Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding 8 patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but because the sedative effect of midazolam shows marked inter-individual variability, a “corrected midazolam dose” was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in subgroup analysis of the 103 patients who received midazolam. In subgroup analysis using the corrected midazolam dose as an explanatory variable, only corrected midazolam dose correlated with a change in D-dimer ≥ 1.0 μg/mL in multivariate analysis (odds ratio [OR]=1.5, 95% confidence interval [CI] 0.43–0.95; P=0.030). Corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of RT-PCR and qRT-PCR found that the relative expression of PLD6 gene in the testicular tissues of 2-year-old Simmental calves was significantly higher than that of 6-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker VASA. Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piRNA binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and PIWIL2. In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

Missing observation is a common problem in scientific and industrial experiments, particularly in a small-scale experiment. They often present significant challenges when experiment repetition is infeasible. In this research, we propose a multi-objective genetic algorithm as a practical alternative for generating optimal mixture designs that remain robust in the face of missing observation. Our algorithm prioritizes designs that exhibit superior D-efficiency while maintaining a high minimum D-efficiency due to missing observation. The focus on D-efficiency stems from its ability to minimize the impact of missing observations on parameter estimates, ensure reliability across the experimental space, and maximize the utility of available data. We study problems with three mixture components where the experimental region is an irregularly shaped polyhedral within the simplex. Our designs have proven to be D-optimal designs, demonstrating exceptional performance in terms of D-efficiency and robustness against missing observations. We provide a well-distributed set of optimal designs derived from the Pareto front, enabling experimenters to select the most suitable design based on their priorities using the desirability function.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as "optimal" and those shown by the healthy population, but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D [25(OH)D] in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th;95th percentile, 14.3;45.8)ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30ng/mL, 23.4% below 20ng/mL and 6.4% below 15ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20ng/mL, or even ≥30ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20ng/mL and close to 15ng/mL as adequate for the general population.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

Lichen secondary metabolites are generally considered as repellent compounds for lichen feeders. Nevertheless, if the only food available consists in lichens rich in secondary metabolites, lichenophages such as Notodiscus hookeri, a gastropod native from the Possession Island, seem able to implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites appears to play a key role in their feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behavior of Notodiscus hookeri fed exclusively with Usnea taylori, a lichen rich in usnic acid and arabitol. Snail feeding choice experiments with intact lichens vs acetone-rinsed lichens were carried out to study the influence of secondary metabolites. Simultaneously, usnic acid and arabitol were quantified and localized within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution induce preferential snail grazing. Then, no-choice feeding experiments were devised using usnic acid and arabitol embedded in artificial diet, separately or together. This case study demonstrated that the nutritional activity of N. hookerii was governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolites (usnic acid).

In this paper, we investigate the effects of certain variants of the commutative laws on properties of several families of algebras which are in general not commutative, such as groups, linear algebras, or actually quite anti-commutative, such as $BCK$-algebras and $d$-algebras among others. From results obtained it becomes clear that by considering these variants in the presence of yet other axioms it is to be expected that a quite rich and varied set of results may be obtained both in the general and the particular setting of which what has been accomplished in this paper is a substantial sample.

Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.

Corona loss generated from conductors is one of the important design factors on ac transmission lines. Based on helical charge simulation method, the 3-D corona loss calculation model considering the conductors’ outer strands in the corona cage is established. With regard to 2-D corona-loss calculation method, the calculation model proposed in this paper can take the electric field strength’s nonuniformity along the axial direction of stranded conductor into consideration, furthermore, it can also calculate the corona loss when the conductor has sag. The calculation results of the LGJ-300/40 and LGJ-400/35 in the small corona cage well coincide with the measurement results, which indicates that the corona-loss calculation model is appropriate. In addition, the corona loss of the bundle conductors 4 × LGJ720 with sag in UHV corona cage is also analyzed.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

Three-dimensional (3D) geological modeling technology offers intricate geological information services and technical support for the research of urban geological conditions and their evolutionary mechanisms. It further facilitates the analysis of environmental geological problems, encompassing their distinguishing features and genetic mechanisms. The precision of such three-dimensional models is predominantly influenced by the caliber of modeling data, the chosen modeling methodologies, and the intricacy of the modeled geological objects. This research, exemplified by the three-dimensional geological structure modeling of the Wuhan metropolitan development area, aims to explore a comprehensive three-dimensional modeling framework for urban geology, particularly in scenarios with large-scale and complex geological conditions. This study holds significant technical value in enhancing the application of 3D geological modeling, as well as practical importance for urban geological investigations and research.

The superfamily of Acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the Structural Catalytic Core (SCC), which packs all conserved substructure elements around the catalytic machinery, and which can be found in all enzymes of the Acid proteases superfamily. The SCC is a dimer of several structural blocks, such as the DD-link, the D-loop and the G-loop, around two catalytic aspartates in each protease subunit or within an individual chain. The dimer of two D-loop/DD-link substructures makes a DD-zone, and the dimer of two D-loop/G-loop substructures makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation and protein engineering.

The coseismic surface three-dimensional deformation fields were significant for quantified the geometric and kinematic characteristics of earthquake rupture faults. Traditional geodetic techniques were constrained by their intrinsic limitations, such as InSAR, which could only extract far-field deformation fields due to its incoherence, and GNSS, which could only acquire deformations at discrete points. The recently developing optical pixel correlation technique based on high resolution remote sensing images could acquire the near-field coseismic horizontal deformation. In this study, the vertical displacement field of the 2022 Mw 6.6 Menyuan earthquake was obtained by differencing the pre- and post-earthquake DEMs from GaoFen-7 stereo satellite images. Further, the line-of-sight (LOS) and azimuthal (AZI) directions far-field deformations by InSAR, the horizontal near-field deformation by optical pixel correlation based on pre- and post-earthquake GF-2/7 images, and the vertical deformation by differencing the pre- and post-earthquake DEMs, were incorporated to comprehensively solve the complete three-dimensional deformation fields of the 2022 Mw 6.6 Menyuan earthquake. Firstly, the vertical displacement field by differencing DEMs indicated there were significant vertical displacements about 1 m at the bend region, which was induced by the local compressive stress. In addition, at the epicenter on the middle segment of ruptured Lenglongling fault (LLLF), the maximum lifting occurred on the southern sides of the main and secondary faults exceeded 2 m. Secondly, the three-dimensional deformation fields solved by multiple deformation data demonstrated that the near-field deformation field calculated by optical pixel correlation method could quantify the displacements distributed over the rupture fault zone, which were not available on the InSAR deformation maps. Finally, the surface 2D strain derived from the displacement maps calculated by optical pixel correlation revealed high strain concentration on the rupture fault zone. Our study focused on the complete surface three-dimensional deformation estimation from multiple far- and near-field deformation data, and provided a new perspective for a deeper understanding of the characteristics of coseismic surface deformation and the rupture pattern of the fault.

Smart City has emerged as the mainstream paradigm for urban governance innovation, sustainable development, and strategy upgrades, which is drawing attention from scholars worldwide. However, current frameworks for Smart City assessment remain incomplete and simplistic. In is paper, 30 national or provincial capitals in China were selected and we designed a tri-dimensional SPI model—Social, Physical, and Information Space—for smart city spatial development assessment. Utilizing methods such as entropy weighting, coupled coordination degree models, and the Dagum Gini coefficient, this study assesses the spatial development and coupled coordination of 30 cities from 2011 to 2019. Finally, by means of BP neural networks, the study examines the contribution of each indicator to the spatial coupled coordination. The results indicated that with a narrowing disparity in development speeds among different regions, the spatial coupled coordination development level of smart capitals in China has steadily increased, presenting a pattern of staggered distribution. Moreover, the IS subsystem plays the most significant role in coupled coordination. The significance of this research lies in its tri-dimensional spatial perspective of the spatial development and coupled coordination differences of the Smart City, providing evidence-based support for the regional layout and optimization in China.

Multiple valued logic (MVL) has proven to be a better alternative and solution to the challenges of traditional binary logic because of its fast computation, fewer interconnects, and small die. It is a potential candidate for future digital design because it allows energy-efficient, low-complex, and high-speed circuits. This paper introduces a new resistive-load two-dimensional field effect transistor-based ternary logic gates, wherein the active resistive-load is replaced with memristor to reduce chip area and power consumption. A memristor-based standard ternary inverter (STI) is designed using GNRFET, MoS2 FET, WSe2 FET, and FinFET, and their performance metric such as delay, power, and energy delay product (EDP) are analyzed. The results show that the proposed design achieves 50% reduction in circuit area, the average power dissipation is reduced by 11.7X, 6.8X, and 3.2X for GNRFET, MoS2 FET, and WSe2 FET, respectively, as compared to FinFET-based ternary inverter. Moreso, other logic gates such as OR, NOR, AND and NAND were simulated in T-SPICE EDA tool, and the results and truth table are in good agreement.

There are two major proposed forms of dark energy: the cosmological constant and the quintessence scalar field. However, the former has the cosmological constant problem and the latter does not have observational evidence to support the theory. In this paper, we propose a dark energy paradigm to solve the cosmological constant problem and to predict lepton masses as evidence. The dark energy paradigm is a unified dark sector that is based on Planck's dimensional analysis, Lambda CDM, energy conservation, and force equilibrium. We find that dark energy can vary from the cosmological constant to the Planck scale. We find that the predicted values of lepton masses based on the dark energy paradigm agree with the observed values to 1% (or within error ranges).

Two-dimensional (2D) materials show advantages as surface enhanced Raman scattering (SERS) substrate over traditional noble metals, such as chemically inert flat surface and uniform SERS signals. However, due to the low density of free electrons of 2D materials, the enhancement mechanism is mainly restricted to chemical enhancement instead of electromagnetic enhancement, resulting a relatively low enhancement factor. In this work, we reported a sensitive 2D SERS substrate based on chemical vapor deposited MoN nanosheets with electromagnetic enhanced mechanism. The maximum enhancement factor can be 3×105 with a limit of detected concentration of 4×10-8 M, which is comparable to those noble metal SERS substrates without hot spots. The MoN nanosheets show strong surface plasmon resonance in the visible range as evidenced by the UV-vis absorption spectroscopy and first principle calculation. The MoN nanosheets SERS substrates exhibit excellent Raman signal uniformity within the nanosheets. Meanwhile, Distinct thickness dependent sensitivity was observed in the MoN nanosheets, higher sensitivity can be achieved by decreasing the thickness of the nanosheets. Furthermore, the MoN nanosheets SERS substrate also show high thermal stability, which can be annealed in air for more than 300℃ and maintain its SERS activity. The high stability of MoN nanosheets allows it to be reused for 20 cycles without obvious signal decay. The high sensitivity, stability, reusability and Raman signal uniformity, makes MoN nanosheets an ideal 2D SERS substrate for practical applications.

A mathematical model that comprehensively captures the real behavior of riverbed deformation, encompassing all pertinent effects, is developed. The underwater slope reformation process, with the generatrix aligned along the flow velocity in the model, is considered. A numerical model is introduced to calculate the flow involving a deformable bottom, and the model's validation is established through rigorous analysis of experimental findings. The research firmly confirms the suitability of the proposed mathematical and numerical model for describing deformations in uneven and unsteady river flows, including the movement of dredging slots and channel quarries. The model's minimal equation count and reliance on empirical constants demonstrate the model's efficiency. The model's predictions align strongly with experimental data, although optimal values of empirical coefficients vary slightly across different experiments. Hence, there is a call for further investigation to derive more universally applicable closure relationships for the model. The importance of validating the model with reliable field data and its potential extension to accommodate hydraulically diverse soils is emphasized. Such an extension is feasible due to the concentration transfer equation, enabling independent calculations for particle fractions of varying sizes as long as the total particle concentration in the stream remains within reasonable limits. This dedicated research contributes significantly to understanding riverbed deformations and advancing accurate modeling and management of riverine environments.

Polyamide 11 (PA11) is a plant-based nylon made from castor beans. Powder bed fusion laser sintering (PBF-LS) is an additive manufacturing process used for PA11 which allows the reuse of the unsintered powder. The unsintered powder is mixed with virgin powders at different refresh rates which has been studied extensively for most semi-crystalline polyamides. However, there is lack of information on the effect of using 100% reused PA11 powder and the number of times it is reused on its own during powder bed fusion laser sintering. This paper investigates the effect of reusing PA11 powder in PBF-LS and number of times it is reused on the dimensional accuracy, density, thermal and tensile properties. From 100% virgin powder to 3rd use of the powder, there is a decrease in powder wastage, decrease in crystallinity and tensile strength. These was associated with the polymerisation and cross-linking process of polymer chains, upon exposure to high temperature. This results in a higher molecular weight and hence density. From the 4th use to 10th reuse, the opposite was observed which was associated to an increase in high-viscosity and un-molten particles which resulted in defects in the PBF-LS parts.

Consciousness results from comprehending the living creature from its existence in time and space. Thought and consciousness are distinguishing factors between humans and machines having artificial intelligence. No algorithm has been offered for artificial self-awareness based on Thinking. Previous studies have not studied the relationship between consciousness, thinking and time. In this study, the relationship between consciousness, thinking, memories and speech over time has been studied. A deep logical connection exists between consciousness, thinking, and time. An algorithm can be designed for artificial consciousness based on this research findings.

Over the past two decades, covalent organic frameworks (COFs) have become the most widely studied porous crystalline materials. Its specific physical and chemical properties are determined by the arrangement of atoms (crystal structure). Therefore, the determination of its structure is arguably the most important characterization step for COFs. Although single crystal X-ray diffraction (SCXRD) is the most widely used method for structure determination, the size of COF crystals is too small, or their crystal quality is so poor that confirmation of their structure is limited to lattice fringes by transmission electron microscopy (TEM). At present, many 2D-COFs have clear PXRD patterns, but not all 2D-COFs can obtain specific lattice fringes. This severely hinders the development of the COF field. Here, we discover the lattice shrinkage behavior of COFs under electron beam irradiation by comparing the lattice fringes of 2D-COFs under different conditions. By comparing the lattice fringes of TAPT-TFPT COF at room temperature and under liquid nitrogen freezing conditions, we found that the lattice fringes are in good agreement with the Powder X-ray diffraction (PXRD) and theoretical values of COF (2.213 nm) under freezing conditions, however, the lattice fringe spacing is only 1.656 nm at room temperature. The discovery not only provides new insights into the TEM characterization of COFs, but also further expands the range of crystalline COF materials.

The field dynamics of neutral and charged matter (treated as gauge fields) beyond the event horizon of black holes are investigated. As an extension of the work done in Ganesan (2023) [1], the analysis was done using the combined dynamics of the two-dimensional Yang-Mills and Liouville gravity fields beyond the event horizon. The quantum interactions and symmetry breaking mechanisms of the combined two-dimensional fields are discussed. The second part of this paper explores the quantum dynamics occurring at the event horizon. By considering the structure of the event horizon as a Möbius strip (embedded in three-dimensional space), a formulation for the lower bound of the first energy eigenvalue of a quantum particle (electron) at the event horizon is obtained.

Human pose estimation is a complex detection task in which the network needs to capture the rich information contained in the images. In this paper, we propose MSTPose (Multi-Scale Transformer for human Pose estimation). Specifically, MSTPose leverages a high-resolution Convolution neural network (CNN) to extract texture information from images. For the feature maps from three different scales produced by the backbone network, each branch performs the coordinate attention operations. The feature maps are then spatially and channel-wise flattened, combined with keypoint tokens generated through random initialization, and fed into a parallel Transformer structure to learn spatial dependencies between features. As the Transformer outputs one-dimensional sequential features, the mainstream two-dimensional heatmap method is abandoned in favor of one-dimensional coordinate vector regression. The experiments show that MSTPose outperforms other CNN-based pose estimation models and demonstrates clear advantages over CNN + Transformer networks of similar types.

The three-dimensional structure of Gulf of Mexico’s warm-core rings, detaching from the Loop Current, is investigated using satellite altimetry and a large set of ARGO float profiles. Reconstruction of the Loop Current rings (LCRs) vertical structure from sea surface height observations is made possible by the use of the gravest empirical modes method (GEM). The GEMs are transfer functions that associate a value of temperature and salinity for each variable pair {dynamic height;pressure}, and are computed by estimating an empirical relationship between dynamic height and the vertical thermohaline structure of the ocean. Between 1993 and 2021, 40 LCRs were detected in the altimetry and their three-dimensional thermohaline structure was reconstructed, as well as a number of dynamically relevant variables (geostrophic and cyclogeostrophic velocity, relative vorticity, potential vorticity, available potential energy and kinetic energy density etc.). The structure of a typical LCR was computed by fitting an analytical stream function to the LCRs dynamic height signature and reconstructing its vertical structure with the GEM. The total heat and salt contents and energy of each LCR were computed and their cumulative effect on the Gulf of Mexico’s heat, salt and energy balance is discussed. We show that LCRs have a dramatic impact on these balances and estimate that residual surface heat fluxes of -13 Wm−2 are necessary to compensate their heat input, while the fresh water outflow of the Mississippi river approximately compensates for their salt excess input. An average energy dissipation of O[10−10−10−9] Wkg−1 would be necessary to balance their energy input.

This study aims to evaluate the land surface temperature (LST) and the thermal characteristics of the Urban Canopy Layer (UCL) of the urban canyon in Avenida Rio Branco in the Central Business District (CBD) of Rio de Janeiro during summer. In order to conduct this evaluation, two methods were employed: 1) TIRS Landsat-8 sensor for data selection and processing (latest generation, 2011-2020); ; 2) field survey using nine sampling points — seven along two mobile transects, one fixed point, and one vertical measurement point, which required the use of a RPA (Remotely Piloted Aircraft). Three categories of analysis were established for the field survey based on the prevailing synoptic situations: stability, instability, and post-instability. The CBD is characterized by extensive areas with surface heat islands, in which temperatures were higher than 38.9°C; the areas with milder LSTs were Campo do Santana, Avenida Rio Branco, and one of the Mixed-Use Zones (Praça Mauá). With respect to Rio Branco Avenue, the LST niches of lowest elevation were derived through building shadowing; however, the orbital data diverged from the observation data of the ten field-study days. In situ data revealed that the characteristics urban morphology of Avenida Rio Branco is susceptible to the formation of heat islands, presenting heat islands of very strong magnitude (over 6.1°C) in atmospheric stability, strong magnitude (4.1-6.0°C) in atmospheric instability, and moderate magnitude (2.1°C-4.0°C) in post-atmospheric instability. Despite the synoptic situation, thermal cores were concentrated at 1 pm. The intersection between Avenida Rio Branco, Rua do Ouvidor, and Praça Mauá stored most of the solar energy received during the day due to the greater sky obstruction caused by the verticalization. Finally, vertical analysis demonstrated the formation of a thermal inversion on the night of the highest mean air temperature (29.5°C), probably, due to the roughness and number of buildings in the urban canyon.

We create a model universe by equipping a topological surface (system) with compact dimensions insulated by an information blocking horizon. The insulated compact WF can produce entanglement independent of distance. Interaction between the system and the WF changes the curvature of the first and the quantum state (frequency) of the second in an interconnected relationship. Thus, the field curvature measures the evolution of the particle WF as time. Positive field curvature creates pressure, whereas negative field curvature generates a vacuum, satisfying the Borsuk-Ulam Theorem and the Page and Wootters mechanism of static time. The accumulation of pressure or vacuum generates poles with contrasting dimensionalities, two-dimensional black hole horizons (time infinite), and four-dimensional cosmic voids (time zero). The orthogonality of the field and the compact WF give rise to global self-regulation that fine-tunes the cosmic parameters and can promote fractal topology. The four-dimensional vacuum in cosmic voids can produce an accelerating expansion without dark energy. When gravity effects are eliminated, we find a new, so far unexplored, order-increasing side of entropy. The verifiable and elegant hypothesis satisfies Mach's principle.

Two-dimensional mass spectrometry (2D MS) is a method for tandem mass spectrometry that relies on manipulating ion motions to correlate precursor and fragment ion signals. 2D mass spectra are obtained by performing a Fourier transform in both the precursor ion mass-to-charge ratio (m/z) dimension and the fragment ion m/z dimension. The phase of the ion signals evolves linearly in the precursor m/z dimension and quadratically in the fragment m/z dimension. This study demonstrates that phase-corrected absorption mode 2D mass spectrometry improves signal-to-noise ratios by a factor of 2 and resolving power by a factor of 2 in each dimension compared to magnitude mode. Furthermore, phase correction leads to an easier differentiation between ion signals and artefacts, and therefore easier data interpretation.

Urban form is associated with both socio-economic and urban physical properties. This study explores the differences among urban forms in the Seoul Metropolitan Region with a comparison between census-based socioeconomic variables and landscape metrics computed from remotely sensed data. To accomplish this, factor analysis and multi-dimensional scaling were used with the selected variables and metrics. When all of the measures are considered together, four types of cities and towns emerged: 1) exurban-fragmented high growth, 2) exurban-fragmented low growth, 3) compact-extensive urban core and 4) sub-urban compact-high growth. The results indicate that the fusion of knowledge of the physical urban layout and that of socio-economic characteristics is beneficial for a better understanding of urban spatial patterns. However, there remain challenges in delineating each urbanized area and with indicator selection for comparing urban form across cities and towns.

In this paper, we analyze the Hawking radiation phenomenon for types of Banados-Teitelboim-Zanelli-like (BTZ-like) black holes. For this purpose, using the Hamilton-Jacobi method, we consider semi-classical WKB approximation to calculate the tunneling probabilities of massive boson particles. For these particles, we use the equation of motion for the Glashow-Weinberg-Salam model. Using quantum tunneling process of charged massive bossons, we compute the corresponding Hawking temperatures. Furthermore, we discuss the effects of rotation parameter on tunneling probability and temperature.

This report describes the collection of a large dataset (6930 measurement) on dimensional error in the fused deposition modeling (FDM) additive manufacturing process for full-density parts. Three different print orientations were studied, as well as seven raster angles (0°, 15°, 30°, 45°, 60°, 75°, and 90°) for the rectilinear infill pattern. All measurements were replicated ten times on ten different samples to ensure a comprehensive dataset. Eleven polymer materials were considered: acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), high-temperature PLA, wood-composite PLA, carbon-fiber-composite PLA, copper-composite PLA, aluminum-composite PLA, high-impact polystyrene (HIPS), polyethylene terephthalate glycol-enhanced (PETG), polycarbonate, and synthetic polyamide (nylon). The samples were ASTM-standard impact testing samples, since this geometry allows the measurement of error on three different scales; the nominal dimensions were 3.25mm thick, 63.5mm long, and 12.7mm wide. This dataset is intended to give engineers and product designers a benchmark for judging the accuracy and repeatability of the FDM process for use in manufacturing of end-user products.

This paper presents a new scientific contribution on the two-dimensional (2-D) subdomain technique in polar coordinates taking into account the finite relative permeability of the ferromagnetic material. The constant relative permeability corresponds to linear part of the nonlinear B(H) curve. As in conventional technique, the method of separation of variables and the Fourier’s series are used for the resolution of magnetostatic Maxwell’s equations in each region. Although, the general solutions of magnetic field in the subdomains and boundary conditions (BCs) between regions are different in the conventional and proposed method. In this later, the magnetic field solution in each subdomain is a superposition of two magnetic quantities in the two directions (i.e., r- and Q-axis) and the BCs between two regions are also in both directions. For example, the scientific contribution has been applied to an air- or iron-cored coil supplied by a constant current. The distribution of local quantities (i.e., the magnetic vector potential and flux density) has been validated by a corresponding 2-D finite-element analysis (FEA). The obtained semi-analytical results are in very good agreement with those of numerical method.

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

Human RAD51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. The activator protein Swi5-Sfr1 and Ca2+ ions stimulate different reaction steps and induce a perpendicular orientation of DNA bases in the presynaptic complex. To investigate the importance of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) requires Ca2+ concentrations greater than 5 mM, while 1 mM is sufficient for strand exchange between two oligonucleotides. The structural change, which is evidenced by an increase in fluorescence intensity of poly(dεA) (a poly(dA) analog), reaches a plateau at 1 mM Ca2+. Meanwhile, the linear dichroism signal intensity at 260 nm, which is indicative of rigid perpendicular DNA base orientation, requires >2 mM Ca2+ for saturation and thus correlates with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.3 mM and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. We further discuss the parallels between Mg2+ activation of RecA and Ca2+ activation of HsRad51.

D-Glucaric acid is an important bio-based building block of polymers and is a high value-added chemical that can be used in a variety of applications. In the present study, the Udh target genes from Pseudomonas putida and Pseudomonas syringae were used together to construct the expression vector pETDuet-2×Udh. The transformants of BL21(DE3) with vector pETDuet-2×Udh was applied to produce glucaric acid from glucuronic acid. After optimization of induction conditions, the highest Udh expression were achieved when 0.4 mmol L-1 isopropyl-β-d–thiogalactoside (IPTG) was added to cell cultures at an OD600 value of 0.6 followed by culture at 26℃ for 6 hours. The production of glucaric acid substantially reached 5.24 ± 0.015 g L-1 in fed-batch cultures in a 30 L tank. In the present study, a new system for glucaric acid production was established, which was more economic and friendly to environment.

Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPL). Preeclampsia (PE) complicates about 10-17% of pregnancies with APS. However, only early onset PE (< 34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset PE and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as PE or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and PE and therefore not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose-aspirin and low-molecular- weight-heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation despite basic treatment. Several additional treatment options have been proposed, with Hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as additional intervention as well.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults, and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One-hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of participants. In conclusion, this study found micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by an insufficient consumption of food groups rich in B vita-mins. Our preliminary results in those remeasured after a digitally-enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support in a “food as medicine” approach complemented with supplementation where needed.

Water reuse for irrigation is increasingly recognized as an essential and economical strategy in areas with water scarcity. A simple, low-cost, low-maintenance, and highly efficient Pond-In-Pond (PIP) treatment system can be used for wastewater reuse. PIP is a treatment technology in which two types of ponds -- anaerobic and aerobic -- are combined into a single pond and consist of a deeper inner section entirely submerged within the outer pond. Previous studies on PIPs and PIP-like systems have reinforced the potential for reuse through promising performance results with BOD removal over 80% and a reduction in land area requirements by approximately 40%. Yet, no prior efforts have been made to understand the performance mechanism of such systems. This study makes use of two, 2-D modeling tools in developing a fundamental understanding of PIP flow dynamics and the expected performance. The modeling results showed that the PIP configuration offers improved flow diversion along with reduced flow velocity. Additionally, the PIP retained approximately 17% more (p<0.05) particles than the traditional pond with most of the particles concentrated within the inner pond. Lower velocity and the higher solids retention in the PIP thus allowed for better treatment performance compared to traditional ponds. The findings from this study can be used as preliminary data for future in-depth investigations of the PIP system leading toward effective and optimal designs. This will help address the major societal concern of water scarcity with low-cost and effective wastewater treatment.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Increased construction activities in Australia have led to the generation of a massive volume of construction and demolition (C&D) waste annually. Management of this volume of waste requires an effective waste framework. The literature reported that the current Australian waste framework does not meet expectations and needs immediate improvements. This study was therefore conducted to seek the key C&D stakeholders' opinion about various issues identified in this waste stream. The specific objectives of this study are identification of the main barriers to effective C&D waste management, the impact of current regulations and opportunities to enhance the current C&D waste management system. A survey was conducted in 2019 to capture the stakeholders' perception. 132 participants from various industries and government agencies based in various Australian jurisdictions took part in the survey. The key results showed that the main barriers towards an effective management system are "overregulation, tough acceptance criteria, and increased testing requirements", "lack of local market" and "culture, poor education and low acceptance". Furthermore, a low number of participants indicated that the current legislation encourages waste recovery activities. The main areas of improvements included "providing a guideline that determines the accepted level of contamination for reusing C&D waste”, "preparation of guidelines on requirements of using recycled C&D materials in different industries" and "setting target for reduction, reusing, and recycling C&D waste". The results can inform policy development and be used as evidence for a broader discussion to solve lasting issues in C&D waste management.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Gradients of smooth functions with non-independent variables are relevant for exploring complex models and for the optimization of functions subjected to constraints. In this paper, we investigate new and simple approximations and computations of such gradients by making use of independent, central and symmetric variables. Such approximations are well-suited for applications in which the computations of the gradients are too expansive or impossible. The derived upper-bounds of the biases of our approximations do not suffer from the curse of dimensionality for any $2$-smooth function, and theoretically improve the known results. Also, our estimators of such gradients reach the optimal (mean squared error) rate of convergence (i.e., $\mathcal{O}(N^{-1})$) for the same class of functions. Numerical comparisons based on a test case and a high-dimensional PDE model show the efficiency of our approach.

While there are well-known synthetic methods in the literature to find the image of a point under circular inversion in l2−normed geometry (Euclidean geometry), there is no similar synthetic method in Minkowski geometry, also known as the geometry of finite-dimensional Banach spaces. In this study, we have succeeded in giving a synthetic construction for the circular inversion in l1−normed spaces, which is one of the most fundamental examples of Minkowski geometry. Moreover, this synthetic construction has been given using the Euclidean circle, independently of the l1−norm.

This paper introduces a rigorous and comprehensive approach for the assessment of marine shafting systems through the utilization of an advanced Pi-Theorem based scaling methodology. Integrating journal bearing similarity assessment and shaft-line scaling methodology with advanced dimensional analysis, the study aims to provide a methodology foundation for systematic replication and analysis of marine shafting systems through scaled models. The proposed scaling methodology ensures geometric and mechanical similarity in terms of shaft-line deflection, considering key scaling parameters such as shaft length, diameter, weight, loads, rotational speed, material properties, bearing locations, and offsets. The advanced dimensional analysis computes specific non-dimensional ratios to guarantee a close resemblance between a real-size system and a scaled lab model, enabling meaningful experimentation. The methodology is analytically derived and validated with numerical simulations for a case study, conducting comparative analysis, evaluating discrepancies, and utilizing the integrated framework for experimentation.

The Double Random Phase Encoding (DRPE) image encryption method has garnered significant attention in color image processing and optical encryption, thanks to its parallel encryption of R, G, B. However, DRPE-based color image encryption faces two challenges. Firstly, it disregards the correlation of R, G, and B, compromising the encrypted image's robustness. Secondly, DRPE schemes relying on Discrete Fourier Transform (DFT) and Discrete Fractional Fourier Transform (DFRFT) are vulnerable to linear attacks, such as Known Plaintext Attack (KPA) and Chosen Plaintext Attack (CPA). Quantum walk stands out as a remarkable tool for designing modern cryptographic mechanisms, offering resistance to potential attacks from both classical and quantum computers.Therefore, this study presents an optical color image encryption algorithm that combines two-dimensional quantum walk with 24-bit plane permutation, dubbed OCT. This approach employs pseudo-random numbers generated by Two-Dimensional Quantum Walking (TDQW) for phase modulation in DRPE and scrambles the encrypted image's real and imaginary parts using the Generalized Arnold Transform. The 24-bit plane permutation helps reduce correlation of the R, G, B, while the Generalized Arnold Transform bolsters DRPE's resistance to linear attacks. By incorporating TDQW, the key space is significantly expanded. Experimental results validate the effectiveness and security of proposed method.

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

We present a new penalized method for estimation in sparse logistic regression models with group structure. Group sparsity suggests us to consider the Group Lasso penalty. Being different from penalized log-likelihood estimation, our method can be viewed as a penalized weighted score function method. Under some mild conditions, we provide non-asymptotic oracle inequalities promoting group sparsity of predictors. A modified block coordinate descent algorithm based on a weighted score function is also employed. The net advantage of our algorithm over the existing Group Lasso-type procedures is that the tuning parameter can be pre-specified. The simulations show that this algorithm is considerably faster and more stable than competing methods. Finally, we illustrate our methodology with two real data sets.

Agricultural drainage canals that connect upstream fish spawning areas to downstream rivers and lakes serve as crucial habitats for migrating fish. However, disconnections, such as drops and chutes, have been constructed in these canals due to agricultural modernization and flood control measures, hindering the movement of fish with limited swimming abilities. Portable fishways offer a promising solution to reconnect water bodies in agricultural canals, as they can be easily removed during high water discharges to avoid impeding the canals' drainage function. In addition to experimental assessments of fishway functionality, employing a hydrodynamic model to explore effective placement strategies for portable fishways is essential to maximize their effectiveness. This study presents a method to determine the best horizontal location of a portable fishway in an agricultural drainage canal using two-dimensional hydrodynamic simulations within the specified cases. The applicability of this method is demonstrated by addressing the positioning challenge of a portable fishway on a chute in an agricultural drainage canal in Japan. Results indicate that the proposed method allows for the selection of a suitable location, considering preferable hydraulic conditions both within the portable fishway and around its entrance.

Due to the intermittency and fluctuation of photovoltaic (PV) output power, a high proportion of grid-connected PV power generation systems has a significant impact on power systems. Accurate PV power forecasting can alleviate the uncertainty of the PV power and is of great significance for the stable operation and scheduling of the power systems. Therefore, in this study, a feature rise-dimensional (FRD) two-layer ensemble learning (TLEL) model for short-term PV power deterministic forecasting and probability forecasting is proposed. First， based on the eXtreme Gradient Boosting (XGBoost), Random Forest (RF), CatBoost, and Long-short-term memory (LSTM) models, a TLEL model is constructed utilizing the ensemble learning algorithm. Meanwhile, the FRD method is introduced to construct the FRD-XGBoost-LSTM (R-XGBL), FRD-RF-LSTM(R-RFL), and FRD- CatBoost - LSTM (R-CatBL) models. Subsequently, the above models are combined to construct the FRD-TLEL model for deterministic forecasting, and perform probability interval forecasting based on quantile regression(QR). Finally, the performance of the proposed model is demonstrated with a real-world dataset. By comparing with other models, the proposed model displays better forecasting accuracy for deterministic forecasting and reliable forecasting intervals for probability forecasting, and good generalization ability in the datasets of different seasons and weather types.

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin-(s,(2t−1)/2) with nearest neighbors and the external magnetic field. We establish the partition function of the model by means of the transfer matrix. Under a null boundary condition, we compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model’s free energy, entropy, magnetization, and susceptibility. By examining the model’s associated iterative equations, we use the cavity approach to investigate the phase transition problem. We numerically determine the model’s periodicity.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

Manipulation of radiation pattern control is challenging, especially at low frequencies. In this paper, we demonstrate that acoustic metamaterials as an effective array of quadrupoles can remarkably improve the directionality of acoustic radiation at low frequencies, compared with previous metamaterials as monopole and dipole structures. The directivity of the acoustic radiation can be adjusted by changing the characteristic parameter and the symmetry of the structure, which provide a flexible method of adjustable radiation di-rections. The directionality can be further improved by constructing linear array of structure. Our work opens an approach of acoustic radiation control via quadrupolar metamaterials.

The Finite size Lyapunov exponent (FSLE) has been used extensively since the late 1990’s to diagnose turbulent regimes from Lagrangian experiments and to detect Lagrangian coherent structures in geophysical flows and two-dimensional turbulence. Historically, the FSLE was defined in terms of its computational method rather than via a mathematical formulation, and the behavior of the FSLE in the turbulent inertial ranges is based primarily on scaling arguments. Here we propose an exact definition of the FSLE based on conditional averaging of the finite amplitude growth rate (FAGR) of the particle pair separation. With this new definition, we show that the FSLE is a close proxy for the inverse structural time, a concept introduced a decade before the FSLE. The (in)dependence of the FSLE on initial conditions is also discussed, as well as the links between the FAGR and other relevant Lagrangian metrics, such as the finite time Lyapunov exponent and the second order velocity structure function.

General Linear Modelling (GLM) has been widely employed to estimate the hemodynamic changes evoked by cognitive processing, which are more likely to be nonlinear than linear. First, this study re-analyzed the fNIRS data (N = 38, Mage = 5.0 years, SD = 0.69 years, 17 girls) collected in the Mixed-Order Design Dimensional Change Card Sort (DCCS) task. The results indicated that the quadratic equation was better than GLM to model HbO changes in this task. Second, analysis of a new set of data indicated that the Habit-DisHabit design of DCCS was more effective in identifying the neural correlates of cognitive shifting than the Mixed-Order Design. Third, this study found that the Non-users were more attentive and engaged than the Heavy-users, with a slower but more steady increase of brain activation in BA8 and BA9.

This study aims to examine the impact of tablet use on preschoolers’ executive function during the Dimensional Change Card Sort Task (DCCS) task using the functional near-infrared spectroscopy (fNIRS). Altogether 38 Chinese preschoolers (Mage = 5.0 years, SD = 0.69 years, 17 girls) completed the tasks before the COVID-19 lockdown. Eight children never used tablets, while 16 children were diagnosed as the ‘heavy-user'. The results indicated that: (1) the 'Non-user' outperformed the 'Heavy-user' with a significantly higher correct rate in the DCCS task; (2) the two groups differed significantly in the activation of the prefrontal cortex (BA 9): the 'Non-user' pattern is normal and healthy, whereas the 'Heavy-user' pattern is not normal and needs further exploration.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

Inspired by amazing result obtained by Semay [1], this study revisits generalised Kepler's third law of an n-body system from the perspective of dimension analysis. To be compatible with Semay's quantum n-body result, this letter reports a conjecture which had not be included in author's early publication [2] but formulated in the author's research memo. The new conjecture for quantum N-body system is proposed as follows: Tq|Eq|^3/2 = πG/√2[(Σ^N_i=1 Σ^N_j=i+1 m_im_j)³/(Σ^N_k=1 m_k)]^1/2. This formulae is, of course, consistent with the Kepler's third law of 2-body system, and exact same as Semay's quantum result for identical bodies.

Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption; disruptions in this complex can affect bone metabolism. Methods: This study analyzed the changes in RANKL, OPG and 25(OH)D levels, the RANKL/OPG ratio, and other bone turnover markers (BTM) from diagnosis to complete remission in children with acute lym-phoblastic leukemia (ALL). This is a prospective observational cohort study. This study was carried out in the Instituto Mexicano del Seguro Social in Mexico City. Thirty-three patients (4-17 years) with newly diagnosed B-cell ALL were included. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A pe-ripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p=0.001) and osteocalcin (p

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

This research provides a computationally efficient numerical tool for predicting 3-D turbulent flows over hydrofoils. It addresses a gap in existing numerical methods by extending the capabilities of the laminar VIScous Vorticity Equation (VISVE) solver to handle 3-D turbulent flow scenarios. The implementation integrates the k − ω SST model into the 3-D VISVE solver using the Finite Volume Method (FVM), extending its capability to handle turbulent flows. The turbulence model is also parallelized to improve computational efficiency. The application of the newly developed model to 3-D hydrofoil cases expands its scope and serves as preparatory work for future rotational propeller applications. Rigorous testing includes a convergence analysis concerning grid numbers and time step sizes, and validation against a Reynolds-Averaged Navier-Stokes (RANS) solver ensures the reliability and accuracy of the enhanced VISVE solver for turbulent flow simulations. The turbulent VISVE solver offers advantages such as reduced computational domain and costs through a vorticity-based approach. Turbulence concentration within boundary layers and free shear flows does not compromise the advantages of the small computational domain. The simplified meshing process, automatically generated by denoting the number of panels on the hydrofoil, makes the solver accessible for researchers and engineers.

Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

This article shows that the recently proposed latent D-scoring model of Dimitrov is statistically equivalent to the two-parameter logistic item response model. An analytical derivation and a numerical illustration are employed for demonstrating this finding. Hence, estimation techniques for the two-parameter logistic model can be used for estimating the latent D-scoring model. In an empirical example using PISA data, differences of country ranks are investigated when using different metrics for the latent trait. In the example, the choice of the latent trait metric matters for the ranking of countries. Finally, it is argued that an item response model with bounded latent trait values like the latent D-scoring model might have advantages for reporting results in terms of interpretation.

The 3D reconstruction method using RGB-D camera has a good balance in hardware cost, point cloud quality and automation. However, due to the limitation of inherent structure and imaging principle, the acquired point cloud has problems such as a lot of noise and difficult registration. This paper proposes a three-dimensional reconstruction method using Azure Kinect to solve these inherent problems. Shoot color map, depth map and near-infrared image of the target from six perspectives by Azure Kinect sensor. Multiply the 8-bit infrared image binarization with the general RGB-D image alignment result provided by Microsoft to remove ghost images and most of the background noise. In order to filter the floating point and outlier noise of the point cloud, a neighborhood maximum filtering method is proposed to filter out the abrupt points in the depth map. The floating points in the point cloud are removed before generating the point cloud, and then using the through filter filters out outlier noise. Aiming at the shortcomings of the classic ICP algorithm, an improved method is proposed. By continuously reducing the size of the down-sampling grid and the distance threshold between the corresponding points, the point clouds of each view are continuously registered three times, until get the complete color point cloud. A large number of experimental results on rape plants show that the point cloud accuracy obtained by this method is 0.739mm, a complete scan time is 338.4 seconds, and the color reduction is high. Compared with a laser scanner, the proposed method has considerable reconstruction accuracy and a significantly ahead of the reconstruction speed, but the hardware cost is much lower and it is easy to automate the scanning system. This research shows a low-cost, high-precision 3D reconstruction technology, which has the potential to be widely used for non-destructive measurement of crop phenotype.

Cathepsin D (CatD; EC 3.4.23.5) family peptidases of parasitic organisms are regarded as potential drug targets as they play critical roles in the physiology and pathobiology of parasites. Previously, we characterized the biochemical features of cathepsin D isozyme 2 (CatD2) in the carcinogenic liver fluke Clonorchis sinensis (CsCatD2). In this study, we performed all-atomic molecular dynamics simulations by applying different systems for the ligand-free/bound forms under neutral and acidic conditions to investigate the pH-dependent structural alterations and associated functional changes in CsCatD2. CsCatD2 showed several distinctive characteristics as follows: 1) CsCatD2-inhibitor complex formed more hydrogen bonds; 2) acidic pH caused major conformational transitions from open to closed state in this enzyme; 3) neutral pH induced displacement of the N-terminal part to hinder the accessibility of the active site and open allosteric site of this enzyme; and 4) the flap dynamics metrics, including distance (d1), TriCα angles (θ1 and θ2), and dihedral angle (ϕ), account for the asymmetrical twisting motion of the active site of this enzyme. These findings provide an in-depth understanding of the pH-dependent structural dynamics of CsCatD2 and basic information for the rational design of an inhibitor as a drug targeting CsCatD2.

At present, the world is at the peak of production of traditional fossil fuels. Much of the resources that humanity has been consuming (oil, coal and natural gas) are coming to an end. The human being faces a future that must necessarily go through a paradigm shift, which includes a progressive movement towards increasingly less polluting and energetically viable resources. In this sense, nanotechnology has a transcendental role in this change. For decades, new materials capable of being used in energy processes have been synthesized that undoubtedly will be the cornerstone of the future development of the planet. In this review, we report on the current progress in the synthesis and use of one-dimensional (1D) nanostructured materials (specifically nanowires, nanofibers, nanotubes and nanorods), with compositions based on oxides, nitrides, or metals, for applications related to energy. Due to its extraordinary surface-volume relationship, tunable thermal and transport properties, and its high surface area, these 1D nanostructures have become fundamental elements for the development of energy processes. The most relevant 1D nanomaterials, their different synthesis procedures, and useful methods for assembling 1D nanostructures in functional devices will be presented. Applications in relevant topics such as optoelectronic and photochemical devices, hydrogen production or energy storage, among others, will be discussed. The present review concludes with a forecast on the directions towards which future research could be directed on this class of nanostructured materials.

This study aims to test empirical research on the effect of financial resource ability, research and development (R &amp; D) on innovation orientation and competitive position. This study also examines the critical mediating role of innovation orientation and competitive position to achieving new products performance (NPP). This study used a quantitative research approach by comparing data from service industry and manufacture industry in Indonesia included in Indonesian-State-Ownership companies. The analysis unit in this study used middle managers and top managers who responsible for managing divisions within the Indonesian-State-Ownership companies. The number of respondents studied in this study was 287 sample. The purposive sampling technique was used in taking the research sample. This study indicated that financial resources abilities, research and development (R &amp; D) abilities positive effect on innovation orientation and competitive position. This study also testing the importance role of innovation orientation and a competitive position to enhancing new products performance (NPP).

Phospholipase Dα1 (PLDα1) belongs to phospholipases, a large phospholipid hydrolyzing protein family. PLDα1 has a substrate preference for phosphatidylcholine leading to enzymatic production of phosphatidic acid, a lipid second messenger with multiple cellular functions. PLDα1 itself is implicated in biotic and abiotic stress responses. We present here a shot-gun differential proteomic analysis on roots of two pldα1 mutants compared to the Col-0 wild type. Our data suggest new roles of PLDα1 in endomembrane transport, mitochondrial protein import and protein quality control and glucosinolate biosynthesis. Thus, we identified proteins involved in endocytosis, endoplasmic reticulum-Golgi transport and attachment sites of endoplasmic reticulum and plasma membrane (V-type proton ATPases, protein transport protein SEC13 homolog A, vesicle-associated protein 1-2, vacuolar protein sorting-associated protein 29, syntaxin-32, all upregulated in the mutants), mitochondrial import and electron transport chain (mitochondrial import inner membrane translocase subunits TIM23-2 and TIM13, mitochondrial NADH dehydrogenases, ATP synthases, cytochrome c oxidase subunit 6b-1, ADP,ATP carrier protein 2, downregulated in the mutants) and glucosinolate biosynthesis (3-isopropylmalate dehydrogenases 1, 2 and 3, methylthioalkylmalate synthase 1, cytochrome P450 83B1, Glutathione S-transferase F9, indole glucosinolate O-methyltransferase 1, adenylyl-sulfate kinase 1, all upregulated in mutants). Our results suggest broader biological roles of PLDα1 as anticipated so far.

The mechanisms by which bacteriophage T4 converts the metabolism of its E. coli host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950’s through the 1980’s. At this point, a wide range of phages are starting to be used therapeutically and in many other applications and also the range of available phage sequence data is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions.

In this work, we introduce the concepts of r-fuzzy soft δ-open (resp. semi-open and α-open) sets on fuzzy soft topological space, the relations of these sets with each other are established. Next, we introduce the concepts of fuzzy soft δ-continuous (resp. β-continuous, semi-continuous, pre-continuous and α-continuous) functions, and some properties of these functions along with their mutual relationships are investigated. Also, a decomposition of fuzzy soft semi-continuity and a decomposition of fuzzy soft α-continuity are given. Finally, as a weaker form of fuzzy soft continuity by Aygunoglu et al. (2014), the concepts of fuzzy soft almost (resp. weakly) continuous functions are introduced, and some properties are specified. Moreover, we explore the notion of continuity in a very general setting namely fuzzy soft (L, M, N, O)-continuous functions, and a historical justification are obtained.

The objective of this paper was to verify the applicability of statistical learning (SL) compared to human reasoning with respect to the Universal Thermal Climate Index (UTCI), a complex tool for the assessment of outdoor thermal stress. UTCI is an equivalent temperature index based on the 48-dimensional output of an advanced model of human thermoregulation formed by 12 variables at four consecutive 30-minute intervals, which were calculated for 105642 thermal conditions from extreme cold to extreme heat. Comparing the performance of SL algorithms to the results accomplished by an international endeavor involving more than 40 experts from 23 countries, we found that random forests and k-nearest neighbors closely predicted UTCI values, but that clustering applied after dimension reduction algorithms (principal component analysis and t-distributed stochastic neighbor embedding) were inadequate for risk assessment in relation to the UTCI stress categories. This indicates a potential supportive role for SL, as it will not (yet) fully replace the bio-meteorological expert knowledge.

This paper is devoted to the study of multi-dimensional integral transform with Fox H-function in the kernel in weighted spaces integrable functions in the domain R+n with positive coordinates. Mapping properties such as the boundedness, the range, the representations of the considered transformation are established.

First, a recently developed eigenfunction expansion technique, based in part on separation of the thickness-variable and partly utilizing a modified Frobenius type series expansion technique in conjunction with the Eshelby-Stroh formalism, is employed to derive three-dimensional singular stress fields in the vicinity of the front of an interfacial crack weakening an infinite bicrystalline superlattice plate, made of orthorhombic (cubic, hexagonal and tetragonal serving as special cases) phases, of finite thickness and subjected to the far-field extension/bending, in-plane shear/twisting and anti-plane shear loadings, distributed through the thickness. Crack-face boundary and interface contact conditions as well as those that are prescribed on the top and bottom surfaces of the bicrystalline superlattice plate are exactly satisfied. It also extends a recently developed concept of lattice crack deflection (LCD) barrier to a superlattice, christened superlattice crack deflection (SCD) energy barrier for studying interfacial crack path instability, which can explain crack deflection from a difficult interface to an easier neighboring cleavage system. Additionally, the relationships of the nature (easy/easy, easy/difficult or difficult/difficult) interfacial cleavage systems based on the present solutions with the structural chemistry aspects of the component phases (such as orthorhombic, tetragonal, hexagonal as well as FCC (face centered cubic) transition metals and perovskites) of the superlattice are also investigated. Finally, results pertaining to the through-thickness variations of mode I/II/III stress intensity factors and energy release rates for symmetric hyperbolic sine distributed load and their skew-symmetric counterparts that also satisfy the boundary conditions on the top and bottom surfaces of the bicrystalline superlattice plate under investigation, also form an important part of the present investigation.

Sheep’s milk is a significant source of nucleotides monophosphate (NMPs) but can also contain undesirable residues from veterinary drugs, posing a potential human health risk. This study introduces a novel application of 2D-LC, in heart-cutting mode, for the simultaneous determination of nucleotides and veterinary drug residues in sheep’s milk. Two-dimensional liquid chromatography (2D-LC) allows for the separation of these compounds in a single chromatographic run despite their differing physicochemical properties. The proposed method separates six veterinary drug residues and five NMPs in a single injection. The compounds were separated using a C18 reversed-phase column in the first dimension and a Primesep SB analytical column in the second dimension. The method performance was evaluated in terms of linearity range, detection and quantification limits, matrix effects, precision, and accuracy. The results demonstrated good linearity and sensitivity, with quantification limits allowing for the quantification of veterinary drugs at the maximum residue level and nucleotides at typical levels found in milk samples. The method has been successfully applied to the analysis of sheep’s milk samples acquired from local supermarkets, with recoveries within a range of 70-119 % and 82-117 % for veterinary residues and NMPs, respectively.

The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated in the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.

Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Edible oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. In this research, low field NMR (LF-NMR) relaxation characteristic data of various sample oils were analyzed. We also suggest a new method for prediction size of edible oil molecules using LF-NMR relaxation time distributions. According to the relative molecular mass, carbon chain length, transverse relaxation time of different sample oils, combined with oil viscosity and other factors, the relationship between carbon chain length and transverse relaxation time rate was analyzed. Various oils and fats in the mixed fluid are displayed, reflecting the composition information of different oils. To study the correlation between the rotation correlation time and molecular information of oil molecules. The molecular composition of the resulting fluid determines its properties, such as viscosity and phase behavior. The results show that low-field NMR can obtain information on the composition, macromolecular aggregation, and molecular dynamics of complex fluids. Measurements of grease in the free fluid state show that the relaxation time can reflect the intrinsic properties of the fluid. It is shown that the composition characteristics and states of complex fluids can be measured by low-field nuclear magnetic resonance.

Magnetometric Resistivity(MMR) Method, which can use the power supply method of the traditional apparent resistivity method to measure the magnetic field. At present, the application research abroad is relatively extensive, but the domestic(China) research on the application of the MMR method is very few, and it is not even well-known. This paper is based on the MMR theoretical method under the point source DC condition, combined with the abnormal potential method and the modified Biot-Savart law, and using the three-dimensional numerical calculation method of the finite difference method to calculate the abnormal potential field, electric field, and magnetic field on the matlab2018a platform. Calculate, realize the multi-physics simulation in the electromagnetic field through Matlab platform programming, and verify the correctness of the algorithm by the spherical anomaly model with an analytical solution. Through the visual simulation of the three-dimensional data volume of the multi-physics field in the electromagnetic field, we can better understand the response mechanism of the electromagnetic field under DC conditions and grasp their three-dimensional spatial distribution rules. It is hoped that the research in this article can help the research of MMR Personnel better use this method for exploration.

The understanding of water quality and its underlying processes is important for the protection of aquatic environments enabling the rare opportunity of access to a domain expert. Hence, an explainable AI (XAI) framework is proposed that is applicable to multivariate time series resulting in explanations that are interpretable by a domain expert. The XAI combines in three steps a data-driven choice of a distance measure with explainable cluster analysis through supervised decision trees. The multivariate time series consists of water quality measurements, including nitrate, electrical conductivity, and twelve other environmental parameters. The relationships between water quality and the environmental parameters are investigated by identifying similar days within a cluster and dissimilar days between clusters. The XAI does not depend on prior knowledge about data structure, and its explanations are tendentially contrastive. The relationships in the data can be visualized by a topographic map representing high-dimensional structures. Two comparable decision-based XAIs were unable to provide meaningful and relevant explanations from the multivariate time series data. Open-source code in R for the three steps of the XAI framework is provided.

The symmetry properties of an ornament contain information about its civilisation and its interactions with other cultural sources. Two-dimensional periodic ornaments can be strictly classified into a limited set of 17 mathematical symmetry groups, also known as wallpaper groups. The collection of ornaments thus classified for a civilisation is characteristic of the cultural group and serves as a fingerprint to identify that group. If the distribution of wallpaper groups is available for several societies, mathematical methods can be applied to determine similarities and differences between the art practices of these communities. This method allows a systematic approach to the general ornamental practices within a culture and their interactions in the form of similarity of fingerprints. We test the feasibility of the method on examples of medieval Armenians, Byzantium, Seljuks first in Persia and then in Anatolia and among Arabs in the Middle East. For this purpose we present the distribution of the planar ornaments and calculate the Euclidean distances in pairs. We tested to what extend geographical and religious factors could account for the observed similarity of ornamental groups between cultures. The results suggest an intensive interaction between the Seljuk Turks and Arab craftsmen who produced the ornaments. Therefore the cultural interactions are religiously motivated.

Multispectral remote sensing data may contain component images which are heavily corrupted by noise and pre-filtering (denoising) procedure is often applied to enhance these component images. To do this, one can use reference images – component images having relatively high quality and which are similar to the image subject to pre-filtering. Here we study the following problems: how to select component images that can be used as references (e.g., for the Sentinel multispectral remote sensing data) and how to perform the actual denoising. We demonstrate that component images of the same resolution as well as component images of a better resolution can be used as references. Examples of denoising of real-life images demonstrate high efficiency of the proposed approach.

The most significant assumptions in the subdomain technique (i.e., based on the formal resolution of Maxwell's equations applied in subdomain) is defined by: “The iron parts (i.e., the teeth and the back-iron) are considered to be infinitely permeable so that the saturation effect is neglected”. In this paper, the author presents a new scientific contribution on improving of this method in two-dimensional (2-D) and in Cartesian coordinates by focusing on the consideration of iron. The subdomains connection is carried out in the two directions (i.e., x- and y-edges). For example, the improvement was performed by solving magnetostatic Maxwell's equations for an air- or iron-cored coil supplied by a direct current. To evaluate the efficacy of the proposed technique, the magnetic flux density distributions have been compared with those obtained by the 2-D finite-element analysis (FEA). The semi-analytical results are in quite satisfying agreement with those obtained by the 2-D FEA, considering both amplitude and waveform.

Alzheimer’s disease(AD) progression correlates with the propagation of hyperphosphorylated Tau (pTau) from the entorhinal cortex to the hippocampus and neocortex. Neutral sphingomyelinase2(nSMase2) is critical in the biosynthesis of extracellular vesicles (EVs), which play a role in pTau propagation. We recently conjugated DPTIP, a potent nSMase2 inhibitor, to hydroxyl-PAMAM-dendrimer nanoparticles which can improve brain delivery. We showed that dendrimer-conjugated-DPTIP (D-DPTIP) robustly inhibited pTau spread in an AAV-pTau propagation model. To further evaluate its efficacy, we tested D-DPTIP in the PS19 transgenic mouse model. Unexpectantly, D-DPTIP showed no beneficial effect. To understand this discrepancy, we assessed D-DPTIP’s brain localization. Using immunofluorescence and fluorescence-activated cell-sorting, D-DPTIP was found to be primarily internalized by microglia where it selectively inhibited microglial nSMase2 activity with no effect on other cell types. Furthermore, D-DPTIP inhibited microglia-derived EV release into plasma without affecting other brain-derived EVs. We hypothesize that microglial targeting allowed D-DPTIP to inhibit tau propagation in the AAV-hTau model, where microglial EVs play a central role in propagation. However, in PS19 mice, where tau propagation is independent of microglial EVs, it had a limited effect. Our findings confirm microglial targeting with hydroxyl-PAMAM dendrimers and highlight the importance of understanding cell-specific mechanisms when designing targeted AD therapies.

Green credit policy as an important tool to guide China's sustainable economic development, how to effectively play the function of capital deployment and improve the efficiency of industrial green innovation is an important issue facing the construction of ecological civilization. This paper uses China's Green Credit Guideline introduced in 2012 as a quasi-natural experiment , based on relevant panel data of industries from 2007 to 2018, uses the Super-SBM model including non-expected output to measure the green innovation efficiency of 35 industries in China, and constructs the PSM-DID model to explore how green credit policy impact on the green innovation efficiency of heavily polluted industries, the results show that : green credit policy significantly contributes to green innovation efficiency of heavily polluted industries with a lag. Further study finds that green credit policy pushes heavily polluted industries to improve green innovation efficiency by increasing financing cost and R&D investment; meanwhile, the heterogeneity test shows that the higher the state-owned share of industry, the greater the promoted effect of green credit policy on green innovation efficiency of heavily polluted industries. Finally, in order to accelerate the implementation of green credit policy and promote the green innovation efficiency of heavily polluted industries, relevant countermeasures are proposed from three aspects: banks, enterprises and government.