Non-enzymatic glucose sensing is a crucial field of study because of the current market demand. This study proposes a novel design of glucose sensor with enhanced selectivity and sensitivity by using graphene Schottky diodes, which is composed of Graphene/Platinum Oxide/n-Silicon heterostructure. The sensor was tested with different glucose concentrations and interfering solutions to investigate its sensitivity and selectivity. Different structures of the device were studied by adjusting the platinum oxide film thickness to investigate its catalytic activity. It was found that the film thickness plays a significant role in the efficiency of glucose oxidation and hence in overall device sensitivity. Moreover, theoretical investigations were conducted using Density Function Theory (DFT) to better understand the detection method and the origins of selectivity. The working principle of the sensors puts it in a competitive position with other non-enzymatic glucose sensors. DFT calculations provided a qualitative explanation of the charges distributed across the graphene sheet within a system of a platinum substrate with D-glucose molecules above. The proposed graphene/PtO/n-Si heterostructure has proven to satisfy these factors, which opens the door for further developments of more reliable non-enzymatic glucometers for continuous glucose monitoring systems.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Although most biological processes are characterized by a strong temporal asymmetry, several popular mathematical models neglect this issue. Maximum entropy methods provide a principled way of addressing time irreversibility, which leverages powerful results and ideas from the3literature of non-equilibrium statistical mechanics. This article provides a comprehensive overview of these issues, with a focus in the case of spike train statistics. We provide a detailed account of the5mathematical foundations and work out examples to illustrate the key concepts and results from non-equilibrium statistical mechanics

We evaluate the complexity of Colombian climate from extreme behavior of gauge temperature and precipitation, using the the novel Tsallis' non-extensive entropy principle based on physical information through the q-index. We find the spatial structure of non additive universal categories (q-index) and compare with some complex systems with the potential to have some degree of dynamical affinity. Our results evidence the great dynamical variability of regional climate expressed in the large range of values of $q$-index, and the high degree of non-extensitivity for both temperature and precipitation.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

This paper considers a non-mixture cure model for right censored data. It utilizes the maximum likelihood method to estimate model parameters in the non-mixture cure model. The simulation study is based on Fréchet susceptible distribution to evaluate the performance of the method. Comparing with Weibull and exponentiated exponential distributions, the non-mixture Fréchet distribution is shown to be the best in modeling a real data on allogeneic marrow HLA-matched donors and ECOG phase III clinical trial e1684 data.

Field and numerical investigations at Happisburgh, East coast of England, UK, sought to characterize beach thickness and determine geologic framework controls on coastal change. After a major failure of coastal protection infrastructure, removal of about 1 km of coastal defense along the otherwise protected cliffed coastline of Happisburgh triggered a period of rapid erosion over 20 years of ca. 140 m. Previous sensitivity studies suggested that that beach thickness plays a major role in coastal recession. These studies were limited, however, by a lack of beach volume data. In this study, we have integrated the insights gained from our understanding of the Quaternary geology of the area, a novel non-intrusive passive seismic survey method, and a 3D novel representation of the subsurface source and transportable material into a coastal modelling environment to explore the role of beach thickness on the back wearing and down wearing of the cliffs and consolidated platform, respectively. Results show that beach thickness is non-homogeneous along the study site: we estimate that the contribution to nearshore sediment budget via platform down wearing is of a similar order of magnitude as sediment lost from the beach and therefore non-negligible. We have provided a range of evidence to support the idea that the Happisburgh beach is a relatively thin layer perched on a sediment rich platform of sand and gravel. This conceptualization differs from previous publications, which assumes that the platform was mostly till and fine material. This has direct implication on the regional sediment management of along this coastline. The present study contributes to our understanding of a poorly known aspect of coastal sediment budgeting and outlines a quantitative approach that allows for simple integration of geological understanding for coastline evolution assessments worldwide.

RNAi is considered a major antiviral defense mechanism in insects but its relative importance compared to other antiviral pathways has not been evaluated comprehensively. Here, it is attempted to give an overview of the antiviral defense mechanisms in Drosophila that involve both RNAi and non-RNAi to acquire a sense of their relative importance. While RNAi is considered important in most viral infections, many other pathways can exist that confer antiviral resistance. It is noted that very few direct recognition mechanisms of virus infections have been identified in Drosophila and that the activation of immune pathways may be accomplished indirectly through cell damage incurred by viral replication. In several cases, protection against viral infection can be obtained in RNAi mutants by non-RNAi mechanisms, confirming the variability of the RNAi defense mechanism according to the type of infection and the physiological status of the host. This analysis invites to investigate more systematically the relative contribution of RNAi in the antiviral response and more specifically to ask whether RNAi efficiency is affected when other defense mechanisms predominate. While Drosophila can function as a useful model, this issue may be more critical for economically important insects that are either controlled (agricultural pests and vectors of diseases) or protected from parasite infection (beneficial insects as bees) by RNAi products.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

The present essay illustrates the methodological and theoretical premises of an emerging research area carrying out both ethological and (bio)ethical implications: the ethology of the freed animal (EFA). Unlike existing ethological fields, EFA focuses neither on non human (NH) animals in natural conditions of freedom in their own environment, nor on NH animals kept in conditions of “captivity”. Rather, EFA consists of a comparative study of NH animals that are released from a condition of more or less abusive captivity and instead relocated in an environment more appropriate to their species-specific and individual characteristics and inclinations. Ideal places for this study are contexts like “Animal sanctuaries” and parks/reserves provided with a camp or station for researchers, where a previously-captive NH animal can be reintroduced in his/her natural habitat. Even though EFA exists already, as a de facto practice of the specialized and/or volunteer personnel running sanctuaries and parks, the field still lacks a recognizable scholarly paradigm, and it is yet to be acknowledged at institutional/academic level. By consequence, one important aim for creating a field like this lies in the establishment of an active interaction between the two parties involved (researchers and sanctuaries/parks operators).

This work updates the characterization of winter fish communities in salt marsh areas of Guadiana estuary (SE-Portugal) and discusses the potential risks of habitat dominance by a non-indigenous species (NIS). To this effect, six field campaigns were carried out during winter season targeting the collection of fish species. Individuals from seven different families (marine and estuarine) were collected although the community was dominated by two estuarine species – the native Pomatoschistus sp. (goby) and the NIS Fundulus heteroclitus (mummichog). Goby controlled the majority of salt marsh habitats, except one specific, marsh pool, where extreme environmental conditions were registered, namely high temperature and salinity. Such conditions may have boosted the intrusion of mummichog in this area. This species is well adapted to a wide range of abiotic factors enabling them to colonize habitats where no predators inhabit. Impacts of mummichog intrusion in the Guadiana salt marsh area are still unpredictable since this is the first recorded in such high density. Nevertheless, in scenarios of increased anthropogenic pressure and, consequently, habitat degradation, there is a potential risk of mummichog spread to other habitats and therefore compete for space and food resources with native species.

Remote sensing image registration plays an important role in military and civilian fields, such as natural disaster damage assessment, military damage assessment and ground targets identification, etc. However, due to the ground relief variations and imaging viewpoint changes, non-rigid geometric distortion occurs between remote sensing images with different viewpoint, which further increases the difficulty of remote sensing image registration. To address the problem, we propose a multi-viewpoint remote sensing image registration method which contains the following contributions. (i) A multiple features based finite mixture model is constructed for dealing with different types of image features. (ii) Three features are combined and substituted into the mixture model to form a feature complementation, i.e., the Euclidean distance and shape context are used to measure the similarity of geometric structure, and the SIFT (scale-invariant feature transform) distance which is endowed with the intensity information is used to measure the scale space extrema. (iii) To prevent the ill-posed problem, a geometric constraint term is introduced into the L2E-based energy function for better behaving the non-rigid transformation. We evaluated the performances of the proposed method by three series of remote sensing images obtained from the unmanned aerial vehicle (UAV) and Google Earth, and compared with five state-of-the-art methods where our method shows the best alignments in most cases.

The performance of modified electrode of nanocomposite film consisting of polypyrrole-chitosan-titanium dioxide (Ppy-CS-TiO2) has been explored as non-enzymatic glucose biosensors. The synergy effect of TiO2 nanoparticles and conducting polymer on the current response of electrode resulted in higher sensitivity for nanocomposite modified electrode. The incorporation of TiO2 nanoparticles in the nanocomposite films were confirmed by XPS spectra. The FESEM and HR-TEM provided more evidences for the presence of TiO2 in Ppy-CS structure. Glucose biosensing properties were determined by amperommetry and cyclic voltammetry (CV) methods. The interfacial properties of nanocomposite electrodes were studied by electrochemical impedance spectroscopy (EIS). The developed biosensors showed a good sensitivity over the liner range of 1-14 mM with a detection limit of 614 μM for glucose. It also exhibited good selectivity and long term stability with no interference effect. The Ppy-CS-TiO2 nanocomposites film presented high electron transfer kinetics.

Cyclic straining simulations using incompatibility-incorporated crystal plasticity-FEM, which exhibit PSB ladder structure evolutions as detailed in Part I, are coupled with diffusion analyses of produced vacancies. We introduce a new vacancy source model based on the Field Theory of Multiscale Plasticity (FTMP), interpreting the relationship between the incompatibility rate and the flux of dislocation density as edge dipole annihilation processes. Both direct and indirect coupling diffusion analyses, with and without cyclic straining, demonstrate that varying incompatibility rates tend to further promote vacancy diffusion, leading to surface grooving, enhanced extension rates, and eventual transition to cracks. The findings reveal that: (i) the evolved PSB ladder structure serves as a site for vacancy formation, (ii) it provides a diffusion path toward the specimen surface, and (iii) it significantly enhances groove extension rates. These factors effectively facilitate the transition from a "groove" to a "crack," evidenced by the abrupt acceleration of the extension rate, mirroring systematic experimental observations by Nakai et al. These achievements validate the FTMP's capability to simulate complex phenomena and significantly deepen our understanding of slip band-fatigue crack transition mechanisms.

The opinion dynamics literature argues that the way people perceive social influence depends not only on the opinions of interacting individuals, but also on the individuals’ non-opinion characteristics, such as age, education, gender, or place of residence. The current paper advances this line of research by studying longitudinal data that describe the opinion dynamics of a large sample (~30,000) of online social network users, all citizens of one city. Using these data, we systematically investigate the effects of users’ demographic (age, gender) and structural (degree centrality, the number of common friends) properties on opinion formation processes. We revealed that females are less easily influenced than males. Next, we found that individuals that are characterized by similar ages have more chances to reach a consensus. Besides, we report that individuals who have many common peers find an agreement more often. We also demonstrated that the impacts of these effects are virtually the same, and despite being statistically significant, are far less strong than that of opinion-related features: knowing the current opinion of an individual and, what is even more important, the distance in opinions between this individual and the person that attempts to influence the individual is much more valuable. Next, after conducting a series of simulations with an agent-based model, we revealed that accounting for non-opinion characteristics may lead to not very sound but statistically significant changes in the macroscopic predictions of the populations of opinion camps, primarily among the agents with radical opinions (≈ 3% of all votes). In turn, predictions for the populations of neutral individuals are virtually the same. Besides, we demonstrated that the accumulative effect of non-opinion features on opinion dynamics is seriously moderated by whether the underlying social network correlates with the agents’ characteristics. After applying the procedure of random shuffling (in which the agents and their characteristics were randomly scattered over the network), the macroscopic predictions have changed by ≈ 9% of all votes. What is interesting, the population of neutral agents was again not affected by this intervention.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Dietary polyphenols exist in two forms; extractable polyphenols (EPP) or compounds solubilised by aqueous/organic solvents, and non-extractable polyphenols (NEPP) or compounds remain in the corresponding residues after the extraction. At present, most researchers focus on EEP fractions, while NEPP is neglected. Thus, this study aimed to release NEPP from the remaining powder residue of Barhi date palm kernels (BDPK) with acid hydrolysis. The related extraction conditions were determined and optimised using response surface methodology (RSM) for maximisation of NEPP with highest cytotoxic and antioxidant activities. The face-centred central composite design (FCCCD) was used to establish treatments based on three independent variables, namely; extraction temperature, time, and solvent/sample ratio. Under the optimal conditions, the experimental values for DPPH radical-scavenging capacity of NEPP (IC50=57.52µg/mL), and cytotoxicity of NEPP against A549 and HT29 cells were IC50=17.4 µg/mL and 31.4µg/mL, respectively. The experimental values were in agreement with those predicted by RSM models, confirming the suitability of the model employed and the success of RSM for optimisation of the extraction conditions for NEPP from BDPK. These results indicate that NEPP from industrial date fruit waste could be a promising candidate as natural antioxidants with significant antiproliferation effect against A549 and HT29 cancer cells in-vitro.

In this work the existence and nonexistence of stationary radial solutions to the elliptic partial differential equation arising in the molecular beam epitaxy are studied. Since we are interested in radial solutions we arrive at the following fourth-order differential equation

This paper presents a proposal for a non-isolated bidirectional converter (NIBC) controlled by a deep neural network (DNN) to enable vehicle-to-vehicle (V2V) and vehicle-to-grid (V2G) charging, which contributes to the development of more efficient and sustainable transportation and energy systems. The DNN controller manages power flow in both directions, making it possible to charge electric vehicles (EVs) and discharge power from EVs to the grid with improved efficiency and performance compared to traditional control methods. The non-isolated topology used in this proposal offers several benefits, including reduced cost, smaller size, and higher efficiency. To train the DNN controller, a large dataset of simulations was used, and the results were validated with a hardware setup. The real-time performance of the DNN controller was compared to a proportional-integral (PI) based controller through simulated results. The findings of the study show that the DNN controller outperforms traditional PI controllers.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

In the current context of worldwide honey bee colony losses, among which the varroa mite plays a major role, hope to improve honey bee health lies in part in the breeding of varroa resistant colonies. To do so, methods used to evaluate varroa resistance need better understanding. Repeatability and correlations between traits such as Mite Non-Reproduction (MNR), Varroa Sensitive Hygiene (VSH) and hygienic behaviour are poorly known, due to practical limitations and to their underlying complexity. We investigate (i) the variability, (ii) repeatability of the MNR score and (iii) its correlation with other resistance traits. To reduce the inherent variability of MNR scores, we propose to apply an Empirical Bayes correction. On the short-term (ten days) MNR had a modest repeatability of 0.4 whereas on the long- term (a month) it had a low repeatability of 0.2, similar to other resistance traits. Within our dataset there was no correlation between MNR and VSH. Although MNR is amongst the most popular varroa resistance estimates in field studies, its underlying complex mechanism is not fully understood. Its lack of correlation with better described resistance traits and low repeatability suggest that MNR need to be interpreted cautiously, especially when used for selection.

The response of building elements during earthquakes has been an area of concern for different researchers around the world. The NSEs are the first elements to attain failure, the buildings after damages in safety priority are classified as in “Life Safety” mode, but in reality, they are in “Collapse Safety” mode and the occupants inside the buildings are in a state of “Non-Life Safety” as a result of falling of the hazardous NSE’s like cladding's, partitions, hanging objects. In addition to the Life Cycle Cost Assessment (LCCA), the Social Life Cycle Assessment (SLCA) is overlooked by the majority of the researchers, the community must be prepared to respond to an event more efficiently without any major casualties or loss of life. It is expected that by the end of 2050, almost double the construction will take place, the embodied energy during the pre-construction, post-construction and demolition generates a lot of CO2s into the environment, hence sustainability should be given due importance, helping in the achievement of Sustainable Developmental Goals (SDGs).

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19 associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4% respectively). Mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported mortality of candidemia from previous studies at our center. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs 78.1%; P =0.76). Performing ophthalmic examination (P = 0.002), CVC removal during the 48 hours following the candidemia (P = 0.008) and identifying the Candida spp. (P = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species like C. auris.

Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be infected more frequently with flaviviruses due to their arboreal and diurnal habits, their genetic similarity to humans and their relative closeness to humans. However, the only known flavivirus in America that is maintained by sylvatic cycles involving NPs is Yellow Fever virus (YFV), and the NPs role as potential hosts of flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 free range and captive NPs of Costa Rica to evaluate their involvement in flavivirus transmission cycles and their potential as flavivirus hosts. We used a highly-specific micro plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, Dengue virus 1-4 (DENV), Zika virus, West Nile Virus (WNV) and Saint Louis Encephalitis virus (SLEV). We found evidence of seropositive NPs to DENV-1 8.2% (homotypic –3/86, heterotypic – 4/86), SLEV 15.1% (homotypic – 10/86, heterotypic – 2/86), WNV 2.3% (homotypic – 2/86) and 8.1% (7/86) undetermined Flavivirus species. No antibodies against YFV or ZIKV were found. This work provides compelling serological evidence of exposure in NPs of flaviviruses associated with urban cycles, i.e. DENV, and confirms decades of circulation of SLEV in the same environments. Also, the range of years of sampling and the socioeconomic region was statistically significant for the presence of Dengue and Flavivirus undetermined seropositive individuals, respectively. Both the years and socioeconomic regions with greater seroprevalence coincide with the years and socioeconomic regions with high numbers of Dengue human cases for the country. Our work suggests bidirectional? circulation of different flaviviruses between humans and wildlife with public health importance and underscores the necessity of further surveillance for flaviviruses in the humans/wildlife interface in Central America.

Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interests because of their potential health effects. With the aim of contributing to major insights into their structure-activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and ‘Sun Black’ tomato). PASs from the above-mentioned plant material have been evaluated for their antioxidant capacity, using TEAC and ORAC assays. In human endothelial cells, we analysed the biological activity of different PASs by measuring their effects on the expression of endothelial inflammatory markers, including endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection.

The approach based on molecular modeling was developed to study dNTP derivatives characterized by new polymerase-specific properties. For this purpose, the relative efficiency of PCR amplification with modified dUTPs was studied using Taq, Tth, Pfu, Vent, Deep Vent, Vent (exo-), and Deep Vent (exo-) DNA polymerases. The efficiency of PCR amplification with modified dUTPs was compared with the results of molecular modeling using the known 3D structures of KlenTaq polymerase–DNA–dNTP complexes. The dUTPs were C5-modified with bulky functional groups (the Cy5 dye analogs) or lighter aromatic groups. Comparing the experimental data and the results of molecular modeling revealed the decrease of PCR efficiency in the presence of modified dUTPs with an increase in the number of non-covalent bonds between the substituents and the DNA polymerase (about 15% decrease per one extra non-covalent bond). Generalization of the revealed patterns to all the studied polymerases of the A and B families is discussed herein. The number of non-covalent bonds between the substituents and polymerase amino acid residues is proposed to be a potentially variable parameter for regulating enzyme activity.

Laser energy per unit surface, necessary to trigger the material removal, decreases with the pulse shortening becoming the pulse-time independent in the sub-picosecond range. These pulses are shorter the electron-to-ion energy transfer time and electronic heat conduction time minimizing the energy losses. The electrons receiving the energy larger than the threshold, drag the ions off the surface in the mode of electrostatic ablation. We show that the pulse shorter than the ion period (Shorter-the-Limit (StL)) ejects conduction electrons with the energy larger than the work function (from a metal) leaving the bare ions immobile in a few atomic layers. The electrons emission is followed by the bare ion’s explosion, ablation, and THz radiation from expanding plasma. We compare this phenomenon to the classic photo effect, nanocluster Coulomb explosions, show differences and consider possibilities for detecting the new mode of ablation experimentally by emitted THz radiation and consider applications of high-precision nano-machining with this low intensity irradiation.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

The current work reports the upper bound of the state variable of the of the Pointwise Steady Fluid Flow Approximation (PSFFA) model of non-stationary M/Ek/1 queueing system.

In the present paper, the effect of the non-linear thermal radiation on the neutral gas mixture in the unsteady state is investigated for the first time. The unsteady BGK technique of the Boltzmann kinetic equations for a neutral non-homogenous gas is solved. The solution of the unsteady case makes the problem more general significance than the stationary one. For this purpose, the moments' method, together with the traveling wave method, is applied. The temperature and concentration are calculated for each gas component and mixture for the first time.Furthermore, the study is held for aboard range of temperatures ratio parameter and a wide range of the molar fraction. The distribution functions are calculated for each gas component and the gas mixture. The significant non-equilibrium irreversible thermodynamic characteristics the entire system is acquired analytically. That technic allows us to investigate the consistency of Boltzmann's H-theorem, Le Chatelier principle, and thermodynamics laws. Moreover, the ratios among the different participation of the internal energy alteration are evaluated via the Gibbs formula of total energy. The final results are utilized to the argon-helium non-homogenous gas at different magnitudes of radiation force strength and molar fraction parameters. 3D-graphics are presented to predict the behavior of the calculated variables, and the obtained results are theoretically discussed.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p&lt;0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed transcriptomic changes observed in epidermal PPARγ deficient mice (Pparg-/-epi). Gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis and cell survival. Single cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and or mouse actinic keratoses (AK) and cutaneous squamous cell carcinomas (SCCs) revealed strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AK and SCC. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably. these changes are not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes while Ppard was highly expressed in myofibroblasts, suggesting a role for PPARδ in myofibroblast differentiation. In conclusion, these data indicate PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

The finite-time turnpike property describes the situation in an optimal control problem where an optimal trajectory reaches the desired state before the end of the time interval and remains there. We consider a machine learning problem with a neural ordinary differential equation that can be seen as a homogenization of a deep ResNet. We show that with appropriate scaling of the quadratic control cost and the non-smooth tracking term the optimal control problem has the finite-time turnpike property, that is the desired state is reached in the interior of the time interval and the optimal state remains there until the terminal time $T$. This property is useful to achieve a compromise between the depth of the network and the size of the optimal system parameters which we hope will be useful to determine optimal depths for neural network architectures in the future.

Empirical models for intensive or extensive margins of trade that relate measures of exports to firm characteristics are usually estimated by variants of (generalized) linear models. Usually, the firm characteristics that explain these export margins enter the empirical model in linear form, sometimes augmented by quadratic terms or higher order polynomials, or interaction terms, to take care or test for non-linear relationships. If these non-linear relationships do matter and if they are ignored in the specification of the empirical model this leads to biased results. Researchers, however, can never be sure that all possible non-linear relationships are taken care of in their chosen specifications. This note uses for the first time the Kernel-Regularized Least Squares (KRLS) estimator to deal with this issue in empirical models for margins of exports. KRLS is a machine learning method that learns the functional form from the data. Empirical examples show that it is easy to apply and works well. Therefore, it is considered as a useful addition to the box of tools of empirical trade economists.

The effect of spanwise wing non-planarity, implemented in conjunction with a Gurney flap is presented. Testing was undertaken in a low speed wind tunnel using a rectangular wing with an aspect ratio of 3. The outer 1/3 of the wing was non-planar which took the form of dihedral or a circular arc. A 2% high Gurney flap was implemented such that it could extend over the entire span, or the planar inboard section. Loads were measured using a sting balance. The data shows that non-planarity increases the maximum lift coefficient and the wing’s lift curve slope. Gurney flap lift modulation was enhanced in the presence of non-planarity. The addition of Gurney flaps caused a greater minimum drag coefficient increment for the non-planar wings. The Gurney flaps reduced the lift dependent drag of the wings; however, the minimum drag coefficient was observed to increase. The Gurney flaps reduced the maximum lift to drag ratio (L/D) for the non-planar wings; however, the flat wing showed a small L/D increment with flap addition.

Mexico is a well-known seismically active country, which is primarily affected by several tectonic plate interactions along the southern Pacific coastline and by active structures in the Gulf of Baja California. In this paper we investigate this seismicity in the context of a non-extensive statistical approach based on Tsallis entropy. The analysis is performed using data from the corrected Mexican seismic catalogue provided by the National Seismic Service, spanning a period from January 2000 to October 2023. The Gutenberg-Richter law fitting to the earthquake sub-catalogues for all six regions studied indicates magnitudes of completeness between 3.30 and 3.76. All six regions display values of the entropic index in the range 1.52≲q≲1.61, which are lower than the previously estimated range 1.54≲q≲1.70 using catalogue data from 1988 to 2010. The cause of this discrepancy is certainly due to the use of modern recording devices, which are sensitive enough to detect a larger number of low-magnitude events compared to older instrumentation.

The identification of fetal cells in the blood and tissues of healthy mothers raised questions about the potential alloreactive origins of various diseases, such as autoimmunity, diabetes, arteriosclerosis, and cancer. However, the extent to which alloreactivity contributes to these diseases remains unverified. This study presents a basic mathematical disease model based on the genes’ origin and immunological interactions. This model, grounded in set theory, classifies these immunological interactions based on their intrinsic, extrinsic, and allogeneic nature. Therefore, this model offers an unexpected common theoretical foundation for understanding alloreactivity, genetic diseases, and infections. Furthermore, this model provides a valuable framework for scrutinizing the role of alloreactivity in health and disease.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Background: Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in broader range of patients. Methods: Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g. documented history of HF, left ventricular ejection fraction ≤40%, or BNP levels ≥100 pg/mL). Participants, aged 61±10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. Results: Lower baseline BNP correlated with reduced AFEQT scores. Post-CA, all groups showed significant AFEQT score improvements. Lower BNP group displayed notable enhancements (18.2±1.2, 15.0±1.1, 12.6±1.2, 13.6±1.2, p<0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/ml) exhibited significant QOL improvements. Comparing PAF and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. Conclusion: This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvement.

Multiple sources influence air quality and regional climate in complicated atmospheric emission situations like urban agglomerations. To resolve pollution plumes and source influences in polluted areas, a comprehensive chemical fingerprinting of sources utilizing non-methane hydrocarbons (NMHCs) and the identification of acceptable tracer molecules and emission ratios is required, in contrast to pristine locations, where reliance on a single or a few chemical tracers is frequently sufficient. We have characterized the prevalence of NMHCs fingerprints in the urban areas and quantified the correlation of windspeed with the concentration of these pollutants. eNose sensors and Air quality management stations provide the data to identify the emission sources of such pollutants. Based on our analysis, the average NMHC concentration in 2021 has been recorded 0.424 ppm at point 1 AQMS whereas at point 2 AQMS it was 0.256 ppm. Such outcomes could be attributed to the proximity of emissions sources, the direction and speed of the wind, or both. Moreover, traffic can be a major contributor to pollution levels in any urban area. More research based on a larger dataset is required before definitive conclusions can be drawn, and viable solutions can be proposed.

The continuous casting tundish is non-isothermal due to heat losses and temperature variation from the inlet stream generating relevant convection forces. This condition is commonly avoided through qualitative fluid dynamic analysis only. This work searches to establish the conditions for which non-isothermal simulations are mandatory or for which isothermal simulations are enough to accurately describe the fluid dynamics inside the tundish by quantifying the buoyant and inertial forces. The mathematical model, simulated by CFD software, considers the Navier-Stokes equations, the realizable k- model for solving the turbulence, and the Lagrangian discrete face to track the inclusion trajectories. The results show that temperature does not significantly impact the volume fraction percentages or the mean residence time results, nevertheless, bigger velocity magnitudes under non-isothermal conditions than in isothermal conditions and noticeable changes in the fluid dynamics between isothermal and non-isothermal cases in all the zones where buoyancy force dominates over inertial forces were observed. Because of the results, it is concluded that isothermal simulations can accurately describe the flow behavior in tundishes when the flow control devices control the fluid dynamic, but the simulation without control devices or with a weak fluid dynamic dependence on the control devices requires non-isothermal simulations.

Serine/threonine kinase (AKT) signaling regulates diverse cellular processes and is one of the most important aberrant cell survival mechanisms associated with tumorigenesis, metastasis, and chemoresistance. Targeting AKT has become an effective therapeutic strategy for the treatment of many cancers. AKT3 (PKBγ), the least studied isoform of the AKT family, has emerged as a major contributor to malignancy. AKT3 is frequently overexpressed in human cancers, and many regulatory oncogenic or tumor suppressor small non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have recently been identified to be involved in regulating AKT3 expression. Therefore, a better understanding of regulatory miRNA/AKT3 networks may reveal novel biomarkers for diagnosis of patients with cancer and provide invaluable information for developing more effective therapeutic strategies. The aim of this review is to summarize current research progress in the isoform-specific functions of AKT3 in human cancers and the roles of dysregulated miRNA/AKT3 in specific types of human cancers.

Amorphous germanium films on non-refractory glass substrates were annealed by ultrashort near-infrared (1030 nm, 1.4 ps) and mid-infrared (1500 nm, 70 fs) laser pulses. Crystallization of germanium irradiated at a laser energy density (fluence) range from 25 to 400 mJ/cm2 under single-shot and multi-shot conditions was investigated using Raman spectroscopy. The dependence of the fraction of the crystalline phase on the fluence was obtained for picosecond and femtosecond laser annealings. The regimes of almost complete crystallization of germanium films over the entire thickness are obtained (from the analysis of Raman spectra with excitation of 785 nm laser). The possibility of scanning laser processing is shown, which can be used to create films of micro and nanocrystalline germanium on flexible substrates.

We present a mixing length based algebraic turbulence model calibrated to pipe flow; the main purpose of the model is to capture the increasing turbulence production-to-dissipation ratio observed in connection with the high Reynolds number transition region. The model includes the mixing length description by Gersten and Herwig which takes the observed variation of the von Kármán number with Reynolds number into account. Pipe wall roughness effects are included in the model. Results are presented for area-averaged (integral) quantities which can be used both as a self-contained model and as initial inlet boundary conditions for computational fluid dynamics simulations.

This article is devoted to methods of processing random processes. Of particular relevance is the task of processing broadband non-stationary random processes. The processing of random processes is usually related to the assessment of their probabilistic characteristics. Very often, a non-stationary broadband random process is represented by a single implementation in a priori uncertainty about the type of distribution function. Such random processes occur in information and measuring communication systems in which information is transmitted at a real time pace (for example, radio telemetry systems of spacecraft). The use of methods of traditional mathematical statistics, for example, maximum likelihood methods to determine probability characteristics, in this case is not possible. The article discusses a method of processing non-stationary broadband random processes based on the use of non-parametric methods of decision theory. An algorithm for dividing the observation interval into stationary intervals using non-parametric Kendall statistics is considered, as well as methods for estimating probabilistic characteristics on the stationary interval using ordinal statistics. The article presents the results of statistical modeling using the Mathcad program.

The zero-catch problem is a key issue in CPUE(Catch Per Unit Effort) standardization, and previous studies have treated all zero-catch data uniformly, but this actually loses some correctly-labeled samples. On the other hand, for the main catches with few zero-catch samples, the problem of low performance of fisheries forecasting remains unsolved even though the forecasting model structure is updating constantly, since we cannot know whether the samples are correctly recorded. In this paper, we propose a method based on confident learning theory to detect anomalous samples in the datasets and unify zero-catch and non-zero samples as noise through an overarching framework of learning with noisy labels, which reveals the heterogeneity among zero-catch samples (as well as among non-zero samples) and the homogeneity between zero-catch samples and non-zero samples. Using three species of tuna in the tropical Atlantic Ocean with the spatial resolution of 0.5 ◦ × 0.5 ◦ and time resolution of days from 2016 to 2019 as experimental material, performance on all three classical machine learning models(Random forest, Support Vector Machine and XGBoost) is significantly improved compared to each baseline.This confirms that we propose a self-adaptive, effective method for detecting and repairing anomalous samples in the fishery dataset.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

Microbial fuel cells (MFCs) offer sustainable solutions for various biotechnological applications and are a crucial area of research in biotechnology. MFCs can effectively treat wastewater and biodiesel waste by decomposing organic matter and generating electricity. Certain Pseudomonas species possess extracellular electron transfer (EET) pathways, enabling them to transfer electrons from organic compounds to the MFC's anode. Moreover, Pseudomonas species can grow under low oxygen conditions, which is advantageous considering that the electron transfer process in an MFC typically leads to reduced oxygen levels at the anode. This study focuses on evaluating MFCs inoculated with a new Pseudomonas species, grown with 1 g.L-1 glycerol, a common byproduct of biodiesel production. Pseudomonas sp. BJa5 exhibited a maximum power density of 39 mW.m-2. Also, the observed voltammograms and genome analysis indicate the potential production of novel redox mediators by BJa5. Additionally, we investigated the bacterium's potential as a synthetic biology non model chassis. Through testing various genetic parts, including constitutive promoters, replication origins, and cargos using pSEVA vectors as a scaffold, we assessed the bacterium's suitability. Overall, our findings offer valuable insights into utilizing Pseudomonas spp. BJa5 as a novel chassis for MFCs. Synthetic biology approaches can further enhance the performance of this bacterium in MFCs, providing avenues for improvement.

The splitting method developed in a previous study for linear, multi – component, convection-diffusion mass transfer equations is extended to non-linear, multi-component, convection-diffusion mass transfer equations. The diffusion term is non-linear (the diffusion coefficients depend on chemical species concentrations). Theoretical results about the splitting error are presented, as well as numerical simulations for mixtures with n ≤ 5. The numerical experiments show second-order accuracy and stability for the present splitting algorithm.

The assessment of an organization/product's environmental footprint is based on the protocols developed by the Joint Research Centre of the European Union, which take into account 16 impact categories. Among the categories covered are toxicity to freshwater ecosystems and to humans. Standard protocols use only chemical parameters as input data, preventing the true impact of entire complex mixtures, such as emissions discharged into the environment, from being determined. Biological assays allow us to bridge this gap: in the current study, assays were used to determine baseline toxicity towards aquatic organisms (green algae, luminescent bacteria, and crustaceans) as well as specific toxicity (mutagenicity and carcinogenicity). Expected impacts were compared using two approaches (standard and bioassay-centered results obtained are not always in line and, in general, the traditional method underestimates impacts). This demonstrates the importance of these assays and suggests that they be used in LCA (Life Cycle Assessment) protocols as well.

Usually in quantum optics, the theory of large- and small-scale waveguide beam splitters is the same. In this paper it is shown that the theory of the nanoscale waveguide beamsplitter has a significant difference from a similar device, but of a larger scale. It is shown that the previously known theory of the waveguide beam splitter is a particular case of the theory presented here. The wave function at the output ports of the nanoscale beam splitter is analyzed. The results obtained are sensitive to the size of the beam splitter, the coupling parameter of the two waveguides, and the degree of nonmonochromaticity of the photons entering the first and second ports of the beam splitter. The results are important for quantum technologies using a nanosized beam splitter.

Dormancy is a physiological state that confers winter hardiness to and orchestrates phenological phase progression in temperate perennial plants. Weather fluctuations caused by climate change increasingly disturb dormancy onset and release in many plant species including tree crops leading to aberrant growth, flowering, and fruiting. Currently, research in this field is impeded by the lack of affordable non-invasive methods for on-line monitoring of dormancy. We report on an automatic framework for low-cost, long-term, and scalable dormancy studies in deciduous plants. The proposed method is based on continuous near-field sensing of the photosynthetic activity of shoots via pulse-amplitude modulated chlorophyll fluorescence sensors connected remotely to a data processing system. The resulting high-resolution time series of JIP-test parameters indicative of the responsiveness of the photosynthetic apparatus to environmental stimuli are subjected to frequency-domain analysis. The proposed approach allows to overcome the variance coming from diurnal changes of insolation and to derive estimations on the depth of dormancy. Our approach was validated over three seasons in an experimental apple (Malus × domestica Borkh.) orchard by collating the non-invasive estimations with the results of traditional methods (growing of the cuttings obtained from the tress at different phases of dormancy) and the output of commonly used chilling requirement models. We discuss the advantages of the proposed monitoring framework such as prompt detection of freeze damages along with its potential limitations.

Electrospinning has gained a lot of attention in recent years due to its ability to easily produce high-quality polymeric nanofibers. However, electrospinning suffers from limited production capacity and a method to readily scale up this process is needed. One obvious approach includes the use of multiple electrospinning needles operating in parallel. Nonetheless, such an implementation has remained elusive, partly due to the uneven electric field distribution resulting from the Coulombic repulsion between the charged jets and needles. In this work, the uniformization of the electric field was performed for a linear array of twenty electrospinning needles using lateral charged plates as auxiliary electrodes. The effect of the auxiliary electrodes was characterized by investigating the semi-vertical angle of the spun jets, as well as the deposition area and diameter of the fibers. Finite element simulation was also used to analyze the impact of the auxiliary electrodes on the electric field intensity below each needle. Implementing parallel lateral plates as auxiliary electrodes was shown to help achieve uniformization of the electric field, the semi-vertical angle of the spun jet, and the deposition area of the fibers for the multi-needle electrospinning process. The high-quality morphology of the polymer nanofibers obtained by this improved process was confirmed by scanning electron microscopy (SEM). These findings help resolve one of the primary challenges that have plagued the large-scale industrial adoption of this exciting polymer processing technique.

Regression models are mostly used in all fields of sciences for modelling the relationship between a dependent variable and independent variable(s). The least square method is often used to estimate the parameters in a linear model because it is the best linear unbiased estimator. These estimates can only be reliable if the assumption of normality is satisfied. In some cases the dependent variable might be bimodal and shows a non-linear relationship with the independent variable(s). In this case, a non-linear model should be used. In non-linear model, the standard errors are often obtained by linearizing the nonlinear function around the parameter, assuming central limit theorem. After the linearization, the least square parameter estimates are obtained. It should be noted that the error of the non-linear model is different from that of the transformed linear model. Thus, there is a need to transform back to the original non-linear model. In this note, a novel non-linear function was developed into a non-linear regression model, called Normal-Power model. The least square method was used to estimate the parameter of the transformed model. Its usefulness in regression model was demonstrated using real data of Nigeria Economy-Tourism model.

Being able to ascertain the physiological condition of the buds on a young apple tree before bud burst could help farmers manage their orchards more efficiently, especially if they could do so without destroying the buds in the process. The experiments carried out in this study were conducted with the aim of distinguishing shoot from non-shoot buds before bud burst using a visible/near-infrared spectrometer, a device that does not destroy the buds being tested. Tests on spring-planted (April 30, 2021) trees were conducted to check shoot and non-shoot bud physiology and the winter dormancy of young ‘Jonagold’, ‘Miyabi Fuji’ and ‘Orin’ apple trees. The light absorbance of the shoot buds before bud burst was much lower than the light absorbance of the non-shoot buds as checked on the visible/near-infrared spectrometer. The highest first factor effect was determined by a PCA test conducted on shoot and non-shoot ‘Jonagold’ buds (99.9%) at a range of 640-652 nm, ‘Miyabi Fuji’ buds (99.7%) at 654-680 nm and ‘Orin’ buds (99.6%) at 704-766 nm seven days before bud burst. We also found that the highest level of accuracy, using the Classifier analysis, between shoot and non-shoot ‘Jonagold’ buds (76.6%) was one day before bud burst, for ‘Miyabi Fuji’ buds (82.1%) it was three days before and for ‘Orin’ buds (76.3%) it was two days before. These findings suggest that growers can more effectively manage the development of the young trees in their orchards with a visible/near-infrared spectrometer.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

In this paper, we introduce a non-invasive approach for monitoring bridge infrastructure with ground-based interferometric radar. This approach is called the mirror mode, since it utilises the flat surface of the bridge underside as a mirror to reflect the signal to a corner reflector on the ground placed opposite of the radar sensor. For proving the feasibility of this approach, a measurement campaign has been carried out at an exemplary bridge in Karlsruhe (Germany) including a radar sensor in mirror mode, a second radar sensor in the default mode and a laser profile scanner. We investigate the potential of this approach to monitor the bridge displacement in vertical direction and compare the results with the two other sensors. The derived results reveal the potential for monitoring bridge infrastructure. Finally, we propose further research aspects of this approach to analyse its capabilities and limitation in the context of non-invasive infrastructure monitoring.

Biological invasions represent a threat to ecosystems, through competition and habitat destruction, which may result in significant changes of the invaded community. Asparagopsis armata is a red macroalgae (Rodophyta) globally recognized as an invasive species. It is found from the intertidal to shallow subtidal areas, on rock or epiphytic, forming natural vegetation belts on exposed coasts. This study evaluated the variations on native intertidal seaweed and macroinvertebrate assemblages inhabiting rock pools with and without the presence of the invasive macroalgae A. armata. To achieve this, manipulation experiments on Atlantic (Portugal) rock pools were done. Three rock pools were maintained without A. armata by manual removal of macroalgae, and three others were not experimentally manipulated during the study period and A. armata was freely present. In this study the variations between different rock pools were assessed. Results showed different patterns in the macroalgae composition of assemblages but not for the macrobenthic communities. Ellisolandia elongata was the main algal species affected by the invasion of A. armata. Invaded pools tended to show less species richness, showing a more constant and conservative structure, with lower variation of its taxonomic composition than the pools not containing A. armata, where the variability between samples was always higher. Despite the importance of the achieved results, further data based on observation of long-term series are needed, in order to further understand more severe effects of the invader A. armata on native macroalgal assemblage.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

This paper aims to investigate the criteria of behaviour of certain type of third order neutral generalized difference equations with distributed delay. With the technique of generalized Riccati transformation and Philos-type method, some oscillation criteria are obtained to ensure convergence and oscillatory solution of suitable example is listed to illustrate the main result.

In this paper, we are interested in a model of exact asymptotically flat charged hairy black holes in the background of dilaton potential. We study the weak gravitational lensing in the spacetime of hairy black hole in Einstein-Maxwell theory with a non-minimally coupled dilaton and its non-trivial potential. In doing so, we use the optical geometry of the flat charged hairy black hole for some range of parameter $\gamma$. For this purpose, by using Gauss-Bonnet theorem, we obtain the deflection angle of photon in a spherically symmetric and asymptotically flat spacetime. Moreover, we also investigate the impact of plasma medium on weak gravitational lensing by asymptotically flat charged hairy black hole with a dilaton potential. Our analytically analyses show the effect of the hair on the deflection angle in weak field limits.

The motivation of this work is to investigate experimentally the influence of non-thermal plasma (NTP) application on the reaction kinetics of atmospheric pressure steam gasification of charcoal using a thermostatically controlled drop tube reactor. A gliding-arc generator provides about 1 kW electrical power NTP. For comparison thermal gasification is investigated under comparable flow and specific energy input conditions providing additional heat to the steam. Optical temperature measurement 20 cm flow down of the NTP zone is utilized to characterize the specific enthalpy of the reactive flow. The composition of produced syngas is measured by a gas analyzer and used for the calculation of gas flow rates. The results show a NTP-enhancement on the production of individual syngas components (H2, CO, CH4), especially on hydrogen production by around 39%. The syngas-based carbon conversion and hydrogen release are calculated from the carbon and hydrogen balance between the correspondent content in syngas and in the feedstock. The NTP promoted the carbon conversion and hydrogen release by 25% and 31%, respectively. The first-order reaction kinetics are determined by data-fitting in an Arrhenius diagram. The plasma enhanced the reaction rate coefficients by 27%. Based on experimental results and other literature, possible plasma-induced reactions are proposed.

The aim of this study was to determine the impact of information technology in management of risks in the capital market-listed company is in Tehran Stock Exchange. The purpose of the present study is an applied descriptive approach. The target population for the survey, companies that from 2009 to the first half of 2015 have been a member of the Tehran Stock Exchange, through Cochranʼs sample size of 140 companies, respectively. We used cluster sampling method. In order to collect data from two questionnaires: risk management questionnaire Foakeh (2013) has 38 items and a standard questionnaire Chanvyas (2006) has 40 items, the whole five-item Likert scale questionnaire is above has been used. Data gathered through the questionnaire, sign the application was 21spss. For inferential analysis of the variables and to analyze the data from different statistical tests and regression was used Kolmogorov-Smirnov test. The results showed that information technology on risk management and its dimensions (primary market risk, market risk and the risk of secondary non-financial) impact.

In this paper, we established the existence of PC-mild solutions for non local fractional impulsive functional integro-differential equations with finite delay. The proofs are obtained by using the techniques of fixed point theorems, semi-group theory and generalized Bellman inequality. In this paper, we have used the distributed characteristic operators to define the mild solution of the system. Results obtained here improve and extend some known results.

We study the existence or absence of non-Shannon inequalities for variables that are related by functional dependencies. Although the power-set on four variables is the smallest Boolean lattice with non-Shannon inequalities there exist lattices with many more variables without non-Shannon inequalities. We search for conditions that excludes the existence of non-Shannon inequalities. It is demonstrated that planar modular lattices cannot have non-Shannon inequalities. The existence of non-Shannon inequalities is related to the question of whether a lattice is isomorphic to a lattice of subgroups of a group.

In this work we present the results obtained with an artificial neural network (ANN) which we trained to predict the expected output of high-order harmonic generation (HHG) process, while exploring a multi-dimensional parameter space. We argue on the utility and efficiency of the ANN model and demonstrate its ability to predict the outcome of HHG simulations. In this case study we present the results for a loose focusing HHG beamline, where the changing parameters are: the laser pulse energy, gas pressure, gas cell position relative to focus and gas cell length. The physical quantity which we predict here using ANN is directly related to the total harmonic yield in a specified spectral domain (20-40 eV). We discuss the versatility and adaptability of the presented method.

The definition of a Smart-complex of educational discipline and its technology is given. Attention is focused on the form of the Smart-complex and constructive elements: the creative educational environment, the author's environment, the non-verbal environment, the encyclopedia, the creative / self-realization environment, the monitoring / self-evaluation environment.A feature of the Smart-complex of the academic discipline is the integration into it of the structural equalization block. Constructive alignment (alignment) is based on the design of the student's own learning participation in educational projects. Alignment refers to creating an appropriate learning environment and involves selecting the most appropriate training activities and evaluating each learning outcome. If the result of the training is to develop analytical skills, then for the assessment it is necessary to build questions and scenarios for their development.Two main components of the structural alignment are considered: 1) the first component is based on cognitive psychology and constructivist theory, recognizes the importance of linking new material with the concepts and experiences of students and extrapolation to possible future scenarios in the process of mission activity - they comprehend what they are doing during training; 2) the second component is based on the declaration by the teacher of the correspondence between the planned educational activities and the results of the training of students. This makes planning of educational activities and development of self-assessment criteria for organizing feedback. It is necessary to take into account the impact of Smart-complexes of educational disciplines on three think-tank training networks: 1) effective networks (why learn) - several ways of presenting to give students different ways of obtaining information and knowledge; 2) recognition networks (learning outcomes) - several ways of expressing them to provide them with an alternative for demonstrating what they know; 3) strategic exercises (how to learn) - several ways to increase the motivation for learning to attract their attention to both their own learning project and its technical and historical decision. Smart-complexes of educational disciplines should be: 1) scientific; 2) with user-friendly interface; 3) have a connection with LMS; 4) structured; 5) with visual material; 6) working in Off-line mode; 7) used on various devices in an educational institution, as well as at home.

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) are now widespread and are often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, they need to be translated into specific and observable behavioral markers. To this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part to simulations. The tool was used as guide for the Io and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were highly positive, around 4 in a 5-point scale. The CRM observational tool is therefore a useful, quick and easy solution to facilitate the debriefing, the peer-to-peer feedback and, most of all, the transfer of safe behavior from simulation to everyday practice.

Today, the style of light construction materials used in building is one of the most important factors in reducing building's dead load and better performance of the structures in the earthquake. One of the ways to reduce the structure weight is to use lightweight blocks instead of using traditional materials. The main purpose of this research is to compare density, compressive strength and water absorption volume of non-load-bearing lightweight blocks made of natural and artificial lightweight aggregates. Scoria lightweight aggregates of Sanandaj, Ghorveh mine, pumice in Tabriz, Bostanabad mine, and Leca in Leca enterprise have been used to make the samples. Given the importance of the materials used, grading of coarse-grained materials has been conducted based on the standard of 7657 and grading of fine materials have been conducted based on the standard of 302.The experiments' results show that Scoria blocks due to hard texture, and high mechanical resistance of their lightweight aggregates, have had higher compressive strength, and density and lower water absorption volume compared to pumice and Lika lightweight aggregate blocks. Pumice blocks despite having desirable compressive strength and lower density compared to the two other blocks have higher water absorption volume, and do not meet the standard conditions. This same factor causes it faces with less interest. Among these Lika blocks with density of 1151.94 (kg per cubic meter) below 2000 kilograms per cubic meter of Iran density standard of 7782 (28-day compressive strength of 2.57 MPa), higher than 2.5 MPa of Iran compressive strength standard of 7782 (and water absorption volume of 282.92 kg per cubic meter) below 288 kilograms per cubic meter of Iran water absorption volume standard of 7782 (as a non-load-bearing lightweight block) have been diagnosed desirable.

The paper discusses the 2022 Nobel Prize in physics for experiments of entanglement “establishing the violation of Bell inequalities and pioneering quantum information science” in a much wider, including philosophical context legitimizing by the authority of the Nobel Prize a new scientific area out of “classical” quantum mechanics relevant to Pauli’s “particle” paradigm of energy conservation and thus to the Standard model obeying it. One justifies the eventual future theory of quantum gravitation as belonging to the newly established quantum information science. Entanglement, involving non-Hermitian operators for its rigorous description, non-unitarity as well as nonlocal and superluminal physical signals “spookily” (by Einstein’s flowery epithet) synchronizing and transferring some nonzero action at a distance, can be considered to be quantum gravity so that its local counterpart to be Einstein’s gravitation according to general relativity therefore pioneering an alternative pathway to quantum gravitation different from the “secondary quantization” of the Standard model. So, the experiments of entanglement once they have been awarded by the Nobel Prize launch particularly the relevant theory of quantum gravitation grounded on “quantum information science” thus granted to be nonclassical quantum mechanics in the shared framework of the generalized quantum mechanics obeying rather quantum-information conservation than only energy conservation. The concept of “dark phase” of the universe naturally linked to the very well confirmed “dark matter” and “dark energy” and opposed to its “light phase” inherent to classical quantum mechanics and the Standard model obeys quantum-information conservation, after which reversible causality or the mutual transformation of energy and information are valid. The mythical Big Bang after which energy conservation holds universally is to be replaced by an omnipresent and omnitemporal medium of decoherence of the dark and nonlocal phase into the light and local phase. The former is only an integral image of the latter and borrowed in fact rather from religion than from science. Physical, methodological and proper philosophical conclusions follow from that paradigm shift heralded by the 2022 Nobel Prize in physics. For example, the scientific theory of thinking should originate from the dark phase of the universe, as well: probably only approximately modeled by neural networks physically belonging to the light phase thoroughly. A few crucial philosophical sequences follow from the break of Pauli’s paradigm: (1) the establishment of the “dark” phase of the universe as opposed to its “light” phase, only to which the Cartesian dichotomy of “body” and “mind” is valid; (2) quantum information conservation as relevant to the dark phase, furthermore generalizing energy conservation as to its light phase, productively allowing for physical entities to appear “ex nihilo”, i.e., from the dark phase, in which energy and time are yet inseparable from each other; (3) reversible causality as inherent to the dark phase; (4) the interpretation of gravitation only mathematically: as an interpretation of the incompleteness of finiteness to infinity, for example, following the Gödel dichotomy (“either contradiction or incompleteness”) about the relation of arithmetic to set theory; (5) the restriction of the concept of hierarchy only to the light phase; (6) the commensurability of both physical extremes of a quantum and the universe as a whole in the dark phase obeying quantum information conservation and akin to Nicholas of Cusa’s philosophical and theological worldview.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Respiratory viral infections (RVI) are common reasons for healthcare consultations. The inpatient management of RVI consumes significant resources. From 2009-2014, we assessed the costs of RVI management in 4776 hospitalized chil-dren aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by de-tailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (“non-ICU”) versus management requiring ICU-care (“ICU”) added up to 2,767.14€ (non-ICU) vs. 29,941.71€ (ICU) for Influenza, 2,713.14€ (non-ICU) vs. 16,951.06€ (ICU) for RSV infections, and 2,767.33€ (non-ICU) vs. 14,394.02€ (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all 8 RVI studied: Influenza, RSV, hRV, ade-novirus (hAdV), metapneumovirus (hMPV), parainfluenzavirus (hPIV), bocavirus (hBoV) and seasonal coronavirus (hCoV) infections. ICU-costs for Influenza however, ex-ceeded all other RVI. At the time of the study, Influenza was the only RVI with antivi-ral treatment options available for children, but only 9.8% of Influenza patients (non-ICU) and 1.5% of ICU-patients with Influenza received antivirals; only 2.9% were vac-cinated. Future studies should investigate the economic impact of treatment and pre-vention of Influenza-, COVID-19-, and RSV post vaccine introduction.

Regular regimes of oil and oil products pipelines are studied. The problem is to develop an algorithm of effective pipeline system control that ensures the fulfillment of specified boundary conditions at the system boundaries. The product is pumped in batches, the flow is characterized by a change in temperature and pressure flow parameters over time. The developed solution method uses the principle of decomposition in the sense that each computational iteration is im-plemented in 3 stages, in three nested loops. The inner cycle is connected with the material bal-ance relations, at the next cycle the flow equations are introduced and the fulfillment of the 2nd Kirchhoff's law is monitored. If the flow process is significantly affected by temperature, then an external cycle is also implemented, correcting the solution so that the energy conservation equa-tion is satisfied. In the calculation procedure, some computational difficulties may arise, which consist in choosing an appropriate optimization method. On a specific example, the possibility of using various library programs to solve the problem was checked. The developed method is suita-ble for the analysis of systems of arbitrary topology. Since the method is not time-consuming, it can be recommended for online control of oil and oil products supply systems. The paper opens a new direction in the theory of hydraulic circuits. It uses both traditional methods of continuum mechanics and stochastic models.

The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for directly and simply obtaining surfactant compositions of mixtures of D-mannuronic acid and L-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in derived compounds and in compositions having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.

Indirect imaging methods involve at least two steps, namely optical recording, and computational reconstruction. The optical recording process uses an optical modulator that transforms the light from the object into a typical intensity distribution. This distribution is numerically processed to reconstruct the object’s image corresponding to different spatial and spectral dimensions. There have been numerous optical modulation functions and reconstruction methods developed in the past years for different applications. In most cases, a compatible pair of optical modulation function and reconstruction method gives optimal performance. A new reconstruction method termed non-linear reconstruction (NLR) was developed in 2017 to reconstruct the object image in the case of optical scattering modulators. During the years, it was revealed that the NLR could reconstruct an object’s image modulated by an axicons, bifocal lenses and even exotic spiral diffractive elements, which generate deterministic optical fields. Apparently, NLR seems to be a universal reconstruction method for indirect imaging. In this review, the performance of NLR has been investigated for many deterministic and stochastic optical fields. Simulation and experimental results for different cases are presented and discussed.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

In this paper, we study the deflection angle for wormhole-like static aether solution by using Gibbons and Werner technique in non-plasma, plasma and dark matter mediums. For this purpose, we use optical spacetime geometry to calculate the Gaussian optical curvature, then implement the Gauss-Bonnet theorem in weak field limits. Moreover, we compute the deflection angle by using a technique known as Keeton and Petters technique. Furthermore, we analyze the graphical behaviour of the bending angle ψ with respect to the impact parameter b, mass m as integration constant and parameter q in non-plasma and plasma mediums. We examine that deflection angle is exponentially increasing as direct with charge. Also, we observe that for small values of b, ψ increases and for large values of b the angle deceases. We also considered an analysis to the shadow cast of the wormhole relative to an observer at various locations. Comparing it the the Schwarzschild shadow, shadow cast is possible for wormhole as r<2m. At r>2m, the Schwarzschild is larger. As r → ∞, we have seen that the behavior of the shadow, as well as the weak deflection angle, approaches that of the Schwarzschild black hole. Overall, the effect of plasma tends to decrease the value of the observables due to the wormhole geometry.

Objetives: Adequate donor-recipient matching is necessary to achieve the best renal function after transplantation. The nephron load received from the donor, which can be reflected in variables such as age, sex and body mass index, may influence the evolution of the graft. Our objetive was develop a combined score according to the donor-recipient pairing in age, sex and body mass index, and assess its influence on the evolution of the renal graft. Materials and methods: Transplant patients between 2013 and 2020 who had at least 1 year of post-transplant follow-up. A ranking of 0 to 2 points was awarded according to the match between donor and recipient for sex, age and body mass index individually, with higher rank to greater mismatch. Subsequently, a Score with value of 0 to 6 points was created with the combined ranking of the indivudual variables, analyzing its influence on the evolution of the graft by multivariate linear regression. Results: 280 patients followed for 4.3 years of median. Worse renal function was observed at the end of follow-up as the range of each variable increased separately, and the Score created, with a worsening of renal function as the combined Score increased in the multivariate analysis: Coefficient B= -2.4 ml/min, p=0.018. Conclusions: An adequate match between donor and recipient in age, sex and body mass index using this combined Score can help achieve better kidney function after transplantation.

The inability to delineate a unified physical ontology that accounts simultaneously for the laws of special relativity and the results of quantum experiments has been a defining problem in physics for more than 100 years. This analysis addresses the problem by positing a novel mixed ontology composed of a “discrete” 4D spacetime and a physical, ultra-high dimensional (3 x N) “Planck Space.” Together, Planck Space and the three spatial dimensions of 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the “Dual Ontology”).Critically, the Dual Ontology’s structure replaces 1) the continuous, differentiable manifold of 4D spacetime with a discrete, background-independent 4D spacetime that is intrinsically curved and 2) mathematical spaces with a physical (3 x N) Planck Space. Moreover, the Dual Ontology is structurally and dynamically predicated on the one-to-one mapping and identity between the discrete spatial units that simultaneously form 4D spacetime and Planck Space. The one-to-one mapping and identity of the discrete spatial units support an integrated quantum dynamics based upon the dynamic evolution of single and N-body quantum states in 4D spacetime in full compliance with the laws of special relativity and the instantaneous collapse of all quantum states in an ontic Planck Space, where special and general relativity and more generally, 4D spacetime’s laws of physics, do not apply.

Multilingual classrooms are becoming more common worldwide due to increasing mobility. Teaching foreign languages using the mother tongue in multilingual classrooms has become problematic; some of the significant concerns in Japanese language acquisition – such as the high contextuality of the language, vocabulary and kanji learning – make the direct teaching method confusing for many students, especially at the beginner and elementary levels. This article provides the preliminary results of a study carried out as a component of a more extensive empirical research project on instructional languages in classrooms teaching Japanese as a foreign language. It aims to gather, analyse and synthesise data from a survey conducted at a supranational level. The results of the first two sections of a questionnaire containing closed and open-ended questions were used for a quantitative analysis of the profile of Japanese language instructors with a focus on finding possible connections. The wide geographic distribution of the respondents (274 teachers from fifty-seven countries and regions) made it possible to collect data from a more representative sample and draw meaningful conclusions about the spread of multilingual classrooms that would be impossible in smaller-scale research. The study’s primary results show the proportion of multilingual classrooms among countries in different regions and across different educational stages, the distribution of Japanese language instructors in various educational stages depending on the highest level of formal education attained, and the proportion of part-time instructors working in different academic institutions.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines’ storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, rather than thrombolysis performed, to avoid potential adverse events of the latter in the setting of SCAD.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

Pericentromeric regions of chromosomes enriched in tandemly repeated satellite DNA although representing a significant part of eukaryotic genomes are still understudied mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability and evolution. Thus, the idea of satellite DNA as a junk part of the genome was refuted. Integration of data about molecular composition, chromosome behaviour and details of in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions of pericentromeric regions non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between cerntomeric regions of X chromosome and autosomes, and associations between centromeric regions of autosomal bivalents forming chromocenters. We conclude that X chromosome form temporary synaptic associations with different autosomes in early meiotic prophase I which normally can be found at pachytene-diplotene without signs of pachytene arrest. These associations are formed between the satellite DNA-enriched centomeric regions of X chromosome and different autosomes but not involve the satellite-poor centromeric region of Y-chromosome. We suggest the mechanism of X chromosome competitive replacement from such associations during synaptic correction. We showed that centromeric region of the X chromosome remains free of γH2Ax-dependent chromatin inactivation, while Y chromosome is completely inactivated. This findings highlights the predominant role of associations between satellite DNA-enriched regions of different chromosomes including X. We assume that X-autosome temporary associations is a manifestation of an additional synaptic disorders checkpoint. These associations are normally corrected before the late diplotene. We revealed that the intense spreading conditions applied to the spermatocytes I nuclei did not lead to destruction of stretched chromatin fibers i.e. elongated chromocenters enriched in satellite DNA. Revealed by us tight associations between pericentromeric regions of different autosomal bivalents and X chromosome may represent the basis for repeat stability maintenance in autosomes an X chromosome. The consequences of our findings are discussed. We obtained the preparations of mouse spermatocytes nuclei in the meiotic prophase I using two approaches: standard and extremely intense surface spread techniques. Using immuno-FISH we visualized tandemly repeated mouse Major and Minor satellite DNA located in the pericentromeric regions of chromosomes and performed a morphological comparison of the standard- and intensely spreaded meiotic nuclei. Based on our results, we assume the remarkable strength of the chromocenter-mediated associations, “chromatin “bridges”, between different bivalents at the pachytene and diplotene stages. We have demonstrated that the chromocenter “bridges” between the centromeric ends of meiotic bivalents are enriched in both tandemly repeated Major and Minor satellite DNA. Association of centromeric regions of autosomal bivalents and X-chromosome but not with Y-chromosome correlates with the absence of Major and Minor satellites on Y-chromosome. We suggest that revealed tight associations between pericentromeric regions of bivalents may represent the network-like system providing dynamic stability of chromosomal territories, as well as add new data for the hypothesis of ectopic recombination in these regions which supports sequence homogeneity between non-homologous chromosomes and does not contradict the meiotic restrictions imposed by the crossing-over interference near centromeres. We conclude that nuclear architecture in meio-sis may play an essential role in contacts between the non-homologous chromosomes providing the specific characteristics of pericentromeric DNA.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

Since its emergence, COVID-19 has caused a great impact in health and social terms. Governments and health authorities have attempted to minimize this impact by enforcing different mandates. Recent studies have addressed the relationship between various socioeconomic variables and compliance level to these interventions. However, little attention has been paid to what constitutes people's response and whether people behave differently when faced with different interventions. Data collected from different sources show very significant regional differences across the United States. In this paper, we attempted to shed light on the fact that a response may be different depending on the health system capacity and each individuals’ social status. For that, we analyzed the correlation between different societal variables (i.e. education, income levels, population density, etc.) along with healthcare capacity related variables (i.e. hospital occupancy rates, percentage of essential workers, etc.) with regards to people's level of compliance with three main governmental mandates in the United States: mobility restrictions, mask adoption, and vaccine participation. Our aim was to isolate the most influential variables impacting behavior in response to these policies. We found that there was a strong relationship between individuals' educational levels and political preferences with respect to compliance with each of these mandates.

Non-convex optimization is a critical tool in advancing machine learning, especially for complex models like deep neural networks and support vector machines. Despite challenges such as multiple local minima and saddle points, non-convex techniques offer various pathways to reduce computational costs. These include promoting sparsity through regularization, efficiently escaping saddle points, and employing subsampling and approximation strategies like stochastic gradient descent. Additionally, non-convex methods enable model pruning and compression, which reduce the size of models while maintaining performance. By focusing on good local minima instead of exact global minima, non-convex optimization ensures competitive accuracy with faster convergence and lower computational overhead. This paper examines the key methods and applications of non-convex optimization in machine learning, exploring how it can lower computation costs while enhancing model performance. Furthermore, it outlines future research directions and challenges, including scalability and generalization, that will shape the next phase of non-convex optimization in machine learning.

The search for materials with exceptional properties has led to significant advances in the field of non-carbon diamond-like conductive thin films (DLC-CTFs). These films, synthesized by chemical vapor deposition (CVD) and other techniques, are being actively researched for their potential in high-tech applications. This literature review discusses the synthesis methods, material properties, and applications of DLC-CTFs, highlighting the role of non-carbon dopants in enhancing electrical conductivity. This literature review aims to provide a comprehensive overview of the historical development, synthesis techniques, material properties, characterization methods, and applications of DLC-CTFs, with a focus on the impact of non-carbon doping on their conductive properties. By reviewing the literature. The review also addresses the challenges faced and suggests future research directions.

Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor have inter-donor and inter-subtype variabilities been taken into consideration. Here we provide the first identification and annotation of the human BORG lncRNA gene. Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes, and with epithelial-mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to triple-negative breast cancer tumors. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG levels in human TNBC tumors, indicating that human BORG is a novel driver of the highly aggressive basal TNBC tumor phenotype.