45). Work package 2 â earlier risk models for posterior capsule rupture and visual acuity loss were broadly affirmed (C-statistic for posterior capsule rupture 0.64; visual acuity loss 0.71). Work package 3 â the Cat-PROM5-based self-reported outcome regression models were derived based on 1181 participants with complete data (R2âââ30% for each). Of the four preference-based health economic indices assessed, two demonstrated reasonable performance. Cat-PROM5 was successfully calibrated to health economic indices; adjusted limited dependent variable mixture models offered good to excellent fit (root-mean-square error 0.10â0.16). The personalised quantitative risk information was generally perceived as beneficial. A cataract decision aid and cataract decision quality measure were successfully developed based on the views of patients and health-care professionals. Work package 4 â data completeness was good for the feasibility study primary and secondary variables both before and after intervention/surgery (data completeness range 100â88%). Considering ability to recruit, the sample size required, instrumentation and availability of necessary health economic data, a fully powered randomised controlled trial (patients, nâ=â800, effect size 0.2 standard deviations, power 80%; pâ=â0.05) of the cataract decision aid would be feasible following psychometric refinement of the primary outcome (the cataract decision quality measure). The cataract decision aid was generally well-received by patients and health-care professionals, with cautions raised regarding perceived time and workload barriers. Discordant outcomes mostly related to patient dissatisfaction, with no clinical problem found.
Limitations
The National Ophthalmology Database data are expected to include some errors (mitigated by large multicentre data aggregations). The feasibility randomised controlled trial primary outcome (the cataract decision quality measure) displayed psychometric imperfections requiring refinement. The clinical occurrence of discordant outcomes is uncommon and the study team experienced difficulty identifying patients in this situation.
Future work
Future work could include regular review of the risk models for adverse outcomes to ensure currency, and the technical precision of complex-numbers analysis of refractive outcome to invite opportunities to improve post-operative spectacle-free vision. In addition, a fully powered randomised controlled trial of the cataract decision aid would be feasible, following psychometric refinement of the primary outcome (the cataract decision quality measure); this would clarify its potential role in routine service delivery.
Conclusions
In this research programme, evidence-based clinical tools have been successfully developed to improve pre-operative decision-making in cataract surgery. These include a psychometrically robust, patient-reported outcome measure (Cat-PROM5); prediction models for patient self-reported outcomes using Cat-PROM5; prediction models for clinically adverse surgical events and adverse visual acuity outcomes; and a cataract decision aid with relevant general information and personalised risk/benefit predictions. In addition, the successful mapping of Cat-PROM5 to existing health economic indices was achieved and the performances of indices were assessed in patients undergoing cataract surgery. A future full-powered randomised controlled trial of the cataract decision aid would be feasible (patients, nâ=â800, effect size 0.2 standard deviations, power 80%; pâ=â0.05).
Trial registration
This trial is registered as ISRCTN11309852.
Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 9. See the NIHR Journals Library website for further project information
Ideas and Perspectives: A Strategic Assessment of Methane and Nitrous Oxide Measurements In the Marine Environment
In the current era of rapid climate change, accurate characterization of climate-relevant gas dynamics-namely production, consumption, and net emissions-is required for all biomes, especially those ecosystems most susceptible to the impact of change. Marine environments include regions that act as net sources or sinks for numerous climateactive trace gases including methane (CH4) and nitrous oxide (N2O). The temporal and spatial distributions of CH4 and N2O are controlled by the interaction of complex biogeochemical and physical processes. To evaluate and quantify how these mechanisms affect marine CH4 and N2O cycling requires a combination of traditional scientific disciplines including oceanography, microbiology, and numerical modeling. Fundamental to these efforts is ensuring that the datasets produced by independent scientists are comparable and interoperable. Equally critical is transparent communication within the research community about the technical improvements required to increase our collective understanding of marine CH4 and N2O. A workshop sponsored by Ocean Carbon and Biogeochemistry (OCB) was organized to enhance dialogue and collaborations pertaining to marine CH4 and N2O. Here, we summarize the outcomes from the workshop to describe the challenges and opportunities for near-future CH4 and N2O research in the marine environment
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