This work explores an additive-manufacturing-enabled combination-of-function approach for design of modular products. AM technologies allow the design and manufacturing of nearly free-form geometry, which can be used to create more complex, multi-function or multi-feature parts. The approach presented here replaces sub-assemblies within a modular product or system with more complex single parts that are designed and manufactured using AM technologies. This approach can increase the reliability of systems and products by reducing the number of interfaces, as well as allowing the optimization of the more complex parts during the design. The smaller part count and the ability of users to replace or upgrade the system or product parts on-demand should reduce user risk, life-cycle costs, and prevent obsolescence for the user of many systems. This study presents a detailed review on the current state-of-the-art in modular product design in order to demonstrate the place, need and usefulness of this AM-enabled method for systems and products that could benefit from it. A detailed case study is developed and presented to demonstrate the concepts.

The implementation of neural networks (NN) on edge devices enables local processing of wireless data but faces challenges such as high computational complexity and memory requirements when deep neural networks (DNN) are used. Shallow neural networks customized for specific problems are more efficient, requiring fewer resources, and resulting in a lower latency solution. An additional benefit of the smaller network size is that it is suitable for real-time processing on edge devices. The main concern with shallow neural networks is their accuracy performance compared to DNNs. In this paper, we demonstrate that a customized adaptive activation function (AAF) can meet the accuracy of a DNN. We designed an efficient FPGA implementation for a customized segmented spline curve neural network (SSCNN) structure to replace the traditional fixed activation function with an AAF. We compared our SSCNN with different neural network structures such as real-valued time delay neural network (RVTDNN), augmented real-valued time delay neural network (ARVTDNN), and deep neural networks with different parameters. Our proposed SSCNN implementation uses 40% fewer hardware resources and no Block RAMS compared to the DNN with similar accuracy. We experimentally validate this computationally efficient and memory-saving FPGA implementation of SSCNN for digital predistortion of RF power amplifiers using the AMD/Xilinx RFSoC ZCU111. The implemented solution uses less than 3% of the available resources. The solution also enables an increase of the clock frequency to 221.12 MHz, allowing the transmission of wide bandwidth signals.

[Objective] To investigate the expression of ALDH2 in hepatocellular carcinoma and its correlation with macrophage infiltration and with the activation of specific subtypes of macrophages. [Methods] Transcriptome and clinical data from patients with hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases and analyzed and collated using R and Perl software. In the TCGA hepatocellular carcinoma dataset, the Wilcoxon test was used to identify macrophage activation-related gene sets that show differential expression between hepatocellular carcinoma and normal tissues. Single-cell sequencing combined with bulk data was used to analyze macrophage infiltration of hepatocellular carcinoma immune cells and the activation and recruitment of different subtypes of macrophages. Single-factor Cox regression and minimum absolute convergence and selection operator (Lasso) were used to identify survival-related genes and construct prognostic models of HCC. The patients were divided into two groups based on their model scores. The Wilcoxon test was used to identify differentially expressed genes (DEGs) between the two groups, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the DEGs were performed. Single-sample gene set enrichment analysis (ssGSEA) was performed to explore the possible mechanism underlying the differences in prognosis. The reliability of the model was verified using the ICGC hepatocellular carcinoma dataset. A Kaplan‒Meier curve was constructed and used to analyze the influence of macrophage activation-related gene expression on survival and prognosis in patients with hepatocellular carcinoma. The log-rank test and the independent t test were used to analyze survival time data and to compare immune cell infiltration in the two groups. [Results] In a comparison of hepatocellular carcinoma and paracancerous tissues, the expression of six of 137 macrophage activation-related genes (ALDH2, CCNB2, CYP2C9, CYP3A4, F9 and KLKB1) was found to be significantly correlated with overall survival time (OS) in patients with hepatocellular carcinoma. Based on this finding, a prognosis assessment model for hepatocellular carcinoma was constructed. The OS of the patients in the high-scoring group was significantly shorter than the OS of the patients in the low-scoring group (P<0.05), and the model predicted the prognosis of patients with hepatocellular carcinoma independently of sex, age, tumor grade and stage. The area under the receiver operating characteristic (ROC) curve of the model used to predict 1-, 2-, and 3-year survival was greater than 0.7 in both the test set and the validation set. GO enrichment of DEGs between the high- and low-scoring groups of the model suggested that the DEGs are mainly related to immune function. GSEA suggested that the tumor-infiltrating immune cells in the high-scoring group were macrophages, Th2 cells and Treg cells and showed that the number of tumor-infiltrating immune cells, including NK cells, was lower in the high-scoring group than in the low-scoring group. With respect to immune function, the immune checkpoint of the high-scoring group was higher than that of the low-scoring group. Single-cell sequencing data indicated the recruitment of B cells, M0 cells, M1 cells and M2 cells to the hepatocellular carcinoma microenvironment and suggested that ALDH2 regulates related signaling pathways in a way that promotes the differentiation of macrophages into M2-type macrophages. [Conclusion] M2-type macrophages are the dominant type of macrophages associated with immune infiltration in hepatocellular carcinoma. The macrophage-associated activation gene ALDH2 activates the macrophage polarization signaling pathway and negatively regulates the differentiation of macrophages into M2-type macrophages.

Despite limited research on the effects of a combined physical exercises on static and proactive postural control and neuromuscular functions in older adults with sarcopenic obesity (SO), this study addresses the gap by examining the efficacy of a 4-month Total Mobility Plus (TMP) regimen. The study enrolled 40 older adults with SO, split into an intervention group (n=25, mean age = 76.1 ± 3.5 years; mean BMI = 34.4 ± 4.0 kg/m²) and a control group (n=25, mean age = 75.9 ± 5.4 years; mean BMI = 32.9 ± 2.3 kg/m²). Participants in the IG engaged in 60-minute TMP sessions three times a week for four months, while the CG maintained their typical daily activities. Standardized evaluations were performed before and after the intervention, including the Romberg and Timed Up and Go (TUG) tests, Center of pressure (CoP) parameters during different conditions, muscle activation and strength of plantar and dorsal flexors. Post-intervention results revealed significant reduction of the standing time measured in the Romberg (-15.6%, p<0.05), and TUG (-34.6%, p<0.05) tests. Additionally, CoP area and velocity, were notably reduced in various conditions (p<0.05). Postural control improvements were associated with an increase of strength and decrease of ankle muscle activation. These findings validate the TMP program as a safe and effective method for enhancing static and proactive postural control and neuromuscular capabilities in older adults with SO.

In the present study, the ability of novel carbon microspheres (CMs) derived from a date palm (Phoenix dactylifera) biomass using a hydrothermal carbonization (HTC) process and activated using phosphoric acid in removing methylene blue dye was investigated. Three types of palm-based wastes (seeds, leaflet and inedible crystallized date palm molasses) were used and converted to CMs via HTC process. The prepared samples were then activated using phosphoric acid via incipient wetness impregnation method. The CMs samples before and after activation were analyzed using scanning electron microscopy (SEM), elemental analysis and scanning (CHNS), Fourier Transform-Infrared (FTIR) and Brunauer–Emmet–Teller (BET) method. The samples exhibited high BET surface areas after activation (1,584 m2/g). The methylene blue adsorption results showed good fittings to the Langmuir and Redlich-Peterson isotherm models for all activated samples. The maximum adsorption capacity achieved was 409.84 mg/g for activated CM obtained from the palm date molasses, indicating high potential for application as dye-based adsorption materials.

RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more implementable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is expedient to increase its selectivity by e.g. a prodrug approach to activate the siRNAs upon external triggering, e.g. by using light. Red light is especially well suitable for in vivo applications due to its low toxicity and higher tissue penetration. Known molecular (not nanoparticle based) red light activatable siRNA prodrugs rely on singlet oxygen (1O2) mediated chemistry. 1O2 is highly cytotoxic. Additionally one of the side products in the activation of the known siRNA prodrugs is anthraquinone, which is also toxic. We here report on an improved red light activatable siRNA prodrug, which do not require 1O2 for their activation. The 5’ terminus of its antisense strand is protected with an electron-rich azobenzene promoiety. It gets reduced and cleaved upon red light exposure in the presence of Sn(IV)(pyropheophorbide a)dichloride acting as a catalyst and ascorbate required as a bulk reducing agent producing active siRNAs.

Self-healing ceramic composites are promising smart materials for high-temperature applications. To better understand their behaviors under service conditions, numerous studies have been performed both experimentally and numerically, and kinetics parameters such as activation energy and frequency factor are reported to be indispensable for investigating healing phenomena. Here, we propose a method for determining the kinetic parameters of self-healing ceramic composites based on the oxidation kinetics model of strength recovery. These parameters are determined by an optimization method using experimental strength recovery data under various healing temperatures and times and microstructural features on the fractured surfaces. Alumina and mullite matrix-based self-healing ceramic composites, such as Al2O3/SiC, Al2O3/TiC, Al2O3/Ti2AlC (MAX phase), and mullite/SiC, were selected as target materials. The theoretical strength recovery behaviors of the cracked specimens obtained from the determined kinetic parameters were compared with the experimental results. The determined parameters are within the previously reported range, and the predicted strength recovery behaviors are reasonably agreed with the experimental values. The proposed method can also be applied to other self-healing ceramics with matrices reinforced with different healing agents to evaluate oxidation rate, crack healing rate, and theoretical strength recovery behaviors for designing self-healing materials used in high temperature applications. Furthermore, the healing ability of composites can be fairly discussed regardless of the type of strength recovery test.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally-related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers Iba1 and iNOS (###p<0.001), as well as the pro-inflammatory mediators IL-1β, IL-6, Itgam and CD68 (###p<0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped soma (48.41% vs 31.36% in LPS-treated). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.

Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Over the past decade, the One Strain Many Compounds (OSMAC) approach has been established for silent gene cluster activation and elicitation of secondary metabolite production, but so far the full secondary metabolome of a biosynthetically promising bacterium has not been elucidated yet. Here, we investigate the ability of seven categories of OSMAC conditions to enhance the diversity of new mass features from bacterial strains with little literature coverage but high biosynthetic potential. The strains Bacillus. amyloliquefaciens DSM7, Corallococcus. coralloides DSM2259, Pyxidicoccus. fallax HKI727, Rhodococcus. jostii DSM44719, and Streptomyces. griseochromogenes DSM40499 were selected after genome mining with antiSMASH. After cultivation under OSMAC conditions, the generated extracts were subjected to LC-MS and MZmine analysis to determine new mass features and evaluate the tested culture conditions. 4 predicted compounds, bacillibactin, desferrioxamine B, myxochelin A, and surfactin, were identified and up to 147 new mass features were detected in the generated extracts, which greatly surpasses the number of predicted gene clusters. Among the new mass features are bioactive compounds that were so far unreported for the strains such as cyclo-(Tyr-Pro) from DSM7 and nocardamin from DSM2259. Furthermore, the tested culture conditions were evaluated regarding their suitability for the generation of new mass features from the selected strains and promising new starting points for further screenings are postulated. Especially culture conditions with little prior literature coverage are responsible for the activation of predicted gene clusters

To circumvent the thermodynamic limitation of the synthesis of oxazolidinones starting from 2-aminoethanols and CO2 and realize incorporation CO2 under atmospheric pressure, a protic ionic liquid-facilitated three-component reaction of propargyl alcohols, CO2 and 2-aminoethanols was developed to produce 2-oxazolidinones along with equal amount of α-hydroxyl ketones. The ionic liquid structure, reaction temperature and reaction time were in detail investigated. And 15 mol% [TBDH][TFE] (1,5,7-triazabicylo[4.4.0]dec-5-ene trifluoroethanol) was found to be able to synergistically activate the substrate and CO2, thus catalyzing this cascade reaction under atmospheric CO2 pressure. By employing this task-specific ionic liquid as sustainable catalyst, 2-aminoethanols with different substituents were successfully transformed to 2-oxazolidinones with moderate to excellent yield after 12 h at 80 oC. This three-component reaction running under atmospheric pressure proves to be a clever detour to avoid the thermodynamic issue in the synthesis of 2-oxazolidinones starting from 2-aminoethanols and CO2.

