948 resultados para Kirkman, Thomas P.
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The James Webb Space Telescope (JWST) will likely revolutionize transiting exoplanet atmospheric science, due to a combination of its capability for continuous, long duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) Cycle 1 program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful transiting exoplanet characterization programs in later cycles. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed “community targets”) that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations. The latter are a unique challenge compared to transit observations because of their significantly longer durations. Using only a single mode, we propose to observe a full-orbit phase curve of one of the previously characterized, short-orbital-period planets to evaluate the facility-level aspects of long, uninterrupted time-series observations.
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<p>Background Neutrophils play a role in the pathogenesis of asthma, chronic obstructive pulmonary disease, and pulmonary infection. Impaired neutrophil phagocytosis predicts hospital-acquired infection. Despite this, remarkably few neutrophil-specific treatments exist. p><p>Objectives We sought to identify novel pathways for the restoration of effective neutrophil phagocytosis and to activate such pathways effectively in neutrophils from patients with impaired neutrophil phagocytosis. p><p>Methods Blood neutrophils were isolated from healthy volunteers and patients with impaired neutrophil function. In healthy neutrophils phagocytic impairment was induced experimentally by using β2-agonists. Inhibitors and activators of cyclic AMP (cAMP)-dependent pathways were used to assess the influence on neutrophil phagocytosis in vitro. p><p>Results β2-Agonists and corticosteroids inhibited neutrophil phagocytosis. Impairment of neutrophil phagocytosis by β2-agonists was associated with significantly reduced RhoA activity. Inhibition of protein kinase A (PKA) restored phagocytosis and RhoA activity, suggesting that cAMP signals through PKA to drive phagocytic impairment. However, cAMP can signal through effectors other than PKA, such as exchange protein directly activated by cyclic AMP (EPAC). An EPAC-activating analog of cAMP (8CPT-2Me-cAMP) reversed neutrophil dysfunction induced by β2-agonists or corticosteroids but did not increase RhoA activity. 8CPT-2Me-cAMP reversed phagocytic impairment induced by Rho kinase inhibition but was ineffective in the presence of Rap-1 GTPase inhibitors. 8CPT-2Me-cAMP restored function to neutrophils from patients with known acquired impairment of neutrophil phagocytosis. p><p>Conclusions EPAC activation consistently reverses clinical and experimental impairment of neutrophil phagocytosis. EPAC signals through Rap-1 and bypasses RhoA. EPAC activation represents a novel potential means by which to reverse impaired neutrophil phagocytosis.p>
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Poly(methylvinylether-co-maleic acid) (PMVE/MA) is commonly used as a component of pharmaceutical platforms, principally to enhance interactions with biological substrates (mucoadhesion). However, the limited knowledge on the rheological properties of this polymer and their relationships with mucoadhesion has negated the biomedical use of this polymer as a mono-component platform. This study presents a comprehensive study of the rheological properties of aqueous PMVE/MA platforms and defines their relationships with mucoadhesion using multiple regression analysis. Using dilute solution viscometry the intrinsic viscosities of un-neutralised PMVE/MA and PMVE/MA neutralised using NaOH or TEA were 22.32 ± 0.89 dL g-1, 274.80 ± 1.94 dL g-1 and 416.49 ± 2.21 dL g-1 illustrating greater polymer chain expansion following neutralisation using Triethylamine (TEA). PMVE/MA platforms exhibited shear-thinning properties. Increasing polymer concentration increased the consistencies, zero shear rate (ZSR) viscosities (determined from flow rheometry), storage and loss moduli, dynamic viscosities (defined using oscillatory analysis) and mucoadhesive properties, yet decreased the loss tangents of the neutralised polymer platforms. TEA neutralised systems possessed significantly and substantially greater consistencies, ZSR and dynamic viscosities, storage and loss moduli, mucoadhesion and lower loss tangents than their NaOH counterparts. Multiple regression analysis enabled identification of the dominant role of polymer viscoelasticity on mucoadhesion (r > 0.98). The mucoadhesive properties of PMVE/MA platforms were considerable and were greater than those of other platforms that have successfully been shown to enhance in vivo retention when applied to the oral cavity, indicating a positive role for PMVE/MA mono-component platforms for pharmaceutical and biomedical applications.
