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Study question Whether the CNV load differs in fetal tissues of miscarriages from families with recurrent and sporadic pregnancy loss? Summary answer In RPL group duplications are more common than deletions, de novo variants than inherited ones. Pathogenic CNVs (dup16p11.2, del22q13, dupXq28) were found in both groups. What is known already Data on CNVs in tissues of miscarriages can be found in more than 24 articles. Altogether 7732 samples were analyzed by aCGH and NGS; 988 CNVs of uncertain clinical significance were found in 636 samples (8.2%). The origin was determined for 130 variants: 85 maternal (65.4%), 34 paternal (26.2%), 11 de novo (8.4%) CNVs. No aberration unambiguously associated with miscarriage was found so far. Comparative analysis of CNVs in family trios with recurrent and sporadic miscarriage may help to characterize structural genome variations associated with embryo lethality both from embryo and parental side. Study design, size, duration Identification of structural genome variations (SGV) at the CNV level was performed by aCGH-analysis for family trios: mother, father and fetal. Characteristics of SGV associated with embryo lethality included such parameters as CNV type (deletion/duplication) and its origin. It was assumed that the structure of genomic variability may differ in recurrent pregnancy loss (RPL) and sporadic pregnancy loss (SPL) both in embryonic tissues and in parents. Participants/materials, setting, methods Eleven family trios (7 RPL and 4 SPL) were included in the research. Standard G-banding was performed for all abortion samples to exclude aneuploidy. STR-haplotyping for the SRY gene was used to exclude maternal cell contamination. Finally all samples were analyzed for CNVs using SurePrint G3 Human CGH+SNP 4 × 180K microarrays (Agilent Technologies). Average gestation age was 7.9 weeks. Average maternal and paternal age was 30.8 and 30.5 years, respectively. Main results and the role of chance In seven and four embryos from RPL and SPL groups 110 and 60 CNVs were identified, respectively. In RPL, there was a tendency towards an increase in the frequency of duplications over deletions (72:38) in comparison to SPL (36:24) (p = 0.5). Duplications prevailed over deletions in five of seven embryos from RPL group; while there were two cases of each combination in SPL. One can suggest that some SPL cases can move into RPL group over time. De novo variants prevailed over inherited in the RPL group (76:43) and inherited prevailed in the SPL (32:28) (p Limitations, reasons for caution No one CNV unambiguously associated with pregnancy loss has been described so far. Possibly, total structural genome variations level should be considered as pathogenic factor for embryo development. There is no adequate algorithm of clinical significance CNV interpretation for the embryonic period. Wider implications of the findings Prenatal or preimplantation genetic testing should be considered if one of the parents is a carrier of CNV associated with microdeletion/microduplication syndrome. This study was supported by the Russian Science Foundation № 21-65-00017, https://rscf.ru/project/21-65-00017/. Trial registration number Russian Science Foundation № 21-65-00017

Study question Does tissue-specific compartmentalization of segmental aneuploidies in first-trimester miscarriages reflect their postzygotic de novo origin or correction of inherited copy number variants (CNV)? Summary answer Most of mosaic CNVs (84%) in spontaneous abortions with normal karyotype arose de novo, but 16% resulted from postzygotic tissue-specific correction of maternally inherited variants. What is known already Chromosomal mosaicism is a hallmark of early human embryogenesis affecting significantly developmental potential of blastocysts, it’s implantation and delivery rates. Most of the currently available data are related to mosaic aneuploidies for a whole chromosome in IVF cycles, whereas little is known about origin and fate of mosaic segmental CNVs due to inherent limitations of NGS and aCGH for detection of copy number changes less for 5-10 Mb in size after single-cell whole genome amplification. Study design, size, duration Chorionic villi (CV) and extraembryonic mesoderm (EM) of miscarriages as well as maternal and paternal peripheral blood DNA samples were evaluated by aCGH+SNP arrays to detect the prevalence and tissue-specific distribution of segmental aneuploidies. As far as CV and EM are derivatives of trophectoderm and inner cell mass lineages, comparative analysis of both tissues allows to investigate the origin of mosaic CNVs by postzygotic de novo appearance or correction of the inherited variants. Participants/materials, setting, methods Eleven trios (mother, father, CV and EM samples from spontaneous abortion with normal karyotype by G-banding) were included in the study. Mean gestational age was 7.9 weeks. Mean maternal and paternal ages were 30.8 and 30.5 years, respectively. aCGH+SNP analysis was performed by SurePrint G3 Human CGH + SNP 4 × 180K microarrays (Agilent Technologies) with 13 kb median aCGH probes spacing. Main results and the role of chance Altogether 116 CNVs were detected in CV and EM samples from 11 abortions. Fifty four (46.6%) variants were present in both tissues, while 29 (25%) were confined by CV and 33 (28.4%) by EM. Most of tissue-specific segmental aneuploidies in CV (90%) and EM (79%) arose de novo, whereas others were inherited from parents. It is important that 5 maternally inherited microduplications in some clinically significant regions like 1p21.1 (103 kb in size), 2p21 (3.56 kb), 3p22.3 (128 kb), 7q36.3 (42.7 kb), and Xq28 (182 kb) were confined by EM, whereas two at 4p16.3 (22.3 kb) and 19q13.43 (2.2 kb) by CV. No cases of tissue-specific maternally inherited microdeletions or paternal CNVs were observed in our study. One can suggest that confined placental mosaicism for inherited maternal microduplications arisen by trisomy rescue mechanism with loss of additional maternal chromosome copy in CV or EM after its divergence around the time of blastocyst implantation. This hypothesis is confirmed by comparative SNP-haplotype analysis of DNA samples from both CV and EM tissues as well as parental samples in the subchromosomal regions of microduplications and adjusted loci. Limitations, reasons for caution Control group of induced (social) abortions of the same developmental terms are required to estimate the prevalence and distribution of mosaic segmental aneuploidies in embryonic and extraembrionic tissues during normal human embryo development. Wider implications of the findings Tracing of tissue-specific mosaic segmental aneuploidies in first-trimester miscarriages allows to estimate the level of karyotype instability and self-correction during human embryo development. This study was supported by the Russian Science Foundation, № 21-65-00017, https://rscf.ru/project/21-65-00017/ Trial registration number not applicable

The article analyzes various forms of protection of the rights of individuals to compensation for harm caused by a medical specialist, which are used in different countries around the world. In particular, special attention is paid to those approaches to pre-trial and out-of-court dispute resolution arising from patient harm relationships used in the United States. Among the most common ways of resolving such disputes are seeking help from a separate body or unit of a medical institution (risk management), mediation and negotiations in medical disputes, pre-trial inspections ("screening panels"), which allow to find a more compromise way to protect individual rights, affected by the actions of medical specialist. Accordingly, the first part of the article carries out a terminological analysis of the category "relationship of harm to a health worker" and the search for the closest term ("medical malpractice"), which allows for research in English-language scientific sources. The second part of the article is devoted to the analysis and generalization of the methods used in the practice of other countries to compensate for damage caused by a medical specialist (medical malpractice). The last part of the article analyzes the Ukrainian legislation and practice of national courts, which showed that in cases of compensation for damage caused by a medical specialist, there are no common approaches and single law approaches. In particular, attention is paid to the procedure for assessing the quality of medical services provided in 2016 by clinical expert commissions of the Ministry of Health of Ukraine. The study provided an opportunity to justify in the conclusions the need and feasibility of introducing additional out-of-court methods of resolving disputes arising from the relationship of harm to medical workers.

Until recently, it was thought that there were no lymphatic vessels in the central nervous system (CNS). Therefore, all metabolic processes were assumed to take place only in the circulation of the cerebrospinal fluid (CSF) and through the blood-brain barrier’s (BBB), which regulate ion transport and ensure the functioning of the CNS. However, recent findings yield a new perspective: There is an exchange of CSF with interstitial fluid (ISF), which is drained to the paravenous space and reaches lymphatic nodes at the end. This circulation is known as the glymphatic system. The glymphatic system is an extensive network of meningeal lymphatic vessels (MLV) in the basal area of the skull that provides another path for waste products from CNS to reach the bloodstream. MLV develop postnatally, initially appearing around the foramina in the basal part of the skull and the spinal cord, thereafter sprouting along the skull’s blood vessels and spinal nerves in various areas of the meninges. VEGF-C protein (vascular endothelial growth factor), expressed mainly by vascular smooth cells, plays an important role in the development of the MLV. The regenerative potential and plasticity of MLV and the novel discoveries related to CNS drainage offer potential for the treatment of neurodegenerative diseases such as dementia, hydrocephalus, stroke, multiple sclerosis, and Alzheimer disease (AD). Herein, we present an overview of the structure and function of the glymphatic system and MLV, and their potential involvement in the pathology and progression of neurodegenerative diseases.

In the work investigated the direction of introduction of technology for the organization of multiply-units speed trains, which will reduce the cost of developing variable demand of train routes, and improve the quality of passenger service. In order to increase the efficiency of transportation in high-speed trains, it is necessary to use organizational technologies, which are based on concepts, that meet the requirements of the variable basis of the organization of passenger transportation and allow to provide a flexibility for companies-carriers. Was analyzed experience of operating high-speed electric trains on multiply-units control system. The modular operation of high-speed trains offers the ability to combine trains into two or even three trains with the possibility of adapting to changing time and space requirements. This makes it possible to use short-haul trains, which can be combined with trains of higher complexity to meet variable demand on railway network. In the work we find a solution for the problem of constructing a plan for the formation of connected high-speed trains on the network graph, and proposed an improved model of the current variant of the Intercity+ high-speed train on the Kiev-Przemysl route using connecting two high-speed trains.

The multiobjective robust control synthesis method of parameters for nonlinear multi-mass rolling mills main electric drives with uncertain plant parameters to improve the control accuracy of such systems is developed. Multi-criteria game solution based method. Basic requirements which the main electric drives must satisfy in various modes of its operation based payoff vectors. Modeling of the synthesized system with different input signals and for various values of the plant parameters for various modes of the system operation based payoff vectors calculation. Particles multiswarm optimization algorithms based multi criterion game solution. Theoretical and experimental research of the effectiveness of two -mass and three-mass rolling mills main electric drives with synthesis of robust controllers are presented. Comparison of the dynamic characteristics of the synthesized rolling mills main electric drives with the existing system is completed. In comparison with the existing system the use of synthesized robust controllers allowed to improve the accuracy parameters and reduce the sensitivity of the system to changes of plant parameters.

The amygdala is one of the most discussed structures of the brain. Correlations between its level of activity, size, biochemical organization, and various pathologies are the subject of many studies, and can serve as a marker of existing or future disease. It is hypothesized that the amygdala is not just a structural unit, but includes many other regions in the brain. In this review, we present the updated neuroanatomical and physiological aspects of the amygdala, discussing its involvement in neurodegenerative and neurological diseases. The amygdala plays an important role in the processing of input signals and behavioral synthesis. Lesions in the amygdala have been shown to cause neurological disfunction of ranging severity. Abnormality in the amygdala leads to conditions such as depression, anxiety, autism, and also promotes biochemical and physiological imbalance. The amygdala collects pathological proteins, and this fact can be considered to play a big role in the progression and diagnosis of many degenerative diseases, such as Alzheimer’s disease, chronic traumatic encephalopathy, Lewy body diseases, and hippocampal sclerosis. The amygdala has shown to play a crucial role as a central communication system in the brain, therefore understanding its neuroanatomical and physiological features can open a channel for targeted therapy of neurodegenerative diseases.

Full detector simulation was among the largest CPU consumer in all CERN experiment software stacks for the first two runs of the Large Hadron Collider (LHC). In the early 2010's, the projections were that simulation demands would scale linearly with luminosity increase, compensated only partially by an increase of computing resources. The extension of fast simulation approaches to more use cases, covering a larger fraction of the simulation budget, is only part of the solution due to intrinsic precision limitations. The remainder corresponds to speeding-up the simulation software by several factors, which is out of reach using simple optimizations on the current code base. In this context, the GeantV R&D project was launched, aiming to redesign the legacy particle transport codes in order to make them benefit from fine-grained parallelism features such as vectorization, but also from increased code and data locality. This paper presents extensively the results and achievements of this R&D, as well as the conclusions and lessons learnt from the beta prototype., 34 pages, 26 figures, 24 tables

This article examines the historical stages of development of marketing as a science and practice.

Background:Uveitis (U) is one of the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). It is usually revealed in 10-20% of children with JIA, often asymptomatic and sometimes the onset of U precedes the onset of arthritis. Being inappropriately treated, U leads to vision loss in up to 20% of children. Despite the efforts of the Standardization of Uveitis Nomenclature (SUN) Working Group and the European initiative Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) which optimized management of JIA-associated U [1], the actual treatment is mostly based on physicians’ experience. Initial treatment typically includes topical glucocorticoids (G) or systemic immunosuppressive therapy if topical G don’t work. Methotrexate (MTX) is the first-line systemic immunosuppressive agent, followed by tumor necrosis factor inhibitors (TNFi) [1,2].Objectives:To provide treatment recommendations for JIA-associated U based on monitoring of 221 patients during 7 years.Methods:Data collected during 2240 hospitalisations of 221 patients aged 3 - 17 years treated at the State Pediatric Medical University in years 2014 - 2020 were analyzed. U and JIA were diagnosed according to the SUN and ACR recommendations. Initial treatment of U included topical G or non-steroidal anti-inflammatory drugs (NSAIDs). Treatment of JIA included systemic NSAIDs, cytostatics (MTX, Cyclosporine or Cyclophosphamide) and biologics: Adalimumab (Ada), Infliximab (Inf), Etanercept (Eta), Abatacept (Aba), Tocilizumab (Toc), Golimumab (Gol). Statistical analysis included traditional Descriptive Statistics, Spearman Rank Order Correlation (SROC) and Multivariate Exploratory Techniques [Statistica for Windows, Statsoft].Results:Of all patients with JIA-associated U the proportion of those treated with biologics during the monitoring increased from 60 to 70% (of them, Ada 79 - 93%, Inf 7 - 1%, Eta 5 - 1%, Aba 7 - 3%, Toc 7 - 0%, Gol 0 - 3%). Of all children in whom U was diagnosed later than arthritis 36% were treated with systemic NSAIDs, 25% - with cytostatics (MTX - 84%, Cyclosporine - 8%, Cyclophosphamide - 8%), 23% - with systemic G, 6% - with biologics (Eta - 83%, Toc - 17%). Of patients in whom U and arthritis were diagnosed simultaneously, 95% were treated with cytostatics (MTX - 95%, Cyclosporine - 15%), 93% - with topical G, 91% - with topical NSAIDs, 81% - with systemic G, 60% - with systemic NSAIDs. Efficacy of treatment in terms of SROK showed evidence of steady improvement already after 1 month of therapy with TNFi or with MTX (increase of r during the first year from 0.37 to 0,62, pConclusion:1. The likelihood of improvement of U treated with TNFi (Eta excepted) after one month, after 1 and after 3 years of therapy was 37%, 62% and 84% respectively. For MTX this likelihood was 37% after 1 month and 55% after 3 months.2. TNFi (Eta excepted) in treatment of JIA prevents the onset of U, thereby supposing its early administration.3. Eta neither prevents nor treats U.4. Topical NSAIDs and G can hardly be recommended as a reliable means for treatment of U without TNFi and MTX.5. Systemic NSAIDs neither prevent nor treat JIA-associated U.References:[1]Constantin T, Foeldvari I, Anton J, et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative Ann Rheum Dis 2018;77:1107–1117[2]Angeles-Han ST, Ringold S, Beukelman T, Lovell D et al., 2018 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken). 2019 June; 71(6): 703–716Disclosure of Interests:None declared

The author analyzes the Federal State Standard on Higher Professional Education of the third generation and Federal State Standard on Higher Education area of training “Jurisprudence”in search of means of shaping this competence. The author also formulates defi nition and diff erentiates of the concepts “professional competence”and “professionally applied competence”. These normative documents identifi ed requirements for the formation of professional communicative competence. As a result, the analysis identifi ed the proportion of communicative competences of the whole volume of all formed competencies. Matrix, passport and program competencies, basic educational programs and programs of educational disciplines of the Perm institute of the Federal Service for the Execution of Sanctions of Russia are analyzedconcerning formation of professional communicative competence of graduates. The author suggests forming professional communicative competence, not only within the discipline “Russian language and Standard of Speech”, but also to include the communicative blocks of profi le orientation in the cycles of General and professional disciplines, and program practices in the framework of implementation of the basic educational program. This is due to the fact that in the training plan there are not linguistic disciplines (except “Russian language and Standard of Speech”) aimed at building these competencies.

Background:Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA). Usually uveitis developed during first two years after arthritis occurred [1]. In the previous studies was shown the shorter time interval between arthritis and uveitis the severe uveitis course was observed [2]. Information about course of uveitis developed before arthritis is scarce.Objectives:We aimed to evaluate the clinical features and therapy of JIA-associated uveitis, which developed before and after joint manifestation.Methods:In the retrospective study 191 pediatric autoimmune uveitis included. The onset age ranged from 1 to 17 years. We evaluated differences in clinical, laboratorial and treatment differences between groups, i) where uveitis developed before (n=58) and ii) after (n=133) arthritis. Chronic autoimmune uveitis without joint manifestations was excluded.Results:Uveitits before arthritis developed in 58 (30.4%) cases. Patients whom uveitis developed before arthritis had were elder and characterized equal gender involvement, rare ANA positivity, and rare use of immunosupression, e.g. corticosteroids, biologics and methotrexate, due to treatment by ophthalmologist predominantly. Patients developed uveitis before arthritis received biologics earlier due to severity of uveitis (LogRank test, p=0.016, HR=1.97 (95%CI: 1.3; 3.1, p=0.004). Data are in the Table 1 and Figure 1.Conclusion:Patients with JIA associated uveitis with initial ocular presentation demonstrated more severe course and delayed diagnostics and treatment due to lack of contacts with pediatric rheumatologist. Cooperation between ophthalmologist and pediatric rheumatologist is strictly required in all cases with chronic anterior uveitis.Table 1.Table 1.ParameterUveitis before arthritis (n=58)Uveitis after arthritis (n=133)pSex, female32 (55,2)97 (72,9)0.016Onset age, years6.7 (4.6; 10.2)3.2 (2; 6.1)0.000001JIA categoryOligoarthritis41 (70.7)84 (63.6)0.174Polyarthritis9 (15.5)36 (27.3)Enthesytis-related arthritis8 (13.8)12 (9.1)Type of uveitisAnterior44 (75.9)111 (84.1)0.315Peripheral3 (5.2)2 (1.5)Posterior3 (5.2)3 (2.3)Panuveitis8 (13.8)16 (12.1)Unilateral uveitis, n (%)19 (32.8)48 (36.1)0.632ANA posititivity, n (%)25/54 (46.3)72/110 (65.5)0.019HLA B27 positivity, n (%)8/35 (22.9)13/62 (21.0)0.828Methotrexate, n (%)3 (5.2)57/132 (43.2)0.0000001Systemic corticosteroids, n (%)3 (5.2)44/131 (33.6)0.00003Biologic, n (%)26 (44.8)88 (66.2)0.006ESR, mm/h19.0 (4.0; 25.0)23 (15.0; 32.0)0.095CRP, mg/l97.0 (0.1; 107.5)8.1 (0.9; 57.4)0.493Time between arthritis and uveitis, years2.7 (0.9; 4.3)4.0 (2.0; 7.1)0.016Time before biologic, years2.5 (0.9; 3.5)1.3 (0.5; 5.0)0.462This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001).References:[1]Verazza S, et al. Pediatr Rheumatol Online J 2008;6(Suppl 1):77.[2]Zannin ME, et al. Acta Ophthalmol 2012;90:91-5.Disclosure of Interests:None declaredFigure 1.

Field experimental research of the effectiveness of single-circuit active shielding system of magnetic field generated by group of overhead high voltage power lines with various control algorithms carried out. It is shown that the efficiency of closed-loop system with feedback control, open-loop system with forward control and combine closed-loop and open-loop system with feed forward control is approximately the same and is more than 4 units. Experimentally established that effectiveness of closed-loop system with feedback control depends on the location of the magnetic field sensors in the shielding zone. Comparison of the results of experimental and calculated values of magnetic field induction in the shielding zone shows that their spread does not exceed 20%.

The analysis of the space-time characteristics of power frequency magnetic field generated by different types of high voltage power lines is given. The authors show the possibility of reducing magnetic field level with strongly elongated ellipse of space-time characteristics with single compensating coil. The method of active screening system synthesis of power lines magnetic field with uncertainties of plant is improved. An example of active screening system synthesis of magnetic field generated by single-circuit with vertical arrangement of power lines current conductors is given. It is shown that the magnetic field level inside of five-storey building can reduce to sanitary norms by using a single compensating coil.

The GeantV project aims to research and develop the next generation simulation software describing the passage of particles through matter, targeting not only modern CPU architectures, but also more exotic resources such as GPGPU, Intel© Xeon Phi, Atom or ARM, which cannot be ignored any more for HEP computing. While the proof of concept GeantV prototype has been mainly engineered for CPU threads, we have foreseen from early stages a bridge for such accelerators, materialized in the form of architecture/technology specific backend templates. This approach allows to abstract out not only basic types such as scalar/vector, but also to formalize generic computation kernels using transparently library or device specific constructs based on several industry leading libraries. While the main goal of this approach is performance and access to functionality, this comes as bonus with the insulation of the core application and algorithms from the technology layer, allowing our application to be long term maintainable and versatile to changes at the backend side. The talk will present the early results of basket-based GeantV geometry navigation on the Intel© Xeon and Intel© Xeon Phi KNC architecture, as well as the work done for making the transport NUMA aware. We will present a detailed scalability and vectorization study conducted using Intel performance tools, as well as our preliminary conclusions on the use of accelerators for GeantV transport. We will also describe the current work and preliminary results for using the GeantV transport kernel on GPUs.

GeantV is a complex system based on the interaction of different modules needed for detector simulation, which include transport of particles in fields, physics models simulating their interactions with matter and a geometrical modeler library for describing the detector and locating the particles and computing the path length to the current volume boundary. The GeantV project is recasting the classical simulation approach to get maximum benefit from SIMD/MIMD computational architectures and highly massive parallel systems. This involves finding the appropriate balance between several aspects influencing computational performance (floating-point performance, usage of off-chip memory bandwidth, specification of cache hierarchy, etc.) and handling a large number of program parameters that have to be optimized to achieve the best simulation throughput. This optimization task can be treated as a black-box optimization problem, which requires searching the optimum set of parameters using only point-wise function evaluations. The goal of this study is to provide a mechanism for optimizing complex systems (high energy physics particle transport simulations) with the help of genetic algorithms and evolution strategies as tuning procedures for massive parallel simulations. One of the described approaches is based on introducing a specific multivariate analysis operator that could be used in case of resource expensive or time consuming evaluations of fitness functions, in order to speed-up the convergence of the black-box optimization problem.

The recent emergence of hardware architectures characterized by many-core or accelerated processors has opened new opportunities for concurrent programming models taking advantage of both SIMD and SIMT architectures. GeantV, a next generation detector simulation, has been designed to exploit both the vector capability of mainstream CPUs and multi-threading capabilities of coprocessors including NVidia GPUs and Intel Xeon Phi. The characteristics of these architectures are very different in terms of the vectorization depth and type of parallelization needed to achieve optimal performance. In this paper we describe implementation of electromagnetic physics models developed for parallel computing architectures as a part of the GeantV project. Results of preliminary performance evaluation and physics validation are presented as well.

Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here., Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 835, ISSN:0168-9002, ISSN:1872-9576

The fungus Fusarium bulbigenum var. blasticola distinguished by secondary tumor-like growth (TLG) in aging was taken as a novel test system for antitumor drugs. EPR spectroscopy was used to assess the effect of various drugs introduced into the growth medium on the type and content of free radicals in the primary mycelium and TLGs. The EPR spectra in all cases featured a single slightly asymmetrical line of ΔH ∼ 0.4–0.6 mT and g = 2.0036 ± 0.0006, whereby the paramagnetic centers could be assigned to melanin radicals. The content of free radicals was always higher in TLGs than in the primary mycelium, which could naturally be due to more intense metabolism. A number of antitumor drugs (fluorouracil, hydroxyurea, methotrexate, etoposide) completely prevented TLG, with varying effect on free radicals in mycelia. Another group (cyclophosphane, dacarbazine, adriablastine, vinblastine), on the contrary, promoted TLG and increased the free radical content in all fungal cells. The third group (mercaptopurine, thioguanine, pharmorubicin) were weakly suppressive for TLG despite the elevated free radical content therein. Vitamins B2, B12, C, and PP were stimulatory for TLG, whereas in combination with antitumor drugs they could enhance or attenuate their effects.

Thread-parallelization and single-instruction multiple data (SIMD) ”vectorisation” of software components in HEP computing has become a necessity to fully benefit from current and future computing hardware. In this context, the Geant-Vector/GPU simulation project aims to re-engineer current software for the simulation of the passage of particles through detectors in order to increase the overall event throughput. As one of the core modules in this area, the geometry library plays a central role and vectorising its algorithms will be one of the cornerstones towards achieving good CPU performance. Here, we report on the progress made in vectorising the shape primitives, as well as in applying new C++ template based optimizations of existing code available in the Geant4, ROOT or USolids geometry libraries. We will focus on a presentation of our software development approach that aims to provide optimized code for all use cases of the library (e.g., single particle and many-particle APIs) and to support different architectures (CPU and GPU) while keeping the code base small, manageable and maintainable. We report on a generic and templated C++ geometry library as a continuation of the AIDA USolids project. As a result, the experience gained with these developments will be beneficial to othermore » parts of the simulation software, such as for the optimization of the physics library, and possibly to other parts of the experiment software stack, such as reconstruction and analysis.« less

Detector simulation is consuming at least half of the HEP computing cycles, and even so, experiments have to take hard decisions on what to simulate, as their needs greatly surpass the availability of computing resources. New experiments still in the design phase such as FCC, CLIC and ILC as well as upgraded versions of the existing LHC detectors will push further the simulation requirements. Since the increase in computing resources is not likely to keep pace with our needs, it is therefore necessary to explore innovative ways of speeding up simulation in order to sustain the progress of High Energy Physics. The GeantV project aims at developing a high performance detector simulation system integrating fast and full simulation that can be ported on different computing architectures, including CPU accelerators. After more than two years of R&D the project has produced a prototype capable of transporting particles in complex geometries exploiting micro-parallelism, SIMD and multithreading. Portability is obtained via C++ template techniques that allow the development of machine- independent computational kernels. Furthermore, a set of tables derived from Geant4 for cross sections and final states provides a realistic shower development and, having been ported into a Geant4 physics list, can bemore » used as a basis for a direct performance comparison.« less

An intensive R&D; and programming effort is required to accomplish new challenges posed by future experimental high-energy particle physics (HEP) programs. The GeantV project aims to narrow the gap between the performance of the existing HEP detector simulation software and the ideal performance achievable, exploiting latest advances in computing technology. The project has developed a particle detector simulation prototype capable of transporting in parallel particles in complex geometries exploiting instruction level microparallelism (SIMD and SIMT), task-level parallelism (multithreading) and high-level parallelism (MPI), leveraging both the multi-core and the many-core opportunities. We present preliminary verification results concerning the electromagnetic (EM) physics models developed for parallel computing architectures within the GeantV project. In order to exploit the potential of vectorization and accelerators and to make the physics model effectively parallelizable, advanced sampling techniques have been implemented and tested. In this paper we introduce a set of automated statistical tests in order to verify the vectorized models by checking their consistency with the corresponding Geant4 models and to validate them against experimental data.

The recent progress in parallel hardware architectures with deeper vector pipelines or many-cores technologies brings opportunities for HEP experiments to take advantage of SIMD and SIMT computing models. Launched in 2013, the GeantV project studies performance gains in propagating multiple particles in parallel, improving instruction throughput and data locality in HEP event simulation on modern parallel hardware architecture. Due to the complexity of geometry description and physics algorithms of a typical HEP application, performance analysis is indispensable in identifying factors limiting parallel execution. In this report, we will present design considerations and preliminary computing performance of GeantV physics models on coprocessors (Intel Xeon Phi and NVidia GPUs) as well as on mainstream CPUs.

e260 of GF utilization occurred in the first 6 months and > 75% occurred in the first 9 months. BORT cost differentials were driven by higher usage intensity and cost per GF-using patient. Among 393 patients identified with second-line MM, monthly GF costs in the LEN-treated group declined from $211 at treatment initiation to $99 18 months later, while monthly GF costs in the BORT group increased from $364 to $693. Based on the Wilcoxon Rank-sum test, the difference between average GF costs per month across 18+ months after treatment initiation for MM patients was statistically significant ($242, p-value < 0.001) in favor of LEN. Treatment groups were comparable at baseline. Conclusion: BORT is associated with higher monthly GF use and cost during MM treatment, contributing to the significant overall cost disadvantage for BORT vs. LEN-based regimens.

The GeantV project aims to research and develop the next-generation simulation software describing the passage of particles through matter. While the modern CPU architectures are being targeted first, resources such as GPGPU, Intel© Xeon Phi, Atom or ARM cannot be ignored anymore by HEP CPU-bound applications. The proof of concept GeantV prototype has been mainly engineered for CPU's having vector units but we have foreseen from early stages a bridge to arbitrary accelerators. A software layer consisting of architecture/technology specific backends supports currently this concept. This approach allows to abstract out the basic types such as scalar/vector but also to formalize generic computation kernels using transparently library or device specific constructs based on Vc, CUDA, Cilk+ or Intel intrinsics. While the main goal of this approach is portable performance, as a bonus, it comes with the insulation of the core application and algorithms from the technology layer. This allows our application to be long term maintainable and versatile to changes at the backend side. The paper presents the first results of basket-based GeantV geometry navigation on the Intel© Xeon Phi KNC architecture. We present the scalability and vectorization study, conducted using Intel performance tools, as well as our preliminary conclusions on the use of accelerators for GeantV transport. We also describe the current work and preliminary results for using the GeantV transport kernel on GPUs.

The fungus Fusarium bulbigenum var. blasticola in which secondary tumor-like formations appear under certain conditions in aging was used as a new test system to examine the action of antitumor preparations. Free radicals in the primary mycelium and tumor-like formations without introduction of preparations (control samples) and after the introduction of preparation into the cultivation medium of the fungus have been studied by EPR spectroscopy. The EPR spectra of the fungus represent single, somewhat asymmetrical lines with a width of deltaH = 0.4 divided by 0.6 mT and g = 2.0036 +/- 0.006, which enabled one to assign the paramagnetic centers observed to melanine radicals. It was found that the concentration of free radicals in tumor-like formations is always higher than in the primary mycelium, which may be related to intensive metabolism in tumor-like formations. It has been established that several antitumor preparations (fluorouracil, hydrea, methotrexat, and vepezide) completely inhibit the growth of tumor-like formations. Another group of preparations (cyclophosphanum, dacarbazin, adriablastin, and vinblastin), on the contrary, stimulate their growth, which is accompanied by an increase in the concentration of free radicals in cells of the primary mycelium and tumor-like formations. The preparations of the third group (mercaptopurine, lanvis, and farmorubicin), despite the increased level of free radicals in cells, have a weak inhibitory effect. It has been shown that, in the concentration range studied, vitamins B2, B12, C, and PP stimulate the growth of tumor-like formations, and, when used in combination with antitumor preparations, enhance or reduce the inhibitory properties of these preparations.