Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

Commercial development of tidal stream energy is hampered by technical and financial challenges, and impeded by uncertainty about potential environmental effects that drive environmental risk assessments and permitting (consenting) processes. The effect of greatest concern for operational tidal stream energy devices is the potential for marine animals to collide with turbine blades, resulting in injury or death. Due to the turbulent and often turbid waters that frequently characterize tidal turbine sites, there is an absence of empirical evidence about collisions with marine animals. This paucity of observations often leads to risk-averse permitting decisions that further restrict the deployment of tidal energy devices that are needed to collect this evidence. This paper relies on the framework of stressors and receptors that is used widely in marine energy studies and outlines a stepwise probabilistic methodology that applies existing knowledge to further elucidate the risk to marine animals from operational tidal turbines. A case study using striped bass from the Bay of Fundy, Canada, accompanies the methodology, to partially demonstrate its application.

Despite the recognized influence of maximum or acceleration strength on combat techniques and countermovement jump (CMJ) performance, the relationship between body segment weights and combat techniques remains unexplored. This study aimed to examine the impact of body segment weights, including striking arm weight (SAW), kicking leg weight (KLW), and trunk weight (TW), on the dynamics of direct punches (DP), palm strikes (PS), elbow strikes (ES), front kicks (FK), and CMJ performance. Sixteen male military cadets (22.3±1.8 years, 181.4±7.0 cm, 83.0±8.1 kg) performed combat techniques, with performance measured by using a force plate and body segment weights assessed by Dual-energy X-ray absorptiometry. Spearman's correlation analysis was applied. Results indicated a strong correlation between KLW and FK impulse (r = 0.64, p ≤ 0.01) and CMJ impact force (r = 0.80, p ≤ 0.01). SAW showed moderate correlations with DP impulse (r = 0.53, p ≤ 0.05) and ES impulse (r = 0.54, p ≤ 0.05). Additionally, FK peak and impact forces were strongly correlated with CMJ jump height (r = 0.74, p ≤ 0.01; r = 0.77, p ≤ 0.01), and FK peak force moderately correlated with CMJ peak velocity (r = 0.63, p ≤ 0.05). These findings suggest targeted arm strength training could enhance striking abilities, while improvements in leg acceleration strength may directly boost kicking performance and vertical jump capabilities, which are crucial in combat scenarios.

Infant cry is evolutionarily, psychologically, and clinically significant. During the last 60 years, several researchers and clinicians assessed the possibility of investigating the acoustical properties of cry for medical purposes. However, there is a lack of standardization in conducting and reporting cry-based studies. In this work, methodologies and procedures employed in infant cry analysis are reviewed, and best practices for reporting studies are provided. First, available literature on vocal and audio acoustic analysis have been examined to identify critical aspects of participant information, data collection, methods, and data analysis. Then, 180 peer-reviewed research articles have been assessed to certify the presence of identified critical information. Results show a general lack of critical description. Researchers in the field of infant cry need to agree on a standard set of criteria to report experimental studies, to better demonstrate the validity of the methods and obtained results.

Artocarpus camansi Blanco or breadnut (Family: Moraceae) is primarily found in tropical regions of the world. Different parts of the plant provide potential use in medicine, nutraceutical development, and livelihood. The present review attempts to document literature on the traditional use, nutritional value, phytochemistry, and pharmacological investigation carried out with breadnuts. The included literatures of the plant were collected from various sources and databases like Google scholar, PubMed, ScienceDirect, Crossref, and Scopus. Breadnuts are rich in secondary metabolites. Studies have reported the isolation of several triterpenoid compounds and the broad spectrum of its pharmacological activities such as antidiabetic, antimalarial, antioxidant, anti-tumor, antibacterial, and immunomodulatory properties. The approximate composition of the seed and the fruit also highlights the nutritional importance of this plant. A. camansi Blanco is an underutilized tree that holds significant potential if further research and sustainable conservation is applied. Efforts to mainstream its use as functional food and increase awareness among the locals should also be given attention.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

An Environmental Decision Support System (EDSS) can be used as an important tool for rehabilitation and preservation of ecosystems. Nonetheless, high assimilation costs (both money and time) are one of the main reasons that these tools are not widely adapted in practice. This work presents a low-cost paradigm of "EDSS as a Service", this paradigm is demonstrated for developing Water Quality EDSS as a Service that utilizes the well-known CE-QUAL-W2 model as a kernel for deriving optimized decisions. The paradigm is leveraging new open-source technologies in software development (e.g. Docker, Kubernetes, and Helm) with cloud computing in order to significantly reduce assimilation costs of the EDSS for organizations and researchers working on rehabilitation and preservation of water bodies.

Volatile organic compounds (VOCs) released from plants have been correlated with disease-status. Analysis of VOCs using GC-MS is time-consuming, laboratory-based, and requires specialist training. Electronic nose devices (E-nose) provide a portable alternative. Three different E-nose devices were compared to assess how accurately they could detect Mango Twig Tip Dieback and Panama disease in banana. The devices were initially trained on known volatiles, then pure cultures of Pantoea sp., Staphylococcus sp., and Fusarium odoratissimum, and finally, on infected and healthy mango leaves and field-collected, infected banana pseudo-stems. The experiments were repeated three times with six replicates for each host-pathogen pair. The variation between healthy and infected host materials was evaluated by principal component and linear discriminant analysis, cross-validation and chemometric data analysis. GC-MS analysis was conducted contemporaneously and identified an 80% similarity between healthy and infected plant material. The portable C 320 was 100% successful in discriminating known volatiles but had a low capability in differentiating healthy and infected plant substrates. The advanced devices (PEN 3 / MSEM 160) successfully detected healthy and diseased samples with a high variance. The results suggest that E-nose devices are more sensitive and accurate in detecting changes of VOCs between healthy and infected plants compared to headspace GC-MS.

Chinese-speaking parents are argued to use less cognitive mental-state-talk than their English-speaking counterparts due to their goals in socializing their children to follow an interdependence script. To extend this research, we investigated bilingual Mandarin-English Singaporean mothers who associate different functions for each language as prescribed by their government: English for school and Mandarin for in-group contexts. English and Mandarin maternal mental-state-talk from bilingual Mandarin-English mothers with their toddlers was examined. Mothers produced more cognitive terms in English than in Mandarin and more desire terms in Mandarin than in English. We show that mental-state-talk differs between bilingual parents’ languages, suggesting that mothers adjust their mental-state-talk to reflect each language’s function.

Postpartum depression (PPD), a condition that affects up to the 15% of mothers in high-income countries, reduces attention toward the needs of the child and it is among the first causes of infanticide. PPD is usually identified using self-report measures and therefore the diagnosis may not always be valid. Previous studies highlighted the presence of significant differences in the acoustical properties of the vocalizations of children of depressed and healthy mothers. In this study, cry episodes of infants of depressed and non-depressed mothers are analyzed to investigate the possibility that a machine learning model can identify PPD in mothers from the acoustical properties of infants' vocalizations. Acoustic features (F0, F1-4, Intensity) are first extracted from recordings of crying infants, then novel cloud-based artificial intelligence models are employed to identify maternal depression versus non depression from estimated features. Trained model shows that commonly adopted acoustical features can be successfully used to individuate Post-Partum Depressed mothers with very high accuracy (89.5%).

This study investigated the associations of imageability with fear reactivity. Imageability ratings of four word classes: positive and negative (i) emotional and (ii) propriosensitive, neutral and negative (iii) theoretical and (iv) neutral concrete filler, and fear reactivity scores – degree of fearfulness towards different situations (TF score) and total number of extreme fears and phobias (EF score), were obtained from 171 participants. Correlations between imageability, TF and EF scores were tested to analyze how word categories and their valence were associated with fear reactivity. Imageability ratings were submitted to recursive partitioning. Participants with high TF and EF scores had higher imageability for negative emotional and negative theoretical words. The correlations between imageability of negative emotional words and negative theoretical words for EF score were significant. Males showed stronger correlations for imageability of negative emotional words for EF and TF scores. High imageability for positive emotional words was associated with lower fear reactivity in females. These findings were discussed with regard to negative attentional bias theory of anxiety, influence on emotional systems, and gender-specific coping styles. This study provides insight into cognitive functions involved in mental imagery, semantic competence for mental imagery in relation to fear reactivity, and a potential psycholinguistic instrument assessing fear tendency.

The paper investigated the components of savings accumulation in Nigeria over the period 1980 to 2017. Secondary data were collated from World Development Index (WDI). In evaluating the objectives, the study employed the Auto Regressive Distributive Lag (ARDL) and Vector Error Correction Model (VECM) estimation methods. The key findings of the study show that the components of savings identified in literature understudied in the paper specifically, GDP per capita, foreign direct investment, financial deepening, interest rate, inflation rate exchange rate significantly influence savings accumulation in Nigeria either in short run, long run or both. Financial deepening was found statistically significant but influences savings negatively. Inflation rate was statistically insignificant although negative. The result from the VECM causality test revealed that short run and long run causal relationship exist between savings and the afore mentioned components in Nigeria. Hence, the study recommends careful manipulation of the identified savings components in a manner that they will not yield a counterproductive result in the economy rather contribute to the growth of savings and ultimately, the growth of Nigeria economy as a whole. It further recommends that the Nigerian government through its financial institutions encourage savings from both small and big savers which to large extent will assuage the perceived undeserved influence of financial deepening on savings accumulation.

Synesthesia is a psychological phenomenon where sensory signals become mixed. Input to one sensory modality produces an experience in a second, unstimulated modality. In “grapheme-color synesthesia”, viewed letters and numbers evoke mental imagery of colors. The study of this condition has implications for increasing our understanding of brain architecture and function, language, memory and semantics, and the nature of consciousness. In this work, we propose a novel application deep learning to model perception in grapheme-color synesthesia. Achromatic letter images, taken from database of handwritten characters, are used to induce synesthesia. Results show the model learns to accurately create a colored version of the inducing stimulus, according to a statistical distribution from experiments on a sample population of grapheme-color synesthetes. The spontaneous, creative mental imagery characteristic of the synesthetic perceptual experience is reproduced by the model. A model of synesthesia that generates testable predictions on brain activity and behavior is needed to complement large scale data collection efforts in neuroscience, especially when articulating simple descriptions of cause (stimulus) and effect (behavior). The research and modeling approach reported here begins to address this need.

Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have implications for drug disposition and ultimately affect the clinical outcome in this vulnerable population. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict the effect of malnutrition as it links physiological changes to pharmacokinetic (PK) consequences. However, the absence of detailed information on body composition and the limited availability of controlled clinical trials in malnourished children complicates the establishment and evaluation of a generic PBPK model in this population. In this manuscript we describe the creation of physiologically-based bridge to a malnourished pediatric population, by combining information on a) the differences in body composition between healthy and malnourished adults and b) the differences in physiology between healthy adults and children. Model performance was confirmed using clinical reference data. This study presents a physiologically-based translational framework for prediction of drug disposition in malnourished children. The model is readily applicable for dose recommendation strategies to address the urgent medicinal needs of this vulnerable population.

We propose the traditional goal of cancer therapists to develop a single drug or drug combination that can, by itself, eliminate all cancer cells within a host has neglected potential treatments that may achieve curative outcomes by strategically combining agents that are individually effective but non-curative. We derive basic principles for such an approach from the eco-evolutionary dynamics of background extinctions in which a “first strike” reduces the size and heterogeneity of the initial population and is followed immediately by demographic and ecological “second strikes” that push the population below an extinction threshold. This proposed strategy appears identical to the empirically-derived curative therapy in childhood Acute Lymphocytic Leukemia.

Transforming Small-Scale LNG Business, Enhancing Efficiency and Resilience in an Evolving Supply Chain In various industries, innovative systems have proven their value due to their efficiency and adaptability. A prime example of this lies in the rapid growth of the liquefied natural gas (LNG) market. LNG, a fuel derived from natural gas, has gained significant traction in recent years. In light of this, we aim to explore optimal strategies for small-scale LNG businesses, with a focus on revolutionizing their supply chain to ensure adaptability and sustainability. Our objective is to enhance efficiency and sturdiness in this evolving sector. By devising innovative methods and implementing cutting-edge technologies, we aim to revolutionize the small-scale LNG market, paving the way for a more optimized and resilient supply chain. Through this transformation, we strive to create a sustainable and adaptable framework that will drive the growth and success of a small-scale LNG businesses.LNG' ability to be transported and stored more cost-effectively in its reduced volume compared to natural gas in its original state is a significant advantage. The distribution network for LNG starts at numerous supply terminals and extends to a diverse range of consumption centers, each with varying tank capacities. In the broader economic context, the establishment of efficient routes for LNG Truck tank plays a critical role.To tackle the challenge of selecting a pickup location and determining optimal destinations with specific unloading volumes for liquefied natural gas (LNG), this research presents an innovative solution utilizing state-of-the-art machine learning techniques. The proposed approach combines the power of reinforcement learning, recurrent neural networks, online learning, and graph theory. By leveraging these cutting-edge techniques, we aim to develop an intelligent system that can effectively determine the most efficient pickup location and sequence of destinations for LNG delivery. This system will take into account various factors such as transportation costs tank capacity, and demand fluctuations. Through the integration of reinforcement learning, the system will continuously learn and improve its decision-making process in real-time. The recurrent neural networks will allow for the analysis of historical aim to model and optimize the complex network of pickup and delivery routes, considering factors such as distance, capacity constraints, and operational efficiencies. With this innovative approach, we strive to revolutionize the selection and planning process for LNG pickup and delivery, ultimately enhancing efficiency and reducing cost within the LNG supply chain.Improving the distribution network offers several financial benefits, including cost reduction, faster delivery times, more affordable distribution, and enhanced efficiency in the utilization of tanker trucks for LNG transportation. By optimizing the distribution network, transit costs associated with LNG transportation can be significantly lowered. This can be achieved through intelligent route planning, taking into account factors such as distance, traffic conditions, and fuel consumption. Minimizing transit costs contributes to overall savings for businesses operating in the LNG market. Faster delivery times are another advantage of an enhanced distribution network. By designing efficient routes and eliminating unnecessary detours or delays, the time taken for LNG to reach its intended destinations can be reduced. This not only improves customer satisfaction but also allows for more frequent deliveries and better coordination of supply and demand. Cheaper distribution is a direct outcome of an optimized distribution network. By strategically planning pickup locations, destinations, and intermediate stops, the costs associated with transferring LNG between terminals and consumption centres can be minimized. This leads to savings in transportation expenses, ultimately benefiting both businesses and end-users. Efficient utilization of tanker trucks is crucial for maximizing profitability in the LNG industry. An improved distribution network enables better allocation of resources, ensuring that tanker trucks are utilized optimally. This includes reducing empty or underutilized trips, maximizing load capacities, and minimizing idle time. Such efficiency improvements translate to cost savings and increased revenue for businesses involved in LNG transportation. Overall, the financial gains from improving the distribution network are substantial. Lower transit costs, faster delivery times, cheaper distribution, and more efficient use of tanker trucks contribute to increased profitability, competitiveness, and sustainability in the LNG market.

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.

In recent years, food and drink marketers have become increasingly interested in the question of whether there are any meaningful sex/gender differences in the world of taste/flavour perception. However, it turns out that while there are a large number of individual differences in the experience of food/drink, few, if any, fall neatly along sex/gender lines. As such, the marketers of food and drink need to tread very carefully when it comes to marketing food or beverage products specifically at men, or more usually, women. All too often, the brands entering this space soon find their attempts branded crass and/or sexist. Adopting a stealthy or implicit gender-based product development strategy is therefore perhaps more likely to succeed than the explicit targeting of food/beverage-related products in what is undoubtedly a highly-politicized area. That said, the one area where the public appear willing to accept products that are explicitly targeted at men or women is in the case of nutritional foods/supplements.

As a result of an increasing population of aged people in sub-Saharan Africa, dementia is predicted to surge up to 90% by 2030. This review is set to assess the prevalence of dementia, for 65+ aged population in sub-Saharan states and particularly in Tanzania. Subsequently, the review will identify the possible risks factors – age, gender, level of education, cardiovascular problems, diabetes and mild cognitive impairment – and will lay out the challenges of reducing the dementia burden in Tanzania. Additionally, the review explores the current approaches in solving dementia disorders, including a general view of the public understanding of dementia. Also, the review recognises the gaps in government funding to mental health, a barrier to service access and the need for further research on Alzheimer’s and other dementias. Lastly, the review links the sustainable development goals (SDGs) addressed and appreciate the impact of the coronavirus pandemic on the fight against dementia.

The paper presents models of path and control planning for parking, docking, and movement of autonomous vehicles at low speeds considering space constraints. Given the low speed of motion, and in order to test and approve the proposed algorithms, vehicle kinematic models are used. Recent works on the development of parking algorithms for autonomous vehicles are reviewed. Bicycle kinematic models for vehicle motion are considered for three basic types of vehicles: passenger car, long wheelbase truck, and articulated vehicles with and without steered semitrailer axes. Mathematical descriptions of systems of differential equations in matrix form and expressions for determining the linearization elements of nonlinear motion equations that increase the speed of finding the optimal solution are presented. Options are proposed for describing the interaction of vehicle overall dimensions with the space boundaries, within which a maneuver should be performed. An original algorithm that considers numerous constraints is developed for determining vehicle permissible positions within the closed boundaries of the parking area, which are directly used in the iterative process of searching for the optimal plan solution using nonlinear model predictive control (NMPC). The process of using NMPC to find the best trajectories and control laws while moving in a semi-limited space of constant curvature (turnabouts, roundabouts) are described. Simulation tests were used to validate the proposed models for both constrained and unconstrained conditions and the output (state-space) and control parameters' dependencies are shown. The proposed models represent an initial effort to model the movement of autonomous vehicles for parking and has the potential for other highway applications.

Pneumonic plague outbreaks are relatively infrequent in modern times but in the early part of the 20th century, they were commonplace including several well-documented epidemics responsible for the deaths of thousands. The transmissibility of this disease seems to be discontinuous since in some outbreaks few transmissions occur, while in others, the progression of the epidemic is explosive. Modern epidemiological studies explain that transmissibility within populations is heterogenous with relatively few subjects likely to be responsible for most transmissions and that ‘super spreading events’, particularly at the start of an outbreak, can lead to a rapid expansion of cases. These findings concur with outbreaks observed in real-world situations. It is often reported that pneumonic plague is rare and not easily transmitted but this view could lead to unnecessary complacency since future risks such as the spontaneous incidence of anti-microbial strains, climate change leading to a disruption of natural cycles within plague foci and use of plague as a bioweapon cannot be discounted. Carers and first responders are vulnerable, particularly in poorer countries where access to medicines may be limited, out-breaks occur in inaccessible areas or where there is a lack of surveillance due to a paucity of funds.

In recent years, several brands have received much negative press coverage when trying to market their food and drink products specifically at women. This is, in part, because the taste preferences/sensitivities of men and women are actually quite similar. In fact, perhaps the one and only area where consumers are willing to accept (or should that be swallow) ingested products explicitly targeted at women or men is in the case of nutritional foods/supplements. Such products are not really sold on the basis of their taste/flavour anyway. Many consumers are also sensitive to the so-called pink tax, when near-identical products cost more when sold to women rather than to men (e.g., as in the case of female razors). As the four recent examples discussed in this review make clear, it can be difficult to roll-out a new food or beverage product, or else extend a pre-existing product line, that is especially for women without coming across as sexist/condescending. As such, marketers need to tread carefully, otherwise they may end-up generating unwanted negative publicity. Ultimately, therefore, adopting an implicit approach to gender-based marketing, should that be the direction that a brand wants to take, will likely have more chance of avoiding negative publicity than the explicit targeting of food/beverage-related products in what is undoubtedly a highly-politicized area.

Earnings management and financial distress are two critical facets of financial management in corporations that have lately been the focus of thorough research from both scholars and practitioners. The purpose of the research is to evaluate the influence of financial distress on the earnings management of companies listed at the NSE during the pre- and post-COVID eras. Multiple linear regression was applied in this study to examine the causal association between earnings management and financial distress. To assess the effect of financial distress on earnings management, the study analyzed data from 37 listed companies during the pre-COVID and post-COVID periods. The methodology also takes into account control factors like firm size, GDP, and inflation. The pre-COVID research indicates a significant positive correlation between financial strain and earnings management. In contrast, the correlation between financial distress and earnings management is not statistically significant in the post-COVID analysis. However, research shows that firm size has a statistically significant negative influence on managing earnings. The results of this study show that smaller firms are more inclined to engage in earnings management during the post-COVID era than bigger ones.

A semi-structured interview (SSI) is one of the essential tools in conduction qualitative research. This essay draws upon the pros and cons of applying semi-structured interviews (SSI) in the qualitative research method. Moreover, the challenges of SSI during the coronavirus pandemic are critically discussed to provide plausible recommendations.

