2,710 research outputs found
Asymptotic behavior of global entropy solutions for nonstrictly hyperbolic systems with linear damping
In this paper we investigate the large time behavior of the global weak
entropy solutions to the symmetric Keyftiz-Kranzer system with linear damping.
It is proved that as t tends to infinite the entropy solutions tend to zero in
the L p nor
Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif
Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation
Magnetic Properties of Ab initio Model for Iron-Based Superconductors LaFeAsO
By using variational Monte Carlo method, we examine an effective low-energy
model for LaFeAsO derived from an ab initio downfolding scheme. We show that
quantum and many-body fluctuations near a quantum critical point largely reduce
the antiferromagnetic (AF) ordered moment and the model not only quantitatively
reproduces the small ordered moment in LaFeAsO, but also explains the diverse
dependence on LaFePO, BaFe2As2 and FeTe. We also find that LaFeAsO is under
large orbital fluctuations, sandwiched by the AF Mott insulator and weakly
correlated metals. The orbital fluctuations and Dirac-cone dispersion hold keys
for the diverse magnetic properties.Comment: 4 pages, 4 figure
Symmetry breaking orbital anisotropy on detwinned Ba(Fe1-xCox)2As2 above the spin density wave transition
Nematicity, defined as broken rotational symmetry, has recently been observed
in competing phases proximate to the superconducting phase in the cuprate high
temperature superconductors. Similarly, the new iron-based high temperature
superconductors exhibit a tetragonal to orthorhombic structural transition
(i.e. a broken C4 symmetry) that either precedes or is coincident with a
collinear spin density wave (SDW) transition in undoped parent compounds, and
superconductivity arises when both transitions are suppressed via doping.
Evidence for strong in-plane anisotropy in the SDW state in this family of
compounds has been reported by neutron scattering, scanning tunneling
microscopy, and transport measurements. Here we present an angle resolved
photoemission spectroscopy study of detwinned single crystals of a
representative family of electron-doped iron-arsenide superconductors,
Ba(Fe1-xCox)2As2 in the underdoped region. The crystals were detwinned via
application of in-plane uniaxial stress, enabling measurements of single domain
electronic structure in the orthorhombic state. At low temperatures, our
results clearly demonstrate an in-plane electronic anisotropy characterized by
a large energy splitting of two orthogonal bands with dominant dxz and dyz
character, which is consistent with anisotropy observed by other probes. For
compositions x>0, for which the structural transition (TS) precedes the
magnetic transition (TSDW), an anisotropic splitting is observed to develop
above TSDW, indicating that it is specifically associated with TS. For
unstressed crystals, the band splitting is observed close to TS, whereas for
stressed crystals the splitting is observed to considerably higher
temperatures, revealing the presence of a surprisingly large in-plane nematic
susceptibility in the electronic structure.Comment: final version published in PNAS, including supplementary informatio
Influencia del conocimiento financiero en el bienestar financiero de usuarios de tarjeta de cr?dito y/o pr?stamos personales entre 18 y 79 a?os en Per? en el 2019
En raz?n de que existe incertidumbre y vac?os de informaci?n relacionados a la vulnerabilidad econ?mica y su relaci?n con el conocimiento financiero, esta investigaci?n tiene como objetivo determinar si el nivel de conocimiento financiero influy? significativamente en el bienestar financiero de los usuarios de tarjetas de cr?dito y pr?stamos personales de 18-79 a?os en el Per? en el a?o 2019. La metodolog?a empleada fue de tipo correlacional transversal, con dise?o no experimental. Se utiliz? como base de datos, la informaci?n de la Encuesta Nacional de Capacidades Financieras 2019, realizada por la SBS entre julio y agosto del 2019 a nivel nacional; y, como gu?a de determinaci?n de variables, metodolog?a y an?lisis, las provistas por la SBS y la OECD/INFE. La poblaci?n contiene 1205 observaciones; y, la muestra 219. Para el an?lisis se aplicaron: Prueba de Alfa de Cronbach; Prueba de correlaci?n de Pearson; Prueba de Rachas; y, Pruebas Logit Binomiales y Multinomiales. El estudio concluy? que el conocimiento financiero influy? significativamente en el bienestar financiero de los usuarios de tarjetas de cr?dito y pr?stamos personales de 18-79 a?os en el Per? en el a?o 2019
Do consistent models mimic General Relativity plus ?
Modified gravity models are subject to a number of consistency requirements
which restrict the form that the function can take. We study a
particular class of functions which satisfy various constraints that
have been found in the literature. These models have a late time accelerating
epoch, and an acceptable matter era. We calculate the Friedmann equation for
our models, and show that in order to satisfy the constraints we impose, they
must mimic General Relativity plus throughout the cosmic history,
with exponentially suppressed corrections. We also find that the free
parameters in our model must be fine tuned to obtain an acceptable late time
accelerating phase. We discuss the generality of this conclusion.Comment: 8 pages, 4 figures. References adde
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial
Background Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics. Methods Patients aged ≥ 12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. The primary end point was RFS per investigator review; DMFS per investigator review was secondary. Subgroups of interest were melanoma subtype (nodular vs non-nodular), tumor thickness ( ≤ 4 mm vs \u3e 4 mm), presence of ulceration (yes vs no), mitotic rate ( \u3c 5 per mm 2 (median) vs ≥ 5 per mm 2), and presence of tumor-infiltrating lymphocytes (TILs; absent vs present). Results Between September 23, 2018, and November 4, 2020, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 27.4 months (range, 14.0-39.4). The HR (95% CI) for RFS was 0.54 (0.37 to 0.79) for nodular and 0.77 (0.53 to 1.11) for non-nodular melanoma; 0.57 (0.37 to 0.89) for thickness ≤ 4 mm and 0.69 (0.50 to 0.96) for \u3e 4 mm; 0.66 (0.50 to 0.89) for ulceration and 0.57 (0.32 to 1.03) for no ulceration; 0.57 (0.35 to 0.92) for mitotic rate \u3c 5 per mm 2 and 0.57 (0.40 to 0.80) for ≥ 5 per mm 2; and 0.89 (0.52 to 1.54) for TILs absent and 0.51 (0.34 to 0.76) for TILs present. DMFS results were similar. In a Cox multivariate analysis, treatment arm, tumor thickness, and mitotic rate were significant independent factors for RFS, and treatment arm and mitotic rate were significant independent factors for DMFS. Conclusions In this post hoc analysis, the benefit of pembrolizumab was largely consistent with the overall study population regardless of histopathologic characteristics. These results support the use of adjuvant pembrolizumab in patients with resected stage IIB or IIC melanoma. Trial registration number ClinicalTrials.gov, NCT03553836
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial
Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics.
Methods: Patients aged ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. The primary end point was RFS per investigator review; DMFS per investigator review was secondary. Subgroups of interest were melanoma subtype (nodular vs non-nodular), tumor thickness (≤4 mm vs >4 mm), presence of ulceration (yes vs no), mitotic rate (<5 per mm(median) vs ≥5 per mm), and presence of tumor-infiltrating lymphocytes (TILs; absent vs present).
Results: Between September 23, 2018, and November 4, 2020, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 27.4 months (range, 14.0–39.4). The HR (95% CI) for RFS was 0.54 (0.37 to 0.79) for nodular and 0.77 (0.53 to 1.11) for non-nodular melanoma; 0.57 (0.37 to 0.89) for thickness ≤4 mm and 0.69 (0.50 to 0.96) for >4 mm; 0.66 (0.50 to 0.89) for ulceration and 0.57 (0.32 to 1.03) for no ulceration; 0.57 (0.35 to 0.92) for mitotic rate <5 per mmand 0.57 (0.40 to 0.80) for ≥5 per mm; and 0.89 (0.52 to 1.54) for TILs absent and 0.51 (0.34 to 0.76) for TILs present. DMFS results were similar. In a Cox multivariate analysis, treatment arm, tumor thickness, and mitotic rate were significant independent factors for RFS, and treatment arm and mitotic rate were significant independent factors for DMFS.
Conclusions: In this post hoc analysis, the benefit of pembrolizumab was largely consistent with the overall study population regardless of histopathologic characteristics. These results support the use of adjuvant pembrolizumab in patients with resected stage IIB or IIC melanoma.
Trial registration number: ClinicalTrials.gov,NCT03553836
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