455 research outputs found
Development of a germanium-68 radionuclide production technology by irradiation of enriched isotope zinc-66 in the R7M
In the present study, we performed the evaluation and experimental determination of 68Ge production using alpha particle beams in the R7M cyclotron of the Tomsk Polytechnic University
Supporting the Integrated Visual Analysis of Input Parameters and Simulation Trajectories
The visualization of simulation trajectories is a well-established approach to analyze simulated processes. Likewise, the visualization of the parameter space that configures a simulation is a well-known method to get an overview of possible parameter combinations. This paper follows the premise that both of these approaches are actually two sides of the same coin: Since the input parameters influence the simulation outcome, it is desirable to visualize and explore both in a combined manner. The main challenge posed by such an integrated visualization is the combinatorial explosion of possible parameter combinations. It leads to insurmountably high simulation runtimes and screen space requirements for their visualization. The Visual Analytics approach presented in this paper targets this issue by providing a visualization of a coarsely sampled subspace of the parameter space and its corresponding simulation outcome. In this visual representation, the analyst can identify regions for further drill-down and thus finer subsampling. We aid this identification by providing visual cues based on heterogeneity metrics. These indicate in which regions of the parameter space deviating behavior occurs at a more fine-grained scale and thus warrants further investigation and possible re-computation. We demonstrate our approach in the domain of systems biology by a visual analysis of a rule-based model of the canonical Wnt signaling pathway that plays a major role in embryonic development. In this case, the aim of the domain experts was to systematically explore the parameter space to determine those parameter configurations that match experimental data sufficiently well
Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice.
Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson\u27s disease. The expression of the shRNA was tightly regulated and, when induced, silenced the Pink1 gene product by more than 95% in mouse brain. However, these mice did not develop dopaminergic neurodegeneration, suggesting that silencing of the Pink1 gene expression from embryo in mice is insufficient to cause similar biochemical or morphological changes that are observed in Parkinson\u27s disease. The results demonstrate that silencing of the PINK1 gene does not induce a reliable mouse model for Parkinson\u27s disease, but that technically the inducible U6 promoter is useful for conditional RNAi in vivo
Разработка бизнес-модели стартапа системы совместного использования велосипедов
В работе приведены теоретические основы построения бизнес-моделей и оценки их эффективности. Исследована сфера систем совместного использования велосипедов, выявлены проблемы и перспективы. На основе проведенной работы была проведена разработка и тестирование бизнес-модели стартап-проекта системы совместного использования велосипедов. В результате была описана концепция данного проекта, практическая значимость которой заключается в запуске проекта системы совместного использования велосипедов в формате стартапа. Методы исследования включают в себя: конкурентный анализ, анализ научной и бизнес литературы, изучение актуальной практики, сравнение, а также customer development, инвестиционный анализ.The theoretical foundations of building business models and assessing their effectiveness are presented in the dissertation. The bicycle sharing systems has been investigated, problems and prospects have been identified. Based on the work carried out, the development and testing of a business model of a startup project for a bicycle sharing system was carried out. As a result, the concept of this project was described, the practical significance of which lies in the launch of a project for a bicycle sharing system in a startup format. Research methods include: competitive analysis, analysis of scientific and business literature, study of current practice, comparison, as well as customer development, investment analysis
Targeted Ablation of Oligodendrocytes Triggers Axonal Damage
Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage
Національні інтереси держави в інформаційній сфері
На сьогодні Україна перебуває в умовах протиборства, в яких саме забезпечення інформаційної безпеки грає ключовий аспект в формуванні національних інтересів держави. В даній роботі розглянуто сучасний стан інформаційної сфери як пріоритетний напрямок національних інтересів України
Physical activity monitoring in Alzheimer’s disease during sport interventions: a multi-methodological perspective
IntroductionAssessment methods for physical activity and fitness are of upmost importance due to the possible beneficial effect of physical conditioning on neurodegenerative diseases. The implementation of these methods can be challenging when examining elderly or cognitively impaired participants. In the presented study, we compared three different assessment methods for physical activity from the Dementia-MOVE trial, a 6-months intervention study on physical activity in Alzheimer’s disease. The aim was to determine the comparability of physical activity assessments in elderly participants with cognitive impairment due to Alzheimer’s disease.Material or methods38 participants (mean age 70 ± 7 years) with early-stage Alzheimer’s disease (mean MoCA 18.84 ± 4.87) were assessed with (1) fitness trackers for an average of 12 (± 6) days, (2) a written diary on daily activities and (3) a questionnaire on physical activity at three intervention timepoints. For comparison purposes, we present a transformation and harmonization method of the physical assessment output parameters: Metabolic equivalent of task (MET) scores, activity intensity minutes, calorie expenditure and moderate-to-vigorous physical activity (MVPA) scores were derived from all three modalities. The resulting parameters were compared for absolute differences, correlation, and their influence by possible mediating factors such as cognitive state and markers from cerebrospinal fluid.ResultsParticipants showed high acceptance and compliance to all three assessment methods. MET scores and MVPA from fitness trackers and diaries showed high overlap, whilst results from the questionnaire suggest that participants tended to overestimate their physical activity in the long-term retrospective assessment. All activity parameters were independent of the tested Alzheimer’s disease parameters, showing that not only fitness trackers, but also diaries can be successfully applied for physical activity assessment in a sample affected by early-stage Alzheimer’s disease.DiscussionOur results show that fitness trackers and physical activity diaries have the highest robustness, leading to a highly comparable estimation of physical activity in people with Alzheimer’s disease. As assessed parameters, it is recommendable to focus on MET, MVPA and on accelerometric sensor data such as step count, and less on activity calories and different activity intensities which are dependent on different variables and point to a lower reliability
Deoxy-sphingolipids, oxidative stress, and vitamin C correlate with qualitative and quantitative patterns of small fiber dysfunction and degeneration
Defined by dysfunction or degeneration of Aδ and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy-confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxy-sphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Aδ fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Aβ fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2 , plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia ( P 25 kg/m 2 ), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P < 0.01) and higher 1-deoxy-sphingolipid levels (arterial hypertension: P < 0.001, overweight: P < 0.001, hyperlipidemia: P < 0.01). Lower vitamin C levels correlated with functional Aβ involvement ( P < 0.05). Reduced glutathione was lower in patients with Aδ dysfunction ( P < 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration
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