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BACKGROUND: Gestosis (preeclampsia) is an important problem of modern obstetrics. Despite the improvement of methods of prevention and treatment, there is an increase in the rate of this pregnancy complication. In this regard, the search for new approaches to the treatment of preeclampsia is an important problem of modern perinatology. AIM: The aim of this study is studying of the effect of taurine on experimental gestosis in rats. MATERIALS AND METHODS: Preeclampsia was induced on female rats by sodium nitrite and lipopolysaccharide. 2-aminoethanesulfonic acid was administered at a dose of 44.3 mg / kg (in terms of taurine) from the 16th to the 19th day of pregnancy. The number of implantation sites, resorption sites, live fetuses, weight of placentas and fetuses, lactate dehydrogenase activity, content of lactic and pyruvic acids, nitric oxide, malondialdehyde and creatine were evaluated. RESULTS: It has been shown that 2-aminoethanesulfonic acid leads to normalization of the metabolic processes (the level of malondialdehyde, nitric oxide, lactate and lactate dehydrogenase activity) in the body of pregnant female rats with induced preeclampsia in the last trimester of pregnancy. Taurine reduced the quantity of resorption, increased the weight of placentas and fetuses. Along with a correction of the lactate level, pyruvate and lactate dehydrogenase activity, it was observed a decrease of creatine level in placentas. CONCLUSIONS: Obtained results allows us to recommend taurine, which has antioxidant, antihypoxic, membrane stabilizing, detoxifying, osmoregulating and diuretic effects, for the treatment of placental disorders with preeclampsia.

INTRODUCTION: To fully realize the intellectual potential of high school students with enhanced abilities, it is crucial to create conditions that promote and preserve their physical and mental health. METHODS: To scientifically support the system of assisting students with enhanced mental abilities in the face of risk factors within the educational environment, a one-stage study was conducted at a multidisciplinary lyceum for gifted adolescents. The study focused on identifying risk factors associated with the organization and intensity of the educational process and daily routine of students in grades 911. To further support the use of biofeedback in the school medical system, students were taught the diaphragmatic breathing technique. The effectiveness of this technique was evaluated through a comparative analysis of the functional state of the central nervous- and cardiovascular systems, as well as the psycho-emotional status of students before and after two weeks of functional biofeedback training. RESULTS: We found that students were at risk for health problems due to poorly organized educational activities, high intensity of studies and neglect of health-promoting habits such as adequate sleep and walking. However, it has also been found that academic demands can enhance mental performance, albeit at the cost of increased stress on the body's regulatory systems. Therefore, it is crucial to establish a support system for students that addresses these concerns. One promising intervention is diaphragmatic breathing training, which has been shown to reduce anxiety and improve mental performance and adaptability in students. CONCLUSION: Our findings have enabled the scientific substantiation and development of a comprehensive system to support students with enhanced abilities throughout their educational path. This system involves assessment of the psychophysiological state of students, identifying those at risk and those in good health, and organizing a range of corrective, health-promoting, and health-protecting measures. These measures are designed to enhance compensatory capabilities and psychophysiological reserves, as well as to strengthen students' health during the learning process.

Thioredoxin is a low molecular weight protein found in all organisms. It is associated with the regulation of numerous cellular processes such as gene expression, antioxidant response, apoptosis, and proliferation. In humans, thioredoxin is represented by two functionally different forms, Trx1 and Trx2. The review contains the results of studies on the biological role of thioredoxin, with special attention paid to its role in the regulation of the physiological aging process. The aim of the study was to study the available literature sources that publish materials on the biological role of thioredoxin, paying special attention to its significance in the regulation of the physiological aging process. Materials and methods. To achieve the goal of the study, methods of analysis, generalization, comparison and systematization of these publications of domestic and foreign authors were used. Results. The main function of the thioredoxin-dependent system is antioxidant activity. Trx and glutathione (GSH) play a central role in counteracting oxidative stress. In addition to its antioxidant properties, Trx, unlike other antioxidant enzymes, plays an important role in maintaining the redox state of cells and in regulating redox signaling. There is a lot of evidence in the literature that shows the stimulating effect of thioredoxin on tissue proliferation. The Trx system is hypothesized to promote the development and spread of cancer through various mechanisms, including inhibition of apoptosis, promotion of cell growth, and maintenance of angiogenesis. There is also evidence of an important role of the thioredoxin system in aging. Conclusions. Thus, there are data on the participation of the thioredoxin system in the processes of aging, carcinogenesis, regulation of proliferation, and apoptosis. However, the role of thioredoxin in age-related changes in organs has not been studied enough, so additional studies are needed.

Brain temperature, regulated by the balance between blood circulation and metabolic heat generation, is an important parameter related to neural activity, cerebral hemodynamics, and neuroinflammation. A key challenge for integrating brain temperature into clinical practice is the lack of reliable and non-invasive brain thermometry. The recognized importance of brain temperature and thermoregulation in both health and disease, combined with limited availability of experimental methods, has motivated the development of computational thermal models using bioheat equations to predict brain temperature. In this mini-review, we describe progress and the current state-of-the-art in brain thermal modeling in humans and discuss potential avenues for clinical applications.

The research of the blood-brain barrier began at the turn of the 18th19th centuries. To date due to the large number of studies conducted, it is obvious that this system has an impossibly complex structure at the organ, tissue and molecular genetic levels. Scientific interest in the changes in the blood-brain barrier that occur during pathological neoplastic processes is increasing. As it turned out, the restructuring of this system is an important and integral stage in the pathogenesis of glioblastoma, a tumor of the central nervous system with the most unfavorable prognosis. Heterogeneous structure with the formation of areas of altered cellular composition, uneven and uncontrolled permeability, provided by a large number of transport vesicles and the destruction of tight contacts between endotheliocytes, active outflow of molecules from the parenchyma due to the continuous synthesis of new portions of ABC-carrier proteins, the creation of an immature vascular network under the influence of high expression of VEGF by tumor cells the main characteristics of the hematopoietic barrier, formed in glioblastoma and supporting its survival. The further research of the features of the structure and mechanisms of functioning of the blood-brain barrier in glioblastoma is a new and promising task in modern neurooncology, the solution of which will not only expand the understanding of the biology of the most common and malignant brain tumor but will also improve the effectiveness of treatment of patients and improve the prognosis.

International audience; The photoluminescence (PL) of monolayer tungsten disulfide (WS2) is locally and electrically controlled using the nonplasmonic tip and tunneling current of a scanning tunneling microscope (STM). The spatial and spectral distribution of the emitted light is determined using an optical microscope. When the STM tip is engaged, short-range PL quenching due to near-field electromagnetic effects is present, independent of the sign and value of the bias voltage applied to the tip–sample tunneling junction. In addition, a bias-voltage-dependent long-range PL quenching is measured when the sample is positively biased. We explain these observations by considering the native n-doping of monolayer WS2 and the charge carrier density gradients induced by electron tunneling in micrometer-scale areas around the tip position. The combination of wide-field PL microscopy and charge carrier injection using an STM opens up new ways to explore the interplay between excitons and charge carriers in two-dimensional semiconductors.

The linguistic means of creating a language game in French advertising texts at the phonetic, lexical, word-formation, grammatical levels of the language are investigated. Homophones and paronyms are distinguished on the phonetic level, stylistic tropes – on the lexical, stylistic figures – on the grammatical, contamination – on the word-formation. Cases of combinations of different tropes and figures in some advertising texts are established.

Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing the electric field in the pairs (180° direction change) caused 2-fold (1 Hz) or 20-fold (833 kHz) weaker electroporation than the train of single nsEPs. Reducing the angle between pulse directions in the pairs weakened cancellation and replaced it with facilitation at angles

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in YP uptake. The respective proteins could be part of electropermeabilization lesions or increase their lifespan. In contrast, as many as 39 genes were identified as likely hits for the increased YP uptake, meaning that the respective proteins contributed to membrane stability or repair after nsEP. The expression level of eight genes in different types of human cells showed strong correlation (R > 0.9, p < 0.02) with their LD50 for lethal nsEP treatments, and could potentially be used as a criterion for the selectivity and efficiency of hyperplasia ablations with nsEP.

Immunotherapy is a promising and rapidly developing method of therapy patients with different oncological pathology. Considering the demonstrated efficacy in the treatment of patients with some solid tumors, as well as low survival rates and the absence of a significant effect in the standard treatment of most patients with glioblastomas, the question of the use of immunotherapy for malignant gliomas of the brain was raised. However, to decision this problem, it is necessary to consider the interaction of the immune system with tumors of this group. The modern view of the interaction of immunity and glioblastoma is presented. Special attention is paid to the mechanisms of tumor escape and suppression of the functional activity of immune system. The current immunotherapeutic approaches in the treatment of patients with glioblastoma are presented. Interaction of glioblastoma with immune system at all the stages of tumor growth is a complex process. While planning the immunotherapy of this pathology its necessary to take into consideration all mechanisms used by the tumor cells to avoid the immune response and suppress it. However, the clinical studies of this type of therapy proved to be less successful than expected. Further detailed studies of immune-resistance and escape of gliobloastoma must contribute to working out more effective immunotherapy tactics.

DU8ML, a fast and accurate machine learning-augmented density functional theory (DFT) method for computing nuclear magnetic resonance (NMR) spectra, proved effective for high-throughput revision of misassigned natural products. In this paper, we disclose another important aspect of its application: correction of unusual reaction mechanisms originally proposed because of incorrect product structures.

Tuberculosis remains a common and dangerous chronic bacterial infection worldwide. It is long-established that pathogenesis of many autoimmune diseases is mainly promoted by inadequate immune responses to bacterial agents, among them Mycobacterium tuberculosis. Tuberculosis is a multifaceted process having many different outcomes and complications. Autoimmunity is one of the processes characteristic of tuberculosis; the presence of autoantibodies was documented by a large amount of evidence. The role of autoantibodies in pathogenesis of tuberculosis is not quite clear and widely disputed. They are regarded as: (1) a result of imbalanced immune response being reactive in nature, (2) a critical part of TB pathogenicity, (3) a beginning of autoimmune disease, (4) a protective mechanism helping to eliminate microbes and infected cells, and (5) playing dual role, pathogenic and protective. There is no single autoimmunity-mechanism development in tuberculosis; different pathways may be suggested. It may be excessive cell death and insufficient clearance of dead cells, impaired autophagy, enhanced activation of macrophages and dendritic cells, environmental influences such as vitamin D insufficiency, and genetic polymorphism, both of Mycobacterium tuberculosis and host.

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is associated with the misfolding and aggregation of the metalloenzyme protein superoxide dismutase 1 (SOD1) via mutations that destabilize the monomer-dimer interface. In a cellular environment, crowding and electrostatic screening play essential roles in the folding and aggregation of the SOD1 monomers. Despite numerous studies on the effects of mutations on SOD1 folding, a clear understanding of the interplay between crowding, folding, and aggregation in vivo remains lacking. Using a structure-based minimal model for molecular dynamics simulations, we investigate the role of self-crowding and charge on the folding stability of SOD1 and the G41D mutant where experimentalists were intrigued by an alteration of the folding mechanism by a single point mutation from glycine to charged aspartic acid. We show that unfolded SOD1 configurations are significantly affected by charge and crowding, a finding that would be extremely costly to achieve with all-atom simulations, while the native state is not significantly altered. The mutation at residue 41 alters the interactions between proteins in the unfolded states instead of those within a protein. This paper suggests electrostatics may play an important role in the folding pathway of SOD1 and modifying the charge via mutation and ion concentration may change the dominant interactions between proteins, with potential impacts for aggregation of the mutants. This work provides a plausible reason for the alteration of the unfolded states to address why the mutant G41D causes the changes to the folding mechanism of SOD1 that have intrigued experimentalists.

Weak interaction of temporal cavity solitons due to gain saturation and recovery in a delay differential model of a long cavity semiconductor laser is studied numerically and analytically using an asymptotic approach. It is shown that in addition to the usual soliton repulsion leading to a harmonic mode-locking regimes a soliton attraction is also possible in a laser with nonzero linewidth enhancement factor. It is shown numerically that this attraction can lead either to a pulse merging or to a pulse bound state formation., 8 pages, 6 figures

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with dementia of the Alzheimer type (DAT) and asymptomatic individuals with brain amyloid deposition. Brain AG decreases with age but the functional significance of this decrease with regard to the development of DAT symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption and glucose utilization—from which we derive AG—we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher than that seen in typical, cognitively unimpaired, amyloid negative adults. Similar findings were not seen for blood flow nor oxygen consumption. Finally, in cognitively unimpaired adults, white matter hyperintensity burden was found to be specifically associated with decreased youthful brain AG. Our results implicate preserved AG as a factor in brain resilience to amyloid pathology and suggest that white matter disease may be a cause and/or consequence of this impaired resilience.

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca2+ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them less vulnerable to electroporation. We infer that damage to SMC from nsPEF ablation of esophageal malignancies can be minimized by applying the electric field parallel to the predominant SMC orientation.

A personal selection of recent misassigned structures of natural products and their revision with the aid of DU8ML, a machine learning-augmented DFT computational method for fast and accurate calculations of NMR chemical shifts and coupling constants.

In the wake of the Covid-10 pandemic, the Baltic region saw a dramatic reduction in tourist flows in 2000—2021; the decrease was as much as tenfold in some destinations. This study aims to classify the 16 transboundary tourist and recreational mesoregions of the Baltic region according to 2019 tourist flows. The research evaluates, for the first time, the 2020— 2021 decline in tourist flows across these regions. The main outcome of this study is grouping the mesoregions into three orders according to the size of 2019 tourist flows. Four mesoregions were assigned to the first order (with over 500,000 arrivals), three of them located in the southwest Baltic region; nine, the second order (from 100,000 to 500,000 arrivals); three, the third order (from 50,000 to 100,000 arrivals). The most substantial fall in tourist flows occurred in 2020—2021 in the mesoregins including Sweden and Russia and the least marked in those involving Denmark, Germany, Finland, Estonia and Latvia. The findings may help track the future restoration of transboundary tourist flows in the countries of the Baltic region.

BACKGROUND: The ability of a person in the process of active activity to adapt to changing environmental conditions is largely related to his creative potential. Creativity, like other physical and mental personality traits, has its own genetic base, which has not been sufficiently studied to date. Certain genes involved in this process are regularly described. The search for an association with new candidate genes for the creative potential of practically healthy, young respondents selected for work in the extreme conditions of the North is extremely important in the selection of people for work and service in difficult conditions. AIM: Search for the correlation of candidate gene polymorphism and the psychological state of the examined. MATERIALS AND METHODS: The psychological block of the pilot study included determining the degree of creativity, as well as the degree of tension of key psychological defense mechanisms. All the techniques used within its framework are part of the standard psychodiagnostic tools that have been tested in domestic conditions. Genotyping was performed by real-time PCR, determining the corresponding alleles of candidate genes, and then the data were compared by the method of analysis of variance. RESULTS: As candidate genes, we selected the angiotensin-converting enzyme gene, the serotonin 2A receptor gene, the neurotrophic factor BDNF, and alpha-actinin-3. According to the literature, all these genes are associated with the ability to adapt and / or psychotic states, which suggests their possible connection with creativity. The most interesting results are associated with the polymorphism of the BDNF gene: respondents with the BDNF Val/Val genotype are characterized by the maximum level of creativity and the minimum level of intensity of basic psychological defenses and coping strategies by types of distancing, as well as seeking social support. On the contrary, their maximum level is associated with the Met/Met genotype. Thus, it has been reliably shown that optimal adaptation to extreme external conditions is most likely to be ensured genetically by the presence of the Val / Val genotype, and psychologically by enhanced use of creative ability. The respondents with the ACTN3 RX genotype (with increased cold resistance) are characterized by a minimum level of creativity, and those with the RR genotype its maximum level. It is also shown that respondents with the ACE DD genotype are characterized by a minimum level of creativity. There were no associations with creativity with the serotonin 2A receptor gene polymorphism. CONCLUSIONS: The totality of the results obtained as a result of this pilot study allows us to consider a systematic study of creative ability and its molecular biological correlates to be correct and constructive for the development of a fundamental problem of the interaction of molecular biological and psychological mechanisms that provide active adaptation, as well as very expedient for solving the complex. scientific and applied tasks for the selection and correction of the state of persons directed to work in special and / or extreme conditions.

