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.

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.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Sport nutrition knowledge has been shown to influence dietary habits of athletes. The purpose of the current study was to examine relationships between sport nutrition knowledge and body composition and examine potential predictors of body weight goal in collegiate athletes. Participants included National Collegiate Athletic Association Division III women (n=42, height: 169.9 ± 6.9 cm; body mass: 67.1 ± 8.6 kg; fat-free mass: 51.3 ± 6.6 kg; body fat %: 24.2 ± 5.3%) and men (n=25, height: 180.8 ± 7.2 cm; body mass: 89.2 ± 20.5 kg; fat-free mass: 75.9 ± 12.2 kg; body fat %: 13.5 ± 8.9%) athletes. Body composition was assessed via air displacement plethysmography. Athletes completed a validated questionnaire designed to assess sport nutrition knowledge and were asked questions about their perceived dietary energy and macronutrient requirements, as well as their body weight goal (i.e. lose, maintain, gain weight). Athletes answered 47.98 ± 11.29 % of questions correctly on the nutrition questionnaire with no differences observed between sexes (men: 49.52 ± 11.76% vs. women: 47.03 ± 11.04%; p=0.40). An inverse relationship between sport nutrition knowledge scores and body fat percentage (r = -0.330; p=0.008), and fat mass (r = -.268; p=0.032) was observed for all athletes. Fat mass (β = 0.224), BF % (β = 0.217), and BMI (β = 0.421) were all significant (p<0.05) predictors of body weight goal in women. All athletes significantly (p<0.001) underestimated daily energy (-1,360 ± 610.2 kcal/d), carbohydrate (-301.6 ± 149.2 g/d), and fat (-41.4 ± 34.5 g/d) requirements. Division III collegiate athletes have a low level of sport nutrition knowledge, which was associated with a higher BF %. Women athletes with a higher body weight, BF % and BMI were more likely to select weight loss as a body weight goal. Athletes also significantly underestimated their energy and carbohydrate requirements based upon the demands of their sport, independent of sex.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

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.

We aimed at analyzing Chlorophyll-a and CDOM dynamics from field measurements and at assessing the potential of multispectral satellite data for retrieving water-quality parameters in three small surface reservoirs in the Brazilian semiarid region. More specifically, this work comprises i) analysis of Chl-a and trophic dynamics; ii) characterization of CDOM; iii) estimation of Chl-a and CDOM from OLI/Landsat-8 and RapidEye imagery. The monitoring lasted 20 months within a multi-year drought, which contributed to water-quality deterioration. Chl-a and trophic state analysis showed a highly eutrophic status for the perennial reservoir during the entire study period, while the non-perennial reservoirs ranged from oligotrophic to eutrophic, with changes associated with the first events of the rainy season. CDOM characterization suggests that the perennial reservoir is mostly influenced by autochthonous sources, while allochthonous sources dominate the non-perennial ones. Spectral-group classification assigned the perennial as CDOM-moderate and highly eutrophic reservoir, whereas the non-perennial ones were assigned as CDOM-rich and oligotrophic-dystrophic reservoirs. The remote sensing initiative was partially successful: the Chl-a was best modelled using RapidEye for the perennial; whereas CDOM performed best with Landsat-8 for non-perennial reservoirs. This investigation showed high potential for retrieving water quality parameters in dry areas with small reservoirs.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematological malignancy in humans and dogs. Several studies disclosed some similarities between the two species, including the constitutive activation of NF- κB pathway as a fundamental underlying pathogenetic mecha-nism. In humans, downregulation of IL-1R8 is implicated in DLBCL development, but its role in dogs has not been explored so far. To gain insight into the pathogenesis of this tumor in dogs, we evaluated the mRNA and protein expression of IL-1R8 in 12 hyperplastic lymph nodes ob-tained from dogs not bearing tumors and from 50 dogs with DLBCL. Moreover, we analysed through qRT-PCR the expression of TLR7, TLR9, MYC, and p52 genes that are known to be in-volved in the IL-1R8 regulatory network. IL-1R8 and p52 were downregulated in DLBCLs com-pared to control lymph nodes (p<0.001), while a higher expression of TLR7, TLR9 and MYC was observed in tumors (p<0.01). Immunohistochemistry confirmed gene expression results, reveal-ing a significantly lower IL-1R8 staining score in DLBCLs compared to control lymph nodes (p<0.0001). Taken together, these results suggest that IL-1R8 downregulation may represent one of the mechanisms driving DLBCL pathogenesis in dogs, mainly through dysregulation of the Toll-like/Interleukin receptors signalling cascade and the aberrant activation of classical NF-κB pathway.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

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.

