Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19, PON1, ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods: This was a cross-sectional, population-based study of 200 unrelated “Guthrie” cards specimens from newborns registered in the Puerto Rican Newborn Screening program (PRNSP) between 2004 and 2014. Taqman® SNP assay techniques were used for genotyping. Results: Minor Allele Frequencies (MAF) were 46% for PON1 (rs662), 41% for ABCB1 (rs1045642), 14% for CYP2C19*17, 13% for CYP2C19*2, 12% for P2RY12-H2 and 0.3% for CYP2C19*4. No carriers of the CYP2C19*3 variants were detected. All alleles and genotype proportions were found to be in Hardy-Weinberg equilibrium (HWE). Overall, there were no significant differences between MAFs of these variants in Puerto Ricans and the general population (n=453) of the 1,000 Genome project, except for the Yoruba in Ibadan from Nigeria (YRI, West-African ancestry; p<0.05). As expected, the prevalence of these markers in Puerto Ricans most resembled those in the 181 subjects from reference populations of the Americas. Conclusions: These prevalence data provide a necessary groundwork for future clinical studies of clopidogrel pharmacogenetics in Caribbean Hispanics.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

The pervasive presence of atmospheric pollution, particularly polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene, instigates aberrant cellular and tissue conditions, precipitating oxidative damage and inflammatory cascades conducive to the onset of cancer, notably mammary cancer. Given the hepatic metabolism of 7,12-dimethylbenz(a)anthracene, the imperative of employing natural antioxidants becomes apparent. In this study, we delve into the antioxidant and hepato-protective properties of Pistacia lentiscus against 7,12-dimethylbenz(a)anthracene-induced toxicity, alongside exploring its potential anticancer attributes. Our investigations unveil Pistacia lentiscus's anti-proliferative efficacy against human breast cancer cell lines. Notably, 7,12-dimethylbenz(a)anthracene-intoxication escalates body weight, disrupts lipid profiles, and incites serum oxidative damage. Concurrently, hepatic and renal oxidative stress ensue, accompanied by heightened antioxidant enzyme activity in the 7,12-dimethylbenz(a)anthracene-exposed-group compared to controls (p&lt;0.05). Nonetheless, Pistacia lentiscus co-administration rectifies biochemical imbalances, significantly attenuates oxidative stress aberrations, and augments antioxidant enzyme responses (p&lt;0.05). Importantly, histological analysis evinces Pistacia lentiscus's shielding effect against 7,12-dimethylbenz(a)anthracene induced hepatocyte injury and steatosis. Our findings underscore Pistacia lentiscus's robust anti-proliferative, antioxidant, and hepato-protective capacities, mitigating metabolic disturbances, oxidative stress propagation in liver and kidney functions, and potential histological alterations, thereby impeding 7,12-dimethylbenz(a)anthracene-induced mammary cancer initiation. We posit that Pistacia lentiscus may serve as a prophylactic agent against breast cancer instigated by this carcinogen.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology, with a major genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, the presence of autoantigens and several external factors. The major act of IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation leading to the development of psoriatic lesions. Genome wide association studies (GWAS) along offered a better view of psoriasis pathogenic pathways, with approximately one third of psoriasis genetic impact on psoriasis development is associated to MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Between the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, exhibiting less variety and the involvement of pathogenic bacteria, cand induce a burst of proinflammatory consequences, both cutaneous and gut microbiome being involved in psoriasis pathogenic process. A complex understanding of the major pathways that interplay in order to initiate and perpetuate psoriatic diseases and its associated comorbidities can help the current clinical practice by properly evaluating completely and individualized each patient and establish the proper therapeutic management.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p&lt;0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.

The body of evidence available in paediatrics population is limited for making clinical decisions regarding pharmacotherapy optimization of tacrolimus. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in paediatric population. This was a longitudinal cohort study, with two-year follow-up of 77 patients under 18 who had liver transplant over the period 2009-2012 at the Paediatric Hospital J. P Garrahan. Tacrolimus levels from day 5 to 2-year post-transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) were performed in liver biopsies of both the donor and the recipient. Recipients frequency of CYP3A5 *1 expression was 37.1% and 32.2% for Donors. Patient who received an organ expresser showed lower Co/dose especially after 90 days post-surgery. The role of each polymorphism is different according to days after transplantation proceeds and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phase.

Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40, and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters such as the area under the curve, C_max, and T_max varied according to the administered dose. AUC and C_max values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Particulate matter (PM) is one of the problems faced in environmental science. It has health effects on man and animals in both developed and developing countries. Research and efforts have been on it several years back. Policy statements and efforts have been published. This review paper is an added information on air pollution. In it, efforts were made in discussing these: classification, effects, methodology, case studies and source apportionment. It is hoped that this paper would contribute to existing knowledge on PM.

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and its binding activity to the EGFR antigen were evaluated. Furthermore, the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the significant accumulation and sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 minutes and 1, 2, 4 and 6 hours after IV and oral SS administrations. Plasma SA concentrations were determined using high performance liquid chromatography with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T_{1/2 el}) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 hours. Mean bioavailability of SA was 64%, and mean T_{1/2 el} was 1.90 ± 0.35 hours, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) required to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 hour in this study. Experiments on pharmacokinetic-pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low dose. Secondary aims were to identify associated behavioural side effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, a single intravenous bolus of 1 mg/kg racemic ketamine was administered over 2 minutes. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 minute, followed by an infusion at 0.01 mg/kg/min for 1 hour. Blood samples were collected from the left cephalic vein for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. However, levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady state racemic ketamine plasma concentration of 150 ng/mL was 1.7 mg/kg/h. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

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

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

Rare ginsenoside compound K (CK), is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development as well as ginsenosides-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bio-conversion processes. Current research shows that CK has a wide range of pharmacological actions including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, anti-inflammatory, and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signal-ing pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on nonalcoholic fatty liver disease, obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of the berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by developing a method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 324.4→308.3 for demethyleneberberine and 465.5→350.3 for IS. After oral administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution, and excretion of desmethylberberine in rats and mice were comparatively studied for the first time. The plasma concentration of desmethylberberine reached its peak within 5 min after oral administration in both rats and mice. The bioavailability of rats and mice was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of desmethylberberine in urine, feces and bile is 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on desmethylberberine.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Concrete is more stable than filler as a false roof in a downward approach type infill quarry, but the mechanical model of a concrete false roof is not clear. As a result, there has been limited application. Therefore, it is necessary to establish the mechanical model of a concrete artificial false roof to enhance the stability of the downward approach infill quarry. This paper combines theoretical analysis, model derivation, finite element analysis and field application methods. Firstly, the basic assumptions of thin plate theory and elasticity mechanics are used as the premise to establish the differential equations of the deflection curve of the concrete thin plate false roof. Then, the three types of bending moment generation of the concrete thin plate false roof are explored. Secondly, the relationship between the location of dangerous surface and dangerous point in hard-supported weak-slab structure and soft-supported weak-slab structure is analyzed, and the type of uniform load and calculation model of concrete thin-slab false roof are improved. Finally, according to the established mechanical model of thin slab false roof, finite element analysis and field application were carried out. The results show that there are three types of deflection curve differential equations in the concrete thin slab false roof perpendicular to the strike, and three extreme points exist in the middle section of the thin slab and on both sides of the surrounding rock. The hazardous surface of the hard-supported weak-slab structure is present at the intersection of the encircling rock and the thin-slab fake ceiling, with the perilous point situated on the top of this surface. The hazardous surface of the soft-supported weak-slab structure can be found in the centre section of the thin-slab fake ceiling, with the perilous point being located at the bottom of this surface. Moreover, the damage mode for both structures is that of maximum tensile stress damage. Upon conducting a finite element analysis, the results indicate that the concrete's maximum tensile stress is significantly high.