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PURPOSE: The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact in the context of a prospective randomized trial. PATIENTS AND METHODS: We analyzed the ATM gene in 224 patients treated on the Leukemia Research Fund Chronic Lymphocytic Leukemia 4 (LRF-CLL4) trial with chlorambucil or fludarabine with and without cyclophosphamide. ATM status was analyzed by denaturing high-performance liquid chromatography and was related to treatment response, survival, and the impact of TP53 alterations for the same patient cohort. RESULTS: We identified 36 ATM mutations in 33 tumors, 16 with and 17 without 11q deletion. Mutations were associated with advanced disease stage and involvement of multiple lymphoid sites. Patients with both ATM mutation and 11q deletion showed significantly reduced progression-free survival (median, 7.4 months) compared with those with ATM wild type (28.6 months), 11q deletion alone (17.1 months), or ATM mutation alone (30.8 months), but survival was similar to that in patients with monoallelic (6.7 months) or biallelic (3.4 months) TP53 alterations. This effect was independent of treatment, immunoglobulin heavy chain variable gene (IGHV) status, age, sex, or disease stage. Overall survival for patients with biallelic ATM alterations was also significantly reduced compared with those with ATM wild type or ATM mutation alone (median, 42.2 v 85.5 v 77.6 months, respectively). CONCLUSION: The combination of 11q deletion and ATM mutation in CLL is associated with significantly shorter progression-free and overall survival following first-line treatment with alkylating agents and purine analogs. Assessment of ATM mutation status in patients with 11q deletion may influence the choice of subsequent therapy.
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Thesis (Ph.D.)--University of Washington, 2016-08
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Cheddar cheese was made using control culture (Lactococcus lactis subsp. lactis), or with control culture plus a galactose-metabolising (Gal+) or galactose-non-metabolising (Gal-) Streptococcus thermophilus adjunct; for each culture type, the pH at whey drainage was either low (pH 6.15) or high (pH 6.45). Sc. thermophilus affected the levels of residual lactose and galactose, and the volatile compound profile and sensory properties of the mature cheese (270 d) to an extent dependent on the drain pH and phenotype (Gal+ or Gal-). For all culture systems, reducing drain pH resulted in lower levels of moisture and lactic acid, a higher concentration of free amino acids, and higher firmness. The results indicate that Sc. thermophilus may be used to diversify the sensory properties of Cheddar cheese, for example from a fruity buttery odour and creamy flavour to a more acid taste, rancid odour, and a sweaty cheese flavour at high drain pH.
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Purpose The aim of this study was to test the effects of sprint interval training (SIT) on cardiorespiratory fitness and aerobic performance measures in young females. Methods Eight healthy, untrained females (age 21 ± 1 years; height 165 ± 5 cm; body mass 63 ± 6 kg) completed cycling peak oxygen uptake ( V˙O2V˙O2 peak), 10-km cycling time trial (TT) and critical power (CP) tests pre- and post-SIT. SIT protocol included 4 × 30-s “all-out” cycling efforts against 7 % body mass interspersed with 4 min of active recovery performed twice per week for 4 weeks (eight sessions in total). Results There was no significant difference in V˙O2V˙O2 peak following SIT compared to the control period (control period: 31.7 ± 3.0 ml kg−1 min−1; post-SIT: 30.9 ± 4.5 ml kg−1 min−1; p > 0.05), but SIT significantly improved time to exhaustion (TTE) (control period: 710 ± 101 s; post-SIT: 798 ± 127 s; p = 0.00), 10-km cycling TT (control period: 1055 ± 129 s; post-SIT: 997 ± 110 s; p = 0.004) and CP (control period: 1.8 ± 0.3 W kg−1; post-SIT: 2.3 ± 0.6 W kg−1; p = 0.01). Conclusions These results demonstrate that young untrained females are responsive to SIT as measured by TTE, 10-km cycling TT and CP tests. However, eight sessions of SIT over 4 weeks are not enough to provide sufficient training stimulus to increase V˙O2V˙O2 peak.
