22 research outputs found
Space-time evolution of electron cascades in diamond
Here we describe model calculations to follow the spatio-temporal evolution
of secondary electron cascades in diamond. The band structure of the insulator
has been explicitly incorporated into the calculations as it affects
ionizations from the valence band. A Monte-Carlo model was constructed to
describe the path of electrons following the impact of a single electron of
energy E 250 eV. The results show the evolution of the secondary electron
cascades in terms of the number of electrons liberated, the spatial
distribution of these electrons, and the energy distribution among the
electrons as a function of time. The predicted ionization rates (5-13 electrons
in 100 fs) lie within the limits given by experiments and phenomenological
models. Calculation of the local electron density and the corresponding Debye
length shows that the latter is systematically larger than the radius of the
electron cloud. This means that the electron gas generated does not represent a
plasma in a single impact cascade triggered by an electron of E 250 eV energy.
This is important as it justifies the independent-electron approximation used
in the model. At 1 fs, the (average) spatial distribution of secondary
electrons is anisotropic with the electron cloud elongated in the direction of
the primary impact. The maximal radius of the cascade is about 50 A at this
time. As the system cools, energy is distributed more equally, and the spatial
distribution of the electron cloud becomes isotropic. At 90 fs maximal radius
is about 150 A. The Monte-Carlo model described here could be adopted for the
investigation of radiation damage in other insulators and has implications for
planned experiments with intense femtosecond X-ray sources.Comment: 26 pages, latex, 13 figure
Quantum Electronics
Contains research objectives and summary of research on eight projects in three sections and reports on two research projects.U. S. Air Force - Office of Scientific Research (Contract F44620-71-C-0051)Joint Services Electronics Program (Contract DAAB07-74-C-0630)University of California, Livermore (Subcontract No. 7877409)U. S. Army Research Office - Durham (Contract DAHC04-72-C-0044
Quantum Electronics
Contains reports on three research projects.U. S. Air Force - Office of Scientific Research (Contract F44620-71-C-0051)Joint Services Electronics Program (Contract DAAB07-74-C-0630)University of California, Livermore (Subcontract 7877409
Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.
Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)
Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants with Treatment Resistance in Schizophrenia
Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P =.001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P =.04). Conclusions and Relevance: In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance
Energy utilization in fluctuating biological energy converters
We have argued previously [Szoke et al., FEBS Lett. 553, 18-20 (2003); Curr. Chem. Biol. 1, 53-57 (2007)] that energy utilization and evolution are emergent properties based on a small number of established laws of physics and chemistry. The relevant laws constitute a framework for biology on a level intermediate between quantum chemistry and cell biology. There are legitimate questions whether these concepts are valid at the mesoscopic level. Such systems fluctuate appreciably, so it is not clear what their efficiency is. Advances in fluctuation theorems allow the description of such systems on a molecular level. We attempt to clarify this topic and bridge the biochemical and physical descriptions of mesoscopic systems