Monte Carlo simulation of a sputtering hollow-cathode discharge for laser applications

We report on a kinetic model that computes the electron behaviour in a hollow cathode discharge. It is a part of the PLASIMO toolkit and is based on a Monte-Carlo technique. The model is tested by varying the input parameters and by comparing the output with the output obtained by the freeware Boltzmann equation solver BOLSIG+. The results show that the Monte-Carlo model gives reliable information about the behavior of the electrons in the discharge. The Monte-Carlo module is applied to the case of a hollow cathode discharge for laser applications. Analysis of the output data and its adequateness is done. Future developments of the model are discussed

Monte Carlo simulation of electron kinetics in a hollow cathode discharge

A kinetic model is reported computing the electron behavior in a hollow cathode discharge based on the Monte Carlo technique. It is a part of the PLASIMO modelling toolkit. The model allows the electrons to be closely followed while they travel and undergo collisions in the discharge. The Monte Carlo modulewas applied to the case of a HCD used as an excitation medium of atoms obtained by laser ablation. Results are obtained on the electron energy distribution function and the mean electron energy under typical discharge conditions. The output data and future development of the model and its applications are analyzed and discussed

Identification of tomato accessions as source of new genes for improving heat tolerance: from controlled experiments to field

Background: Due to global warming, the search for new sources for heat tolerance and the identification of genes involved in this process has become an important challenge as of today. The main objective of the current research was to verify whether the heat tolerance determined in controlled greenhouse experiments could be a good predictor of the agronomic performance in field cultivation under climatic high temperature stress. Results: Tomato accessions were grown in greenhouse under three temperature regimes: control (T1), moderate (T2) and extreme heat stress (T3). Reproductive traits (flower and fruit number and fruit set) were used to define heat tolerance. In a first screening, heat tolerance was evaluated in 219 tomato accessions. A total of 51 accessions were identified as being potentially heat tolerant. Among those, 28 accessions, together with 10 accessions from Italy (7) and Bulgaria (3), selected for their heat tolerance in the field in parallel experiments, were re-evaluated at three temperature treatments. Sixteen tomato accessions showed a significant heat tolerance at T3, including five wild species, two traditional cultivars and four commercial varieties, one accession from Bulgaria and four from Italy. The 15 most promising accessions for heat tolerance were assayed in field trials in Italy and Bulgaria, confirming the good performance of most of them at high temperatures. Finally, a differential gene expression analysis in pre-anthesis (ovary) and post-anthesis (developing fruit) under heat stress among pairs of contrasting genotypes (tolerant and sensitive from traditional and modern groups) showed that the major differential responses were produced in post-anthesis fruit. The response of the sensitive genotypes included the induction of HSP genes, whereas the tolerant genotype response included the induction of genes involved in the regulation of hormones or enzymes such as abscisic acid and transferases. Conclusions: The high temperature tolerance of fifteen tomato accessions observed in controlled greenhouse experiments were confirmed in agronomic field experiments providing new sources of heat tolerance that could be incorporated into breeding programs. A DEG analysis showed the complex response of tomato to heat and deciphered the different mechanisms activated in sensitive and tolerant tomato accessions under heat stress

Pattern electroretinography as an objective method for study the visual analyzer function in patients with diabetes mellitus with initial diabetic retinopathy

Цел: Целта на нашето проучване е да се изследва обективно функцията на зрителния анализатор чрез патерна електроретинография (ПЕРГ) при пациенти със захарен диабет (ЗД) с начална диабетна ретинопатия (ДР) и получените резултати да се сравнят с контролната група, както и според типа на диабета.Материал и методика: Изследвана е група от 81 човека (162 очи), от които 47 здрави лица (контроли) - 94 очи. Пациентите със ЗД са 34 (68 очи), от които със ЗД тип 1 са 11 лица и 23 са с тип 2 ЗД. Извършена е ПЕРГ. Основните показатели, които са отчетени при анализа на резултатите са латентни времена и амплитуди, отразяващи се на конфиrурацията на вълновите форми.Резултати: При сравнителния анализ на стойностите на компонентите на ПЕРГ с контролната група, както и според типа ЗД, се установиха значителни различия. При сравнителния анализ на стойностите на компонентите на ПЕРГ между пациенти със ЗД с ДР и контроли се установи, че двете групи статистически се различават по амплитудите на всички компоненти на ПЕРГ при всички отвеждания при 15o и 30o.При латентностите сигнификантни различия се установиха при компонент Р50 при всички отвеждания при 15o и 30o. Пациентите със ЗД имат сигнификантно по-удължени латентности и по-ниски амплитуди, в сравнение с контролната група. При сравнителния анализ според типа ЗД, сигнификантни различия се получиха при амплитуден компонент P50-N95 при 15o и30o при дясно око, което потвърждава асиметричното засягане на очите при ЗД. Амплитудите на ПЕРГ при ЗД тип 2 са сигнификантно по-ниски от тези на пациентите със ЗД тип 1.Заключение: ПЕРГ би могла да се използва като обективен метод за регистриране на ранни изменения във функцията на зрителния анализатор (ЗА) като усложнение на З)J,. Също така и за проследяване на промените в динамика, тъй като изследването е неинвазивно, безвредно, по-бързо, повторяемо и обективно, по-евтино в сравнение с флуоресцеиновата ангиография (ФА), оптината кохерентна томография (ОСТ) и ангио-ОСТ.Aim: The aim of the study was to examine objectively the visual analyzer function by pattern electroretinography (PERG) in patients with diabetes mellitus (DM) with initial diabetic retinopathy (DR) and to compare the results with the control group as well as according to the type of diabetes. Material and methods: A group of 81 people (162 eyes) were studied. Patients with DM were 34 (68 eyes), 11 patients with type 1 DM and 23 with type 2 DM. The control group consisted of 47 healthy individuals (94 eyes). PERG was performed. The main variables that were considered in the results analysis were the latency and amplitudes, reflecting the configuration of the wave forms.Results: The comparative analysis of PERG components between patients with DM with DR and controls as well as according to the type of DM demonstrated significant differences. In latencies, significant differences were found for component P50 at all electrode positions at 15o and 30o. Patients with DM had significantly longer latencies and lower amplitudes compared to the control group. In the comparative analysis according to the type of DM, significant differences were found in amplitude component P50-N95 at 15o and 30o in the right eye, which confirms the asymmetrical eye involvement in DM. The PERG amplitudes in type 2 DM were significantly lower than those of type 1 DM patients.Conclusion: PERG could be used as an objective method for registration of early changes in the visual analyzer function as a DM complication. Also, to monitor the changes in dynamics as it is non-invasive, harmless, faster, and less expensive than fluorescein angiography (FA), OCT and angio-OCT

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Copy number variation in bipolar disorder.

Large (>100 kb), rare (500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4))

Phenotypic insights into ADCY5-associated disease

BACKGROUND: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. METHODS: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole-exome sequencing. RESULTS: Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. CONCLUSION: We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5-associated dyskinesia may be under-recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia

A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband–parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams–Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 × 10−6). This was largely explained by enrichment for members of the N-methyl-D-aspartate receptor (NMDAR) (P=4.24 × 10−6) and neuronal activity-regulated cytoskeleton-associated protein (ARC) (P=3.78 × 10−8) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia

Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia

Context: Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date. Objectives: To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia. Design: A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray. Setting: The Wellcome Trust Case Control Consortium. Participants: There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents. Main Outcome Measures: Overall load of CNVs and presence of rare CNVs. Results: The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder. Conclusions: Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder