Investigation into the Parameters of Driver Circuits for Power Electronic and DC-DC Converters

The paper focuses exclusively on the analysis of the simulation software and the main parameters of the driver circuits for power electronic converters. A mathematical model of the driver circuit in the Matlab Simunink software environment has been created. This model enables the analysis of the process of frequency formation through the boostrap capacitor and examines the interaction between the protection of the scheme at  ,  and the other digital blocks in the circuit. Considered, additionally, are the basic physical processes behavior of a driver with a similar structure in Infineon designer

The elucidation of metabolic pathways and their improvements using stable optimization of large-scale kinetic models of cellular systems

Metabolic engineering of cellular systems to maximize reaction fluxes or metabolite concentrations still presents a significant challenge by encountering unpredictable instabilities that can be caused by simultaneous or consecutive enhancements of many reaction steps. It can therefore be important to select carefully small subsets of key enzymes for their subsequent stable modification compatible with cell physiology. To address this important problem, we introduce a general mixed integer non-linear problem (MINLP) formulation to compute automatically which enzyme levels should be modulated and which enzyme regulatory structures should be altered to achieve the given optimization goal using non-linear kinetic models of relevant cellular systems. The developed MINLP formulation directly employs a stability analysis constraint and also includes non-linear biophysical constraints to describe homeostasis conditions for metabolite concentrations and protein machinery without any preliminary model simplification (e.g. linlog kinetics approximation). The framework is demonstrated on a well-established large-scale kinetic model of the Escherichia coli central metabolism used for the optimization of the glucose uptake through the phosphotransferase transport system (PTS) and serine biosynthesis. Computational results show that substantial stable improvements can be predicted by manipulating only small subsets of enzyme levels and regulatory structures. This means that while more efforts can be required to elucidate larger stable optimal enzyme level/regulation choices, no further significant increase in the optimized fluxes can be obtained and, therefore, such choices may not be worth the effort due to the potential loss of stability properties. The source for instability through saddle-node and Hopf bifurcations is identified, and all results are contrasted with predictions from metabolic control analysis

Immunobiochemical Reconstruction of Influenza Lung Infection—Melanoma Skin Cancer Interactions

It was recently reported that acute influenza infection of the lung promoted distal melanoma growth in the dermis of mice. Melanoma-specific CD8+ T cells were shunted to the lung in the presence of the infection, where they expressed high levels of inflammation-induced cell-activation blocker PD-1, and became incapable of migrating back to the tumor site. At the same time, co-infection virus-specific CD8+ T cells remained functional while the infection was cleared. It was also unexpectedly found that PD-1 blockade immunotherapy reversed this effect. Here, we proceed to ground the experimental observations in a mechanistic immunobiochemical model that incorporates T cell pathways that control PD-1 expression. A core component of our model is a kinetic motif, which we call a PD-1 Double Incoherent Feed-Forward Loop (DIFFL), and which reflects known interactions between IRF4, Blimp-1, and Bcl-6. The different activity levels of the PD-1 DIFFL components, as a function of the cognate antigen levels and the given inflammation context, manifest themselves in phenotypically distinct outcomes. Collectively, the model allowed us to put forward a few working hypotheses as follows: (i) the melanoma-specific CD8+ T cells re-circulating with the blood flow enter the lung where they express high levels of inflammation-induced cell-activation blocker PD-1 in the presence of infection; (ii) when PD-1 receptors interact with abundant PD-L1, constitutively expressed in the lung, T cells loose motility; (iii) at the same time, virus-specific cells adapt to strong stimulation by their cognate antigen by lowering the transiently-elevated expression of PD-1, remaining functional and mobile in the inflamed lung, while the infection is cleared. The role that T cell receptor (TCR) activation and feedback loops play in the underlying processes are also highlighted and discussed. We hope that the results reported in our study could potentially contribute to the advancement of immunological approaches to cancer treatment and, as well, to a better understanding of a broader complexity of fundamental interactions between pathogens and tumors

LAPS GM IPE Care Homes 06092024

This document has been designed to provide information about Interprofessional Training Care Home placements, specifically in the context of physiotherapy learners, and the support required to ensure a successful placement experience.The guidelines have been endorsed by the Chartered Society of Physiotherap

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Selection and Analysis of Minimal Sets of Enzyme Levels and Regulatory Structures for Optimization of Microbial Overproduction Using Large-Scale Kinetic Models of Cellular Systems

We introduce a hybrid deterministic/stochastic optimization modeling framework to identify minimal sets of enzyme levels and enzyme regulatory structures to meet significant overproduction requirements using large-scale kinetic models of microbial metabolism and essential protein machinery. Specifically, a simulated annealing algorithm is used to navigate through the discrete space of enzyme levels and regulatory structures, while a sequential quadratic programming method is utilized to identify optimal enzyme levels and regulatory kinetic parameters. The framework is demonstrated on a large-scale and chemically-detailed kinetic model of central metabolism in Escherichia coli (wild-type strain W3110) for the optimization of the glucose uptake through the phosphotransferase system (PTS) and serine biosynthesis. Computational results show that by optimally modulating enzyme levels and carefully altering enzyme regulatory properties, a stable 8-fold increase in the PTS uptake rate and a stable 22-fold increase in serine biosynthesis can be achieved. Importantly, substantial improvements in the targeted fluxes can be predicted by manipulating only small subsets of enzyme levels and regulatory structures. For example, the modulation of only three enzyme levels leads to a flux increase, which is almost 50% of the best predictions, and the manipulation of only six enzyme levels already leads to a flux increase of 80% of the best predictions. Remarkably, by optimally modulating 10 enzyme levels, the total central metabolism's enzyme overexpression capability is reached and any further increase in the targeted fluxes can be only possible if the pathway regulation is additionally altered, though at the expense of the loss of the pathway's steady state stability properties (i.e., no steady state can exist or oscillatory regimes may be encountered). The developed framework has also demonstrated a strong synergism between the redesign of control architectures for tightly regulated reaction steps (e.g., phosphofructokinase) and the overexpression of those enzymes which lack any type of regulatory properties (e.g., glyceraldehyde-3-phosphate dehydrogenase). Although the nonlinear optimization predictions are found in a good agreement with Metabolic Control Analysis (MCA) and large control coefficients can be indicative of the corresponding "rate limiting" enzymes and critical feedback regulatory parameters, the non-linear stable optimization predictions could not be found from the MCA alone. The proposed optimization framework thus provides a new versatile modeling strategy and computational tool for systematic optimal elucidation of minimal sets of controlling enzymes and their critical regulatory properties with broad implication in biotechnological studies

Features of Physical Activity of Russian and Foreign Students: Motivators, Barriers, Self-Esteem

Introduction. Intense physical activity is associated with good health and wellbeing of an individual, and its manifestations in students can have gender and socio-cultural features. The purpose of the study is to identify the features of physical activity of Russian and foreign students of a regional university through the assessment of its motivators, barriers and interrelation with self-esteem indicators, the knowledge of which can be used as the basis for creating personalized preventive health promotion programs. Materials and Methods. An online survey among 423 Russian and foreign students of a regional university was conducted using the Godin-Shephard Leisure-Time Physical Activity Questionnaire using the Ashton Motivators and Barriers Scale and the modified method of Dembo – Rubinstein. The data obtained were statistically processed with the calculation of Student’s t-test, chi-square, and Pearson’s correlation coefficient. Results. It has been revealed that two-thirds of the respondents have an optimal level of physical activity, and its motivators (the desire to improve health, physical shape, and body) and barriers (lack of time) are universal. Russian female university students surpass foreign ones in terms of the duration of physical activities, and foreign girls are inferior to foreign young men in terms of the frequency of classes. Barriers specific to Russian girls have been identified: Inappropriate weather and the belief that physical activity is not a right occupation for women. Russian young men have mentioned the lack of conditions for training as a barrier. The difference between Russian young men and foreign ones is that foreigners find positive correlation between physical activity, confidence, and physical attractiveness. Discussion and Conclusion. The results obtained may be useful for teaching personnel of university departments of physical education, medical and psychological services, and student self-government organizations. It is recommended that university prevention programs be gender-specific, culturally oriented, aimed at neutralizing the system of internal and social barriers to attending classes, and based on the student's self-esteem potential

Elucidation and structural analysis of conserved pools for genome-scale metabolic reconstructions

ABSTRACT In this article, we introduce metabolite concentration coupling analysis (MCCA) to study conservation relationships for metabolite concentrations in genome-scale metabolic networks. The analysis allows the global identification of subsets of metabolites whose concentrations are always coupled within common conserved pools. Also, the minimal conserved pool identification (MCPI) procedure is developed for elucidating conserved pools for targeted metabolites without computing the entire basis conservation relationships. The approaches are demonstrated on genome-scale metabolic reconstructions of Helicobacter pylori, Escherichia coli, and Saccharomyces cerevisiae. Despite significant differences in the size and complexity of the examined organism’s models, we find that the concentrations of nearly all metabolites are coupled within a relatively small number of subsets. These correspond to the overall exchange of carbon molecules into and out of the networks, interconversion of energy and redox cofactors, and the transfer of nitrogen, sulfur, phosphate, coenzyme A, and acyl carrier protein moieties among metabolites. The presence of large conserved pools can be viewed as global biophysical barriers protecting cellular systems from stresses, maintaining coordinated interconversions between key metabolites, and providing an additional mode of global metabolic regulation. The developed approaches thus provide novel and versatile tools for elucidating coupling relationships between metabolite concentrations with implications in biotechnological and medical applications

Self-correction of spontaneous errors by S toggles.

<p><b>Panel (A)</b> shows the S toggle which cannot self-correct a (9:1)-spontaneous synchronization error for a small value of the diffusion parameter <i>d</i> = 0.01 (a weak coupling between all cells). <b>Panels (B) and (C)</b> show the S toggle which can self-correct a (9:1)-spontaneous synchronization error for a medium (<i>d</i> = 10) and large (<i>d</i> = 100) values of parameter <i>d</i> (a medium and strong coupling between all cells, respectively). For the values of parameter <i>d</i> used in Panels (B) and (C), the mixed states become unstable, see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004881#pcbi.1004881.g009" target="_blank">Fig 9</a>.</p

Examples of monotone parametric dependencies for a (1:1)-mixed state.

<p>Panels (A) and (B) correspond to dependencies of LacI and TetR levels on parameter <i>δ</i>_<i>g</i>, respectively. Panels (C) and (D) correspond to dependencies of LacI and TetR levels on parameter <i>δ</i>_<i>r</i>, respectively. The dependencies for the G-subpopulation are shown only, within which LacI is activated, while TetR is repressed. Green and red solid curves correspond to stable branches of (1:1)-equilibrium solutions, while all blue curves correspond to unstable branches of the solutions. Red filled circles correspond to an LP-bifurcation point. In panel (A), projections of stable and unstable branches coincide and, so, only the stable branch is shown.</p