How Nature discovered genetic coding is a largely ignored question, yet the answer is key to explaining the transition from biochemical building blocks to life. Other, related puzzles also fall inside the aegis enclosing the codes themselves. The peptide bond is unstable with respect to hydrolysis. So, it requires some form of chemical free energy to drive it. Amino acid activation and acyl-transfer are also slow and call for catalysis. All living things must thus also convert free energy and synchronize cellular chemistry. Most importantly, functional proteins occupy only small, isolated regions of sequence space. Nature evolved heritable symbolic data processing to seek out and use those sequences. That system has three parts: a memory of how amino acids behave in solution and inside proteins, a set of code-keys to access that memory, and a scoring function. The code-keys themselves are the genes for cognate pairs of tRNA and aminoacyl-tRNA synthetases, AARS. I outline the surprising links between all these questions and the structural duality of the base-pairing that holds genes together and how those links arise from the experiments.

Turnovers in the National Football League (NFL) occur whenever a team loses possession of the ball due to a fumble, or an interception. Turnovers disrupt momentum of the offensive team, and represent lost opportunities to advance downfield and score. Teams with a positive differential turnover margin in a given game win $70\%$ of the time. Turnovers are statistically rare events, occurring apparently randomly. These characteristics make them difficult to predict. This investigation advances the hypothesis that turnovers are predictable in NFL football. Machine learning models are developed to learn the concept: At any point within a football game, what is the likelihood that a turnover will be observed on the next play from scrimmage? Results presented suggest evidence to support the working hypothesis. Under certain conditions, both fumbles and interceptions can be anticipated at low false discovery rates (less than $15\%$). This approach may be useful to inform in-game strategies to mitigate the negative consequences of turnovers by an offensive team, or to maximize their probability by a defensive squad.

The Anthropocene has emerged as the dominant conceptualization of the current geological epoch and, more significantly, of Humanity’s relation to nature. By its proponents the Anthropocene is espoused as a “solution formulation,” an analytical tool which clarifies Humanity’s multifarious impacts on nature and nature’s subsequent crises; and further as a conceptual apparatus from which to launch mitigation and adaption strategies, promising deliverance from or at least engagement with ecological crises. However, the Anthropocene is not a neutral concept, merely illuminating transition within ecological conditions and connections between human activities and nature; rather, it is a particular prism from which to understand humanity’s relation to nature. And, as the Anthropocene becomes ascendant both analytically and politically, it becomes vital to question its imaginary, how it constructs nature and Humanity, how it influences and constrains responses to ecological crises, and what the long-term implications of operating within this imaginary are. I argue that the Anthropocene as a political/analytical prism rests upon flawed conceptions of nature, history, and humanity, rending it an impotent construct from which to respond to ecological crises; offering only partial and presumptive “solutions” in the form of intensified governmental regulation and the application of manifold technological “fixes” through the geoengineering of Earth’s systems, in an attempt to address isolated aspects of ecological destruction.

2003 it is shown that after the Chernobyl accident, childhood leukemia by single age and year of birth in the 0-4y cohort increased significantly in Wales and Scotland combined in the period 1986-1990 compared with controls born 1970-1985 and 1991-1994. Relative risk RR = 1.41; 95% CI 1.20<RR<1.65; p = 0.00004. These exposure periods were chosen because whole body Caesium-137 monitoring had demonstrated that internal exposures persisted for more than 4 years. The dose-response exhibits saturation and reversal, interpreted as biological censoring effects in the developing individual.

By defining a constant probabilistic orbit of and iterated functions, the stability dynamics of these functions in possible interactions through connectivity provides the formation of a dynamic fixed point as a metric space between both iterated functions. The presence of a dynamic fixed point identifies qualitatively phases of iteration time lengths and interaction orbits of the event. Qualitative results show that the greater the average distance from one of the functions to the fixed point of the other (all possible solutions), the higher the iteration expression on time (false asymptotic effect) of one of the functions and in the opposite hand, the lower the average distance, the higher orbit’s interactions proximity between iterated functions (stability). This feature reveals asymptotic (well-defined) behavior between functions f and g within a well-defined Lyapunov stability.

Utilizing relational networking and cultural assets provide an arena for village development associations (VDAs) to fill the gaps in infrastructure in resource limited communities of Cameroon’s north-western region. Through case study, this study interrogates the foundational thesis of relational networking and cultural assets deployed to deal with social development challenges. Semi-structured interviews were undertaken with community participants. Purposive sampling was used, and data were analysed and critically synthesized with comparable literature. Communities increasingly shoulder their own development through a multiplicity of agency with internal and external stakeholders. The analysis captures a typology of incremental cultural assets, galvanised and re-engineered, promoting a rejuvenated community. A multi-layered approach centred on intersecting elements with unvarying input from community members are perceptible. Though the translational benefits are not clear-cut, relational networking and incremental cultural assets hold out the prospect for community transformation in infrastructure provision - supply of fresh water, equipping schools, community halls, building roads, bridges and community halls. In the process, social inequality and other barriers of disadvantage are narrowed.

Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.

In this manuscript, an automated framework dedicated to design space exploration and design optimization studies is presented. The framework integrates a set of numerical simulation, computer-aided design, numerical optimization, and data analytics tools using scripting capabilities. The tools used are open-source and freeware, and can be deployed on any platform. The main feature of the proposed methodology is the use of a cloud-based parametrical computer-aided design application, which allows the user to change any parametric variable defined in the solid model. We demonstrate the capabilities and flexibility of the framework using computational fluid dynamics applications; however, the same workflow can be used with any numerical simulation tool (e.g., a structural solver or a spread-sheet) that is able to interact via a command line interface or using scripting languages. We conduct design space exploration and design optimization studies using quantitative and qualitative metrics, and to reduce the high computing times and computational resources intrinsic to these kinds of studies, concurrent simulations and surrogate-based optimization are used.

This review article focuses on the upstream pertinent pathophysiology leading to neurodegenerative disease. Specifically, the nexus appears to be blood brain barrier (BBB) leakiness resulting in a two-prong inflammatory disease spectrum damaging the microvasculature and corrupted protein synthesis and degradation with accumulating misfolded toxic proteins. The suboptimal results of removing misfolded proteins means a new approach to disease in the preclinical state is required aimed at other targets.Validated noninvasive imaging and serologic biomarkers of early preclinical disease implemented in the high-risk patient cohort along with periodic surveillance once effective treatments are developed will be required.This review discusses the physiology and pathophysiology of the BBB, new MRI imaging techniques identifying the leak and altered fluid dynamic effects in the preclinical state. The risk factors for disease development, preventative measures, and potential treatment targets are also discussed.

Dietary habits, including meal frequency, meal timing, and skipping meals, have been extensively studied due to their association with the development of non-communicable diseases (NCDs). This study describes dietary habits, meal timing, meal frequency, skipping meals, and late-night eating in Kuwaiti adults. The Kuwait National Nutrition Surveillance System data was utilized to reach the objectives of this study. The findings reveal that approximately 50% of the adults in Kuwait eat after 10 p.m., 29% skip breakfast, and 9.8% skip dinner. Furthermore, adults in Kuwait consume 4.4 meals per day on average. Women skip breakfast more often and have extended night fasting than men (p&lt;0.001). Married adults skip breakfast and dinner less than unmarried adults (p&lt;0.001). In conclusion, this descriptive study provides valuable insights into the dietary habits of Kuwaiti adults, emphasizing the importance of further investigating the association between meal timing, meal frequency, and the prevalence of NCDs in Kuwait.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

Abstract: More than 40 hypotheses predict associations between features of nest architecture and at least one measure of reproductive success. However, quantitative studies of reproductive consequences of nest characteristics remain scarce. In addition, most studies were conducted on model species of which nests can be easily monitored with artificial nest-boxes. Here we review the replicability of research protocols and findings in model species with many repeat studies focusing mainly on nest-size components, animal-derived nest material, or fresh greenery in blue tits (Cyanistes caeruleus), great tits (Parus major), tree swallows (Tachycineta bicolor), and starlings (Sturnus spp.). The studies looked for correlations between nest traits and aspects of breeding performance that can be easily quantified in the field, such clutch size, brood size at hatching or fledging, the % of eggs that hatch or fledge, or nestling characteristics assumed to reflect qualities associated with survival probabilities (e.g., morphometry, body condition, blood profiles). We discuss the consequences of poor replicability of research methodologies and provide explanations for why many of these studies reported poor associations between nest design and breeding success at different spatiotemporal scales. We also make suggestions for future research. Keywords: Nest design, Breeding success, Nest-box, Cavity-nesting birds, Replicability

Individuals with metabolic syndrome have increased risk for developing health conditions, in-cluding cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary pat-terns and habits are extremely successful in controlling more than one of the metabolic syn-drome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardi-ovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple medi-ation analysis revealed that all three potential mediators played a role in mediating the associa-tion. However, in the parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43—0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31—0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003—0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to resolution of questions regarding the pathogenesis of PASC.

Recent theory of tachyon neutrinos, providing an explanation for Dark Matter, leads to two sets of experiments for testing that theory. One predicts an enhanced signal in detection of the Cosmic Neutrino Background. The other compares models of Dark Matter used to fit data on galaxy rotation curves and also gravitational lensing. In addition, an apparent contradiction within the new theory, related to Dark Energy, is identified and addressed.

Introduction: Weighting is widely used in applied statistics especially while dealing with survey data. In recent years, multilevel modeling under complex survey designs has increased, resulting into demand for level weights. However, survey data that are accessible to the public for use usually do not contain level weights that are useful in multilevel modeling, but final survey weights that are only appropriate for single level analyses. In this paper, we demonstrate how the final survey weights can be used to estimate level weights for multilevel data analysis, and compare a model that applied level weights with one that applied the final survey weights. Methods: A framework for approximating level weights proposed by the Demographic Health Survey (DHS) program was used to estimate the level weights. Models were fitted using a multilevel mixed effects logistic regression method. Estimates from a model that applied survey weights was compared to those from a model that applied level weights. Results: Application of final survey weights instead of level weights underestimated standard errors and led to loss of precision of model estimates. Conclusions: Use of level weights produces estimates with high precision and yields correct values of standard errors hence appropriately informing inference.

The mission here is to see if we can find bound states for tachyons in some gravitational environment. That could provide an explanation for the phenomena called Dark Matter. Starting with the standard Schwarzschild metric in General Relativity, which is for a static and spherically symmetric source, it appears unlikely that such localized orbits exist. In this work the usual assumption of isotropic pressure is replaced by a model that has different pressures in the radial and angular directions. This should be relevant to the study of neutrinos, especially if they are tachyons, in cosmological models. We do find an arrangement that allows bound orbits for tachyons in a galaxy. This is a qualitative breakthrough. Then we go on to estimate the numbers involved and find that we do have a fair quantitative fit to the experimental data on the Galaxy Rotation Curve. Additionally we are led to look in the neighborhood of a Black Hole and there we find novel orbits for tachyons.

To activate gene expression, the initiation of transcription is a highly regulated process involving the interaction of proteins and DNA nucleotides at the promoter site, which consists of a small number of base pairs. As it involves interactions at the atomic scale, it is challenging to determine the mechanism of binding responsible for the great specificity between the amino acid residuals comprising the transcription binding protein and the DNA nucleotides comprising the promoter. Here, a new approach to characterize the transcription initiation process is developed and verified from analysis of comparative pharmacological efficacy data and elemental modeling. The newly developed description of a mechanism for transcription initiation involves the direct binding of small molecule ligands of approximately twenty carbon atoms, which are both structurally symmetric to DNA nucleotides, and also chemically complementary in its functional groups for interaction with the oxygen element at the carbon two position of thymine and with the phosphodiester chain. The results indicate that the activating ligands are transported to the DNA nucleotide promoter site by protein transcription factors, which serve as delivery vectors, for transfer of the ligand to the DNA nucleotide pairs. The ligands examined in this study include the steroid hormones, synthetic steroid molecules, derivatives of vitamin D, and prostaglandins, particularly PGJ2 and 15d-PGJ2. The transcription factors evaluated include glucocorticoid receptors, VDR, PPAR, and TBP. Through the developments, it is shown that because of the chemically complementary binding of the ligand to DNA nucleotide pairs, the resultant intermolecular complex produces three hydrogen bonds for the A-T and T-A configurations, which matches that of G-C and C-G. The orientation of the nucleotide base pairs is also seen to adjust as an inversion of the nominal position of the nucleobases to a dimer configuration presented via TBP transcription factor. The developments comprise a new approach to characterizing the initiation of the transcription process comprising the direct binding and interaction of ligands with DNA nucleotides as verified through comparative analysis of pharmacological activity and through perfect structural correspondence between the steroid hormone class as ligands with Watson-Crick DNA nucleotide pairings.

Exogenous RNA comprises the genetic material associated with several diseases which require immediate treatment, and thus mechanisms to hinder intracellular translation and reproduction of RNA viral agents are of great importance. Applying recent developments from this lab in methods relating to the interaction of DNA with steroid hormones, cyclic compounds are presented for intermolecular binding to nucleic acids. The requirements to achieve binding with RNA nucleotide pairs are described, which involve at a minimum functional elements positioned to interact with the lateral phosphate groups for each of the RNA strands through coupling with a positively charged ion, such as Mg2+, Ca2+, or Zn2+ ions; and an intermolecular hydrogen bond with the oxygen element of uracil at the carbon two location. Additional features of the binding molecules are examined for enhancements and differentiation in binding capability and include aromatic groups that have both a structural role of steric hindrance and a functional role to stabilize the binding mechanisms. Several categories of cyclic compounds are associated to have specific binding capabilities, and the interaction of these structures with potential receptor molecules are evaluated for assessment in delivery and binding of the compound to nucleic acids.

Retiring coal power plants can reduce air pollution and health damages. However, the spatial distribution of those impacts remains unclear due to complex power system adjustments and pollution chemistry and transport. Focusing on coal retirements in Pennsylvania (PA), we analyze six counterfactual scenarios for 2019 that differ in retirement targets (e.g., reducing 50% of coal-based installed capacity vs. generation) and priorities (e.g., closing plants with higher cost, closer to Environmental Justice Areas, or with higher CO₂ emissions). Using a power system model of the PJM Interconnection, we find that coal retirements in PA shift power generation across PA and the Rest of PJM region leading to scenario-varying changes in the plant-level release of several air pollutants. Due to air pollution chemistry and transport and socio-demographics, these changes in turn give rise to a reduction of 10 to 182 PM_2.5-attributable deaths in PJM across the six scenarios, with most reductions occurring in PA. Scenarios that reduce more coal power generation yield greater aggregate health benefits due to air quality improvements in PA and adjacent downwind regions. In addition, vulnerable populations—in both PA and Rest of PJM—benefit most in scenarios that prioritize plant closures in PA near Environmental Justice Areas. These results demonstrate the importance of considering cross-regional linkages and socio-demographics in designing equitable retirement strategies.

Cognitive impairment is a condition which affects aging patient populations and is becoming more prevalent as the geriatric population expands. It is categorized by the extent of cognitive decline, memory loss, functional abilities, and the capability to perform daily tasks. Based on the degree of impairment, it is classified as mild cognitive impairment or dementia. Considering the debilitating nature of cognitive decline and its impact on quality of life, prevention is key. In addition, given the gradual progression of the underlying causes of cognitive decline, early diagnosis and appropriate management has the potential to offer clinical advantages and better patient outcomes. Management options discussed vary from pharmaceutical regimens to neurosurgical interventions, with differing outcomes based on etiology of cognitive impairment.

Analysis of immediate effects of the COVID-19 pandemic on SMEs in Rwanda aims to assess and quantify the economic and financial impacts of the pandemic during the lockdown and presents options adopted by SMEs to reopen their business opera-tions. It also seeks to recommend options for sustainable and resilient economic recovery from the scars of COVID-19. This analysis used data collected from nearly 220 SMEs located across the country and applied an Exploratory Data Analysis (EDA) and multivariate linear regression models to measure the pandemic effects. The study revealed that firms downsized employment by 36.4 per cent, but data depict significant deviation within SMEs by their size. The COVID-19 pandemic has had a greater magni-tude of negative effects on sales levels among small businesses. Tax amounts were reduced amidst the crisis however, data do not show any significant variations among SMEs. Additionally, SMEs owners applied various coping mechanisms during re-opening. The study used firm-level data, providing detailed and reliable effects of the shocks on business performance. This analysis recommends establishing the medium-term financing and technical support for SMEs to ensure steady and sustainable recovery from pandemic effects as well as strengthening their resilience to any other socio-economics shocks.

We study the light rays in a static and spherically symmetric gravitational field of null aether theory (NAT). To this end, we employ the Gauss-Bonnet theorem to compute the deflection angle by a NAT black hole in the weak limit approximation. Using the optical metrics of the NAT black hole, we first obtain the Gaussian curvature and then calculate the leading terms of the deflection angle. Our calculations show how gravitational lensing is affected by the NAT field. We also show once again that the bending of light stems from a global and topological effect.

Traditional winglets are designed as fixed devices attached at the tips of the wings. The primary purpose of the winglets is to reduce the lift-induced drag, therefore improving aircraft performance and fuel efficiency. However, because winglets are fixed surfaces, they cannot be used to control lift-induced drag reductions or to obtain the largest lift-induced drag reductions at different flight conditions (take-off, climb, cruise, loitering, descent, approach, landing, and so on). In this work, we propose the use of variable cant angle winglets which could potentially allow aircraft to get the best all-around performance (in terms of lift-induced drag reduction), at different flight phases. By using computational fluid dynamics, we study the influence of the winglet cant angle and sweep angle on the performance of a benchmark wing at Mach numbers of 0.3 and 0.8395. The results obtained demonstrate that by adjusting the cant angle, the aerodynamic performance can be improved at different flight conditions.

Grape foods fermented with probiotics are sources of beneficial bacteria for the GI tract and also have a high antioxidant capacity. The addition of probiotics to ferment food has always been a traditional process; therefore, probiotic dairy and non-dairy products might contribute to a daily antioxidant diet to improve consumers’ life quality and health. This research was undertaken to determine the viability of 4 wild isolates of Lactobacillus for storage at 5 and 25ºC within 90 days in simulated synthetic grape media and a standard grape marmalade formulation. Changes in active culture numbers, pH level, glucose concentration, and antioxidant properties were evaluated. Most of the isolates demonstrated higher growth in the grape marmalade than the synthetic grape marmalade, which was greater than 7 Log cfu/g within 90 days of storage at 5ºC. In addition, most of the wild isolates grew beyond the critical count of 106 cfu/g in sampling between 60 and 90 days of storage. Moreover, fermented grape marmalade with probiotics showed a strong antioxidant capacity that failed to differ significantly with the synthetic medium. The study confirmed L. paraplantarum, L. plantarum, W. paramesenteroides, and E. feacalis were ideal probiotics for fermentation process of grape marmalade.

EuAP2 genes are famous for their role in flower development. A legacy of the founding member of this subfamily of transcription factor, whose mutants lacked petals in Arabidopsis. However, studies of other euAP2 genes in several species have accumulated evidence highlighting the diverse roles of euAP2 genes in other aspects of plant development. Here, we emphasize other developmental roles of euAP2 genes in various species and suggest a shift from regarding euAP2 genes as just flowering genes to consider the global role they may be playing in plant development. We hypothesize that their almost universal expression profile and pleiotropic effects of their mutation suggest their involvement in fundamental plant development processes.

In Newtonian mechanics, time as well as space are perceived as absolute entities. In 2 Einstein’s special relativity, time is frame dependent. Time is also affected by gravitational field 3 and as the field varies in space, time also varies throughout space. In the present article, a 4 thermodynamic-based time is investigated. The entity is called "irreversibility", which is generated 5 when availability (also known as exergy) is destroyed. Since each thermodynamic system may 6 generate different amount of irreversibility, this quantity is system dependent. The time’s arrow is 7 automatically satisfied, since irreversibility generation always proceeds in one direction (toward 8 future). We have demonstrated that, like common time, irreversibility is frame dependent, and 9 affected by gravity in the similar manner as the common time. For this reason, we propose to 10 assign the entity irreversibility of the system as thermodynamic time. A possible application of the 11 thermodynamic time is an interpretation and managing of the aging of biological systems. The 12 metabolic efficiency is related to the irreversibility of the chemical processes and affect the aging of 13 the system. Our sensation of time-flow may be attributed to the flow of availability and destruction 14 of it through the living system. It is shown by other authors that entropy generation (equivalent to 15 irreversibility) is a parameter for the human life span. Since the thermodynamic time is based on a 16 concept of thermodynamics that is universal, further applications to other subjects, such as biological 17 clock, telomere, and cosmology are possible.

The article analyzes Bernoulli 's binary sequences in representation of empirical events about the distribution of natural resources and population sizes. Considering the event as a nonlinear system, and consisting of two dependent random variables, with memory and probabilities in maximum finite or infinite lengths, constant and equal to ½ for both variables (stationary process). The expressions of the possible trajectories remain constant in sequences that are repeated alternating the presence or absence of one of the variables at each iteration (asymmetric). There are constant oscillations in the event except if the variables X₁ and X₂ are regulated as a function of time Y. It is observed that the variables X₁ and X₂ assume in time T_k → ∞ specific behaviors (geometric variable) that can be used as management tools for random systems. In this way, the article seeks to know from this analyzes, the maximum entropy of information in the system by a theoretical view and how to model resources distribution or containment in the given problem.

Background: There are major air pollution monitoring gaps in sub-Saharan Africa. Developing capacity in the region to conduct air monitoring in the region can help estimate exposure to air pollution for epidemiology research. The purpose of our study is to develop a land use regression (LUR) model using low-cost air quality sensors developed by a research group in Uganda (AirQo). Methods: Using these low-cost sensors, we collected continuous measurements of fine particulate matter (PM2.5) between May 1, 2019 and February 29, 2020 at 22 monitoring sites across urban municipalities of Uganda. We compared average monthly PM2.5 concentrations from the AirQo sensors with measurements from a BAM-1020 reference monitor operated at the US Embassy in Kampala. Monthly PM2.5 concentrations were used for LUR modeling. We used eight Machine Learning (ML) algorithms and ensemble modeling; using 10-fold cross validation and root mean squared error (RMSE) to evaluate model performance. Results: Monthly PM2.5 concentration was 60.2 µg/m³ (IQR: 45.4-73.0 µg/m³; median= 57.5 µg/m³). For the ML LUR models, RMSE values ranged between 5.43 µg/m³ - 15.43 µg/m³ and explained between 28% and 92% of monthly PM2.5 variability. Generalized additive models explained the largest amount of PM2.5 variability (R²=0.92) and produced the lowest RMSE (5.43 µg/m³) in the held-out test set. The most important predictors of monthly PM2.5 concentrations included monthly precipitation, major roadway density, population density, latitude, greenness, and percentage of households using solid fuels. Conclusion: To our knowledge, ours is the first study to model the spatial distribution of urban air pollution in sub-Saharan Africa using air monitors developed from the region itself. Non-parametric ML for LUR modeling performed with high accuracy for prediction of monthly PM2.5 levels. Our analysis suggests that locally produced low-cost air quality sensors can help build capacity to conduct air pollution epidemiology research in the region.

The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

The mere co-presence of another person synchronizes physiological signals, but no study has systematically investigated effects of type of emotional context and type of relationship in eliciting dyadic physiological synchrony. In this study, we investigated the synchrony of pairs of strangers, companions, and romantic partners while watching a series of video clips designed to elicit different emotions. Maximal cross-correlation of heart rate variability (HRV) was used to quantify dyadic synchrony. The findings suggest that an existing social relationship might reduce the predisposition to conform one's autonomic responses to a friend or romantic partner during social situations that do not require direct interaction.

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable global disruption to clinical practice. This article will review the impact that the pandemic has had on oncology clinical trials. It will assess the effect of the COVID-19 situation on the initial presentation and investigation of patients with suspected cancer. It will also discuss the impact of the pandemic on the subsequent management of cancer patients and how clinical trial approval, recruitment and conduct were affected during the pandemic. An intriguing aspect of the pandemic is that clinical trials investigating treatments for COVID-19 and vaccinations against the causative virus, SARS-CoV-2, have been approved and conducted at unprecedented speed. In light of this, this re-view will also discuss the potential that this enhanced regulatory environment could have on the running of oncology clinical trials in the future.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Dengue is the most prevalent arthropod-borne disease globally and affects approximately 2.5 billion people living in over 100 countries. The increasing geographic expansion of Aedes aegypti mosquitoes which transmit the virus has made dengue fever a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue therefore remains largely supportive to date; hence research efforts are being intensified for the development of antivirals against dengue. The NS3 and NS5 nonstructural proteins have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses including dengue. Its multifunctionality makes it an attractive target for antiviral development against dengue, but research efforts are hindered due to its limited structural characterization compared to the NS5 of other flaviviruses like the Zika virus. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development against dengue.

This study aimed at testing the effectiveness of novel combinations of chemical and physical methods to control Prosopis juliflora, an invasive weed in the Moshi and Simanjiro districts of Nothern Tan-zania. Six different treatments including manual uprooting, glyphosate, bark chop with chemical application, two separate chemical mixtures and control were tested in a total of 32 plots, which represented two land use types (grazing land and farmland) found in the two districts. Each plot covered 20m×30m plot area. Two response variables (stem count and tree volume) were recorded to compare weed population density before and after treatment six months later. An analysis of the untreated control plots, showed that the inherent growth potential of P. juliflora was higher in Moshi than in Simanjiro district. The number of stems increased during the experiment for all six treatments showing that the P. juliflora population had not yet reached the local carrying capacity. For the manual control treatment, the increase was reduced compared to the untreated control. For all other treatments, the increase in stem count was on par with that in the untreated control or even higher. Thus, we conclude that only manual uprooting had a controlling effect but not to the extent that it eradicated P. juliflora. Thus, it is for P. juliflora as for weed control in general: weed control must be an ongoing effort.

Exposure to air pollution have detrimental effects on the elderly, women, people with pre-existing medical conditions, people living in poverty and children. The aim of the study was to investigate the extent of community awareness and knowledge on the health risks associated with exposure to air pollution. A cross-sectional study design was used for the study, using self-administered questionnaires. A simple random sampling technique was used to select 376 respondents. Systematic sampling method was applied to select the households. SPSS version 26 was used to analyze data. Of 376 respondents, 221 were males and 154 females. 113 were aged between 23-47years and 353 were aware that if they don’t protect themselves against polluted air, they may get sick, with age and educational status associated with their awareness (p &lt; 0.05). About 361 knew what air pollution is and 188 think the air they breathe in Annadale is moderate. A total number of 278 said they feel sick/uncomfortable when the quality of air is bad. About 293 knew that people are exposed to air pollution by breathing contaminated air and 237 identified sewage smell as the main cause of air pollution. Respondents who identified internet and television as the main source of information were 199 and 177 respectively. Those who were not aware of actions implemented to reduce air pollution were 180. Based on the results of the study, respondents are aware of the dangers of exposure to polluted air, and it is necessary that air pollution risk communication strategies be implemented to empower residents.

Folk nomenclature is habitually established for species that have attained high utilitarian and cultural significance by custodians of such plants worldwide. Such folk names assigned to species often carry etymological values such as therapeutic effects, morphological features, mythical connotations, and their allegorical values. This research sought to unveil the etymology in folk nomenclatures of Sphenostysis stenocarpa (Hosch ex A. Rich) Harms (African Yam Bean). Three hundred and fifty respondents were randomly selected from 13 local communities in Ebonyi State in South-eastern, Nigeria. Data were collected through oral interviews with semi-structural questionnaires, along with focused group discussions. Analysis of data was carried out using simple statistical methods involving frequencies and percentages. The results recorded ten folk nomenclatures assigned to this species in seven dialects affiliated to cultural values within these communities. Etymologically, the results also revealed that out of the ten folk names of AYB cryptic connotations, five reflected their trust in the gods that answered their prayers, two were attributed to the healing potentials inherent in this crop for medicine, three names were associated with the seeds, while one referred to feminist attachment to the crop, another to its resilience/ adaptability to climatic stress and one as a sustainer of farmers. Considering that folk nomenclature is based mainly on qualitative data and the information outside the scientific domain, they are nonetheless highly valued because they are based on long-term interactions, utilization and observations of the custodians of these natural resources. However, these data are equally vulnerable to erosion if not properly documented and conserved for posterity.

Background: Healthcare workers are exposed to several hazardous chemicals in the workplace that can result in numerous adverse health effects. Several published studies from many different countries have documented the presence of metabolites from antineoplastic drugs in the urine of healthcare workers and demonstrated contaminated working surfaces with these agents. This study is a literature review that aims to compare the prevalence and degree of exposure to cyclophosphamide (CP), ifosfamide (IFO), and methotrexate (MTX) in physicians, nurses, and pharmacists in the hospital setting. Methods: An extensive search was conducted on PubMed, Google Scholar, HINARI, OARE, and Science Direct where applicable research about healthcare workers and antineoplastic drugs exposure were identified. Medical Subject Headings (MeSH) keywords: occupational exposure, antineoplastic drugs (cytotoxic drugs, cyclophosphamide, ifosfamide, methotrexate), hazardous chemicals, healthcare workers (healthcare professionals, nurses, pharmacists, physicians), hospital setting, and adverse health outcomes were used. Thereafter, relevant articles from 2000 to 2020 were selected to perform this literature review. Results: Review of literature demonstrated that cyclophosphamide was the most prevalent contaminant in the hospital setting. Additionally, pharmacists are among the group of healthcare workers with the highest prevalence of antineoplastic agents in urine samples while nursing stations had the highest rate of surface contamination. Conclusion: There is an urgent need to develop a system to monitor and detect the pathway of environmental exposure to antineoplastic drugs in the healthcare setting, and to evaluate the effectiveness of the existing protective measures. Well designed studies focusing on improving the standard safety precautions is a priority to protect healthcare workers.

The first diastereoselective synthesis of (–)-1-epi-lentiginosine stars from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate tras-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

Patients hospitalized with COVID-19 are at a higher risk of thrombotic events following discharge, however the role of extended thromboprophylaxis remains controversial. The purpose of this study is to evaluate current extended post-discharge thromboprophylaxis practice and its outcomes.This study was a single-center, retrospective chart review of patients within Hennepin Healthcare hospitalized with COVID-19 from April 1^st 2020 to December 31^st 2021 with increased risk of thrombotic event based on D-dimer. The primary outcome was to describe current prescribing practices based on the number of patients who were eligible and received anticoagulants on discharge. Secondary outcomes included comparing the patient’s risk for thromboembolism based on a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE) score to the current internal prescribing practice guideline, evaluating efficacy outcomes based on new thromboembolic events, and assessing safety of extended-thromboprophylaxis using the International Society of Thrombosis and Hemostasis criteria for major bleeding within 30 days of hospitalization discharge.Of 1984 patients who were hospitalized with COVID-19 infection, 961 patients were eligible to receive thromboprophylaxis at discharge, with a total of 191 patients who received anticoagulation according to the Hennepin Healthcare practice guideline. However, using the IMPROVE-VTE score, only 206 patients qualified for post-discharge thromboprophylaxis, and 63 total patients received anticoagulation. A new thromboembolic event occurred in 20 patients (5.8%) and 14 patients (4.1%) experienced major bleeding.The Hennepin Healthcare guideline for extended thromboprophylaxis at discharge encompassed more patients compared to the IMPROVE-VTE score. The incidence of a new thromboembolic event and major bleeding were low in both groups, although venous thrombotic events occurred more in thromboprophylaxis group than in patients who did not receive anticoagulation at discharge, more clinical data are needed for a conclusion.

In this research article we solve the problem of synchronization and anti-synchronization of chaotic systems described by discrete and time-delayed variable fractional order differential equations. To guarantee the synchronization and anti-synchronization of these systems, we use the well-known PID control theory and the Lyapunov-Krasovskii stability theory for discrete systems of variable fractional order.We illustrate the results obtained through simulation with examples, in which it can be seen that our results are satisfactory, thus achieving synchronization and anti-synchronization of chaotic systems of variable fractional order with discrete time delay.

In Uganda, the common bean (Phaseolus vulgaris) is often infested by a complex of insect pests, but the bean stem maggots, aphids, bean leaf beetles, and flower thrips are the most important. Whereas yield losses due to these pests have been established, there is limited information on their population dynamics at different stages of crop growth and their effect on yield and yield components. In order to describe the population dynamics of selected common bean pests at various phases of bean crop growth, and their impact on yield and yield components, a study was carried out in Uganda during 2016 second rains and 2017 first rains in three agro-ecological zones. Bean fly, bean aphids, bean leaf beetles, whitefly, striped bean weevil, leaf hoppers, and caterpillars of Lepidopteran species were the main insects observed. Pesticide spray schedules were imposed to generate different populations of insect pests whose effects on yield and its components were determined. The findings indicate that spray regimes significantly influenced the abundance of bean fly, aphids, whitefly, striped bean weevil, and leaf hoppers but not bean leaf beetles and caterpillars. Additionally, except caterpillars, insect pests were significantly influenced by crop growth stages, but only aphids, whiteflies, bean flies and leaf hoppers exhibited a significant negative relationship with grain yield. Furthermore, yield and yield components varied significantly between spray regimes, agro-ecological zones, and seasons. Our study is important in informing growers on the stage of crop growth at which management tactics such as use of insecticides can be applied for different insect pests.

Abstract Epithelial ovarian carcinoma (EOC) is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. EOC is poorly responsive to immune check-point inhibitors due to immunologic features including limited tumor mutational burden (TMB), poor infiltration by immune cells and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of preexisting immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC) which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of DCVAC were more pronounced in patients with EOC with lower than-median TMB and scant CD8+ T cells infiltration. Thus, DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically „cold“ EOC. Our findings underscore the need for personalized immunotherapy and clinical relevance of potential tumor-related biomarkers within immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of TMB and immune infiltrate at baseline as biomarkers to guide the clinical management of EOC.

Matrix Metaloproteinase-2 (MMP-2) is an extracellular Zn²⁺ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed 10 families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamics cross correlation analysis indicated domain movements corresponding to opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the MMPBSA-interaction entropy analysis method and revealed strong binding energies for the catalytic Zn²⁺ ion 1, Ca²⁺ ion 1, and Ca²⁺ ion 3 with significant conformational stability at the binding sites of Zn²⁺ ion 1 and Ca²⁺ ion 1. Ca²⁺ ion 2 diffuses freely away from its crystallographically defined binding site. Zn²⁺ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca²⁺ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain.

Dynamic crossflow filtration (DCF) is the state-of-the-art technology for solid-liquid separation from viscous and sensitive feed streams in the food and biopharma industry. Up to now, the potential of industrial processes is often not fully exploited because fixed recipes are usually applied to run the processes. Therefore, a digital twin has been developed to optimize an industrial brownfield DCF plant. The core of the digital twin is a mechanistic-empirical process model combining fundamental filtration laws with process expert knowledge. The effect of variation of selected process and model parameters on plant productivity has been assessed using a model-based design-of-experiments approach and a regression metamodel has been trained with the data. A cyclic program that bidirectionally communicates with the DCF asset serves as frame of the digital twin. It monitors the process dynamics membrane torque and transmembrane pressure and feeds back the optimum permeate flow rate setpoint to the physical asset in almost real-time during process runs. The presented digital twin framework is a simple example how an industrial established process can be controlled by a hybrid model-based algorithm. With a digital process dynamics model at hand, the presented metamodel optimization approach can be easily transferred to other (bio)chemical processes.

Ecological niche models have become exceptionally important, since their results allow to un-derstand many aspects related to the biology of the species being studied, even understanding its evolutionary relationships or their response to past or future projections. In this research, models were prepared to create climatic surfaces so as to produce bioclimatic layers based on the mete-orological data of the south of Peru. Temperature and precipitation data from 119 stations were obtained and homogenized. Then, using geographic and orographic covariates, models were prepared so as to obtain climatic surfaces of maximum and minimum temperature, and precipi-tation. The produced layers were evaluated through root-mean-square deviation (RMSD), mean absolute deviation of error (MAD) and goodness of fit (R2), and they were compared to other models for the area. Finally, the 19 bioclimatic surfaces were created. The results show general patterns for temperature and precipitation, some of them being particular. The climatic layers produced showed acceptable values for RMSD, MAD and R2. Comparison with other models shows statistically significant differences. Both the climatic and the produced bioclimatic surfaces were entered into a database for free access. Finally, comments are made on the importance and application of the bioclimatic layers produced here.

The Betz limit sets a theoretical upper limit for the power production by turbines expressed as a maximum power coefficient of 16/27. Betz’s theory is accurate and it is based on the calculation of kinetic energy.

One of the most promising advancements in healthcare is the application of digital twin technology. Digital twins are virtual replicas of real-world human patients and can be used for monitoring, and diagnosis, and as a tool to design treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and predicting the effects of drugs and other chemical substances in development. This review article delves into the various data sources and methodologies that contribute to the construction of digital twins. Each data source, including blood glucose levels, heart MRI and CT scans, cardiac electrophysiology, written reports, and multi-omics data, comes with different challenges regarding standardization, integration, and interpretation. We showcase how various datasets and methods are used to overcome these obstacles and generate a digital twin. While digital twin technology has seen significant progress, there are still hurdles in the way to achieving a fully comprehensive patient digital twin. Developments in non-invasive and high-throughput data collection, as well as advancements in modeling and computational power will be crucial to improve digital twin systems. We discuss a few critical developments in light of the current state of digital twin technology. Despite challenges, digital twin research holds great promise for personalized patient care and has the potential to shape the future of healthcare innovation.

Groundwater is the most extracted raw material in the world with global annual withdrawal rates of 800–1500 km3/year. In East and Southern Africa, 70 % of the population are reliant on shallow groundwater as their primary drinking water source. With increased population growth, intensification of agriculture and industrialization, conflicting demands on groundwater present a challenge to achieve the Sustainable Development Goals (6,3,11,12,15). Between 2015 and 2018, the Horn of Africa was affected by a series of climatic induced events, namely El Nino, La Nina and the Indian Ocean Diopole. These events modified the variability of rainfall patterns and resulted in long periods of low rainfall, low recharge and high evapotranspiration. As a result, shallow aquifers in alluvial deposits of Somali region have low yields and produce brackish and saline water. That situation prompted humanitarian water professionals to finance the transportation of water from selected locations with high groundwater potential through water trucks to areas facing groundwater depletion and drought. To address this challenge, UNICEF explored alternative, sustainable deeper groundwater sources that could be extracted using solar water pumping technology for multi water use. This paper describes a three-phase methodology of deep groundwater development of wells in the Ogaden Jesoma sandstone aquifers of the Somali region of the Horn of Africa to a depth of 600 meters below ground level. The results concluded that the deep sandstone aquifer of Jesoma can provide fresh water with yields of 15 l/s to the local population of Somali region. to the study provided insights into deep groundwater identification and development as well as adaptive deep boreholes drilling as a source for climate resilient water supplies.

Unlike trees, shrubs (i.e., multiple-stemmed woody plants) do not need evenly spaced large diameter structural roots and thus can spread further per unit belowground biomass. We therefore hypothesized that compared to trees, shrubs respond more to asymmetric distributions of nutrients and reach nutrient-rich patches of soil faster and with less below-ground biomass. To test these hypotheses we planted individual seedlings of shrubs (Cornus racemosa, Rhus glabra, and Viburnum dentatum) and trees (Acer rubrum, Betula populifera, and Fraxinus americana) in the centers of sand-filled rectangular boxes. In one direction we created stepwise gradients of increasing soil nutrients with slow-release fertilizer; in the other direction no fertilizer was added. Seedlings were harvested when their first root reached the plexiglass-covered fertilized end of their box; time taken as well as above- and below-ground biomass by nutrient segment were determined. There were no consistent differences between the shrubs and trees in belowground architectural plasticity (= ratio of biomass in fertilized and unfertilized volumes of soil) or in the rate and efficiency of lateral growth. Interspecific variation appeared more related to edaphic characteristics of the native habitats than to growth form. The fastest and most efficient roots were produced by the shrub (R. glabra) and the tree (B. populifolia) that are characteristic of poor soils. Root foraging by R. glabra was also facilitated by rapid rhizomatous expansion. The tested shrubs and trees did not consistently differ in nutrient foraging efficiencies or rates but further study is warranted with larger plants and more species.

We are losing love. By studying porn movies to understand love, I discovered that love originally comes from the body, from positive emotions and vibrations of the wonderful body, from the heart and all other parts of the body, such as sexual organs. António Damásio made Descartes’ error by postulating that feelings increase their power from homeostasis (mechanisms of life regu-lation from bacteria to humans). He made this mistake unconsciously because many people un-consciously have a very bad opinion of sexual organs. We consider them ugly because they come from the prehistoric period. I have combined António and Hanna Damásio’s work (body emotions, thinking and language). I discovered that porn actors do not talk during sex, and this is striking. Porn actors mirror what happens in society. This means that people come from prehistory, do not talk during sex, and still unconsciously behave like primitive animals during sexual intercourse; we do not respect the body sufficiently during sex. Therefore, love, which comes from the body, is smothered and buried. We must very delicately talk to the wonderful, delicious and respectful body to wake up love feelings, body emotions and vibrations during sex. We must invent talking movies with porn films. Language of positive emotions associated with the language of wonderful and delicious body will warm love feelings and will give envy to love through sexual intercourse because António Damásio discovered that emotions are social.

Filter Media (FM) sourced from recycled organic and mineral material offers a low cost and effective means of treating urban stormwater. Using recycled materials rather than from an increasingly scarce source of virgin materials (typically sandy loam soil) can ensure a sustainable long-term economy and environment. This paper presents results from the laboratory analysis and mathematical modeling to highlight the performance of recycled organic and mineral material in removing nutrients and metals from stormwater. Analysis included physical and chemical characterisation such as particle size distribution, saturated hydraulic conductivity (Ksat), bulk density, effective cation exchange capacity, and pollutant removal performance. Design mixes (DM), comprising a combination of organic and mineral materials, were characterised and used to develop/derive modelling design within the Model for Urban Stormwater Improvement Conceptualisation (MUSIC v6) [1]. Comparison is made to the Adoption Guidelines for Stormwater Biofiltration Systems - Summary Report [2] which were based on the Facility for Advancing Water Biofiltration (FAWB) guidelines to assist in the development of biofiltration systems, including the planning, design, construction and operation of those systems. An observed outcome from over two decades of biofiltration guideline development has been the exclusion of alternative biofilter materials due to claims of excessive leaching. Results from this study indicate that high nutrient and metal removal rates can be achieved over a range of hydraulic conductivities using design mixes of recycled organic and mineral materials that have a demonstrated equivalence to existing guideline specifications.

This study investigates via Lie symmetry analysis the Hunter-Saxton equation, an equation relevant to the theoretical analysis of nematic liquid crystals. We employ the multiplier method to obtain conservation laws of the equation derived from first-order multipliers. Conservation laws of the Hunter-Saxton equation, in combination with the Lie point symmetries of the equation, enable us to perform symmetry reductions through employment of the double reduction method. The method exploits the relationship between Lie point symmetries and conservation laws to effectively reduce both the number of variables and the order of the equation. Five nontrivial conservation laws of the Hunter-Saxton equation are derived, four of which are found to have associated Lie point symmetries. Applying the double reduction method to the Hunter-Saxton equation results in a set of first-order ordinary differential equations, the solutions of which represent invariant solutions for the equation.

Imaging of the ocular vasculature can provide new insights into the pathophysiology of ocular diseases. This study proposes a novel high-frequency super-resolution ultrasound localization microscopy (SRULM) technique and evaluates its ability to measure in vivo perfusion changes in the rat eye at elevated intraocular pressure (IOP). A 38.4 MHz center frequency linear array transducer on a VisualSonics Vevo F2 imaging platform was used to collect high frame rate (1 kHz) radiofrequency data of the posterior rat eye following systemic microbubble contrast injection. Following clutter and spatiotemporal non-local means filtering, individual microbubbles were localized and tracked. The microbubble tracks were accumulated over 10,000 frames to generate vascular images quantifying perfusion velocity and direction. Experiments were performed using physiologic relevant controlled flow states for algorithm validation and subsequently performed in vivo on the rat eye at 10 mm Hg IOP increments from 10 to 60 mm Hg. The posterior vasculature of the rat eye, including the ophthalmic artery, long posterior ciliary arteries and their branches, central retinal artery and retinal arterioles and venules were successfully visualized, and velocities quantified at each IOP level. Significant reductions in arterial flow were measured as IOP was elevated. High-frequency SRULM can be used to visualize and quantify perfusion velocity of the rat eye in both the retrobulbar and intraocular vasculature simultaneously. The ability to detect ocular perfusion changes throughout the depth of the eye may help elucidate the role ischemia has in the pathophysiology of ocular diseases such as glaucoma.

We investigate alternative candidates to dark energy that can explain the current state of the universe in the framework of the generalized teleparallel theory of gravity f(T ) where T denotes the torsion scalar. To achieve this, we carried out a series of reconstruction taking into account to the ordinary and entropy-corrected versions of the holographic and new agegraphic dark energy models. These models used as alternative to dark energy in the literature in order describe the current state of our universe. It is remarked that the models reconstructed indicates behaviors like phantom or quintessence models. Furthermore, we also generated the EoS parameters associated to entropy-corrected models and we observed a transition phase between quintessence state and phantom state as showed by recent observational data. We also investigated on the stability theses models and we created the {r − s}. The behavior of certains physical parameters as speed of sound and the Statefinder parameters are compatible with current observational data.

Background: With a rapid rise in our older adult population globally and due to their multimorbidities, our older adults are more likely to engage in the services provided in the emergency department at a higher rate than younger adults. The current emergency service delivery model may be ineffective against such an ageing phenomenon. Research reports most older adults having one or more co-morbidities including functional decline, dementia, and frailty. Studies have shown that older adults have been undertriaged with physicians not being able to comprehend their complex needs related to their presenting complaints in the emergency department. Geriatric emergency departments have incepted worldwide to better manage this care deficiency in the rapidly ageing society around the world. Data Sources: A search of published literature from 2010-2020 using (keywords) as described below was undertaken of which, relevant literature were selected for an informed review. Implications for Nursing: Understanding geriatric emergencies can enable healthcare workers to reduce undertriaging and provide appropriate care that improves patient's health outcomes currently and in the future in the emergency department. Further education in gerontology can also be a platform for our nurses to enhance their care and thought process, likewise upskilling themselves for the future geriatric population seeking treatment. Older healthcare workers will also be able to enhance their current job scope before retirement. In-house teachings from trained gerontologists or certified programs can shed light on the special care needs of our senior citizens globally. Conclusion: With our rapidly increasing population, we can expect an influx of our older patients both from home and long-term care facilities to present to the emergency department with a wide range of geriatric emergencies. By being able to create a geriatric screening process and tailored care models, healthcare workers will be able to understand their care process and in turn, improve patients' health outcomes and provide a quicker transition of care.

We exploit the properties of complex time to obtain an analytical relationship based on considerations of causality between the two conserved quantities of a system’s Hamiltonian and its Entropy Production. In natural units, when complexified, the one is simply the Wick-rotated complex-conjugate of the other. A Hilbert transform relation is constructed in the formalism of Quantitative Geometrical Thermodynamics which enables system irreversibility to be handled analytically within a framework that unifies both the microscopic and macroscopic scales, and which also unifies the treatment of both reversibility and irreversibility as complementary parts of a single physical description. In particular the thermodynamics of two unitary entities are considered: the alpha particle which is absolutely stable (that is, trivially reversible with zero entropy production), and a black hole whose absolute disequilibrium (unconditional irreversibility) is characterized by a non-zero entropy production for which we show an alternate derivation confirming our previous one (Universe 7, 2021, 325). The thermodynamics of a canonical decaying harmonic oscillator are also considered. In this treatment the complexification of time also enables a meaningful physical interpretation of both “imaginary time” and “imaginary energy”.

In this study the impact of terrorist attacks on exchange rate is estimated. Particularly, the study focuses on Turkish terrorist attacks and its implication on Turkish lira versus pound sterling exchange rate. In order, to find the causal effect the study employed Autoregressive distributive lag (ARDL) bound testing approach as an estimation technique. Accordingly, the analysis reveals that terrorist attack has a negative impact on the exchange rate in both short and long-run. However, the negative effect of terrorism tends to be small in both the short-run and long-run. More precisely, terrorist attack depreciates the exchange rate between Turkish lira and pound sterling by approximately 0.00072 in the next trading day. The long-term effect also shows that terrorist attack depreciates the exchange rate on average by 0.00212.

Abstract: Seismic performance and loss assessments can have widely varying degrees of uncertainty. An essential issue is whether a particular assessed seismic loss or performance result has sufficient reliability to serve as the basis for risk management decisions and actions, including whether or not a code prescribed performance level is met, or if an assessed loss level is acceptable. A method is developed measuring the reliability of performance and loss assessments for individual buildings and for portfolios. Consideration is given to how well the building investigation and corresponding evaluation process have been performed, the qualifications of the person(s) doing the assessment, the thoroughness of the evaluation, and the technical validity of the assessment procedure or model. The approach characterizes the uncertainty of each component of the assessment procedure for each building in qualitative terms. The resulting reliability measure is likely to be most useful for the cases where an entity is determining whether/or not a building has acceptable life safety performance, or if a portfolio has an acceptably low risk of seismic damage loss over a given period of time. In both cases, the reliability must either be sufficient to warrant action, or serve to indicate need for improved assessment.

We present a partition of quantum observables in an open quantum system which is inherited from the division of the underlying Hilbert space or configuration space. It is shown that this partition leads to the definition of an inhomogeneous continuity equation for generic, non-local observables. This formalism is employed to describe the local evolution of the von Neumann entropy of a system of independent quantum particles out of equilibrium. Crucially, we find that all local fluctuations in the entropy are governed by an entropy current operator, implying that the production of entanglement entropy is not measured by this partitioned entropy. For systems linearly perturbed from equilibrium, it is shown that this entropy current is equivalent to a heat current, provided that the system-reservoir coupling is partitioned symmetrically. Finally, we show that any other partition of the coupling leads directly to a divergence of the von Neumann entropy. Thus, we conclude that Hilbert-space partitioning is the only partition of the von Neumann entropy which is consistent with the Laws of Thermodynamics.

The Principle of Indifference (“PI”: the simplest non-informative prior in Bayesian probability) has been shown to lead to paradoxes since Bertrand (1889). Von Mises (1928) introduced the “Wine/Water Paradox” as a resonant example of a “Bertrand paradox”, and which has been presented as demonstrating that the PI must be rejected. We now resolve these paradoxes by a Maximum Entropy (MaxEnt) treatment of the PI that also includes information provided by Benford’s “Law of Anomalous Numbers” (1938). We show that the PI should be understood to represent a family of informationally-identical MaxEnt solutions; each solution being identified with its own explicitly justified boundary condition. In particular, our solution of the Wine/Water Paradox exploits Benford’s Law to construct a non-uniform distribution representing the universal constraint of scale invariance, which is a physical consequence of the Second Law of Thermodynamics.

With the rapid expansion of intelligent resource-constrained devices and high-speed communication technologies, Internet of Things (IoT) has earned a wide recognition as the primary standard for low-power lossy networks (LLNs). Nevertheless, IoT infrastructures are vulnerable to cyber-attacks due to the constraints in computation, storage, and communication capacity of the endpoint devices. From one side, the majority of newly developed cyber-attacks are formed by slightly mutating formerly established cyber-attacks to produce a new attack tending to be treated as a normal traffic through the IoT network. From the other side, the influence of coupling the deep learning techniques with cybersecurity field has become a recent inclination of many security applications due to their impressive performance. In this paper, we provide a comprehensive development of a new intelligent and autonomous deep learning-based detection and classification system for cyber-attacks in IoT communication networks leveraging the power of convolutional neural networks, abbreviated as (IoT-IDCS-CNN). The proposed IoT-IDCS-CNN makes use of the high-performance computing employing the robust CUDA based Nvidia GPUs and the parallel processing employing the high-speed I9-Cores based Intel CPUs. In particular, the proposed system is composed of three subsystems: Feature Engineering subsystem, Feature Learning subsystem and Traffic classification subsystem. All subsystems are developed, verified, integrated, and validated in this research. To evaluate the developed system, we employed the NSL-KDD dataset which includes all the key attacks in the IoT computing. The simulation results demonstrated more than 99.3% and 98.2% of cyber-attacks’ classification accuracy for the binary-class classifier (normal vs anomaly) and the multi-class classifier (five categories) respectively. The proposed system was validated using k-fold cross validation method and was evaluated using the confusion matrix parameters (i.e., TN, TP, FN, FP) along with other classification performance metrics including precision, recall, F1-score, and false alarm rate. The test and evaluation results of the IoT-IDCS-CNN system outperformed many recent machine-learning based IDCS systems in the same area of study.

