One-dimensional Model of a Gamma Klystron

A new scheme for amplification of coherent gamma rays is proposed. The key elements are crystalline undulators - single crystals with periodically bent crystallographic planes exposed to a high energy beam of charged particles undergoing channeling inside the crystals. The scheme consists of two such crystals separated by a vacuum gap. The beam passes the crystals successively. The particles perform undulator motion inside the crystals following the periodic shape of the crystallographic planes. Gamma rays passing the crystals parallel to the beam get amplified due to interaction with the particles inside the crystals. The term `gamma klystron' is proposed for the scheme because its operational principles are similar to those of the optical klystron. A more simple one-crystal scheme is considered as well for the sake of comparison. It is shown that the gamma ray amplification in the klystron scheme can be reached at considerably lower particle densities than in the one-crystal scheme, provided that the gap between the crystals is sufficiently large.Comment: RevTeX4, 22 pages, 4 figure

A Multi-Level Optimization Algorithm and a Ship Design Application

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97130/1/AIAA2012-5555.pd

EXPERIENCE WITH A NdFeB BASED 1 Tm DIPOLE*

Abstract A 30° Green Magnet based on permanent NdFeB magnets has been developed and installed in the injection line at the ASTRID2 synchrotron light source. The cost efficient design is optimized for a 1 T field at a length of 1 m using shaped iron poles to surpass the required field homogeneity. The inherent temperature dependence of NdFeB has been passively compensated to below 30 ppm/°C. A study of potential demagnetization effects has been performed by irradiation of NdFeB samples placed directly in a 100 MeV e-beam. A high permanent magnet work point was found to result in enhanced robustness, and the risk of demagnetization was found to be negligible for typical synchrotron applications. The magnet has successfully been in operation at ASTRID2 since autumn 2013

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP-001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 7 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions

What determines how we see nature? Perceptions of naturalness in designed urban green spaces

1. The multiple benefits of ‘nature’ for human health and well-being have been documented at an increasing rate over the past 30 years. A growing body of research also demonstrates the positive well-being benefits of nature-connectedness. There is, however, a lack of evidence about how people's subjective nature experience relates to deliberately designed and managed urban green infrastructure (GI) with definable ‘objective’ characteristics such as vegetation type, structure and density. Our study addresses this gap.2. Site users (n = 1411) were invited to walk through woodland, shrub and herbaceous planting at three distinctive levels of planting structure at 31 sites throughout England, whilst participating in a self-guided questionnaire survey assessing reactions to aesthetics, perceived plant and invertebrate biodiversity, restorative effect, nature-connectedness and socio-demographic characteristics.3. There was a significant positive relationship between perceived naturalness and planting structure. Perceived naturalness was also positively related to the perceived plant and invertebrate biodiversity value, participants’ aesthetic appreciation and the self-reported restorative effect of the planting. A negative relationship was recorded between perceived naturalness and perceived tidiness and care. Our findings showed that participants perceived ‘naturalness’ as biodiverse, attractive and restorative, but not necessarily tidy. Perceived naturalness was also related to participants’ educational qualifications, gender and nature-connectedness, with women and more nature-connected participants perceiving significantly greater levels of naturalness in the planting.4. These findings are highly significant for policymakers and built environment professionals throughout the world aiming to design, manage and fund urban GI to achieve positive human health and biodiversity outcomes. This applies particularly under austerity approaches to managing urban green spaces where local authorities have experienced cuts in funding and must prioritise and justify GI maintenance practices and regimes

Rare coding variants in genes encoding GABA_A receptors in genetic generalised epilepsies: an exome-based case-control study

BACKGROUND: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. METHODS: For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes. FINDINGS: Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41-4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05-2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 [95% CI 1·02-2·08]; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors. INTERPRETATION: Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy. FUNDING: EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund)

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path