Bioprospecting native Australian plants offers potential discovery of latent and novel bioactive compounds. Promising cytotoxic and antibacterial activity of methanolic extracts of Pittosporum angustifolium and Terminalia ferdinandiana led to further fractionation and isolation using our laboratory’s bioassay guided fractionation protocol. Hence, the aim of this study was to further evaluate the bioactivity of the fractions and subfractions and characterize bioactive compounds using liquid chromatography mass spectroscopy (LC-MS/MS) and gas chromatography MS (GC-MS). Compounds tentatively identified in P. angustifolium Fraction 1 using LC-ESI-QTOF-MS/MS were chlorogenic acid and/or neochlorogenic acid, bergapten, berberine, 8’-epitanegool and rosmarinic acid. GC-MS analysis data showed the presence of around 100 compounds, mainly comprising of carboxylic acids, sugars, sugar alcohols, amino acids, and monoalkylglycerols. Furthermore, the fractions obtained from T. ferdinandiana flesh extracts showed no cytotoxicity, except against HT29 cell lines, and only Fraction 2 exhibited some antibacterial activity. The reduced bioactivity observed in the T. ferdinandiana fractions could be attributed to the potential loss of synergy as compounds become separated within the fractions. As a result, further fractionation, and separation of compounds in these samples were not pursued. However, additional dose-dependent studies are warranted to validate the bioactivity of T. ferdinandiana flesh fractions, particularly since this is an understudied species. Moreover, LC-MS/GC-MS studies confirm the presence of bioactive compounds in P. angustifolium Fraction 1/subfractions which helps to explain the significant acute anti-cancer activity of this plant. The screening process designed in this study has the potential to pave the way for developing scientifically validated phytochemical/bioactivity information on ethnomedicinal plants, thereby facilitating further bioprospecting efforts, and supporting the discovery of novel drugs in modern medicine.

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.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

To search for novel thermostable esterase for optimized industrial applications, esterase from a thermophilic eubacterium species, Thermoanaerobacter tengcongensis MB4 was purified and characterised in this work. Sequence analysis of T. tengcongensis esterase with other homologous esterases of the same family revealed an apparent tail at the C-terminal that is not conserved across the esterase family. Hence, it was hypothesized that the tail is unlikely to have an essential structural or catalytic role. However, there is no documented report of any role for this tail region. We probed the role of the C-terminal domain on the catalytic activity and substrate preference of Thermoanaerobacter tengcongensis esterase EstA3 with a view to see how it could be engineered for enhanced properties. To achieve this, we cloned, expressed, and purified the wild-type and the truncated version of the enzyme. In addition, a naturally occurring member of the family (from B. brevis) that lacks the C-terminal tail was also made. In vitro characterization of the purified enzymes showed that the C-terminal domain contributes significantly to the catalytic activity and distinct substrate preference of T. tengcongensis esterase EstA3. All the three recombinant enzymes showed highest preference to paranitrophenyl butyrate (pNPC4), which suggests they are true esterases, not lipases. kinetic data revealed that truncation had a slight effect on the substrate-binding affinity. Thus, the drop in preference towards long-chain substrates might not be a result of substrate binding affinity alone.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

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

This scoping review aims to identify the available evidence concerning the clinical and psychosocial impacts of the communication of oral potentially malignant disorders (OPMDs), and to map and analyze knowledge gaps regarding truth-telling about risk factors, malignant transformation, treatment, and follow-up approaches. Search strategy was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Each publication involved a different study design, study population, types of OPMDs, and results on the important aspects of the professional-patient communication about the diagnosis of OPMDs. Although specific protocols on OPMDs communication have not yet been reported, there is an elevated interest on this topic since the strategies and skills on professional communication could provide better clinical outcomes to the patients. A list of recommendation strategies on how to communicate an OPMD diagnosis is proposed; however, future studies are still needed to design specific communication protocols for OPMD.

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.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

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.

