Detection of Antibodies Recognizing Puumala Virus Nucleocapsid and Glycoprotein Peptides in NE Serum

© 2016, Springer Science+Business Media New York.Nephropatia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an endemic zoonosis in the Republic of Tatarstan, Russia. Humans become infected by inhaling an aerosol contaminated with Puumala virus, a member of genus Hantavirus. NE diagnosis is based on detection of anti-hantavirus antibodies using ELISA. Antibodies to hantavirus nucleocapsid (N) protein are detected early in the course of infection, suggesting that this viral protein is the most immunogenic. Several epitopes were previously identified on N protein as well as glycoproteins of Puumala viruses endemic in Europe. However, there is limited knowledge about Puumala virus N protein antigenic epitopes in NE patients in the Republic of Tatarstan. The aim of the present study is to identify N protein and glycoprotein epitopes which induce a humoral immune response in NE cases. Analysis of NE serum using an array of overlapping N protein and glycoprotein peptides identified the most immunogenic epitopes, which can then be used for developing Puumala virus-specific vaccine

CALIBRATION LABORATORY RISK MANAGEMENT AS AN INNOVATIVE APPROACH TO THE MANAGEMENT OF WEATHERFORD

This article describes the goals, objectives, definition and analysis of typical risks as an innovative approach to management in the verification of measuring instruments in a metrological laboratory

Innovative Approach to Company Management in the Part of Risk Management of a Calibration Laboratory

В статье описаны цели, задачи, определение и анализ типовых рисков как инновационный подход к управлению при поверке средств измерений в метрологической лаборатории.This article describes the goals, objectives, definition and analysis of typical risks as an innovative approach to management in the verification of measuring instruments in a metrological laboratory

High Triglycerides Are Associated with Low Thrombocyte Counts and High VEGF in Nephropathia Epidemica

© 2016 Ekaterina V. Martynova et al.Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN-γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN-γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity

Задача о роботах на Марсе (мультиагентный подход к задаче Дейкстры)

We continue our study of multiagent algorithms for a problem that we call the Mars Robot Puzzle. This problem could be considered as a special case of a graph-theoretic problem (Discrete Mathematics), as a combinatorial geometry problem (Computer Science), or as a very special case of a path-planning problem (Artificial Intelligence). Our algorithms grew up from a local search (heuristic) solution of the problem suggested by E.W. Dijkstra. In the paper we present a series of new multiagent algorithms solving the problem, prove (manually) their correctness, model check some of these algorithms, and discuss further research topics. All our algorithms are multiagent in contrast to "centralized" graph and combinatorial algoritms; correctness of our algorithms is formally proven, while the testing is used for validation of path-planning algorithms.Изучаются мультиагентные алгоритмы для так называемой задачи о роботах на Марсе. Эту задачу можно рассматривать как задачу из теории графов (дискретная математика), как комбинаторную геометрическую задачу (теоретическое программирование) или как частный случай задачи планирования перемещений (искусственный интеллект). Наши алгоритмы основаны на эвристическом поиске, предложенном Э. Дейкстрой. В статье представлен ряд новых мультиагентных алгоритмов, решающих задачи о роботах на Марсе, доказана их корректность, приведены результаты проверки на модели некоторых из этих алгоритмов, предложены направления дальнейших исследований. Новизна представленной работы состоит в том, что в отличие от теоретико-графового и комбинаторно-геометрического подходов, ориентированных на централизованное решение задачи, мы развиваем мультиагентный подход, но, в свою очередь, наша работа отличается от работ по планированию перемещений математической строгостью доказательств корректности предложенных алгоритмов. Я, робот. А. Азимо

Верификация алгоритмов мультиагентного анализа данных с помощью системы проверки моделей SPIN

The paper presents an approach to formal verification of multi-agent data analysis algorithms for ontology population. The system agents correspond to information items of the input data and the rule of ontology population and data processing. They determine values of information objects obtained at the preliminary phase of the analysis. The agents working in parallel check the syntactic and semantic consistency of tuples of information items. Since the agents operate in parallel, it is necessary to verify some important properties of the system related to it, such as the property that the controller agent correctly determines the system termination. In our approach, the model checking tool SPIN is used. The protocols of agents are written in Promela language (the input language of the tool) and the properties of the multi-agent data analysis system are expressed in the liner time logic LTL. We carried out several experiments to check this model in various modes of the tool and various numbers of agents.В статье представлен подход к формальной верификации алгоритмов мультиагентного анализа данных для пополнения онтологий. Агенты системы на основе входных данных устанавливают значения элементов объектов, полученных на предварительной стадии анализа. Агенты параллельно осуществляют проверку семантической и синтаксической согласованности, используя правила пополнения онтологий и обработки данных. Поскольку агенты действуют параллельно, необходимо верифицировать некоторые важные свойства системы, связанные с этим, например, свойство корректности определения завершения работы системы. В нашем подходе используется инструмент проверки моделей SPIN. Протоколы агентов записаны на языке Promela, а свойства мультиагентной системы анализа данных выражены в логике LTL. Мы провели ряд экспериментов по проверке данной модели

Human Mesenchymal Stem Cells Overexpressing Interleukin 2 Can Suppress Proliferation of Neuroblastoma Cells in Co-Culture and Activate Mononuclear Cells In Vitro

High-dose recombinant interleukin 2 (IL2) therapy has been shown to be successful in renal cell carcinoma and metastatic melanoma. However, systemic administration of high doses of IL2 can be toxic, causing capillary leakage syndrome and stimulating pro-tumor immune response. One of the strategies to reduce the systemic toxicity of IL2 is the use of mesenchymal stem cells (MSCs) as a vehicle for the targeted delivery of IL2. Human adipose tissue-derived MSCs were transduced with lentivirus encoding IL2 (hADSCs-IL2) or blue fluorescent protein (BFP) (hADSCs-BFP). The proliferation, immunophenotype, cytokine profile and ultrastructure of hADSCs-IL2 and hADSCs-BFP were determined. The effect of hADSCs on activation of peripheral blood mononuclear cells (PBMCs) and proliferation and viability of SH-SY5Y neuroblastoma cells after co-culture with native hADSCs, hADSCs-BFP or hADSCs-IL2 on plastic and Matrigel was evaluated. Ultrastructure and cytokine production by hADSCs-IL2 showed modest changes in comparison with hADSCs and hADSCs-BFP. Conditioned medium from hADSC-IL2 affected tumor cell proliferation, increasing the proliferation of SH-SY5Y cells and also increasing the number of late-activated T-cells, natural killer (NK) cells, NKT-cells and activated T-killers. Conversely, hADSC-IL2 co-culture led to a decrease in SH-SY5Y proliferation on plastic and Matrigel. These data show that hADSCs-IL2 can reduce SH-SY5Y proliferation and activate PBMCs in vitro. However, IL2-mediated therapeutic effects of hADSCs could be offset by the increased expression of pro-oncogenes, as well as the natural ability of hADSCs to promote the progression of some tumors

Use of Biologically Active 3D Matrix for Extensive Skin Defect Treatment in Veterinary Practice: Case Report

Objectives: Large full-thickness skin defects represent a serious veterinary problem.Methods: We have developed novel bioactive 3D-matrixes based on fibrin glue Tissucol (Baxter), containing the combination of the adenoviral constructs with genes vascular endothelial growth factor 165 (VEGF165) and fibroblast growth factor two (FGF2; construct Ad5-VEGF165 + Ad5-FGF2) or multipotent mesenchymal stem cells, genetically modified with these constructs.Results:In vitro studies confirmed the biosynthesis of VEGF165 and FGF2 mRNA in the transduced cells. Ad5-VEGF165 + Ad5-FGF2- transduced multipotent mesenchymal stem cells showed an enhanced capacity to form capillary-like tubes in vitro. Bioactive 3D-matrix application enhanced granulation tissue formation and epithelialization of non-healing, large bite wounds in a dog. Successful wound healing was observed with a positive clinical outcome for the canine patient. This research and application of regenerative gene therapy alongside a novel bioactive 3D-matrix shows promising clinical applications for the future in both dogs and other mammals including humans

Assessment of the psycho-emotional state of patients after COVID-19-associated pneumonia in relationship with laboratory indicators

The aim. To study peculiarities and association of psychological and laboratory indicators in patients with cardiovascular diseases (CVD) who underwent COVID-19 to clarify the factors affecting the possibility of developing delayed psychological and cardiovascular adverse events.Methods. The study enrolled 350 patients with COVID-19. Group 1 consisted of 92 patients without CVD, Group 2 – of 258 patients with CVD. Indicators of laboratory and psychological parameters were assessed according to the data of psychological questionnaire using GAD-7 (General Anxiety Disorder-7), PHQ-9 (Patient Health Questionnaire-9), PSS (Perceived Stress Scale) screening scales and SF-36. Parameters of complete blood count and biochemical blood tests were measured during hospitalization and three months after discharge from the monohospital.Results. After three months, in the general group of patients, signs of anxiety and depression were detected in more than 30 % of the examined patients, signs of stress – in 10.4 %. In the group with CVD, psycho-emotional disorders were identified in 1/4 of the patients, and severe stress – in 8 % of those included in the study. In addition, it was registered that the indicators of erythrocyte sedimentation rate, fibrinogen, high-sensitivity C-reactive protein (CRP), homocysteine and IL-6 remained at a higher level in the second group.Correlation analysis showed that the psychological component of health is interconnected with the level of neutrophils (p = 0.044) and fibrinogen (p = 0.050); the physical component of health is correlated with the level of erythrocytes (p = 0.030), hemoglobin (p = 0.015), CRP (p = 0.002), creatine phosphokinase (p = 0.036) and glucose (p = 0.017). Regression analysis revealed that in patients with CVD three months after hospitalization, an increased glucose index contributes to deterioration, and increased hematocrit and mean hemoglobin concentration improve the quality of life of patients.Conclusion. Laboratory markers that maintain the duration of a prolonged vascular reaction, violation of the rheological and metabolic properties of blood, determine the nature of the development of both psychological and cardiovascular complications

Tandem Delivery of Multiple Therapeutic Genes Using Umbilical Cord Blood Cells Improves Symptomatic Outcomes in ALS

© 2016, Springer Science+Business Media New York. Current treatment options of chronic, progressive degenerative neuropsychiatric conditions offer only marginal efficacy, and there is no therapy which arrests or even reverses these diseases. Interest in genetic engineering and cell-based approaches have constantly been increasing, although most of them so far proved to be fruitless or at best provided very slight clinical benefit. In the light of the highly complex patho-mechanisms of these maladies, the failure of drugs aimed at targeting single molecules is not surprising. In order to improve their effectiveness, the role of a unique triple-combination gene therapy was investigated in this study. Intravenous injection of human umbilical cord blood mononuclear cell (hUCBMC) cotransduced with adenoviral vectors expressing vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) resulted in prominent increase of life span and performance in behavioral tests in amyotrophic lateral sclerosis (ALS). Expression of the recombinant genes in hUCBMCs was confirmed as soon as 5 days after transduction by RT-PCR, and cells were detectable for as long as 1 month after grafting in lumbar spinal cord by immunofluorescent staining. Xenotransplantation of cells into mice blood without any immunosuppression demonstrated a high level of hUCBMCs homing and survivability in the central nervous system (CNS), most conspicuously in the spinal cord, but not in the spleen or liver. This study confirms an increased addressed homing and notable survivability of triple-transfected cells in lumbar spinal cord, yielding a remarkably enhanced therapeutic potential of hUCBMCs overexpressing neurotrophic factors