Report of conference evaluation committee

A general classification is made of a number of approaches used for the prediction of turbulent shear flows. The sensitivity of these prediction methods to parameter values and initial data are discussed in terms of variable density, pressure fluctuation, gradient diffusion, low Reynolds number, and influence of geometry

Traditional Japanese Herbal Medicine Yokukansan Targets Distinct but Overlapping Mechanisms in Aged Mice and in the 5xFAD Mouse Model of Alzheimer’s Disease

Yokukansan (YKS) is a traditional Japanese herbal medicine that has been used in humans for the treatment of several neurological conditions, such as age-related anxiety and behavioral and psychological symptoms (BPSD) related to multiple forms of dementia, including Alzheimer’s disease (AD). However, the cellular and molecular mechanisms targeted by YKS in the brain are not completely understood. Here, we compared the efficacy of YKS in ameliorating the age- and early-onset familial AD-related behavioral and cellular defects in two groups of animals: 18- to 22-month-old C57BL6/J wild-type mice and 6- to 9-month-old 5xFAD mice, as a transgenic mouse model of this form of AD. Animals were fed food pellets that contained YKS or vehicle. After 1–2 months of YKS treatment, we evaluated the cognitive improvements in both the aged and 5xFAD transgenic mice, and their brain tissues were further investigated to assess the molecular and cellular changes that occurred following YKS intake. Our results show that both the aged and 5xFAD mice exhibited impaired behavioral performance in novel object recognition and contextual fear conditioning (CFC) tasks, which was significantly improved by YKS. Further analyses of the brain tissue from these animals indicated that in aged mice, this improvement was associated with a reduction in astrogliosis, microglia activation and downregulation of the extracellular matrix (ECM), whereas in 5xFAD mice, none of these mechanisms were evident. These results show the differential action of YKS in healthy aged and 5xFAD mice. However, both aged and 5xFAD YKS-treated mice showed increased neuroprotective signaling through protein kinase B/Akt as the common mode of action. Our data suggest that YKS may impart its beneficial effects through Akt signaling in both 5xFAD mice and aged mice, with multiple additional mechanisms potentially contributing to its beneficial effects in aged animals

Investigation of three-dimensional shock wave/turbulent-boundary-layer interaction initiated by a single fin

Three-dimensional shock wave/turbulent-boundary-layer interaction of a hypersonic flow passing a single fin mounted on a flat plate at a Mach number of five and unit Reynolds number 3.7×10^7 was conducted by a large-eddy simulation approach. The performed large-eddy simulation has demonstrated good agreement with experimental data in terms of mean flowfield structures, surface pressure distribution, and surface flow pattern. Furthermore, the shock wave system, flow separation structure, and turbulence characteristics were all investigated by analyzing the obtained large-eddy simulation dataset. It was found that, for this kind of three-dimensional shock wave/turbulent-boundary-layer interaction problem, the flow characteristics in different regions have been dominated by respective wall turbulence, free shear layer turbulence, and corner vortex motions in different regions. In the reverse flow region, near-wall quasi-streamwise streaky structures were observed just beneath the main separation vortex, indicating that the transition of the pathway of the separation flow to turbulence may occur within a short distance from the reattachment location. The obtained large-eddy simulation results have provided a clear and direct evidence of the primary reverse flow and the secondary separation flow being essentially turbulent

N-acetylcysteine relieves neurologic signs of acute ethanol hangover in rats

Orally administered NAC before acute ethanol intoxication led to a decrease in the severity of neurological deficiency in rats and reduced the amnesic effect of ethanol. This could be due to an improvement of ethanol metabolism and a decrease in the severity of disorders associated with oxidative stress and liver dysfunctio

Considerations for Permitted Daily Exposure Calculation for Contaminants in Medicinal Products Manufactured in Shared Facilities

The manufacture of different medicinal products in shared facilities creates a risk of cross-contamination. One of the approaches to select the limits for possible contaminants is based on calculating the permitted daily exposure (PDE), i.e. the dose of an active pharmaceutical ingredient or any other substance contaminating a medicinal product that will not be associated with any adverse events in a human in the case of lifetime exposure. The aim of this study was to provide practical guidance on selecting adjustment factors for calculating PDEs to establish limits for potential contaminants in multi-purpose pharmaceutical facilities. The authors analysed the regulatory requirements and literature needed to establish critical effects of contaminants, outlined possible assumptions in the use of quantitative indicators for measuring toxicity, and described the relationship between the PDE and other indicators of the safety of chemical compounds for human health. The article presents an example of PDE calculation for an investigational hypoglycemic medicinal product using a limited amount of open-source literature data. Thus, the article demonstrates the role of information on the primary pharmacodynamic effects of medicinal products in the assessment of their critical effects, which is necessary to implement the most conservative approaches to PDE calculation. The example of PDE calculation presented in the article may be used to assess cross-contamination risks associated with non-dedicated manufacturing facilities

Large-eddy simulation of hypersonic flows. Selective procedure to activate the sub-grid model wherever small scale turbulence is present

A new method for the localization of the regions where small scale turbulent fluctuations are present in hypersonic flows is applied to the large-eddy simulation (LES) of a compressible turbulent jet with an initial Mach number equal to 5. The localization method used is called selective LES and is based on the exploitation of a scalar probe function! which represents the magnitude of the stretching tilting term of the vorticity equation normalized with the enstrophy (Tordella et al., 2007) [3]. For a fully developed turbulent field of fluctuations, statistical analysis shows that the probability that f is larger than 2 is almost zero, and, for any given threshold, it is larger if the flow is under-resolved. By computing the spatial field off in each instantaneous realization of the simulation it is possible to locate the regions where the magnitude of the normalized vortical stretching tilting is anomalously high. The sub-grid model is then introduced into the governing equations in such regions only. The results of the selective LES simulation are compared with those of a standard LES, where the sub-grid terms are used in the whole domain, and with those of a standard Euler simulation with the same resolution. The comparison is carried out by assuming as reference field a higher resolution Euler simulation of the same jet. It is shown that the selective LES modifies the dynamic properties of the flow to a lesser extent with respect to the classical LES. In particular, the prediction of the enstrophy, mean velocity and density distributions and of the energy and density spectra are substantially improved

Особенности расчета допустимой ежедневной экспозиции контаминантов при производстве лекарственных препаратов на общих технологических линиях

The manufacture of different medicinal products in shared facilities creates a risk of cross-contamination. One of the approaches to select the limits for possible contaminants is based on calculating the permitted daily exposure (PDE), i.e. the dose of an active pharmaceutical ingredient or any other substance contaminating a medicinal product that will not be associated with any adverse events in a human in the case of lifetime exposure. The aim of this study was to provide practical guidance on selecting adjustment factors for calculating PDEs to establish limits for potential contaminants in multi-purpose pharmaceutical facilities. The authors analysed the regulatory requirements and literature needed to establish critical effects of contaminants, outlined possible assumptions in the use of quantitative indicators for measuring toxicity, and described the relationship between the PDE and other indicators of the safety of chemical compounds for human health. The article presents an example of PDE calculation for an investigational hypoglycemic medicinal product using a limited amount of open-source literature data. Thus, the article demonstrates the role of information on the primary pharmacodynamic effects of medicinal products in the assessment of their critical effects, which is necessary to implement the most conservative approaches to PDE calculation. The example of PDE calculation presented in the article may be used to assess cross-contamination risks associated with non-dedicated manufacturing facilities.Производство лекарственных препаратов на общих технологических линиях создает риск перекрестной контаминации. Одним из способов выбора пределов содержания возможных контаминантов является подход, основанный на расчете допустимой ежедневной экспозиции (permitted daily exposure, PDE) – дозы активной фармацевтической субстанции или другого контаминирующего вещества, потребление которой в течение всей жизни не будет ассоциировано у человека с нежелательными явлениями. Цель работы – представить методику определения коэффициентов для расчета значений PDE, используемых для установления пределов содержания потенциальных контаминантов на общих технологических линиях фармацевтических производств. Проанализированы требования нормативных документов и источники литературы, необходимые для оценки критически значимых эффектов контаминантов, приведены сведения о возможных допущениях при использовании токсикометрических показателей, описана взаимосвязь PDE с другими показателями, характеризующими безопасность химических соединений в отношении человеческого организма. Рассмотрен пример расчета PDE экспериментального лекарственного средства, обладающего гипогликемической активностью, на основании ограниченного объема данных, полученных из открытых источников. Продемонстрирована роль сведений о первичных фармакодинамических эффектах лекарственных средств в оценке их критических эффектов, необходимой для реализации наиболее консервативных подходов к расчету PDE. Предложенный в качестве примера порядок расчета значений PDE может быть использован для оценки рисков перекрестной контаминации на технологических линиях фармацевтических производств