Protein tyrosine phosphatases (PTPs) of the polymerase and histidinol phosphatases (PHP) superfamily with characteristic phosphatase activity dependent on divalent metal ions are found in many gram-positive bacteria. Although members of this family are co-purified with metal ions, they still require the exogenous supply of metal ions for full activation. However, the specific roles these metal ions play during catalysis are yet to be well understood. Here, we report the metal ion requirement for phosphatase activities of S. aureus Cap8C and L. rhamnosus Wzb. AlphaFold-predicted structures of the two PTPs suggest that they are members of the PHP family. Like other PHP phosphatases, the two enzymes have catalytic preference for Mn2+, Co2+, and Ni2+ ions. Cap8C and Wzb show an unusual thermophilic property with optimum activities over 75oC. Pre-incubation experiments show that the two enzymes are not inherently thermostable suggesting that certain catalytic step(s) in the reaction mechanism has a high activation energy. Consistent with this model, the activity-temperature profiles of the two enzymes are dependent on the divalent metal ion activating the enzyme.

The morphological aspects of urban growth on wetlands in Africa are under-researched. Using the Densu Delta Ramsar site in Accra, Ghana, as a case study, this paper analyses the morphological patterns and drivers of urban growth and its impact on wetlands. Data were obtained through remote-sensing, ground truthing and limited key informant interviews. The analysis combined land use/land cover, building coverage and multiple regression techniques, with the aid of GIS and STATA software. The findings reveal that urban growth at the Ramsar site follows discernible spatial patterns consistent with the spreading pancake, village magnet and ribbon development models. However, the primary force behind these patterns is growing demand for land to meet housing needs, aided by the failure of state institutions to perform their land use control and wetland protection functions. To achieve sustainable urban development, there is an urgent need to ensure effective wetland management by enforcing existing land use, development control and wetland protection measures. This calls for the strengthening, resourcing and closer collaboration between the various state agencies responsible for urban planning and wetland management. There is also the need to engage and sensitise political leaders to increase their commitment to implementing wetland protection and pro-environmental policies.

Background: Immersive therapy through virtual reality represents a novel strategy used in psychological interventions, but there is still a need to strengthen the evidence on its effects on health professionals’ mental health. Objective: To analyze the results of immersive therapy through virtual reality in the levels of anxiety and secondly, well-being of the health professionals working in a regional hospital in Olot (Spain). Methods: Pilot quasi-experimental study including a group of 35 women (mean age=45.7, SD=8.43) health professionals who undertook immersive therapy for 8 weeks. The intervention was implemented through virtual reality, and its effect on anxiety levels and well-being was evaluated through the Hamilton and Eudemon scales, respectively. Data on age, gender, active pharmacological or psychological treatment, mental health disorders and number of sessions were also collected. Results: Statistically significant (p<0.001) improvement in anxiety and well-being was found, with large and moderate effect sizes (0.90 and 0.63 respectively). In addition, these changes were clinically significant. No significant associations were found between the improvements and the different variables, but a greater trend was identified among the group of professionals with untreated or unidentified levels of anxiety. Conclusion: This group of health professionals showed statistically and clinically significant improvement in anxiety and well-being after the application of immersive therapy using virtual reality. Further studies with a control group are necessary to further analyze this novel intervention.

Many marine animals use chemicals to defend themselves and their eggs from predators. Beyond their ecologically relevant functions, these chemicals may also have properties that make them beneficial for humans, including with biomedical and industrial applications. For example, some chemical defenses are also powerful antimicrobial or anti-tumor agents with relevance to human health and disease. One such chemical defense, Escapin, an L–amino acid oxidase in the defensive ink of the sea hare Aplysia californica, and related proteins have been investigated for their biomedical properties. This review details our current understanding of Escapin’s antimicrobial activity, including the array of chemicals generated by Escapin’s oxidation of its major substrates, L–lysine and L–arginine, and mechanisms underlying these molecules’ bactericidal and bacteriostatic effects on planktonic cells and the prevention of formation and removal of bacterial biofilms. Models of Escapin’s effects are presented, and future directions are proposed.

We describe and analyze the Local Charged Particle Swarm Optimization (LCPSO) algorithm, that we designed to solve the problem of tracking a moving target releasing scalar information in a constrained environment using a swarm of agents. This method is inspired by flocking algorithms and the PSO algorithm for function optimization. Four parameters drive LCPSO: the number of agents; the inertia weight; the attraction/repulsion weight; and the inter-agent distance. Using APF, we provide a mathematical analysis of the LCPSO algorithm under some simplifying assumptions. First, the swarm will aggregate and attain a stable formation, whatever the initial conditions. Second, the swarm moves thanks to an attractor in the swarm, which serves as a guide for the other agents to head for the target. By focusing on a simple application of target tracking with communication constraints, we then remove those assumptions one by one. We show the algorithm is resilient to constraints on the communication range, and the behavior of the target. Results on simulation confirm our theoretical analysis. This provides useful guidelines to understand and control the LCPSO algorithm as a function of swarm characteristics as well as the nature of the target.

Most existing coal-fired power plants were designed for sustained operation at full load to maximize efficiency, reliability, and revenue, as well as to operate air pollution control devices at design conditions. Depending on plant type and design, these plants can adjust output within a fixed range in response to the plant operating or market conditions. The need for flexibility driven by increased penetration of variable and non-dispatchable power generation such as wind and solar is shifting the traditional mission profile of thermoelectric power plants in three ways: more frequent shutdowns when market or grid conditions warrant, more aggressive load ramp rates (rate of output change), and lower minimum sustainable load, which provides a wider operating range and helps avoid costly plant shutdowns. Recent studies have shown that flexibility of a coal-fired power plant can be improved by energy storage. The objective of this work was to analyze a set of energy storage options and determine their impact on flexibility and economics of a representative coal-fired power plant. The effect of three energy storage systems integrated with a coal power plant on plant flexibility and economics was investigated. The results obtained in this project show that Energy Storage Systems integrated with a thermal power plant improves plant flexibility and participation in the Energy and Ancillary Services markets which improves plant financial performance. The study was funded by the U.S. Department Office of Fossil Energy FE-1 under Award Number DE-FE0031903.

Violence against paramedics is widely recognized as a serious, but underreported, problem. While injurious physical attacks on paramedics are generally reported, non-physical violence is less likely to be documented. Verbal abuse can be very distressing, particularly if the harassment targets personal or cultural identities, such as race, ethnicity, gender, or sexual orientation. Leveraging a novel, point-of-event reporting process, our objective was to estimate the prevalence of harassment on identity grounds against paramedics in a single paramedic service in Ontario, Canada, and assess its potentially differential impact on emotional distress. In an analysis of 502 reports filed between February 1, 2021, through February 28, 2022, two paramedic-supervisors independently coded the free-text narrative descriptions of violent encounters for themes suggestive of sexism, racism, and homophobia. We achieved high interrater agreement across the dimensions (k=0.73-0.83), and after resolving discrepant cases, we found that 1 in 4 violent reports documented abuse on at least one of the identity grounds. In these cases, paramedics were 60% more likely to indicate being emotionally distressed than for other forms of violence. Our findings offer unique insight into the type of vitriol paramedics experience in the course of their work and its potential for psychological harm.

Heritage bridges constitute an integral feature of the urban landscape in numerous cities. However, it is common for these structures to surpass their life cycle, rendering them ill-equipped to withstand the dynamic demands of users and extreme events, particularly hydrological occurrences. This research presents a methodology for the assessment of heritage riverine bridges, with a focus on the Grau Bridge in Peru as a case study. The investigation commences with an exhaustive literature review, complemented by a historical examination, followed by a preliminary diagnosis. Subsequently, hydrological and hydraulic studies are conducted, encompassing drone surveys of the riverbed and the bridge, soil analyses, and the application of 1D and 2D models in HEC-RAS. The outcomes of this comprehensive analysis reveal the high vulnerability of the Grau Bridge. Finally, strategic recommendations for its conservation are recommended.

Diarrhoea caused by enterotoxigenic Escherichia coli is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhoea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed eleven single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched Lacto-N-neohexaose (Galbeta4GlcNAcbeta6[Galbeta4GlcNAcbeta3]Galbeta4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity.

One of the non-linear phenomena that affect high bandwidth and long reach communication systems is the non-linear phenomenon called four-wave mixing (FWM). Unfortunately, the simulation of such systems aiming to obtain their design parameter limitations require more time as the number of channels increases. In this paper, we propose a new high-performance computational model to obtain optimal design parameters in a multi san Dense Wavelength Division Multiplexing (DWDM) system, limited by FWM and the intrinsic Amplified Spontaneous Emission (ASE) noise of optical amplifiers employed in each segment. The simulation in this work provides a complete optical design characterization and compares the efficiency and speed improvement of the proposed parallelization model versus a previous sequential model. Additionally, an analysis of the computational complexity of parallel model is presented, where two parallel implementations are used. First, Open Multi−Processing (OpenMP), based on the use of a central, multi-core processing unit is used and secondly the Compute Unified Device Arquitecture (CUDA), which is based on the use of graphics processing unit. Results show that parallelism improves to up to 40 times the performance of the simulation when nested parallelization with CUDA is used, over de sequential method and up to 6 times compared with the implementation with OpenMP using 12 processors. Within our parallel implementation, it is possible to simulate with an increased number of channels, that was unpractical in the sequential simulation.

Climate change is impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes including chromoso-mal inversions and overexpression and/or changes in allele frequencies of thermotoler-ance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investi-gated the impact of thermotolerance on pyrethroid resistance in four populations of malaria vector An. gambiae, from savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38°C, and LT50 of ~44°C. Significantly high permethrin resistance was observed (mortality <50%) in heat-hardened (44°C) larvae from two sites, BUK and Pantami, compared with control, and heat-hardened adult females from Auyo (mortality = 3.00%±1.20, χ2 = 5.83, p<0.01) compared with control (12.00%±4.65). The 2La chromosomal inver-sion was detected at ~50% in larvae and 58% in adult females. Significant association was observed (OR = 7.2, p<0.03) between permethrin resistance and 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites permethrin resistance correlated with 2La/a homozygosity in adult fe-males [OR = 5.02, p=0.01). qRT-PCR identified 6 genes commonly induced/overexpressed, including heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively, trehalose-6-phosphate synthase (AGAP008227), and ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for design/choice of control measures.