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.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Background: dementia is a significant health issue worldwide. Mild cognitive impairment (MCI) can transform into dementia over time. General practitioners may be the first to notice the cognitive deficit, so they may need a screening test in the event of suspicion, which they must be able to use under great time pressure. We examined the usability of the Hungarian Test Your Memory (TYM-Hun) self-administered dementia test in general practice, and with the results of the received tests, we tried to draw conclusions regarding the population. Methods: In the four Hungarian cities with medical universities, general practitioners filled out 368 questionnaires with their clients over 50 years of age. Results: the total scores of the test showed a significant correlation with education and the type of occupation, while a significant negative correlation with age. We found the clock drawing test and recall indicates cognitive decline the earliest. Based on the TYM-Hun results, the prevalence levels for MCI and dementia are slightly higher in Hungary than globally. Conclusion: the test can sensitively indicate MCI and early-stage dementia as a screening test, and two of its subtests can raise the possibility of cognitive impairment at an earlier age than the others.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

AbstractIn the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from static functional to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.Impact StatementWhile functional connectivity has elucidated much MN properties with relation to age, disease, and behavior, effective connectivity has been shown to be useful in MN-informed therapies in adults. Thus, effective connectivity may have potential to impact childhood movement disorder therapies, given the lower to no patient demand.

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.

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.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

: Drought monitoring and early detection have improved greatly in recent decades through the development and refinement of numerous indices and indicators. However, a lack of guidance, based on user experience, exists as to which drought monitoring tools are most appropriate in a given location. This review paper summarizes the results of targeted user engagement and the published literature to improve the understanding of drought across North America, and to enhance the utility of drought monitoring tools. Workshops and surveys were used to assess and make general conclusions about the perceived performance of drought indicators, indices and impacts information used for monitoring drought in the five main Köppen climate types (Tropical, Temperate, Continental, Polar Tundra, Dry) found across Canada, Mexico, and the United States. In Tropical, humid Temperate, and southerly Continental climates, droughts are perceived to be more short-term (less than 6 months) in duration rather than long-term (more than 6 months). In Polar Tundra climates, Dry climates, Temperate climates with dry warm seasons, and northerly Continental climates, droughts are perceived to be more long-term than short-term. In general, agricultural and hydrological droughts were considered to be the most important drought types. Drought impacts related to agriculture, water supply, ecosystem, and human health were rated to be of greatest importance. Users identified the most effective indices and indicators for monitoring drought across North America to be the U.S. Drought Monitor (USDM) and Standardized Precipitation Index (SPI) (or another measure of precipitation anomaly), followed by the Normalized Difference Vegetation Index (NDVI) (or another satellite-observed vegetation index), temperature anomalies, crop status, soil moisture, streamflow, reservoir storage, water use (demand), and reported drought impacts. Users also noted the importance of indices that measure evapotranspiration, evaporative demand, and snow water content. Drought indices and indicators were generally thought to perform equally well across seasons in Tropical and the colder Continental climates, but their performance was perceived to vary seasonally in Dry, Temperate, Polar Tundra, and the warmer Continental climates, with improved performance during warm and wet times of the year. The drought indices and indicators, in general, were not perceived to perform equally well across geographies. This review paper provides guidance on when (time of year) and where (climate zone) the more popular drought indices and indicators should be used. The paper concludes by noting the importance of understanding how drought, its impacts, and indicators are changing over time as the climate warms, and by recommending ways to strengthen the use of indices and indicators in drought decision-making.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

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.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

The main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

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.

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.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

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.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

In this work, an innovative numerical approach for polylinear approximation (polylinearization) of non-self-intersecting compact sensor characteristics (transfer functions) specified either pointwise or analytically is introduced. The goal is to optimally partition the sensor characteristic, i.e. to select the vertices of the approximating polyline (approximant) along with their positions on, the sensor characteristics so that the distance (i.e. the separation) between the approximant and the characteristic is rendered below a certain problem-specific tolerance. To achieve this goal, two alternative non-linear optimization problems are solved, whose essential difference is in the adopted quantitative measure of the separation between the transfer function and the approximant. In the first problem, which relates to absolutely integrable sensor characteristics (their energy is not necessarily finite, but they can be represented in terms of convergent Fourier series), the polylinearization is constructed by numerical minimization of the L^1--metric (a distance-based separation measure), concerning the number of polyline vertices and their locations. In the second problem which covers the quadratically integrable sensor characteristics (whose energy is finite, but they do not necessarily admit a representation in terms of convergent Fourier series), the polylinearization is constructed by minimizing numerically the L^2-metric (area-, or energy-based separation measure) for the same set of optimization variables –the locations, and the number of polyline vertices.

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.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

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.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

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 have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

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.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

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.

In this paper we develop and explore a methodical pipeline for swimmer localisation in outdoor environments. The developed framework is intended to be used for enhancing swimmer safety. A main issue we deal with by the proposed approach is the lack of real world training data in such outdoor environments. Natural lighting changes, dynamic water textures and possibly barely visible swimming persons are key elements to approach. We account for these difficulties by adopting an effective background removal technique with available training data. This allows us to edit swimmers into natural environment backgrounds for the use in subsequent image augmentation. We created 17 training datasets with real images, synthetic images and a mixture of both to investigate different aspects and characteristics of the proposed approach. The datasets are used to train a YOLO architecture for the possible future application in real-time detection. The trained framework is then tested and evaluated on outdoor environment imagery acquired by a safety drone to investigate and confirm the usefulness for outdoor swimmer localisation.

Soil amendments with composted organic materials are recommended to increase soil organic matter (SOM), promote soil fertility, and the Circular Economy. Growing areas of hedged olive groves in southern Iberia peninsula generate huge amounts of olive leaves whose potential as soil organic amendment is not fully studied. An experimental field trial in a hedged olive grove (cv. “Cobrançosa”) was set up near Portalegre, Portugal, to test a compost of olive leaves plus sheep manure (2:1) applied in the row, at soil surface. Three nominal rates (0 or control, 2.5 and 5.0 kg m-2) were used, in a complete randomized block setup (3 treatments, 3 replicas, 9 plots) and soil chemical properties of layers 0-5, 5-15, and 15-30 cm deep were annually monitored. Results (mainly in layer 0-5 cm) showed increases in total N, carbon of the particulate organic matter (POM-C), permanganate oxidizable carbon (POX-C), extractable phosphorus, and zinc, after one year, and increases in soil organic carbon (SOC), C-stock, pHKCl, extractable phosphorus, and zinc, after two years. POX-C was the most sensitive SOM-related indicator, showing increases up to 30 cm deep after one year. This compost improved soil fertility, but should be monitored over longer periods of time, namely for SOC and extractable zinc content.

Biochar application to soil has been proposed as a means for reducing soil greenhouse gas emissions and mitigating climate change. The effects, however, of interactions between biochar, moisture and temperature on soil CO₂ and N₂O emissions, remain poorly understood. Furthermore, the applicability of lab-scale observations to field conditions in diverse agroecosystems remains uncertain. Here we investigate the impact of a mixed wood gasification biochar on CO₂ and N₂O emissions from loess-derived soils using: (1) controlled laboratory incubations at three moisture (27, 31 and 35%) and three temperature (10, 20 and 30°C) levels, and (2) a field study with four cropping systems (continuous corn, switchgrass, low diversity grass mix, and high diversity grass-forb mix). Biochar reduced N₂O emissions under specific temperatures and moistures in the laboratory and in the continuous corn cropping system in the field. However, the effect of biochar on N₂O emissions was only significant in the field, and no effect on cumulative CO₂ emissions was observed. Cropping system also had a significant effect in the field study, with soils in grass and grass-forb cropping systems emitting more CO₂ and less N₂O than corn cropping systems. Observed biochar effects were consistent with previous studies showing that biochar amendments can reduce soil N₂O emissions under specific, but not all, conditions. The disparity in N₂O emission responses at the lab and field scales suggests that laboratory incubation experiments are not reliable for predicting the impact of biochar at the field scale.

Increased proliferation of IT services in all sectors has reinforced the adoption and diffusion across all levels of education and training institutions. However, lack of awareness of and knowledge about the key challenges and opportunities of elearning, seem to allude policymakers, resulting in low adoption or increased failure rate of many e-learning projects. Our study tries to address this problem through a review of relevant literature in e-learning. Our goal was to draw from the existing literature, insights into the opportunities and challenges of e-learning diffusion, and the current state-of-research in the field. To do this, we employed a systematic review of literature on some of the salient opportunities and challenges of e-learning innovation for educational institutions. These results aimed to inform policymakers and suggest some interesting issues to advance the research and adoption and diffusion of e-learning. Moreover, the bibliometric analysis shows that the field is experiencing high research attraction among scholars. However, several research areas in the field witnessed relatively low research paucity. Based on these findings, we discussed topics for possible future research.

Image recovery by dictionary learning is of potential interest for many possible applications. To learn a dictionary, one needs to solve a minimization problem where the solution should be sparse. The K-SVD formalism, which is a generalization of the K-means algorithm, is one of the most popular methods to achieve this aim. We explain the preprocessing that is needed to bring images into a manageable format for the optimization problem.The learning process then takes place in terms of solving for sparse representations of the image batches. The main contribution of this paper is to give an experimental analysis of the recovery for highly textured imagery. For our study, we employ a subset of the Brodatz database. We show that the recovery of sharp edges plays a considerable role. Additionally, we study the effects of varying the number dictionary elements for that purpose.

Quantum logic is a well-structured theory, which has recently received some attention because of its fundamental relation to quantum computing. However, the complex foundation of quantum logic borrowing concepts from different branches of mathematics as well as its peculiar settings have made it a non-trivial task to device suitable applications. This article aims to propose for the first time an approach to use quantum logic in image processing at hand of a process for shape classification. We show how to make use of the principal component analysis to realize quantum logical propositions. In this way we are able to assign a concrete meaning to the rather abstract quantum logical concepts, and we are able to compute a probability measure from the principal components. For shape classification we consider encrypting given point clouds of different objects by making use of specific distance histograms. This enables to initiate the principal component analysis. At hand of experiments, we explore the possibility to distinguish between different geometrical objects and discuss the results in terms of quantum logical interpretation.

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

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.

226Ra and 228Ra are typically monitored for groundwater and surface water compliance at legacy U mining and milling sites. Groundwater monitoring results for combined Ra (226Ra+228Ra) reported by the existing contract laboratory at a former U mine and mill Site (Wyoming, USA) have been highly variable and with increasing trends at the Site compliance and background wells since the method was changed in 2005. Sample reanalysis has indicated poor reproducibility and significant analytical error in 228Ra measurements. An interlaboratory comparison was conducted to evaluate the potential causes of the high variability and analytical error. Two different methods were used for 226Ra (M903.0 and M903.1) and 228Ra (M904.0 and Ra-05). 226Ra results were less variable compared to 228Ra, and 228Ra data from the existing laboratory were qualified as estimated with high bias due to detection of 228Ra in the field blank. Compliance with the 226Ra+228Ra groundwater standard was either met or not met, depending on which laboratory conducted the analyses. Specific laboratory techniques, rather than the analytical method, are contributing to elevated 228Ra values being reported. It was recommended that samples whose 226Ra+228Ra results exceed the Site standard in the future be reanalyzed by the existing laboratory with a sample split also being sent to an outside laboratory for confirmatory analysis.

Given the remarkable progress in global health and overall quality of life, the significant rise in life expectancy has become intertwined with the surging occurrence of neurodegenerative disorders (ND). This emerging trend is poised to pose a substantial challenge to the fields of medicine and public health in the years ahead. In this context, Alzheimer's disease (AD) is regarded as a ND that causes recent memory loss, motor impairment and cognitive deficits. AD is the most common cause of dementia in the elderly and its development is linked to multifactorial interac-tions between the environment, genetics, aging and lifestyle. The pathological hallmarks in AD are the accumulation of beta amyloid (A) peptide, the hyperphosphorylation of tau protein, neuro-toxic events and impaired glucose metabolism. Due to pharmacological limitations and in view of the prevailing glycemic hypometabolism, the ketogenic diet (KD) emerges as a promising non-pharmacological possibility for managing AD, an approach that has already demonstrated efficacy in addressing other disorders, notably epilepsy. KD consists of a food regimen in which carbohydrate intake is discouraged at the expense of increased lipid consumption, inducing met-abolic ketosis, whereby the main source of energy becomes ketone bodies, instead of glucose. Thus, under these dietary conditions, neuronal death through lack of energy would be decreased, inasmuch as the metabolism of lipids is not impaired in AD. In this way, the clinical picture of patients with AD would potentially improve, through the slowing down of symptoms and delaying the progression of the disease. Hence, this review aims to explore the rationale behind utilizing the KD in AD treatment while emphasizing the metabolic interplay between KD and the improvement of AD indicators, drawing insights from both pre-clinical and clinical investigations.

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.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

California and most other coastlines around the world are being impacted by both long-term sea-level rise and short-term extreme events. Because of California’s long and intensively developed coastline, it is an important area for evaluating responses to these challenges. The predominant historic approach to coastal erosion in California and globally has been the construction of hard coastal armoring such as seawalls and rock revetments. The concept of living shorelines – defined as using natural elements like plants, sand or rocks to stabilize the coastline – has been widely proposed as a soft or green response to coastal erosion and flooding. These approaches have very limited application in high-energy environments, however, such as California’s 1,100-mile-long outer coast and are not realistic solutions for protection from wave attack at high tides or long-term sea-level rise. Each of the state’s coastal communities need to identify their most vulnerable areas, develop adaptation plans, and plan eventual relocation strategies in response to an accelerating sea-level rise.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

The large-scale processing of Cassava (Manihot esculenta Crantz.) generates significant quantities of solid wastes annually. Cassava peels (CP) account for 5 wt.% - 30 wt.% of wastes from the processing of cassava tubers. The poor disposal and management of CP pose risks to human health, safety and the environment. Therefore, there is an urgent need to identify and examine low cost, socially acceptable and environmentally friendly strategies to mitigate the immediate and long terms disposal and management challenges. Lack of such measures results in the accumulation of CP wastes, which are currently buried, combusted, or dumped in open fields. Therefore, this paper reviewed the potential routes for the biochemical, thermochemical, and plasma valorisation of CP. The literature reviewed revealed that biochemical technologies such as anaerobic digestion (AD) and fermentation are the most widely utilised approaches currently adopted for CP valorisation. AD produces biogas (methane 50-72 vol. % and carbon dioxide 25-45 vol. %), whereas fermentation yields bioethanol. However, the numerous challenges such as substrate-induced inhibition, associated with the biochemical processes hamper microbial degradation, methane formation, and process efficiency. Furthermore, the processes generate secondary wastes or digestate/sludge, which requires additional processing before disposal. Therefore, innovative thermal, thermochemical, and plasma technologies were proposed to valorise CP into syngas, biofuels, bioenergy, biochemicals, and fertilizers, among others. However, the waste products of fermentation cannot be effectively utilised as bio-fertilizers, whereas bioethanol causes corrosion in engines. Overall, the biochemical, thermal, thermochemical and plasma technologies can effectively valorise CP for effective net energy generation.

This study presents a preliminary analysis of the chemical and thermal fuel properties of Afuze (AFZ) coal extracted from coalfields in Owan East Local Government Area of Edo State, Nigeria. The chemical properties of AFZ were examined by combined scanning electron microscopy-energy dispersive X-ray (EDX), whereas the thermal properties were deduced by thermogravimetric analysis (TGA) under flash (50 °C/min heating rate) oxidative (combustion) and non-oxidative (pyrolysis) conditions. The microstructure and morphology analysis of AFZ revealed has a compact structure comprising small-to-large, irregular shaped and exfoliated grains with a vitreous appearance typically ascribed to metal elements (Ti and Fe) kaolinite, quartz, and other clay minerals. Chemical analysis revealed carbon, oxygen, aluminium, silicon, sulphur, calcium, titanium, and iron in major and minor (trace) quantities. Thermal analysis under oxidative and non-oxidative conditions revealed degradation occurs in three stages, namely; drying or demineralisation, devolatilization or maceral degradation and the formation of char/coke or ash. Lastly, the findings showed that the temperature range for the oxidative thermal degradation process (338.58 - 756.76 °C) was higher than the non-oxidative process (378.43 - 615.34 °C). This observation can be explained by the exothermic nature of the oxidative (combustion) process, which ensures greater heat supply required to thermally soften or degrade the maceral coal components. Overall, the oxidative process yielded the residual mass (RM = 21.97%) and mass loss (ML = 78.03%). The lower ML (49.03%) but higher RM (50.97%) observed during non-oxidative degradation of AFZ could be ascribed to the largely endothermic nature of the process.

Although the phenomenon of serial killers has received great attention from media, governments, and public, very little information is known about them and very few theories are presented by researchers specifically their definition and motives for killing. Through cross tabulation analysis of top ninety-eight serial killers, this present study poses six questions that investigate the correlations between, offender's gender, offender's level of education, time span of killing, killing severity, number of victims, killer's type of abuse, motives for killing, and victim's profile. Findings show that males kill more than females and for longer time, less educated serial killers kill more horribly, female serial killers consider their family members easy target, and finally males kill most for enjoyment and sex and females kill for financial gains.

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.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

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.

The adoption of ADS-B in Latin America has been gradual but steady. Some countries, such as Brazil, Chile and Mexico, have made significant progress in the implementation of this system, while others are still in the early stages. It should be noted that the implementation of ADS-B is used in both military and civilian environments. For this reason, this research aims to provide information on the different characteristics that make up the surveillance systems. However, there are fundamental factors to promote the adaptation of ADS-B in Latin America, since they reduce the risk of collisions and air accidents by providing accurate and real-time information on the position and altitude of aircraft. On the other hand, it allows optimizing flight routes and reducing waiting time on the ground, which translates into fuel and cost savings for airlines. ADS-B increases the number of aircraft that can safely operate in the same airspace, which is especially important in regions with growing air traffic. ADS-B adoption in Latin America is expected to continue to grow in the coming years. The drivers for ADS-B adoption remain in place, and governments in the region are taking steps to accelerate its implementation.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an “open chromatin” state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell development in vivo.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

Abstract: A large number of collecting expeditions were launched in regions of ‘centers of diversity’ and hundreds of thousands of sample have been collected and stored in gene banks as ‘genetic resources’. So far, only a small number of the samples have been evaluated for their biotic and abiotic stress tolerance. Now, their time to become useful has come. A new global phenomenon has arisen – climate change. The crop genetic resources and their wild progenitors that have survived countless years of changing environment during the last 11,000 years could harbor genes that may be useful under the new growing conditions and environmental factors thrown up by climate change and global warming. With the deployment of modern bio-engineering techniques selected genes or gene fragments can be transferred from genetic resources to modern varieties of crop plants to make them well-prepared to mitigate the effects of global warming and climate change. The latter is the most serious issue facing plant breeders today. New pests and diseases could affect crop production. These review paper discusses various impacts and issues as a result of this phenomenon and suggest ways to safeguard our most important crops through better management of crop plant genetic resources in the near future.

The recent Planck Legacy release confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background (CMB) power spectra, which endorses the positive curvature of the early Universe with a confidence level exceeding 99%. In this study, the pre-existing curvature is incorporated to extend the field equations where the derived wave function of the Universe is utilized to model Universe evolution with reference to the scale factor of the early Universe and its radius of curvature upon the emission of the CMB. The wave function reveals both positive and negative solutions, implying that matter and antimatter of early Universe plasma evolve in opposite directions as distinct Universe sides. The wave function indicates that a nascent hyperbolic expansion is followed by a first phase of decelerating expansion away from early plasma during the first 10 Gyr, and then, a second phase of accelerating expansion in reverse directions, whereby both Universe sides free-fall towards each other under gravitational acceleration. Simulations of the predicted conformal curvature evolution demonstrate the fast orbital speed of outer stars owing to the external fields exerted on galaxies as they travel through conformally curved space-time. Finally, the wave function predicts an eventual time-reversal phase comprising rapid spatial contraction that culminates in a Big Crunch, signalling a cyclic Universe. These findings reveal that early plasma could have separated and evolved into distinct sides that collectively and geometrically influencing the Universe evolution, physically explanting the effects attributed to dark matter and energy.

The shrimp industry in the Philippines play a vital role in the local and national economy through exports with markets abroad such as in South Korea, Japan, the USA, and others. This study aimed to describe the various cultural and operational characteristics of small-holder and commercial shrimp farms (P. vannamei) in the Davao region. It also evaluated the current risks and challenges faced by the shrimp farmers. A semi-structured questionnaire that focused on shrimp farmers, and operators in the region was used to collect data with N=41 farmers and operator. The results showed that respondents were engaged in small-holder farming activities which had an average yield of 10 tons/ha. On the other hand, the commercial farms that operate intensively had an average yield of 24 tons/ha. Most small-holder operators used electric generator machines to conduct aeration in their farms using paddlewheels and blowers. For the commercial farms, more paddlewheels and blowers were employed per pond compared to small-holder farms. Generally, the income of a farm was related to the yield of farms or the number of fries rather than social factors or size of farms cultivated. In terms of input costs, feeds were found to have the highest input costs, followed by the fry, fuel, labor, and others (fertilizers and water treatment chemicals). Most of the farmers mentioned that they are affected by diseases such as white spot syndrome (60%), black gills (35%), and red tail (5%). They perceived that the main contamination come from the water source (31%). The main threats mentioned are declining shrimp prices in the market, source of fry, water disposal, and overstocking, and water quality. Based on this study, farmers should follow good shrimp aquaculture practices and there is a need for them to regularly monitor their water quality.

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th Feb and 15th Feb. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a `delayed positive' test during isolation after initially testing negative, at least 7 days after last possible contact.

Brain is the most complex organ in the human body and it is divided into two hemispheres - left and right hemispheres. Left hemisphere is responsible for control of right side of our body whereas right hemisphere is responsible for control of left side of our body. Brain image segmentation from different neuroimaging modalities is one of the important parts in clinical diagnostic tools. Neuroimaging based digital imagery generally contain noise, inhomogeneity, aliasing artifacts, and orientational deviations. Therefore, accurate segmentation of brain images is a very difficult task. However, the development of accurate segmentation of brain images is very important and crucial for a correct diagnosis of any brain related diseases. One of the fundamental segmentation tasks is to identify and segment inter-hemispheric fissure/mid-sagittal plane, which separate the two hemispheres of the brain. Moreover, the symmetric/asymmetric analyses of left and right hemispheres of brain structures are important for radiologists to analyze diseases such as Alzheimer's, Autism, Schizophrenia, Lesions and Epilepsy. Therefore, in this paper we have analyzed the existing computational techniques used to find brain symmetric/asymmetric analysis in various neuroimaging techniques (MRI/CT/PET/SPECT), which are utilized for detecting various brain related disorders.

The use of several light-related variables, such as the Secchi disc depth, the euphotic depth, and in particular, the diffuse attenuation coefficient (Kd), is deeply rooted in phytoplankton research, but these are not the most appropriate indicators of the amount of light available for photosynthesis. We argue that the variable of interest for phytoplankton is the mean light intensity in the mixed layer (Im), which represents the mean light to which phytoplankton cells are exposed throughout their life cycle, while being continuously mixed in the mixed layer. We use empirical data collected in different coastal ecosystems in southern Portugal to demonstrate why Im should be the preferred metric instead of the deeply rooted Kd. We show that, although the relationship between Im and Kd is inversely proportional, it is not always strong or even significant. Different Im values can be associated to the same Kd, but distinct Im have different physiological effects of phytoplankton. Therefore, Kd does not capture the amount of light available for photosynthesis, given that, unlike Im, Kd calculation does not consider the depth of the mixed layer. Therefore, we urge phytoplankton researchers to consider the measurement and calculation of Im when evaluating light-related processes in phytoplankton ecology.

Cladding is typically used to protect components from wear and corrosion while also improving the aesthetic value and reliability of the substrate. The cladding process induces significant residual stresses due to the temperature difference between the substrate and the clad layer. However, these residual stresses could be effectively utilized by modifying processes and geometrical parameters. This paper introduces a novel methodology for using the weld-cladding process as a cost-effective alternative to various existing reinforcement techniques. The numerical analyses are performed to maximize the reinforcement of a cylindrical tool. The investigation of how the weld cladding develops compressive stresses on the specimen in response to a change in the weld beads and the welding sequence is presented. For the benchmark shape, experimental verification of the numerical model is performed. The impact of the distance between the weld beads and the effect of the tool diameter is numerically investigated. Furthermore, the variation in compressive stresses due to temperature fluctuations during the extrusion process has been evaluated. The results showed that adequate compressive stresses are generated on the welded parts through the cladding process after cooling. Hence, the targeted reinforcement of the substrate can be achieved by optimizing the welding sequence and process parameters.

The Industrial Internet of Things (IIoT) paradigm is a key research area derived from the Internet of Things (IoT). The emergence of IIoT has enabled a revolution in manufacturing and production, through the employment of various embedded sensing devices connected with each other by an IoT network, along with a collection of enabling technologies such as artificial intelligence (AI) and edge/fog computing. One of the unrivaled characteristics of IIoT is the inter-connectivity provided to industries; however, this characteristic might open the door for cyber-criminals to launch various attacks. In fact, one of the major challenges hindering the prevalent adoption of the IIoT paradigm is IoT security. Inevitably, an increasing number of research proposals have been introduced over the last decade to overcome these security concerns. To obtain an overview of this research area, conducting a literature survey of the published research is necessary, eliciting the various security requirements and their considerations. This paper provides a literature survey of IIoT security, focused on the period from 2017 to 2023. We identify IIoT security threats and classify them into three categories, based on the IIoT layer they exploit to launch these attacks. Additionally, we characterize the security requirements that these attacks violate. Finally, we highlight how emerging technologies, such as AI and edge/fog computing, can be adopted to address security concerns and enhance IIoT security.

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, congenital heart anomalies, and cystic kidney disease. Whole exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the alpha-helical region of the DNA-binding forkhead box domain. In vitro studies using a heterologous cell system revealed aberrant cytoplasmic localization of FOXC1 harboring the Tyr105* variant, likely precluding downstream transcription function. Meta-analysis of the literature highlighted the intrafamilial variability related to FOXC1 truncating alleles. This study highlights the clinical variability in ASD and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.