This review explores the intersection of developmental biology and differential topology in understanding vertebrate ontogenetic constraints. We examine how the topological organization of gene regulatory networks (GRNs) influences developmental trajectories and evolutionary possibilities. By analyzing the mathematical frameworks of differential topology and their application to chromatin architecture, we demonstrate how spatial gene arrangements create constraints that both channel and limit morphological evolution. Special attention is paid to the role of topologically associating domains (TADs) and their conservation across vertebrate lineages, suggesting their fundamental importance in maintaining developmental stability. We propose that the hierarchical nature of GRN topology serves as a primary mechanism for establishing evolutionary constraints while simultaneously facilitating phenotypic innovation within defined parameters. This synthesis provides new insights into how physical genome organization shapes the possibilities and limitations of vertebrate body plan evolution.

Hox genes represent an important gene family that is involved in the segmentation pattern and identity of the segments during the formation of the body plan in metazoans. For many years, several studies have sought to establish a correlation between the evolution of these genes and the evolution of large groups of metazoans. Here, we use publicly available sequences of Hox gene clusters to reconstruct the evolutionary history of anterior Hox genes. We show that information harbored by these genes, in part, reflects the evolution and diversification of most animal archetypes, but in many cases, there were conflicts between the evolutionary history of some genes and the history of large groups, these cases may have occurred due to specific and similar selective pressures in relatively distant groups, which may have led to evolutionary convergences. Our findings also reveal that the evolution of Hox genes (and clusters) as a multigene family is consistent to a birth-and-death model constrained by development, where there is a trade-off between a relatively fast gene turnover and their central developmental roles

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Background/Objectives: Early diagnosis of ASD a very important factor in improving the quality of life of people on the spectrum, but it still remains a major problem in Europe, especially concerning girls. In this study, we tried to answer the question of what factors affect the age of diagnosis in Poland. Additionally, we tried to establish the time between the first visit to the mental health center and the diagnosis in this population, and what factors affect its length. Methods: 77 children were randomly recruited among the patients who came to local MHC at the Child and Family Health Center in Sosnowiec. All participants were tested using the ADOS-2 protocol. In addition, the study used TAS-20 test and BDI. Results The mean age of the first enrollment in the MHC was 9.09 years for girls and 6.42 for the boys. The time needed to obtain a diagnosis from the first visit was consecutively 2.90 years and 4.29 years, but the difference was not statistically significant (p>0.05). Obtaining a different psychiatric diagnosis did not affect the average time to diagnosis and the age of diagnosis. Conclusions: The results of the study indicate that the diagnosis of ASD is still a significant problem both in Poland and in the world. The long time needed to obtain the correct diagnosis, the frequent need to change diagnosticians in order to obtain it is a common problem. the diagnostic process should be flexible, and the diagnostician should always take into account the axial symptoms, but remain aware that "overdiagnosis" of ASD can also have harmful consequences for the child.

Growth hormone therapy (GHT) can improve growth velocity and final height but can also accelerated the process of bone growth, which is related to structural bone modelling, both in formation and resorption. The study evaluated the capacity of bone turnover markers to predict early growth response to one year GHT in short stature children born as small for gestational age (SGA). 25 prepubertal SGA children were included. We have estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type I), P3NP (N-terminal procollagen type III), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA, IRA and ELISA methods. A statistically significant increase in bone resorption markers (Ctx ) was found both at 6 and 12 months. P1NP bone markers increased at 6 months and after 12 months of therapy. The P3NP marker of collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months and similarly ALP. We have found a significant correlation between height (cm) and Ctx after 6 -12 months as well as P1NP / height (SD) after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We find a strong reaction of bone resorption and bone formation markers during growth hormone therapy that may determine their selection as prediction of GH treatment outcome in SGA children. However, the issue requires further research.

POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the POGZ gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms re-main unclear. To shed light on this, we created two lines of conditional knockout mice for Pogz, one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total Pogz knockout mice. Although the two lines did not display significant morphological ab-normalities in the telencephalon, impaired POGZ function affected the electrophysiological prop-erties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with POGZ gene abnormalities.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Global warming and the associated increasing frequency of heatwaves are on the rise leading to numerous health complications. Diabetic patients are more vulnerable to heat exposure than healthy individuals, owing to their impaired sweating ability, however, little is known about how heat exposure may impact the function of skin cells, commonly keratinocytes. Our recent report provided the first proof-of-concept revealing that the metabolic composition of sweat EVs is associated with metabolic changes in healthy individuals and type 2 diabetes patients. Given this and the shared cellular proprieties of eccrine sweat glands with keratinocytes, we questioned whether the metabolic changes in sweat EVs may mirror the responses of keratinocytes upon heat exposure. To this, we exposed HaCat, which were maintained in low (mimicking healthy condition) and high glucose (mimicking diabetes condition) to acute (90 min), chronic (48 h), and repetitive heat exposure at 40 ⁰C. Through conducting a set of experiments including a targeted metabolomics approach, Greiss assay, western blotting analysis, and electron microscopy studies. The data demonstrate that heat exposure results in substantial changes of metabolite levels belonging to amino acids, pyrimidine metabolism, and glycolysis pathways in high glucose maintained HaCat cells when compared to those noted in low glucose condition. Exploring the molecular mechanisms through which heat exposure may impact the metabolic composition in keratinocytes, our discoveries highlight nitric oxide (NO) as a novel biomarker that the level is correlated with heat duration and frequency. Furthermore, data reveal that the HSP-70 protein levels and mitochondrial morphology are consequently altered. This study provides evidence of shared metabolic alterations in keratinocytes and sweat EVs collected from clinical study and proposes, for the first time, NO as a novel biomarker for monitoring changes in health and diabetes upon heat exposure.

Human development encompasses the integration of neuromotor, psychological, social-emotional, and cognitive processes across time. However, a better understanding of the interconnectedness of motor and cognitive development throughout the lifespan is needed. The integrative and dynamic nature of short-term motor skill acquisition and long-term developmental processes may foster executive functions. Unfortunately, assessments of motor competence have traditionally focused on skillfulness from a movement perspective, using restrictive task protocols that decontextualize performance and limit cognitive involvement. Additionally, traditional motor-cognitive dual-task assessments centered on cognitive involvement during specific movement protocols, have minimized impacts of task complexity and motor competence on cognitive performance. To gain a more ecologically valid understanding of the relation between motor and cognitive development, a novel assessment paradigm using an integrative approach to motor-cognitive dual-tasking is needed. The purpose of the present paper is to: 1) provide a conceptual bridge, based on multidisciplinary evidence, to effectively link the concurrent development of motor competence and executive functions via learning-related and exercise-related neurotrophic mechanisms, and 2) use this conceptual bridge to inform the development of novel motor-cognitive dual-task assessments that account for the role of task complexity, current levels of motor competence, and the continuous decision-making inherent in “real world” performance environments.

Objectives: Teachers’ intention understanding ability reflects their professional insight, which is the basis for effective classroom teaching activities. However, the cognitive process and brain mechanism of how teachers understand students' action intention in class are still unclear; Methods: This study used event-related potential (ERP) technology to explore the cognitive neural differences in intention understanding ability among teachers with different levels of knowledge and experience. The experiment used the comic strips paradigm to examine the ability of expert and novice teachers to understand students’ normative and non-normative classroom actions under different text prompts (“how” and “why”); Results: The results revealed that in the late time window, expert teachers induced larger P300 and LPC amplitudes when they understood students' classroom action intentions, while the N250 amplitudes induced by novice teachers in the early time window were significantly larger. In addition, for both types of teachers, when understanding the intentions behind students’ normative actions, the N250 amplitude was the most significant, while the P300 and LPC amplitudes were more significant for non-normative actions.; Conclusions: This study found that teachers at varying professional development stages had different time processing processes in intention understanding ability, which supported teachers' brain electrophysiological activities related to social ability.

Granular material is one of the most common in nature. Recently, there has been a significant amount of interest in the granular materials, such as powders or sand. It is challenging to describe the motion of such kind of macroscopic size matter, because it behaves like solid, fluid or gas. Size division, pattern formation, avalanches, packing and convection - these are just a few examples from a wide range of observed phenomena that occur during the motion process of granular matter. Most of these processes are based by flow and no wonder that much effort has been devoted to obtain a hydrodynamic description in which granular materials are treated as a continuous medium. During the research of vertically shaken granular medium motion in an opened container it was found that experimental and numerical results are explained by hydrodynamic theory. This paper investigates the motion of a granular matter for a shallow, vertically shaken bed. We assume the Leidenfrost state as initial and the matter resembles a fluid heated up from below.A one-dimensional isothermal and a non-isothermal problem of granular material motion,simulatedby a hydrodynamic model are considered, and the material is assumed to be a continuous medium. The local temporal solvability of isothermal and non-isothermal initial boundary-value problem in Sobolev’s spaces is proved. This work presents a numerical study of the one-dimensional model of granular medium flow. The feature of this model is consideration of the Navier-Stokes equations accounting an interpolation form of VanderWaals constitutive equation for pressure. A finite-difference approximation for numerical solution is proposed.

Proper blood-brain barrier (BBB) function is essential to maintain homeostasis keeping the central nervous system healthy. Disruption of the BBB has been described in nearly all neurological disease and injury contexts. Given the various physical and metabolic roles of the BBB and gliovascular unit (GVU), dysfunction should be assessed across multiple levels to pinpoint the exact nature of the impairment. Here we describe imaging techniques for evaluating various aspects of BBB and GVU integrity and function, tailored for use in mouse models with protocols for quantitative image analysis. These imaging techniques complement classical dye tracer experiments and reveal underlying molecular causes of BBB dysfunction.

Formaldehyde is generated via the biochemical and chemical pathways, and it widely exists in foods. Its chronic exposure causes carcinogenic, neurotoxic, reproductive, allergic, immunological, genetic and respiratory toxicities. However, food-sourced formaldehyde is usually neglected due to its rapid metabolism after intake. Compared with its residual level in processed foods, a large proportion of formaldehyde disappears because of its high reactivity. Nevertheless, its elimination reaction mechanism and the potential consequences remain unclear. In this review, the disappearing pathway of formaldehyde from two aspects, the formation of formaldehyde-derived toxins and aromas, was reviewed. This review article may help food scientists take appropriate strategies to use the beneficial reactions of formaldehyde or divert its harmful effects to beneficial ones.

In this study, we propose a conservative and compact finite difference scheme designed to preserve both the mass change rate and energy for solving the sixth-order Boussinesq equation with the surface tension. Theoretical analysis confirms that the proposed scheme achieves second-order accuracy in temporal discretization and fourth-order accuracy in spatial discretization. The solvability, convergence, and stability of the difference scheme are rigorously established through the application of the discrete energy method. Additionally, a series of numerical experiments are conducted to illustrate the effectiveness and reliability of the conservative scheme for long-time simulations.

Under physiological conditions the blood-brain barrier (BBB) is required for regulating the passage of substances between the bloodstream and the brain. To date, disruption of the BBB has been associated with nearly all neurological diseases. Dye and tracer experiments have been used to assess BBB integrity for decades, yet quantitative assessment of these experiments has only recently been implemented. Further, interpretation of these results requires the consideration of tracer-specific properties. Here, we describe a protocol for evaluating BBB leakage using the small molecule cadaverine in quantitative way. We also cover advantages/disadvantages of using some reagents and highlight limitations in data interpretations based on assays used to assess BBB permeability.

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

Fluctuations in kynurenic acid (KYNA) and brain-derived neurotrophic factor (BDNF) levels in the brain reflect its neurological status. The aim of the study was to investigate the effect of transiently elevated KYNA concentration in the cerebroventricular circulation on the expression of BDNF and its high-affinity tropomyosin-related kinase receptor B (TrkB) in specific structures of the sheep brain. Intracerebroventricularly cannulated anestrous sheep were subjected to a series of four 30-min infusions of KYNA: 4×5 μg/60 μL/30 min (KYNA20, n=6) and 4×25 μg/60 μL/30 min (KYNA100, n=6) or a control infusion (n=6), at 30-min intervals. Sections of the hippocampal CA3 field, amygdala (AMG), prefrontal cortex (PCx), and the hypothalamic medial-basal (MBH) and preoptic (POA) areas were dissected from the brain immediately after the experiment. The highest concentration of BDNF protein was found in the CA3 field (P<0.01), which was 8-fold higher than in the AMG and 12-fold higher than that in the PCx (MBH and POA were not analyzed). The most pronounced BDNF mRNA expression was observed in the MBH followed by the PCx, POA, AMG and CA3, while the highest abundance of TrkB mRNA was recorded in the AMG followed by the MBH, PCx, CA3 and POA. KYNA increased (P<0.05-P<0.01) BDNF protein levels and the expression of its gene in the brain structures examined, with the effect varying by dose and brain region. KYNA, particularly at the KYNA100 dose, also increased (P<0.01) TrkB gene expression, except for the AMG, where the lower KYNA20 dose was more effective (P<0.01). These findings suggest a positive relationships between KYNA levels in the cerebroventricular circulation and BDNF-TrkB expression in specific brain regions in a sheep model. This indicates that a transient increase in CSF KYNA concentration can potentially restore BDNF production, whose deficiency underlies numerous neurological disorders.

The positive relationship between species richness and area is a fundamental principle in ecology. However, this pattern deviates on small islands, where species richness either changes independently of area or increases at a slower rate—a phenomenon known as the Small-Island Effect (SIE). While the SIE has been well-documented in natural ecosystem, its presence in highly fragmented and disturbed urban ecosystem remains unexplored, posing challenges for urban vegetation conservation. Urban remnant vegetation, isolated by surrounding infrastructures, preserves intact zonal vegetation characteristics, serves as a benchmark for restoring near-natural habitats and offers ideal conditions to test the existence of SIE in human-altered landscapes. In this study, we surveyed 17 remnant vegetation patches in Qingdao City, China. In total of 331 plants attributed to 255 genus in 81 families been recorded. Firstly, by using six species-area relationship regression models tested SIE for remnant vegetation with different life form (i.e. annual herb, perennial herb, shrub and tree), we found SIE detected in only woody plants, with area threshold ranging from 6.38 ha (tree) to 11.91 ha (shrub). According to stepwise and generalized linear regression mode analysis we found SIE detected in only woody plants, with area threshold 6.38 ha for tree and 11.91 ha for shrub. Further analysis revealed that the SIE in shrub was driven by landscape shape index, perimeter-area ratio, and the proportion of sealed surface within patch. For trees, the SIE was influenced by the distance to the source of species, GDP, night light intensity and perimeter-area ratio. This finding justifies that conservation in urban planning, construction and development should focus not only on protecting large areas, but also on maintaining and promoting diverse habitats within these areas. At the same time, reducing anthropogenic disturbance and enhancing the connectivity of green spaces are important for the persistence of metacommunities and can contribute to the local species pool, thus potentially improving the ecological resilience of urban environments.

Arbutus unedo (strawberry tree) is a small Mediterranean tree capable of vigorous regrowth after disturbances like fire. Traditionally used for biomass fuel, its bark and branches hold potential for higher-value products through ecovalorisation into liquid mixtures that could replace petro-leum-based materials. This study aimed to explore the chemical composition of various compo-nents of Arbutus unedo and to produce a liquefied material from its internal (IB) and external bark (EB). Chemical compositions of internal and external bark were determined using TAPPI standards including ash, extractive content, lignin, and cellulose. Metal cations were analyzed by ICP. Liquefaction of bark was optimized in a PARR reactor, evaluating factors such as particle size, temperature, and time and the best polyols were monitored by FTIR-ATR. Polyurethane foams were made with internal and external bark liquefied materials by polymerization with isocyanate, a catalyst and water as blowing agent. Results showed that EB has a higher extractive and lignin content, while IB contains more cellu-lose. Liquefaction yields were higher for IB (74%) than EB (68%), with IB yielding polyols that produced stronger and more resilient foams. Mechanical properties of the foams were influenced by the NCO/OH ratio and catalyst levels. Overall, the internal bark demonstrated superior performance for foam production, highlighting its potential as an eco-friendly alternative to petroleum-derived materials.

The design and control of lower limb rehabilitation robots for patients after a stroke has gained significant attention. This paper presents the dynamic analysis and control of a 3-degree-of-freedom lower limb rehabilitation robot using combined position-force control based on the force feed-forward and compensate gravity proportional derivative method. In the lower limb rehabilitation robot, the interaction force between the patient with the joints and links of the robot is uncertain and nonlinear due to the disturbance effect of Coriolis force, centrifugal force, gravitational force, and friction force. During recovery stages, forces exerted by the patient's lower limb are considered disturbances. Therefore, to meet the quality requirements in using the rehabilitation robot with different recovery stages of patient training, combining position control and force control is essential. In this paper, we proposed a combinations of proportional-derivative gravity compensation motion control and force feed-forward control to form an advanced combined controller (Position-Force Feedforward Control - PFFC) for a 3 DOF lower limb functional rehabilitation robot. The forces can be sensed using a 3-axis force sensor. In addition, the robot's position parameters are also measured by encoders. The control algorithm is implemented on the STM32F4 Discovery board. Verified test of the proposed control method is shown in the experiments and shown good performance of the system.

Knowledge is not merely the characteristic of certain pieces of information being deemed true, believed and justifiable, but rather a process. The sentences that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the justification, if concludes successfully with respect to a sentence, it elevates the information to the status of knowledge. We provide a model where we define the fundamental elements of communication and grammar. As a result, knowledge must be \open\ (everyone must be able to acquire it), \free\ (everyone must be able to justifiy) and \tidy\ (everyone must be able to retrace the justification process in all its parts recursively). Ultimately, the development of knowledge processing, referred to as \emph{knowmatic}, represents the evolution of the information technologies (\it).

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are underinvestigated. Here we performed the analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis, molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Due to the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids, independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

This paper presents an approach to assess and improve the cybersecurity infras- tructure of developing countries. We have highlighted and addressed the critical gaps through a hybrid approach encompassing SWOT analysis, benchmarking using Data Envelopment Analysis (DEA) and, Root Cause Analysis (RCA). This approach has provided a strong basis for evaluating cybersecurity performance by combining qualitative insights with quantitative metrics. As a case study, we have compared an underdeveloped country’s (Pakistan) cybersecurity pos- ture to five highly developed countries (Lithuania, Estonia, Singapore, Spain,and Norway). Our analysis has identified cybersecurity shortcomings and pro- vided actionable recommendations within a flexible framework, applicable for all developing countries to identify and address vulnerabilities, and align their cybersecurity infrastructure with international standards.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Polluting discharges are produced at a rate that is inexorably rising in tandem with human activity development. Eutrophication and other matters, such as offensive aquatic life, require wastewater to be treated before being discharged into the environment. Prior releasing into water bodies, the treated waters must to undertake laboratory analysis. For this purpose, an analysis using standard methods was carried out at the Laboratory Waterworks in Debrecen on various samples taken from various wastewater treatment plants (sewage treatment plants) in Hungary. The overall objective of this study was to assess the quality of the effluents from the fourteen (14) wastewater treatment plants and investigate their efficiency by measuring various physicochemical parameters and microbiological parameters as excellent indicators to evaluate the performance of the studied wastewater treatment plants. The microbiological indicator monitored was the heterotrophic count (HPC) by estimating its total number, which provides useful information for the assessment and monitoring of water samples. The determination of physicochemical parameters included biological oxygen demand (BOD5), chemical oxygen demand (COD) and nitrite -N (NO2), ammonia-N (NH3-N), nitrate-N (NO3) total phosphorus (TP), Kjeldahl- Nitrogen (organic N+ammonia-N) (TKN), total inorganic N (TI), total suspended solids (TSS) and total nitrogen (TN). The performance of the wastewater treatment plants examined was checked and the results were conclusive. In the future, solutions should be applied to these wastewater treatment plants and some recommendations are suggested.

Pre-transport management activities can cause stress, injuries, and mortality in poultry. This study aimed to gather information about the current pre-transport practices (selection of unfit chickens, catching preparations, catching, and crating) for spent hens and broilers by questioning Flemish poultry farmers. The results showed that catching preparations such as an extra selection of chickens unfit for transport was performed by a minority of the poultry farmers, and that layer farmers were less in line with the EU-legislation for water and feed withdrawal than broiler farmers. All birds were caught inverted except for one broiler farmer who used mechanical catching (not yet common in Flanders). Additionally, mechanical catching may involve extra costs, increased biosecurity risks, and specific recommendations for the stable (height and width). The broiler farmers preferred mechanical catching for broiler catchers' well-being, while upright catching was considered better for animal welfare than catching more than three chickens by one/two legs, mechanically, or by wings. Awareness of the need to perform an extra selection by the poultry farmers before catching is required. Preparations like closing areas under the aviary system and removing litter (layers) can further streamline the process and reduce animal suffering.

Abstract: Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokines profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone-deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissues including liver, muscle and adipose tissue. Circulating SIRT1 levels have been found to be reduced in obesity while increased in anorexia nervosa and in patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat amount in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight and 24 with obe-sity). SIRT1 serum levels were higher in LDs as compared with normal weight subjects (mean ± SEM: 4.17 ± 0.48 vs. 2.59 ± 0.20 ng/mL) or subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investi-gation.

Phosphorus (P) is an essential element in food production, but it is often largely unavailable for plants as it persists in soils in immobilized forms. Farmers have been using P fertilizers extensively to overcome this unavailability, leading to the exhaustion of non-renewable deposits of phosphorite, rising fertilizers prices and causing several environmental impacts such as eutrophication. Its large-scale utilization is also inefficient since most of the added P becomes quickly unavailable for the plants. Therefore, farming solutions that improve P uptake, P use efficiency of plants and P mobilization in soils are highly important. In this narrative review, we summarized and explored the link between the Silicon (Si) and P cycles in soils. Silicon is quasi-essential for plants, and it has been established that its presence in soil and uptake by plants has several benefits, especially in toxic and nutrient-deficient conditions. Here, we established that Si in soils can affect crop production in P-deficient conditions through: 1) the pH effect – Si improves organic matter decomposition and decreases Al3+ availability; the Si uptake effect – the deposited Si in the plant improves its photosynthetic performance, improves the root ability to uptake P, improves organic matter decomposition and increases P/Mn ration in plant, improving P use; and 3) the Si soil effect – Si stimulates phosphorite rocks weathering and competes with P for the binding places at the surface of Ak and Fe hydroxides, releasing P into soil solution. This positive effect of Si on P mobilization in soils and consequent use by crops should be further disseminated to farmers and other relevant stakeholders.

This study aimed to identify miRNA editing sites during adipose tissue development in Ningxiang pigs and analyze their characteristics and functions. Based on the small RNA-seq data from subcutaneous adipose tissue samples of Ningxiang pigs at four stages (30, 90, 150 and 210 days), we constructed a developmental atlas of the miRNA editome in adipose tissue of Ningxiang pigs. The characteristics and functions of this editome were further explored through bioinformatics analysis. The findings revealed that a total of 505 miRNA editing sites were identified with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G and G-to-U. Importantly, these four types of miRNA editing exhibited a base preference. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. In the miRNA seed region, a total of 9 miRNA editing sites were identified with significant differences in editing levels (P < 0.05), and located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and enrichment analysis revealed that the editing of miR-497 may potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.

Differential beamforming has attracted much research since it can utilize the array with small aperture size to form frequency-invariant beampatterns and achieve high directional gains. It has recently been applied to the linear loudspeaker array to produce a broadside frequency-invariant radiation pattern. However, designing steerable frequency-invariant beampatterns for the linear loudspeaker array has yet to be explored. This paper proposes a method to design the steerable differential beamformer with the linear loudspeaker array. We first determine the target differential beampatterns according to the desired direction, the main lobe width, and the beampattern order. Then, we transform the target beampattern into the modal domain for representation. The Jacobi-Anger expansion is subsequently used to design the beamformer so that the resulting beam pattern matches the target differential beam pattern. Furthermore, based on the criterion of minimizing the mean square error between the synthesized beam pattern and the ideal one, a multi-constraint optimization problem is formulated to calculate the optimal desired weighting vector. Simulations and experimental results show that the proposed method can achieve steerable frequency-invariant beamforming over 300 Hz – 4 kHz.

Healthcare crises occur occasionally are very disruptive and resource consuming. The Covid-19 pandemic provided an example of inefficient wasteful resource management that would be unsustainable in the long term. This paper presents a framework for sustainable crisis management that will be applicable for future crises. The methodology is also applicable to other pandemics, wars, multi-casualty natural disasters, industrial disasters, etc. Attention focuses on rapid crisis resolution such as lockdowns. Despite unprecedented investments in healthcare, lack of capacity and timeliness are still problems affecting every country, even the wealthier ones. During the Covid19 pandemic, some healthcare systems around the world have collapsed. For example, Brazil, Spain, Italy, and more. This is due to the lack of a clear methodology for handling such crises. This paper presents a resource-based methodology to cope with healthcare crises considering three scenarios: “Peace”, “War” and “Tsunami”. The paper outlines a methodology for identifying the system bottlenecks for coping with the crisis in each scenario by using established simple tools. These tools assure significant resource frugality that will enhance sustainability. The paper also analyses where the system constraint should be and prescribes how to prepare for such scenarios. A large medical center case study demonstrates our approach. During “peace” times, evolutionary strategies should be used exclusively. During “war” times, a hybrid – evolutionary/disruptive (revolutionary) strategy. During the “Tsunami” scenario, one should rely only on the disruptive (revolutionary) strategy. This methodology can be extended to other scenarios and other lines of research.

The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterwards spread on land. In particular, seed size had a pivotal role as for evolutionary success and agronomic trait, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated as for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size, and how developmental processes are influenced by them. Besides, new insights on the genetic-molecular control of this adaptive trait are presented.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Chikungunya is mosquito born disease that is spread across continents. This research provides valuable insights into the potential functional significance of the hydrophobic tail and cysteine-rich regions in E2 proteins. These findings lay the groundwork for future investigations into the specific roles of the C-terminal domain and post-translational modifications, which could ultimately lead to a better understanding of viral mechanisms and potential therapeutic targets.

Cystic fibrosis (CF) diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All the patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants (PVs) such as [c.1521_1523del, p.(Phe508del), and c.3231_3232del, p.(Phe1078Profs*77)]. A targeted search of a dataset of 2,217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings led us to hypothesize a founder effect for the p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican patients with CF, probably through migration from the French-Canadian population in Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.

The paper presents the findings of research on companies in the early stage of development based on the concept of ensuring their sustainability. The starting point is attributes shaping a sustainable model of start-ups. A solution has been proposed and examined that identifies the factors dynamising a business model, which give the company the ability to make fast changes in the configuration of the business model, and that applies stabilizing factors based on the concept of the Triple Bottom Line. The research problem is a response to the phenomena of the bankruptcy of many start-ups that cannot find a way to survive in the long term. The business models of companies in the early stage of development should be designed taking into account the possibility of their dynamic and iterative changes when the earlier assumptions do not work when implemented in practice. A cognitive gap has been observed as the relevant literature does not propose a systemic solution to the problem of instability of the startups viewed from the perspective of the business model concept. The research problem, therefore, is to identify potential new methods to ensure the sustainability of young companies trying to combine aspects dynamising changes in business models, taking into account economic, environmental and social aspects. The findings of research on companies in the early stage of development show that when the methods of increasing the flexibility of the business model are applied and attention is drawn to environmental and social activities and a strong emphasis is put on financial performance, reflecting the expectations of shareholders, the concept of ensuring the sustainability of young companies from the point of view of sustainable business model attributes emerges.

Interspecific competition between mosquito larvae may affects adult vectorial capacity, potentially reducing disease transmission. It also influences population dynamics, cannibalistic and predatory behaviors. However, knowledge of interspecific competition between Ae. aegypti and Anopheles species is limited. The study examined interspecific competition between Ae. aegypti larvae and either An. arabiensis, An. gambiae, or An. funestus on individual fitness in semi-field settings. The experiments involved density combinations of 100:100, 200:0, and 0:200 (Ae. aegypti: Anopheles), reared with and without food, in small habitat (8.5 cm height × 15 cm diameter) with 0.5 litre and medium habitats (15 cm height × 35 cm diameter) with 1 litre of water. The first group received Tetramin® fish food (0.02 g), while the second group was unfed to assess cannibalism and predation. While, interspecific competition affected both genera, Anopheles species experienced greater effect, with reduced survival and delayed development, compared to Ae. aegypti. The mean wing lengths of all species were significantly small in small habitats in mixed population (p < 0.001). The presence of food reduced cannibalism and predation compared to its absence. These interactions have implications for diseases transmission dynamics and can serve as biological indicators to signal the impacts of vector control interventions.

Additive Manufacturing (AM) methods are increasingly beign abopted in the industry as an alternative for mass production. In particular, Fused Deposition Modeling (FDM) technology is leading the way in this field. However, the adhesion of layers in products produced using FDM technology is an important issue. These products are particularly vulnerable to forces acting parallel to the layers and specially to impact strength. This study aims to optimize the impact strength against loads acting parallel to the layers (ZX orientation) of PA6, one of the most widely used materials in the industry. This orientation is critical in term of mechanical properties, and the mechanical characteristics are significantly lower compared to other orientation. In this study, filaments containing pure PA6 with 15% short carbon fiber and 30% glass fiber were utilized. Additionally, printing temperature, layer thickness and heat treatment duration were used as independent variables. An L9 orthogonal array was employed in this study, and each experiment was repeated three times to conduct impact strength tests. Characterization, Taguchi optimization, a factor analyses were performed, followed by fracture surface characterization by SEM. As a result, the highest impact strength was achieved with pure PA6 at 8.9 kJ/m2, followed by PA6 GF30 at 8.1 kJ/m2 and the lowest impact strength was obtained with PA6 CF15 at 6.258 kJ/m2. When compared to the literature and manufacturer datasheets, it was concluded that the impact strength values have significantly increased, and the chosen experimental factors and their levels, particularly nozzle temperature, were effective.

Research shows that observers and agents, as key concepts in physics and intelligence science respectively, exhibit profound intrinsic consistency. Based on this understanding, we propose and construct Theory of Universal Intelligent Evolution, known as Omega Theory, which offers an innovative exploration of Theory of Everything (ToE) from the perspective of intelligence science. Within the framework of Omega Theory, this paper unifies the research subjects and dynamic mechanisms of physics and intelligence science, revealing that the intelligence level of the observer is the fundamental source of the differences among classical mechanics, relativity, and quantum mechanics. Furthermore, this paper proposes that core concepts such as subjectivity and objectivity, determinism and uncertainty, as well as time and space, are inherently related to the intelligent state of agents and Universe.Omega Theory consists of three core models: Standard Agent Model, General Model of Agent Evolution, and Intelligent Universe Evolution Model. Standard Agent Model serves as a foundational axiom, defining the unified structure and functional framework of agents, and it is the cornerstone of the theory. Building upon this, we derive General Model of Agent Evolution and Intelligent Universe Evolution Model. Omega Theory posits that the fundamental units of Universe are agents, and that the entire universe is itself an agent. Matter is a special manifestation of agents, and each agent continuously evolves between the states of absolute zero intelligence and omniscience and omnipotence, driven by two intelligent forces that are derived from the theory.To validate this theory, we have designed a thought experiment in the "Experimental Universe 1," where classical mechanics, relativity, and quantum mechanics experiments can be simultaneously conducted. By adjusting the intelligence level of the observer, we observe that different physical theory scenarios emerge in succession as the observer's intelligence level changes.

The use of C-type natriuretic peptide (CNP) in the interaction with the oocyte and in the temporary postponement of spontaneous meiosis resumption has already been well described. However, its action in pre-implantation developmental stage embryos remains to be understood. Thus, our study aimed to detect the presence of the canonical CNP receptor (natriuretic peptide receptor, NPR2) in germinal vesicle (GV), metaphase II (MII), presumptive zygotes (PZ), morula (MO), and blastocyst (BL) stage embryos and, later, to observe possible modulations on the embryos when co-cultured with CNP. In the Experiment I, we detected and quantified the NPR2 on the above-mentioned embryo stages. Following, Experiment II, intended to test different concentrations (100, 200, or 400 nM of CNP) at different times of inclusion in the in vitro culture (IVC; inclusion from the beginning, i.e. day 1, or from day 5). In Experiment III, it was used 400 nM of CNP on day 1 (D1) in the IVC, which did no demonstrate to be embryotoxic, and it showed potentially promising results in blastocyst production rate, when compared to the control. Thus, we analyzed the embryonic development rates of bovine embryos (D7) and hatching kinetics (D7, D8, and D9). Subsequently, morula and blastocyst were collected and evaluated for transcript abundance to competence and quality (apoptosis, oxidative stress, proliferation and differentiation) and lipid metabolism. Differences with probabilities less than P < 0.05, and/or Foldchange (FC) ˃1.5 were considered significant. We demonstrate the presence of NPR2 until the blastocyst development stage when there was a significant decrease in membrane receptors. There was no statistical difference in production rate after co-culture with 400 nM CNP. However, when we evaluated the abundance of morula transcripts, there was an upregulated transcription in ADCY6 (P=0.057), and downregulated transcripts, in BMP15 (P= 0.013), ACAT1 (P= 0.040), CASP3 (P=0.082). In addition, a total of 12 transcriptions in morula presented variation FC ˃1.5. In blastocysts, the treatment with CNP induced upregulation in BID, CASP3, SOX2, HSPA5 transcripts, and downregulation in BDNF, NLRP5, ELOVL1, ELOVL4, IGFBP4, and FDX1 transcripts (FC >1.5). Thus, our study identified and quantified the presence of NPR2 in bovine pre-implantation embryos. Furthermore, 400 nM of CNP in IVC, a concentration not previously described in the literature, modulated some transcripts related to embryonic metabolism and it was not embryotoxic morphologically.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD and identifying potential therapeutic strategies. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 hours post-fertilization. After the exposure, embryos were transferred to fish water and the effects on behavior and neurotransmitters profile were analyzed at both larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. Neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the interest of this model in the study of ASD.

The increasing energy consumption and industrial activities that release carbon dioxide (CO2) emissions into the atmosphere have become one of the most serious environmental issues of today. This article discusses the current status in Azerbaijan regarding the development of effective approaches to reduce carbon emissions and ensure sustainable development, and it proposes relevant strategies for managing the carbon footprint. By exploring the interrelationship between the economy and the environment, it aims to contribute to the formation of more effective policies for managing CO2 emissions in Azerbaijan. According to the results of the econometric model established within the research for the period of 1990-2023, as the Azerbaijan economy grows, per capita CO2 emissions tend to increase, which can be linked to rising industrial activity, energy consumption, and other factors driving economic growth. The presence of a positive long-term relationship between population growth and per capita CO2 emissions can be attributed to higher overall energy consumption, increased demand for goods and services, and rising transportation needs. The strong correlation between economic growth and CO2 emissions suggests that it may be too early to assert the validity of the Kuznets curve for Azerbaijan economy as a developing country.

Orthostatic hypotension (OH) is a condition marked by a significant drop in blood pressure upon standing, resulting from impaired autonomic regulation of vascular tone and blood volume. This study investigates the prevalence, physiological mechanisms, and occupational risk factors for OH among high-risk professions in Nepal, such as traffic police, security guards, and shopkeepers. Using a cross-sectional design, participants were evaluated for blood pressure variability, autonomic function, and fluid balance. The findings reveal a high incidence of OH, linked to reduced baroreceptor sensitivity and impaired sympathetic activation due to prolonged standing and inadequate hydration. This study highlights the need for tailored clinical interventions and workplace modifications to mitigate OH in vulnerable occupational groups.

Until the 1950s, developmental dyslexia was defined as a hereditary visual disability, selectively affecting reading without compromising oral or non-verbal reasoning skills. This changed radically after the development of the phonological theory of dyslexia; this not only ruled out any role for visual processing in its aetiology, but also cast doubt on the use of discrepancy between reading and reasoning skills as a criterion for diagnosing it. Here I argue that this theory is set at too high a cognitive level to be explanatory; we need to understand the pathophysiological visual and auditory mechanisms that cause children’s phonological problems. I discuss how the ‘magnocellular theory’ attempts to do this in terms of slowed and error prone temporal processing which leads to dyslexics’ defective visual and auditory sequencing when attempting to read. I attempt to deal with the criticisms of this theory and show how it leads to a number of successful ways of helping dyslexic children to overcome their reading difficulties.

The working environment of mining electric locomotives is wet and muddy coal mine 1 roadway. There may be idling or slipping between the wheels and rails of mining electric locomotives 2 due to low friction between the wheel and rail and insufficient utilization of creep rate. Therefore, it 3 is necessary to control the creep rate within a reasonable range. In this paper, the autonomous control 4 algorithm for mining electric locomotives based on improved ε-greedy is theoretically proven to be 5 convergent and effective firstly. Secondly, after analyzing the contact state between the wheel and rail 6 under wet and slippery road conditions, it was concluded that the value of creep rate is an important 7 factor affecting the autonomous driving of mining electric locomotives. Therefore, the autonomous 8 control method for mining electric locomotives based on creep control is proposed in this paper. 9 Finally, the effectiveness of the proposed method was verified through simulation. The problem of 10 wheel slipping and idling caused by insufficient friction of mining electric locomotives in coal mining 11 environments is effectively suppressed. Autonomous operation of vehicles with optimal driving 12 efficiency can be achieved through quantitative control and utilization of the creep rate between 13 wheels and rails

Introduction: Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the “hunger hormone”, it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential for developing comprehensive strategies for optimizing long-term outcomes for candidates for bariatric surgery, especially sarcopenic patients. Methods: This was a randomized controlled study with two groups (n=22). The patients in both groups have obesity and sarcopenia. A Roux-en-Ygastric bypass (RYGB) procedure was performed in all patients. The intervention group participated in a structured exercise program three times per week beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after completion of the exercise program. The control group received the usual standard of care and was assessed similarly. Results: After surgery, weight, BMI and lean mass decreased significantly in both groups from baseline to the second assessment. Leptin was not significantly different from baseline to the second assessment in the physical exercise group but was significantly lower in the control group (p=0.05). Ghrelin increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between leptin and sarcopenia parameters (muscle strength and mass), as well as with bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-score (p<0.05). Conclusion: Exercise has been shown to have a significant effect on leptin and ghrelin levels after bariatric surgery. By incorporating regular physical activity into their lifestyle, bariatric patients can optimize their weight loss outcomes and improve their overall health. After the physical exercise protocol, patients in the intervention group revealed more established leptin levels, which may indicate a protected pattern concerning decreased leptin levels. An unfavorable profile was evidenced, according to which greater weight loss, sarcopenia, and osteoporosis were associated with lower leptin levels.

Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for a wide variety of diseases, offering the potential to modulate gene expression with a high degree of specificity. These small, synthetic nucleic acid-like molecules provide unique advantages over traditional pharmacological treatments, including the ability to target previously "undruggable" genes. Despite this promise, several biological barriers severely limit their clinical efficacy Upon administration, ASOs primarily enter cells through endocytosis, becoming trapped inside membrane-bound vesicles known as endosomes. Studies estimate that only 1-2% of ASOs successfully escape endosomal compartments to reach the cytosol, and ultimately the nucleus, where they bind target mRNA and exert their therapeutic effect. Endosomal entrapment and inefficient nuclear localization are therefore critical bottlenecks in the therapeutic application of ASOs. This review explores the current understanding of endosomal escape, and nuclear transport of ASOs. Furthermore, we examine strategies aimed at overcoming these challenges, including the use of endosomal escape agents, peptide-ASO conjugates, non-viral delivery vehicles, and nuclear localization signals. By improving both endosomal escape and nuclear localization, significant advances in ASO-based therapeutics can be realized, ultimately enhancing their potency and expanding their clinical utility

The gut, often referred to as the "second brain," has significant contributions in the maintaining of the good bacteria contribute enormous role such as digestion, produce essential vitamins, support the immune system, and protect against harmful bacteria. The beneficial flora including Akkermansia muciniphila, Adlercreutzia equolifasciens, Barnesiella, Christensenella minuta, and Oxalobacter formigenes, along with their derived bioactive metabolites emerged as a key player in maintaining host metabolic and immune health. Dietary choices such as blending of prebiotic, fermented, symbiotic, anti-inflammatory foods, and secondary metabolites from a wide variety of plants and fruits promotes the diversity, composition, and stability of beneficial intestinal microbes. The colourful plant foods rich in phytochemicals bioactive compounds such as carotenoids, flavonoids, polyphenols, alkaloids, anthocyanins, and capsaicin offer a wide array of unique properties such as analgesics, antioxidants, anti-inflammatory, antimicrobials effect and promoting the abundance of beneficial gut bacteria and their bioactive metabolites confer numerous health-promoting effects. Here, we present knowledge about most beneficial gut bacteria and their derived metabolites in terms of their sources and health benefits. Finally, we discuss best foods that skew towards promoting healthy intestinal microbes.

Chronic mountain sickness (CMS) poses a significant health risk to individuals who rapidly ascend to high altitudes, potentially endangering their lives. Inorganic nanoparticles offer an effective means of transporting and delivering drugs, protecting nucleic acids from nuclease degradation, and mediating the expression of target genes in specific cells. These nanoparticles are almost non-toxic, easy to prepare and store, possess a large surface area, exhibit good biocompatibility and degradability, and maintain good stability. They can be utilized in the treatment of CMS to enhance the therapeutic efficacy of drugs. This paper provides an overview of the impact of inorganic nanomaterials on CMS, discussing their roles as nanocarriers and their potential in CMS treatment. It aims to present novel therapeutic strategies for the clinical management of CMS and summarizes the relevant pathways through which nanomaterials contribute to plateau disease treatment, providing a theoretical foundation for future clinical research.

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (&lt;20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Insurance companies need to calculate solvency capital requirements in order to ensure that they can meet their future obligations to policyholders and beneficiaries. The solvency capital requirement is a risk management tool essential for, when extreme catastrophic events occur, resulting in a high number of possibly interdependent claims. This paper studies the problem of aggregating the risks coming from several insurance business lines and analyses the effect of reinsurance in the level of risk. Our starting point is to use a Hierarchical Risk Aggregation method, which was initially based on 2-dimensional elliptical copulas. We then propose the use of copulas from the Archimedean family and a mixture of different copulas. Our results show that a mixture of copulas can provide a better fit to the data than an individual copula and consequently avoid over or underestimating of the capital requirement of an insurance company. We also investigate the significance of reinsurance in reducing the insurance company’s business risk and its effect on diversification. The results show that reinsurance does not always reduce the level of risk, but can also reduce the effect of diversification for insurance companies with multiple business lines.

In GNSS/IMU integrated navigation systems, factors such as satellite occlusion and non-line-of-sight conditions can lead to degradation of satellite positioning results, Subsequently affecting the overall accuracy of the integrated navigation system. To address this issue and ef-fectively utilize historical pseudorange information from satellites, this paper proposes a graph optimization-based GNSS/IMU model with virtual constraints. These virtual constraints are con-structed using satellite ‘s position from previous time step, the rate of change of pseudoranges, and ephemeris data. This virtual constraint can serve as an alternative solution for individual satellites in case of signal anomalies, ensuring the integrity and continuity of the graph optimi-zation model. Additionally, this paper conducts an analysis of the graph optimization model constructed using these virtual constraints, comparing it with traditional integrated navigation graph optimization model, and analyzes and reconstructs the marginalization process based on these virtual constraints. The experimental results, compared with tightly coupled Kalman fil-tering and the original graph optimization method on a set of real-world data, demonstrate that the introduction of virtual pseudoranges maintains high positioning accuracy. The RMSE error between it and the original graph optimization remains within 5%, affirming the high feasibility of this approach.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

This research paper examines a cosmological model in flat space-time via $f(R,G)$ gravity where $R$ and $G$ are respectively the Ricci scalar and Gauss-Bonnet invariant. Our model assumes that $f(R,G)$ is an exponential function of $G$ combined with a linear combination of $R$. We scrutinize the observational limitations under a power law cosmology that relies on two parameters - $H_0$, the Hubble constant, and $q$, the deceleration parameter, utilizing the 57-point $H(z)$ data, 8-point BAO data, 1048-point Pantheon data, joint data of $H(z)$ + Pantheon, and joint data of $H(z)$ + BAO + Pantheon. The outcomes for $H_0$ and $q$ are realistic within observational ranges. We have also addressed Energy Conditions, $Om(z)$ analysis and cosmographical parameters like Jerk, Lerk and Snap. Our estimate of $H_0$ is remarkably consistent with various recent Planck Collaboration studies that utilize the $\Lambda$CDM model. According to our study, the power law cosmology within the context of $f(R,G)$ gravity provides the most comprehensive explanation for the important aspects of cosmic evolution.

Abstract: Remarkably, the p53 transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify p53‑dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that p53‑dependent transcription is first detected in late mouse blastocysts, that p53 activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on p53. Furthermore, p53 does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, p53 accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are p53-independent. In embryonic fibroblasts, p53 induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.

Macro-autophagy (autophagy hereafter) is an evolutionarily conserved cellular process that has long been recognized as an intracellular mechanism for maintaining cellular homeostasis. It involves the formation of a membraned structure called the autophagosome, which carries cargo that includes toxic protein aggregates and dysfunctional organelles to the lysosome for degradation and recycling. Autophagy is primarily considered and studied as a cell-autonomous mechanism. However, recent studies have illuminated an underappreciated facet of autophagy, i.e., non-autonomously regulated autophagy. Non- autonomously regulated autophagy involves the degradation of autophagic components, including organelles, cargo, and signaling molecules, and is induced in neighboring cells by signals from primary adjacent or distant cells/tissues/organs. This review provides insight into the complex molecular mechanisms governing non-autonomously regulated autophagy, highlighting the dynamic interplay between cells within tissue/organ or distinct cell types in different tissues/organs. Emphasis is placed on modes of intercellular communication that include secreted molecules, including microRNAs, and their regulatory roles in orchestrating this phenomenon. Furthermore, we explore the multidimensional roles of non-autonomously regulated autophagy in various physiological contexts, spanning tissue development and aging, as well as its importance in diverse pathological conditions, including cancer and neurodegeneration. By studying the complexities of non-autonomously regulated autophagy, we hope to gain insights into the sophisticated intercellular dynamics within multicellular organisms, including mammals. These studies will uncover novel avenues for therapeutic intervention to modulate intercellular autophagic pathways in altered human physiology.

High rates of phosphorus (P) currently being applied to soils for the production of vegetables in the Mekong Delta, Vietnam has led to the concern of its negative effect on the economics and the environment. This research presents a comprehensive study on the determination of P supplying capacity in this region of Vietnam to examine the possibility of reducing P fertilizer input. One hundred twenty (120) soil samples were collected to evaluate total P and Bray 1 available P in the soils. Phosphorus maximum sorption, degree of P saturation, P release, and the effect of P fertilizer on corn (Zea mays L.) yield in greenhouse and fields were also determined. Total P concentrations of 56.7% soil samples evaluated yielded high P concentrations (>560 mg P/kg), while 74.2% of the samples had high Bray 1 available P concentrations (>20 mg P/kg soil). Maximum P sorption ranged from 149 to 555 mg P/kg soil, respectively and has negative correlation to available P (r = - 0.63*), degrees of P saturation ranged from 0.63 to 5.46% correlated to available P (r = 0.98**) and maximum P release ranged from 1.2 to 61.9 mg P/kg soil, respectively correlated to available P (r = 0.96**). Corn grown in soils with available P concentrations >15 mg P/kg did not respond to P fertilizer in greenhouse or field experiments. We conclude that many farmers in this region can reduce P fertilizer input, thus increasing their profits and reducing negative environmental impacts associated with excess soil P for sustainable agriculture.

Rice yield underperformance coupled with production instability in Odisha state of India is primarily due to low irrigation potential, the spatiotemporal disparity in rainfall pattern and relentless confrontation with biotic and abiotic stresses. System of Rice Intensification (SRI) was introduced in the state with the promises of higher production horizon. However, the present scenario of patchy adoption pattern has necessitated comprehensive study on dynamics and determinants of adoption of SRI. We found that, 57 percent farmers continued SRI, 28 percent discontinued and rest were practicing conventional rice farming. The focused group discussion among the farmers helped us to triangulate the determinants of SRI adoption.The increased SRI area allocation was observed at the expense of reduced number of adopting farmers. Economic scarcity of skilled labour, difficulties in transplantation and mechanical weeding, low irrigation potential and poor on-farm water management were major constraints in SRI practice. Farmers’ compliance in following different resilient SRI components that also varied spatiotemporally has resulted in realized incremental yield. SRI was proved to be resilient to severe drought during 2015-16 and yielded 27 percentage higher than conventional one with considerable decline in hazardous chemicals usage. Farmers’ decision on SRI adoption/discontinuation was analysed using probit regression analysis. The results indicated that, active social involvements of NGOs, on-farm training and demonstrations, and realized incremental rice income influenced SRI adoption. On the other hand, SRI area expansion hindered mainly because of infeasible land topography, area saturation and lack of farmers’ interest. The sustainability index was developed to analyse SRI’s performance to other conventional methods at farm level. Comparatively, SRI adopters benefitted in terms of incremental net return by enhancing ecological balance and sustained productivity of soil, use of eco-friendly and own farm inputs. Nonetheless, higher women labour displacement observed under SRI can be curtailed by providing training to young farm women.

Background: Urinary tract infections (UTI) are a significant health concern, particularly in women, with almost half of them experiencing at least one UTI in their lifetime. This problem is further compounded by the high recurrence rate within 6-12 months. Postmenopausal women are especially vulnerable to recurrent UTI due to the natural decline in estrogen levels, which alters the urogenital epithelium and subsequently affects the urogenital microbiome. Methods: This study included 674 female patients that were admited at "Dr. Carol Davila" Central Military Emergency University Hospital in Bucharest over a period of 3 years. Results: Of the 674 women with urinary tract infection, 435 (79.3%) had more than one positive culture, and 239 (35.4%) experienced at least one recurrent urinary tract infection 6-12 months after the initial diagnosis. The mean age of women with urinary tract infection was 63 (± 15.61 years). Recurrent urinary tract infections were most prevalent in those aged 65-80 years (52%). Escherichia coli was detected in 71% of the positive cultures. Conclusions: The management of recurrent urinary tract infections in women presents a complex challenge that necessitates a multifaceted approach. The emerging understanding of the urobiome and its role in bladder health offers promising avenues for developing targeted interventions. As research in this field advances, it is imperative to integrate these new insights into clinical practice to balance traditional antibiotic treatments with novel strategies that consider the intricate microbial ecosystem of the urinary tract.

The Kraaipan and Amalia greenstone belts in South Africa occurs in the western part of the Kaapvaal Craton. The two belts stretch discontinuously in an approximately north-south orientation over a distance of about 250 km from southern Botswana in the north to the Vaal River near Christiana in the south and are separated by a distance of about 90 km. Gold mineralization is hosted in banded iron-formation at both the Kalahari Goldridge deposit (Kalgold) in the Kraaipan greenstone belt in the north, and the Amalia deposit in the Amalia greenstone belt in the south, with the mineralization associated with quartz-carbonate veins. The footwall of these deposits is generally composed of mafic volcanic schist and hanging wall consisting of graywackes, schist and shale units. The Kalgold and Amalia gold deposits show some variation in the redox condition of the mineralizing system, mineralization temperatures and fluid chemistry. The ore mineral assemblage is characterized by magnetite-pyrrhotite-pyrite at Kalgold, which is indicative of reducing conditions, and magnetite-hematite-pyrite assemblage at Amalia that suggest a relatively oxidizing environment. Average mineralizing temperatures determined from chlorite geothermometry were relatively higher at the Kalahari Goldridge deposit ranging from 350 to 400oC compared to 335 to 370oC (mean, 352± 18, n = 113) at Amalia. The composition of the fluids derived from fluid inclusions are indicative of low salinity H2O-CH4-CO2-rich fluids at Kalgold against relatively H2O-CO2-rich fluids at Amalia. Evidence from strontium-carbon-oxygen isotopic ratios from carbonates suggests differences in redox conditions in the deposits could be attributed to different flow pathways by the evolving fluid from a common source (with minimum 87Sr/86Sr=0.70354) to the sites of gold deposition; with significant ore fluid interaction with thick sequence of carbonaceous meta-pelitic rock units at the Kalahari Goldridge deposit, that is absent in the Amalia deposit.

Device to Device (D2D) is a pivotal technology in the next generation of communication, allowing for direct task offloading between mobile devices (MDs) to improve the efficient utilization of idle resources. This paper proposes a novel algorithm for dynamic task offloading between active MDs and idle MDs in the D2D-MEC (Mobile Edge Computing) system by deploying multi-agent deep reinforcement learning (DRL) to minimize the long-term average delay of delay-sensitive tasks under deadline constraints. Our core innovation is a dynamic partitioning scheme for idle and active devices in the D2D-MEC system, accounting for stochastic task arrivals and multi-time-slot task execution, which has been insufficiently addressed in existing literature. We adopt a queue-based system to formulate a dynamic task offloading optimization problem. To address the challenges of large action space and coupling of actions across time slots, we model the problem as a Markov Decision Process (MDP) and perform the multi-agent DRL through Multi-Agent Proximal Policy Optimization (MAPPO). We employ a centralized training with decentralized execution (CTDE) framework to enable each MD to make offloading decisions solely based on its local system state. Extensive simulations demonstrate the efficiency and fast convergence of our algorithm. In comparison with the existing sub-optimal results deploying single-agent DRL, our algorithm reduces the average task completion delay by 11.0% and the ratio of dropped tasks by 17.0%.

Background: Nanotechnology has emerged as a promising field of study, aiming to revolutionize healthcare through the innovative development of drugs, diagnostic tools, and medical devices. As a result, healthcare professionals in training are constantly faced with the challenge of understanding and applying these emerging technologies. The objective of this study is to determine the factors to consider for including the teaching of nanotechnological tools in medical specialty postgraduate programs. Methods: A study based on the Nominal Group Technique (NGT) was conducted to identify the factors that promote and hinder the implementation of nanotechnology in certain postgraduate programs where nanotechnology is employed, such as Internal Medicine, Critical Care Medicine, Family Medicine, and Clinical Pharmacology at the School of Medicine of Universidad de La Sabana. A framework analysis was used to analyze the collected data. Results: Based on the two research questions, several aspects were identified for the inclusion of nanotechnology in the medical practice of specialties. Key challenges include lack of knowledge and resource availability, misinformation, and lack of knowledge, as well as paradigmatic analysis as the main obstacles to the use of nanotechnology. Conclusions: The findings provide a first-time study on nanotechnology curricula within medical specialty programs in Colombia, with potential extrapolation to similar situations in other medical schools.

European strategic policy directions towards a sustainable blue economy have strengthened interest in maritime investments, thus increasing sectoral competition for marine space. Emerging repercussions out of such a rising interest need to be handled by Marine Spatial Planning (MSP) as a means for: properly allocating marine space to diverse uses; managing conflicts and promoting synergies among them; and pursuing a multi-use perspective of this space. A critical stage of each MSP exercise is the exploration of land-based spatial/developmental directions and their current or potential repercussions in the marine environment in order for constraints but also perspectives in policy choices/maritime uses in the MSP context to be featured; and attainment of a successful coherence or coordination between land and marine spatial/developmental policies to be ensured, by analyzing Land-Sea-Interaction (LSI) and embedding it in the MSP. The latter is the focus of this paper aiming to illuminate critical issues emerging from land-based (terrestrial) policy frameworks for feeding MSP endeavors; and is accomplished in the Northern Aegean Sea, Greece. Towards this end, a multilevel approach is adopted, delving into diverse policy contexts at the local, regional and national/European level and aiming to attain more informed MSP decisions in the specific study region.

This paper analyzes and compares models for predicting average magnet losses in interior permanent-magnet motors with fractional-slot concentrated windings due to harmonics in the armature reaction (assuming sinusoidal phase currents). Particularly, loss models adopting different formulations and solutions to the Helmholtz equation to solve for the eddy currents are compared to a simpler model relying on an assumed eddy-current distribution. Boundaries in terms of magnet dimensions and angular frequency are identified (numerically and using an identified approximate analytical expression) to aid the machine designer whether the more simple loss model is applicable or not. The assumption of a uniform flux-density variation (used in the loss models) is also investigated for the case of V-shaped and straight interior permanent magnets. Finally, predicted volumetric loss densities are exemplified for combinations of slot and pole numbers common in automotive applications.

The production of recombinant proteins in Escherichia coli is often challenged by cytoplasmic expression due to proteolytic degradation and inclusion body formation. Extracellular expression can overcome these problems by simplifying downstream processing and improving protein yields. This study aims to compare the efficiency of two Bacillus subtilis chitosanase signal peptides in mediating extracellular secretion in E. coli. We identified a naturally occurring mutant signal peptide (mCsn2-SP) from B. subtilis CH2 chitosanase (CH2CSN), which is characterized by a deletion of six amino acids in the N-region relative to the signal peptide (Csn1-SP) from B. subtilis CH1 chitosanase (CH1CSN). The CH1CSN and CH2CSN genes were cloned into the pET-11a vector and protein secretion was evaluated in E. coli BL21(DE3) host cells. Expression was induced with 0.1 mM and 1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) at 30°C for one and three days. CH2CSN showed higher secretion levels compared to CH1CSN under all experimental conditions, especially with 0.1 mM IPTG induction for 3 days, which resulted in a 2.37-fold increase in secretion. Furthermore, it was demonstrated that mCsn2-SP is capable of secreting human Cu,Zn-superoxide dismutase (hSOD) in E. coli BL21(DE3) and successfully translocating it to the periplasmic region. This study represents the inaugural investigation into the utilisation of a naturally modified signal peptide, thereby corroborating the assertion that signal peptide deletion variants can influence protein secretion efficiency. Furthermore, the findings substantiate the proposition that such variants can serve as a viable alternative for the secretion of heterologous proteins in E. coli.

In this paper, we introduce the (ρ,q)-analogue of the p-adic factorial function. By utilizing some properties of (ρ,q)-numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic (ρ,q)-gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2. We also derive more representations of the p-adic (ρ,q)-gamma function in general case. Moreover, we consider the p-adic (ρ,q)-Euler constant derived from the derivation of p-adic (ρ,q)-gamma function at x = 1. Furthermore, we provide a limit representation of aforementioned Euler constant based on (ρ,q)-numbers. Finally, we consider (ρ,q)-extension of the p-adic beta function via the p-adic (ρ,q)-gamma function and we then investigate various formulas and identities.

This research ventures into the critical public health challenge of childhood obesity by exploring the dynamic interplay between psychological well-being and Body Mass Index (BMI) throughout various developmental stages of childhood. It delves into how emotional regulation, attachment dynamics, and social relationships correlate with obesity from early childhood to adolescence. Highlighting key findings, such as the negative correlation between psychological resilience and higher BMI in young children, the impact of social relationships on obesity risk during pre-adolescence, and the link between adaptive emotional strategies and higher BMI in adolescents, this study brings to the fore the nuanced relationship between psychological factors and obesity. Utilizing the interdisciplinary process of bioinformatics, this research synergizes psychometric and biomedical data to unearth psychological markers critical for crafting targeted, age-appropriate interventions. This study advocates for a holistic healthcare approach, emphasizing the integration of psychological support within obesity prevention and management strategies, thereby underscoring the indispensable role of psychological factors in the fight against childhood obesity. The application of bioinformatics methods to analyze complex datasets demonstrates how collaboration across medical specialties can enrich our understanding and response to childhood obesity, contributing significantly to the development of comprehensive, bioinformatics-enhanced healthcare solutions.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

Aluminum (Al) toxicity and low phosphorus availability (LP) are the top two co-existing edaphic constraints limiting agriculture productivity in acid soils. Plants have evolved versatile mechanisms to cope with the two stresses alone or simultaneously. However, the specific and common molecular mechanisms, especially those on flavonoids and carbohydrate metabolism, are still unclear. Laboratory studies were conducted on two wheat genotypes, Fielder (Al-tolerant and P-efficient) and Ardito (Al-sensitive and P-inefficient), exposed to 50 μM Al and 2 μM Pi (LP) in hydroponic solutions. After 4 days of stress, wheat roots were analyzed via transcriptomic and targeted metabolomic techniques. A total of 2296 differentially expressed genes (DEGs, 1535 up and 761 down) under Al and 3029 DEGs (1591 up and 1438 down) under LP were identified in Fielder. Similarly, 4404 DEGs (3191 up and 1213 down) under Al and 1430 DEGs (1176 up and 254 down) under LP were identified in Ardito. The GO annotation analysis results that 4079 DEGs annotated to the metabolic processes term. These DEGs were significantly enriched in the phenylpropanoid, flavonoid, flavone and flavonol biosynthesis, and carbohydrate metabolism pathways by performing the KEGG enrichment analysis. The targeted metabolome analysis detected 19 flavonoids and 15 carbohydrate components in Fielder and Ardito under Al and LP. More responsive genes and metabolites were involved in flavonoid metabolism under LP than Al in the Fielder, while an opposite trend in the Ardito. In the carbohydrate metabolism pathway, the genes and metabolites were higher in Fielder than in Ardito. The combined transcriptome and metabolome analysis revealed that the flavonoid and carbohydrate genes and metabolites differed between Fielder and Ardito under Al and LP, which may be an important reason for Fielder’s high Al and LP resistance. The results of this study lay a foundation for pyramiding genes and breeding multi-resistance varieties.

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

In this paper, we introduce a new class of $(p,q)$-analogue type of Fubini numbers and polynomials and investigate some properties of these polynomials. We establish summation formulas of these polynomials by summation techniques series. Furthermore, we consider some relationships for $(p,q)$-Fubini polynomials associated with $(p,q)$-Bernoulli polynomials, $(p,q)$-Euler polynomials and $(p,q)$-Genocchi polynomials and $(p,q)$-Stirling numbers of the second kind.

The goal is the optimal synthesis of the parameters of the control law for a nonlinear satellite attitude control system under constraints related to the saturation effect of reaction wheels. The maximum stability degree of the control system is considered as a criterion for the optimality of the parameters of the control law, and the absolute values of the control torques and angular velocities of the reaction wheels, achievable within the limits of the physical characteristics of the drives, are considered as constraints. The solution to the optimal synthesis problem is based on the transformation of the nonlinear control system model into a linear model, within the framework of the problem of global asymptotic stability of the control system is also guaranteed. The problem is decomposed into a subproblems of obtaining the optimal transient process shape in the control system and considering the constraints. A method of synthesizing the optimal transient process shape based on the criterion of maximum stability degree had been developed. An analytical method of determining the optimal values of the control law parameters, based on decomposing the normalized characteristic polynomial in the linear model into three identical factors had been proposed. A method with regards to the constraints of the control torque and angular speed of the reaction wheels, based on transitioning from relative to real time is developed. An algorithm for calculation of the transition scale from relative to real time, ensuring the fulfillment of all constraints in the optimal synthesis problem, is proposed. An example demonstrating the efficiency and simplicity of the proposed methods and algorithm for targeted selection of technical characteristics of the control system, considering the maximum absolute values of angular speeds and control torques of the reaction wheels, is provided.

The species and bio-availability of phosphorus (P) in primary, secondary and digested sludge were fractionated and further analyzed in this study. Results showed that inorganic P (IP) was the primary P fraction in the secondary sludge and digested sludge, in which non-apatite IP (NAIP) amounted to 91.6% and 69.3% of IP, respectively. Organic P (OP), accounting for about 71.7% of total P (TP), was the dominant P composition in primary sludge. The content of bio-available P was about 9.7, 43.4, 29.8 mg-P/g-TS in primary sludge, secondary sludge and digested sludge, respectively, suggesting secondary sludge is the optimal choice when land application of sewage sludge is taken into consideration, followed by digested sludge and primary sludge. Polyphosphate and orthophosphate, comprising approximately 54.3% and 89.2% of TP, was the dominant P species in the secondary sludge and digested sludge, respectively. Monoester-P (54.6% of TP in extract) and diester- P (24.1%) were identified as OP species in primary sludge by Phosphorus-31 nuclear magnetic resonance (31PNMR). The present results would be helpful for P recovery and recycle from sewage sludge in wastewater treatment plant.

Recent studies with ApoE knockout (ApoE-/-) mice deficient for PACAP (pituitary adenylate cyclase-activating polypeptide) or its receptor PAC1 provide evidence for a possible involve-ment of immune- and vasoregulatoy PACAP signaling at the PAC1 receptor in atherogenesis and plaque associated vascular inflammation. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE-/- atherosclerosis model for possible anti-atherogenic effects. Adult male ApoE-/- mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treat-ed with Maxadilan, M65 or Sham. Effects of treatment on atherosclerotic plaques, lumen stenosis, apoptosis and pro-inflammatory signatures were analyzed in the brachiocephalic trunk (BT). The percentage of Maxadilan treated mice exhibiting plaques under SC and CED was lower than that of Sham or M65 treatment indicating opposite effects of Maxadilan and M65. Maxadilan ap-plication inhibited lumen stenosis under SC and CED compared to Sham. In spite of significantly increased cholesterol levels, lumen stenosis of Maxadilan-treated mice was similar under CED and SC. In contrast, M65 under SC or CED did not reveal a significant influence on lumen steno-sis. Maxadilan significantly reduced the TNF-α+ area in the plaques under CED, but not under SC. In contrast, the IL-1β+ area was reduced after Maxadilan treatment under SC, but remained unchanged under CED compared to Sham. Maxadilan reduced the caspase-3+ area in the media under both SC and CED without affecting lipid content in plaques. Despite persisting hypercholesterolemia, Maxadilan reduces lumen stenosis, apoptosis and TNF-α driven inflammation. Our data suggest that Maxadilan provides atheroprotection by act-ing downstream of cholesterol-induced vascular inflammation. This implicates the potential of PAC1-specific agonist drugs against atherosclerosis even beyond statins and PCSK-9.

The lightweight and displacement-stable design of the mechanical support structure within the APTS (Acquisition, Pointing, and Tracking System) is crucial for enhancing the payload capacity of remote sensing, satellite communication, and laser systems, while still meeting specified functional requirements. This paper adopts the Solid Isotropic Material with Penalization (SIMP) method to investigate the structural topology optimization of the L-shaped bracket in the APTS, aiming to minimize structural compliance while using volume, key point displacement, and maximum stress as constraints. In the optimization model, differences in the topology of the L-shaped bracket structure are explored to minimize structural compliance, which is done under volume, key point displacement, and stress constraints, the results are compared with the initial reinforced structure. The innovative L-shaped bracket structure obtained through topology optimization uses significantly less material than the initial reinforced design, while still meeting the displacement and stress constraints. After smoothing, rounding, and finite element analysis, the displacement and stress performance of the optimized L-shaped bracket structure satisfies the set constraints. The method proposed in this paper offers an innovative solution for the lightweight design of mechanical support structures in APTS, with significant engineering application potential.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanism by which spiders respond to heavy metals at the molecular level. In this study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. Ultimately, 3450 cDNA simple sequence repeats were identified and validated as potential molecular markers in the unigenes. A total of 2939, 2491 and 3759 DEGs were detected among the three libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanism underlying spiders' responses to heavy metal stress.

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possible due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore playing a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed, and at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.

The voice contains elementary social communication cues, conveying speech, as well as paralinguistic information pertaining to the emotional state and the identity of the speaker. In contrast to vocal-speech and vocal-emotion processing, voice-identity processing has been less explored. This seems surprising, given the day-to-day significance of person recognition by voice. A valuable approach to unravel how voice-identity processing is accomplished is to investigate people who have a selective deficit in recognising voices. Such a deficit has been termed phonagnosia. In the present chapter, we provide a systematic overview of studies on phonagnosia and how they relate to current neurocognitive models of person recognition. We review studies that have characterised people who suffer from phonagnosia following brain damage (i.e. acquired phonagnosia) and also studies, which have examined phonagnosia cases without apparent brain lesion (i.e. developmental phonagnosia). Based on the reviewed literature, we emphasise the need for a careful behavioural characterisation of phonagnosia cases by taking into consideration the multistage nature of voice-identity processing and the resulting behavioural phonagnosia subtypes.

The main objective of the present study is to demonstrate the possibility of actively influencing the position of the bow shock wave and the main parameters of supersonic flow over a blunt body by organizing a gas discharge near the front surface, in the region between the body and the bow shock wave. The research is carried out using both experimental and numerical methods. The working gas was xenon. It is shown that the steady bow shock wave stand-off distance along with the current and power of the discharge, is associated with the change in the adiabatic index of the plasma created by the discharge, which, in turn, is determined by the plasma parameters, such as the degrees of nonequilibrium and the degree of ionization. It is shown that the adiabatic index with the power supplied to the impact zone in the range of 30-120 kW can both increase and de-crease in the range of 1.25-1.288. The study of the discharge created plasma zone was conducted and the correspondence between the discharge current and power, and the average parameters in the plasma zone created by the discharge is presented. A good agreement between the numerical and experimental data was shown. The results may be useful in developing control systems for high-speed civil aircrafts.

Objective: To explore the acceptability and feasibility of conducting comprehensive, community-based, hy-brid (in-person and virtual) mental health screening and feedback with diverse youth in the community. Methods: The Screening and Support for Youth intervention provides comprehensive assessment and thera-peutic feedback in community settings including symptoms, diagnoses, functional impairment, suicide, and clinical risk. Symptom severity, seven diagnoses and suicidality were assessed with the Kiddie Computer-ized Adaptive Test. Functional impairment was evaluated by youth self-report on the Weiss Functional Im-pairment Rating Scale. Measures were scored according to nationally developed norms and an algorithm was developed to aggregate symptoms and functioning to determine clinical risk. The results were discussed with participants in a motivational interview to promote insight and engagement in an online intervention. Results: Methodological innovations included using a QR code for recruitment, integrated in-person and virtual participation, and expansion from in-person recruitment within the schools to virtual engagement with youth throughout the community. The final sample included disproportionately more Black or African American and Hispanic youth as compared to school and community statistics, suggesting that hybrid re-search may facilitate recruitment of diverse populations. Qualitative interviews indicated that the screening and feedback raised youth awareness of their wellbeing and/or distress, its impact on their functioning, and engagement with options for improving wellbeing. Conclusion: Hybrid research, developed as a necessity during the pandemic, proved advantageous to the feasibility and acceptability of community-based recruit-ment of at risk, minoritized youth.

Standard Model is well-performing under the three-generation, but in the wake of more physics, fourth-generation leptons and quarks are introduced. In this paper, We will be reviewing various constraints surrounding quarks and leptons of 4th Generation and tried to show the importance of quarks to understand the baryogenesis. We talked about, reviewed existing parameters and set the updated lower limits of t’ and b’ by analysis. And predicted an updated version of lower mass bounds quarks and leptons. It is also reviewed that fourth generation leptons are primarily not possible because of disintegration of Higgs Boson and an interpretation has been setup. And in final, we talked about the Unified Standard Model.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

This paper presents the design and analysis of a novel 3-degree-of-freedom (3-DOF) parallel ma-nipulator equipped with self-sensing Ni-Ti (Nitinol) actuators. The manipulator's architecture and mechanical design are elucidated, emphasizing the integration of Nitinol actuators. The self-sensing technique implemented in a previous work was extended to a 20 mm actuator length, and the actuator was used to design the 3 DOF manipulator. Kinematic analyses were conducted to eval-uate the manipulator's performance under various operating conditions. A dynamic model was implemented for the dynamic dimensioning of the actuators, which work synergistically with a bias spring. The manipulator was realized, and a control strategy was implemented. Experimental tests, although documenting some positioning accuracy issues, show the efficacy and potential applica-tions of the proposed manipulator in robotics and automation systems, highlighting the advantages of self-sensing Nitinol actuators in small parallel manipulator designs.

The persistent challenge of IPF, characterized by disease progression and high mortality, underscores the urgent need for innovative therapeutic strategies. We have developed a novel small molecule – catechin derivative ABI-171 – selectively targeting DYRK1A and PIM1 kinases, crucial in the pathogenesis of fibrotic processes. We employed the Bleomycin-induced (intratracheal) mouse model of pulmonary fibrosis (PF) to evaluate the therapeutic efficacy of ABI-171. Mice with induced PF were treated QD with ABI-171 either prophylactically or therapeutically using oral and intranasal routes. Pirfenidone (100mg/kg, TID) and Epigallocatechin gallate (EGCG, 100 mg/kg, QD), a natural catechin currently in a Phase 1 clinical trial, were used as reference compounds. ABI-171, administered prophylactically, led to a significant reduction in hydroxyproline levels and fibrotic tissue formation compared to the control group. Treatment with ABI-171 improved body weight, indicating mitigation of disease-related weight loss. Additionally, ABI-171 demonstrated anti-inflammatory activity, reducing lymphocyte and neutrophil infiltration. In the therapeutic setting, ABI-171, administered 7 days post-induction, reduced mortality rates (P = 0.04) compared with the bleomycin and EGCG control groups. ABI-171 also ameliorated the severity of lung injuries assessed by improved Masson’s trichrome scores when administered both orally and intranasally. ABI-171 significantly decreases bleomycin-induced PF and improves survival in mice, showcasing promising therapeutic potential beyond current medications like Pirfenidone and EGCG for patients with IPF. Based on these results, further studies with ABI-171 are ongoing in preclinical studies.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

Employee turnover is a significant issue for financial institutions, impacting productivity, increasing recruitment costs, and disrupting critical operations. In this project, this study aimed to predict employee turnover using a dataset containing attributes such as employee satisfaction, performance, and tenure. By framing the task as a binary classification problem, this study employed CatBoost and XGBoost, two advanced regression-based algorithms, to develop predictive models. This paper's analysis demonstrated that CatBoost outperformed XGBoost across all evaluation metrics, including MAE, MSE, RMSE, and R², making it the more effective model for predicting turnover in the financial sector. The study highlights key factors contributing to employee attrition, such as job satisfaction, tenure, and promotion opportunities, offering actionable insights for retention strategies. Additionally, by predicting probabilities rather than binary outcomes, this study aims to make more detailed decisions about employee retention. This research provides valuable tools for financial institutions to mitigate the risk of turnover, retain critical talent, and ensure operational continuity.

This article investigates robust optimality and duality for a class of nonsmooth multiobjective programming problems with vanishing constraints under data uncertainty (in short, UNMPVC) via convexificators. Using the properties of convexificators, we introduce generalized standard Abadie constraint qualification (in short, GS-ACQ) for the considered problem UNMPVC. Moreover, we introduce generalized robust version of nonsmooth stationary conditions, namely, weakly stationary point (in short, RW-Stationary), T-stationary point (in short, RT-Stationary), M-stationary point (in short, RM-Stationary) and S-stationary point (in short, RS-Stationary) for UNMPVC. By employing GS-ACQ, we establish that the RS-Stationary is the necessary first-order optimality condition for a local Pareto solution of UNMPVC. Moreover, under generalized convexity assumptions, we establish sufficient optimality criteria for UNMPVC. Furthermore, we formulate the Wolfe-type (in short, WRD) and Mond-Weir-type (in short, MWRD) robust dual models corresponding to the primal problem UNMPVC.

A seroepidemiological study conducted from 2020 to 2022 in Guangzhou, China, aimed to evaluate varicella antibody levels. We measured varicella antibody concentrations using an enzyme-linked immunosorbent assay (ELISA) in a cohort of 3,300 subjects. The mean varicella IgG-specific antibody level was 171.2 mIU/mL (95% CI: 158.9, 184.4), with an overall positivity rate of 67.00% (95% CI: 65.37, 68.60). Varicella antibody levels were found to be influenced by age, vaccination dosage, and history of varicella infection. Notably, antibody concentrations increased with age and the number of vaccinations. Subjects with a vaccination history maintained positive antibody levels six years post-vaccination. We recommend two doses of the varicella vaccine for both children and adults. Before incorporating the varicella vaccine into Guangzhou's routine immunization programs, a comprehensive assessment of disease burden and the economic viability of vaccination strategies is essential.

An analysis of the physical and chemical phenomena accompanying the electrical discharges was carried out, principal factors inactivating microorganisms is studied. Characteristic factors of an electric discharge in cavitation mode providing a synergistic effect when disinfecting water with a discharge and chemical reagents are identified in order of importance. As a result of the integral action of cavitation, the inactivation of bacteria is intensified both due to the emergence of chem-ically active particles and due to local shock waves, acoustic currents and ultraviolet radiation in the area of cavitating bubbles. The similarity of cavitation processes in water systems implemented by underwater electric discharges and with the ultrasound has been experimentally proved. The main advantage of electric discharge cavitation in comparison with ultrasonic one is the wide band of ultrasonic frequencies of radiation inherent in electric discharge, high intensity and power of cav-itation processes, and, accordingly, the possibility of a significant increase in the volume of the disinfected liquid. The study enable better understanding and prediction of the effects that occur during a high-voltage underwater electrical discharge and have a bactericidal effect.

Software Engineering education has grown during the past couple of decades as a specialized branch of computer science education to address employment demands. Software Engineering education is constantly evolving because of its dynamic nature. However, there are still some gaps between the skills being taught in the universities and skills required for employment. In this paper, we present our experience of designing and delivering a new module to enhance skills for employment. We have taken a structured approach to analyze the gap through literature review and our personal experiences of engaging with employers of our students. Based on the analysis, we arrived at a set of gaps between what we teach and what the employers of our students need. We prioritized the gaps and envisaged a new module ‘Contemporary Software Engineering’ to address the gaps and subsequently help our students for an easy transition to job. As part of our experience, we present the background, design and delivery of the module and reflect on our journey of delivering the module for a few years.

Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4αR subunit. Blockade of IL-4/13 is effective in reducing Th2-oriented response including the release of proinflammatory cytokines, chemokines, and IgE. These mechanisms are known as mediators in the pathogenesis of atopic dermatitis, food allergy, allergic rhinitis with and without polyposis, and asthma. We report the clinical case of a patient in which the Th2-mediated inflammatory substrate is evident in comorbid allergic manifestations who show a good response after treatment with Dupilumab for moderate atopic dermatitis.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

Naturally fermented dairy products are an important component of the human diet. They are a valuable source of nutrients as well as vitamins and minerals. Their importance as a source of probiotic bacterial strains should not be overlooked. A number of studies highlights the positive effects of species of the Lactobacillacea on the intestinal microbiota, the overall homeostasis of the body, as well as a complementary treatment for some diseases. However, data on the effects on intestinal epithelial cells of postmetabolites released by bacteria are incomplete. This is likely due to the fact that these effects are species and strain specific. In the present study, we investigated the effects of postmetabolites produced by a pre-selected candidate probiotic strain Limosilactobacillus fermentum on HT-29 intestinal epithelial cells. Our data showed a pronounced proliferative effect, evaluated by flow cytometry, quantification of cell population, and determination of mitotic index. This was accompanied by stabilization of the cell monolayer, measured by increase of TEER (trans epithelial electric resistance) and reorganization of actin filaments. The data obtained are a clear indication of the positive effects, that the products secreted by L. fermentum strain 53 have on the intestinal epithelial cells.

This article provides a literature review on tubal carcinoma to offer an updated insight into its preventative strategies, diagnosis, treatment, and oncological surveillance. In addition to the search string utilized, the authors' focus extended to key scientific studies, consensus statements, guidelines, and relevant case reports essential for the proper clinical management of the disease, providing a methodologically well-structured literature review combined with the practical expertise in the oncological field. The article also includes two emblematic clinical cases that emphasize the importance of understanding the physiopathology and the current state of the art in the anatomopathological advancements of tubal/ovarian/peritoneal carcinoma, often assimilated into a single clinical entity.

We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.

This paper proposes a metaphysical framework for distinguishing between human and machine intelligence. It posits two identical deterministic worlds -- one comprising a human agent and the other a machine agent. These agents exhibit different information processing mechanisms despite their apparent sameness in a causal sense. Providing a conceptual modeling of their difference, this paper resolves what it calls “the vantage point problem” – namely, how to justify an omniscient perspective through which a determinist asserts determinism from within the supposedly deterministic universe.

Development encompasses processes that occur at multiple length-scales, includ- ing gene regulatory interactions, cell movements and reorganisation, cell signalling and growth. It is essential that the timing of events in all of these different processes are coordinated to generate well patterned tissues and organs. However, how the timing of intrinsic cell state changes is coordinated with events at the multi-tissue and whole organism level is unknown. Here, we argue that an important mechanism which accounts for integration of timing across levels of organisation is provided by tissue tectonics: i.e. how morphogenetic events driving tissue shape change result in the relative displacement of signalling and responding tissues and coordinate devel- opmental timing across scales. In doing so, tissue tectonics provides a mechanism by which the cell specification events intrinsic to cells can be modulated by the temporal exposure to extracellular signals. This exposure is in turn regulated by higher-order properties of the embryo such as their physical properties, rates of growth and the combination of dynamic cell behaviours impacting tissue morphogenesis. Tissue tec- tonics creates a downward flow of information from higher to lower levels of biological organisation, providing an instance of downward causation in development.

Preschoolers with disabilities and their family caregivers are missed out in many public health initiatives especially in low-income countries. Yet they can benefit from early intervention to promote their development from soon after birth and to provide a better quality of life for their families. In this paper, we describe how a community-based approach has been implemented with minimal funding in two areas in Zimbabwe: a township in Harare and in rural areas of Manicaland Province. Our aim in sharing this information – allied with references to research studies recently undertaken in Africa – is that it will enable similar supports to be replicated in other communities by local personnel. A logic model is used to describe the situation in which the two projects work, the various inputs they have provided to their community and the different forms of support they have offered to the children and their caregivers. The project outputs are listed in terms of the number of beneficiaries helped and activities undertaken. The outcomes achieved for the children, the family and communities are reported. The sustainability and extensions of community-based projects to address unmet needs are discussed. The main conclusion is that disadvantaged communities can be energized to address the needs of their most marginalized residents.