147 research outputs found
Exploring N-rich phases in LixNy clusters for hydrogen storage at nano-scale
We have performed cascade genetic algorithm and ab initio atomistic
thermodynamics under the framework of first-principles density functional
theory to study the (meta-)stability of a wide range of LixNy clusters. We
found that hybrid xc-functional is essential to address this problem as a
local/semi-local functional simply fails even to predict a qualitative
prediction. Most importantly, we find that though in bulk Lithium Nitride, Li
rich phase, i.e. Li3N, is the stable stoichiometry, in small LixNy clusters
N-rich phases are more stable at thermodynamic equilibrium. We further show a
that these N-rich clusters are promising hydrogen storage material because of
their easy adsorption and desorption ability at respectively low (< 300K) and
moderately high temperature (> 600K).Comment: 5 pages, 4 figure
Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. OBJECTIVE: This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. METHODS: From our registry, we have analyzed a total of 500 unselected patients with HLH. RESULTS: Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. CONCLUSION: We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL.Supported by grants from Associazione Italiana Ricerca Istiocitosi (AIRI), Associazione Ciemmeesse-Girotondo per il Meyer, Ministero della Salute (Bando Malattie Rare RF-TOS-2008-1219488), and the Seventh Framework Programme (FP7) of the European Commission (“FIGHT-HLH” Project no. 306124 to M.A.).
Disclosure of potential conflict of interest: D. Pende receives royalties paid to her institution. G. M. Griffiths has received research support from the Wellcome Trust. L. Luzzatto is on the Alexion Pharmaceuticals SAB and has received consultancy fees from GlaxoSmithKline.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jaci.2015.06.04
Genetic predisposition to hemophagocytic lymphohistiocytosis: report on 500 patients from the Italian registry
Background Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. Objective This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. Methods From our registry, we have analyzed a total of 500 unselected patients with HLH. Results Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. Conclusion We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL
Hemophagocytic lymphohistiocytosis in 2 patients with underlying IFN-γ receptor deficiency
The Soliton-Ricci Flow with variable volume forms
We introduce a flow of Riemannian metrics and positive volume forms over
compact oriented manifolds whose formal limit is a shrinking Ricci soliton. The
case of a fixed volume form has been considered in our previous work. We still
call this new flow the Soliton-Ricci flow. It corresponds to a forward Ricci
type flow up to a gauge transformation generated by the gradient of the density
of the volumes. The new Soliton-Ricci flow exist for all times and represents
the gradient flow of Perelman's functional with respect to a
pseudo-Riemannian structure over the space of metrics and normalized positive
volume forms. We obtain an expression of the Hessian of the
functional with respect to such structure. Our expression shows the elliptic
nature of this operator in directions orthogonal to the orbits obtained by the
action of the group of diffeomorphism. In the case the initial data is K\"ahler
then the Soliton-Ricci flow preserves the K\"ahler condition and the symplectic
form. The space of tamed complex structures embeds naturally to the space of
metrics and normalized positive volume forms via the Chern-Ricci map. Over such
space the pseudo-Riemannian structure restricts to a Riemannian one. We perform
a study of the sign of the restriction of the Hessian of the
functional over such space. This allows us to obtain a finite dimensional
reduction, and thus the solution, of the well known problem of the stability of
K\"ahler-Ricci solitons.Comment: 134 pages, no figure
Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.
Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals
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