150 research outputs found

    A Review of Rare Pion and Muon Decays

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    After a decade of no measurements of pion and muon rare decays, PIBETA, a new experimental program is producing its first results. We report on a new experimental study of the pion beta decay, Pi(+) -> Pi(0) e(+) Nu, the Pi(e2 gamma) radiative decay, Pi(+) -> e(+) Nu Gamma, and muon radiative decay, Mu -> e Nu Gamma. The new results represent four- to six-fold improvements in precision over the previous measurements. Excellent agreement with Standard Model predictions is observed in all channels except for one kinematic region of the Pi(e2 gamma) radiative decay involving energetic photons and lower-energy positrons.Comment: 10 pages, 6 figures, 2 tables, invited talk presented at MESON 2004, 8th Int'l. Workshop on Meson Production, Properties and Interaction, Krakow, Poland 4-8 June 200

    Protein conformational entropy is not slaved to water

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    Conformational entropy can be an important element of the thermodynamics of protein functions such as the binding of ligands. The observed role for conformational entropy in modulating molecular recognition by proteins is in opposition to an often-invoked theory for the interaction of protein molecules with solvent water. The solvent slaving model predicts that protein motion is strongly coupled to various aspects of water such as bulk solvent viscosity and local hydration shell dynamics. Changes in conformational entropy are manifested in alterations of fast internal side chain motion that is detectable by NMR relaxation. We show here that the fast-internal side chain dynamics of several proteins are unaffected by changes to the hydration layer and bulk water. These observations indicate that the participation of conformational entropy in protein function is not dictated by the interaction of protein molecules and solvent water under the range of conditions normally encountered

    Evaluation of a new arterial pressure-based cardiac output device requiring no external calibration

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    <p>Abstract</p> <p>Background</p> <p>Several techniques have been discussed as alternatives to the intermittent bolus thermodilution cardiac output (CO<sub>PAC</sub>) measurement by the pulmonary artery catheter (PAC). However, these techniques usually require a central venous line, an additional catheter, or a special calibration procedure. A new arterial pressure-based cardiac output (CO<sub>AP</sub>) device (FloTrac™, Vigileo™; Edwards Lifesciences, Irvine, CA, USA) only requires access to the radial or femoral artery using a standard arterial catheter and does not need an external calibration. We validated this technique in critically ill patients in the intensive care unit (ICU) using CO<sub>PAC </sub>as the method of reference.</p> <p>Methods</p> <p>We studied 20 critically ill patients, aged 16 to 74 years (mean, 55.5 ± 18.8 years), who required both arterial and pulmonary artery pressure monitoring. CO<sub>PAC </sub>measurements were performed at least every 4 hours and calculated as the average of 3 measurements, while CO<sub>AP </sub>values were taken immediately at the end of bolus determinations. Accuracy of measurements was assessed by calculating the bias and limits of agreement using the method described by Bland and Altman.</p> <p>Results</p> <p>A total of 164 coupled measurements were obtained. Absolute values of CO<sub>PAC </sub>ranged from 2.80 to 10.80 l/min (mean 5.93 ± 1.55 l/min). The bias and limits of agreement between CO<sub>PAC </sub>and CO<sub>AP </sub>for unequal numbers of replicates was 0.02 ± 2.92 l/min. The percentage error between CO<sub>PAC </sub>and CO<sub>AP </sub>was 49.3%. The bias between percentage changes in CO<sub>PAC </sub>(ΔCO<sub>PAC</sub>) and percentage changes in CO<sub>AP </sub>(ΔCO<sub>AP</sub>) for consecutive measurements was -0.70% ± 32.28%. CO<sub>PAC </sub>and CO<sub>AP </sub>showed a Pearson correlation coefficient of 0.58 (<it>p </it>< 0.01), while the correlation coefficient between ΔCO<sub>PAC </sub>and ΔCO<sub>AP </sub>was 0.46 (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Although the CO<sub>AP </sub>algorithm shows a minimal bias with CO<sub>PAC </sub>over a wide range of values in an inhomogeneous group of critically ill patients, the scattering of the data remains relative wide. Therefore, the used algorithm (V 1.03) failed to demonstrate an acceptable accuracy in comparison to the clinical standard of cardiac output determination.</p

    Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

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    We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains

    Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1

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    Complex conformational dynamics are essential for function of the dimeric molecular cha- perone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimer- ization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity of human Hsp90 is markedly enhanced by the co-chaperone Aha1. However, the cellular concentration of Aha1 is substoichiometric relative to Hsp90. Here we report that initial recruitment of this cochaperone to Hsp90 is markedly enhanced by phosphorylation of a highly conserved tyrosine (Y313 in Hsp90α) in the Hsp90 middle domain. Importantly, phosphomimetic mutation of Y313 promotes formation of a transient complex in which both N- and C-domains of Aha1 bind to distinct surfaces of the middle domains of opposing Hsp90 protomers prior to ATP-directed N-domain dimerization. Thus, Y313 represents a phosphorylation-sensitive conformational switch, engaged early after client loading, that affects both local and long-range conformational dynamics to facilitate initial recruitment of Aha1 to Hsp90

    EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

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    More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

    Building a transdisciplinary expert consensus on the cognitive drivers of performance under pressure: An international multi-panel Delphi study

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    IntroductionThe ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure.MethodsInternational experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance.ResultsSixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control—Performance Monitoring; (3) Arousal and Regulatory Systems—Arousal; (4) Cognitive Control—Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control—Response Selection and Inhibition/Suppression; (6) Working memory—Flexible Updating; (7) Working memory—Active Maintenance; (8) Perception and Understanding of Self—Self-knowledge; (9) Working memory—Interference Control, and (10) Expert-suggested—Shifting.DiscussionOur results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization
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