The effect of the acetylene and hydrogen gases mixture ratios in direct low-temperature vacuum carburization was investigated. The gas ratio is an important parameter for producing the free radicals in the carburization. The free radicals can remove the natural oxide film by the strong reaction of the hydrocarbons, and then thermodynamically activity can be increased. When the gas ratio was below 1, the supersaturation expanded austenite layers were formed on the surface of the AISI 316L stainless steel, which had the maximum carbon solubility up to 11.5 at.% at 743 K, were formed. On the other hand, when the gas ratio was above 1, the carbon concentration of them remained low even if the process time was enough increased to reach the maximum carbon solubility. As a result, the carbon concentration underneath the surface was determined to be highly dependent on the gas mixture ratio of acetylene and hydrogen. In conclusion, it is necessary to restrict the ratio of acetylene and hydrogen gases to total mixture gases to form the expanded austenite layer with the high carbon concentration in the direct low-temperature vacuum carburization.

The ongoing expansion in volume, velocity and variety of geospatial data has stimulated the development of artificial intelligence applications and associated online cartographic visualizations. In this context, the cartographic communication through peer-reviewed media evolved to incorporate Findability, Accessibility, Interoperability and Re-usability (FAIR) principles. In this paper, we review the functionalities proposed by current international peer-reviewed media for accessing, exploring and re-using geospatial data, and situate them on a diagram conceived for peer-reviewed cartography in the artificial intelligence era. We then present an overview of the cartographic infrastructure and workflow currently available in the Terra Digitalis journal for the online publication of massive spatiotemporal data. This free and opensource based solution allows a smooth integration, from data submission to final peer reviewed publication, of dynamic, interactive 2D and 3D maps. As a proof of concept, we present two maps derived from massive spatiotemporal data, related, respectively, to a climate numerical model (raster data) and a bike sharing system’s origin-destination dataset (vector data). We argue that the combination of technologies used in the journal provides an efficient and low-cost solution, unmatched by other publication media, to boost the accessibility and FAIR principles for geospatial big data.

In this research, the concept of the instability of tension in Microgrid still becomes the focus of study and purpose. Scrutinously, First-Swing Instability occurs in the system in noted changes with properties of making the system unstable or restore to a state of stability. The latter calls itself as a phenomenon of re-synchronization. Allied to aspects of system instability, it is evident that by connecting fast electric chargers for battery-electric vehicles to the distribution system from microgrids, they increase the necessary basic electrical charges and reduce the stability of the electrical energy system. Transient electrical currents have the characteristic of severely impacting microgrids not prepared in connected states or island of the main system. The occurrences of the electromagnetic incompatibility of the inrush current, due to their unpredictability and intermittent characteristic, have complex identification studies. With the elevation of electricity demand by battery-electric vehicle chargers, concerns about the effects of the integration of the electricity grid increase proportionally. The research described in this article emphasizes the influence of fast chargers’ initialization on the power variation related to the re-synchronization phenomenon and its mitigation of the stability of electricity microgrid. An optimization algorithm based on particle swarm optimization (PSO) implements the development of virtual impedances. The PSO optimization algorithm analyzes all possible operating points and aims to maximize the stability index of microgrid, maintaining reactive energy incompatibilities at the minimum level supported. The fractional objective function facilitates the service to these goals simultaneously. The optimization algorithm is implemented in a case study and the corresponding virtual impedance is incorporated into the microgrid. Voltage levels are verified as a condition in the optimization process, comparing system effectiveness.

Tuberculosis (TB) remains a global healthcare crisis with an estimated 10 million new cases and 1.4 million deaths per year TB is caused by infection with the major human pathogen Mycobacte-rium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models which capably mimic all physiological condi-tions of the infection, and high-throughput drug screening platforms. Microfluidic-based tech-niques provide single-cell analysis which reduces experimental time, the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review out-lines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculo-sis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.

We introduce firm solar forecasts as a strategy to operate optimally overbuilt solar power plants in conjunction with optimally sized storage systems so as to make up for any power prediction errors, hence entirely remove load balancing uncertainty emanating from grid-connected solar fleets. A central part of this strategy is plant overbuilding that we term implicit storage. We show that strategy, while economically justifiable on its own account, is an effective entry step to least-cost ultra-high solar penetration where firm power generation will be a prerequisite. We demonstrate that in absence of an implicit storage strategy, ultra-high solar penetration would be vastly more expensive. Using the New York Independent System Operator (NYISO) as a case study, we determine current and future cost of firm forecasts for a comprehensive set of scenarios in each ISO electrical region, comparing centralized vs. decentralized production and assessing load flexibility’s impact. We simulate the growth of the strategy from firm forecast to firm power generation. We conclude that ultra-high solar penetration enabled by the present strategy, whereby solar would firmly supply the entire NYISO load, could be achieved locally at electricity production costs comparable to current NYISO wholesale market prices.

During the last two decades several cases of venous thrombosis (VTE) after a prolonged period at a computer has been described, denominated “eThrombosis”. Video gaming on a computer has become very popular and can be a social activity where several players are gathered to play against each other or in a virtual environment for several days (“LAN (i.e., Local Area Network) parties”) where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate a potential coagulation activation during a 42 hour LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 hours, and plasma was analyzed for thrombin generation, and Thrombin-antithrombin-complexes (TAT), prothrombin Fragment 1+2 (F1+2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h gaming with minimal physical activity. Although an increased activity cannot be excluded, it does not directly indicate a risk of VTE in general. It may be specific and particularly susceptible in-dividuals who are prone to thrombosis and, therefore, are at risk of developing e-thrombosis.

Transcutaneous nerve stimulation has several neuromodulatory applications, including pain management, sensory restoration, and motor recovery. Transcutaneous stimulation delivered via electrode arrays offers ease of use and reconfigurability through non-invasive means. Also, employing electrode arrays allows regulation of the permeated electric fields for greater control over the stimulation performance. Field shaping involves the regulation of permeated electric fields and is a well-established practice for deep brain stimulation; however, its applicability to peripheral nerve stimulation still needs exploration. Adopting such techniques can help to overcome current limitations with transcutaneous stimulation, like poor targetability, early onset of fatigue, and perceived discomfort. This article provides a perspective on the applicability of field-shaping techniques in improving the overall stimulation outcome.

During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca2+oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction ability.

In order to utilize high-alumina coal gangue (HACG) as auxiliary cementitious admixture, it is of fundamental significance to thermally activating Al2O3 effectively in HACG and promoting formation of hydratable products containing Al2O3. In this paper, a new preparation technology is developed to make HACG auxiliary cementitious admixture by thermal activation of HACG-Ca(OH)2 (CH) mixture. HACG powders mixed with 20wt.% CH were calcined within a temperature range of 600-900oC, the thermal transformation and mineral phase formation were analyzed by thermogavimetric analyzer (TGA), X-ray diffractometer (XRD), scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS). The hydration reaction between activated HACG-CH mixture and cement was also investigated. HACG experienced a conventional transformation from kaolinite to metakaolin at 600oC and finally to mullite at 900oC. However, CH underwent an unexpected transformation process from CH to CaO, then to CaCO3, and finally to CaO again with increasing calcining temperature. These substances states were associated with dehydroxylation of CH, chemical reaction between CaO and CO2 generating from combustion of carbon in HACG, and decomposition of CaCO3, respectively. It is the formation of a large amount of CaO above 800oC that favors the formation of hydratable products containing Al2O3 in the calcining process and C-A-H gel in hydration process. The mechanical properties of HACG-cement mortar specimens were measured, from which the optimal calcination temperature for preparing HACG auxiliary cementitious admixture was determined to be 850oC. As compared with pure cement mortar specimens, the maximum 28-d flexural and compressive strength of HACG-cement mortar specimens increased by 5.4% and 38.2%, respectively.

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Non-linear activation functions are one of the main parts of deep neural network architectures. The choice of the activation function can affect model speed, performance and convergence. Most popular activation functions don't have any trainable parameters and don't alter during the training. We propose different activation functions with and without trainable parameters. Said activation functions have a number of advantages and disadvantages. We'll be testing the performance of said activation functions and comparing the results with widely known activation function ReLU. We assume that the activation functions with trainable parameters can outperform functions without ones, because the trainable parameters allow the model to "select'' the type of each of the activation functions itself, however, this strongly depends on the architecture of the deep neural network and the activation function itself.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

Oncology clinical pharmacists are uniquely positioned to make interventions to increase patient activation and engagement. To accomplish this goal, pharmacists can target health system-related, provider-related, and patient-related factors to help enhance patient-centered care and drive behavioral health changes. Interventions that pharmacists must tackle include educating team members and patients on the medication acquisition process, communicating urgency of treatment, optimizing workflows, facilitating guideline recommendations, preventing, and managing treatment toxicities, and promoting patient self-advocacy through education and shared decision-making. As crucial members of the healthcare team, oncology clinical pharmacists can simplify highly complex treatment regimens to facilitate and optimize patients’ ownership of their care. This review will focus on the example of venetoclax treatment in acute myeloid leukemia to demonstrate the impact that pharmacists provide that leads to behavioral change of patients and clinicians.

Although oncolytic viruses are currently being evaluated for cancer treatment in clinical trials, systemic administration is hindered by many factors that prevent them from reaching the tumor cells. When administered systemically, mesenchymal stem cells (MSCs) target tumors, and therefore constitute good cell carriers for oncolytic viruses. Methods: MSCs were primed with trichostatin A under hypoxia, which upregulated the expression of CXCR4, a chemokine receptor involved in tumor tropism, and coxsackievirus and adenovirus receptor that plays an important role in adenoviral infection. After priming, MSCs were loaded with conditionally replicative adenovirus that exhibits limited proliferation in cells with a functional p53 pathway and encodes Escherichia coli nitroreductase (NTR) enzymes (CRAdNTR) for targeting tumor cells. Results: Primed MSCs increased tumor tropism and susceptibility to adenoviral infection, and successfully protected CRAdNTR from neutralization by anti-Adenovirus antibodies both in vitro and in vivo, and specifically targeted p53-deficient colorectal tumors when infused intravenously. Analyses of deproteinized tissues by UPLC-MS/QTOF revealed that these MSCs converted the co-administered prodrug CB1954 into cytotoxic metabolites, such as 4-hydroxylamine and 2-amine, inducing oncolysis and tumor growth inhibition without being toxic for the host vital organs. Conclusion: This study shows that the combination of oncolytic viruses delivered by MSCs with the activation of prodrugs is a new cancer treatment strategy that provides a new approach for the development of oncolytic viral therapy for various cancers.

In recent years, the field of deep learning achieved considerable success in pattern recognition, image segmentation and may other classification fields. There are a lot of studies and practical applications of deep learning on images, video or text classification. In this study, we suggest a method for changing the architecture of the most performing CNN models with the aim of designing new models to be used as stand-alone networks or as a component of an ensemble. We propose to replace each activation layer of a CNN (usually a ReLu layer) by a different activation function stochastically drawn from a set of activation functions: in this way the resulting CNN has a different set of activation function layers.

Novel collector lead(II)-benzohydroxamic acid (Pb(II)-BHA) complexes in aqueous solution were characterized by using experimental approaches, including Ultraviolet-visible (UV-Vis) spectroscopy and electrospray ionization–mass spectrometry (ESI-MS), as well as first-principle density functional theory (DFT) calculations with consideration for solvation effects. The Job plot delineated that a single coordinated Pb(BHA)⁺ should be formed first, and the higher coordination number complexes can be formed subsequently. Moreover, the Pb(II)-BHA species can aggregate with each other to form complicated structures, such as Pb(BHA)₂ or highly complicated complexes. ESI-MS results validated the existence of Pb-(BHA)_n=1,2 under different solution pH values. Further, the first-principles calculations suggested that Pb(BHA)⁺ should be the most stable structure, and the Pb atom in Pb(BHA)⁺ will act as an active site to attack nucleophiles. These findings are meaningful to further illustrate the adsorption mechanism of Pb(II)-BHA complexes in mineral processing.

Integrated disaster risk reduction in schools represents a key component of safety strategies within the educational sector of every country. In this study, a series of 850 face-to-face interviews (650 with students and 200 with teachers) were conducted throughout 2023 in 10 out of the total 18 municipalities in the Western Morava Basin of the Republic of Serbia. The paper proposes two central hypotheses regarding school-based disaster risk reduction. Firstly, it suggests that gender, age, parent's employment, academic achievement, living situation, paternal and maternal education levels, and engagement with social media collectively influence students' perspectives on this matter. Secondly, it posits that gender, age, marital status, parenthood, and educational background significantly impact teachers' viewpoints on school-based disaster risk reduction. Multivariate linear regression was used to explore predictors of students' and teachers' insights on school-based disaster risk reduction. Various statistical tests including Chi-square, t-tests, one-way ANOVA, and Pearson's correlation were employed to investigate the influence of demographic and socioeconomic factors on these insights. The results of multivariate regression analyses indicate that age, gender and marital emerge as the primary predictors across various facets of students' and teachers' insights on school-based disaster risk reduction (awareness of disasters, disaster education activities, attitudes on disaster risk reduction education, enhancement of disaster information accessibility, etc). The results of this study provide insight into the key factors influencing students' and teachers' perceptions of disaster risk reduction in schools. As such, they can serve as a basis for improving educational programs, developing policies and strategies, normative educational frameworks, teacher training, and further research in disaster education.

The impact of long-term soil and crop management practices on soil biological and chemical properties in oilseed brassica-based production systems were deliberated for holistic soil health improvement in the present study. Different tillage, crop residue re-cycling and cropping systems were studied for 5-years in 0-15 and 15-30 cm soil profiles. No-till permanent beds with crop residue (PB+R) noticeably improved soil organic carbon (SOC), microbial biomass carbon (MBC), enzymes [dehydrogenase (DHA) and alkaline phosphatase (AlP)], nitrogen fractions (available, nitrate and total), and available phosphorus and potassium content in both the soil layers compared to conventional tillage without crop residues. Though, the plow soil layer (0-15 cm) showed higher concentration of soil carbon, enzymes, N fractions and available P than in the sub soil (15-30 cm). The dynamic soil biological and chemical properties were also varied with the crop stage, and recorded higher MBC at 30 days, SOC and enzymatic activities at 60 days, and N fractions and available P and K at harvest of mustard crop. Green gram-mustard rotation showed higher values of biological and chemical parameters. Thus, the legume-based mustard crop rotation following no-till permanent beds and residue re-cycling found holistic in improving soil health, and nutrient cycling.

Objective: To highlight opportunities for future nutrition intervention research within early childhood and education care (ECEC) settings, with a focus on generating evidence that has applicability to real-world policy and practice. Methods: An overview of opportunities to progress the field was developed by authors using a collaborative writing approach and informed by recent research in the field. The group developed a list of recommendations aligned with the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework. Pairs of authors drafted individual sections of the manuscript, which was then reviewed by a separate pair. The first and senior author consolidated all sections of the manuscript and sought critical input on draft iterations of the manuscript. Results: Interventions that employ digital platforms (Reach) in ECEC settings, as well as research in the family day care setting (Effectiveness) were identified as areas of opportunities. Research understanding the determinants of and effective strategies for dissemination (Adoption), implementation of nutrition programs, in addition to de-implementation (Implementation) of inappropriate nutrition practices, is warranted. For maintenance, there is a need to better understand sustainability and sustainment of interventions, in addition to undertaking policy-relevant research. Conclusions: The ECEC setting is prime for innovative and practical nutrition intervention research.

To get more data concerning the influence of fertilizers (organic and mineral) on different forage plants existing in North-eastern Romanian grassland, the mass fractions of 14 essential, enzymatic, or considerd toxic elements was determined by Instrumental Neutron Activation Analysis together with the amount of crude proteins, ash, fibres as well as ether fact extract. Final results showed a significant variance of the content of analysed elements on organic as well as on mineral fertilized experimental plots, i.e. the content increased in 24% of plots, decreased in 23%, and remained unchanged in 45% while in 8% of plots their content was below the detection limits, as the case of Se. At the same time, an increase content of crude protein and ether extract was evidenced in fertilized grasses for all applied fertilizers while other global indicators such as neutral and acid fibre of sufuric lignin content decreased, suggesting significant higher nutritional values of fertilized forage plant.

To win a taekwondo competition, more points must be scored, and the key to scoring points is to improve the motor performance of the kick. The wing kick is an offensive and defensive maneuver. Core stability appears to be important for improving athletic performance, but the specific relationship and effect of core stability on athletic performance in the aerial phase of taekwondo is unclear. The aim of this study was to investigate the relationship between core stability and athletic performance in taekwondo in order to provide appropriate theoretical support for training and to help coaches and athletes to improve athletic performance. A total of 16 subjects (height: 167.34±9.2 cm; weight: 61±8.96 kg; age: 24.7±3.25 years) were studied. Data were captured using 13 infrared cameras at 120Hz, kinematic and kinetic data were captured using a motivated motion capture system, and the data were exported to Visual3D in order to calculate the execution time of the aerial phase, the angular momentum of the left lower extremity, and MVC analysis of the EMG using EMG works. The core stability level of the subjects were measured using the Sahrmann Core Stability Test (SCST) to correlate with the other data, and then the subjects were grouped according to their core stability levels and the data from both groups were analyzed with t-tests. Results During the double fly lifting of aerial segments, SCST levels showed a very strong negative correlation with execution time (r= -0.739) and there was a statistically significant difference in execution time between high and low SCST levels (p &lt; 0.001), and the desired negative correlation was also seen in lower limb angular momentum X-axis (thigh r= -0.6294, shank r= -0.536, foot r= -0.6175), especially in the X-axis. The left rectus femoris (LRF) data had greater activation in the low SCST group(p=0.0019*). Through this experiment, we found that athletes with high core stability had faster execution times, lower angular momentum, and higher core muscle activation. Therefore, we conclude that incorporating core stability training into taekwondo training has the potential to improve kicking performance.

Melting, solidification and viscosity properties of a multicomponent Fe-Cu-Nb-Mo-Si-B alloys with low aluminum addition up to 0.42 at.% Al were studied using an oscillating cup viscometer. It is shown that melting and solidification are divided into two stages with a knee point at 1461 K. The temperature dependences of the liquid fraction between the liquidus and solidus temperatures during melting and solidification are calculated. It has been proven that aluminum accelerates the processes of melting and solidification and leads to an increase in liquidus and solidus temperatures. In the liquid state at temperatures above 1700 K in an alloy with a low aluminum content, the activation energy of viscous flow increases. This growth was associated with the liquid – liquid structure transition caused by the formation of large clusters based on the metastable Fe23B6 phase. Aluminum atoms attract iron and boron atoms and contribute to the formation of clusters based on the Fe2AlB2 phase and metastable phases of a higher order.

The surprisingly high catalytic activity of gold has been known to the heterogeneous catalysis community since the mid-1980s. Significant effort has been directed towards improving the reactivity of these surfaces towards important industrial reactions. One such strategy is the introduction of small amounts of other metals to create Au-based surface alloys. In this work, we investigate the synergistic effect of Pt doping of the Au(111) surface towards decreasing the activation barrier of the methanol dehydrogenation elementary step, within first-principles density functional theory. To this aim we construct several models of \ce{Pt}-doped Au(111) surfaces, including a full \ce{Pt} overlayer and monolayer. The effect of \ce{Pt} surface doping is then investigated via the computation of adsorption energies of the various chemical species involved in the catalytic step, and the estimation of activation barriers of methanol dehydrogenation. Both electronic and strain effects induced by \ce{Pt} surface doping concur in substantially lowering the activation energy barrier of this important reaction elementary step. Morever, in the presence of preadsorbed atomic oxygen, \ce{Pt} surface doping can be used to reduce the activation energy for methanol dehydrogenation to as low as 0.1 eV.

Polyhedral Oligomeric Silsesquioxanes (POSS) are one of the smallest silica nano particles. The presence of ordered ladder-like or cage conformation in their structure leads to remarkable thermal stability far greater than that for a linear polysiloxane. Reinforcement with nano particles is one of the recently favored strategy used to enhance the performance of polymers materials. The cyclic silica structure present in POSS ensures excellent thermal and mechanical stability. As a reinforcing filler, POSS can enhance the resistance of polymer matrix against pyrolysis and corrosion. In this paper, amine-terminated POSS with ladder like structure was synthesized by condensation of hydrolyzed aminosilane coupling agent. The ladder-like structure of POSS severely limits the motion of the chain backbone. The absence of phase transition for the synthesized POSS was confirmed by differential scanning calorimetry (DSC). Thermogravimetric analysis (TGA) was utilized to evaluate the thermal stability of POSS. TGA data show that the ladder-like POSS reported here has high char yield of about 75 % in nitrogen atmosphere and 54% in air atmosphere at 800℃. The TGA derivative curves show that the degradation of ladder-like POSS involves multiple stages and that the degradation rate is directly proportional to the heating rate. With the aid of Fourier Transform Infrared Spectroscopy (FT-IR), the cyclic structure of Si-O-Si bonding was determined to be the predominant structure. By analyzing the FTIR spectra of the cured POSS residue obtained at the specified temperatures, the detailed degradation mechanism of POSS was inferred. From the FTIR spectra of the low temperature cured samples, it was shown that the terminal silanol group was eliminated below 400℃. Some intermediate polymeric siloxane structures were observed by means of FT-IR and they eventually transitioned into silica which is the final product of pyrolysis of POSS. The presence of the FTIR transmission peaks at 1000 and 1100 cm-1, due to asymmetrical vertical and horizontal stretching of Si-O-Si, were the key evidence for the inferred ladder-like structure of POSS.

Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis that often results in severe cognitive and neurological sequelae and increases the mortality rate in patients with sepsis. Microglia are resident macrophages in the brain that play essential roles in the pathological and physiological processes of SAE. Depending on the nature of the stimulus, microglia can adopt two polarization states (M1/M2), which correspond to altered microglial morphology, gene expression, and function. Therefore, we systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE. We demonstrated that microglia are closely related to occurrence and development of SAE and concomitant cognitive impairement. Finally, we outlined some potential therapeutic approaches that can prime microglia and neuroinflammation towards the beneficial restorative microglial phenotype in SAE.

Due to the severe environmental impact of the CO2 emissions associated with the production of Ordinary Portland Cement (OPC) and the increasing demand for this commodity material, the development of alternative products has become a global concern. One alternative to OPC, or alitic-based clinkers, are amorphous-wollastonitic low calcium hydraulic binders (AWLCs). This new class of hydraulic binders, described in the literature for the first time in 2015, may significantly reduce the CO2 emissions associated with its production, resulting from its lower calcium content, but also from the fact that its production technology can be fully electrified. In this paper it is provided a state-of-the-art review, providing a comprehensive description on the latest research, summarizing both the physico-chemical and mechanical characteristics for this type of hydraulic binders, as well as possible routes for its production at an industrial scale.

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have been recently developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments on radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors such as primary liver and gastro-entero-pancreatic cancer, or in regions with unfavorable tumor-to-background ratio at FDG-PET/CT (i.e. brain), as well as in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at presents, and definitive conclusion about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center, prospective studies powered for efficacy are needed.

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

With the targets of petroleum exploration transferred to the deep and ancient strata, abundant oil and gas resources have been found in the Lower Paleozoic and older strata in central and western China. Due to complex evolutionary processes including multiple episodes of hydrocarbon accumulation and ubiquitously accompanied by secondary alterations, significant uncertainties were remained for the generation time and accumulation processes of these revealed petroleum. In this paper, relative pure Re and Os elements existing in the asphaltene fractions of Lower Cambrian solid bitumen collected from the Guangyuan area, western Sichuan Basin, SW China and another Middle–Lower Ordovician heavy oils in the Aiding area of the Tahe oilfield in the Tarim Basin, NW China were successfully obtained by the sample pre-treatments, and Re–Os isotopic analysis was subsequently carried out for the dating of these two petroleum. The Re–Os isotopic composition indicates a generation time of Guangyuan bitumen to locate between 572 Ma and 559 Ma, corresponding to the late Sinian period of Neoproterozoic era. By the means of Re–Os isochron ages, initial 187Os/188Os ratios, and carbon isotopic compositions, the Lower Cambrian bitumen is supposed to be originated from source rocks of the Doushantuo Formation in the Sinian strata and subsequently migrated into the reservoirs of Dengying Formation. These previously reserved petroleum had been transformed to present bitumen by the destruction of reservoirs caused by tectonic uplift. The Re–Os dating results of Middle–Lower Ordovician heavy oil of Tarim Basin supposed that it was formed between 450 Ma to 436 Ma, corresponding to the Late Ordovician–Early Silurian system, and the generated petroleum is likely to migrate into the Middle–Lower Ordovician karst reservoirs to form early oil reservoirs. With tectonic uplift, these oil reservoirs were degraded and reformed to be present heavy oil reservoirs.

Microscopic vision plays an important role in automated micro-assembly. However, some uncertain factors in the assembly process, such as occlusion and stains can lead to the mistakes of feature extraction. Herein, to solve the problem, the deep learning techniques are introduced into the feature recognition tasks, focusing on the attention mechanism and visualizing CNNs for DL-based microscopic vision. The main contributions are summarized as follows: The CBAM attention mechanism is combined with the YOLOv5 algorithm to improve the accuracy and robustness of feature extraction. The micropart feature occlusion experiment results show that at 70% occlusion degree, YOLOV5-CBAM can reach 97.9% mAP@0.5, which is 4.6% higher than the original one. Visualization analysis of DL-based model is conducted using Grad-CAM to make the decision result more transparent and avoid potential visual detection risks during assembly. The heatmap matching degree between GT area and high-light area is increased by 27.81% on average, which further verify the effectiveness of attention mechanism in micropart feature localization. Additionally, micropart surface stain and droplet quality classification models based on ResNet50 are trained to replace the manual sorting. The visual results are consistent with human eye discernment and judgement, confirming the reliability of parts and droplets sorting.

The purpose of the present study was to investigate the effect of post-activation performance enhancement (PAPE) induced by eccentric half-squat exercise on vertical jump performance in male jumpers. The jumping height, peak power, and work were measured and evaluated in twenty male jumpers. Participants performed five eccentric half-squats at 85% of their one-repetition maximum (1 RM), with a knee angle below 90°, followed by immediate and 2min delayed jump assessments using Squat Jump (SJ) and Countermovement Jump (CMJ) tests. Results showed that this specific PAPE protocol did not significantly improve jump performance for both SJ and CMJ tests. Factors such as stimulus specificity, rest intervals, muscle length, and the balance between potentiation and fatigue may explain these results. The study highlights the complexity of PAPE responses and suggests that a single set of eccentric squats with a short rest may not improve jump performance in male jumpers. Further research is required to optimize the interplay between conditioning stimulus and rest periods to maximize PAPE effects in athletic performance enhancement.

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

Nowadays the preservation and restoration of historical building needs to be faced in accordance with a novel sensibility regarding environment to preserve the future generations. In this context, the scientific community is focusing on novel and sustainable materials and techniques allowing durability and mechanical performances and at the same time compatibility with the existing heritage. Alkali activated materials represent a great challenge to produce new materials starting from the existing ones with reducing consumption, emission of greenhouse gases and environmental impact. This study deals with the valorization of waste materials coming from demolition and construction activities in the manufacture of geocomposites suitable for restoration and conservation of historical heritage. In particular, waste from tuff sawing and brick grinding were used as raw materials, then the geopolymeric samples produced were characterized from physical-chemical and mechanical point of view in order to investigate their performance and evaluate their suitability as materials for historical buildings recovery. Brick waste based geocomposites resulted to be more compact than the tuff-based ones as showed by the higher density values and the lower values of open porosity and water absorption and as further confirmed by the trend of the mechanical performance. Moreover, experimental data showed that physical and mechanical properties of both bricks and tuff waste-based geocomposites, even with different waste content, are compatible with existing building materials and to all the traditional repairing products.

CO2 is widely used in the prevention and control of coal spontaneous combustion. In this manuscript, three low-rank coals with different metamorphic degrees were selected as the research objects. The temperature-programmed experiments, in-situ infrared cooling experiments, simulation of competitive adsorption of CO2 and O2 in coal pores, and simulation study of CO2 inhibition of coal oxygen composite reaction were used to obtain the role and effect of CO2 in preventing oxygen adsorption in coal at low-temperature oxidation stage. It is concluded that CO2 can displace the O2 near the pore wall to physically prevent the adsorption of O2. Through the change law of heating rate and kinetic analysis, it is found that CO2 can increase its activation energy by 5.3%-108.3% during the slow heating stage of coal, and reduce its heating rate. At around 120°C, coal loses the protective effect of CO2. From the changes of functional groups, it can be seen that when coal is cooled in CO2 atmosphere, mainly pyrolysis and condensation reactions occur due to the lack of O2. In addition, CO2 can also inhibit the chain reaction of coal's chemical adsorption of oxygen. This work provides a theoretical basis for CO2 prevention and control of coal spontaneous combustion.

The administration of regional neuraxial analgesia for pain relief during labor is widely recognized as a safe and effective method involving medication delivery into the epidural or subarachnoid space in the lower back. This study proposes an innovative semantic image segmentation methodology emphasizing enhanced interpretability using convolutional Random Fourier Features and layer-wise weighted class-activation maps tailored explicitly for foot segmentation in regional analgesia monitoring. Namely, our contribution is twofold: i) a novel Random Fourier Features layer is introduced to deal with image data to enhance three well-known architectures (FCN, UNet, and ResUNet); ii) three novel quantitive measures are presented to evaluate the interpretability of a given deep learning model devoted to segmentation tasks. Our approach is rigorously evaluated on a demanding dataset of foot thermal images from pregnant women who received epidural anesthesia. Its small size and considerable variability characterize the dataset. Our validation results demonstrate that the proposed methodology not only achieves competitive foot segmentation performance but also significantly enhances the explainability of the process, rendering it well-suited for applications such as epidural insertion during labor.

Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including the regulation of local inflammation and activation of further bone-remodeling cells. Previous studies suggested the growth differentiation factor 15 (GDF15) as important pro-inflammatory regulator during the PdLFs mechanoresponse. However, the precise mechanism remains to be clarified, as GDF15 may act both intracrine and by receptor binding, potentially also in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we detected an altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLFs differentiation and their mechanoresponse.

To address the problems of poor recognition, low detection accuracy, a large number of model parameters and computation, complex network structure, and unfavorable portability to embedded devices in traditional tennis ball detection algorithms, this study proposes a lightweight tennis ball detection algorithm YOLOv5s-Z based on Robomater EP. The main work is as follows: Firstly, constructing lightweight G-Backbone and G-Neck network layers to reduce the number of parameters and computation of the network structure. Secondly, the convolutional coordinate attention is incorporated in G-Backbnone to embed the location information into the channel attention, which makes the network obtain the location information in a larger area through multiple convolutions and enhances the expression ability of the mobile network learning features. In addition, the Concat module in the original feature fusion is modified into a weighted bi-directional feature pyramid W-BiFPN with settable learning weights to improve the feature fusion capability and achieve efficient weighted feature fusion and bi-directional cross-scale connectivity. The EIOU loss is introduced to split the influence factor of aspect ratio and calculate the length and width of the target frame and anchor frame respectively, combined with Focal-EIOU Loss to solve the problem of imbalance between difficult and easy samples. The activation function Meta-ACON is introduced to achieve an adaptive selection of whether to activate the neurons and improve the detection accuracy. Finally, the experimental results show that compared with the original algorithm, the YOLOv5s-Z algorithm reduces the number of parameters and computation by 42$\%$ and 44$\%$, the model size by 39$\%$, and 2$\%$ improvement in average accuracy mean value, which verifies the effectiveness of the improved algorithm and the light weight of the model to meet the deployment requirements of embedded devices, and adapts Robomaster EP for accurate detection and real-time recognition of tennis balls.

This work aims to investigate the effect of catalyst content and reaction time by catalytic upgrading from pyrolysis vapors of residual fat at 450 °C and 1.0 atmosphere, on the yields of reaction products, physicochemical properties (density, kinematic viscosity, refractive index, and acid value) and chemical composition of organic liquid products (OLP), over a catalyst fixed bed reactor, in semi pilot scale. Pellets of Red Mud chemically activated with 1.0 M HCl were used as catalysts. The experiments were carried out at 450 °C and 1.0 atmosphere, using a process schema consisting of a thermal cracking reactor of 2.0 L coupled to a catalyst fixed bed reactor of 53 mL, without catalyst and using 5.0, 7.5, and 10.0% (wt.) Red Mud pellets activated with 1.0 M HCl, in batch mode. Samples of liquid phase products were withdrawn during the course of reaction at 40, 50, 60, 70 and 80 min in order to analyze the process kinetics. The physicochemical properties (density, kinematic viscosity, acid value, and refractive index) of OLP were determined by official methods. The chemical functions present in OLP determined by FT-IR and the chemical composition by GC-MS. The thermal catalytic cracking of residual fat show OLP yields from 54.4 to 84.88 (wt.%), aqueous phase yields between 2.21 and 2.80 (wt.%), solid phase yields (coke) between 1.30 and 8.60 (wt.%), and gas yields from 11.61 to 34.22 (wt.%). The yields of OLP increases with increasing catalyst content while those of aqueous, gaseous and solid phase decreases. For all the thermal and thermal catalytic cracking experiments, the density, kinematic viscosity, and acid value of OLP decreases with increasing reaction time. The GC-MS of liquid reaction products identified the presence of hydrocarbons (alkanes, alkenes, cycloalkanes, and aromatics) and oxygenates (carboxylic acids, ketones, esters, alcohols, and aldehydes). For all the thermal and thermal catalytic cracking experiments, the hydrocarbon content within OLP increases with reaction time, while those of oxygenates decrease, reaching concentrations of hydrocarbons up to 95.35% (area.). The best results for the physicochemical properties (density, kinematic viscosity, and acid value) and the maximum hydrocarbon content of OLP were obtained at 450 °C and 1.0 atmosphere, using a catalyst fixed bed reactor, with 5.0% (wt.) Red Mud pellets activated with 1.0 M HCl as catalyst.

Background/methods: For mechanistic studies, in vitro human B cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T cell-dependent (TD) and T cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols makes interpretation of results challenging. The aim of the present study was to achieve the most optimal B cell differentiation conditions using isolated CD19⁺ B cells and PBMC cultures. We addressed multiple seeding densities, different durations of culturing and various combinations of TD stimuli and TI stimuli including B cell receptor (BCR) triggering. B cell expansion, proliferation and differentiation was analyzed after 6 and 9 days by measuring B cell proliferation and expansion, plasmablast and plasma cell formation and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared. Results: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B cell and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2500 and 25.000 B cells per culture well for TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B cell cultures, which allows dismissal of additional B cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed little effect on phenotypic B cell differentiation, however it interferes with Ig secretion measurements. Addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B cell differentiation and Ig secretion in B cell but not in PBMC cultures. With this approach, efficient B cell differentiation and Ig secretion was accomplished when starting from fresh or cryopreserved samples. Conclusion: Our methodology demonstrates optimized TD and TI stimulation protocols for more indepth analysis of B cell differentiation in primary human B cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B cell differentiation of patient samples from different cohorts of B cell-mediated diseases.

This study has investigated the effect of nutrition labeling on consumer guilt, in situations where consumers ingest products that have an unhealthy image. The first investigation has examined the effects of types of nutrition labeling (adding healthy ingredients/reducing unhealthy ingredients). The second investigation has examined the influence of two goal-activation types(utilitarian and hedonic) and nutrition labeling on consumer guilt. The findings reveal that the utilitarian-goal-activation group felt less guilty about consuming a product with a reduced unhealthy ingredient than they did about consuming a product with an added healthy ingredient. In addition, there were interactions between the two variables, since consumer goal activation had more effect on consumer guilt about products with reduced unhealthy ingredients than on products with added healthy ingredients. Based on these results, the academic and practical implications of the present study are discussed. and proposes several directions for future research.

Two of the most common activation functions (AF) in deep neural networks (DNN) training are Sigmoid and ReLU. Sigmoid was tend to be more popular the previous decades, but it was suffering with the common vanishing gradient problems. ReLU has resolved these problems by using zero gradient and not tiny values for negative weights and the value “1” for all positives. Although it significant resolves the vanishing of the gradients, it poses new issues with dying neurons of the zero values. Recent approaches for improvements are in a similar direction by just proposing variations of the AF, such as Leaky ReLU (LReLU), while maintaining the solution within the same unresolved gradient problems. In this paper, the combining of the Sigmoid and ReLU in one single function is proposed, as a way to take the advantages of the two. The experimental results demonstrate that by using the ReLU’s gradient solution on positive weights, and Sigmoid’s gradient solution on negatives, has a significant improvement on performance of training Neural Networks on image classification of diseases such as COVID-19, text and tabular data classification tasks on five different datasets.

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the N-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.

The small satellite market continues to grow year after year. A compound annual growth rate of 17% is estimated during the period between 2020 and 2025. Low-cost satellites can send a vast amount of images to be post-processed at the ground to improve the quality and extract detailed information. In this domain lies the resolution enhancement task, where a low-resolution image is converted to a higher resolution automatically. Deep learning approaches to Super-Resolution (SR) reached the state-of-the-art in multiple benchmarks; however, most of them were studied in a single-frame fashion. With satellite imagery, multi-frame images can be obtained at different conditions giving the possibility to add more information per image and improve the final analysis. In this context, we developed and applied to the PROBA-V dataset of multi-frame satellite images a model that recently topped the European Space Agency’s Multi-frame Super Resolution (MFSR) competition. The model is based on proven methods that worked on 2D images tweaked to work on 3D: the Wide Activation Super Resolution (WDSR) family. We show that with a simple 3D CNN residual architecture with WDSR blocks and a frame permutation technique as data augmentation better scores can be achieved than with more complex models. Moreover, the model requires few hardware resources, both for training and evaluation, so it can be applied directly from a personal laptop.

Influence of particle size on the mechanical strength of alkali activated material from waste refractory monolithic was investigated in this study. Precursor was chemically and mineralogically analysed, separated on 4 fractions and alkali activated with Na-water glass. Alkali activated materials were thoroughly investigated under SEM and XRD to evaluate the not predicted differences in mechanical strength. Time dependence of curing temperature on mechanical strength was investigated in the sample prepared from a fraction that caused the highest compressive strength.

Normally, the Nernst voltage calculated from the concentration of the reaction gas in the flow channel is considered to be the ideal voltage (reversible voltage) of the oxyhydrogen fuel cell, but actually it will cause a concentration gradient when the reaction gas flows from the flow channel through the gas diffusion layer to the catalyst layer. The Nernst voltage loss in fuel cells in most of the current literature is thought to be due to the difference in concentration of reaction gas in the flow channel and concentration of reaction gas on the catalyst layer at the time when the high net current density is generated. Based on the Butler-Volmer equation in oxyhydrogen fuel cell, this paper demonstrates that the Nernst voltage loss is caused by the concentration difference of reaction gas in flow channel and on the catalytic layer at the time when equilibrium potential (Galvanic potential) of each electrode is generated.

Background: After the increasingly common anterior cruciate ligament reconstruction (ACLR) procedure in competitive athletes, rehabilitation is crucial for facilitating a timely return to sports (RTS) and preventing re-injury. This pilot study investigates the biomechanical and psychological outcomes of postoperative rehabilitation in competitive athletes, comparing supervised rehabilita-tion (SVR) and home-based rehabilitation (HBR). Methods: After ACLR, 60 (out of 74 screened) athletes were recruited and equally divided into 2 groups using non-probability convenience sam-pling: 30 HBR and 30 SVR (each group comprising 15 males and 15 females). Rehabilitation out-comes in respective groups were evaluated at 8 months using measures (Tegner-Activity-Scale [TAS], International Knee Documentation Committee subjective knee form [IKDC-SKF], ACL Return to Sport after Injury [ACL-RSI]) and objective parameters (isometric muscle strength, hamstring/quadriceps asymmetry). RTS was evaluated at 9 months; with ACL re-injury rates rec-orded approximately 6 months post-RTS. Results: Both groups exhibited decreased TAS scores (HBR: 8 to 6, SVR: 8 to 7), with the SVR group demonstrating superior post-operative IKDC-SKF scores (81.82 vs. 68.43) and lower ACL-RSI scores (49.46 vs. 55.25). Isometric and isokinetic mus-cle strength, along with asymmetry values, favored the SVR group 8 months post-ACLR (p

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

A graphene-containing LDH was prepared by re-hydration of the oxides produced by the calcination of an organic LDH. While the memory effect is a widely recognized effect on oxides produced by inorganic LDHs, it is unprecedented from the calcination/re-hydration of organic ones. Different temperatures (400, 600 and 1100 °C) were tested, on the basis of thermogravimetric data. Water instead of a carbonate solution was used for the re-hydration, with CO₂ available from water itself and/or air to induce a slower process with an easier and better intercalation of the carbonaceous species within the layers. The samples were characterized by X-ray Powder Diffraction (XRPD), IR and Raman spectroscopy and scanning electron microscopy (SEM). XRPD indicate the presence of carbonate LDH mixed with a layered phase with a larger d-spacing. IR confirmed that the prevailing anion is carbonate, coming from the water used for the re-hydration and/or air. Raman data indicated the presence of low-ordered graphenic species moieties and SEM the absence of separated graphene of graphitic sheets, suggesting an intimate mixing of the carbonaceous phase with reconstructed LDH. Organic LDHs gave better memory effect after calcination at 400 °C. Conversely, the graphenic species are observed after rehydration of the sample calcined at 600 °C with a reduced memory effect, demonstrating the interference of the carbonaceous phase with LDH reconstruction and the bonding with LDH layers to form a graphene-LDH nanocomposite.

Treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone by block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (7 horses per group) and 18 months (7 MSC- and 5 control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation-, lameness- and ultrasonography scores improved more over time in the MSC-group. The lameness score difference significantly improved in the MSC- compared to the control-group after 6 months. In the MSC-group, 5 out of 7 horses were free of re-injuries and back to training until 12 and 18 months. In the control-group, 3 out of 7 horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for treatment of early phase tendon disease and provide a basis for a larger controlled study.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

The fixation and activation of the dinitrogen molecule, N2 by hexametallic clusters of the general formula {[(μ2-L)M)]6(μ-η1:η3-Ν2)}0/+6 (L = CH2-, NH2-, PH2-, OH-, SH-, BH2- and NH2-, M = Ru(II) or Os(II)) were scrutinized by means of density functional theory calculations. In these systems, the dinitrogen molecule, acts as a ligand that bridges the two opposite facing triangular metallic rings, cyclo-M3 of the {[(μ2-L)M)]6(μ-η1:η3-Ν2)}0/+6 clusters The hexametallic clusters, that mimick the six Fe cluster of nitrogenase, were found to strongly activate N2, converting it into a hydrazido-like group, N24-. This is substantiated by the calculated N-N bond lengths, Re(N-N) and the stretching frequencies of the N-N bond of dinitrogen, vs(N-N) found in the ranges 1.299 – 1.487 Å and 780 – 1270 cm-1 respectively. Based on the Re(N-N) and vs(N-N) values, the dinitrogen activation depends upon the nature of the hexametallic cluster. Accordingly, the Os(II) clusters were found to activate more strongly the dinitrogen molecule as compared to their Ru(II) counterparts. The nature of the ligand L also affects the extent of the N2 activation by the hexametallic clusters, which follows the order BH2- &lt; NH2- &lt; OH- &lt; CH2- &lt; NH2- &lt; PH2-, SH- for M = Ru(II) and the order BH2- &lt; NH2- &lt; OH- &lt; NH2- &lt; CH2- &lt; PH2- &lt; SH- for M = Os(II). Thus, the strongest N2 activation is observed for the {[(μ2-SH)Os)]6(μ-η1:η3-Ν2)}+6 cluster and the weakest for the {[(μ2-BH)Ru)]6(μ-η1:η3-Ν2)}0 cluster. The calculated Nitrogen-15 NMR isotropic chemical shielding tensors, σiso(15N) exhibit shielding (upfield) upon N2 fixation to the metal centers of the hexametallic clusters, as a results of electron density transfer towards its constituent N nuclei. A multitude of electronic charge distribution partitioning schemes were applied to assist in delineating the bonding properties of the {[(μ2-L)M)]6(μ-η1:η3-Ν2)}0/+6 clusters. Accordingly, it is found that there is a donation/backdonation interaction between the bridging N2 ligand and the two opposing cyclo-M3 rings located on either side. The dinitrogen ligand forms six bonds of mixed covalent/electrostatic nature with the six metal centers of the {[(μ2-L)M)]6)}0/+6 clusters.

Support effect is an important issue in heterogeneous catalysis while the explicit role of a catalytic support is often unclear for catalytic reactions. A systematic density functional theory computational study is reported in this paper to elucidate the effect of a model boron nitride (BN) support on the first N-H bond activation step of NH3 on Run (n =1, 2, 3) metal clusters. Geometry optimizations and energy calculations were carried out using density functional theory (DFT) calculation for intermediates and transition state from the starting materials undergoing the N-H activation process. The primary findings are summarized as follows. The involvement of the model BN support does not significantly alter the equilibrium structure of intermediates and transition state in the most favorable pathway (MFP). Moreover, the involvement of BN support decreases the free energy of activation, ΔG≠, thus improving the reaction rate constant. This improvement is more obvious at high temperatures like 673 K than low temperatures like 298 K. The BN support effect leading to the ΔG≠ decrease is most significant for the single Ru atom case among all three cases studied. Finally, the involvement of model BN may change the spin transition behavior of the reaction system during the N-H bond activation process. All these findings provide a deeper insight into the support effect on the N-H bond activation of NH3 for supported Ru catalyst in particular and for supported transition metal catalysts in general.

Building deep learning models proposed by third parties can become a simple task when specialized libraries are used. However, a great deal of mystery still surrounds the design of new models or the modification of existing ones. These tasks require in-depth knowledge of the different components or building blocks as well as their dimensions. This information is limited and broken up in different literature. In this article, we collect and explain in-depth the building blocks to design deep learning models, starting from the artificial neuron to the concepts involved in building deep neural networks. Furthermore, the implementation of each building block is exemplified using the Keras library.

Introduction: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in amitochondriate anaerobic protozoa such as Trichomonas vaginalis. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by T. vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of T. vaginalis and anaerobic bacteria to metronidazole. Aims: To analyze the phylogenetic distribution of PFOR in selected protozoa and bacteria using proteins encoded by housekeeping genes as controls. Using comparative bioinformatics to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer from bacteria, proteome-wide analysis and gene expression analysis to identify other genes that were putatively acquired through horizontal gene transfer from bacteria to protozoa. Methods: Sequence similarity queries were performed using the proteins of interest against the NCBI non-redundant protein sequence database with BLASTP version 2.12.0+ from the NCBI website. Multiple sequence alignments were performed with MEGA version X software using the Muscle algorithm. These were then exported in Mega format to construct phylogenetic trees using the neighbor-joining algorithm and the Poisson substitution model. Complete proteomes of representative protozoan and bacterial species were downloaded in fasta format from the ensemblgenomes database. HMM profile libraries were used to screen the proteomes with hmmscan of the HMMer package. Whole proteome BLAST searches were performed between protozoan species of interest against closely related protozoa. The results were compared to the proteome BLAST against the intestinal bacteria Desulfovibrio vulgaris. Gene enrichment analysis was performed between the exclusively present proteins in the protozoa and D. vulgaris. Only results with p-values <0.05 were considered for analysis. Results and conclusions: A plausible explanation for the restricted occurrence of PFOR in protozoa is based on the hypothesis that bacteria serve as potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The expanded cladograms of Entamoeba and Cryptosporidium with their closely related genera substantiated this hypothesis. The exclusively expressed proteins obtained from E. histolytica and the putative bacterial gene donor, D. vulgaris, showed an over-representation of eleven genes involved in small molecule metabolism, generation of precursor metabolites, and carbohydrate metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria. Subsequent syntenic analyses of the significantly enriched genes would be required to provide further information regarding the positional relatedness of these genes at the chromosomal level. Since metronidazole is an established and well tolerated drug for treating infections caused by PFOR-possessing pathogens, it can be considered as a potential drug candidate for the treatment of infections caused by Cryptosporidium, Spironucleus and Blastocystis.

Deep learning has been applied in many areas that have had a significant impact on applications that improves real-life challenges. The success of deep learning in a wide range of areas is due in part to the use of activation functions, which are particularly effective at solving non-linear problems. Activation functions are a key focus for researchers in artificial intelligence who aim to improve the performance of neural networks. This article provides a comprehensive explanation and comparison of different activation functions, with a focus on the arc tangent and its variations specifically. The paper presents experimental results that show that variations of the arc tangent using irrational numbers such as pi, the golden ratio, and Euler’s number, as well as a self-arctan function, produce promising results. Since we experimented with promising activation functions on two different problems, and datasets, we reached a result that different irrationals work well for different problems. In other words, arctan ϕ gives the best results mostly for multiclass classification and arctan e gives the best results for time series prediction problems. The paper focuses on a multiclass classification problem applied to the Reuters Newswire dataset and a time-series prediction problem on Türkiye energy trade value to show the impacts of activation functions.

This work aims to investigate the influence of reaction time and catalyst-to-residual fat ratio by catalytic upgrading from pyrolysis vapors of residual fat at 400 °C and 1.0 atmosphere, on the yields of reaction products, physicochemical properties (density, kinematic viscosity, and acid value) and chemical composition of bio-oils, over a catalyst fixed bed reactor of activated carbon pellets impregnated with 10.0 M NaOH, in semi pilot scale. The experiments were carried out at 400 °C and 1.0 atmosphere, using a process schema consisting of a thermal cracking reactor of 2.0 L coupled to a catalyst fixed bed reactor of 53 mL, without catalyst and using 5.0, 7.5, and 10.0% (wt.) activated carbon pellets impregnated with 10.0 M NaOH, in batch mode. Samples of liquid phase products were withdrawn during the course of reaction at 50, 60, 70, 80, 90, 100 and 120 minutes in order to investigate the process kinetics. The physicochemical properties (density, kinematic viscosity, and acid value) of bio-oils were determined by official methods. The chemical composition of bio-oils determined by GC-MS. The thermal catalytic cracking of residual fat show bio-oils yields from 55.55 to 30.22 (wt.%), aqueous phase yields between 2.83 and 3.19 (wt.%), solid phase yields between 13.56 and 9.75 (wt.%), and gas yields from 27.89 to 55.60 (wt.%). The yields of bio-oil decreases from 74.41 to 30.22% (wt.) with increasing catalyst-to-Tallow kernel oil ratio, while that of gaseous phase increases from 12.87 to 55.60% (wt.). For all the thermal and thermal catalytic cracking experiments, the density, kinematic viscosity, and acid value of bio-oils decreases as the reaction time increases varying from 0.9266 to 0.8220 g/cm³, 8.10 to 2.24 mm²/s, and 144.14 to 2.37 mg KOH/g. The GC-MS of liquid reaction products identified the presence of hydrocarbons (alkanes, alkenes, ring-containing alkanes, ring-containing alkenes, and aromatics) and oxygenates (carboxylic acids, ketones, esters, alcohols, and aldehydes). For all the pyrolysis and catalytic cracking experiments, the hydrocarbon selectivity in bio-oil increases with increasing reaction time, while those of oxygenates decrease, reaching concentrations of hydrocarbons up to 95.35% (area.). The best results for the physicochemical properties density, kinematic viscosity, and acid value were 0.8220 g/cm³, 3.03 mm2/s, and 2.37 mg KOH/g, respectively, with a maximum hydrocarbon concentration of 97.194% (area.) and 2.806% ketones (area.) were obtained at 400 °C and 1.0 atmosphere, 80 minutes, without catalyst. For the catalytic cracking experiments, the maximum hydrocarbon content of 75.763% (area.) and 17.041% (area.) carboxylic acids, 4.702% (area.) ketones (area.), and 2.494% (area.) non-identified oxygenates was obtained at 400 °C and 1.0 atmosphere, 90 minutes, using a catalyst fixed bed reactor, with 10.0% (wt.) activated carbon pellets impregnated with 10.0 M NaOH as catalyst.

Ceramic samples based on b-calcium pyrophosphate b-Ca2P2O7 were prepared using firing at 900, 1000, and 1100 oC from powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratios Ca/P=1; 0,975 and 0,95. To prepare powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratio Ca/P=1; 0,975 and 0,95 powder mixtures based on calcium lactate pentahydrate Ca(C3H5O3)2⋅5H2O and, monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O were treated in an aqua medium in mechanical activation conditions, dried, disaggregated in acetone, and heat-treated at 600 oC. The phase composition of powder mixtures after treatment if planetary mill in aqua medium included both brushite CaHPO4⋅2H2O or monetite CaHPO4, and starting salts. The phase composition of all powder mixtures after disaggregation in acetone in planetary mill included monetite CaHPO4 and starting salts. After heat treatment at 600 oC according to the XRD data phase composition of all powder mixtures was presented by g-calcium pyrophosphate g-Ca2P2O7. The grain size of ceramics increased both with the growth of firing temperature and with decreasing of molar ratio Ca/P of powder mixtures. Calcium polyphosphate (t melt =960–968 oC) formed from monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O acted like a liquid phase sintering additive. It was confirmed by tests in vitro, that prepared ceramic materials with preset molar ratio Ca/P=1; 0,975 and 0,95 and phase composition presented by b-calcium pyrophosphate b-Ca2P2O7 according to XRD data were biocompatible and could maintain bone cells proliferation.

Creep deformation behaviour in single phase γ-TiAl alloy has been an extensively studied topic since the late 1970s. A lot of literatures have reported creep behaviour of γ-TiAl alloys, manufactured using different processing techniques [1]–[7]. The present discussion revisits the original work on understanding the tensile creep deformation behaviour of wrought single-phase γ-TiAl alloy by Hayes et al. [8] and is aimed to develop an understanding of steady state creep, through strain vs strain rate and strain vs ln(strain rate) plots. Besides, it also attempts to study the variation of stress exponent with temperature between 760-900⁰C and also, to determine activation energies using the two most common approaches, namely: Zener-Hollomon (Z-H) [9] and Sherby-Dorn (S-D, temperature compensated time approach) [10] for stress levels of 69 and 103.4 MPa between 760-900⁰C.

Understanding of the decisive role of the interaction mechanism and kinetics in the combustion processes is highly relevant for the elaboration of optimal conditions for obtaining Mo-Cu composite powders. From this perspective, the efficient delivery of the reduction mechanism of copper and molybdenum oxides with combined Mg + C reducing agents at high heating rates is crucial to develop a valuable approach for the combustion synthesis of Mo-Cu composite powders. Herein, we shed light on the mechanism of the reactions in all the studied binary, ternary and quaternary systems contemporaneously demonstrating the effect of the heating rate on the conversion degree. The combination of two highly exothermic and speedy reactions (MoO3+3Mg and CuO+Mg vs MoO3+CuO+4Mg) led to a slow interaction with weak self-heating (dysynergistic effect) due to a change in the reaction mechanism. On the other hand, it has been shown that during the simultaneous utilization of the Mg and C reducing agents, the process begins exclusively with carbothermic reduction, and at relatively high temperatures it continues with magnesiothermic one. The effective activation energy values of the magnesiothermic stages of the studied reactions were determined by Kissinger isoconversional method.

In the author's opinion, many global problems that face humanity - in the fields of education, medicine, management etc can be tackled more effectively if the cyclic nature of self-reproducing systems – including living beings – is taken into account. Summarizing the main physiological findings of the last decades on "adaptation reactions", one can very roughly say that the way of action which is effective in the sense of productive activity of people happens at the same time to be healthy, and it gives the participants of the process the feeling of happiness. The present paper represents a very short overview of the contemporary concepts of the adaptation reactions based on the fundamental understanding of their cyclic nature due to general properties of self-reproducing systems. One interesting feature of self-reproduction cycles is its first "phase of orientation" which was not discussed in detail in the past but plays a key role in the whole cycle.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Prostate cancer (PCa) is a major cause of cancer-related mortality worldwide, with a rising incidence observed over the years. The androgen receptor (AR) signaling pathway plays a pivotal role in male development and maintaining masculine characteristics. Dysregulation of AR signaling in prostate cancer can lead to disease progression and resistance to standard therapies. Understanding the intricate regulation and function of AR in both healthy and diseased states is crucial for developing effective treatment strategies. This review comprehensively explores the role of androgen receptors in prostate cancer susceptibility, disease progression, and treatment response by analyzing recent literature. An extensive search of peer-reviewed publications in major databases, including PubMed, Scopus, and Web of Science, was conducted using specific keywords related to androgen receptor, prostate cancer, disease progression, and treatment resistance. Relevant conference abstracts and clinical trial reports were also included. The review presents an overview of the role of androgen receptors in prostate cancer initiation, progression, and treatment resistance. It highlights emerging biomarkers associated with AR signaling dysregulation and their potential utility for early detection and personalized treatment approaches. Additionally, recent advances in targeting the AR pathway for novel therapeutic strategies to improve patient outcomes and overcome treatment resistance in advanced prostate cancer are discussed. The findings contribute to a comprehensive understanding of the AR signaling pathway in prostate cancer and offer insights into its multifaceted role in disease development and treatment response. They may pave the way for innovative therapeutic interventions and precision medicine approaches based on specific AR signaling profiles, enhancing patient care and reducing the burden of this lethal disease.

An evaluation of emerging issues in One Health (OH) in Sub-Saharan Africa was undertaken to map the existing OH initiatives in Sub-Saharan African (SSA) countries. Desk review, expert opinions survey, limited interviews and wider consultations with selected OH stakeholders were conducted. The strengths, weaknesses, opportunities and threats to OH initiatives were identified. OH influence, interest and impacts were evaluated. One Health is transiting from multidisciplinary to transdisciplinary concepts and OH viewpoint should move from ‘proxy for zoonoses’, to include issues of climate change, nutrition and food safety, social sciences, geography, policy and planning, economics, welfare and well-being, antimicrobial resistance (AMR), vector-borne diseases, toxicosis and pesticides issues. While the identified major strengths should be boosted, the weaknesses should be addressed.OH Networks in SSA were spatially and temporally spread across SSA and stakeholders were classified as key, latent, marginal and OH defenders. Imbalance in stakeholders’ representation led to hesitation in buying-in from stakeholders who are outside the main networks. Theory of change, monitoring and evaluation frameworks, and tools to standardized evaluation of OH policies is needed for sustained future of OH and the future OH engagement should be outputs and outcomes-driven and not activity-driven.National roadmap for OH implementation and institutionalization is necessary and proofs of concepts in OH should be verified and scaled-up. Dependence on external funding is unsustainable and must be addressed. Necessary policy and legal instrument to support OH nationally and sub-nationally should be implemented taking cognizance of contemporary issues like urbanization, endemic poverty and other emerging issues. Utilizing current technologies and OH approach to address ongoing pandemic of COVID-19 and other emerging diseases is desirable. Finally, OH implementation should be anticipatory and not reactive to significantly benefit budgeting and contain disease outbreaks in animal sources before the risk of spillover to human can be envisaged.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

This research examines the fire resistance of geopolymer composites (GCs), formulated using alka-li-activated metakaolin and aluminum powder. The production method involves spray-coating carbon steel plates with fresh GCs, followed by a 28-day curing period at room temperature. Sub-sequently, fire performance and aging tests are conducted to evaluate fire resistance. The study investigates GC properties, including apparent density, bending strength, compression strength, thermal conductivity, porosity, and production cost. Morphological changes before and after fire and aging tests are analyzed using scanning electron microscopy (SEM). Results demonstrate GC foams' outstanding thermal insulation, providing up to 75 minutes of fire resistance with a 6 mm coating, reducing temperatures by 300 °C compared to uncoated steel. GCs exhibit a density of 670 kg/m³, thermal conductivity of 0.166 W/m·K, 68% porosity, and cost efficiency at 250 dollars per cubic meter. This study underscores the potential of foamed geopolymer coatings for effective and economical surface protection.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

Weathering and erosion transport minerals and organics toward the sea or lake bottoms over geologic time. The finest solids are deposited in lower, less turbulent areas, such as lake bottoms and continental shelves. They sometimes stack up to thicknesses of kilometers, and begin compacting. These sediment sections are called shales, and as initially deposited in water, shales can have porosities up to 50-80{\%} water, As they are buried, many alteration products from oil to slate are produced due to overburden and temperature increasess, making them important to study. A preceeding paper \cite{1} showed that pressure solution is the primary mechanism for porosity reduction, with possible mechanical compaction at shallow depths. Without naming the mineral(s) involved, it postulated that the greater the product of the water and pore interfaces, the faster the reaction would proceed. This term is $ \varphi^{4m/3}(1-\varphi)^{4n/3}$ , where $\varphi$ is porosity and m and n are numbers close to unity. The large exponents, {\em 4/3}, recognize that the reaction occurs at the molecular scale at which the surfaces are rough. A second term, $\exp^{(-E/RT)}$ , indicates that the reaction is impeded by a quantum energy barrier, E, with diminished impeding power as increased available thermal energy, represented by the absolute temperature, T, becomes available at greater depths in the Earth. These two factors combine to allow porosity $\varphi$ to reduce with time, or equivalently for the fraction of solids, $(1-\varphi)$, to increase with time,$\left. \frac{\partial(ln(1-\varphi) ) }{\partial t } \right |_{\sigma} = (\varphi )^{4m/3}( 1-\varphi )^{4n/3}Ae^{-E/(RT)}$. { \em Here it is shown that this equation can cover quantitatively any actual deposition rates which may have been experienced by the six sections studied, the actual deposition rates being unknown for these cases. Hence a time-depth depositional history for any new shale section, known in detail, would allow determination of the parameters m, n, E and a lumped proportionality constant A. This was accomplished by showing that, for a wide range of depositional rates, r, the range of E for any of the studied sections is small compared to laboratory measurements of quartz solution\cite{2}, 24+-15kJ/mol. Results were obtained over this range of r's using the previously determined m and n, and porosity and temperature profiles. The presently existing porosity profiles necessarily incorporate any overpressure or underpressure conditions that may have existed in the past or currently, as the net difference between overburden and pore pressure is a primary driving force for pressure solution. $SiO_2$ usually comprises 20-50{\%} of shales. In conclusion, pressure solution of quartz can account for vertical compaction of shales quantitatively in the studied examples. Separately, a quasi-eqivalent method for discussing reduced porosities in Macron 2 versus Macron 1 as increased vertical stress, rather than additional horizontal stress, is illustrated. Experiments are suggested to clarify the pressure solution mechanism. The role of horizontal forces is discussed.

Deep learning has been applied in many areas that have had a significant impact on applications that improves real-life challenges. The success of deep learning in a wide range of areas is due in part to the use of activation functions, which are particularly effective at solving non-linear problems. Activation functions are a key focus for researchers in artificial intelligence who aim to improve the performance of neural networks. This article provides a comprehensive explanation and comparison of different activation functions, with a focus on the arc tangent and its variations specifically. The paper presents experimental results that show that variations of the arc tangent using irrational numbers such as pi, the golden ratio, and Euler’s number, as well as a self-arctan function, produce promising results. Since we experimented with promising activation functions on two different problems, and datasets, we reached a result that different irrationals work well for different problems. In other words, arctan ϕ gives the best results mostly for multiclass classification and arctan e gives the best results for time series prediction problems. The paper focuses on a multi-class classification problem applied to the Reuters Newswire dataset and a time-series prediction problem on Türkiye energy trade value to show the impacts of activation functions.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

Geminiviruses possess single-stranded, circular DNA genomes, and control the transcription of their late genes, including BV1 of many bipartite begomoviruses, through transcriptional activation by the early expressing AC2 protein. DNA binding by AC2 is not sequence-specific, hence the specificity of AC2 activation is thought to be conferred by plant transcription factors (TFs) recruited by AC2 in infected cells. However, the exact TFs AC2 recruits are not known for most viruses. Here we report a systematic examination of the BV1 promoter (PBV1) of mungbean yellow mosaic virus (MYMV) for conserved promoter motifs. We found that MYMV PBV1 contains three abscisic acid (ABA)-responsive elements (ABREs) within its first 70 nucleotides. Deleting these ABREs, or mutating them all via site-directed mutagenesis, abolished the capacity of PBV1 to respond to AC2-mediated transcriptional activation. Furthermore, ABRE and other related ABA-responsive elements were prevalent in more than a dozen Old World begomoviruses we inspected. Together these findings suggest that ABA-responsive TFs may be recruited by AC2 to BV1 promoters of these viruses to confer specificity to AC2 activation. These observations are expected to guide the search for the actual TF(s), furthering our understanding of the mechanism of AC2 action.

We asked whether the level of peripheral fatigue would differ when three consecutive exercise trials were completed to task failure, and whether there would be delayed recovery in maximal voluntary contraction (MVC) force, neuromuscular activation and peripheral fatigue following task failure. Ten trained sport students performed three consecutive knee extension isometric trials (T1, T2, T3) to task failure without breaks between trials. T1 and T2 consisted of repeated 5-s contractions followed by 5-s rest. In T1, contractions were performed at a target force at 60% pre-exercise MVC. In T2, all contractions were MVCs, and task failure occurred at 50% MVC. T3 was a sustained MVC performed until force fell below 15% MVC. Evoked force responses to supramaximal electrical femoral nerve stimulation were recorded to assess peripheral fatigue. Electromyography signals were normalized to M-wave amplitude to assess neuromuscular activation. Lower levels of evoked peak forces were observed at T3 compared to T2 and T1. Within 5 s of task failure in T3, MVC force and neuromuscular activation recovered substantially without any recovery in evoked peak force. Neuromuscular activation 5-10 s after T3 was unchanged from pre-exercise values, but evoked peak forces were substantially reduced. These results challenge the existence of a critical peripheral fatigue threshold that reduces neuromuscular activation. Since neuromuscular activation changed independently of any change in evoked peak force, immediate recovery in force production after exercise is due to increased central recruitment and not to peripheral mechanisms.

The outstanding occurrences of red wood ant nests (RWA; Formica rufa-group) at two study sites in the Oberpfalz, NE Bavaria, Germany, could be confirmed by the 2023 re-inventory (a total of 5,393 nests and an increase by ≈8 %). RWA nests preferred mature and medium mature pine-dominated forests. Standing and downed dead wood do not negatively influence nests. Nest counts with woodpecker cavities and the diversity of the herb layer increased. The highly clustered nests in NW-SE direction suggests a strong interaction between nests distributions and the tectonic environment. Our developed (re-)inventory approach in combination with the comprehensive photo database is a valuable tool for a) monitoring the entire forest habitat including woodpecker cavities and dead wood in, at and around nests, and b) identifying GeoBio-Interactions. Such a comprehensive approach leads to more accurate and realistic counts of RWA nests during (re-)inventories and provides scientific evidence of the status quo of RWA occurrence. Our results disproved the unfounded and scientifically unsubstantiated blanket statement by laymen of the ASW Landesverband Bayern e.V. that RWA nest numbers in the Oberpfalz or even in the entire Bavaria are in sharp decline. We suggest seven to eight years as a suitable time interval for re-inventories.

The space shuttle, a revolutionary spacecraft that has played a significant role in human space exploration, was composed of various advanced materials that were carefully selected to meet the extreme demands of spaceflight. This review paper provides a comprehensive examination of the materials historically employed in the construction of space shuttles and explores the latest trends shaping the field. The evolution of space shuttle materials is traced from the inception of the space program to contemporary missions, highlighting key milestones, challenges, and breakthroughs. Emphasis is placed on the critical role that materials play in the overall performance, safety, and sustainability of space shuttles. The paper begins by elucidating the diverse requirements that materials must fulfill in the harsh and complex environment of space, encompassing extreme temperatures, radiation exposure, and mechanical stresses. A detailed analysis of the materials utilized in the fabrication of various shuttle components, such as thermal protection systems, structural elements, and propulsion systems, is presented. Special attention is given to the challenges posed by re-entry and the strategies employed to mitigate heat-related issues. Furthermore, the review explores recent innovations and emerging materials that are reshaping the landscape of space shuttle design. Advancements in nanotechnology, composite materials, and additive manufacturing are discussed in the context of their potential applications for enhancing shuttle performance and reducing mission costs. The paper also addresses the importance of sustainability in space exploration, exploring materials with lower environmental impact and improved recyclability. The review concludes with a forward-looking perspective on the future of materials, considering ongoing research, development, and the potential incorporation of cutting-edge technologies. Insights are provided into how the evolving landscape of materials science may influence the design and manufacturing processes of the next generation of space vehicles. This paper provides an overview of the materials used in the construction of the space shuttle, including their properties, applications, and challenges. The materials used in the space shuttle are critical in ensuring the safety, performance, and longevity of the spacecraft, and understanding their characteristics and performance in space is crucial for the advancement of aerospace engineering.

(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin-system (RAS) is critically involved in their pathophysiology and is counterbalanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin-system (KKS). Considerable research interest with respect to COVID-19 treatment is, thus, currently directed towards the components of these systems. In an earlier study, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and partially excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized (HoP) COVID-19 patients and a sub-group of covalescent patients, while in the majority of the probands recovering from the disease these values had returned to normal. The data had been obtained using bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE, and they were supplemented by serum proteomics of the same patient cohort. We hypothesized that the data could be indicative of Long COVID, which had not been fully appreciated at the time of our study.; (2) Methods: The data were re-evaluated in the light of Long COVID. The recent literature on the RAS in COVID-19, antihypertensiva, and Long COVID was briefly reviewed.; (3) Results: While the levels of the BK serum degradation products should return to normal concentrations during convalescence, this was not true for some patients. This could be due to persisting liver problems, because CPN is synthesized there, but also to a dysregulated RAS. This was not reflected in the levels of selected RAS/KKS serum proteins like angiotensinogen (AGT), although AGT correlated with disease severity in HoP. However, standard tests in routine patient care in Long COVID often come back normal, and it may be that BK degradation is specific in some pathophysiologies. Moreover, the HoP group was sub-divided based on the serum protein profiles and COVID-19 severity.; (4) Conclusions: We point out two insights: 1) Sensitive technology such as omics methods might provide unexpected significant differences within the pre-defined patient groups of a clinical study. Those can only be explored, if the cohorts are large enough and properly matched with respect to the parameters known beforehand (e.g., age, gender, co-morbidities). 2) Results of the BK-reporter serum protease activity assay could be indicative of persisting liver problems and/or potentially of Long COVID. Clinical studies are required to test this hypothesis.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC), implicated in tumorigenesis, invasion, and drug resistance, and characterized by elevated expression of stem cell markers, such as CD133. We previously showed that siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. The current study investigates underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRASQ61K and NRASQ61R drivers, after CRISPR-Cas9 CD133 knockdown or Dox-inducible expression of CD133. To maintain stable expression of CD133, MACS-sorted CD133(+) positive cells were expanded by ROCK-mediated conditional reprogramming of BAKP melanoma cells (BAKR). BAKR showed increased survival via reduced apoptosis after exposure to trametinib or DTIC, compared to BAKP. CRISPR-Cas9- mediated CD133 knockdown in BAKR cells (BAKR-T3) re-sensitized the cells, while CRISPR-Cas9 knockdown of CD133 in parental BAKP and POT cells even further increased trametinib-induced apoptosis (cleaved PARP) by reducing levels of anti-apoptotic BCL-xL, p-AKT, and p-BAD, and increasing pro-apoptotic BAD and active BAX. Dox-induced CD133 overexpression had the opposite effect, and blocked trametinib-induced apoptosis in both cell lines, coincident with elevated p-AKT, p-BAD, BCL-2 and BCL-xL and decreased levels of the active form of BAX and caspases-3 and -9. The roles of CD133 in AKT and BAD phosphorylation, or in the upregulation of anti-apoptotic BCL-2 family members, was further investigated by AKT knockout with siRNA, or inhibition of BCL-2 family members with navitoclax (ABT-263). Similar to CD133 knockdown, AKT1/2 siRNA knockdown in BAKP cells also reduced p-BAD. CD133 knockdown (T3)-mediated reduction of pBAD levels was equivalent in AKT-knockdown or AKT control cells indicating that CD133 may be upstream of AKT signaling. In BAKP cells treated with trametinib and/or ABT-263, effects of ABT-263 mirrored CD133 knockdown, since levels of active BAX and cleaved-PARP in BAKP-SC (CD133-) cells increased to the same level as that exhibited by BAKP-T3 cells (CD133+). CD133 may therefore activate a survival pathway where 1) increased phosphorylation of AKT induces 2) phosphorylation and inactivation of BAD, 3) decrease in the active form of BAX, and 4) reduction in caspase-mediated PARP cleavage, indicating apoptosis suppression leading to drug resistance in melanomas. Targeting survival pathways by which CD133 may confer chemoresistance in MICs can contribute to development of more effective treatments for patients with high-risk melanoma.

The construction of carbon-carbon bonds by direct involvement of two unactivated carbon-hydrogen bonds, without any directing group, ensures an high atom economy of the entire process. Here it is described a simple protocol for the Pd(II)/Cu(II)-promoted intermolecular cross-dehydrogenative coupling (CDC) of 5-arylimidazoles, benzimidazoles, benzoxazole and 4,5-diphenylimidazole at their C-2 position with functionalized styrenes. This specific CDC, known as Fujiwara-Moritani reaction or oxidative Heck coupling, allowed also the C-4 alkenylation of the imidazole nucleus when both 2 and 5 positions are occupied.

Clients are increasingly looking for fast and effective means to quickly and frequently survey and communicate the condition of their buildings so that essential repairs and maintenance work can be done in a proactive and timely manner before it becomes too dangerous and expensive. Traditional methods for this type of work commonly comprise of engaging building surveyors to undertake a condition assessment which involves a lengthy site inspection to produce a systematic recording of the physical condition of the building elements, including cost estimates of immediate and projected long-term costs of renewal, repair and maintenance of the building. Current asset condition assessment procedures are extensively time consuming, laborious, and expensive and pose health and safety threats to surveyors, particularly at height and roof levels which are difficult to access. We propose a method for automated detection and localisation of key building defects from images using deep learning and convolution neural networks. The proposed model is based on a pre-trained VGG-16 classifier with Class Activation Mapping (CAM) for object localisation. The model has proven to be robust and able to accurately detect and localise mould growth, stains, and paint deterioration defects arising from dampness in buildings. The approach is being developed with potentials to scale-up to support automated detection of defects and deterioration of buildings in real-time using mobile devices and drones.

In this short review paper we have assembled the main characteristics of partial oxidation reactions (oxidative dehydrogenation and selective oxidation to olefins or oxygenates, as aldehydes and carboxylic acids and nitriles), as well as total oxidation, particularly for depollution, environmental issues and wastewater treatments. Both gas-solid and liquid-solid media have been considered with recent and representative examples within these fields. We have also discussed about their potential and prospective industrial applications. Particular attention has been brought to new raw materials stemming from biomass and to liquid-solid catalysts cases. This review paper also summarizes the progresses made in the use of unconventional activation methods for performing oxidation reactions, highlighting the synergy of these technologies with heterogeneous catalysis. Focus has been centered on usual catalysts activation methods but also on less usual ones, such as the use of ultrasounds, microwaves, grinding (mechanochemistry) and photo-activated processes, as well as their combined use.

Structural self-organizing and pattern formation are universal and key phenomena observed during growth and cluster-assembling of the carbyne-enriched nanostructured metamaterials at the ion-assisted pulse-plasma deposition. Fine tuning these universal phenomena opens access to designing the properties of the growing carbyne-enriched nano-matrix. The structure of bonds in the grown carbyne-enriched nano-matrices can be programmed by the processes of self-organization and auto-synchronization of nanostructures. We propose the innovative concept, connected with application of the universal Cymatics phenomena during the predictive growth of the carbyne-enriched nanostructured metamaterials. We also propose the self-organization approach for increase stability of the long linear carbon chains. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon and their distribution by the spatial structure and properties of the nanostructured metamaterial grows region through the new synergistic effect. Mentioned effect will be provided through the vibration-assisted self-organized wave patterns excitation along with simultaneous manipulating by their properties through the electric field. We propose to use acoustic activation of the plasma zone of nano-matrix growing. Interaction between the inhomogeneous electric field distribution generated on the vibrating layer and the plasma ions will serve as the additional energizing factor controlling the local pattern formation and self-organizing of the nano-structures. Suggested concept makes it possible to provide precise predictive designing the spatial structure and properties of the advanced carbyne-enriched nanostructured metamaterials.

The epistemology of the traditional risk assessment examined has a taxonomy based upon deterministic, behaviouristic and compatibilist methodologies which are likely driven by neo-liberal market related requirements for bigger, faster cheaper wind-turbines. Analysis of available risk assessments suggested that there is no conscious effort to deceive the reader although the intended audience is unclear. The language, and scoring mechanisms utilized indicates the presence of conformity bias, confirmation bias, and numerical inconsistency leading to data ossification. By reverse engineering risk assessment content, Pragmatic and Social Psychological aspects can be investigated, and the adequacy of the document can be evaluated using evidence-based models.

In recent years, pedestrian re-identification has gained a lot of interest due to its importance for many purposes such as security and safety. Many types of solutions have been proposed to solve this problem, where the majority are based on a features extraction such Convolution Neural Networks (CNNs). These approaches assume that only the identities that are in the training data can be recognized. The pedestrians in the training data are called In distribution (ID). However, in real world scenarios, new pedestrians and objects can appear in the scene and the model should detect them as Out Of Distribution (OOD). In our previous study , we proposed a pedestrian re-identification based on von-Mises Fisher (vMF) distribution. Each identity is embedded in the unit sphere as a compact vMF distribution far from other identities distributions. The embedding is done through a base CNN. Recently, proposed a framework called Virtual Outlier Synthetic (VOS), that detects OOD based on synthesising virtual outlier in the embedding space in an online manner. Their approach assumes that the samples from the same object maps to a compact space. This assumption aligns with the vMF based approach. Therefore, in this paper, we revisited the vMF approach and merged with VOS in order to detect OOD data points. We present our approach to merge both frameworks. We conducted several experiments to evaluate our proposed framework. Results showed that our framework was able to detect new pedestrian that do not exist in the training data in the inference phase. It also slightly helped to improve the re-identification performance.

We re-inventoried red wood ant nests (RWA) in 12 study sites (≈1281 ha) in the Westeifel Volcanic Field, Germany, in an area-wide and integrated ecosystem approach after 12 years. Combined with the re-identification of previously mapped nests using a photo database, this approach leads to more accurate nest counts in (re)inventories. A total increase of nests from 1144 (2009) to 1252 (2021), and a dramatic one for the Heidberg site by 52-fold (2009) and 85-fold (2021) compared to a 1984 inventory was observed, contrasting with earlier postulations of a decline in RWA. Early to medium mature (41-80 years) and mature (³81–140 years) spruce forests were the preferred habitat. Large increase in small nest sizes suggests an increase in new nest settlements also in clearings, despite climate-induced forest dieback over the past decade. A decline in biodiversity in the herbaceous layer was observed; highly proliferating blackberries had no negative impact on RWA nests. Monitoring of woodpecker cavities in RWA nests is suggested as an indirect indicator tool for evaluating populations in forests. Positive ground movement rates caused by the Eifel plume are suggested another factor favoring nest settlements. This study contributes to the urgent update of statistically valid data required to a) effectively substantiate the status-quo of RWA occurrences, b) protect RWA as ecosystem engineers, c) advance understanding of Geo-Bio-Interactions in the wake of climate change, and c) contribute to the German government's Insect Conservation Action Program.

In this work, Density Functional Theory (DFT) calculations were employed to study the photocatalytic CO2 to CO reduction by a series of Pt(II) square planar complexes with general formula [Pt(5-R-dpb)Cl] (dpb = 1,3-di(2-pyridyl)benzene anion, R = H, N,N-dimethylaniline,T thiophene, diazaborinine). The CO2 to CO conversion process is thought to proceed via two main steps, namely the photocatalytic/reduction step and the main catalytic step. The simulated absorption spectra exhibit strong bands in the 200 – 400 nm UV-Vis region. The calculated excited state reduction potentials are in the range 0.32 — -0.36 V revealing that the reductive quenching of the T1 state of the complexes could be modulated with suitable changes of the N^C^N pincer ligands. The CO2 fixation and activation by the ‘real’ three coordinated Pt(II) catalyst/intermediate is predicted to be favorable with Pt-CO2 bond dissociation energies, D0 in the range -36.9—-10.3 kcal/mol. The nature of the Pt-CO2 bond is complex with covalent, hyperconjugative and H-bonding interactions prevailing the repulsive electrostatic interactions. The main catalytic cycle is estimated to be a favorable exergonic process.

Egg activation is a cellular transition of an arrested mature oocyte into a developing embryo through a coordinated series of events. Previous studies in Hymenoptera have indicated that mechanical pressure can induce egg activation. In this study, we developed the first egg activation protocol for the haplodiploid insect pest, Sirex noctilio (Hymenoptera: Siricidae), from two climatically different regions in South Africa. In addition, activated eggs were exposed to three treatments involving water, pine sawdust, and the fungal symbiont of S. noctilio, Amylostereum areolatum (Russulales: Amylostereaceae), to confirm the hypothesised prerequisite of the symbiotic fungus for egg development. A rearing protocol was developed for emerged first instar larvae using a modified Anoplophora glabripennis (Coleoptera: Cerambycidae) artificial diet. A significant difference between mean survival rates of activated eggs from the two different regions was observed. Amylostereum areolatum was shown to be unnecessary for egg survival and adversely affected egg eclosion. Maximum larval survival duration on the artificial diet was 92 days. The egg activation and rearing protocol developed in this study enables opportunities for research on the physiology, ecology, symbioses, and genetics of S. noctilio, which can be exploited for new genetic pest management strategies.

Optical characterization and thermal aging tests are performed on a sputter-deposited coating, consisting of SiO₂/Cr₂O₃/Cr/Cr₂O₃ layers, designed and developed as a selective solar absorber to be used for unconcentrated solar thermal applications. Both measurements are performed by using a home-made apparatus, which mimics a flat plate collector under high vacuum. A Performance Criterion (PC_η(T)), based on absorber efficiency is proposed, and a forecast of service lifetime is obtained. As a result of the thermal aging tests, the selective solar absorber under study appears to be highly efficient at mid temperatures (up to 573 K) and thermally stable at temperatures (up to 690 K).

Unlike electron microscopy, which can achieve very high resolutions, but to date can only be used to study static structures, time-resolved X-ray diffraction from contracting muscles can, in principle, be used to follow the molecular movements involved in force generation on a millisecond timescale albeit at moderate resolution. However, previous X-ray diffraction studies of resting muscles have come up with structures for the head arrangements in resting myosin filaments that are different from the apparently ubiquitous interacting heads motif (IHM) found by single particle analysis of electron micrographs of isolated myosin filaments from a variety of muscle types. This head organization is supposed to represent the super-relaxed state of the myosin filaments where ATP usage is minimized. Here we have tested whether the interacting heads motif structures will satisfactorily explain the observed low-angle X-ray diffraction patterns from resting vertebrate (bony fish) and invertebrate (insect flight) muscles. We find that the interacting heads motif does not, in fact, explain what is observed. Previous X-ray models fit the observations much better. We conclude that the X-ray diffraction evidence has been well interpreted in the past and that there is more than one ordered myosin head state in resting muscle. There is, therefore, no reason to question some of the previous X-ray diffraction results on myosin filaments; time-resolved X-ray diffraction should be a reliable way to follow crossbridge action in active muscle and may be one of the few ways to follow molecular changes in myosin heads on a millisecond timescale as force is actually produced.

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted for by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs compound 1 [P(op)T(est)162] and compound 3 (PT167) represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166). The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2's structure was determined by X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 both not only stop the growth of cancer cells to ±0% (cancerostatic effect), but completely kill nearly all 60 cancer cells to a level of almost −100% (tumoricidal effect). Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function which results in a decrease of cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21^Waf1/p21^Cip1.