The rapid convergence of Artificial General Intelligence (AGI), autonomous drones, and applied robotics presents a transformative opportunity for many sectors. However, this advancement also raises critical ethical and existential questions, particularly in warfare. This paper explores the concept of entropy as a metaphor for the potential disorder introduced by these increasingly complex technologies. We examine the risks of AGI surpassing human control in conflict situations, where autonomous decision-making could have disastrous consequences. We then analyze autonomous drones, scrutinizing their impact on warfare tactics and the ethical dilemmas surrounding independent, real-time decision-making. Finally, we investigate applied robotics in military operations, focusing on the delicate balance between enhanced capabilities and the potential for uncontrollable systems. Through a multidisciplinary lens, drawing on technology ethics, military strategy, and AI safety, this paper utilizes the concept of entropy to highlight the need for caution in developing these technologies. We propose a scientifically grounded and ethically sound framework to guide policymakers, technologists, and ethicists in navigating the path between innovation and global stability. This framework concludes with recommendations for responsible development and deployment strategies that can mitigate the risks associated with these powerful tools.

The increasing demand for higher power in rocket launchers is driving the development of higher power nozzles, achieved essentially by increasing the expansion ratio. However, this can lead to flow separation and resulting unsteady, asymmetrical forces, called side loads, which can limit the life of both the nozzle itself and other engine components. If this problem can be overcome, engine performance can be significantly increased. Therefore, various separation control methods have been proposed, but none have been fully implemented to date due to the uncertainties associated with modeling and predicting the flow phenomena. A numerical study of high area ratio rocket engine is presented to analyze the aeroelastic performance of the structure under the condition of flow separation. The finite volume method, the 2nd order upwind scheme and the extended wall function are used to analyze the flow inside the rocket nozzle and the transition of the Free Shock Separation (FSS) to Restricted Shock Separation (RSS) separation pattern ) to be discussed in detail. Since the location of the flow separation point depends heavily on the flow.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

This paper presents MADS (Multi-Agents for Data Science), an innovative and simple open-source multi-agent framework designed for systemic pipeline execution in applied supervised machine learning. By leveraging the capabilities of multi-agent systems (MAS), we introduce a universal approach to optimize and streamline machine learning pipelines. Our framework highlights the differences between various types of agents, such as reinforcement learning (RL) agents and large language model (LLM) agents, and their distinct contributions to the process. While we currently employ LLM agents to automate and enhance machine learning tasks, we acknowledge the potential of incorporating RL agents in future iterations to further improve performance and adaptability. The primary objective is to enhance the efficiency, scalability, and adaptability of supervised learning applications across various domains. This integration addresses the complexity and manual effort typically associated with machine learning workflows, paving the way for more automated, robust, and scalable solutions. Our approach demonstrates significant improvements in task automation, reduced human intervention, and enhanced model performance. The MADS framework, which will soon be available as an open-source implementation, represents a pivotal contribution to the field of machine learning, promising to facilitate broader adoption and collaborative advancement.

The paper presents a proposal for an in-house mathematical model of a liquid flat-plate solar collector. The proposed model is a one-dimensional distributed parameter model enabling simulations of the collector operation under arbitrarily variable boundary conditions. The model is based on the solution of energy balance equations for all components of the collector. The formulated differential equations are solved iteratively using an implicit difference scheme. In order to obtain a stable numerical solution, it is necessary to use appropriate steps of the time and spatial division. These were found by comparing the results obtained from the model with the results of the analytical solution available in the literature for the transient state, which constitutes the novelty of the present study. The accuracy of the results obtained from the model was verified experimentally by comparing the measured and the calculated history of the fluid temperature at the outlet of the collector. The calculation of the collector time constant is proposed in the paper as an example of the model practical application. The results of the time constant calculation were compared with the values obtained experimentally on the test stand. This is another novelty of the presented research. The analysed collector instantaneous efficiency was then calculated for selected outdoor conditions. The presented mathematical model can also be used to verify the correctness of the collector operation. Comparing, on an ongoing basis, the measured and the calculated values of the fluid temperature at the collector outlet, conclusions can be drawn about the process of solar glass fouling or glycol gelling. The model's simplicity and the low computational demands enable such comparisons in an online mode.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Variable flow emitters are a new type of emitter for underground drip irrigation that are used in locations where soil moisture is difficult to transport to the surface, which leads to crop emer-gence difficulties. The flow channel structure parameters of emitters affect the hydraulic per-formance of the emitter and its anticlogging ability. In this study, the variable flow emitter at the conventional low–flow water supply stage is taken as the research object. A combination of CFD numerical simulation of a two–phase flow of water and sand and clear water testing of test samples is applied to study the influence laws of 10 groups of variable flow emitter structural combinations on the effluent flow rate (q), flow index (x), particle passage rate and flow field inside the flow channel. The results show that the Realizable k–ε turbulence model can be used to simulate the flow field inside the variable flow emitter flow channel. The nRMSE between the measured and simulated values of q is 11.23%, and the relative error between the measured and simulated values of x is 4.66%, which gives a high simulation accuracy. The polar analysis shows that the tooth angle A has the smallest effect on the effluent flow rate q0.1 under 0.1 MPa, x, and particle passage rate of the variable flow emitter. The depth of the flow channel D, the spacing of the teeth B, and the height of the teeth E have a different order of precedence in the influence of the three indices, which are D > B > E > A, B > E > D > A, and E > B > D > A, respectively. The value of particle passage rate is positively correlated with the mean flow velocity (v) and the mean turbulent kinetic energy (k) in the flow channel, and particle passage rate tends to increase and then decrease with the increase of x. The retention time (t) of the particles in the flow channel is closely related to the magnitude of v and k. Three multivariate linear regression equations (R2 = 0.883 ~ 0.995) were constructed for q0.1, x, and particle passage rate versus the flow channel structural parameters. Using the scipy.optimize.minimize function in Python, we de-termined the three optimal combinations of flow channel structural parameters corresponding to better hydraulic performance: q0.1 is 1.5 or 2 L/h (objective function y = min x), better clogging resistance (y = max particle passage rate), and both (y = min (0.5 x - 0.5 particle passage rate)). The research results can provide a ref-erence for the optimal design of variable flow emitters.

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.

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, 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 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, showing 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.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

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.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

The theory of water transport in trees, according to which the main driving force of water movement is the suction created by the evaporation of water by the meniscus (the curved surface of the capillary liquid column) on the evaporating elements, supported from below by root pressure, is flawed. The capillary effect in nature is around one meter. In the case of open-air gaps, the leaf cannot suck in the water against gravity because, in this case, the plant would not be sucking in water, but air through the open-air gap. If not, how do trees transport water? When evaporation occurs, there is no suction towards the canopy, but pressure is due to a reduction in the cross-section of the water pipe caused by heat loss through evaporation. At night, when evaporation stops, a thermal equilibration process is triggered, which restores the original cross-section of the pipe. This generates suction and draws water from the soil. As the hydrostatic pressure in the pipe is high for tall trees, the pipe is cut off. To prove my theory, I have given several examples. Water transport is not based on physical mechanical laws alone. There may be complex physiological, biochemical, and biophysical processes behind the operation of the pipe system.

Flow cytometric detection of intracellular (IC) signaling proteins and transcription factors (TFs) will help elucidate the regulation of B cell survival, proliferation and differentiation. However, simultaneous detection of signaling proteins or TFs, with membrane markers (MM) can be challenging as required fixation and permeabilization procedures can affect functionality of conjugated antibodies. Here, a phosphoflow method is presented for detection of activated NF-κB p65 and phosphorylated STAT1, STAT3, STAT5 and STAT6 together with B cell differentiation MM CD19, CD27 and CD38. Additionally, a TF-flow method is presented that allows detection of B cell TFs; PAX5, c-MYC, BCL6, AID and antibody-secreting cell (ASC) TFs BLIMP1 and XBP-1s together with MM. Applying these methods on in vitro induced human B cell differentiation cultures showed significantly different steady-state levels, and responses to stimulation, of phosphorylated signaling proteins in CD27-expressing B cell and ASC populations. The TF-flow protocol and UMAP analysis revealed heterogeneity in TF-expression within stimulated CD27 or CD38-expressing B cell subsets. The methods presented here allow for sensitive analysis of STAT and NF-κB p65 signaling and TFs together with B cell differentiation MM at single-cell resolution. This will aid further investigation of B cell responses in both health and disease.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

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.

This study reports rapid hydrolysis, acylation, and lipolysis with lipase B from Candida antarctica (CalB) and nanofructosome encapsulated CalB (CalB@NF) enzymes immobilized on silica-coated magnetic nanoparticles (Si-MNPs). Enzymatic hydrolysis was confirmed for conversion to p-nitrophenol (p-NP, λex=400 nm) from p-nitrophenyl butyrate (p-NPB, λex=270 nm), and various catalytic parameters such as Km, Vmax, and Kcat were calculated from Michaelis-Menten and Lineweaver-Burk plot. Efficiency of enzymatic hydrolysis was in the order of CalB > Si-MNPs@CalB > CalB@NF > Si-MNPs@CalB@NF, and reusability was much better with the enzyme immobilized on Si-MNPs than with the native enzyme. Enzymatic acylation was confirmed by the formation of benzyl benzoate (λex=229 nm) from benzoic anhydride (λex=240 nm), and efficiency exceeded 99% in all samples. Finally, enzymatic lipolysis was confirmed by the decomposition of olive oil to fatty acid such as oleic acid (λex=230 nm) using thin-layer chromatography (TLC), column chromatography, and proton nuclear magnetic resonance (1H -NMR). The lipases immobilized on Si-MNPs have the advantage of good thermal stability and reusability and are thus applicable to a wide range of industries.

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 <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.

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.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

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;

The alternating stress caused by periodic high-pressure injection and extraction in gas storage can potentially induce fault slippage, compromising the sealing integrity of faults within these facil-ities. Understanding the mechanical behavior of faults under alternating stress is crucial for en-suring the long-term stability and safety of gas storage operations. To explore the impact of fault dip angle and fault gouge strength on fault slip characteristics, fault samples were prepared with uniaxial compressive strengths of 20.1, 30.2, 42.4, and 51.4 MPa at two distinct dip angles. Triaxial compression experiments were conducted under alternating stress conditions corresponding to operational pressures at a specific gas storage in China. Results indicate that faults with dip angles of 30° and 45° tend to fail at their weakest points. Increasing strength of fault gouge shifts failure mechanisms from interfacial failure between gouge and surrounding rock towards internal gouge failure, often accompanied by shear failure across sections, resulting in characteristic "X"-shaped conjugate shear failures. The decrease in the ratio of bedrock strength to fault gouge strength elucidates the observed phenomena of initial reduction followed by increased fault deformation. Transition points for faults with 30° and 45° dips occur around the strength ratios of 1.7/1 and 1.2/1, respectively. Fault damage exhibits a negative correlation with fault gouge strength and a positive correlation with fault dip angle. Samples with higher strength fault gouge at a 30° dip angle generally incur less damage compared to those with lower strength fault gouge at a 45° dip angle. Moreover, higher maximum static friction coefficients denote greater fault resistance to slipping, with 30° faults consistently demonstrating superior resistance compared to 45° faults. Additionally, higher strength fault gouge consistently enhances slip resistance under identical dip angles.

Toll plaza optimization is essential for improving traffic flow and easing congestion on road networks. This study aims to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer facilitation. Different resources are used for data collection, like the National Highway Authority of Pakistan. Physical data is collected from the established Toll Plaza of Peshawar, along with the development of each line. The goal of this study is to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer happiness. The analysis of present traffic patterns, the detection of bottlenecks, and the creation of plans to ease congestion and enhance overall traffic flow are all part of the optimization process. The approaches used in this study include data analysis, simulation, and traffic modeling. PTV VISSIM is software for transportation planning, design, and analysis. The simulations consider various conditions, such as variable traffic volumes, toll collection methods, and lane configurations. When comparing the different optimization strategies, performance indicators like trip time, latency, and queue length are utilized to determine which approach is practical. Waiting time Vs. Existing each lane, etc, is explained. In the end, comparing queue lengths and throughput across different lane scenarios shows that maximizing throughput with existing lanes yields up to 45% improvement with E-tag lanes, 40% with existing E-tag lanes, 38% with E-tag plus additional toll and cash lanes, 32% with three cash lanes, and 28% with two E-tag lanes. Failure to regularly monitor and adjust the existing lane pattern scenario based on traffic patterns can lead to queues being 20% longer. Without proactive evaluation and optimization, there is a potential 63% opportunity for queue length improvement

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

The production of recombinant enzymes, mainly used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to produce recombinant α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500 respectively, using the pBE-S shuttle vector, and to characterize them. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their own signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700-750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. The SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which was in accordance with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 amylase was significantly reduced when exiting the producer cells. Ca2+ had no significant activating effect on the activities of Amy1974 amylase and Amy3500 amylase, likely due to its tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45-70°C, with a maximum at 65°C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards cyclodextrins. The Amy1974 amylase converts starch to dextrins of varying lengths, whereas Amy3500 almost entirely converts starch into glucose.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

The majority of existing numerical simulations of the effect of bridge piers on water movement are based on a limited number of bridge piers at a laboratory scale. Furthermore, some 2D numerical simulations for actual bridge projects have deficiencies, including the use of overly large mesh sizes and an inadequate treatment of bridge piers. In this study, we compare three methods of structural mesh encryption, suspension mesh, and nonstructural mesh based on Delft3D, and apply the optimization scheme to a real bridge project. It is demonstrated that optimal results can be achieved by utilising a grid size comparable to the pier diameter (Dp) in the region away from the piers. In the vicinity of the piers, the grid cell size should be no larger than 1/9 Dp. The suspended grid technique (DD Boundary) can yield results consistent with those obtained using a full-area high-resolution grid, provided that the total number of grids can be reduced and the computational time is considerably reduced. In this study, the unstructured mesh (Deflt3D Flexible Mesh) scheme was unable to capture the oscillations of the wake flow behind the bridge piers. However, the application of the optimized scheme in bridge engineering has demonstrated its practical value. The findings of this study on mesh resolution and suspension mesh scheme can be applied to the Delft3D software and are also useful for other numerical simulation work.

The integration of diverse distributed generation (DG) units, encompassing both Renewable Energy Sources (RES) and non-RES technologies delves into voltage levels, current distributions, and power flows, aiming to optimize and effectively manage the distribution network. An RES-based DGs such as photovoltaic systems and wind turbines, alongside non-RES units like fuel cells and micro turbines. This study proposes a hybrid approach the Multi-Objective Genetic Algorithm - Grey Wolf Optimizer (MOGA-GWO). By merging the strengths of multi-objective genetic algorithms with the efficiency of the Grey Wolf Optimizer, this advanced algorithm seeks semi-optimal solutions for multi-objective optimization problems. The algorithm aims to improve convergence speed without compromising solution quality, offering a promising solution for optimizing the characteristics of DG and RES integration in distribution networks compared to Cuckoo Search and Simulation Annealing Techniques. Key algorithmic operations include individual representation, initialization, fitness function computation, selection, crossover, mutation, and ending conditions. The DG optimal power flow problem is explored with a focus on minimizing generation costs, improving voltage profiles, minimizing losses, enhancing reliability, integrating renewable energy, reducing environmental impact, managing congestion, and ensuring compliance with operational constraints. Beyond traditional considerations, the study emphasizes neglected objectives and constraints, such as cyber-security concerns, real-time operation, regulatory frameworks, social acceptance, lifecycle environmental impact, grid resilience, data privacy, aging infrastructure compatibility, and economic viability.

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 ml/kg delivered at 5 – 15 Hz equivalent to 300 – 900 breaths per minute. Few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease, therefore oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

Fractional flow reserve (FFR) is regarded as the gold standard for assessing the functional significance of coronary artery lesions, yet it remains underutilized in clinical practice. Our objective was to investigate whether FFR results have the potential to alter treatment decisions for coronary lesions compared to visual assessments of angiographic images made by three operators at a high-volume interventional center. In this retrospective study, we aimed to reassess the angiographic images of 63 patients presenting with chronic coronary syndrome (n=39, 61.9%) and acute coronary syndrome (n=24, 38.1%) who underwent FFR. Three experienced interventional cardiologists (with >300 PCI procedures per year) reevaluated, blinded to FFR results, 105 ambiguous lesions in 63 patients to determine angiographic significance and treatment strategy. The observers reached a concordant agreement (≥2 operators made the same decision) to perform PCI in 60 (57.1%) of the lesions based on angiographic evaluation. Interestingly, 9 (15%) of these lesions were functionally non-significant (FFR >0.80). The observers agreed to defer PCI in 45 (42.9%) of the lesions; however, 4 (8.9%) of these were functionally significant (FFR ≤0.80) and required PCI. Thus, inter-observer concordance in visual-guided therapeutic decision-making is variable and not always confirmed by the functional significance of coronary lesions.

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.

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.

The accompanying mechanical behavior during the flow of ore-rock dispersion is an important factor leading to the instability and failure of the orepass in the ore storage section. It is of great significance to accurately understand the instability characteristics of the well wall in the ore section, during the ore drawing process by understanding the flow characteristics and internal mechanical transfer mechanism of ore-rock dispersion. Using the discrete element method to analyze the flow characteristics, contact compactness, stress distribution characteristics and contact force probability distribution of the ore-rock dispersion, it realizes the quantitative characterization of the damage degree of ore-rock flow, and reveals the damage mechanism of mine storage wall. The results show that: (1) The friction between ore-rock particles, between ore-rock and well wall is an important reason for the change of the macroscopic flow form of ore-rock from “one” to “V” type. (2) The compactness and stress concentration of ores are increasing with the increase of storage depth, which is shown that with the increase of storage depth, the greater the probability of well wall instability. (3) The probability distribution of contact force strength between particles decreases exponentially in the whole process of ore drawing, in which the strong chain plays a major role in the stability of the dispersion system. (4) The number of overpressure and the overpressure coefficient can be used to quantitatively characterize the wall damage degree under the action of ore-rock flow. The dynamic side pressure decreases periodically in the form of exponential fluctuations, and the dynamic load formed by the ore-rock flow mainly played a role in the lower area of the ore storage section.

This study aimed on evaluating the potential diagnostic value of a novel, sonographic, B-Flow Imaging (BFI)-based sign (“flashlight sign”, FLS) for the detection of wall-adherent, floating arterial structures (WAFAS). The FLS, characterized by a fast moving, very bright, intraluminal signal was detected in 28 patients with WAFAS. We divided this cohort into three subgroups, depending on the affected vascular segments: (1) peripheral arteries (n = 10), (2) native abdominal aorta (n = 8), and (3) abdominal aorta after endovascular aortic repair (EVAR; n = 10). Clinical characteristics were analyzed and BFI-findings were compared with contrast enhanced ultrasound (CEUS) and computed tomography angiography (CTA). Seven patients (25%) suffered from arterial embolism downstream to the FLS (EVAR, n = 4; native abdominal aorta, n = 1; peripheral arteries, n = 2). WAFAS of the abdominal aorta (native or after EVAR), as indicated by the FLS, were visible by CEUS and CTA in 60% and 93.3%, respectively. Based on the so far largest cohort of patients with WAFAS, we propose a clinically useful, BFI-based sonographic sign for detection of these so far underrated arterial pathologies in the abdominal aorta and the peripheral arteries.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of >95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

This paper presents an analysis of the power flow within the Northern Interconnected Grid of Cameroon. The Newton-Raphson method has been performed, known for its accuracy, under MATLAB software, to model and solve complex power flow equations. This study simulates a series of outage scenarios to evaluate the responsive-ness of the grid. The results obtained underline the crucial importance of reactive power management and highlight the urgent need to consolidate the grid infrastructure of North Cameroon. To increase grid resilience and stability, the paper recommends the strategic integration of renewables and the development of interconnections with other power grids. These measures are presented as viable solutions to meet cur-rent and future energy distribution challenges, ensuring a reliable and sustainable power supply for Cameroon.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Classifying network flow subsequences in an Industrial IoT gateway is an effective method for identifying Industrial IoT faults. This paper proposes a subsequence classification algorithm SSGBUL-IKNN based on unsupervised learning encoding to address the problem of low classification accuracy. Firstly, we built a network module based on unsupervised learning to encode the flow sequence of the Industrial IoT gateway. In the encoding module, a subsequence calibration algorithm controls the increasing error during the coding process. Then, the specific fault type is obtained through an improved KNN classification algorithm based on the indication distance source from the integrated coding sequences converted by multi-dimensional network flow sequences. The test result on three Industrial IoT datasets of a sewage treatment plant shows that the accuracy of SSGBUL-IKNN in this paper exceeds 92%, significantly higher than the algorithm DTW and TSF. It reaches the classification requirements of Industrial IoT fault diagnosis.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Systemic Lupus Erythematosus (lupus) and B-cell lymphoma (lymphoma) are serious diseases. Lupus and lymphoma co-occur at higher-than-expected rates and primarily depend on B-cells for their pathology, implicating shared inflammation-related B-cell molecular mechanisms as a potential cause of co-occurrence. We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B-cell RNA-seq data to find shared- and contrasting mechanisms potentially targetable for treatment. We observed 8,562 genes significantly dysregulated in both lupus and lymphoma. Of those genes, we found 5,335 to have a significant immune imbalance, defined as significant dysregulation by both diseases, as determined by IIT. Gene Ontology (GO) term and pathway enrichment of IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, validating that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 389 IIT gene products are drug-targetable with established or repurposed drugs. Among our results, we found 40 known and 349 novel lupus targets, along with 151 known and 238 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. We anticipate the IIT algorithm and shared and contrasting gene mechanisms uncovered here will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients.

Drag reduction by laminarization, an innovative technology in aerodynamics design, provides the possibility to improve significantly the aerodynamic performance of aircraft and remains to be one of the most promising and effective technologies. In this paper, the design method for transonic natural laminar flow (NLF) wing at high Reynolds number is investigated in details and a new optimization model is established to solve conflicts between the increase of a laminar flow region and the shock wave strength at the trailing edge. In order to numerically handle this competitive situation efficiently, a two-objective hierarchical variable fidelity Pareto evolutionary optimization model based on search space contraction is proposed and implemented. Numerical experiments show that it can capture simultaneously a Pareto front of the two-objectives: a wave drag minimization and a laminar flow region maximization. The results also show that both wave drag and skin friction drag performances of non-dominated Pareto members can be significantly improved via the optimal laminar wing shape and shock wave control device. Nearly 40% of the laminar flow area on the wing surface is achieved at the Reynolds number of 107. It is concluded that the present hierarchical variable-fidelity multi-objective evolutionary optimization method is computationally efficient, and illustrate its potential for solving complex engineering design problems.

The most important plastic resins used for wire coating are Polyvinyl Chloride (PVC), Nylon, Polysulfone and Low-high density polyethylene (LDPE / HDPE). In this article,the coating process is performed using elastic-viscous fluid as a coating material for wire coating in a pressure type coating die. The elastic-viscous fluid is electrically conducted in the presence of an applied magnetic field. The governing non-linear equations are modeled and then solved analytically by utilizing an Adomian decomposition method (ADM). The convergence of the series solution is established. The results are also verified by Optimal Homotopy Asymptotic Method (OHAM). The effect of different emerging parameters such as non-Newtonian parameters α and β, magnetic parameter M and the Brinkman number Br on solutions (velocity and temperature profiles) are discussed through several graphs. Additionally, the current result also compares with the published work already available in the literature.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

In nature and engineering applications, flexible fiber beds covering biological surfaces can play a role in reducing resistance. These fibers deform under the action of fluids, and this deformation affects the fluid flow state, forming a complex fluid-solid interaction phenomenon. To quantitatively analyze such issues, the physical model is simplified to the deformation problem of an soft hair bed caused by Stokes flow, and the deformation problem of a single fiber caused by Stokes flow is further studied. The deformation problem of an elastic single fiber in a channel caused by Stokes flow can be described by a nonlinear integral equation. We have obtained a new series solution, which has been compared with the previous perturbation method to verify the accuracy and effectiveness of the series solution. Meanwhile, we have further provided an extended form of flexible fiber deformation through experimental fitting. This fluid-solid interaction problem involves multiple fields and is very important in many natural and engineering systems. The research in this paper can not only help us better understand complex phenomena in nature but also delve into the interaction mechanism between fluids and solids, providing a theoretical basis for future scientific research and engineering applications.

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.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Abstract: Due to sever land degradation throughout Ethiopia, the government has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. However, most of the rivers in Ethiopia carry huge amount of sediment in rainy season and streams dried up in the dry period. Planned research was conducted on two paired micro-catchments Mt.Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were collected from 22/11/2020 to 8/11/2022 on both micro-catchments at their outlets and center respectively. Base flow separation was done using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software was employed for data analysis. Flow duration curve (FDC) for both watersheds were developed. The FDC indicated that the base flow from treated micro-catchment ishigher and sustained in the dry season while it is low and un-sustained in untreated micro-catchment. From statistical analysis, there is a significant difference in base flow enhancement between the treated and untreated micro-catchment (P<0.001). Hence, catchment treatment contributed to improve groundwater recharge and sustain base flow in the dry season by reduce surface runoff during rainy season.

Abstract: Severe land degradation is the principal environmental problem in Ethiopian highlands in the form of soil erosion, and soil fertility loss, which is caused by human intervention for food, shelter, and energy demands. Soil erosion contributes to the loss of precious soil and water resources which are the basis of agricultural production and provide numerous other eco-system services. The Ethiopian highlands are one of the most degraded regions in the world. To combat such problems, the government of Ethiopia has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. Mount Yewel is one of the highlands in Northeastern Ethiopia where intensive soil and water conserva-tion has been implemented. Despite the massive investment in soil and water conservation measures, most of the rivers in the highlands of Ethiopia carry huge amounts of sediment with high flood risks in the wet season and streams are dried up in the dry period. Nonetheless, the impact of soil and water conservation measures on flood reduction and dry season flow en-hancement has not yet been quantified and evaluated. This research was then conducted on paired micro-catchments of Mount Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were col-lected from 22/11/2020 to 8/11/2022 on paired micro-catchments of Mount Yewel at their outlets and centers respectively. Base flow separation was done from the stream hydrograph using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software were employed for data analysis. Flow duration curves (FDC) for both watersheds were developed to compare the stream flow patterns between treated and untreated micro-catchments of Mount Yewel. The FDC indi-cated that the base flow from treated micro-catchment is higher and sustained in the dry season while it is low and unsustained in untreated micro-catchment. From statistical analysis, there is a significant (P

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated if immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations can be overcome by immunization with VVX001 (i.e., Alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by ELISA and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by CFSE staining and subsequent FACS analysis. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the NTCP attachment site. IgG reactivity to sub-viral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusion: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.

This paper introduces a three-layer system, proposing a comprehensive model of granular mixture transport over a mobile sloped bed in a steady flow. This system, consisting of the bottom, contact and upper zones, provides complete, continuous sediment velocity and concentration vertical profiles. The model considers gravity’s effect on sediment transport in the bottom (dense) layer, a crucial factor often overlooked in previous studies. The induced movement in the mobile sublayer of the dense layer causes an increase in velocity at the upper boundary of this layer, significantly affecting the vertical distributions of velocity and concentration above this layer. We described the interactions between fractions and an intensive sediment mixing and sorting process in the contact layer. The proposed shear variation, with an increase in its maximum value at the bed, adds to the novelty of our approach. The data sets used for the model’s validation cover various conditions, including slopes, grain diameters, densities and grain mobility conditions, from incipient motion to a fully mobilised bed. This extensive validation process instils confidence in the theoretical description and its applicability to real-world scenarios.

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 extensive use of polypropylene (PP) in various industries has heightened interest in devel-oping efficient methods for recycling and optimising its mixtures. This study focuses on formu-lating predictive models for the Melt Flow Rate (MFR) and shear viscosity of PP blends. The in-vestigation involved characterising various grades, including virgin homopolymers, copolymers, and post-consumer recyclates, in accordance with ISO 1133 standards. The research examined both binary and ternary blends, utilising traditional mixing rules and symbolic regression to predict rheological properties. High accuracy was achieved with the Arrhenius and Cragoe models, at-taining R² values over 0.99. Symbolic regression further enhanced these models, offering signif-icant improvements. To mitigate overfitting, empirical noise and variable swapping were in-troduced, increasing the models' robustness and generalisability. The results demonstrated that the developed models could reliably predict MFR and shear viscosity, providing a valuable tool for improving the quality and consistency of PP mixtures. These advancements support the de-velopment of recycling technologies and sustainable practices in the polymer industry by opti-mising processing and enhancing the use of recycled materials.

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 oscillating heat pipe (OHP) is a new member in the family of heat pipes, and it has great potential applications in energy conservation. However, the fluid flow and heat transfer in the OHP as well as the fundamental effects of inner diameter on them have not been fully understood, which are essential to the design and optimization of the OHP in real applications. Therefore, by combining the high-speed visualization method and infrared thermal imaging technique, the fluid flow and thermal performance in the OHPs with inner diameters of 1, 2 and 3 mm are presented and analyzed. The results indicate that three fluid flow motions, including small oscillation, bulk oscillation and circulation, coexist or, respectively, exist alone with the increasing heating load under different inner diameters, with three flow patterns occurring in the OHPs, viz. bubbly flow, slug flow and annular flow. These fluid flow motions are closely correlated with the heat and mass transfer performance in the OHPs, which can be reflected by the characteristics of infrared thermal images of condensers. The decrease in the inner diameter increases the frictional flow resistance and capillary instability while restricting the nucleate boiling in OHPs, which leads to a smaller proportion of bubbly flow, a larger proportion of short slug flow, a poorer thermal performance, and easier dry-out of working fluid. In addition, when compared with the 2 mm OHP, the increasing role of gravity induces the thermosyphon effect and weakens the 'bubble pumping' action, which results in a little smaller and bigger thermal resistances of 3 mm OHP under small and bulk oscillation of working fluid, respectively.

This paper aims to outline the effectiveness of modern universal gate quantum computers when utilizing different configurations to solve the B-SAT(Boolean Satisfiability) problem. The quantum computing experiments are performed using Grover’s Search algorithm to find a valid solution. The experiments are performed under different variations to demonstrate their effects on the results. Changing the number of shots, qubit mapping, and using a different quantum processor are all among the experimental variables. The study also branches into a dedicated experiment highlighting a peculiar behavior that IBM quantum processors exhibit when running circuits with a certain number of shots.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

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.

An accurate assessment of the stage-discharge relationship in open channel flows is necessary and important to the design and management of hydraulic structures and engineering in practical hydrosystems such as rivers and streams. While the flow structures and patterns at open channel junctions are interesting and have been widely studied in the literature, this paper focuses further on the effect of flow junctions on stage-discharge relationship at mountain river confluences. In this study, both the flume and physical model experiments are designed and performed carefully to test and analyze the complex flow structures and characteristics at river confluences with different configurations and hydraulic conditions. The impacts of the flow junctions on the traditional stage-discharge relationship are analyzed in this study. The results of this study are discussed in the paper for the understanding of flow structures at flow junctions and the design and management of hydraulic structures in river engineering.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

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.

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.

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

This paper proposed three-dimensional numerical simulation method by coupling of electrostatic and fluid fields to evaluating the performance of electrical sensor in the concentration measurement of gas/solid two-phase flow. Compared with the static numerical simulation, this real-time dynamic 3-D simulation method can research on a designed capacitance sensor combining the dynamic characteristics of the two-phase flows for concentration measurement. Several fluid-electrostatic models of transmission pipes with different sensor structures are built. Under different test positions and different particle concentrations, the flow characteristics and the corresponding electric signals can be obtained, and the correlation coefficient between the concentration values and the capacitance values are used for performance evaluation of the sensors. The effects of flow regimes on concentration measurement are also been investigated in this paper. To validate the results of simulation, an experimental platform with horizontal straight pipe for phase volume concentration measurement of solid/air two-phase flow is built, and the experimental results agree well with simulation conclusions. The simulation and test results show that the coupling models can give constructive reference opinions for the sensor design and collection of installation position in different transmission pipelines, which are very important for the practical process of pneumatic conveying system.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

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.

With the aim of developing an innovative water treatment approach for developing countries in the Global South, we have applied the method of treating a cavitating water stream with a plasma discharge under real conditions. To this end, we have optimised the approach after investigating the effects that occur in the treated medium during such a treatment. Based on the obtained light absorption curves of treated model solutions of titanium oxysulphate and potassium bichromate, it was found that inside the reactor the main role in the destruction of chemical contaminants is played by hydroxide ions, while outside the reactor the main chemical interaction takes place with hydrogen peroxide. The plasma treatment unit was tested in the biological wastewater treatment plants of a health resort on the territory of the Russian Federation (Almetyevsk, Republic of Tatarstan). Water samples taken directly from the tertiary decantation tank were used as real wastewater samples instead of adding chemical reagents for disinfection. It was found that with different modes of operation of the plasma treatment plant, the concentration levels of coliform bacteria, coliphages and Escherichia coli decrease significantly and fall below the limit of permissible concentrations for wastewater discharge. At the same time, the possible effect of the plasma on persistent inorganic compounds was investigated. It was shown that the plasma discharge in the flow of the incoming liquid can almost completely destroy compounds that are difficult to remove, such as hydrogen sulphide and chlorides. In the course of the study, the optimum frequency of the electrical pulses of 68 kHz was selected, which ensures the lowest consumption of electrical energy while maintaining the required efficiency.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

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.

The implementation of Emissions Trading System (ETS) poses significant challenges for the Indian maritime sector. This paper investigates the regulatory implications of ETS, focusing on how these regulations impact compliance and operational practices within the Indian shipping sector. It also analyzes the economic effects, including the financial burden and competitive dynamics faced by the Indian shipping companies in a global context. Additionally, the paper explores various adaptation strategies, emphasizing technological innovations and operational adjustments essential for navigating ETS requirements. By integrating recent industry data and case studies, this study offers a comprehensive overview of how the Indian shipping industry can effectively address the evolving regulatory landscape of ETS.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

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 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.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

The current work reveals the fine tuning between stability zones and randomness of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing D/M/1 system. More specifically, this clearly provides more insights into developing a contemporary PSFFA theory that unifies non-stationary queueing theory with chaos theory and fields in both theoretical physics and chaotic systems. This opens new grounds for stability analysis of non-stationary queueing systems.

Non steady applied magnetic field impact on a liquid metals has good prospects for industry. For a better understanding of heat and mass transfer processes under these circumstances, numerical simulations are needed. A combination of finite elements and volumes methods was used to calculate the flow and solidification of liquid metal under electromagnetic influence. Validation of numerical results was carried out by means of measuring with ultrasound Doppler velocimetry technique, as well as with neutron radiography snapshots of the position and shape of the solid/liquid interface. As a result of the first part of the work, a numerical model of electromagnetic stirring and solidification was developed and validated. This model could be an effective tool for analyzing the electromagnetic stirring during the solidification process. In the second part, the dependences of the velocity pulsation amplitude and the melt velocity maximum value on the magnetic field pulsation frequency are obtained. It was found numerically the ability of the pulsating force action to develop higher values of the liquid metal velocity at a frequency close to the MHD resonance. Obtained characteristics give a more detailed description of the electrically conductive liquid behaviour under action of pulsating traveling magnetic field.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HC) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI, and contributes to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as biomarker for disease activity.

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.

In this work, zinc oxide (ZnO)/ granular activated carbon (GAC) composites at different ZnO concentration (0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC) were prepared by an in-situ hydrothermal method and demonstrated synergistic photocatalytic degradation and ad-sorption of Rhodamine B (RhB). The thermal stability, morphological structure, elemental com-position, crystallographic structure, and textural properties of developed catalysts were charac-terized by thermal gravimetric analysis (TGA/DTG), scanning electron microscopy equipped with energy dispersive-x-ray (SEM-EDS), x-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) analysis. Successful loading of ZnO onto GAC was confirmed by SEM-EDS and XRD analysis. The BET surface areas of GAC, 0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC were 474 m2/g, 450 m2/g, 453 m2/g, and 421 m2/g, respectively. The decrease in GAC could be attributed to the successful loading of ZnO on the GAC surface. Notably, 0.5M-ZnO@GAC exhibited the best photocatalytic degradation efficiency of 82% and 97% under UV-A and UV-C light over 120 min, attributed to improved crystallinity and visible light absorption. The photocatalytic degradation parameters revealed that lowering the RhB concentration, raising the catalyst dosage and pH be-yond the point of zero charge (PZC) would favor the RhB degradation. Photocatalytic reusability was demonstrated over 5 cycles. Scavenger tests revealed that the hydroxyl radicals (•OH), su-peroxide radicals (O2−•), and photoinduced hole (h+) radicals play a major role during the RhB degradation process. Based on the TOC results, the RhB mineralization efficiency of 79.1% was achieved by 0.5M-ZnO@GAC. Additionally, GAC exhibited a strong adsorptive performance towards RhB with adsorption capacity and RhB removal of 487.1 mg/g and 99.5% achieved within 90 min equilibrium time. The adsorption characteristics were best described by pseu-do-second-order kinetics, suggesting chemical adsorption. This research offers a new strategy for the development of effective photocatalyst materials with potential for wider wastewater treat-ment applications.

Two-dimensional periodic Stokes flow of viscous incompressible fluid in a rectangular cavity with constant velocities applied to the top and bottom walls is considered. The study of chaotic advection regimes is reduced to the sequential solving of two problems. To solve the first problem, the analytical method of superposition, that allows to obtain any desired accuracy of the velocity field, is used. To solve the second problem, which is associated with obtaining the trajectories of individual fluid particles, numerical calculations of the Cauchy problem were performed. An analysis of the boundary conditions accuracy was performed based on the control of local integration. The advection of the selected volume of fluid in the rectangular cavity under the periodic motion of walls for a finite period time based on piecewise spline cubic interpolation is modelled. The obtained numerical results agree with well-known experimental data.

Majority of the studied MADS box members are linked with flowering and fruit traits. However, higher volumes of studies on the type II of their two types so far suggest that florigenic effect of the gene members could just be tip of the iceberg. In current study we used a systematic approach to have general overview on the MADS box members their cross-trait and multifactor associations as well as their pleiotropic potentials based on local reference database curated for MADS box members. While doing so, we screened for the co-occurrence of the terms of interest within the title or abstract of each reference with threshold of 3 hits. Analysis results showed that our approach can retrieve multi-faceted information on the subject of study (MADS box gene members in current case) which could otherwise have been skewed depending on the authors’ expertise and/or volume of literature reference base. Overall, our study discusses on the roles of MADS box members in association with plant organs and traits-linked factors among plant species. Our assessment showed that plants with majority of the MADS box member studies include tomato, apple, rice etc., after Arabidopsis. Furthermore, based on the degree of their multi-trait associations, FLC, SVP, SOC1, etc. are suggested to have relatively higher pleiotropic potential among others in plant growth, development and flowering process. The approach devised in this study is expected applicable for having basic understanding on any study subject of interest regardless of depth prior knowledge.

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.

Scedosporium species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. Diagnosis of Scedosporium infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Scedosporium-specific biomarkers. Here we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a Scedosporium-specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens of between ~15 kDa and 250 kDa secreted during hyphal growth of the pathogens. The test is compatible with human serum, and allows the detection of the Scedosporium species most-frequently reported as agents of human disease (Scedosporium apiospermum, Scedosporium aurantiacum, and Scedosporium boydii), with limits of detection (LOD) of the EPS biomarkers in human serum of ~0.81 ng/mL (S. apiospermum), ~0.94 ng/mL (S. aurantiacum), and ~1.95 ng/mL (S. boydii). The Scedosporium-specific LFD (ScedLFD) test therefore provides a potential novel opportunity for the detection of infections caused by different Scedosporium species.

Background: Inflammatory Bowel disease (IBD) is one of the worldwide health issues with increasing incidence. Recent data point out that those patients can have a defective immune system, rendering response to vaccinations suboptimal. Since 1990, Hepatitis B Virus (HBV) vaccination has been introduced among the compulsory childhood vaccinations in Oman. Given the questionable immunogenicity of vaccinations in IBD patients, we designed this study to quantify the immune response to scheduled HBV vaccine in IBD patients and compare it with that in a matching control cohort of healthy blood donors at Sultan Qaboos University Hospital (SQUH). Methods: This is a retrospective case-control study that was conducted between the 1st of July 2023 and the 31st of May 2024 at SQUH. Using the hospital information System (HIS), a total of 252 participants were enrolled in our study and divided into two groups. Group (1) included 126 IBD patients and group (2) included 126 healthy controls. Baseline demographics, medical comorbidities and viral serologies before and after vaccination were collected. The primary outcome of the study was to compare the long term immune response to HBV vaccine between the two groups. The secondary outcomes included identifying possible risk factors for suboptimal vaccine response. Results: One hundred and twenty-six participants were included in each group. Durable protective immune response to HBV vaccine was attained in 29 patients (23%) of the IBD group compared to 109 participants (86.5%) of the control group. There was a statistically significant association (p = 0.0156) between prednisolone treatment and low immune response to HBV vaccine. Moreover, esomeprazole usage exhibited a statistically significant association (p < 0.0001) with suboptimal response to HBV vaccine. Meanwhile, there was no statistically significant correlation between low immunogenicity to HBV vaccine and age, sex, type of IBD, comorbidities, and BMI. Conclusions: IBD patients are less immunogenic to HBV vaccination compared to healthy controls. Factors like esomeprazole and/or corticosteroid therapy might be associated with poor immune response. These findings highlight the importance of reassessing the immunogenicity of HBV vaccination and probably other protective vaccinations in all IBD patients as part of their standard of care.

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.

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.

Ovarian cancer is among the most common causes of female mortality. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1) was examined. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both on cancer stem cells (CSCs), marked as CD49f+ and non-CSCs (CD49f-) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (P &lt; 0.001). The expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P&lt;0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P &lt; 0.001)

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.

Electromagnetic interference (EMI) generated by switching operations within high voltage DC (HVDC) converter stations is an issue that has been addressed by CIGRE and methods to manage EMI should be considered in the design phase using electromagnetic modeling techniques. It is shown that method of moments-based techniques that have been used in many previous studies may not be sufficient. Here, the finite-difference time-domain method is used to study the properties of single switching events using a realistic model of an HVDC converter station with special emphasis on determining the impact of the valve hall on shielding EMI. It is shown that the valve hall does not confine high frequency electromagnetic fields to the valve hall; rather it delays them from exiting through bushings in the wall. Further, it is shown that incorporating electromagnetic absorbing material into the valve hall design can significantly reduce EMI outside the converter station.

In today’s fast paced, attention-demanding society, executive functions and attentional resources are often taxed. Individuals need ways to sustain and restore these resources. We first review the concepts of attention and restoration, as instantiated in Attention Restoration Theory (ART). ART emphasizes the role of nature in restoring attention. We then discuss essentials of experiments on the causal influences of nature. Next, we expand the concept of ART to include modern, designed environments. We propose a wider perspective termed attentional ecology, in which attention behavior is viewed within a larger system involving the human and their interactions over time with environmental demands. When the ecology is optimal, mental functioning can be a positive “flow” that is productive, sustainable for the individual, and sometimes creative.