36 research outputs found
Bone Marrow–Derived Antigen-Presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (Tap)-Dependent and -Independent Pathways of Antigen Presentation
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Seismic imaging of reservoir flow properties: Time-lapse amplitude changes
Asymptotic methods provide an efficient means by which to infer reservoir flow properties, such as permeability, from time-lapse seismic data. A trajectory-based methodology, much like ray-based methods for medical and seismic imaging, is the basis for an iterative inversion of time-lapse amplitude changes. In this approach a single reservoir simulation is required for each iteration of the algorithm. A comparison between purely numerical and the trajectory-based sensitivities demonstrates their accuracy. An application to a set of synthetic amplitude changes indicates that they can recover large-scale reservoir permeability variations from time-lapse data. In an application of actual time-lapse amplitude changes from the Bay Marchand field in the Gulf of Mexico we are able to reduce the misfit by 81% in twelve iterations. The time-lapse observations indicate lower permeabilities are required in the central portion of the reservoir
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Seismic imaging of reservoir flow properties: Time-lapse amplitude changes
Asymptotic methods provide an efficient means by which to infer reservoir flow properties, such as permeability, from time-lapse seismic data. A trajectory-based methodology, much like ray-based methods for medical and seismic imaging, is the basis for an iterative inversion of time-lapse amplitude changes. In this approach a single reservoir simulation is required for each iteration of the algorithm. A comparison between purely numerical and the trajectory-based sensitivities demonstrates their accuracy. An application to a set of synthetic amplitude changes indicates that they can recover large-scale reservoir permeability variations from time-lapse data. In an application of actual time-lapse amplitude changes from the Bay Marchand field in the Gulf of Mexico we are able to reduce the misfit by 81% in twelve iterations. The time-lapse observations indicate lower permeabilities are required in the central portion of the reservoir
A Milestoning Study of the Kinetics of an Allosteric Transition: Atomically Detailed Simulations of Deoxy Scapharca Hemoglobin
Atomically detailed simulations are used to compute the kinetics of the R-to-T transition in deoxy Scapharca hemoglobin. A computational approach called milestoning is utilized that combines 1), an efficient reaction path algorithm; and 2), a “fragment and glue” approach for classical trajectories. Milestoning computes the R-to-T transition kinetics on the microsecond timescale based on atomically detailed trajectories that rarely exceed a nanosecond. Eleven reference hypersurfaces (milestones) are constructed along the reaction coordinate, which is computed with a global path optimization algorithm. Two-hundred classical trajectories are calculated for each of the milestones to collect local distributions of first passage times. These local distributions are used in a non-Markovian theory to compute the overall timescale. Exponential enrichment of reactive trajectories, an important component of the milestoning approach, makes these calculations possible. The overall timescale of the reaction is estimated as 10 ± 9 μs, in accord with available experimental data. The barrier is not sharp and is spread over four milestones. Even after the most significant structural changes are completed (phenylalanine F4 ring flips), highly collective and activated motions continue. The calculations suggest an additional late free energy barrier
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Cross-sectional validation of the PROMIS-Preference scoring system.
ObjectivesThe PROMIS-Preference (PROPr) score is a recently developed summary score for the Patient-Reported Outcomes Measurement Information System (PROMIS). PROPr is a preference-based scoring system for seven PROMIS domains created using multiplicative multi-attribute utility theory. It serves as a generic, societal, preference-based summary scoring system of health-related quality of life. This manuscript evaluates construct validity of PROPr in two large samples from the US general population.MethodsWe utilized 2 online panel surveys, the PROPr Estimation Survey and the Profiles-Health Utilities Index (HUI) Survey. Both included the PROPr measure, patient demographic information, self-reported chronic conditions, and other preference-based summary scores: the EuroQol-5D (EQ-5D-5L) and HUI in the PROPr Estimation Survey and the HUI in the Profiles-HUI Survey. The HUI was scored as both the Mark 2 and the Mark 3. Known-groups validity was evaluated using age- and gender-stratified mean scores and health condition impact estimates. Condition impact estimates were created using ordinary least squares regression in which a summary score was regressed on age, gender, and a single health condition. The coefficient for the health condition is the estimated effect on the preference score of having a condition vs. not having it. Convergent validity was evaluated using Pearson correlations between PROPr and other summary scores.ResultsThe sample consisted of 983 respondents from the PROPr Estimation Survey and 3,000 from the Profiles-HUI survey. Age- and gender-stratified mean PROPr scores were lower than EQ-5D and HUI scores, with fewer subjects having scores corresponding to perfect health on the PROPr. In the PROPr Estimation survey, all 11 condition impact estimates were statistically significant using PROPr, 8 were statistically significant by the EQ-5D, 7 were statistically significant by HUI Mark 2, and 9 were statistically significant by HUI Mark 3. In the Profiles-HUI survey, all 21 condition impact estimates were statistically significant using summary scores from all three scoring systems. In these samples, the correlations between PROPr and the other summary measures ranged from 0.67 to 0.70.ConclusionsThese results provide evidence of construct validity for PROPr using samples from the US general population
Cross-sectional validation of the PROMIS-Preference scoring system.
ObjectivesThe PROMIS-Preference (PROPr) score is a recently developed summary score for the Patient-Reported Outcomes Measurement Information System (PROMIS). PROPr is a preference-based scoring system for seven PROMIS domains created using multiplicative multi-attribute utility theory. It serves as a generic, societal, preference-based summary scoring system of health-related quality of life. This manuscript evaluates construct validity of PROPr in two large samples from the US general population.MethodsWe utilized 2 online panel surveys, the PROPr Estimation Survey and the Profiles-Health Utilities Index (HUI) Survey. Both included the PROPr measure, patient demographic information, self-reported chronic conditions, and other preference-based summary scores: the EuroQol-5D (EQ-5D-5L) and HUI in the PROPr Estimation Survey and the HUI in the Profiles-HUI Survey. The HUI was scored as both the Mark 2 and the Mark 3. Known-groups validity was evaluated using age- and gender-stratified mean scores and health condition impact estimates. Condition impact estimates were created using ordinary least squares regression in which a summary score was regressed on age, gender, and a single health condition. The coefficient for the health condition is the estimated effect on the preference score of having a condition vs. not having it. Convergent validity was evaluated using Pearson correlations between PROPr and other summary scores.ResultsThe sample consisted of 983 respondents from the PROPr Estimation Survey and 3,000 from the Profiles-HUI survey. Age- and gender-stratified mean PROPr scores were lower than EQ-5D and HUI scores, with fewer subjects having scores corresponding to perfect health on the PROPr. In the PROPr Estimation survey, all 11 condition impact estimates were statistically significant using PROPr, 8 were statistically significant by the EQ-5D, 7 were statistically significant by HUI Mark 2, and 9 were statistically significant by HUI Mark 3. In the Profiles-HUI survey, all 21 condition impact estimates were statistically significant using summary scores from all three scoring systems. In these samples, the correlations between PROPr and the other summary measures ranged from 0.67 to 0.70.ConclusionsThese results provide evidence of construct validity for PROPr using samples from the US general population
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PROMIS® Adult Health Profiles: Efficient Short-Form Measures of Seven Health Domains.
BackgroundThere is a need for valid self-report measures of core health-related quality of life (HRQoL) domains.ObjectiveTo derive brief, reliable and valid health profile measures from the Patient Reported Outcomes Measurement Information System® (PROMIS®) item banks.MethodsLiterature review, investigator consensus process, item response theory (IRT) analysis, and expert review of scaling results from multiple PROMIS data sets. We developed 3 profile measures ranging in length from 29 to 57 questions. These profiles assess important HRQoL domains with highly informative subsets of items from respective item banks and yield reliable information across mild-to-severe levels of HRQoL experiences. Each instrument assesses the domains of pain interference, fatigue, depression, anxiety, sleep disturbance, physical function, and social function using 4-, 6-, and 8-item short forms for each domain, and an average pain intensity domain score, using a 0-10 numeric rating scale.ResultsWith few exceptions, all domain short forms within the profile measures were highly reliable across at least 3 standard deviation (30 T-score) units and were strongly correlated with the full bank scores. Construct validity with ratings of general health and quality of life was demonstrated. Information to inform statistical power for clinical and general population samples is also provided.ConclusionsAlthough these profile measures have been used widely, with summary scoring routines published, description of their development, reliability, and initial validity has not been published until this article. Further evaluation of these measures and clinical applications are encouraged
De novo Synthesis and Assembly of rRNA into Ribosomal Subunits during Cold Acclimation in Escherichia coli
Age- and gender-stratified mean scores in the PROPr Estimation sample.
<p>HUI 2 is the Health Utilities Index Mark 2, HUI 3 is the Health Utilities Index Mark 3, EQ-5D US Mapped is the Euroqol-5D-5L mapped to the US valuation set, PROPr is the PROMIS-Preference score.</p