In this work, we theoretically investigate the impact of the atomic scale lattice imperfections of graphene nanoflakes on their nonlinear response enhanced by the resonance between an incident electromagnetic field and localized plasmon. As a case study, we address the second harmonic generation from graphene plasmonic nanoantennas of different symmetries with missing carbon atom vacancy defects in the honeycomb lattice. Using the many-body time-dependent density matrix approach, we find that one defect in the nanoflake comprising over five thousand carbon atoms can strongly impact the nonlinear hyperpolarizability and override the symmetry constraints. The effect reported here cannot be captured using the relaxation time approximation within the quantum or classical framework. Results obtained in this work have thus important implications for the design of nonlinear graphene devices.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231184365 for A new framework for metabolic connectivity mapping using bolus [18F]FDG PET and kinetic modeling by Tommaso Volpi, Giulia Vallini, Erica Silvestri, Mattia De Francisci, Tony Durbin, Maurizio Corbetta, John J Lee, Andrei G Vlassenko, Manu S Goyal and Alessandra Bertoldo in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231184365 for A new framework for metabolic connectivity mapping using bolus [18F]FDG PET and kinetic modeling by Tommaso Volpi, Giulia Vallini, Erica Silvestri, Mattia De Francisci, Tony Durbin, Maurizio Corbetta, John J Lee, Andrei G Vlassenko, Manu S Goyal and Alessandra Bertoldo in Journal of Cerebral Blood Flow & Metabolism

We consider the problem of construction of determinant formulas for the partition function of the six-vertex model with domain wall boundary conditions. In pioneering works of Korepin and Izergin a determinant formula was proposed and proved using a recursion relation. In later works, another determinant formulas were given by Kostov for the rational case and by Foda and Wheeler for the trigonometric case. Here, we develop an approach in which the recursion relation is replaced by a system of algebraic equations with respect to one set of spectral parameters. We prove that this system has a unique solution. The result can be easily given as a determinant parametrized by an arbitrary basis of polynomials. In particular, the choice of the basis of Lagrange polynomials with respect to the second set of spectral parameters leads to the Izergin-Korepin representation, and the choice of the monomial basis leads to the Kostov and Foda-Wheeler representations., Comment: 18 pages, 2 figures; v2: minor corrections

Tourism suffered more than many other sectors amid Covid-19 travel restrictions. This article looks at the impact of the pandemic on the territorial redistribution of tourist flows in the Baltic region. The study draws on regional annual and monthly data on international and domestic tourist arrivals between 2019 and 2021, available on the websites of the statistical offices of the Baltic Region countries. The regions earlier dependent on tourist arrivals from Russia experienced the largest drop in inbound tourism during the Covid-19 pandemic. Yet, domestic tourism burgeoned in most of the region’s countries. In 2021, the most dramatic increase in domestic arrivals occurred, year on year, in the border regions of Russia’s Northwest Federal District; the growth was also notable in Finland and the Baltic States. Domestic tourist flow compensated, partially or even fully, for the decrease in inbound tourist flow in most regions. The structure of inbound tourism changed markedly during the pandemic, with the share of tourists from the Baltic States growing. The strongest rise was in some regions of southern Finland and more modest in Latvia and Lithuania.

A phenomenon of bipolar cancellation stands for the suppression of bioeffects of nanosecond electric pulses (nsEP) when the electric field polarity is reversed. In contrast, the bioeffects of unipolar nsEP can be increased at sub-MHz frequency (summation effect). To explore cell responses at all other angles of electric field vector change, we employed an isosceles triangle and a pyramid electrode configurations for 2D and 3D cell models, respectively. In both cases, the electrode at the apex was always connected to the ground, while the other two electrodes were energized in alternation. This way, the electric field lines from either active electrode converged on the apex electrode, merging into a single long pulse. In other words, the electric field direction between the electrodes at the base of the triangle (pyramid) changed by 180°, but this angle gradually decreased to 0° closer to the apex electrode. Experiments with ablation of BPAE cell monolayers by 0.833 kHz 600-ns pulses showed maximum bipolar cancellation (13-fold vs a unipolar pulse) at 180° vector change. At angles less than 90°-120°, cancellation was replaced by summation, i.e., the effects became stronger (3-fold at 22°). The cancellation of nsEP effects near the base electrodes and the summation of them close to the apex electrode led to focal (one electrode) cell electroporation. Similarly, experiments with 3D cell model (potato tissues) and the pyramid electrode configuration qualitatively showed the ablated area near the apex electrode only. Additionally, we employed this technique to evoke electroporation and excitation (measured by Ca2+ mobilization) in smooth muscle cell monolayers. The cell response was observed near the apex electrode while avoiding it at two base electrodes, despite the stronger electric field there. Lastly, strobe imaging revealed a nanosecond kinetics of membrane potential change in single CHO-K1 cells upon sub-MHz nsEP train stimulation. The temporal summation of membrane polarization occurred near the apex electrode, in contrast to area between the base electrodes. These findings can be essential for multielectrode treatments including focal cancer ablation and brain stimulation.

We present the first implicit computational framework for simulating crack propagation along contact interfaces and surfaces under load in three-dimensional bodies, which is distinct from modelling the contact interaction associated with crack closure. We restrict ourselves to brittle fracture and frictionless contact and focus on numerical challenges associated with the coupling of unilateral constraints emerging from the Griffith’s criterion and the contact conditions. The formulation is based on the configurational mechanics framework and is solved using the finite element method. The approach utilises a monolithic Arbitrary Lagrangian–Eulerian formulation permitting simultaneous resolution of crack propagation and unilateral contact constraints. Contact is embedded in the model using the well-known mortar contact formulation. Evolving cracks are explicitly modelled as displacement discontinuities within the mesh. Heterogeneous approximation of arbitrary order is used to discretise spatial displacements, enabling hp-adaptive refinement around the crack front and the contact interfaces traversed by the crack. The result is a holistic approach which handles issues associated with thermodynamic consistency, numerical accuracy and robustness of the computational scheme. Several numerical examples are presented to verify the model formulation and implementation; they also highlight how contact pressure and load applied on surfaces traversed by cracks influence their propagation. The robustness of the approach is validated by comparison of our simulations with existing numerical results and an industrial experiment involving cracks of complex morphologies propagating along contact interfaces between multiple deformable bodies.

A neutral delay differential equation (NDDE) model of a Kerr cavity with external coherent injection is developed that can be considered as a generalization of the Ikeda map with second and higher order dispersions being taken into account. It is shown that this model has solutions in the form of dissipative solitons both in the limit, where the model can be reduced to the Lugiato- Lefever equation (LLE), and beyond this limit, where the soliton is eventually destroyed by the Cherenkov radiation. Unlike the standard LLE the NDDE model is able to describe the overlap of multiple resonances associated with different cavity modes.

The phenomenon of cell electropermeabilization induced by applied electric fields (EF) has been known for several decades. However, due to the small size and dynamic response of individual membrane lesions to changes in EF, their visualization remains a challenging task. The lack of adequate tools for direct observation and tracking of these lesions hinders the investigation of electropermeabilization. To address this challenge, methodologies such as molecular dynamic simulations, artificial membrane and cellular models have been applied. However, several aspects of the phenomenon, including long-lasting membrane permeabilization, remain incompletely understood. In this study, we have developed a novel approach for detecting and monitoring individual electropores in live HEK293 cells. The method involves combining the whole-cell patch clamp technique on a cell attached to an indium tin oxide (ITO) surface and total internal reflection fluorescence (TIRF) imaging to visualize Ca2+ "puffs". Application of EF between a patch pipette and ITO surface induced membrane polarization to approximately -260 mV, followed by a sudden decrease in membrane resistance (indication of electroporation). The use of TIRF time-lapse imaging allowed for the identification and tracking of individual lesions at the membrane level in both time and space, while simultaneously recording the applied potential and corresponding current. The applied EF created short-lived electropores (few milliseconds) as well as electropores that remained permeable to Ca2+ for over a minute. The respective changes in the transmembrane current corresponded to lesion conductance of 80-200 pS, suggesting that each puff represents an individual membrane pore. This study presents, for the first time, the visualization of individual electropores in live cells. The method provides a valuable tool for investigating the mechanisms of electropermeabilization and understanding the dynamics of individual electropores. Furthermore, it lays a foundation for future studies on electroporation using nanosecond EF pulses.

PurposeMetabolic connectivity (MC) has been previously proposed as the covariation of static [18F]FDG PET images across participants, which we callacross-individualMC (ai-MC). In few cases, MC has also been inferred from dynamic [18F]FDG signals, similarly to fMRI functional connectivity (FC), which we termwithin-individualMC (wi-MC). The validity and interpretability of both MC approaches is an important open issue.Here we reassess this topic, aiming to 1) develop a novel methodology for wi-MC estimation; 2) compare ai-MC maps obtained using different [18F]FDG parameters (K1, i.e. tracer transport rate,k3, i.e. phosphorylation rate,Ki, i.e. tracer uptake rate, and the standardized uptake value ratio,SUVR); 3) assess the interpretability of ai-MC and wi-MC in comparison to structural and functional connectivity (FC) measures.MethodsWe analyzed dynamic [18F]FDG data from 54 healthy adults using kinetic modelling to quantify the macro- and microparameters describing the tracer behavior (i.e.Ki,K1, k3). We also calculatedSUVR. From the across-individual correlation ofSUVR, Ki, K1, k3, we obtained four different ai-MC matrices. A new approach based on Euclidean distance was developed to calculate wi-MC from PET time-activity curves.ResultsWe identified Euclidean similarity as the most appropriate metric to calculate wi-MC. ai-MC networks changed with different [18F]FDG parameters (k3MC vs.SUVRMC, r = 0.44). We found that wi-MC and ai-MC matrices are dissimilar (maximum r = 0.37), and that the match with FC is higher for wi-MC (Dice similarity: 0.47-0.63) than for ai-MC (0.24-0.39).ConclusionOur data demonstrate that individual-level MC from dynamic [18F]FDG data using Euclidean similarity is feasible and yields interpretable matrices that bear similarity to resting-state fMRI FC measures.

Dicyclopropanated 5-vinyl-2-norbornene (dcpVNB) is a strained polycyclic hydrocarbon compound with a high energy content, which makes it promising for the development of propellant components based on it. In this work, the genotoxic properties of dcpVNB were studied using whole-cell lux-biosensors based on Escherichia coli and Bacillus subtilis. It was shown that the addition of dcpVNB to bacterial cells leads to the appearance of DNA damage inducing the SOS response and Dps expression with slight activation of the OxyR-mediated response to oxidative stress. The highest toxic effect of dcpVNB is detected by the following lux-biosensors: E. coli pColD-lux, E. coli pDps, B. subtilis pNK-DinC, and B. subtilis pNK-MrgA, in which the genes of bacterial luciferases are transcriptionally fused to the corresponding promoters: Pcda, Pdps, PdinC, and PmrgA. It was shown that lux-biosensors based on B. subtilis, and E. coli are almost equally sensitive to dcpVNB, which indicates the same permeability to this compound of cell wall of Gram-positive and Gram-negative bacteria. The activation of Pdps after dcpVNB addition maintains even in oxyR mutant E. coli strains, which means that the Pdps induction is only partially determined by the OxyR/S regulon. Comparison of specific stress effects caused by dcpVNB and 2-ethyl(bicyclo[2.2.1]heptane) (EBH), characterized by the absence of cyclopropanated groups, shows that structural changes in hydrocarbons could significantly change the mode of toxicity.

The photoluminescence (PL) of monolayer tungsten disulfide (WS