Chinese texts often feature a substantial volume of normative content, and their analysis has increasingly become a focal point in recent semantic analysis endeavors. Enhancing the effectiveness of text classification and clustering is pivotal in unveiling the intricate semantics within extensive textual data. Empirical research within the realm of computational social science has underscored the need for improved explanatory power when it comes to general text clustering methods applied to normative texts. This study introduces an innovative hierarchical clustering method that incorporates part-of-speech (POS) features and pioneers a novel semantic network model. It achieves this by amalgamating a POS-based feature weight calculation method with hierarchical clustering techniques. To assess its efficacy, the method is rigorously evaluated across three diverse text datasets, encompassing normative reports, news articles, and social media content. The experimental results unequivocally demonstrate the superior performance of the POS-HC method, surpassing the traditional TF and TF-IDF feature extraction methods in terms of clustering accuracy, and surpassing some existing clustering methods. Furthermore, its classification effectiveness exhibits notable advantages, particularly in the semantic classification of normative texts.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

In his best-selling book An Introduction to Probability Theory and its Applications, W. Feller established a way of ending the St. Petersburg Paradox by the introduction of an entrance fee, and provided it for the case in which the game is played with a fair coin. A natural generalization of his method is to establish the entrance fee for the case in which the probability of head is θ (0 < θ < 1/2). The deduction of those fees is the main result of Section 2. We then propose a Bayesian approach to the problem. When the probability of head is θ (1/2 < θ < 1) the expected gain of the St. Petersburg Game is finite, therefore there is no paradox. However, if one takes θ as a random variable assuming values in (1/2,1) the paradox may hold, what is counter-intuitive. On Section 3 we determine a necessary and sufficient condition for the absence of paradox on the Bayesian approach and on Section 4 we establish the entrance fee for the case in which θ is uniformly distributed in (1/2,1), for in this case there is paradox.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their size, size distribution and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and PEGylated nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, and can impact quality of life significantly. Tamsulosin and mirabegron combination therapy has been studied as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, 3-period, drug-drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), and a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron reduced by approximately 17%, when administered along with tamsulosin. No clinically significant changes in safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug-drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination therapy could be a promising treatment option for patients with OAB.

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

The advancement of autonomous capabilities in maritime navigation has gained significant attention, with a trajectory moving from decision support systems to full autonomy. This push towards autonomy has led to extensive research focusing on collision avoidance, a critical aspect of safe navigation. Among the various possible approaches, Dynamic Programming is a promising tool for optimizing collision avoidance maneuvers. This paper presents a DP formulation for collision avoidance of autonomous vessels. We set up the problem framework, formulate it as a multi-stage decision process, define cost functions and constraints focusing on the actual requirements a marine maneuver must comply with, and propose a solution algorithm leveraging parallel computing. Additionally, we present a greedy approximation to reduce algorithm complexity. Through case studies, we demonstrate the effectiveness of the proposed approach in navigating complex scenarios, contributing to the future of autonomous maritime navigation. Through case studies, we show the efficacy of our approach in navigating complex scenarios.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

This paper introduces an innovative energy circuit that challenges conventional understandings of energy conservation, marking a significant departure from traditional frameworks. Seeking to enhance energy generation within existing paradigms, this innovation holds promise for addressing pressing global issues such as the energy crisis and environmental sustainability, while also stimulating scientific inquiry. In contrast to prevalent misconceptions rooted in philosophical and scientific constraints, this study refutes the notion of generating energy from nothing and questions the viability of perpetual motion machines as conceptual models. Instead, it proposes a novel circuit design derived from an unconventional electrical short circuit, which is shown to disrupt the established principles of energy conservation. This circuit offers a transformative approach with diverse applications, including self-recharging capabilities for electric vehicles, bolstering microgrid infrastructure, and facilitating the integration of renewable energy sources. Transcending conventional scientific boundaries, this paper prompts philosophical reflections on the evolving nature of scientific exploration. Ultimately, the energy circuit represents a pivotal step towards mitigating the global energy crisis by reducing reliance on finite resources and fostering sustainability. The paper concludes by illustrating the circuit's potential to revolutionize energy systems and contribute to a more resilient and sustainable future.

One of the major concerns in structural health management (SHM) is the early detection of a growing crack. Using this, future damage due to crack propagation can be mitigated or eliminated by implementing proper repair and maintenance. Acoustic Emission (AE) is a non-destructive testing (NDT) method with potential applications for locating and monitoring fatigue cracks. The research presented in this paper focuses on SHM using AE. A novel AE signal analysis approach was proposed in order to detect crack initiation and assess small crack lengths. Experimental investigation indicated that initiation of a crack could be identified through the statistical analysis of the resulting features of the AE signals. A probabilistic AE-based model for small fatigue crack sizing was developed and the uncertainties of the model were estimated. In addition, a probabilistic model validation approach was implemented to confirm accurate estimation of the results. The outcome of this research can be used to evaluate the integrity of structures under fatigue loading. The proposed approach can also be applied as an approach to manage health and assess prognosis of structures.

Amid escalating urbanization, devising rational commercial space layouts is a critical challenge. Leveraging machine learning, this study uses a Back-propagation (BP) neural network to optimize commercial spaces in Weinan City's central urban area. The results indicate an increased number of commercial facilities with a trend of multi-centered agglomeration and outward expansion. Based on these findings, we propose a strategic framework for rational commercial space development emphasizing aggregation centers, development axes, and spatial guidelines. This strategy provides valuable insights for urban planners in small and medium-sized cities in the Yellow River Basin and metropolitan areas, ultimately showcasing the power of machine learning in enhancing urban planning.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Background: Tilmicosin, a macrolide antibiotic, has the potential to treat bacterial respiratory infections in donkeys. However, the pharmacokinetics of tilmicosin in donkeys have not been reported. Objectives: The aim of this study was to investigate the pharmacokinetics of tilmicosin in donkey plasma, urine and feces after a single intragastric administration to determine the suitability of tilmicosin for donkeys. Animals: A total of 4 healthy fattening male donkeys were selected with body weights of 148, 140, 145, and 135 kg, with an average body weight of 142.00 ± 4.95 kg. Methods: The donkeys were administered intragastrically a single dose of 10 mg·kg-1 BW tilmicosin. Blood, urine and fecal samples were collected. The concentrations of tilmicosin in plasma, urine, and feces were determined using high-performance liquid chromatography-tandem masss pectrometry. Results: After a single intragastric administration of 10 mg·kg-1 body weight, tilmicosin in donkey plasma reached a maximum concentration of 11.23 ± 5.97 mg·L-1 at 0.81 ± 0.11 h, with a mean residence time of 8.05 ± 2.44 h, a Cl/F of 0.48±0.22 L·kg-1·h-1, and a Vd/F of 9.28 ± 4.10 L·kg-1. The percentage of tilmicosin excreted through the urine of donkeys is (2.47±0.43)%, and the percentage excreted through the feces is (66.43±8.65)%. Conclusions: A single intragastric administration of 10 mg·kg-1 BW of tilmicosin to donkeys was rapidly absorbed and was able to achieve plasma concentrations of against pathogenic bacteria.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

Outdoor lighting is becoming increasingly widespread, and residents are suffering from serious light pollution as a result. Residents’ awareness of their rights to protection has gradually increased. However, due to the sometimes-inaccessible nature of residential vertical light incidence intensity data and the high cost of obtaining specific measurements, there is no appropriate hierarchic compensation for residents suffering from different degrees of light pollution. It is therefore important to measure light pollution levels and their damage at the neighborhood scale to provide residents with basic materials for proper protection and to create more politically suitable solutions. This article presents a light pollution assessment method that is easy to perform, is low-cost, and has a short data-processing cycle. This method can be used to monitor residential zone light pollution in other cities. We chose three open areas to test the spatial variation pattern of light intensity. The results are in accordance with spatial interpolation patterns and can be fit, with high precision, using the IDW method. This approach can also be used in 3 dimensions to quantitatively evaluate the distribution of light intensity distribution. We use a mixed-use zone in Beijing known as The Place as our case study area. The vertical illumination at the windows of residential buildings ranges from 2 lux to 23 lux; the illumination in some areas is far higher than the value recommended by CIE. Such severe light pollution can seriously interfere with people's daily lives and has a serious influence on their rest and health. The results of this survey will serve as an important database to assess whether the planning of night-time lighting is scientific and whether it provides residents with a basis for the protection of their rights.

Most empirical work on sources of economic growth for different countries lack country-specific empirical evidence to guide policy choices in individual developing countries and previous studies of factor productivity tend to focus on the entire economy or a single sector. In this study, we use the recently developed growth accounting tools to explicitly determine the sources of economic growth at both national and sectoral levels in Zambia between 1970 and 2013. We use data from World Development Indicators and Zambia’s Central Statistical Office. On average, total factor productivity (TFP) contributes about 5.7% to economic growth. Sectoral analysis shows that agriculture contributes the least to GDP and that within each sector; factors that contribute to growth differ. Structural transformation has been slow and contributed to the observed inefficiency. We outline the implications of the observed growth and provide recommendations.

The speed-density or flow-density relationship is a fundamental aspect of traffic flow theory. Single-regime models often face challenges in consistently fitting empirical data under diverse traffic conditions. This paper addresses the inaccuracies of single-regime models, attributing them not only to their functional forms but also to data dispersion and sample selection bias. To mitigate these issues, the data is segmented into day and night periods, leading to the creation of separate models for each. Calibration results, conducted on data from two freeways, Tehran-Karaj and Tehran-Qom, reveal distinct challenges, with the former exhibiting high dispersion and the latter showing low dispersion. Surprisingly, single-regime models demonstrate notable effectiveness when applied to distinct day and night data. Further analysis, categorizing data into day and night, results in reduced errors (20-60% improvement in R-Square), emphasizing the potential for enhanced accuracy by considering distinct regimes. Overall, the study underscores the significance of regime-specific considerations for accurate traffic flow modeling. Upon thorough evaluation, the study highlights the superiority of the neural network Multi-layer Perceptron (MLP) over traditional models. The research discusses the implications of incorporating day and night parameters into the models, emphasizing their potential for accuracy enhancement.

Background: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin was found to play a role in pain and function management. Methods: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. Results: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (particularly extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing and side effects. Conclusion: With chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing and side effects are discussed.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

This paper presents a compartmental model aimed at investigating the pharmacokinetics of medical THC after oral administration. The model was developed to be multi-compartmental, describing the kinetics of THC and its metabolites in bodily tissues. Utilizing the law of mass action, the model was converted into ordinary differential equations (ODEs), illustrating the rate of concentration changes of THC and its metabolites in each compartment. Subsequently, we applied the nonstandard finite difference (NSFD) method to construct numerical solution schemes. These schemes were implemented in the MATLAB program, along with estimated pharmacokinetic rate constants. The results of the investigation demonstrate that the simulation curves depicting the plasma concentration-time profiles of THC and THC-OH closely resemble the actual data samples, indicating that this model accurately describes the pharmacokinetics of medical THC and its metabolites. Moreover, the model exhibits predictive capabilities regarding the pharmacokinetics of THC and its metabolites in various tissues. Consequently, the model serves as a valuable tool for enhancing our understanding of the pharmacokinetics of THC and its metabolites and for guiding adjustments to dosage and administration durations for oral medical THC products.

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

In this paper we describe a nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions. Given $N$ independent observations, convexity theory shows that the NPML estimator is discrete with at most $N$ support points. The original infinite NPML problem then becomes the finite dimensional problem of finding the location and probability of the support points. The probability of the support points is found by a Primal-Dual Interior-Point method; the location of the support points is found by an Adaptive Grid method. Our method is able to handle high-dimensional and complex multivariate mixture models.An important application is discussed for the problem of population pharmacokinetics and a non-trivial example is treated.Our algorithm has been successfully applied in hundreds of published pharmacometric studies. In addition to population pharmacokinetics, this research also applies to empirical Bayes estimation and many other areas of applied mathematics.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.

The paper examines the various uncertainties encountered in high-frequency trading (HFT) environments and delves into the multiple challenges faced by HFT firms in navigating the Dodd-Frank Wall Street Reform and Consumer Protection Act (referred to as the "Dodd-Frank Act"), particularly during the initial stages of its enactment. These challenges include the ambiguity surrounding the definition of HFT, the lack of clarity regarding regulatory requirements and boundaries, inconsistencies in enforcement resulting from deviations in understanding the content, and the absence of detailed descriptions of the Act’s provisions. These hurdles significantly impact not only the daily operations of HFT firms but also pose higher demands on their long-term strategic planning and risk management. Drawing upon the Data, Information, Knowledge, Wisdom, and Purpose (DIKWP) model, this study employs an innovative analytical framework. Through the comprehensive application of conceptual space, cognitive space, and semantic space, it provides a systematic methodology for identifying and analyzing the aforementioned issues. This approach not only aids firms in better comprehending and adhering to complex regulatory requirements but also enables them to explore new business opportunities and competitive advantages while ensuring compliance.

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

Accurate measurement of systemic financial risk is critical to maintaining the stability of financial markets. Taking China as the subject of investigation, the Chinese Financial Stress Index (CFSI) indicator system was con-structed by integrating six dimensions and employing Gray Relation Analysis (GRA) for dimensionality reduction of the indicators. The CFSI was derived using the Attribute Hierarchy Model (AHM) method with the Criteria Importance Through the Intercriteria Correlation (CRITIC) method, and an Improved Gravitational Search Algorithm (IGSA) optimized Radial Basis Function Neural Network (RBFNN) was proposed for out-of-sample prediction of CFSI trends from 2024 to 2026. By analyzing the trend of financial pressure indicators, the relationship between financial pressure and economic activity can be effectively identified. The research findings indicate that: (1) The CFSI is capable of accurately reflecting the current financial stress situation in China; (2) The IGSA-RBFNN demonstrates good robustness and generalization capabilities, predicting that the CFSI index will reach a peak value of 0.543 by the end of 2024, and there exists a regular pattern of stress rebound towards the end of each year. The novel methodology benefits policymakers and regulatory authorities to formulate preventive measures and risk management by identifying potential risks and vulnerabilities in advance.

ESG (Environmental, Social, and Governance) responsibility fulfillment increasingly affects enterprise valuation. Although researchers debate about the precise effects, the prevailing view suggests a linear relationship between ESG performance and enterprise value. This study introduces a novel ESG responsibility performance metric through the Regulated Intermediary Model to delve into this relationship within the Chinese context. Our findings reveal an inverted U-shaped relationship between ESG performance and enterprise value, with financing constraints having a significant moderating effect. These findings remain robust after employing instrumental variables to mitigate potential endogeneity. Heterogeneity analysis demonstrates that this inverted U-shaped relationship is particularly pronounced in non-polluting and non-state-owned enterprises. Moreover, a comparison between equity and debt financing mechanisms underscores that improved ESG performance is associated with lower cost of equity financing, thereby enhancing enterprise value. Financial institutions are encouraged to leverage innovative financial instruments to diversify enterprise financing channels and alleviate financing constraints of enterprises that fulfill their ESG responsibilities.

Hepatic carboxylesterase 1(CES1) metabolizes many prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aim to develop a semi-physiologically based pharmacokinetic model(Semi-PBPK model) to simultaneously predict pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis(LC) patients. Six prodrugs(enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. The parameters including organ blood flows, plasma binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate(GFR) and gastrointestinal transit rate were introduced into the simulation. Pharmacokinetic profiles of these drugs and their active metabolites were simulated in 100 virtual subjects. The developed semi-PBPK model, following validation in healthy subjects, was extrapolated to LC patients. Most of the observations are within the 5% and 95% quantile of simulations from 100 virtual patients. The estimated AUC and Cmax are within 0.5-2-fold of observation. The sensitivity analysis showed that the decreased plasma exposure of active metabolite due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model has successfully predicted pharmacokinetics of CES1 substrates and their metabolites in healthy subjects and LC patients, which assists in tailoring dosages of CES1 substrates in LC patients.

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [¹²³I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [¹²³I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [¹²³I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [¹²³I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [¹²³I]IAZA and total radioactivity (total[¹²³I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [¹²³I]IAZA data from healthy volunteers rest. Following exercise stress, both [¹²³I]IAZA and total[¹²³I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t_1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t_1/2β of 195 and 290 min, respectively]. Total body clearance (CL_TB) and the steady state volume of distribution (V_ss) were 0.647 L/kg and 185 mL/min, respectively, for [¹²³I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[¹²³I]. The t_1/2β, CL_TB and V_ss values were comparable to those reported previously for rested volunteers. The t_1/2α was approximately 4-fold shorter for [¹²³I]IAZA and approximately 3-fold shorter for total[¹²³I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [¹²³I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t_1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [¹²³I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [¹²³I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Good governance in natural resource management (NRM) is one of the most challenging issues in developing countries that often inappropriately embedded in national policies and political agendas. It is, in fact, even more important for countries like Bangladesh with exceptionally high pressure and dependence on its natural resources for sustaining rural livelihoods. Globally, nowadays, good governance is considered as one of the key factor for achieving the goal of sustainable development and biodiversity conservation. Bangladesh, of late has responded to that global zeal by involving local communities in the management of country’s declining forest and other natural resources. The colonial legacy of the forestry sector of Bangladesh was planned and, managed as interim projects through donors’ prescriptions. Thus, institutions, management processes and conservation outcomes were problematic. The conventional approach adopted by colonial and post-colonial regimes for forest management also proved to be inefficient due to its top-down management system. The absolute dependency on donor support, and their prescription sometimes worsened the situation both ecologically and socially. Global, regional and local trends supported the need for a different dimension in the governance paradigms. The introduction of a pluralistic approach, known as co-management in protected areas (PAs) is an example of an attempt whereby shared governance mechanism are implemented to attain the desired goals of conservation that will also address the livelihoods and aspirations of communities living in and around PAs of the country. However, in designing future forest and PA regimes the concern of the external aid support and attached conditions remain a reality that needs to be addressed. Adequate attention should be given to our vanishing biodiversity, culture and community livelihoods through devising an appropriate governance mechanism recognizing and supporting local rights, access and participation in the environmental management. It is now time to mainstream the adhoc nature of governance according to our national conservation strategy and policy frameworks in order to achieve the goals and objectives of the Bangladesh NRM sector addressing the human and community right of people in the specific context of forest protected areas management.

Logistics plays an important role in globalized companies and contributes to the development of foreign trade. A large number of external conditions, such as recession and inflation, affect logistics. Therefore, managers should find ways to improve operational performance, enabling them to increase efficiency while considering environmental sustainability due to the industry’s large scale of energy consumption. Based on data collected from the financial reports of top global logistics companies, this study uses a DEA model to calculate corporate efficiency by implementing a Grey forecasting approach to forecast future sustainability values. Consequently, the study addresses the problem of how to enhance operational performance while accounting for the impact of external conditions. This research can help logistics companies develop operation strategies in the future that will enhance their competitiveness vis-à-vis rivals in a time of global economic volatility.

The scope of this study was twofold: first, to introduce a new method in examining measurement invariance, especially with large-scale studies where a large number of group comparisons are involved: the alignment approach, where only configural invariance is necessary to achieve measurement invariance. Second, to evaluate the psychometric robustness of this approach using real-life data. Particularly, we applied this approach to examine whether the factor structure of a cognitive ability test (PGAT) exhibits measurement invariance across the 26 universities of the Kingdom of Saudi Arabia. The sample consisted of 9,849 graduate students from 26 universities around the Kingdom. The results indicated a robust configural model suggesting that the P-GAT subscales were invariant across the 26 universities. Finally, the aligned factor mean values were estimated, and factor mean comparisons of every group’s mean with all other group means were conducted for both cognitive domains (Verbal and Quantitative). In both domains, King Saud University had the highest mean score among all universities. Moreover, its mean factor score was significantly higher than any other university besides Dammam University. On the other hand, several universities allocated at the northern and Southern borders of the country exhibited the lowest factor mean scores.

This study explores the Experience Economy dimensions within fishing tourism, adopting a data science perspective by employing web crawling for extensive data gathering on reviewer profiles from TripAdvisor. Utilizing Natural Language Processing (NLP) techniques, it scrutinizes the relationship between Experience Economy dimensions and user profiling aspects. Findings reveal "Entertainment" as the predominant dimension in tourist reviews, followed by "Aesthetic," "Educational," and "Escapist." Particularly notable are the frequent co-occurrences of "Entertainment"-"Aesthetic" and "Educational"-"Entertainment" pairs. The practical implications underscore the potential socioeconomic benefits of fishing tourism for local communities and fishermen, emphasizing the necessity for governmental support in terms of infrastructure, leadership, legislation, and financial backing to foster sustainable development in this sector. Notably, this research stands as a pioneering effort in its focus on Experience Economy dimensions and user profiling within the context of fishing tourism, drawing data from business pages and user profiles.

Aim was to develop a population pharmacokinetic model for methotrexate (MTX) during high-dose treatment (HDMTX) in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) and to describe the sources of variability. The study included 50 patients (1-18 years) who received 3 or 5 g/m2 of HDMTX. Nonlinear mixed effects modeling approach was applied for data analysis. Parameter estimation was performed by FOCEI, whereas stepwise covariate modeling was used to assess variability factors. The final two-compartment model incorporates the effect of body weight using allometric scaling and the influence of hemoglobin and serum creatinine on MTX clearance (CL). Population pharmacokinetic values for a typical 70 kg subject were: 11 L/h for clearance (CL), 46.5 L and 16.4 L for volume of central (V1) and peripheral compartment (V2), respectively, and 0.168 L/h for intercompartmental clearance (Q). According to the final model, MTX CL decreases with increasing serum creatinine, whereas a positive effect was captured for hemoglobin. A difference of almost 30% in MTX CL was observed among patients’ hemoglobin values reported in the study. In addition to renal function and body weight, it describes the influence of hemoglobin on CL, allowing better understanding of its contribution to HDMTX disposition.

In this paper, we present an experimental procedure to enhance the dimensional accuracy of fabrication via Stereolithography (SLA) of features at the micro-scale. Using a custom benchmark part, deviations in feature dimensions (micro-pores diameters and depths) were detected and measured by confocal microscopy. Samples characterization and experimental observations allowed the identification of inaccuracy sources, mainly due to the laser beam scanning strategy and to the incomplete removal of uncured liquid resin in post-processing (i.e., IPA washing). As a technology baseline, the measured dimensional errors on pores diameters were up to -46%. A compensation method of the nominal laser spot diameter (85m) was defined and implemented resulting in relevant improvements in dimensional accuracy of 9.8% and 11.3% on full-open pores diameter and depth, respectively. Further investigation was performed on a customized test part to adjust the calibration procedure. The measurements revealed that the estimate of the laser beam spot size is 968m. Measurements on micro-pores having different sizes revealed that a constant compensation parameter (i.e., C=85, 96, 120m) is not fully effective at the micro-scale, where average errors still remain at -24%, -18.8%, and -16% for compensations equals to 85, 96 and 120m, respectively. A further experimental campaign allowed the identification of an effective nonlinear compensation law where the compensation parameter depends on the micro-feature size C= f (D). Results show a sharp improvement in dimensional accuracy on micro-pore fabrication, with errors consistently below +8.2%. The proposed compensation method can be extended for the fabrication of any micro-features without restrictions on the specific technology implementation. Concerning the inaccuracy introduced by the laser path, experimentation with a customized part allowed the optimization of the part orientation to reduce the errors and their differences along the X and Y machine axes.

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

Modular steel buildings (MSBs) interlocking inter-module connections (IMCs) have piqued researchers’ interest. However, the existing literature has not yet studied the optimisation of its plate thicknesses. This paper, therefore, focuses on optimising interlocking (IMCs) plate thickness in (MSBs), leveraging previous experimental and numerical simulation methodologies. Various numerical models for four MSBs interlocking (IMCs) with plate thicknesses (4 mm, 6 mm, 10 mm, and 12 mm) were developed under compression loading conditions. The study’s novelty lay in its comprehensive parametric analysis, which evaluated the slip phenomenon in (MSBs) connections and introduced a slip prediction model validated against empirical data. Further innovative machine learning approach was utilised to predict slip values based on applied force through a random forest regression model trained using the 'Treebagger' function. Sensitivity analysis and comparisons with alternative methods were utilised to underscore the reliability and applicability of the findings. The results showed that 11.03 mm was the optimal plate thickness for interlocking (IMCs) in modular steel buildings, with up to 8.08% reduced material costs. Increasing plate thickness boosts its deformation resistance by up to 50.75%. ‘TreeBagger’ random forest for anomaly detection and machine learning improves slip prediction up to 7% at higher force levels.

Single-phase-to-ground fault in non-effectively grounded systems poses serious public safety concern. Along with increasing deployment of low-voltage (LV) sensors, new opportunities and ways are created for solving this traditional problem in distribution systems. A new approach, identifying primary single-phase-to-ground line fault and locating it through measurement data from smart sensors deployed in the secondary side of distribution transformers, is proposed in this paper. When a fault occurs in primary distribution feeder, the transient aerial mode voltage (AMV) of each LV smart sensor is calculated. The fault line can be identified by an abrupt change value of AMV at LV side. Next, by finding the position of the maximum value of this AMV from LV sensors on the fault line, the fault location can be pinpointed to two neighboring distribution transformers. The proposed method has been proven to be efficient and reliable by simulation studies.

The pharmacokinetic profile of fat-soluble vitamins A, E, K1, and D3 co-administered with liquid paraffin or water in an experimental rat model was investigated. Animals received a solution of the four vitamins orally through a probe, followed 10 minutes later by the administration of either the liquid paraffin product dissolved in water (Emuliquen Simple®) or water (control). Vitamin formulations were 20, 50, 0.30 and 0.10 mg/kg for vitamins A, E, K1, and D3, respectively. Blood samples were collected before dosing and at 0.17, 1, 2, 4, 8, and 24 hours post-dosing. Vitamin concentrations were quantified by liquid chromatography coupled with mass spectrometry. No relevant differences in the absorption of vitamins in terms of AUC0-last (area under the curve up to the last measurable concentration) or Cmax in the absence or presence of co-administration of the liquid paraffin product were observed. The difference of these parameters between the treatment groups for all vitamins was in the range of bioequivalence (≤ 20%). The liquid paraffin-based laxative product did not interfere with the absorption of vitamins A, E, K1, and D3 that are ingested in the diet, which is clinically relevant due to the high prevalence of functional constipation in children and adults.

The oil and gas industry in Nigeria, a vital contributor to the nation's economy, has long been associated with significant environmental challenges. Pollution, habitat destruction, and greenhouse gas emissions have raised global concerns about sustainability and corporate responsibility. This empirical study explores the relationship between environmental accounting practices and the financial performance of listed oil and gas companies in Nigeria. We investigated eight oil and gas companies that are publicly traded on the Nigerian Stock Exchange Market (NGX) as of January 17, 2022, from 2011 to 2022. The study employs Driscoll-Kraay standard errors and reveals that environmental accounting had significant effects on returns on assets, earnings per share, and liquidity ratio. The study revealed that the implementation of environmental accounting practices had diverse effects on the performance of oil and gas companies in Nigeria. The findings encourage policymakers and stakeholders in the sector to utilise the insights and design more effective regulations and incentives that promote environmental corporate responsibility. Also, valuable insights into the potential benefits and challenges associated with adopting environmental accounting practices, and influencing the decision-making processes of corporate stakeholders were provided to ensure sustainability in terms of improved financial performance of the oil and gas sector in Nigeria.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

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

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

Large-span post-tensioned (PT) beams play a crucial role in maximizing the benefits of post-tensioning techniques. Bonded and unbonded systems are prevalent, with the latter being more widespread in the United States. While bonded systems are advantageous for creating long spans when multiple tendons are grouped in ducts, limited literature exists on their demolition. In a case study, this paper addresses the unique challenge of demolishing large-span bonded post-tensioned beams due to a building's functional change. Emphasizing insights for engineers, it explores the use of cutting and dismantling methods, considering the presence of prestressed cables. The demolition process is distinctive due to the presence of numerous pre-stressed cables along the beams, necessitating a specialized and cautious cutting approach. This is accomplished through the use of a drilling technique that selectively distresses the tendons, ensuring they are not all affected simultaneously. An intriguing observation discussed in this paper pertains to the occurrence of horizontal cracks accompanied by loud sounds following the drilling process, offering insights from the design perspective of PT systems. The paper details an innovative method for safely demolishing large-span bonded PT beams, using ground-penetrating radar and computer models to navigate structural complexities and ensure nearby structures' safety.

The reviews usefulness has been the aim of several research studies. However, results regarding the significance of usefulness determinants are often contradicting, thus decreasing the accuracy of reviews’ helpfulness estimation. Also, bias in user reviews attributed to differences e.g. in gender, nationality, etc., may result into misleading judgments thus diminishing reviews’ usefulness. Research is needed for sentiment analysis algorithms that incorporate bias embedded in reviews, thus improving their usefulness, readability, credibility, etc. This study utilizes fuzzy relations and fuzzy synthetic evaluation (FSE) in order to calculate reviews’ usefulness by incorporating users’ biases as expressed in terms of reviews’ articulacy and sentiment polarity. It selected and analysed 95.678 hotel user reviews from Tripadvisor, for five nationalities. The findings indicate that there are differences among nationalities. The British are most consistent in their judgments expressed in titles and review documents. The British and the Greek review titles suffice to convey any negative sentiments. The Dutch use fewer words in their reviews than the other nationalities. This study suggests that fuzzy logic captures subjectivity which is often found in reviews, and it can be used to quantify users’ behavioral differences, calculate reviews usefulness, and provide the means for developing more accurate voting systems.

Due to related uncertainties brought by changes in energy consumption and the integration of rooftop photovoltaic systems, the accuracy and availability of load profiling data are difficult to achieve. However, project managers and planners use a precise load profile as a crucial tool when determining whether the feeder must be updated or de-loaded. The paper aims to create a non-intrusive monitoring system that predicts the synthetic load profiles behavior of energy consumption using a Light Gradient Boosted and Support Vector Machine (SVM) machine learning technique. The most effective ML algorithm is chosen, and it has the potential to be assessed and verified using validation curves, residuals model generation, and prediction error metrics based on the following key statistical indicators: Mean Absolute Error, Mean Square Error, Root Mean Square Error, R-Square, Root Mean Squared Logarithmic Error, and Mean Absolute Percentage Error. The most effective ML has the potential to be assessed and verified using validation curves, residual model generation, and prediction error metrics based on the following key statistical indicators. The result shows that the estimation of the Irms avg -based on LightGBM is more accurate than the SVM because of its quick, economical, and difficult to overfit, particularly with high-dimensional data, speed, and efficiency of the MAE (3.0698), MSE (15.2757), RMSE (3.9020), RMSLE (0.1433), and MAPE (0.0049) respectively. Additionally, the machine learning model shows that, when compared to the SVM, the LightGBM model had the highest accurate prediction, with R-Square values of 89.8%, 90.3%, and 88.5% for Irms_A_avg, Irms_B_avg, and Irms_C_avg, respectively for Brakfontein Substation supply region, and best represents a diverse customer base.

The research presented in this article is based on a strategic approach to a rural area in the mountainous region of Romania and is underwritten by specialists in the economy of mountainous regions in order to elaborate relevant solutions to complex problems relating to sustainable development. In essence, the research underlines and promotes the particularities of performing research for the identification and valuation of endogenous resources, that is, creating relevant strategic options for the durable development of the mountainous region, centered on the renewal of economic activities related to the existent endogenous resources, by using methods, work techniques, and instruments of strategic analysis. These factors are subordinate to the process of harmonization to the requirements of community development and environmental protection according to the new strategy for the development of the European Union 2020 (European Green Pact). This pact also emphasizes the necessity of involving the different factor categories of local accountability, promotion, activation, and the development of specific economic activities of different local contexts of sustainability. The research methodology used involves a case study whose complexity necessitated the use of quality and quantity research methods in order to underline specific elements of the rural area in the Romanian mountainous region. Specifically, we used a strategic diagnosis of the Romanian mountainous region using the PESTEL and SWOT models. In order to have relevant strategic options available, the continuity of research was achieved through the use of SOR analysis, creating a problem tree and an objectives tree.

The second article in the series presents the application of the Smoothed Particle Hydrodynamics (SPH) method to modelling of batch crystallisation in stirred tanks. A methodology to integrate the population balance equations (PBE) in parallel and independently from the Navier-Stokes equations is demonstrated. The benefits of the proposed methodology in terms of computational requirements, accuracy and availability of the crystal size distribution are discussed. The specific formulation of the SPH equations where the resulting system of ordinary differential equations is solved using the weighted contributions rather than numerically by solving a linear system of equations allows for massive parallelisation and a very loose coupling of the population balance and the fluid dynamics. It has been demonstrated, that the population balance equations can be solved on a Shared Memory Architecture (SMA) system using the OpenMP interface while the fluid dynamics equations being computed independently on a General Purpose Graphics Processing Unit (GPGPU) using the NVidia CUDA technology. This way, a significant portion of the computational overhead due to the large number of additional transport equations resulting from the discretisation of the population balance was removed: the SPH simulation coupled with 200 population balance equations was only 40% slower compared to SPH-only simulation. Two methods for the solution of population balance equations that preserve full crystal size distribution were implemented: discretised population balance (DPB) and method of characteristics (MOCH). The DPB equations are solved using the high-resolution finite-volume method with flux limiter and the effect of a large number of different flux limiters have been investigated. Both methods were validated using the case studies from the literature where an analytical solution can be derived. The developed models were applied to a numerical solution of coupled computational fluid dynamics and population balance equations to model a batch crystallization process. The effect of the hydrodynamics on the local temperature/supersaturation and the resulting crystal size distribution was captured and compared to the ideal mixing case. The simulation results from the DPB and MOCH methods were compared in terms of computational requirements and accuracy and MOCH selected as computationally more efficient and accurate.

Accurate classification of objects in 3D point clouds is a significant problem in several applications, such as autonomous navigation and augmented/virtual reality scenarios, which has become a research hot spot. In this paper, we presented a deep learning strategy for 3D object classification in augmented reality. The proposed approach is a combination of the GRU and LSTM. LSTM networks learn longer dependencies well, but due to the number of gates, it takes longer to train; on the other hand, GRU networks have a weaker performance than LSTM, but their training speed is much higher than GRU, which is The speed is due to its fewer gates. The proposed approach used the combination of speed and accuracy of these two networks. The proposed approach achieved an accuracy of 0.99 in the 4,499,0641 points dataset, which includes eight classes (unlabeled, man-made terrain, natural terrain, high vegetation, low vegetation, buildings, hardscape, scanning artifacts, cars). Meanwhile, the traditional machine learning approaches could achieve a maximum accuracy of 0.9489 in the best case.

In Indonesia, types of meat are still identified manually due to increasing prices for beef and buf-falo ahead of Idul Fitri. Traders mix beef with pork to thwart the beef scam. Haar wavelet and GLCM, GLCM with angles of 0°, 45°, 90°, and 135°, as well as matrices using contrast, correlation, energy, homogeneity, and entropy, are used in feature extraction. The following are the results of meat image classification testing using k-NN, Haar wavelet, and GLCM: The k-NN algorithm shows superiority in identifying fresh (99%), frozen (99%), and rotten (96%) meat texture images with the most fantastic accuracy results in every situation. Meanwhile, GLCM routinely provides good results, especially regarding the texture image of fresh meat (183.21) and rotten meat (115.79). However, despite delivering less throughput than k-NN and GLCM, Haar wavelets are still helpful, especially when dealing with fresh meat texture images (89,96).

As climate changes, our daily life has been much influenced by abnormal meteorological phenomena such as heavy rainfall, heat wave, heavy snowfall, and fine dust. Atmospheric air quality is worsening day by day and indoor air quality is also affected by interconnected daily activities throughout the inside and outside of buildings and houses. Nowadays, pollutants from various sources are emitted, transformed by sunlight, vapor, and ozone and transported into the city from country to country. Due to these reasons, there have been high demands to monitor the transportation of particulate matters and improve air quality. Monitoring of pollutants and identification of type and its concentration enables us to track and control its generation and consequently find out the solution. However, monitoring of pollutants, especially, particulate matter generation and its transportation is still not fully operated in atmospheric air due to its open nature and meteorological factors. Even though indoor air is relatively easy to monitor and control than outdoor in the aspect of specific volume and contaminant source, but it still needs to consider the meteorological parameters because indoor air is not fully separated from the outdoor air flow and contaminants transportation. In this study, optical approach using spectral sensor was attempted to reveal the feasibility of wavelength and chromaticity values of reflected light from specific particles. From the analysis of reflected light of various particulate matters according to different liquid additives, parameter studies were performed to investigate which experimental conditions can contribute to the enhanced selective sensing of particulate matters. Five different particulate matters such as household dust, soil, talc powder, gypsum powder and yellow pine tree pollen were utilized and observed to elucidate the relationship between property of particulate matter and detected light spectrum. Applicable approaches to assist current particle matter sensors and improve the selective sensing were suggested.

Background: pathophysiological changes like low cardiac output (LCO) impact pharmacokinetics, but its extent may be different throughout pediatrics compared to adults. Physiologically based pharmacokinetic (PBPK) modelling enables further exploration. Methods: A validated propofol model was used to simulate the impact of LCO on propofol clearance across age groups using the PBPK platform, Simcyp® (version 19). The hepatic and renal extraction ratio of propofol was then determined in all age groups. Subsequently, dose explorations were conducted under LCO conditions, targeting a 3 µg/mL (80-125%) propofol concentration range. Results: Both hepatic and renal extraction ratios increased from neonates, infants, children to adolescents and adults. The relative change in clearance following CO reductions increased with age, with the least impact of LCO in neonates. The predicted concentration remained within the 3 µg/mL (80-125%) range under normal CO and LCO (up to 30%) conditions in all age groups. When CO was reduced by 40-50%, a dose reduction of 15% is warranted in neonates, infants and children, 25% in adolescents and adults. Conclusions: PBPK driven, the impact of reduced CO on propofol clearance is predicted to be age-dependent, proportionally greater in adults. Consequently, age group specific dose reductions for propofol are required in LCO conditions.

To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.

One consequence of the global technological advancement in conventional metallurgy is the fast depletion rate of valuable minerals, which are also becoming increasingly difficult to find in pure and economically viable forms. This has spurred more interest in technologies that investigate ability of different microorganisms to mobilize valuable metals from their ores via diverse metabolic processes. This study was carried out therefore to isolate, identify and characterize iron solubilizing bacteria from Iron stones of Agbaja iron ore mining site of Kogi State, Nigeria. Crushed samples in the range of 0.25µm and 0.75µm particle sizes were cultured in a modified 9k media to facilitate bacterial growth and pure cultures were then isolated and sub-cultured for further bioleaching studies. Morphological and biochemical analysis suggests that some of the bacteria identified are members of Acidithiobacillus spp, Pseudomonas spp, and Leptospirillum spp. Studies conducted on pure cultures and mixed consortium of the identified organisms shows that a mixture of the three organisms leached iron ore to about 96.16%. Also results of growth pattern due to bacteria countafter 24-72hours of incubation ranged between 0.1×10³ cfu/ml and 12.3 ×10³ cfu/ml for Acidithiobacillus spp. The need to explore the molecular characteristics of these organisms with a view to generating more information on the quality/quantity of their DNA for future cloning activities was also investigated in this work. DNA was extracted using zymo fungal/bacterial extraction mini prep kit ^TM (cat #6001) and subsequently subjected to 1% agarose gel electrophoresis. Visible bands were obtained with Alpha Innotech Gel Documentation Machine. DNA amplification was carried out using a pettier based thermo cycler PCR machine and electrophoresed on 1.5% agarose gel. Results of the PCR shows a visible band corresponding to 1.5kbp using this primer 27F (5¹-GAGTTTGATCCTGGCTCAG-3¹) and 1492R (5^1-GGTTACCTTGTTACGACT-3¹). DNA purity check shows two of the bacteria possess very good qualities for sequencing for further molecular analysis.

(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLNs assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is at stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: we described a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary to evolve through future IDEAL stage 2b (multi-center studies) and stage 3 (randomized controlled trials) studies.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

Vibration monitoring is a critical aspect of assessing the health and performance of machinery and industrial processes. This study explores the application of machine learning techniques, specifically the Random Forest (RF) classification model, to predict and classify chatter—a detrimental self-excited vibration phenomenon—during machining operations. While sophisticated methods have been employed to address chatter, this research investigates the efficacy of a simplified RF model. The study leverages simulated vibration data, bypassing resource-intensive real-world data collection, to develop a versatile chatter detection model applicable across diverse machining configurations. The feature extraction process combines time-series features and Fast Fourier Transform (FFT) data features, streamlining the model while addressing challenges posed by feature selection. By focusing on the RF model’s simplicity and efficiency, this research advances chatter detection techniques, offering a practical tool with improved generalizability, computational efficiency, and ease of interpretation. The study demonstrates that innovation can reside in simplicity, opening avenues for wider applicability and accelerated progress in the machining industry.

This study delves into the intricate interplay of economic growth components, specifically focusing on Consumption and investment in Saudi Arabia from 2000 to 2022. Employing vector error correction models and cointegration techniques, we analyze the short- and long-term dynamics within the relationship of Consumption, investment, and economic growth. Granger causality analysis is also used to discern these pivotal variables' causal connections. Our empirical analysis reveals a persistent long-term cointegration relationship among the variables, underscoring the enduring nature of their interdependency. Furthermore, our findings highlight Consumption and investment's statistically significant positive impact on economic growth. Notably, the short-term analysis unveils a stable model characterized by an annual adjustment to equilibrium of 100%.Moreover, the Granger causality study demonstrates unidirectional causal linkages between Consumption, investment, and economic growth. These findings hold substantial implications for policy formulation in Saudi Arabia. Policymakers must grasp the ramifications of burgeoning prosperity and evolving private consumption patterns on future environmental outcomes. Achieving sustainable long-term results necessitates equal emphasis on bolstering private Consumption and fostering other facets of economic growth.

The quality of healthcare services is a very important indicator of social welfare in developed and emerging countries. Good quality levels are critical to ensuring patient safety, improving health outcomes, increasing patient satisfaction, optimizing resource utilization, and meeting regulatory requirements. The stable and sustainable operation of medical institutions urgently requires the establishment of a reliable and effective medical quality performance evaluation platform. However, the complexity of the evaluation process, involving numerous evaluators and the consideration of different subjective and objective criteria, poses significant challenges and essentially constitutes a group multi-criteria decision-making problem. This article uses the overall medical environment of the institution, medical service attitude, medical security, administrative service measures, etc. as measurement standards to deal with this challenge. It proposes a medical service quality measurement model suitable for both qualitative and quantitative analysis. In view of the heterogeneity of information, the two-tuple fuzzy language calculation method is introduced to enable evaluators to skillfully manage diverse information and effectively avoid potential information omission problems in the subjective evaluation integration process. The effectiveness and feasibility of the model were demonstrated by applying it to the operational framework of a medical institution in central Taiwan.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

A semi–numerical approach proposed many years ago for describing gravitational collapse in the post–quasi–static approximation , , , , is modified in order to avoid the numerical integration of the basic differential equations the approach is based upon. For doing that we have to impose some restrictions on the fluid distribution. More specifically, we shall assume the vanishing complexity factor condition, which allows for analytical integration of the pertinent differential equations and leads to physically interesting models. Instead, we show that neither the homologous nor the quasi–homologous evolution are acceptable since they lead to geodesic fluids, which are unsuitable for being described in the post–quasi–static approximation. Also, we prove that, within this approximation, adiabatic evolution also leads to geodesic fluids and therefore we shall consider exclusively dissipative systems. Besides the vanishing complexity factor condition, additional information is required for a full description of models. We shall propose different strategies for obtaining such an information, which are based on observables quantities (e.g. luminosity and redshift), and/or heuristic mathematical ansatz. To illustrate the method, we present two models. One model is inspired in the well known Schwarzschild interior solution, and another one is inspired in Tolman VI solution.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

This study examines the effectiveness of a comprehensive psychomotor development program combined with adapted football training for adolescents diagnosed with intellectual disabilities in Romania. Twelve participants, with a mean age of 17.42 years underwent a carefully designed intervention program spanning 36 weeks. The program aimed to enhance fundamental movement skills, integrate these skills into specialized football training, and culminate in a Unified 7-a-side Football Match. Results indicate significant improvements in psychomotor skills, including static and dynamic balance, pulse processing speed, and identified stimuli. Moreover, the intervention positively impacted social interaction among participants. Statistical analysis, employing Pearson Correlation Analysis and Paired Samples t-Test (One-Sample), compared assessments. Results revealed significant differences between pre- and post-intervention measurements, providing robust evidence of the program's efficacy. The positive correlations between physical parameters and social interaction highlight the interconnectedness between physical fitness and social engagement. Our findings suggest that improvements in physical abilities may contribute to increased social interaction among children with intellectual disabilities, underscoring the holistic nature of our intervention, which addresses multiple dimensions of development simultaneously. The findings underscore the holistic benefits of integrating psychomotor development and adapted football programs for adolescents with intellectual disabilities, emphasizing the importance of promoting inclusive physical activities for their overall well-being.

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100×2.1 mm, 5µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/ml range. The intra- and inter-day precisions for nimbolide were ≤ 12.6% and ≤ 13.9 % respectively. Intra-day accuracy ranged from 96.9% – 109.3% while inter-day accuracy ranged from 94.3% – 110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.

In this study, we address the formidable challenge of solving large-scale Max-Cut problems (MCP). We introduce a rapid computational procedure utilizing a hybrid 1-flip/r-flip local search heuristic. This innovative strategy significantly reduces the computational time required for MCP problems while consistently generating solutions of exceptional quality. The paper presents substantial computational insights, showcasing the effectiveness of our approach on very-large-scale Max-Cut instances with varying densities. Our proposed heuristic is rigorously evaluated by comparing its performance against a quantum annealing solver, leveraging a multi-start Tabu Search framework. The results underscore the potency of this unique combination as an efficient and effective solution for large-scale QUBO problems. Notably, our hybrid heuristic consistently delivers high-quality solutions within the stringent CPU time limits of 600 seconds, demonstrating its efficacy across Max-Cut instances ranging from 10,000 to 40,000 variables. This research contributes to advancing the state-of-the-art in large-scale QUBO problem-solving, offering a powerful and time-efficient approach with broad applicability.

This paper investigates the theoretical foundation for developing renewable geothermal resources locally. For this reason, we pay attention to the role of communities in geothermal development. This study presents arguments for a framework that approaches the geothermal resources as an endogenous factor of community development. To analyse it, we create a model that explains the local economic characters of the geothermal exploitation beyond its geological conditions. It aims to conceptualise a community based geothermal development standard referring to the endogeneity principle. Geothermal energy is given attention since the characteristics of this resource determine its use locally. We argue that the role of communities in geothermal exploitation is pivotal in the process of green growth for further expansion of geothermal energy use.

Energy consumption modelling is of critical importance for improving energy efficiency in the drive towards sustainable manufacturing. Modern manufacturing processes and machine tools are very complex as they involve interplay of several advanced technologies. Therefore, energy modelling of modern machine tools is a complex multi-disciplinary task. This paper proposes a systematic and practical framework to choose the appropriate modelling approach for a given industrial problem. The framework was validated by applying it to diverse industrial scenarios.

This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.

Background: A new access technique was developed to reduce postoperative adverse events after the extraction of impacted maxillary wisdom teeth. Hence, this study aimed to assess the occurrence of adverse events after extraction of maxillary impacted wisdom teeth using traditional or modified access. Methods: Two different surgical incision designs were used for bilateral wisdom tooth extractions in 30 patients. The traditional incision was performed distal to the second molar in the center of the tuberosity, followed by a buccal releasing incision. After tooth extraction the wound was secured by sutures. The new technique consists of an oblique incision from the distal palatal aspect of the tuberosity towards the buccal aspect of the second molar. After tooth extraction, cyanoacrylate glue was used on the wound. Results: Lower pain was reported by patients at the site treated with the new technique (p&lt;0.01). Edema, postsurgical bleeding, and hematoma were similar in both groups. The surgical time was shorter for the new technique (p&lt;0.01). Conclusions: The new technique applied for the extraction of impacted maxillary wisdom teeth reduced postsurgical pain and the duration of surgery.

Tourism is the main economic sector in the Balearic Islands (Spain) and hotel housekeepers (HHs) are a large occupational group, in which stress is becoming a major issue. This study aims at exploring in-depth factors perceived as stressors by HHs and key-informants, and their effects on work-life balance (WLB). A qualitative design with phenomenological approach was used, conducting six focus groups with 34 HHs and 10 individual interviews with key-informants. Results were analyzed adopting the job demands-resources model and a gender perspective. High demands –e.g work overload, time pressure, physical burden...-, lack of enough resources and little control –derived from role conflict, unexpected events...- were the most important factors explaining HHs’ stress. Additionally, this imbalance was perceived as leading to health problems –mainly musculoskeletal disorders-. Working schedule was mentioned as a facilitator to WLB, whereas an imbalance between job demands and resources led to work-home conflict –preventing them from enjoying leisure time-. Multiple roles at work and at home increased their stress. HHs experienced their job as invisible and unrecognised. Regarding practical implications, our recommendations for hotel organization include reducing workload and increasing resources, which would improve the job demands-resource balance, diminish negative mental and physical outcomes and improve WLB.

As technology and multimedia production have advanced, there has been a significant rise in attacks on digital media, resulting in duplicated, fraudulent, and altered data and the infringement of copyright laws. This paper presents a robust and secure digital image watermarking technique that has been implemented in the spatial domain and exploits the erratic and chaotic behaviour of the powerful elementary cellular automata rule-30. The crucial characteristics of the watermarking system, i.e., imperceptibility, capacity, and robustness, have been perfectly balanced by the suggested blind watermarking technique. In this approach, prior to embedding, the grayscale watermark image is downsized to its two Most Significant Bits (MSBs). Then, the 2-MSBs watermark is encrypted using an ECA rule-30 so as to level up the security attribute of the system. Then, the host image is scrambled using ECA rule-30 to distribute the watermark pixels throughout the host image and thus achieve the highest robustness against geometrical attacks. Finally, the encrypted watermark data is embedded into the scrambled host image using the ECA rule-30-based embedding key. The proposed method performs better in terms of imperceptibility, capacity, and robustness when compared to several systems with similar competencies. The simulation's findings demonstrate strong imperceptibility as evaluated by the Peak Signal-to-Noise Ratio (PSNR), which has an average value of 58.3735 dB and a high payload. The experimental outcomes, observed across a diverse range of standardized attack scenarios, unequivocally establish the ascendancy of the proposed algorithm over competing methodologies in the realm of image watermarking.

Live video streaming has become one of the main multimedia trends in networks in recent years. Providing Quality of Service (QoS) during live transmissions becomes a challenge due to the stringent requirements for low latency and minimal interruptions. This scenario has led to a high dependence on cloud services, implying a widespread usage of Internet connections, which constrains contexts where an Internet connection is not available. Thus, alternatives such as Mobile Ad Hoc Networks (MANETs) emerge as potential communication techniques. These networks operate autonomously with mobile devices serving as nodes, without the need for coordinating centralized components. However, these characteristics lead to challenges to live-video streaming, such as dynamic node topologies or periods of disconnection. Considering these constraints, this paper investigates the application of Artificial Intelligence (AI)-based classification techniques to provide adaptive streaming in MANETs. For this, a software-driven architecture is proposed to route stream in offline MANETs, predicting the stability of individual links and compressing video frames accordingly. The proposal has been implemented and assessed in a laboratory context, analyzing the model performance and QoS metrics. As a result, the model is implemented in a decision forest algorithm, which provides 95.9% of accuracy. Also, obtained latency values become assumable for video streaming, manifesting a reliable response for routing and node movements.

This work presents the results of an experimental socio-economic study conducted in two shanty towns of Messina as part of a systemic urban regeneration and fight against poverty program called Capacity. The study has shown that the development of a positive attitude towards the future and the confidence in others are associated with the development of the riskiest option, which is the one that can give the highest pay-off. The paper also illustrates the expected and unexpected outcomes of projects for individuals and the community, as well as the economic benefits for the public administration and the society of a strategy that reduces the reliance on social welfare measures as well as the local control exercised by organized crime.