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We develop the a-posteriori error analysis of hp-version interior-penalty discontinuous Galerkin finite element methods for a class of second-order quasilinear elliptic partial differential equations. Computable upper and lower bounds on the error are derived in terms of a natural (mesh-dependent) energy norm. The bounds are explicit in the local mesh size and the local degree of the approximating polynomial. The performance of the proposed estimators within an automatic hp-adaptive refinement procedure is studied through numerical experiments.
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We shall consider the weak formulation of a linear elliptic model problem with discontinuous Dirichlet boundary conditions. Since such problems are typically not well-defined in the standard H^1-H^1 setting, we will introduce a suitable saddle point formulation in terms of weighted Sobolev spaces. Furthermore, we will discuss the numerical solution of such problems. Specifically, we employ an hp-discontinuous Galerkin method and derive an L^2-norm a posteriori error estimate. Numerical experiments demonstrate the effectiveness of the proposed error indicator in both the h- and hp-version setting. Indeed, in the latter case exponential convergence of the error is attained as the mesh is adaptively refined.
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Samples of cultivated Ulva clathrata were collected from a medium scale system (MSS, 1.5 1.5 m tank), or from a large scale system (LSS, 0.8 ha earthen pond). MSS samples were dried directly while the LSS sample was washed in freshwater and pressed before drying. Crude protein content ranged 20–26%, essential amino acids accounting for 32–36% of crude protein. The main analysed monosaccharides were rhamnose (36–40%), uronic acids (27–29%), xylose (10–13%) and glucose (10–16%). Some notable variations between MSS and LSS samples were observed for total dietary fibre (26% vs 41%), saturated fatty acids (31% vs 51%), PUFAS (33% vs 13%), carotenoids (358 vs 169 mg kg1 dw) and for Ca (9 vs 19 g kg1 ), Fe (0.6 vs 4.2 g kg1 ), Cu (44 vs 14 mg kg1 ), Zn (93 vs 17 mg kg1 ) and As (2 vs 9 mg kg1 ). The chemical composition of U. clathrata indicates that it has a good potential for its use in human and animal food.
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Abstract Objective: Evidence shows an association between muscular strength (MS) and health among youth, however low muscular strength cut-points for the detection of high metabolic risk in Latin-American populations are scarce. The aim of this study was two-fold: to explore potential age- and sex-specific thresholds of MS, for optimal cardiometabolic risk categorization among Colombian children and adolescents; and to investigate if cardiometabolic risk differed by MS group by applying the receiver operating characteristic curve (ROC) cut point. Methods: This is a secondary analysis of a cross-sectional study (the FUPRECOL study), published elsewhere. The FUPRECOL study assessments were conducted during the 2014– 2015 school year. MS was estimated by a handle dynamometer on 1,950 children and adolescents from Colombia, using the MS relative to weight (handgrip strength/body mass). A metabolic risk score was computed from the following components: waist circumference, triglycerides, HDL-c, glucose, systolic and diastolic blood pressure. ROC analysis showed a significant discriminatory accuracy of MS in identifying the low/high metabolic risk in children and adolescents and both gender. Results: In children, handgrip strength/body mass level for a low metabolic risk were 0.359 and 0.376 in girls and boys, respectively. In adolescents, these points were 0.440 and 0.447 in girls and boys, respectively. Conclusion: In conclusion, the results suggest a hypothetical MS level relative to weight for having a low metabolic risk, which could be used to identify youths at risk.
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Aus: L'Observateur des tribunaux, Nouv. sér ; 1.1840
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Fil: Peretó Rivas, Rubén.
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Fil: Peretó Rivas, Rubén.