This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

Lead optimization in drug discovery is a crucial phase where initial hits are refined into compounds with improved pharmacological properties. While traditional methods rely on manual experimentation and modifications, AI-driven techniques have revolutionized this process by leveraging big data and predictive modeling. This review explores how AI-driven approaches accelerate lead optimization, showcasing examples like deep neural networks and reinforcement learning. Integration of multi-omic data and experimental validation further enhances AI-driven strategies. The future lies in refining these AI methods, democratizing tools, and interdisciplinary collaboration to streamline drug discovery and address medical needs efficiently.

Heavy metal accumulation in soils used for agricultural purposes is a major issue as it can affect the growth of plants and contain health risks as plants containing heavy metals are taken as food. This study provided the potential of three Bacillus pumilus strains (C-2PMW-8, C-1 SSK-8, and C-1PWK-7) for mitigation of the health factors related to heavy metals on lettuce (Lactuca sativa) grown in chromium contaminated soil from activities related to mining. Lettuce seeds inoculated with B. pumilus strains were grown in pots with garden soil amended with varying amount of chromite mine soil (2.27%, 4.65%, 7.14%). Growth indicators like days to germination, percentage of germination, leaf weight, leaf area and rate of survival decreased with incremental soil chromium levels but improved highly with inoculation of B. pumilus compared to uninoculated controls. When B. pumilus strains were provided, there was also a decreased level in the buildup of chromium in soil as well as lettuce shoots. The results explains that plant growth-promoting B. pumilus strains may be able to lower down the detrimental effects of chromium on lettuce development, hence increment in the effectiveness of phytoremediation.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

Mastitis-causing bacteria can establish persistent infections in the mammary gland of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. The aim of this study was to encapsulate vitamin D3 by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking and investigate the oral administration of encapsulated vitamin D3 in blood serum biomarkers of the immune response in late-lactating dairy goats. Dairy goats (n = 18) in late lactation were randomly assigned to three experimental groups (n = 6), after balancing weight. Dairy goats were orally administered with 0.35 mg vitamin D3/day in the unencapsulated form and 0.35 mg vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. The delivery of vitamin D3 to dairy goats resulted in a marked increase of 25-(OH)-D3 concentration in serum while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. Overall, the capsules in the powder form used in this study kept vitamin D3 highly bioavailable.

Byers Peninsula is considered one of the largest ice-free areas in Maritime Antarctica. Since 2006, the Spanish Polar Program has taken part in a large number of environmental studies involving effects of climate changes in lives cycles, limnology and microbiology. Soils from maritime Antarctica are generally weakly developed and have chemical, physical and morphological characteristics strongly influenced by the parent material. However, biological activity during the short Antarctic summer promotes intense transference of nutrients and organic matter in areas occupied by different species of birds and marine mammals. To mapping and monitoring those areas with high biological occupation, could be very useful to have models of edaphic properties prepared from satellite images. In this approach, Deep Learning and Linear Regression models of soil properties and spectral indexes as explicative variables were performed. We training models of soil properties closely related to biological activity such as Dissolved Organic Carbon (DOC) and the iron fraction associated with organic matter (Fe). We tested the best approach to model the spatial distribution of DOC, Fe and pH by training models of Linear Regression and Deep Learning over Sentinel2 and WorldView2 images. The most robust models were used to track possible areas with ornithogenic soils as well as areas of the Byers Peninsula that could support the highest biological development.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.

Globalization and digitalization have been associated with a number of challenges and opportunities. The purpose of this chapter is to analyze the impact of globalization and digitization on the Sustainable Development Goals (SDGs) and provide recommendations for achieving sustainable development. The study used a multidisciplinary approach that combined diverse research methods. This included a literature review, case studies, and empirical research findings. The findings suggest that while globalization has had both positive and negative impacts on the SDGs, it also poses challenges to social and environmental sustainability. Globalization's impact on sustainable development goals is complex and multifaceted, requiring policymakers to implement diverse measures to mitigate negative effects and promote sustainable development, particularly in less developed regions and marginalized communities. In conclusion, this chapter highlights the need for a coordinated and holistic approach to sustainable development that prioritizes the Sustainable Design Goals in policy and decision-making.

This work reports measurements of calcified gallstone elemental compositions using laser-induced optical emission spectroscopy. The experimental results support the importance of the magnesium concentration in gallstone growth. Granular stones reveal an increased magnesium concentration at the periphery of the granules, suggesting the inhibition of further growth. Non-granular gallstones reveal lower overall magnesium concentrations but with higher values near the center.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Recent advancements in gut microbiome research have highlighted the complex interplay between gut microbiota and various physiological and pathological processes, showing that gut microbiota plays a vital role in human health and disease. Imbalances in the gut microbiota, known as dysbiosis, have been associated with a range of health conditions, including gastrointestinal disorders, metabolic diseases, etc. In response to these findings, probiotics, prebiotics, synbiotics, and postbiotics have emerged as a promising therapeutic strategy to modulate gut microbiota composition and functionality. This review paper explores the latest research on how gut microbiota impacts host physiology, immune responses, and overall well-being. Furthermore, the paper delves into the therapeutic potential of probiotics, postbiotics, prebiotics, and synbiotics in therapeutic applications and curing various diseases. The paper also addresses the challenges and opportunities in the field, highlighting the need for personalized approaches to probiotic therapy and the importance of considering factors such as strain specificity, dosing, and safety.Overall, this review aims to provide a comprehensive overview of the evolving landscape of gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics as novel therapeutic agents. It underscores the potential of harnessing the gut microbiome to improve health, prevent diseases, and complement traditional medical interventions. As research in this field continues to expand, a deeper understanding of the gut microbiota and probiotics, prebiotics, synbiotics, and postbiotics promises new avenues for preventive and therapeutic healthcare strategies.

The process of sexual reproduction in eukaryotes starts when gametes from two different sexes encounter each other. Paramecium, a unicellular eukaryote, undergoes conjugation and uses a gametic nucleus to enter the sexual reproductive process. The molecules responsible for recognizing mating partners, hypothetically called mating-type substances, are still unclear. We have identified an O3-type mating substance polypeptide and its gene sequence using protein chemistry, molecular genetics, immunofluorescence, RNA inter-ference, and microinjection. The O3-type substance is a polypeptide found in the ciliary membranes, located from the head to the ventral side of cells. The O3-type substance has a kinase-like domain in its N-terminal part located outside the cell and four EF-hand motifs that bind calcium ions in its C-terminal part located inside the cell. RNA interference and immunofluorescence revealed that this polypeptide positively correlated with the expression of mating reactivity. Microinjection of an expression vector incorporating the O3Pc-MSP gene induced additional O3 mating type in the recipient clones of different mating types or syngen. Phylogenetic analysis indicates this gene is widely present in eukaryotes and exhibits high homology among closely related species. The O3Pc-MSP gene had nine silent mutations compared to the complementary mating type of the E3 homologue gene.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU) grew within a colloidal suspension of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers MA and ME, respectively). This method, applied for the first time in Semi Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality, since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a twenty-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. ME-based PHU exhibited higher (M_w ) ̅ than MA-based PHU (34,100 Da and 16,400 Da, respectively). Applying the enhanced methodology to prepare ten multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating ME enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when MA was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

The ribonuclease H (RNase H) active site of HIV-1 reverse transcriptase (RT) is the only viral enzyme not targeted by approved antiretroviral drugs. Using a fluorescence-based in vitro assay, we screened 65,239 compounds at a final concentration of 10 µM to identify inhibitors of RT RNase H activity. We identified 41 compounds that exhibited 50% inhibitory concentration (i.e., IC50) values < 1.0 µM. Two of these compounds, 2-(4-methyl-3-(piperidin-1-ylsulfonyl)phenyl)benzo[d]isothiazol-3(2H)-one (1) and ethyl 2-(2-(3-oxobenzo[d]isothiazol-2(3H)-yl)thiazol-4-yl)acetate (2), which both share the same benzisothiazolone pharmacophore, demonstrate robust antiviral activity (50% effective concentrations of 1.68 ± 0.94 µM and 2.68 ± 0.54, respectively) in the absence of cellular toxicity. A limited structure-activity relationship analysis identified two additional benzisothiazolone analogs, 2-methylbenzo[d]isothiazol-3(2H)-one (3) and N,N-diethyl-3-(3-oxobenzo[d]isothiazol-2(3H)-yl)benzenesulfonamide (4), which also resulted in inhibition of RT RNase H activity and virus replication. Compounds 1, 2 and 4, but not 3, inhibited the DNA polymerase activity of RT (IC50 values ~ 1 to 6 µM). In conclusion, benzisothiazolone derivatives represent a new class of multifunctional RT inhibitors that warrants further assessment for the treatment of HIV-1 infection.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

In 2011, commercial aviation contributed approximately 3.5% of global anthropogenic climate change through the emission of greenhouse gases during flight and operational non-CO2 climate effects. Over the last few years, numerous aviation-related organisations have set goals to reduce aviation’s climate impact. These goals, however, lack alignment, are poorly or ambiguously defined, or are internally inconsistent. This increases uncertainty about what aviation should work towards, how various stakeholders can contribute, and introduces problems with respect to accountability. In order to address this issue, this paper presents a comprehensive definition of a climate neutral air transport system as an “air transport system of which the climate effects of all its greenhouse gases and non-carbon dioxide effects throughout the entire life-cycle of each element of the system is balanced”. The proposed definition spans relevant system and encompasses all life cycle phases. To achieve a climate neutral air transport system by 2050, all life-cycle greenhouse gas emissions and non-CO2 climate effects remaining after in-sector reduction should be neutralised, as should all remaining non-CO2 climate forcing from emissions prior to 2050. Clarity on governance is furthermore needed, as the goal and associated targets proposed should be adopted globally.

In this paper the possibility of harvesting energy from the vibrations of a plate is analyzed. The harvester takes the form of a cantilever dynamic vibration absorber equipped with a piezoelectric layer and tuned by means of a tip mass to the first mode of vibration of the plate. A mathematical model of the coupled system composed of the plate and the harvester is presented. The validity of the proposed harvester is proved by means of simulations carried out with the modal expansions approach. Simulation results highlighting the effect of harvester tuning and location are presented as well. Then the validity of the harvester is confirmed by experimental tests carried out both with a concentrated impulsive load and with a distributed pressure load. Simulations and experimental tests show that the cantilever piezoelectric dynamic vibration absorber generates open circuit voltage an order of magnitude larger than the one generated by the same piezoelectric layer when directly bonded to the plate surface.

With the deterioration of the bridge performance and ever-increasing amount of traffic, the bridge safety is becoming a concern for engineering community. A method that can assess the bridge's condition in real-time is urgently needed. The main factors that hinder the bridge condition assessment are the uncertain operational environments. A new moving principal component analysis (MPCA) based method is developed for structural damage detection of bridges in operational environments in this paper. Two main operational environmental factors: the environmental temperature and traffic loads, are studied in the assessment process to verify the robustness and practicality of the proposed method. The numerical and experimental results show that the proposed method is effective and accurate to assess the bridge condition in operational environments.

During the last years the desire and the need for green buildings have been increased. The rise of energy cost, the higher transportation expenses and the international challenges along with the climate change are related with the green buildings market but are also affecting the cost of construction. The aim of this research is to discover and confirm the increased request of green properties and to investigate whether this is related to a new need or just a desire of the buyers. Moreover, the paper examines the people’s knowledge of greenness and sustainability and their wish to live and work in sustainable buildings. Finally, do the buyers will to pay extra in order to purchase a sustainable property and how sustainability can affect the market value and the construction industry. The participants who took part in this research were people that are living and working in Cyprus. One of the significant outcomes was the fact that people who have the knowledge and awareness related to sustainability are willing to pay extra to purchase green properties.

During the last 20 years, with the development of Information and Communication Technologies (ICTs), an emerging interest has appeared in Digital Community Engagement (DCE) in the process of cultural heritage management. Due to a growing need to involve a broader community in the Historic Urban Landscape approach, social media are considered one of the most important platforms to promote the public participation process of urban heritage conservation in the context of rapid urbanization. Despite the growing literature on DCE, which has delivered a general overview of different digital technologies and platforms to enhance heritage conservation, little research has been done on taking stock of the utilization of social media in this process. This study aims to fill the research gap by providing a more comprehensive picture of the functionalities of social media platforms and impacts on sustainable urban development through a systematic literature review. As a result, 19 out of 248 DCE relevant articles are selected as objects to illustrate the contribution of social media. The study identified the characteristics of these applied social media tools, explores their roles and influences in cases. The article concludes with directions for further research.

According to the Cosmological Principle the Universe is isotropic and no preferred direction would be seen by an observer that might be stationary with respect to the expanding cosmic fluid. However, because of observer’s partaking in the solar system peculiar motion, there would appear in some of the observed properties of the Cosmos a dipole anisotropy, which could in turn be exploited to determine the peculiar motion of the solar system. The dipole anisotropy in the Cosmic Microwave Background Radiation (CMBR) has given a peculiar velocity vector 370 km s−1 along l=264∘,b=48∘. However, some other dipoles, for instance, from the number counts, sky brightness or redshift distributions in large samples of distant Active Galactic Nuclei (AGNs), have yielded values of the peculiar velocity many times larger than that from the CMBR, though surprisingly, in all cases the directions agreed with the CMBR dipole. Here we determine our peculiar motion from a sample of 0.28 million AGNs, selected from the Mid Infra Red Active Galactic Nuclei (MIRAGN) sample comprising more than a million sources. From this, we find a peculiar velocity, which is more than four times the CMBR value, although the direction seems to be within ∼2σ of the CMBR dipole. A genuine value of the solar peculiar velocity should be the same irrespective of the data or the technique employed to estimate it. Therefore, such discordant dipole amplitudes, might mean that the explanation for these dipoles, including that of the CMBR, might in fact be something else. But, the observed fact that the direction in all cases, is the same, though obtained from completely independent surveys using different instruments and techniques, by different sets of people employing different computing routines, might nonetheless indicate that these dipoles are not merely due to some systematics, otherwise why would they all be pointing along the same direction. It might instead suggest a preferred direction in the Universe, implying a genuine anisotropy, which would violate the Cosmological Principle, the core of the modern cosmology.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

The research is devoted to the study of geotectonic and geodynamics of the Shu-Ile belt and petrographic composition and intrusive complexes geochemical features analysis. The Shu-Ile suture is an important geological structure of Kazakhstan. It is characterized by the presence of various intrusive formations and deep faults. The material composition of these intrusions is of interest for understanding the geological and metallogenic processes in this region. The research used modern scientific methods, including petrographic and geochemical studies of various compositions intrusion samples. Based on the results of material composition studies of intrusive complexes, their possible connections with other geological structures of Kazakhstan and the metallogeny of the region have been established. Based on the data obtained, a conclusion was made about the intrusive complexes origin and evolution of the Shu-Ile belt, which may be important for further geological research and forecasting of mineral resources in the region.

Chromophobe renal cell carcinoma (chRCC) and oncocytoma (RO) are renal tumor types originating from alpha intercalated cells of the collecting ducts of the kidney. Both tumor types have similar gross histological morphology and increased mitochondria, which leads to difficulties differentiating between these tumors, especially with core biopsy samples. This study aims to apply a machine learning approach to develop a molecular classifier based on transcriptomics data. Here we generated a meta-data set containing 62 chRCC and 45 RO gene expression arrays. Arrays were subjected to quality control steps, and genes were selected based on differential expression and ROC analysis. The final gene list was evaluated with UMAP based dimension reduction followed by density-based clustering with 95.5% accuracy. Molecular profiling by KEGG pathway analysis identified enrichment of fatty acid oxidation pathway in RO. We finally identified and validated the 30-gene signature, with an accuracy of 94.4% to distinguish chRCC from RO on UMAP analysis. Our results show that chRCC and RO have a distinct gene signature that can differentiate these tumors and complement histology for routine diagnosis of these two tumors.

Neurodegenerative diseases that include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS), arise due to numerous causes like protein accumulation and autoimmunity, characterized by neurologic depletion which lead to incapacity in normal physiological function such as thinking and movement in these patients. Glial cells perform a critical role in protective neuronal function; in the case of neuroinflammation, glial cell dysfunction can promote the development of neurodegenerative diseases. MiRNA participates in gene regulation and plays a vital role in many biological processes in the body; in the central nervous system (CNS), it can play an essential part in neural maturation and differentiation. In neurodegenerative diseases, miRNA dysregulation occurs, enhancing the development of these diseases. In this review, we discuss neurodegenerative diseases (Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)) and how miRNA is preserved as a diagnostic biomarker or therapeutic agent in these disorders. Finally, we highlighted miRNA as therapy.

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

The aim of the research was to determine the most productive tree cutting methods and the factors influencing them in flat and sloping terrain in tree plantations in Brazil. The study utilized drone-captured video material from eucalyptus and pine plantations harvesting operations. In both terrains, two cutting methods were compared, differing in the felling to the side method used: either at the edge of the harvesting front or inside. In addition, on flat terrain, the efficiency of forward felling was studied in relation to the aforementioned methods. In slope terrain, the machines were also equipped with a winch assistance system. Statistical tests were used to determine the most productive cutting methods by analyzing differences in productivity. With an average tree size of 0.3 m3, cutting productivity was 45 m3/E0h in pine cuttings and 55 m3/E0h in eucalyptus cuttings. The average cutting productivity on flat terrain was about 11 m3/E0h higher than on sloping terrain, mainly due to the time spent attaching the winch assistance system, which was a necessary phase of the work in sloping terrain. The research results suggest that it would be the most productive to use sideways felling inside the harvesting front method. However, the need for further research is evident if we want to precisely identify the harvesting conditions and work phases in the tree cutting cycle affecting the differences in the productivity of the harvesting chain in tree plantations.

Machine learning models are increasingly being used in critical domains, but their complexity, lack of transparency, and poor interpretability remain problematic. Decision trees (DTs) and rule-based approaches are well-known examples of interpretable models, and numerous studies have investigated techniques for approximating tree ensembles using DTs or rule sets; however, tree ensemble approximators do not consider interpretability. These methods are known to generate three main types of rule sets: DT-based, unordered-based, and decision list-based. However, no known metric has been devised to distinguish and compare these rule sets. Therefore, the present study proposes an interpretability metric to allow comparisons of interpretability between different rule sets, such as decision list- and DT-based rule sets, and investigates the interpretability of the rules generated by the tree ensemble approximators. To provide new insights into the reasons why decision list-based and inspired classifiers do not work well for categorical datasets consisting of mainly nominal attributes, we compare objective metrics and rule sets generated by the tree ensemble approximators and the \textit{Recursive-Rule eXtraction algorithm (Re-RX) with J48graft}. The results indicated that \textit{Re-RX with J48graft} can handle categorical and numerical attributes separately, has simple rules, and achieves high interpretability, even when the number of rules is large.

Vegetation classifications on large geographic scales are necessary to inform conservation decisions and monitor keystone, invasive, and endangered species. These classifications are often effectively achieved by applying models to imaging spectroscopy, a type of remote sensing, data, but such undertakings are often limited in spatial extent. Here we provide accurate, high-resolution spatial data on the keystone species Metrosideros polymorpha, a highly polymorphic tree species distributed across bioclimatic zones and environmental gradients on Hawai'i island, using airborne imaging spectroscopy and LiDAR. We compare two tree species classification techniques, support vector machine (SVM) and spectral mixture analysis (SMA), to assess their ability to map M. polymorpha over 28,000 square kilometers where differences in topography, background vegetation, sun angle relative to the aircraft, and day of data collection, among others, challenge accurate classification. To capture spatial variability in model performance, we applied gaussian process classification (GPC) to estimate the spatial probability density of M. polymorpha occurrence using only training sample locations. We found that, while SVM and SMA models exhibit similar raw score accuracy over the test set (96.0% and 93.4%, respectively), SVM better reproduces the spatial distribution of M. polymorpha than SMA. We developed a final 2 m x 2 m M. polymorpha presence dataset and a 30 m x 30 m M. polymorpha density dataset using SVM classifications that have been made publicly available for use in conservation applications. Accurate, large-scale species classifications are achievable, but metrics for model performance assessments must account for spatial variation of model accuracy.

Despite the abundance of tree diversity in the natural world, and generally high tree species richness in urban areas, urban forests continue to be dominated by a limited number of species. As socio-ecological systems, urban forests are shaped by historical and current management efforts and decision-making of a wide range of human actors. Drawing on past research, we offer a conceptual framework for describing the complex interactions among tree producers and consumers as trees are selected, grown, specified, and planted in private and public urban areas. We illustrate how multiple layers of selection criteria filter down the entirety of potential local tree diversity to a handful of commonly used and accepted tree species. We detail the actors and decision makers who impact tree composition and diversity across several land types. Finally, we identify research, education and outreach needs as they relate to creating more diverse and resilient urban forest ecosystems.

Being able to ascertain the physiological condition of the buds on a young apple tree before bud burst could help farmers manage their orchards more efficiently, especially if they could do so without destroying the buds in the process. The experiments carried out in this study were conducted with the aim of distinguishing shoot from non-shoot buds before bud burst using a visible/near-infrared spectrometer, a device that does not destroy the buds being tested. Tests on spring-planted (April 30, 2021) trees were conducted to check shoot and non-shoot bud physiology and the winter dormancy of young ‘Jonagold’, ‘Miyabi Fuji’ and ‘Orin’ apple trees. The light absorbance of the shoot buds before bud burst was much lower than the light absorbance of the non-shoot buds as checked on the visible/near-infrared spectrometer. The highest first factor effect was determined by a PCA test conducted on shoot and non-shoot ‘Jonagold’ buds (99.9%) at a range of 640-652 nm, ‘Miyabi Fuji’ buds (99.7%) at 654-680 nm and ‘Orin’ buds (99.6%) at 704-766 nm seven days before bud burst. We also found that the highest level of accuracy, using the Classifier analysis, between shoot and non-shoot ‘Jonagold’ buds (76.6%) was one day before bud burst, for ‘Miyabi Fuji’ buds (82.1%) it was three days before and for ‘Orin’ buds (76.3%) it was two days before. These findings suggest that growers can more effectively manage the development of the young trees in their orchards with a visible/near-infrared spectrometer.

Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. Micro-RNAs (miRNAs) are endogenous regulators of gene expression and fine tuners of vascular cell differentiation, thus these non-coding RNAs can modulate the arterial heterogeneity. The identification of a miRNA signature artery-specific would be promising in the therapy of CVDs, especially in frail elderly patients. In the present review we will provide a concise description of the arterial tree heterogeneity on structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity focusing on abdominal aorta and femoral artery, with the final goal of strengthening the search of more targeted therapies in CVDs and stratification approaches in frail elderly patients.

Human-caused anthropogenic greenhouse emissions impact climate globally. In this pilot study, we aim to reveal the impact of oil and gas emissions from local oil deposits in the regime of their natural degradation and development and eco-physiological changes of pine forests in Tatarstan Republic, Russia over the past century. We performed stable carbon isotope analysis in pine tree rings (13Cptrw) to reveal the impact of oil and gas emissions from the giant oil field reservoirs located in Leninogorsk region (UVRT) and the natural reserve site in Raifa. Our results show decreasing 13Cptrw at UVRT in 1943 when oil extraction was started, and in 1970, when it reached the maximum production. We found that 13Cptrw from UVRT indicates on developing unfavourable drier conditions and suppressed tree growth caused by both human-induced oil and deposit infrastructure and natural processes compared to undisturbed Raifa. The 13Cptrw from Raifa is more negative compared to UVRT, which can be explained by higher forest sensitivity to human-induced impact. From an ecophysiological point of view decreasing intercellular to ambient CO2 concentration at the leaf level and increasing intrinsic water use efficiency along with decreasing tree-ring width at UVRT (1970-2021) indicate on development of drought conditions.

Forest vegetation dynamics (succession and dominance) is an ecological phenomenon that is still difficult to characterize and integrate into management practices. In this study, the understanding of forest dynamics is explored based on Grime’s theoretical triangular model of plant adaptive strategies using the example of Lithuania’s forest ecosystems. The idea behind this is the hypothesis that forest dynamics is linked to natural selection as an evolutionary process that exhibits differential species responses to competition, stress, and disturbance. The aim of this study is to explore the adaptive relationships in hemi-boreal forests. Grime’s and Pierce’s secondary CSR strategies, which describe various equilibria between competitiveness (C), stress tolerance (S), and ruderalism (R), were considered to reflect four establishment and development adaptive specialization characteristics of forest tree species. As a result of the study, four types of tree functional groups were identified: stress-resistant ruderals, competitive stress-sensitive ruderals, ruderal stress-sensitive competitors, and stress-resistant competitors. Based on this, we propose that reforestation move away from single species regeneration by implementing the maintenance of these four types of functional groups. In conclusion, forest management must consider the existence of the established equilibria between plant competitiveness, stress tolerance, and ruderalism. The formal concepts presented in this article can serve as a guide for future relevant research and development of appropriate methods for studying real forests. This study is unique in that no previous work has linked forest dynamics and natural selection in the context of Lithuania’s forest ecosystems.

In this paper, we propose a system to create high-precision maps using UAV-LiDAR and to determine the location of individual fruit trees (apple trees) on the maps. The system is based on a UAV-LiDAR system that flies over an actual orchard. A UAV was flown over an actual orchard, and the point cloud of the onboard LiDAR and the location information of RTK-GNSS were obtained. The system records the LiDAR point cloud and RTK-GNSS position information. Automated software processes point cloud data offline and Automated software processes point cloud data offline and automatically segments each apple tree in the map. The RTK-GNSS position information is used for the segmented trees. The positional information obtained from RTK-GNSS was georeferenced to the segmented trees without using ground evaluation points. As a sample, location information was obtained from trees using the Quasi-Zenith Satellite System (QZSS) MICHIBIKI. The positional accuracy of the trees was evaluated using the positional information obtained from the Quasi-Zenith Satellite System MICHIBIKI as a reference. As a result, the alignment accuracy was sufficient to identify individual fruit trees.

The article delves into the intricate phase transitions of 1-Octadecanol and n-Nonadecane within a binary system, unveiling dynamic structural changes under varying conditions. Through Fouri-er-transform infrared (FTIR) analysis, specific molecular vibrations were identified, shedding light on the molecular composition and interactions. The study highlights the challenges in detecting subtle phase transitions and emphasizes the individuality of molecular behaviours in closely related compounds. The findings underscore the complexity of phase transitions in binary systems and advocate for a nuanced approach to studying molecular structures and behaviours. Addi-tionally, the research contributes valuable insights into the molecular dynamics of Organic Polymer Functional Adsorption Materials, offering implications for synthetic waxy layers in plant epidermis.

Background: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC -2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). Methods: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. Results: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p=0,08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p=0,045) and T-category (p=0.,043) and the absence of lymph node (p=0,05) or distant metastasis (p=0,09) in serous carcinomas. HDAC-2 positivity was correlated with absence of lymph node metastasis in serous tumors (p=0,045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p=0,048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p=0,086), a correlation which was not significant in multivariate analysis. Conclusion: These findings suggest a differential expression of HDAC-2, -4 and -5, providing evidence for a potential role in the pathobiology of EOC.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Current trends in systemic risk literature provide new insights into multi-hazard risks that interact and compound with built environments, creating more significant impacts on socio-economic and human systems. Recurrent natural hazards and extreme weather events are more likely to compound and cascade into more impactful events, especially in vulnerable societies. In small-island communities (SICS), including large archipelagos and Small Island Developing States (SIDS), the long-term impact of multi-, compounding-, and cascading-hazards (MCC hazards) can result in persistent vulnerability and residual risks. This is due to delayed responses, limited resources, poverty, fewer evacuation options, and inadequate markets and infrastructure. Using Ternate, a densely populated small volcanic island in North Maluku, Indonesia, as a case study, this paper assesses the impacts of seven types of natural hazards: flash floods, landslides, extreme weather, extreme waves and abrasion, earthquakes, tsunamis, and volcanic eruptions. The research focuses on the multi-hazard impact on population, land use, and infrastructure exposures in 60 villages in Ternate. The findings highlight population density, land use, and infrastructure exposure to multi-hazard risks, providing valuable information on potential losses in future hazard events.

Transportation systems through the ages have seen drastic evolutions in terms of transportation methods, speed of transport, infrastructure, technology, connectivity, influence on the environment, and accessibility. The massive transformation seen in the transportation sector has been fueled by the industrial revolutions which have continued expansion and progress into the fourth industrial revolution. However, the methodologies of data collection and processing used by the many drivers of this progress differ. The significance of standardized data and its mode of collection cannot be overstated as it has a major impact on the process outcomes. In order to achieve a better understanding of the impact of this, this study methodically reviewed the literature on the subject of the data collection and processing mechanism of 4IR technologies in the context of the transport industry with an emphasis on the areas of accomplishment of several studies and drawing attention to their limitations. Although the industry has advanced significantly as a result of the adoption and application of various research studies in this field, considerable focus needs to be placed in the areas of standardized data collection and computational approaches, which will ultimately assist in achieving various benefits in the transportation industry.

Today, air pollution is the greatest threat to organismal healthspan. The environment of our planet earth, the habitat of over eight billion humans and estimated twenty billion billions other animals, is contaminated with a wide variety of pollutants. Unfortunately, humans, out of billions and billions of living organisms on earth, are solely responsible for polluting the environment through emitting pollutants like particulate matter from industry, fuel engine vehicles, biomass combustion, toxic fumes from blasting, and wildfire. In the modern world, human-caused air pollutants induce massive oxidative stress and inflammation, the major contributors in initiation and progression of many diseases including pulmonary, cardiovascular, renal, hepatic, reproductive, neurological, mental, and accelerated biological aging. The provocative question is the following: how can we solve this human-created problem? As it is not realistic to clean the environment at once from human-caused pollution, initiatives have been undertaken to develop novel therapeutic approaches to control air-pollutant-induced oxidative stress and inflammation to protect humans from pollution-induced devastating diseases. In this article, I discuss the key findings of numerous recent preclinical studies documenting first, the role of air pollutant PM2.5 in augmentation of inflammation, oxidative stress, and associated diseases; and second, the efficacies of different natural and synthetic compounds in amelioration of PM2.5-induced oxidative stress, inflammation, pyroptosis, and associated pathologies.

We introduce the notion of p-adic equiangular lines and derive the first fundamental relation between common angle, dimension of the space and the number of lines. More precisely, we show that if $\{\tau_j\}_{j=1}^n$ is p-adic $\gamma$-equiangular lines in $\mathbb{Q}^d_p$, then \begin{align*} (1) \quad\quad \quad |n|^2\leq |d|\max\{|n|, \gamma^2 \}. \end{align*} We call Inequality (1) as the p-adic van Lint-Seidel relative bound. We believe that this complements fundamental van Lint-Seidel \textit{[Indag. Math., 1966]} relative bound for equiangular lines in the p-adic case

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

The literature study delves into novel therapeutic strategies in transplantation medicine, highlighting unique approaches that could revolutionize current practices. It emphasizes novel patterns that have the potential to transform the current landscape. Commencing with a thorough examination of the historical environment, it traces crucial advances and changes in transplantation. The focus is on traditional techniques, emphasizing their limitations and challenges. An extensive examination of contemporary transplantation therapies offers valuable insights into the most recent progress in organ, cellular, and tissue transplantation. This analysis examines the immunological obstacles and outlines the current advancements and constraints. The exploration further navigates into novel models and concepts such as immunomodulation, developments in organ preservation techniques, gene editing, biomaterials, scaffold-based solutions, and the integration of precision medicine, artificial intelligence, and machine learning applications. Each section analyzes the potential for change and current progress in various areas, backed by relevant scientific sources up to 2023. The subsequent sections delve into innovative cellular therapies, biotechnological progress, current clinical trials, and case studies demonstrating effective applications. This examination delves into the ethical and regulatory considerations of innovative therapeutic procedures, emphasizing ethical implications, regulatory frameworks, and the importance of balancing innovation with patient welfare. The literature review concludes by offering a forward-looking perspective, emphasizing potential progress, anticipated challenges, and advocating for collaboration and interdisciplinary approaches to overcome limitations in the field of transplantation medicine.

The goal of the study presented in this article is to investigate interconnection issues of the Intelligent Electrical Networks (IENs) with the existing ones, as well as the deployment of the appropriate load forecasting demand techniques. The concept of IENs has recently emerged as a potential solution to the global energy problem, due to the more flexible dispersed production units that are involved. In the same context, additional issues, such as the reduction of production-transfer-distribution costs as well as power losses are analyzed as well, via the penetration of Renewable Energy Sources (RESs). To this end, it is necessary to use appropriate advanced infrastructure, where in combination with modern telecommunication networks will make possible the full exploitation of IENs. Moreover, to make the electricity system more efficient, to avoid voltage and frequency imbalance issues and to implement optimal production and consumption planning, the Electric Load Forecast (ELF) is a vital process and plays a key role in the planning as well as in the management of electricity systems. Therefore, recent state of the art approaches in ELF methods are discussed as well.

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

Background: SARS-CoV-2 Omicron JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used RT-qPCR SGTF as the proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing for diagnosis of JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed Q229K, usually associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: The CDC should consider Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

The study employed simulation-based measurement approaches to evaluate and compare the performance of conventional networks to IRS-enhanced systems in terms of upstream spectral efficiency. The study discovered that applying IRS greatly improves coverage, or transmitting potency, for 6G services.

Rice blast is the most harmful disease caused by Magnaporthe oryzae, leading to yield loss. The aim of the work is to improve resistance of rice to blast by introducing and pyramiding genes using conventional breeding technique and modern MAS analysis. Pyramiding is the combination of several resistance genes in one genotype, in this case it improves the resistance of rice to pathogens. MAS analysis revealed that 3 out of 4 studied domestic high-yielding rice cultivars (Bakanasski, Aisaule and Aru) contain 1 blast resistance gene (Pi-2). It was discovered 7 pyramidal lines with the introduction of a combination of 2 blast resistance genes (Pi-1 and Pi-ta) into 6 hybrids and 3 genes (Pi-1, Pi-33 and Pi-ta) into 1 line. Phytopathological test of local cultivars and pyramidal lines of rice showed that 3 out of 7 pyramidal lines have moderate resistance: 2 lines (F2 Bakanasski/7667 (var. vulgaris Koern.) and F2 Aisaule/7664 (var. italica Alef.)), containing 2 resistance genes (Pi-1 and Pi-ta) and 1 line – F2 Aisaule/7689 (var. zeravschanica Brsch.), carrying 3 genes (Pi-1, Pi-33 and Pi-ta), while the local cultivars Bakanasski, Aisaule and Aru are susceptible. As a result, the blast resistance of rice was improved by creating pyramidal lines. Pyramided lines can be used for germplasm exchange and in rice breeding programs to improve blast resistance in rice.

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors like half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 display the highest antiproliferative activity against the three cancer cells, therefore, they were subject to further studies. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Furthermore, the expression of some key genes was studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking show that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.

Background and Objectives: In recent years, electric scooters have gained widespread popularity as an easy and affordable mode of transport in urban areas worldwide. Simultaneously, trauma centres have observed an increasing number of associated injuries to users. While injury patterns associated with other vehicles are now well-researched, electric scooter-related injuries are a new topic in the literature. Our study aims to investigate the disparities in injury patterns and other critical accident characteristics among bicycle, electric scooter, and scooter riders. Materials and Methods: In this one-year prospective observational study, we examined patients who sustained injuries while riding bicycles, electric scooters, or scooters between April 2021 and March 2022 at Hungary's largest trauma centre in Budapest. During this one-year period, we identified 1938 patients, 1378 cyclists, 370 electric scooters and 190 scooter users. We collected basic demographic information, recorded injury type and severity, time of day the injury occurred, and alcohol intoxication. Results: While 4.6% of cyclists and 5.8% of scooter riders had consumed alcohol, 26.8% of electric scooter riders were intoxicated at the time of their accident. 45.8% of electric scooter-related injuries occurred at night, compared to only 9.2% and 14.1% of bike and scooter-related injuries, respectively. Sober patients were more likely to suffer mild and severe limb injuries (Odds Ratio (OR): 3.85, P = .0001 and OR: 3.26, P = .0001), but less likely to experience mild and severe head injuries (OR: 0.1, P = .0001 and OR: 0.25, P = .0001) than intoxicated patients. Cyclists had significantly fewer cases of severe head trauma than those injured while using electric scooters (OR: 0.34, P = .0166). Conclusions: Severe craniofacial injuries are more common in intoxicated patients and in patients injured using electric scooters.

Postharvest 1-MCP treatment can inhibit lignification of fruit and vegetables. It has been suggested that the mode of action of 1-MCP is through inhibiting ethylene production, but the effect of 1-MCP and ethylene on lignification of common bean remain unknown. This work compared the effect of 0.5 μL L-1 1-MCP and 100 μL L-1 ethylene on lignification of common bean during storage. Postharvest 1-MCP significantly inhibited the increase of lignified cell group, sclerenchyma became thicker, vascular bundles thickened and lignified cells grew during storage, while ethylene is the opposite. 1-MCP inhibited the increase in respiration rate, sucrose phosphate synthase (SPS), sucrose synthase (SuSy), phenylalanine ammonialyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), and peroxidase (POD) activities, whereas ethylene hastened all. Ethylene treatment can be stimulated and 1-MCP inhibited the decline of reducing sugar and cellulose content. Expression of genes, including PvACO1, PvAOG1, PvSuSy, PvPAL3, and Pv4CL1, PvCOMT1 together with lignin content were significantly increased in common bean during storage. 1-MCP treatment markedly inhibited expression of PvACO1, PvSuSy2, PvPAL3, Pv4CL1 and PvCOMT1 genes, while strengthened expression of PvETR1 and PvAOG1, while ethylene was opposite. This work provides evidence that ethylene plays a key role in regulating the lignin biosynthesis of common bean, and also provides strategies for the maintenance of fruit quality during storage.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells, and SeMNPV or Autographa californica mutiple nucleopolyhedrovirus (AcMNPV) infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in G2/M phase and or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, the BV production and the OB containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post infection (p < 0.05). Finally, arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression regulation.

In celIs, microtubule location, length, and dynamics are regulated by a host of microtubule-associated proteins and enzymes that read where to bind and act based on the microtubule “tubulin code,” which is predominantly encoded in the tubulin carboxy-terminal tail (CTT). Katanin is a highly conserved AAA ATPase enzyme that binds to the tubulin CTTs to remove dimers and sever microtubules. We have previously demonstrated that short CTT peptides are able to inhibit katanin severing. Here, we examine effects of CTT sequences on this inhibition activity. Specifically, we examine CTT sequences found in nature, alpha1A (TUBA1A), detyrosinated alpha1A, Δ2 alpha1A, beta5 (TUBB/TUBB5), beta2a (TUBB2A), beta3 (TUBB3), and beta4b (TUBB4b). We find that these natural CTTs have distinct abilities to inhibit, most noticeably beta3 cannot inhibit katanin. Two non-native CTT tail constructs are also unable to inhibit – despite having 94% sequence identity with alpha1 or beta5 sequences. Surprisingly, we demonstrate that poly-E and poly-D peptides are capable of inhibiting katanin significantly. An analysis of the hydrophobicity of the CTT constructs indicates that more hydrophobic polypeptides are less inhibitory than more polar polypeptides. These experiments not only demonstrate inhibition, but also likely interaction and targeting of katanin to these various CTTs when they are part of a polymerized microtubule filament.

Today major environmental issue facing the universe is Industrial wastewater. They are present in the form of various pollutants like organic/inorganic, heavy metals, and non-disintegrating materials at an enormous amount. As of now, eliminating these pollutants from wastewater from industries in a viable manner has become a significant issue. Productive refinement methodologies are required to eliminate those toxins before removal. Furthermore, nanomaterials are innovationally powerful to purification of water by utilizing inexpensive nanofiltration and nano adsorbent. Heavy metal ions removal in an efficient way from the environment is the first and foremost problem from a biological and ecological perspective, and numerous research practices have been dedicated to the removal of harmful metal particles, involved both in the underground and surface wastewater. This article mainly focuses on the nanomaterials utilization of various contaminating materials removal from industrial wastewater with an exceptional spotlight on rare earth components and nanofiber and nanocomposite films. The objective is to offer references an outline in the field of developing nanomaterials utilization for harmful pollutants removal from industrial wastewater for industrializers and analysts.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops as a consequence of different factors such as oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain, resulting in apoptosis of neuronal cells. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on -secretase (the enzyme the leads to the formation of A), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells was selected. Six Mentha taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Also, their neuroprotective effects on H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. M. requienii extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. M. diemenica and M. requienii extracts lowered caspase activity. Exposure of SH-SY5Y cells to M. diemenica extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. M. diemenica and M. requienii extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.

To understand the health impacts of “hikikomori” lifestyle and to establish its first comprehensive health profile, a cross-sectional study was designed to measure how well the cases of hikikomori youths of Hong Kong were living, in terms of social, mental and physical aspects. This study involved 104 eligible participants at age 19.02 year-old who had completed the set of questionnaires and a series of anthropometric and physical health measurements. Despite SF36 score of 84.0 indicated good physical functioning in general, participants were lived sedentarily with high incidence of hypertension at 15.4% and prehypertension at 31.7%. Occurrence of hypertension in cases living as hikikomori >6 months was 3-times higher than those newly onset cases. The blood pressure levels were correlated with age and all obesity index parameters measured including waist circumference and body mass index. Half of the hypertensive cases involved the elevation of systolic blood pressure, which suggested higher odds of cardiovascular complications. Participants were mentally stable living with moderate levels of perceived stress and state anxiety, but borderline clinical depression. In conclusion, the hikikomori lifestyle could be a risk behavior that may harm the younger generation physically by promoting obesity and hypertension and probably other chronic illnesses.

In this paper, new types of M-fractional wave solutions of mathematical physics model named as truncated M-fractional (1+1)-dimensional non-linear simplified Modified Camassa-Holm model are achieved by applying the modified simplest equation (MSE), Sardar sub-equation and generalized Kudryashov techniques. The gained solutions containing dark, bright, periodic and mixed wave solitons. Effect of fractional order derivative is also discussed. Achieved wave solitons are verified by Mathematica tool. Few of the gained wave solitons are also described through 2-dimensional, 3-dimensional and contour graphs through Mathematica tool. The gained solutions are helpful for the further development of concerned model. Finally, these techniques are simple, fruitful and effective to deal with non-linear FPDEs.

Satellite-based Normalized Difference Vegetation Index (NDVI) time-series data are useful for monitoring the changes of vegetation ecosystems in the context of global climate change. However, there are currently no ideal NDVI datasets that reconcile long-term series with high spatial resolution. Here, we have developed a simple and novel data downscaling algorithm based on the coefficient of variation (CV) statistics, which combines the detailed spatial features of MODIS data with the long-term temporal information of AVHRR data. The proposed data fusion method helps generate a global monthly NDVI database that has a 250 m-resolution and covers the long period of 1982−2018. We evaluated the accuracy of the fused data against MODIS NDVI using the metrics of Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Pearson’s correlation coefficients (R). Validation suggests a high performance of the downscaling algorithm and a high accuracy of the new NDVI database. We further applied the downscaled data to monitor NDVI changes of various vegetation types and in areas having high vegetation heterogeneity, and we obtained stable results similar to MODIS data. The whole data downscaling and validation processes were completed on the Google Earth Engine platform, and here we provide a code for users to easily get the data for any part of the world. The downscaled global-scale NDVI time series has high potential in monitoring the temporal and spatial dynamics of the terrestrial ecosystems under changing environments.

This paper uses the $\exp(-\Phi(\xi))$-Expansion method to investigate solitons to the M-fractional nonlinear Schrödingers equation with cubic nonlinearity. The results obtained are dark solitons, trigonometric function solutions, hyperbolic solutions and rational solutions. Thus, the constraint relations between the model coefficients and the traveling wave frequency coefficient for the existence of solitons solutions are also derived.

Present study on land use land cover analysis and taluka wise combination of cropped area, carried out in Beed district of Maharashtra state in India and studied 11 talukas of the district. Secondary data on land use land cover and area in various crops has been collected, compiled and analyzed from various secondary sources. Simple descriptive statistics used to examine the agricultural land use land cover and J.C. Weaver’s crop combination technique was used for taluka wise analysis of crop combinations and on the basis of highest to smallest area engaged in particular crop, crops have been ranked. The study showed that, in the district as a whole, percentage of uncultivated land other than fallow was about 46 percent as compare to net sown area is only 35 percent in total geographical area (1063855ha) of Beed district. The study further revealed that about 42 percent area engaged in food crops and about 58 percent area occupied by nonfood crops, which includes cereals (25%), cotton (19%), pulses (13%), oilseed (12%), sugarcane (5%) and fruits and vegetables (3%). Results of Weaver’s crop combination technique showed that the Wadwani taluka demarcated as most diversified taluka by means of maximum number (sixteen) of crops combinations with the lowest variance value (14) found in the present investigation. Further, the study revealed that the high crop diversity found in Dharur taluka with eighteen crop combinations and the taluka has given first rank amongst others. To derive the crop diversity ranking, taluka wise maximum to minimum number of crop combinations derived in different talukas and given ranks accordingly. The study concluded that, agricultural land use analysis is essential for solving and optimizing the land use problem, maintaining socio-ecological balance, best utilization of scarce resources. The authors enlightened that the rational use of agricultural land has important for food security and biodiversity which increase the productivity and profitability of the agriculture sector and it indicates the decision making ability of farmers in study area.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Silicon Photomultipliers find applications across various fields. One potential Silicon Photomultiplier application domain is neutrino telescopes, where they may enhance the angular resolution. However, the elevated dark count rate associated with Silicon Photomultipliers represents a significant challenge to their widespread utilization. To address this issue, it is proposed to use Silicon Photomultipliers and Photomultiplier Tubes together. The Photomultiplier Tubes signals would serve as a trigger to mitigate the dark count rate, thereby preventing undue saturation of the available bandwidth. This paper presents an investigation into a fast and resource-efficient method for filtering Silicon Photomultiplier dark count rate. A low-resource and fast coincident filter has been developed, which removes the Silicon Photomultiplier dark count rate by using as trigger the Photomultiplier Tube input signals. The architecture of the coincidence filter, together with the first results obtained, which validate the effectiveness of this method are presented.

We present a discussion and analysis regarding the benefits and limitations of open and non-anonymized peer review based on literature results and responses to a survey on the reviewing process of alt.chi, a more or less open-review track within the CHI conference, the predominant conference in the field of human-computer interaction (HCI). This track currently is the only implementation of an open-peer-review process in the field of HCI while, with the recent increase in interest in open science practices, open review is now being considered and used in other fields. We collected 30 responses from alt.chi authors and reviewers and found that, while the benefits are quite clear and the system is generally well liked by alt.chi participants, they are reluctant to see it used in other venues. This concurs with a number of recent studies that suggest a divergence between support for a more open review process and its practical implementation. The data and scripts are available on https://osf.io/vuw7h/, and the figures and follow-up work on http://tiny.cc/OpenReviews.

Dirofilaria immitis infection is one of the most severe parasitic diseases of dogs. Prevention is achieved by the administration of drugs containing macrocyclic lactones (MLs). These products are very safe and highly effective, targeting the third and fourth larval stages (L3, L4) of the parasite. Until 2011, claims of ineffectiveness of MLs, reported as “Lack of Efficacy” (LOE), were generally attributed to owners’ non-compliance, or other reason for inadequate preventative coverage. There was solid argumentation that a resistance problem is not likely to occur because of i) the great extent of refugia, ii) the complexity of resistance development to MLs, and iii) the possible big number of genes involved in resistance selection. Nevertheless, today it is unequivocally proven that ML resistant D. immitis strains exist, at least in the Lower Mississippi region, USA. Accordingly, tools have been developed, to evaluate and confirm the susceptibility status of D. immitis strains. A simple, in-clinic, microfilariae suppression test, 14-28 days after ML administration, and a “decision tree” (algorithm), including compliance and preventatives’ purchase history, and testing gaps, may be applied for assessing any resistant nature of the parasite. On the molecular level, specific SNPs may be used as markers of ML resistance, offering a basis for validation of clinically suspected resistant strains. In Europe, no LOE/resistance claims have been reported so far, and the existing conditions (stray dogs, rich wildlife, majority of owned dogs not on preventive MLs treatment) do not favor selection pressure on the parasites. Considering the genetic basis of resistance and the epizootiological characteristics of D. immitis, ML resistance neither establishes easily nor spreads quickly, a fact confirmed by the current known dispersion of the problem, which is limited. Nevertheless, ML resistance may propagate from an initial geographical point, via animal and vector mobility, to other regions, while it can also emerge as an independent evolutionary process in a new area. For these reasons and considering the current chemoprophylaxis recommendations and increasing use of ML endectoparasiticides as a potential selection pressure, it is important to remain vigilant for timely detection of any ML LOE/resistance, in all continents where D. immitis is enzootic.

Background: Tuberculosis (TB) continues to be a serious public health threat that affects the most vulnerable population. Patients who are LTFU after TB diagnosis still represent one of the biggest challenges to TB control. Method: In this prospective observational study, we aimed to identify and analyse the risk factors associated with LTFU among TB patients who started first-line TB treatment in the Sanatorium Hospital in Luanda. Result: A total of 113 patients with TB were included between August 2018 and September 2019. Seventy-six (67.3%) patients were cured, 27 (23.9%) were LTFU, 5 (4.4%) died, 4 (3.5%) were transferred and 1 (0.9%) presented a treatment failure. After excluding those dead, transferred or who failed to treatment, we observed that severe TB at the time of diagnosis (OR 9.24, 95% CI 2.18-39.04) and food insecurity were significantly associated with LTFU (OR 5.96, 95% CI 1.66-21.41). Conclusion: The findings of our study are of enormous value to understand the reasons for the LTFU of patients with TB and can guide polices and facilitate designing measures to allow better adherence, and therefore, greater treatment success

Nitrogen fertilization ensures the proper growth of trees. The aim of the study was to evaluate the impact of differentiated nitrogen fertilization on selected parameters. It was assumed that such analysis is an indirect picture of the needs of cherries grown in herbicide fallow. The content of minerals in two layers of the soil, in leaves, and its influence of tree growth, and the content of chlorophyll in leaves were assessed. The experiments were carried out in three different cherry orchards. Three levels of fertilization were applied in each orchard: 0 kg, 60 kg and with 120 kg N ha- 1. As expected the fertilization resulted in an increase in the content of nitrate and ammonium forms of nitrogen in the soil, however, their content was also dependent on precipitation and temperature. Additionally a high nitrogen fertilization increased the content of phosphorus and potassium and decreased the magnesium in the topsoil layer. High nitrogen fertilization caused the decrease of content of phosphorus and potassium in the leaves. The level of calcium and magnesium in leaves increased with fertilization of 60 kg N ha–1 but decreased with the dose to 120 kg N ha–1. The use of nitrogen fertilization increased the vegetative growth of trees measured by leaf area and trunk cross-sectional area. However, the chlorophyll content was not dependent on the amount of nitrogen fertilization.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

It is important to realize the transformation behavior of wüstite because it greatly affects the final structure of the oxide layer and the surface quality of the steel products. In the present study, the transformation behaviors of the wüstite layer are examined under nearly-oxygen-free conditions, to simulate the cooling processes after the hot rolled strip is coiled. As the single phase wüstite was prepared at 950˚C, the 460˚C transformed oxide layer was composed of a mixture of iron and magnetite formed through eutectoid reactions. For the 750˚C-fabricated wüstite, only magnetite was observed after transformation, without iron precipitates and residual wüstite. It is speculated that the unusual transformation behavior of the low-temperature-made wüstite results from the pseudo-structural intermediate phase transformation between wüstite and magnetite. This pseudo-structure is a pre-transformed wüstite and of various concentration of ferrous ion, which is determined by the fabrication conditions. During the hot strip mill process, the so-called wet scale, wüstite, is produced continuously from finish mill to laminar flow sections and ended at 570˚C. Consequently, the final eutectoid transformation below 570˚C is dominantly controlled by the surface temperature ranged from 750˚C to 950˚C for low carbon steel.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine), a widely used anticancer drug, is considered as a gold standard in treating aggressive pancreatic cancers. Gamma-proteobacteria that colonize the pancreatic tumors contribute to chemoresistance against gemcitabine by metabolizing the drug to a less active, deaminated, form. The gemcitabine transporters of these bacteria are unknown to date. Furthermore, there is no complete knowledge on the gemcitabine transporters in Escherichia coli or any other related proteobacteria. In this study, we investigate the complement of gemcitabine transporters in E. coli K-12 and two common chemoresistance-related bacteria (Klebsiella pneumoniae, Citrobacter freundii). We find that E. coli K-12 has two high-affinity gemcitabine transporters with distinct specificity properties, namely NupC and NupG, whereas the gemcitabine transporters of C. freundii and K. pneumoniae include the NupC and NupG orthologs, indistinguishable functionally from their counterparts, and, in K. pneumoniae, one additional NupC variant, designated KpNupC2. All these bacterial transporters have higher affinity for gemcitabine than their human counterparts. The highest affinity (KM 2.5-3.0 μΜ) is exhibited by NupGs of the Bacteria-specific Nucleoside-H+ Symporter (NHS) family followed by NupCs (KM 10-13 μΜ) of the Concentrative Nucleoside Transporter (CNT) family, 15-100 times higher than the affinities reported for the human gemcitabine transporter hENT1/SLC29A1 which is primarily associated with gemcitabine uptake in the pancreatic adenocarcinoma cells. Our results offer a basis for further insight into the role of specific bacteria in drug availability within tumors and understanding the structure-function differences of bacterial and human drug transporters.

On the thirty-fifth anniversary of the first description of O2-sensitive K+ channels in the carotid body chemoreceptors [1], O2 sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K+ channel subtype(s) responsible for O2 sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O2 sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O2 levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility, and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review we will focus on the mechanisms of physiological oxygen chemotransduction by PO2-dependent K+ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach in cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support a role of ERVs in tumor development and encourage further search for antiretroviral agents to treat malignancies in which endogenous retroviruses are active.

Cardiovascular diseases, which are the leading cause of death in Croatia, are linked to the high prevalence of hypertension. Both are associated with high salt intake which was determined almost two decades ago when Croatian Action on Salt and Health (CRASH) was launched. The main objective of the present study was to evaluate salt, potassium, and iodine intake using 24-hour urine samples in a random sample of adult Croatian population, and to analyse trends in salt consumption after the CRASH has intensively started. Methods: In this national population-based EH-UH 2 study performed in 2018-2021 (participation rate 72 %) in which we analysed a single 24-hour urine sample, 1067 adult participants (mean age 57.12 (SD 13.9), men 35%) were included. Results: Mean salt and potassium intakes were 8.6 g/day (IQR 6.2-11.2) and 2.8 g/day (IQR 2.1-3.5), respectively, with sodium-to-potassium ratio of 2.6 (IQR 1.8-3.3). We detected a decrease of 17.6% (2 g/day less) in salt consumption compared to our previous salt-mapping study. However, only 13.7%, and 8.9 % met the WHO salt and potassium recommended target of 5 g/day, and 3.5 g/day, respectively. Salt intake was higher, and potassium ingestion was lower in rural vs. urban regions, and in continental vs. Mediterranean parts of Croatia. Moderate to severe iodine insufficiency was determined in only 3% adult participants. Conclusion: In the last fifteen years, salt consumption has been significantly reduced in Croatian adult population because of intensive and broad CRASH program led by the Croatian Society of Hypertension and the Croatian Hypertension League. However, salt intake is still too high, and potassium ingestion is too low. With expected more active engagement and help of the government, obtained results could be significantly improved. Salt reduction programs are most cost-effective methods of cardiovascular disease prevention and should be considered more seriously by the government and health policy makers.

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In-silico investigation on porcine skin was carried out using the Monte Carlo modelling strategy to evaluate the feasibility and characterise the sensor. Subsequently, an in-vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis.

One of the most used techniques for reducing drag on blunt bodies when they move at speeds above the speed of sound are spikes. An important number of numerical works based on CFD have highlighted the fluid dynamics behind its use, as well as its advantages. However, most of docu-mentation focuses mainly on modified spike physical properties, while keeping constant supersonic or hypersonic flow conditions. In this sense, it is necessary to resort to current numerical techniques as machine learning, which can be obtain the most appropriate technical solution in compared to the costly iterative simulations that can delay the rapid development and testing of new aerody-namic configurations. This investigation postulates a specific hypothesis: that the K-Nearest Neighbours algorithm, renowned for its simplicity and effectiveness in classification problems, can be extrapolated as a robust tool for predicting drag reduction on spike blunt bodies. A wide range of Mach number and aspect ratios between blunt body diameter, spike length, and spike diameter are used for the algorithm dataset. The algorithm presents good predictions of the coefficient with errors of less than 5% percent, applying a multivariable regression method. Even, in the vicinity of the hypersonic speed zone, with a minimum of 3 neighbour nodes. The above validates the flexibility of the method and shows a new area of opportunity for the calculation of aerodynamic properties in a body moving near or above the speed of sound.

The inherent capabilities of the K-means++ algorithm to approximate system dynamics within complex systems are subjected by constructing a network structure that captures interconnections among identified components, extending its original purpose as a data clustering method and transforming it into a tool for systems analysis. Leveraging advanced measurement technologies and sophisticated data collection systems, the K-means++ algorithm unveils hidden relationships among components and identifies critical elements. This study explored the algorithm's potential, facilitating the identification of critical components to enhance system operation, control, optimization, and decision-making and examining the practicality and resiliency of the method in real-world application with noisy and limited data. A case study conducted on power systems (IEEE 39-bus and IEEE 300-bus systems) exemplifies K-means++'s capacity to accurately identify critical components and approximate system dynamics, supported by performance metrics affirming its effectiveness and robustness in system analysis through measurements of bus similarity within clusters based on standard deviation and comparison of net tie-line flows in equivalent networks with the original network across scenarios. Performance metrics, including the Silhouette Score, Davies-Bouldin Index, and Variation of Information (VI) score, further validated K-means++'s performance, yielding reliable and consistent results.

The natural product elaiophylin is a macrodiolide with broad biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein-protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here we elaborate that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similar to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1⍺, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 3D spheroid formation. Finally, a strong inhibition of the same cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.

Myocarditis is the form of an inflammation of the middle layer of the heart wall which is caused by a viral infection and can affect the heart muscle and its electrical system. It has remained as one of the most challenging diagnoses in cardiology. Myocardial is the prime cause of unexpected death in approximately 20% of adults less than 40 years of age. Cardiac MRI (CMR) has been considered as a noninvasive and golden standard diagnostic tool for suspected myocarditis and plays an indispensable role in diagnosing various cardiac diseases. However, the performance of CMR is heavily dependent on the clinical presentation and non-specific features such as chest pain, arrhythmia, and heart failure. Besides, other imaging factors like artifacts, technical errors, pulse sequence, acquisition parameters, contrast agent dose, and more importantly qualitatively visual interpretation can affect the result of the diagnosis. This paper introduces a new deep learning-based model called Convolutional Neural Network-Clustering (CNN-KCL) to diagnose the Myocarditis. The hybrid CNN-KCL method performs the early and accurate diagnosis of Myocarditis. To the best-of-our-knowledge, a Convolutional neural network has never been used before for the diagnosis of Myocarditis. In this study, we used 47 subjects to diagnose myocarditis patients from Tehran's Omid Hospital. The total number of data examined is 10425. Our results demonstrate that CNN-KCL achieves 92.3% in terms of diagnosis myocarditis prediction accuracy which is significantly better than those reported in previous studies.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

We apply hierarchical clustering (HC) of DNA k-mer counts on multiple Fastq files. The tree structures produced by HC may reflect experimental groups and thereby indicate experimental effects, but clustering of preparation groups indicates the presence of batch effects. Hence, HC of DNA k-mer counts may serve as an unspecific diagnostic device. In order to provide a simple applicable tool we implemented sequential analysis of Fastq reads with low memory usage in an R package (seqTools) available on Bioconductor. The approach is validated by analysis of Fastq file batches containing RNAseq data. Analysis of three Fastq batches downloaded from ArrayExpress indicated experimental effects. Analysis of RNAseq data from two cell types (dermal fibroblasts and Jurkat cells) sequenced in our facility indicate presence of batch effects. The observed batch effects were also present in reads mapped to the human genome and also in reads filtered for high quality (Phred > 30). We propose, that hierarchical clustering of DNA k-mer counts provides an unspecific diagnostic tool and a quality criterion and for RNAseq experiments.

Data mining plays a critical role in the sustainable decision making. The k-prototypes algorithm is one of the best-known algorithm for clustering both numeric and categorical data. Despite this, however, clustering a large number of spatial object with mixed numeric and categorical attributes is still inefficient due to its high time complexity. In this paper, we propose an efficient grid-based k-prototypes algorithms, GK-prototypes, which achieves high performance for clustering spatial objects. The first proposed algorithm utilizes both maximum and minimum distance between cluster centers and a cell, which can remove unnecessary distance calculation. The second proposed algorithm as extensions of the first proposed algorithm utilizes spatial dependence that spatial data tend to be more similar as objects are closer. Each cell has a bitmap index which stores categorical values of all objects in the same cell for each attribute. This bitmap index can improve the performance in case that a categorical data is skewed. Our evaluation experiments showed that proposed algorithms can achieve better performance than the existing pruning technique in the k-prototypes algorithm.

The growing demand for high-power DC Fast Charging (DCFC) stations for Electric Vehicles (EVs) is expected to lead to increased peak power demand and reduction of grid power quality. To maximize the economic benefits and station utilization under practical constraints set by regulatory authorities and DCFC station operators, this study explores and provides methods for connecting DCFC stations to the grid employing low power interconnection rules and Distributed Energy Resources (DERs). The system uses automotive Second Life Batteries (SLBs) and Photovoltaic (PV) systems as energy buffers and local energy resource to support EV charging and improve the station techno-economic feasibility through load shifting and charge sustaining. The optimal sizing of the DERs and the selection of the grid interconnection topology is achieved by means of a Design Space Exploration (DSE) by means of exhaustive search approach to maximize the economic benefits of the charging station and to mitigate high-power demand to the grid. Without loosing of generality, this study considers a range of DER sizes, grid interconnection specifications, and related electricity tariffs of American Electric Power (AEP) Ohio and the Public Utility Commission of Ohio (PUCO). Various scenarios and strategies have been defined to account for the interconnection requirements of the grid to the DCFC with DERs. The system’s techno-economic performance of different scenarios has been analyzed and compared using a multitude of metrics.

Sorghum (Sorghum bicolor L.) ranks fifth as the most crucial cereal crop globally, yet its seed morphology remains relatively unexplored. This study investigated seed morphology in sorghum based on 115 mini core and 130 Senegalese germplasms. Eight seed morphology traits encompassing size, shape, and color parameters were assessed. Statistical analyses explored potential associations between these traits and resistance to three major sorghum diseases: anthracnose, head smut, and downy mildew. Furthermore, genome-wide association studies (GWAS) were conducted using phenotypic data from over 24,000 seeds and over 290,000 publicly available single nucleotide polymorphisms (SNPs) through the Genome Association and Prediction Integrated Tool (GAPIT) R package. Significant SNPs associated with various seed morphology traits were identified and mapped onto the reference sorghum genome to identify novel candidate defense genes.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

Al-6%Mg-Sc-Zr alloys with the total ratio of Sc + Zr = 0.32 wt.% make up the target of this research. The content of scandium and zirconium varied with an increment of 0.02%. The alloys were produced by induction casting. Their ultrafine-grained (UFG) microstructure was formed with Equal Channel Angular Pressing (ECAP). Such cast alloys have a homogeneous macrostructure formed by small equiaxed grains in the central part of the ingot and columnar crystals along the edges of the cross section. After ECAP, the average grain size in the alloy specimens is 0.5–1 µm. The average grain size does not depend on the ratio of Sc and Zr in these alloys. Superplasticity tests were performed at temperatures ranging from 300 to 500 °C and at a strain rate varying between 3.3·10-3 and 3.3·10-1 s-1. UFG Al-6%Mg-0.20%Sc-0.12%Zr and Al-6%Mg-0.18%Sc-0.14%Zr alloys exhibit the highest superplasticity. It was suggested that changes in Sc:Zr ratio affect spatial distribution and composition of the following precipitating particles: Al3Sc, Al3Zr, Al3(ScxZr1-x). An increase in Zr concentration is shown to reduce the susceptibility of UFG alloys to cavitation fracture.

An electrothermal analysis for barium titanate based ceramics is presented combining the Heywang–Jonker model for the electric resistivity with a heat dissipation mechanism based on natural convection and radiation in a one dimensional model on the device level with voltage as the control parameter. Both PTC and NTC effects are accounted for through the double Schottky barriers at the grain boundaries of the material. The problem formulated in this way admits uniform and non–uniform multiple steady state solutions that do not depend on the external circuit. The numerical bifurcation analysis reveals that the PTC effect gives rise to several multiplicites above the Curie point, whereas the NTC effect is responsible for the thermal runaway (temperature blowup). The thermal runaway phenomenon as a potential thermal shock could be among the possible reasons for the observed thermomechanical failures (delamination fracture). The theoretical results for the NTC regime and the thermal runaway are in agreement with experimental flash sintering results obtained for 3% and 8% yttria stabilized zirconia.

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

In our previous papers [1,3], using only the concepts of the zero-point energy and quantized space–times, all the fields including gravity were explained. However, the previous papers had the following limitations: First, the concept of the quantized space-time must be experimentally confirmed. Second, we should clarify the meaning of the quantized Einstein’s gravity equation, which is derived in [1]. Moreover, in another paper [2], we succeeded in describing the neutrinos’ self-energy and their oscillations. However, this paper assumes the rest energy of 3-leptons in advance, which is why we needed to uncover the reason why leptons have 3-generations. As mentioned, using the concepts of the zero-point energy and quantized space–times, we derived the quantized Einstein’s gravity equation in our previous paper [1]. The paper provides an analytical solution of this equalized Einstein’s equation, which implies the conservation of angular momentum in terms of quantized space–times. Employing this solution and without the standard big bang model, a unique form of acceleration equation for the acceleration-expansion universe is derived. Moreover, the temperature of the cosmic microwave background (CMB) emission is also obtained. Further, this solution results in an analytical (not numerical) derivation of the gravity wave. Moreover, based on the configuration of quantized space–times in terms of both electric and magnetic fields, we analytically attempted to calculate every equation in terms of electromagnetic and gravity fields, using the solution of the quantized Einstein’s gravity equation. As a result of this theory, first the calculated acceleration and temperature of CMB emission agree with the measurements. Furthermore, the analytical solution of the quantized Einstein’s gravity equation resulted in all the laws of electromagnetic and gravity fields in addition to the analytically derived gravity wave, which agrees well with the recent measurements. Moreover, the calculations of the energies in the basic configuration of the quantized space–times resulted in all 3-leptons’ rest energies. Considering this basic configuration is uniformly distributed everywhere in the universe, we can conclude that τ-particles or static magnetic field energy derived from the basic configuration of the quantized space–times is the identity of dark energy, which also distributes uniformly in the universe.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

The construction industry has a notable negative impact on the environment; thus, the promotion of the use of timber structures is an alternative to mitigate its effects. The research develops an artificial intelligence-based decision approach in the calculation of timber structures focused on the enhancement of the sustainability of roof structures. Based on the optimization carried out through genetic algorithms and the framework established in Eurocode 5, a general set of equations has been proposed for a laminated timber roof structure. The tool, which determines the most suitable roof structure for each strength class of laminated timber, allows for the determination of the dimensions of beams and purlins and their respective separations in order to minimize wood consumption. The ultimate goal is to offer multiple solutions regarding strength classes and structural designs in order to foster informed sustainable choices that promote efficient use of resources in construction.