37 research outputs found
Effect of iron and boron powders on ignition and combustion of aluminized composite solid propellants
Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage
Advantages and diagnostic effectiveness of the two most widely used resequencing approaches, whole exome (WES) and whole genome (WGS) sequencing, are often debated. WES dominated large-scale resequencing projects because of lower cost and easier data storage and processing. Rapid development of 3(rd) generation sequencing methods and novel exome sequencing kits predicate the need for a robust statistical framework allowing informative and easy performance comparison of the emerging methods. In our study we developed a set of statistical tools to systematically assess coverage of coding regions provided by several modern WES platforms, as well as PCR-free WGS. We identified a substantial problem in most previously published comparisons which did not account for mappability limitations of short reads. Using regression analysis and simple machine learning, as well as several novel metrics of coverage evenness, we analyzed the contribution from the major determinants of CDS coverage. Contrary to a common view, most of the observed bias in modern WES stems from mappability limitations of short reads and exome probe design rather than sequence composition. We also identified the similar to 500kb region of human exome that could not be effectively characterized using short read technology and should receive special attention during variant analysis. Using our novel metrics of sequencing coverage, we identified main determinants of WES and WGS performance. Overall, our study points out avenues for improvement of enrichment-based methods and development of novel approaches that would maximize variant discovery at optimal cost
Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size
Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10−5), rs112984085 in VAV3 (p = 4.8 × 10−4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10−4), rs34042554 in PCDHA1 (p = 1 × 10−4), and rs144183813 in PLEKHA5 (p = 1.7 × 10−4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10−5), and rs685523 in ADAMTS13 (p = 1 × 10−6) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations
Analysis of structure and function of Chriz complex in Drosophila melanogaster
Die Chromatinstruktur spielt eine bedeutende Rolle bei der Stadien- und Gewebs-spezifischen Genexpression. Der epigenetische Status von Chromatindomänen wird mit Hilfe einer Anzahl von Proteinen und Histonmodifikationen etabliert und aufrechterhalten. Das Ziel dieser Arbeit ist die Untersuchung der Bedeutung und Funktion des Chriz Protein Komplexes bei Drosophila, der spezifisch in dekondensierten Regionen von Interphase Chromosomen gebunden ist. Meine RNAi Experimente an embryonalen S2 Zellen zeigten, dass die Rekrutierung von Z4 und der Kinase Jil-1 an das Chromatin sowie dessen H3S10 Phosphorylierung während der Interphase von Chriz abhängt. Diese Ergebnisse lieferten einen starken Hinweis auf eine Ähnlichkeit bei der Bildung des Komplexes in polytänen Zellen und diploiden S2 Zellen. Ich führte eine vergleichende Analyse der Bindungsprofile von Proteinen des Chriz Komplex zwischen Speicheldrüsen im 3.Larvenstadium und S2 Zellen im chromosomalen Intervall 61C7-8 durch. Ich fand heraus, dass die Chriz Bindungsprofile im proximalen Teil der Domäne konserviert waren. Dagegen beobachtete ich eine veränderte Chriz Bindung im distalen Teil, die mit einem veränderten Transkriptionsprofil in dieser Region übereinstimmte. Chriz und Z4 RNAi Experimente in S2 Zellen führten zu einer Veränderung der Expression vieler Chriz- und Z4- bindender Gene. Mittels Co-Immunpräzipitation und Protein „Pull-down“ konnte ich die Bindung der Insulator Proteine BEAF-32 und CP190 im Chriz-Komplex nachweisen und die für die Protein-Protein Interaktion notwendigen Proteinabschnitte grob kartieren. Schließlich überprüfte ich die Möglichkeit einer Rekrutierung des Chriz Komplexes durch BEAF-32 durch Induktion von Punktmutationen in bekannten BEAF-32 Bindemotiven. Meine Ergebnisse wiesen eine Wechselwirkung zwischen Chriz und Insulator Proteinen nach und zeigten, dass der Chriz-Komplex eine wichtige Bedeutung bei der strukturellen Organisation von Chromatin Domänen besitzt.Chromatin structure is important for the correct stage and tissue-specific expression of the genetic material. The epigenetic state of chromatin domains is established and maintained by a number of proteins and histone modifications. The aim of current thesis is to investigate the role and function of Chriz protein complex, specifically bound to decondensed regions of interphase chromosomes in Drosophila. Several proteins were known to compose Chriz complex - chromodomain protein Chriz, zinc finger protein Z4 and H3S10 kinase Jil-1. I performed RNAi experiments on S2 cells which demonstrated that recruitment of Z4 and Jil-1 kinase to chromatin and interphase H3S10 phosphorylation are dependent on the presence of Chriz. I accomplished the comparative analysis of binding profiles of Chriz complex components between 3rd instar larvae salivary glands and S2 cell culture within 61C7-8 chromosomal interval. I found that Chriz binding profiles between two tissues are conserved at proximal part, however variant Chriz binding in distal part of 61C7-8 domain coincides with differences in transcription profile in the same region. Publicly available genome-wide data shows a tendency of Chriz to bind near Transcription Start Sites (TSS) and promoter regions of active genes. Chriz and Z4 RNAi experiments, performed in S2 cells resulted in expression changes of many Chriz- and Z4-binding genes. Using co-immunoprecipitation and pull-down assays, I identified insulator proteins BEAF-32 and CP190 to be present in the Chriz complex and performed rough mapping of interacting domains. Using BEAF-32 RNAi and introduced point mutations to BEAF-32 binding motifs I examined the possibility for recruitment of Chriz complex by BEAF-32. The obtained results revealed the interplay between Chriz and insulator proteins and point to important architectural role of Chriz complex in organizing chromatin domains
Effect of Metal Additives on the Combustion Characteristics of High-Energy Materials
Thermodynamic calculation of combustion parameters and equilibrium composition of HEMs combustion products showed, that at the increase of aluminum powder dispersity the specific impulse and combustion temperature of solid propellants are reduced due to the decrease of the mass fraction of active aluminum in particles. Partial or complete replacement of aluminum by metal powder (B, Mg, AlB2, Al\Mg alloy, Fe, Ti and Zr) in HEMs composition leads to the reduce of the specific impulse and combustion temperature. Replacement of aluminum powder by boron and magnesium in HEM reduces the mass fraction of condensed products in the combustion chamber of solid rocket motor. So, for compositions HEMs with boron and aluminum boride the mass fraction in chamber is reduced by 24 and 36 %, respectively, with respect to the composition HEMs with Al powder. But the mass fraction of CCPs in the nozzle exit increases by 13 % for HEMs with aluminum boride due to the formation of boron oxide in the condensed combustion products. Partial replacement of 2 wt. % aluminum powder by iron and copper additives in HEM leads to the reduce of CCPs mass fraction in chamber by 4–10 % depending on the aluminum powder dispersity duo to these metals are not formed condensed products at the HEMs combustion in chamber
Effect of Metal Additives on the Combustion Characteristics of High-Energy Materials
Thermodynamic calculation of combustion parameters and equilibrium composition of HEMs combustion products showed, that at the increase of aluminum powder dispersity the specific impulse and combustion temperature of solid propellants are reduced due to the decrease of the mass fraction of active aluminum in particles. Partial or complete replacement of aluminum by metal powder (B, Mg, AlB2, Al\Mg alloy, Fe, Ti and Zr) in HEMs composition leads to the reduce of the specific impulse and combustion temperature. Replacement of aluminum powder by boron and magnesium in HEM reduces the mass fraction of condensed products in the combustion chamber of solid rocket motor. So, for compositions HEMs with boron and aluminum boride the mass fraction in chamber is reduced by 24 and 36 %, respectively, with respect to the composition HEMs with Al powder. But the mass fraction of CCPs in the nozzle exit increases by 13 % for HEMs with aluminum boride due to the formation of boron oxide in the condensed combustion products. Partial replacement of 2 wt. % aluminum powder by iron and copper additives in HEM leads to the reduce of CCPs mass fraction in chamber by 4–10 % depending on the aluminum powder dispersity duo to these metals are not formed condensed products at the HEMs combustion in chamber
Remote Laser Laboratory: Lifebuoy for Laser Engineering Curriculum
Laboratory experience is one of the essentials of engineering curriculum and even more so for laser engineering specialities. But such experience might be hazardous both for students and for expensive equipment. This paper presents a ready-to-use solution fitting great in both e-learning and safe remote operation paradigms: Remote Laser Laboratory (RLL). Software and hardware solutions are presented. In addition, a short description of ongoing student activities within the RLL framework is given
Effect of metal additives on the combustion characteristics of high-energy materials
Thermodynamic calculation of combustion parameters and equilibrium composition of HEMs combustion products showed, that at the increase of aluminum powder dispersity the specific impulse and combustion temperature of solid propellants are reduced due to the decrease of the mass fraction of active aluminum in particles. Partial or complete replacement of aluminum by metal powder (B, Mg, AlB2, AlMg alloy, Fe, Ti and Zr) in HEMs composition leads to the reduce of the specific impulse and combustion temperature. Replacement of aluminum powder by boron and magnesium in HEM reduces the mass fraction of condensed products in the combustion chamber of solid rocket motor. So, for compositions HEMs with boron and aluminum boride the mass fraction in chamber is reduced by 24 and 36 %, respectively, with respect to the composition HEMs with Al powder. But the mass fraction of CCPs in the nozzle exit increases by 13 % for HEMs with aluminum boride due to the formation of boron oxide in the condensed combustion products. Partial replacement of 2 wt. % aluminum powder by iron and copper additives in HEM leads to the reduce of CCPs mass fraction in chamber by 4–10 % depending on the aluminum powder dispersity duo to these metals are not formed condensed products at the HEMs combustion in chamber