Automatic tuning of Free Electron Lasers

Existing FEL facilities often suffer from stability issues: so electron orbit, transverse electron optics, electron bunch compression and other parameters have to be readjusted often to account for drifts in performance of various components. The tuning procedures typically employed in operation are often manual and lengthy. We have been developing a combination of model-free and model-based automatic tuning methods to meet the needs of present and upcoming XFEL facilities. Our approach has been implemented at FLASH \cite{flash} to achieve automatic SASE tuning using empirical control of orbit, electron optics and bunch compression. In this paper we describe our approach to empirical tuning, the software which implements it, and the results of using it at FLASH. We also discuss the potential of using machine learning and model-based techniques in tuning methods

Remote Prophylaxis of Social and Educational Adaptation of University International Entrants in Total Pandemic

The relevance of the study is due to the trends of the global pandemic, which provoked an extremal transition of all areas of higher education to distance learning, as the only possible way to work with domestic and international entrants and students. In addition, the trends of the pandemic in the current educational environment also determine the special need to develop remote mechanisms for a prophylaxis approach to solving the problems of social and educational adaptation of international entrants – future University students. In this regard, this article is aimed at identifying the features of remote prophylaxis of social and educational adaptation of entrants. The article reveals the transformation of social and educational adaptation of international entrants in the global pandemic; defines the structure and content of remote prophylaxis of social and educational adaptation of international University entrants in the global pandemic. Based on the results of the research, the authors of the article substantiate the prophylaxis model of the educational and software complex for remote prophylaxis of social and educational adaptation of University international entrants. The effectiveness of the model is proved by the results of its use in the process of remote social and educational adaptation of University international entrants in the context of a global pandemic. The materials of the article have practical application and can be useful in the development and implementation of various methods and practices of social and educational adaptation of international entrants – future University students in the context of a global pandemic. It is recommended for University teachers and students, methodologists, curators, Tutors

OPTIMIZATION OF METHOD OF OBTAINING HYDRATES BY CONDENSATION OF MOLECULAR BEAMS

Developed at the Institute of Thermal Physics, Ural Branch RAS method o f producing gas hydrates can be improved by cooling of molecular beam [1]. Trial experiments by cooling the beam in the Laval nozzle were conducted and showed the possibility o f using this method to improve the performance of the experimental arrangement.Работа выполнена при поддержке Российского фонда фундаментальных исследований (проекты № 15-08-02734-а, № 14-08-31007 мол а) и Программы фундаментальных исследований УрО РАН (проект № 15-1-2-7)

Clinical significance of genetic aberrations in secondary acute myeloid leukemia

The study aimed to identify genetic lesions associated with secondary acute myeloid leukemia (sAML) in comparison with AML arising de novo (dnAML) and assess their impact on patients' overall survival (OS). High-resolution genotyping and loss of heterozygosity mapping was performed on DNA samples from 86 sAML and 117 dnAML patients, using Affymetrix Genome-Wide Human SNP 6.0 arrays. Genes TP53, RUNX1, CBL, IDH1/2, NRAS, NPM1, and FLT3 were analyzed for mutations in all patients. We identified 36 recurrent cytogenetic aberrations (more than five events). Mutations in TP53, 9pUPD, and del7q (targeting CUX1 locus) were significantly associated with sAML, while NPM1 and FLT3 mutations associated with dnAML. Patients with sAML carrying TP53 mutations demonstrated lower 1-year OS rate than those with wild-type TP53 (14.3% +/- 9.4% vs. 35.4% +/- 7.2%; P = 0.002), while complex karyotype, del7q (CUX1) and del7p (IKZF1) showed no significant effect on OS. Multivariate analysis confirmed that mutant TP53 was the only independent adverse prognostic factor for OS in sAML (hazard ratio 2.67; 95% CI: 1.335.37; P = 0.006). Patients with dnAML and complex karyotype carried sAML-associated defects (TP53 defects in 54.5%, deletions targeting FOXP1 and ETV6 loci in 45.4% of the cases). We identified several co-occurring lesions associated with either sAML or dnAML diagnosis. Our data suggest that distinct genetic lesions drive leukemogenesis in sAML. High karyotype complexity of sAML patients does not influence OS. Somatic mutations in TP53 are the only independent adverse prognostic factor in sAML. Patients with dnAML and complex karyotype show genetic features associated with sAML and myeloproliferative neoplasms. Am. J. Hematol., 2012

Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2

Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized