RESUMO
We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.
Assuntos
Antivirais/química , Tratamento Farmacológico da COVID-19 , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/química , Inteligência Artificial , Sítios de Ligação , Simulação por Computador , Bases de Dados de Compostos Químicos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Relação Estrutura-AtividadeRESUMO
There was performed the study of the characteristics of the regulation of vertical posture in 42 children of 8-10 years old using school bags of different designs. According to medical examination 25 children have normal posture and 17 children had kyphotic one. The stability of the posture was estimated according to the average variance and the average velocity of the total center of gravity of the body, the area of the ellipse, and the quality of the equilibrium function with computer stabilography. Three models of school bags were used - with traditional, ergonomic and orthopedic back support. Vertical posture stability for children with impaired posture without school bag and when used with traditional and ergonomic back were significantly lower in comparison with children with normal posture. When the orthopedic back was used the stability impairment of the vertical posture in children with kyphotic posture was not observed. It is concluded that for the prevention of spinal deformity for students with kyphotic posture orthopedic school bags should be used.
Assuntos
Curvaturas da Coluna Vertebral , Criança , Desenvolvimento Infantil , Vestuário/efeitos adversos , Vestuário/normas , Feminino , Humanos , Masculino , Teste de Materiais/métodos , Fatores de Risco , Serviços de Saúde Escolar/normas , Serviços de Saúde Escolar/estatística & dados numéricos , Curvaturas da Coluna Vertebral/epidemiologia , Curvaturas da Coluna Vertebral/prevenção & controle , Suporte de Carga/fisiologiaRESUMO
A characteristic feature of the life activity of modern children and adolescents is the couch potato, mostly "sedentary" lifestyle. Biomedical and psychosocial significance of motor activity (MA) stipulates the necessity of the substantiation of scientific and methodological approaches to the formation of the motivation to exercises and sports in children. The purpose of the study was in the scientific substantiation and the delivery of medical, pedagogical and neurophysiological prerequisites for the formation of the motivation to increase MA in students in current conditions of their life activity. There were examined 189 students from 2-5th and 9th classes, out of them 65 students were observed in the dynamics of the school year; 585 students from the 1st-11th classes participated in the survey. Results of the study allowed to reveal the relation of students to the lessons of physical training, to evaluate the impact of a new educational program on the functional possibilities of the body of children from the special medical group "A" and to reveal the neurophysiological features of adolescents with different needs in motion.
Assuntos
Motivação/fisiologia , Atividade Motora/fisiologia , Educação Física e Treinamento/organização & administração , Instituições Acadêmicas , Esportes/fisiologia , Estudantes , Adolescente , Criança , Feminino , Humanos , Masculino , Federação Russa , Inquéritos e QuestionáriosRESUMO
A methodical approach to the hygienic assessment of the educational environment in children's educational institutions was developed and tested for the objective determination of the level ofsanitary and epidemiological welfare and effective planning of preventive measures with bearing in mind environmental factors which have the most negative impact on children's health.
Assuntos
Proteção da Criança/tendências , Saúde Ambiental , Serviços Preventivos de Saúde , Serviços de Saúde Escolar , Instituições Acadêmicas , Adolescente , Criança , Meio Ambiente , Saúde Ambiental/normas , Saúde Ambiental/estatística & dados numéricos , Saúde Ambiental/tendências , Feminino , Humanos , Masculino , Auditoria Médica/normas , Auditoria Médica/tendências , Serviços Preventivos de Saúde/normas , Serviços Preventivos de Saúde/estatística & dados numéricos , Melhoria de Qualidade , Federação Russa , Serviços de Saúde Escolar/normas , Serviços de Saúde Escolar/estatística & dados numéricos , Instituições Acadêmicas/normas , Instituições Acadêmicas/estatística & dados numéricosRESUMO
Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA's field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA's field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today's state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of the angiograms, we developed for the first time a three-dimensional deep learning based algorithm for denoising volumetric OCTA data sets. We showcase its imaging performance and clinical usability by presenting images of patients suffering from diabetic retinopathy.
Assuntos
Angiografia , Oftalmologia , Doenças Retinianas , Tomografia de Coerência Óptica , Humanos , Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia/normas , Doenças Retinianas/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/normas , Angiografia/instrumentação , Angiografia/métodos , Angiografia/normas , Oftalmologia/instrumentação , Oftalmologia/métodosRESUMO
The hygienic evaluation of pedagogical technology for teaching under the active sensory-developing environment and the Intellect technology showed that their implementation caused a reduction in the fatiguing effect of an educational load, by optimizing the organization of a teaching process and enhancing the functional capacities of pupils.
Assuntos
Desenvolvimento do Adolescente/fisiologia , Desenvolvimento Infantil/fisiologia , Tecnologia Educacional/métodos , Nível de Saúde , Ensino/normas , Adolescente , Sistema Nervoso Central/fisiologia , Criança , Avaliação Educacional , Hemodinâmica/fisiologia , Humanos , Saúde Mental , Federação Russa , Estudantes , Ensino/métodos , Ensino/organização & administraçãoRESUMO
We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.
RESUMO
Physiological and hygienic studies under the conditions of a natural hygienic experiment were conducted to examine different variants of the organization of work of new types of general educational establishments--full-day schools. Over 580 pupils from 5 full-day schools were followed up. Organization of teaching children at full-day schools was found to mainly correspond to the age-related capabilities of pupils from primary and secondary classes. Of vital importance for maintenance of mental performance, good emotional and psychosomatic states are the organization of the intraschool environment, including a school plot, as well as the conditions for realization of additional education, motor activity of children, and recess. Health keeping in pupils from full-day schools is favored by the reduction in the duration of lessons to 35 minutes and day sleep for first-form children, the decrease in the number of pupils in a class, outdoor physical exercises in the middle of a school day (a primary school) and strolls after lessons, three meals a day, balanced additional education, medicopsychological accompaniment, optimization of studies and rest in children during a school year.
Assuntos
Proteção da Criança , Higiene/normas , Serviços de Saúde Escolar/organização & administração , Instituições Acadêmicas/organização & administração , Adolescente , Criança , Humanos , Avaliação de Programas e Projetos de Saúde , Federação RussaRESUMO
Different variants of teaching organization at high school have been studied on the basis of a comparative analysis. The 10th-form pupils of specialized classes have been established to have a lower level of mental performance than those of the same age from general educational classes. This is associated with the drastic increase in a weekly summary educational load as compared with that in a ninth form, which was characteristic of the pupils of specialized classes; their educational load is increased by 8.5 hours whereas that is by 2.5 hours in those of educational classes. The adaptation of the pupils of specialized classes to new specialized educational conditions is completed by the 11th form, as suggested by the positive changes in their mental performance. The study of different models of specialized education organization has revealed that a multispecialized model that can individualize an academic process to a greater extent is hygienically most favorable. Recommendations have been developed for the hygienic optimization of an academic process at high school.
Assuntos
Doença Crônica/epidemiologia , Nível de Saúde , Ocupações , Educação Vocacional , Adolescente , Humanos , Federação Russa/epidemiologia , Instituições AcadêmicasRESUMO
The paper briefly presents clinical, epidemiological, virological and serological data on cases of Crimean-Congo hemorrhagic fever (CCHF) in Astrakhan Province. The results indicate annual infection of the regions population with CCHF virus, the main mode of transmission being vector-borne. The advantages of the fluorescence antibody technique and enzyme immunoassay-for diagnosis of the disease were demonstrated.
Assuntos
Febre Hemorrágica da Crimeia/diagnóstico , Doença Aguda , Animais , Animais Recém-Nascidos , Anticorpos Antivirais/análise , Encéfalo/imunologia , Encéfalo/microbiologia , Reservatórios de Doenças , Cobaias , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Febre Hemorrágica da Crimeia/epidemiologia , Febre Hemorrágica da Crimeia/imunologia , Febre Hemorrágica da Crimeia/microbiologia , Humanos , Rim/imunologia , Rim/microbiologia , Fígado/imunologia , Fígado/microbiologia , Camundongos , Federação Russa/epidemiologia , Estações do Ano , Fatores de TempoRESUMO
Paper presents the results of a successful use of a solid-phase immunoassay for indication of the antigen of hemorrhagic fever-Crimean--Congo virus in lays and half-fed female-ticks Hyalomma marginatum marginatum Koch (1795) collected in endemic area, which adds to our knowledge of this disease focus activity.
Assuntos
Antígenos Virais/análise , Vetores Aracnídeos , Bunyaviridae/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Febre Hemorrágica da Crimeia/diagnóstico , Animais , Técnicas ImunoenzimáticasRESUMO
The study of ixodes ticks collected in Astrakhan Province in 1982-1987 has revealed spontaneous infection with Crimean hemorrhagic fever virus in 4 species. It has been established that a proportion of the infected ck suspensions from the imago Hyalomma marginatum marginatum (a back-ground species for the given region) was 3.6% as measured by the method of mouse infection and 8.9% as measured by the enzyme immunoassay. The advantages of the enzyme immunoassay as a method for Crimean hemorrhagic fever virus identification in ticks have been demonstrated.
Assuntos
Vetores Aracnídeos/microbiologia , Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Carrapatos/microbiologia , Animais , Feminino , Masculino , Federação Russa , Estações do Ano , Virologia/métodosAssuntos
Arbovírus/isolamento & purificação , Animais , Animais Recém-Nascidos , Anticorpos Antivirais/análise , Infecções por Arbovirus/imunologia , Infecções por Arbovirus/microbiologia , Arbovírus/imunologia , Arbovírus/patogenicidade , Bovinos , Feminino , Cobaias , Humanos , Masculino , Camundongos , Ratos , Federação Russa , Carrapatos/microbiologiaRESUMO
Cortexin, nootropil and cerebrolysin have been used as neuroprotective medications in the acute period of ischemic stroke (IS). Clinical efficacy of cortexin and nootropil has been compared in 2 therapeutic series in 35 patients and that of cortexin and cerebrolysin--in 45 patients. The efficacy was assessed using several clinical and psychometric scales with statistical processing of the results. The data obtained suggest that in patients with moderate IS the drugs exert a similar and rather marked effect which was stronger comparing to the treatment without these drugs. At the same time, a domestic neuroprotector cortexin has some advantages, especially with regard to the absence of side-effects and "price-dose-therapeutic effect" criterion.
Assuntos
Aminoácidos/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Peptídeos/uso terapêutico , Piracetam/uso terapêutico , Idoso , Encéfalo/efeitos dos fármacos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/psicologia , Ecoencefalografia , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Resultado do TratamentoRESUMO
In this paper we have pointed at the coincidence of vaginal fluor with uroinfections. We undertook examinations and observations on girls from the age of 3 to 15 in 130 cases and have come to the result that the disease of one tract is nearly always connected with some affection of the other one. So both of them are in any case to be examined and--as our cases proved--also to be treated.