149 research outputs found
Molecular Mapping of the Thrombin-Heparin Cofactor II Complex
We used 55 Ala-scanned recombinant thrombin molecules to define residues important for inhibition by the serine protease inhibitor (serpin) heparin cofactor II (HCII) in the absence and presence of glycosaminoglycans. We verified the importance of numerous basic residues in anion-binding exosite-1 (exosite-1) and found 4 additional residues, Gln24, Lys65, His66, and Tyr71 (using the thrombin numbering system), that were resistant to HCII inhibition with and without glycosaminoglycans. Inhibition rate constants for these exosite-1 (Q24A, K65A, H66A, Y71A) thrombin mutants (0.02-0.38 x 10(8) m(-1) min(-1) for HCII-heparin when compared with 2.36 x 10(8) m(-1) min(-1) with wild-type thrombin and 0.03-0.53 x 10(8) m(-1) min(-1) for HCII-dermatan sulfate when compared with 5.23 x 10(8) m(-1) min(-1) with wild-type thrombin) confirmed that the structural integrity of thrombin exosite-1 is critical for optimal HCII-thrombin interactions in the presence of glycosaminoglycans. However, our results are also consistent for HCII-glycosaminoglycan-thrombin ternary complex formation. Ten residues surrounding the active site of thrombin were implicated in HCII interactions. Four mutants (Asp51, Lys52, Lys145/Thr147/Trp148, Asp234) showed normal increased rates of inhibition by HCII-glycosaminoglycans, whereas four mutants (Trp50, Glu202, Glu229, Arg233) remained resistant to inhibition by HCII with glycosaminoglycans. Using 11 exosite-2 thrombin mutants with 20 different mutated residues, we saw no major perturbations of HCII-glycosaminoglycan inhibition reactions. Collectively, our results support a "double bridge" mechanism for HCII inhibition of thrombin in the presence of glycosaminoglycans, which relies in part on ternary complex formation but is primarily dominated by an allosteric process involving contact of the "hirudin-like" domain of HCII with thrombin exosite-1
K -> pi pi and a light scalar meson
We explore the Delta-I= 1/2 rule and epsilon'/epsilon in K -> pi pi
transitions using a Dyson-Schwinger equation model. Exploiting the feature that
QCD penguin operators direct K^0_S transitions through 0^{++} intermediate
states, we find an explanation of the enhancement of I=0 K -> pi pi transitions
in the contribution of a light sigma-meson. This mechanism also affects
epsilon'/epsilon.Comment: 7 pages, REVTE
Implications of response shift for micro-, meso-, and macro-level healthcare decision-making using results of patient-reported outcome measures
Purpose Results of patient-reported outcome measures (PROMs) are increasingly used to inform healthcare decision-making. Research has shown that response shift can impact PROM results. As part of an international collaboration, our goal is to provide a framework regarding the implications of response shift at the level of patient care (micro), healthcare institute (meso), and healthcare policy (macro). Methods Empirical evidence of response shift that can influence patients' self-reported health and preferences provided the foundation for development of the framework. Measurement validity theory, hermeneutic philosophy, and micro-, meso-, and macro-level healthcare decision-making informed our theoretical analysis. Results At the micro-level, patients' self-reported health needs to be interpreted via dialogue with the clinician to avoid misinterpretation of PROM data due to response shift. It is also important to consider the potential impact of response shift on study results, when these are used to support decisions. At the meso-level, individual-level data should be examined for response shift before aggregating PROM data for decision-making related to quality improvement, performance monitoring, and accreditation. At the macro-level, critical reflection on the conceptualization of health is required to know whether response shift needs to be controlled for when PROM data are used to inform healthcare coverage. Conclusion Given empirical evidence of response shift, there is a critical need for guidelines and knowledge translation to avoid potential misinterpretations of PROM results and consequential biases in decision-making. Our framework with guiding questions provides a structure for developing strategies to address potential impacts of response shift at micro-, meso-, and macro-levels.Analysis and support of clinical decision makin
Formation and Evolution of Supermassive Black Holes
The correlation between the mass of supermassive black holes in galaxy nuclei
and the mass of the galaxy spheroids or bulges (or more precisely their central
velocity dispersion), suggests a common formation scenario for galaxies and
their central black holes. The growth of bulges and black holes can commonly
proceed through external gas accretion or hierarchical mergers, and are both
related to starbursts. Internal dynamical processes control and regulate the
rate of mass accretion. Self-regulation and feedback are the key of the
correlation. It is possible that the growth of one component, either BH or
bulge, takes over, breaking the correlation, as in Narrow Line Seyfert 1
objects. The formation of supermassive black holes can begin early in the
universe, from the collapse of Population III, and then through gas accretion.
The active black holes can then play a significant role in the re-ionization of
the universe. The nuclear activity is now frequently invoked as a feedback to
star formation in galaxies, and even more spectacularly in cooling flows. The
growth of SMBH is certainly there self-regulated. SMBHs perturb their local
environment, and the mergers of binary SMBHs help to heat and destroy central
stellar cusps. The interpretation of the X-ray background yields important
constraints on the history of AGN activity and obscuration, and the census of
AGN at low and at high redshifts reveals the downsizing effect, already
observed for star formation. History appears quite different for bright QSO and
low-luminosity AGN: the first grow rapidly at high z, and their number density
decreases then sharply, while the density of low-luminosity objects peaks more
recently, and then decreases smoothly.Comment: 31 pages, 13 figures, review paper for Astrophysics Update
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
The Qur'an and Identity in Contemporary Chinese Fiction
How is it possible to comprehend and assess the impact of the Qurâan on the literary expressions of Chinese Muslims (Hui) when the first full âtranslationsâ of the Qurâan in Chinese made by non-Muslims from Japanese and English appeared only in 1927 and 1931, and by a Muslim from Arabic in 1932? But perhaps the fact that such a translation appeared so late in the history of the Muslim community in China, who have had a continuous presence since the ninth-century, is the best starting point. For it would be possible to address the relationship between the sacred text (as well as language) and identity among minority groups in a different way. This paper looks at the ways in which the Qurâan is imagined then embodied in literary texts authored by two prize-winning Chinese Muslim authors: Huo Da (b. 1945) and Zhang Chengzhi (b. 1948). While Huo Da, who does not have access to the Arabic language, alludes to the Chinese Qurâan in her novel, The Muslimâs Funeral (1982), transforming the its teachings into ritual performances of alterity through injecting Arabic and Persian words for religious rituals into her narrative of a Muslim familyâs fortunes at the turn of the twentieth century, Zhang Chengzhi, who learned Arabic as an adult and travelled widely in the Muslim world, involves himself in reconstructing the history of the spread and persecution of the Jahriyya Sufi sect (an off-shoot of the Naqshabandiyya) in China between the seventeenth and nineteenth centuries in his only historical novel, A History of the Soul (1991), and in education reform in Muslim communities, inventing an identity for Chinese Muslims based on direct knowledge of the sacred text and tradition and informed by the history of Islam not in China alone but in the global Islamic world, especially Arabic Islamic history
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