Theory and simulations of a gyrotron backward wave oscillator using a helical interaction waveguide

A gyrotron backward wave oscillator (gyro-BWO) with a helically corrugated interaction waveguide demonstrated its potential as a powerful microwave source with high efficiency and a wide frequency tuning range. This letter presents the theory describing the dispersion properties of such a waveguide and the linear beam-wave interaction. Numerical simulation results using the PIC code MAGIC were found to be in excellent agreement with the output measured from a gyro-BWO experiment

Microwave pulse compression using a helically corrugated waveguide

There has been a drive in recent years to produce ultrahigh power short microwave pulses for a range of applications. These high-power pulses can be produced by microwave pulse compression. Sweep-frequency based microwave pulse compression using smooth bore hollow waveguides is one technique of passive pulse compression, however, at very high powers, this method has some limitation due to its operation close to cutoff. A special helical corrugation of a circular waveguide ensures an eigenwave with strongly frequency dependent group velocity far from cutoff, which makes the helically corrugated waveguide attractive for use as a passive pulse compressor for very high-power amplifiers and oscillators. The results of proof-of-principle experiments and calculations of the wave dispersion using a particle in cell particle-in-cell (PIC) code are presented. In the experiments, a 70-ns 1-kW pulse from a conventional traveling-wave tube (TWT) was compressed in a 2-m-long helical waveguide. The compressed pulse had a peak power of 10.9 kW and duration of 3 ns. In order to find the optimum pulse compression ratio, the waveguide's dispersion characteristics must be well known. The dispersion of the helix was calculated using the PIC code Magic and verified using an experimental technique. Future work detailing plans to produce short ultrahigh power gigawatt (GW) pulses will be discussed

The Impact of Psychological Violence on Children and Legal Protection Efforts in Indonesia

The research is financed by Postgraduate Programe, Departement of Law, Sam Ratulangi University, Indonesia Abstract Children are an inseparable part of human survival and the survival of a nation and state. Undang- UndangDasar Negara Republik Indonesia Tahun 1945 Article 28b paragraph (2) states that “every child has the right to survival, to grow and develop and has the right to protection from violence and discrimination”. This study discusses the impact of psychological violence and legal protection efforts in Indonesia. The research method used is normative juridical, with descriptive analytical research specifications that provide an in-depth description of a situation related to the problem being studied. The results of the study basically show that violence against children still frequently occur in Indonesia. Psychological violence in children has a very dangerous impact and can affect a child's psychological life. Efforts to guarantee protection of children in Indonesia have not been maximized, although positive laws in Indonesia have provided guarantees for child protection. Protection of children from acts of violence require the participation of the community, family, non-government institutions, and all other parties. Keywords: children's rights, psychological violence, legal protection DOI: 10.7176/JLPG/82-1

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n= 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable

Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies

Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called ‘missing heritability’. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51–62% in the number of genome-wide significant loci and a relative loss in polygenic score R2of 36–38%). Hence, cross-study heterogeneity contributes to the missing heritability

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors