The influence of an electron beam on the frequency of appearance of modifications and mutagens in the residual florula

We have carried out a series of tests for studying an electron beam (Е=4 МеV) influence on adaptive mutability test cultures of the sanitary-model microflora in various regimes (0.4…3.2 kGy) of processing samples of natural water and sewages. Mutafacient properties and modifications of the residual microflora stimulated by the electron beam effect are scarcely pronounced. They do not indicate themselves in the regimes that guarantee the water purification up to the indices stipulated by the corresponding standards.Проведен цикл экспериментов по влиянию электронного пучка (Е=4 МеV) на адаптивную изменчивость тест-культур санитарно-показательной микрофлоры в условиях разных режимов (0,4…3,2 кГр) обработки проб природных и сточных вод. Установлено, что мутагенные свойства и модификация остаточной микрофлоры после воздействия электронного пучка имеют слабо выраженный характер и не проявляются в режимах, которые обеспечивают очистку воды до санитарных норм.Проведено цикл експериментів по впливу електронного пучка (Е=4 МеВ) на адаптивну мінливість тест- культур санітарно-показової мікрофлори в умовах різних режимів (0,4…3,2 кГр) обробки проб природних та стічних вод. Встановлено, що мутагенні властивості та модифікація залишкової мікрофлори після впливу електронного пучка мають слабко виражений характер і не проявляються в режимах, що забезпечують очистку води до санітарних норм

A dimensionally continued Poisson summation formula

We generalize the standard Poisson summation formula for lattices so that it operates on the level of theta series, allowing us to introduce noninteger dimension parameters (using the dimensionally continued Fourier transform). When combined with one of the proofs of the Jacobi imaginary transformation of theta functions that does not use the Poisson summation formula, our proof of this generalized Poisson summation formula also provides a new proof of the standard Poisson summation formula for dimensions greater than 2 (with appropriate hypotheses on the function being summed). In general, our methods work to establish the (Voronoi) summation formulae associated with functions satisfying (modular) transformations of the Jacobi imaginary type by means of a density argument (as opposed to the usual Mellin transform approach). In particular, we construct a family of generalized theta series from Jacobi theta functions from which these summation formulae can be obtained. This family contains several families of modular forms, but is significantly more general than any of them. Our result also relaxes several of the hypotheses in the standard statements of these summation formulae. The density result we prove for Gaussians in the Schwartz space may be of independent interest.Comment: 12 pages, version accepted by JFAA, with various additions and improvement

Relativistic electron influence on sanitary-model microorganisms and antibiotics in model samples

A series of the investigations of the electron beam influence on sanitary-model test cultures and antibiotics in model solutions has been carried out. For each of the test objects, the authors have found the boundary doses of the absorbed radiation. The higher doses cause the sharp increase in the bactericidal influence, which becomes complete. The sanitary-bactericidal indices of the water samples remain stable during 6 days. The samples of antibiotics in various concentrations (from 100 UA) have been irradiated. It is proved that the substratum processing by the beam (in the regimes 30 kGy) causes diminution and complete neutralization of the antibacterial activity in all probes of the samples.Виконано цикл досліджень по впливу електронного пучка на санітарно-показові тест-культури та антибіотики в модельних розчинах.. Для кожного тест-об’єкта визначено граничні дози поглинутого випромінювання, вище яких бактерицидна дія різко посилюється і стає повною. При цьому забезпечується стабільність санітарно-бактеріологічних показників зразків води протягом 6 діб. Показано, що оброблення електронним пучком модельних зразків антибіотиків, взятих в концентраціях до 100 ОА, в режимах до 30 кГр приводило до зменшення та повної нейтралізації антибактеріальної активності у всіх пробах зразків.Выполнен цикл исследований по влиянию электронного пучка на санитарно-показательные тест-культуры и антибиотики в модельных растворах. Для каждого тест-объекта установлены предельные дозы поглощенного облучения, выше которых бактерицидное действие резко усиливается и становится полным. При этом обеспечивается стабильность санитарно-бактериологических показателей образцов воды на протяжении 6 дней. Показано, что обработка электронным пучком модельных образцов антибиотиков, взятых в концентрациях до 100 ОА, в режимах до 30 кГр приводило к уменьшению и полной нейтрализации антибактериальной активности во всех пробах образцов

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch