Blood-Brain Barrier Breakdown in a Single Post-stroke Rodent Brain

Stroke is a major cause of global morbidity and mortality. Middle cerebral artery occlusion (MCAO) has historically been the most common animal model of simulating ischemic stroke. The extent of neurological injury after MCAO is typically measured by cerebral edema, infarct zone, and blood-brain barrier (BBB) permeability. A significant limitation of these methods is that separate sets of brains must be used for each measurement. Here we examine an alternative method of measuring cerebral edema, infarct zone and BBB permeability following MCAO in the same set of brain samples. Ninety-six rats were randomly divided into three experimental groups. Group 1 (n = 27) was used for the evaluation of infarct zone and brain edema in rats post-MCAO (n = 17) vs. sham-operated controls (n = 10). Group 2 (n = 27) was used for the evaluation of BBB breakdown in rats post-MCAO (n = 15) vs. sham-operated controls (n = 10). In Group 3 (n = 42), all three parameters were measured in the same set of brain slices in rats post-MCAO (n = 26) vs. sham-operated controls (n = 16). The effect of Evans blue on the accuracy of measuring infarct zone by 2,3,5-triphenyltetrazolium chloride (TTC) staining was determined by measuring infarct zone with and without an applied blue filter. The effects of various concentrations of TTC (0, 0.05, 0.35, 0.5, 1, and 2%) on the accuracy of measuring BBB permeability was also assessed. There was an increase in infarct volume (p < 0.01), brain edema (p < 0.01) and BBB breakdown (p < 0.01) in rats following MCAO compared to sham-operated controls, whether measured separately or together in the same set of brain samples. Evans blue had an effect on measuring infarct volume that was minimized by the application of a blue filter on scanned brain slices. There was no difference in the Evans blue extravasation index for the brain tissue samples without TTC compared to brain tissue samples incubated in TTC. Our results demonstrate that measuring cerebral edema, infarct zone and BBB permeability following MCAO can accurately be measured in the same set of brain samples

Associations Between Natural Language Processing (NLP) Enriched Social Determinants of Health and Suicide Death among US Veterans

Importance: Social determinants of health (SDOH) are known to be associated with increased risk of suicidal behaviors, but few studies utilized SDOH from unstructured electronic health record (EHR) notes. Objective: To investigate associations between suicide and recent SDOH, identified using structured and unstructured data. Design: Nested case-control study. Setting: EHR data from the US Veterans Health Administration (VHA). Participants: 6,122,785 Veterans who received care in the US VHA between October 1, 2010, and September 30, 2015. Exposures: Occurrence of SDOH over a maximum span of two years compared with no occurrence of SDOH. Main Outcomes and Measures: Cases of suicide deaths were matched with 4 controls on birth year, cohort entry date, sex, and duration of follow-up. We developed an NLP system to extract SDOH from unstructured notes. Structured data, NLP on unstructured data, and combining them yielded six, eight and nine SDOH respectively. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results: In our cohort, 8,821 Veterans committed suicide during 23,725,382 person-years of follow-up (incidence rate 37.18/100,000 person-years). Our cohort was mostly male (92.23%) and white (76.99%). Across the five common SDOH as covariates, NLP-extracted SDOH, on average, covered 80.03% of all SDOH occurrences. All SDOH, measured by structured data and NLP, were significantly associated with increased risk of suicide. The SDOH with the largest effects was legal problems (aOR=2.66, 95% CI=.46-2.89), followed by violence (aOR=2.12, 95% CI=1.98-2.27). NLP-extracted and structured SDOH were also associated with suicide. Conclusions and Relevance: NLP-extracted SDOH were always significantly associated with increased risk of suicide among Veterans, suggesting the potential of NLP in public health studies.Comment: Submitted to JAMA Network Ope

Non-Equilibrium Statistical Physics of Currents in Queuing Networks

We consider a stable open queuing network as a steady non-equilibrium system of interacting particles. The network is completely specified by its underlying graphical structure, type of interaction at each node, and the Markovian transition rates between nodes. For such systems, we ask the question ``What is the most likely way for large currents to accumulate over time in a network ?'', where time is large compared to the system correlation time scale. We identify two interesting regimes. In the first regime, in which the accumulation of currents over time exceeds the expected value by a small to moderate amount (moderate large deviation), we find that the large-deviation distribution of currents is universal (independent of the interaction details), and there is no long-time and averaged over time accumulation of particles (condensation) at any nodes. In the second regime, in which the accumulation of currents over time exceeds the expected value by a large amount (severe large deviation), we find that the large-deviation current distribution is sensitive to interaction details, and there is a long-time accumulation of particles (condensation) at some nodes. The transition between the two regimes can be described as a dynamical second order phase transition. We illustrate these ideas using the simple, yet non-trivial, example of a single node with feedback.Comment: 26 pages, 5 figure

ОПЫТ И ПРОБЛЕМЫ РАЗРАБОТКИ И ВНЕДРЕНИЯ АСУТП ПГУ НА ЭЛЕКТРОСТАНЦИЯХ РОССИИ И БЕЛОРУССИИ

Summed up the experience of the development and implementation I&C of CCPP by the company «Interavtomatika» AG on various types of CCPP. For example, the I&C of 65 Mw CCPP Borisov (Belarus) CHP considered actual problems of modern I&C of CCPP, among which the first is the integration software of the various local PLC groups processing equipment and PLC unit in a unified system of unit management.Обобщен опыт разработки и внедрения АСУТП ПГУ, полученный ЗАО «Интеравтоматика» на ПГУ различного типа. На примере АСУТП ПГУ-65 МВт Борисовской ТЭЦ (РБ) рассмотрены актуальные проблемы создания современных АСУТП ПГУ, среди которых на первое место выходит интеграция выполненных на различных программно-технических средствах блочной АСУТП и локальных АСУ/САУ групп технологического оборудования в единую систему управления объектом

Internal construct validity of the Shirom-Melamed Burnout Questionnaire (SMBQ)

<p>Abstract</p> <p>Background</p> <p>Burnout is a mental condition defined as a result of continuous and long-term stress exposure, particularly related to psychosocial factors at work. This paper seeks to examine the psychometric properties of the Shirom-Melamed Burnout Questionnaire (SMBQ) for validation of use in a clinical setting.</p> <p>Methods</p> <p>Data from both a clinical (319) and general population (319) samples of health care and social insurance workers were included in the study. Data were analysed using both classical and modern test theory approaches, including Confirmatory Factor Analysis (CFA) and Rasch analysis.</p> <p>Results</p> <p>Of the 638 people recruited into the study 416 (65%) persons were working full or part time. Data from the SMBQ failed a CFA, and initially failed to satisfy Rasch model expectations. After the removal of 4 of the original items measuring tension, and accommodating local dependency in the data, model expectations were met. As such, the total score from the revised scale is a sufficient statistic for ascertaining burnout and an interval scale transformation is available. The scale as a whole was perfectly targeted to the joint sample. A cut point of 4.4 for severe burnout was chosen at the intersection of the distributions of the clinical and general population.</p> <p>Conclusion</p> <p>A revised 18 item version of the SMBQ satisfies modern measurement standards. Using its cut point it offers the opportunity to identify potential clinical cases of burnout.</p

Bilingually motivated word segmentation for statistical machine translation

We introduce a bilingually motivated word segmentation approach to languages where word boundaries are not orthographically marked, with application to Phrase-Based Statistical Machine Translation (PB-SMT). Our approach is motivated from the insight that PB-SMT systems can be improved by optimizing the input representation to reduce the predictive power of translation models. We firstly present an approach to optimize the existing segmentation of both source and target languages for PB-SMT and demonstrate the effectiveness of this approach using a Chinese–English MT task, that is, to measure the influence of the segmentation on the performance of PB-SMT systems. We report a 5.44% relative increase in Bleu score and a consistent increase according to other metrics. We then generalize this method for Chinese word segmentation without relying on any segmenters and show that using our segmentation PB-SMT can achieve more consistent state-of-the-art performance across two domains. There are two main advantages of our approach. First of all, it is adapted to the specific translation task at hand by taking the corresponding source (target) language into account. Second, this approach does not rely on manually segmented training data so that it can be automatically adapted for different domains

СОВЕРШЕНСТВОВАНИЕ СИСТЕМ РЕГУЛИРОВАНИЯ ПАРОВЫХ ТУРБИН АЭС И АВТОМАТИЗАЦИЯ ОБОРУДОВАНИЯ МАШИННЫХ ЗАЛОВ АЭС РОССИИ

Typical structure of closed-loop control for steam turbine К-1000-60/3000, designed and implemented by «Interavtomatika» at the unit 4 Kalinin NPP are shown. A wide range of tests confirmed execution of all the functions of control, protection and antifault control. Based on this structure were developed projects of electronic part control system for units K-1200-60/3000 Novovoronezh nuclear power station and the BN800 Beloyarsk nuclear power plant. For turbine 1200 MW of the Belarusian nuclear power plant is expected to use the same proven solutions, but on the basis of new VNIIA developments.Приведена типовая структура системы регулирования паровой турбины К-1000-60/3000, разработанная и внедренная ЗАО «Интеравтоматика» на энергоблоке № 4 Калининской АЭС. Широкий спектр испытаний подтвердил выполнение всех функций управления, защит и противоаварийной автоматики. На основе этой структуры разработаны проекты ЭЧСР энергоблоков К-1200-60/3000 Нововоронежской АЭС и БН800 Белоярской АЭС. Применительно к турбине 1200 МВт Белорусской АЭС предполагается использовать эти же проверенные решения, но на базе новой, разработанной ВНИИА аппаратуре ТПТС НТ

Synthesis and characterization of high-affinity 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-labeled fluorescent ligands for human β-adrenoceptors

The growing practice of exploiting noninvasive fluorescence-based techniques to study G protein-coupled receptor pharmacology at the single cell and single molecule level demands the availability of high-quality fluorescent ligands. To this end, this study evaluated a new series of red-emitting ligands for the human β-adrenoceptor family. Upon the basis of the orthosteric ligands propranolol, alprenolol, and pindolol, the synthesized linker-modified congeners were coupled to the commercially available fluorophore BODIPY 630/650-X. This yielded high-affinity β-adrenoceptor fluorescent ligands for both the propranolol and alprenolol derivatives; however, the pindolol-based products displayed lower affinity. A fluorescent diethylene glycol linked propranolol derivative (18a) had the highest affinity (log KD of -9.53 and -8.46 as an antagonist of functional β2- and β1-mediated responses, respectively). Imaging studies with this compound further confirmed that it can be employed to selectively label the human β2-adrenoceptor in single living cells, with receptor-associated binding prevented by preincubation with the nonfluorescent β2-selective antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]-butan-2-ol (ICI 118551) (J. Cardiovasc. Pharmacol. 1983, 5, 430-437.

Спектрометрия ионной подвижности N-метилимидазола и возможности его определения

Objectives. To determine the ion mobility of N-methylimidazole, establish the structure of ions corresponding to characteristic signals, and determine the detection limit of N-methylimidazole on the ion-drift detector Kerber.Methods. Ion mobility spectrometry was used to study the ionization processes. The enthalpies of the reactions of monomer and dimer ions were calculated in the ORCA 4.1.1 software by the B3LYP density functional method with a set of basic functions 6-31G (d, p).Results. The drift time and ion mobility values of N-methylimidazole were determined. A method for mathematical processing of spectra and a program for its implementation was developed. The changing peculiarities of the ion mobility spectrum during measurement at a given time were studied. According to the interpretation of the spectrum signals, the structure of the generated ions was proposed, and the enthalpies of ion formation were determined.Conclusions. The characteristic signal of the N-methylimidazole ion protonated at the nitrogen atom of the pyridine type was revealed. It was found that two signals in the ion mobility spectra of N-methylimidazole correspond to the presence of the monomer and dimer ions. The detection limit of N-methylimidazole on the ion-drift detector Kerber was determined, amounting to 3 pg.Цели. Определение значений ионной подвижности N-метилимидазола. Установление строения ионов, соответствующих характерным сигналам. Определение предела обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер.Методы. Метод спектрометрии ионной подвижности был использован для исследования процессов ионизации. Энтальпии реакций мономерных и димерных ионов расчитаны в программе ORCA 4.1.1 методом функционала плотности B3LYP с набором базисных функций 6-31G(d,p).Результаты. Определены значения времени дрейфа и ионной подвижности N-метилимидазола. Разработана методика математической обработки спектров и программа для ее реализации. Изучены особенности изменения характера спектра ионной подвижности в процессе измерения в данный момент времени. Предложено строение генерируемых ионов в соответствии с интерпретацией сигналов спектра. Определены энтальпии образования ионов.Выводы. Выявлен характеристический сигнал иона N-метилимидазола, протонированного по атому азота пиридинового типа. Установлено, что два сигнала в спектрах ионной подвижности N-метилимидазола соответствуют наличию мономерной и димерной формы ионов. Определен предел обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер, составляющий 3 пг

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN