Pharmacophores are an established concept for the modelling of ligand-receptor interactions based on the abstract representations of stereoelectronic molecular features. They became widely popular as filters for the fast virtual screening of large compound libraries. Until today a lot of effort has been put into the development of sophisticated algorithms and strategies to increase the computational efficiency of the screening process. However, hardly any focus was put on the development of automated procedures that optimise pharmacophores towards higher discriminatory power, which until today still has to be done manually by a human expert. In the age of machine learning, the researcher has become the decision-maker at the top level, outsourcing analysis tasks and recurrent work to advanced algorithms and automation workflows. Here we propose an algorithm for the automated selection of features driving pharmacophore model quality using SAR information extracted from validated QPhAR models. By integrating the developed method into an end-to-end workflow, we present a fully automated method that is able to derive best-quality pharmacophores from a given input dataset. Finally, we show how the QPhAR-generated models can be used to guide the researcher with insights regarding (un-)favourable interactions for compounds of interest.

BACKGROUND: Over the past few years, there has been an increasing interest to view the diagnosis of Familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare the intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study, conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges were surveyed. Indices of current reasoning ability (attention and concentration, memory, and executive functioning) were compared with an age-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD=9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n=17) of them had anxiety (HADS≥ 8), and twenty-five percent (n=13) had depressive symptoms (HADS≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: To date, there are only a few studies employing the biopsychosocial paradigm to investigate the FH population. The current study indicates that the FH population is marked by an impediment in almost all of the core features that are characteristically assessed by the biopsychosocial approach.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Molecular mimicry between human and microbial/viral/parasite peptides is common and for a long time is associated with the etiology of autoimmune disorders provoked by exogenous pathogens. Increasing evidence accumulated from the past years suggests a strong correlation between the SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between SARS-CoV-2 spike glycoprotein (S-protein and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. Totally the study revealed 14 pentapeptides shared by S-protein of SARS-CoV-2 and autoantigens of thyroid, pituitary, adrenal cortex and Langerhans’ islets beta-cells, 12 of them belong to immunoreactive epitopes of SARS-CoV-2. The discussion of the data links the results with clinical correlates of COVID-associated autoimmune endocrinopathies. Most common of them is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to marker autoantigens of this disease. Most important in pathogenesis of severe COVID-19, according authors’ opinion, can be autoimmunity against adrenals, because their adequate response prevents from excessive systemic action of inflammatory mediators which cause cytokine storm and hemodynamic shock. The criticism of antigen mimicry concept is given with a statement that peptide sharing is not a guarantee, but just a prerequisite of autoimmunity excess provocation. The last event occurs in carriers of certain HLA haplotypes and in case when shared peptide is used in antigen processing only [1 figure, 5 tables, bibliography 38 references].

Safe sample transport is of great importance for infectious diseases diagnostics. Various treatments and buffers are used to inactivate pathogens in diagnostic samples. At the same time, adequate sample preservation, particularly of nucleic acids, is essential to allow an accurate laboratory diagnosis. For viruses with single-stranded RNA genomes of positive polarity, such as foot-and-mouth disease virus (FMDV), however, naked full-length viral RNA can itself be infectious. In order to assess the risk of infection from inactivated FMDV samples, two animal experiments were performed. In the first trial, six cattle were injected with FMDV RNA (isolate A22/IRQ/24/64) into the tongue epithelium. All animals developed clinical disease within two days and FMDV was reisolated from serum and saliva samples. In the second trial, another group of six cattle was exposed to FMDV RNA by instilling it on the tongue and spraying it into the nose. The animals were observed for 10 days after exposure. All animals remained clinically unremarkable and virus isolation as well as FMDV genome detection in serum and saliva were negative. No transfection reagent was used for any of the animal inoculations. In conclusion, cattle can be infected by injection with naked FMDV RNA, but not by non-invasive exposure to the RNA. Inactivated FMDV samples that contain full-length viral RNA carry only a negligible risk of infecting animals.

Recent years have witnessed a boom of fashion bloggings sharing information about clothing and cosmetics on diverse social media platforms. Constant exposure to fashion-related digital information heavily impacts the cognition and behaviour of Chinese youth. Compared to the substantial studies on the impact of social media, scarce research has been conducted on how youth’s cognitive processing of fashion-related digital information interacts with motivational factors to determine the subsequent behaviour. This study made an initial attempt to address this issue by exploring the successive associations between clothing motivation (amotivation, controlled, and autonomous motivation), online critical thinking (for information credibility, objectivity, and relevance), and the subsequent behavioural intentions. A total of 1997 Chinese youths with diverse educational backgrounds voluntarily participated in the study. Results confirmed the direct links between clothing motivation and behavioural intentions, but these links were mediated by different online critical thinking skills. This study provides new insights for both practitioners and scholars in the fields of education, psychology, social media, and marketing.

Segmentation of brain tumor images is a major research topic in medical imaging to have a refined detection and understanding of abnormal masses in the brain. This paper proposes a new segmentation method, consisting of three main steps, to detect brain lesions using magnetic resonance imaging (MRI). In the first step, the parts of the image delineating the skull bone are removed to exclude insignificant data. In the second step, which is the main contribution of this study, the particle swarm optimization (PSO) technique is applied to detect the block that contains the brain lesions. The fitness function, used to determine the best block among all candidate blocks, is based on a two-way fixed-effects analysis of variance (ANOVA). In the last step of the algorithm, the K-means segmentation method is used in the lesion block to classify it as tumor or not. A thorough evaluation of the proposed algorithm is performed using the MRI database provided by the Kouba imaging center in Algiers, Algeria. Estimates of the selected fitness function are first compared to those based on the sum-of-absolute-differences (SAD) dissimilarity criterion and demonstrate the efficiency and robustness of the ANOVA. The performance of the optimized brain tumor segmentation algorithm is then compared to the results of several state-of-the-art techniques, including fuzzy C-means, K-means, Otsu thresholding, local thresholding, and watershed segmentation. The results obtained using Dice coefficient, Jaccard distance, correlation coefficient, and root mean square error (RMSE) measurements demonstrate the superiority of the proposed optimized segmentation algorithm over equivalent techniques.

This paper presents an analytical method for determining the bending stresses and deformations in prismatic noncircular profile shafts with trochoidal cross sections. The so-called higher trochoids can be used as form-fit shaft–hub connections. Hybrid (mixed) higher trochoids (M-profiles) were proposed in [1] and adapted to a practical industrial application in [2]. M-profiles combine the advantages of standardised polygon (DIN 32711 [3]) and spline (DIN 5486 [4]) contours used as shaft–hub connections for the transmission of torsional loads. In this study, the geometric and mechanical properties of the higher hybrid trochoids were investigated using complex functions to simplify the calculations. The pure bending stress and shaft deflection were determined for M-profiles using the bending theory formulated by Muskhelishvili [5]. The loading cases consisted of static and rotating bends. Analytical, numerical, and experimental results agreed well.

The study investigated the comparative effect organic fertilizers on the growth of Khaya senegalensis (Desr). Four treatments were used for this research: T1 20g of poultry manure, T2 (20g of cow dung), T3 (10g of poultry Manure + 10g of cow dung), T4 (Control experiment). Growth parameters such as diameter, plant height and number of leaves were measured weekly over a period of twelve (12) weeks. Data obtained were subjected to ANOVA and mean separated using Duncan Multiple Range Test. on the height parameter assessed on Khaya Senegalensis, the highest plant height mean of 8.40cm was recorded in treatment 1(20g of poultry Manure) while the lowest mean plant height 7.19cm was recorded in treatment 4 (Control experiment). Also, the highest mean stem diameter was recorded in Treatment 1 with a value of 0.309mm from while the least was recorded in Treatment 4 with mean value of 2.1175mm. However, highest mean number of leaves was recorded treatment 1 (20g of poultry manure) while the least was observed in T3 (10g of poultry Manure + 10g of cow dung). The results showed that organic manure has considerable effect on the growth of Khaya senegalensis seedlings and it use should be encouraged. T3 (10g of poultry Manure + 10g of cow dung) is hereby recommended to be the best of all in the growth of Khaya senegalensis.

In this review, several cost-effective thin-film coating methods which include dip-coating, spin-coating, spray-coating, blade-coating, and roll-coating are presented. Each method has its set of advantages and disadvantages depending on the type of application. Not all of them are appropriate for large-scale production due to their certain limitations. That is why the coating method should be selected based on the type and size of substrate including the resolution of the required thin-films. The sol-gel method offers several benefits, such as simplicity in fabrication, excellent film uniformity, the capacity to cover surfaces of any size and over vast areas, and a low processing temperature. Nevertheless, these coating methods are somewhat economical and well managed in low-budget laboratories. Moreover, the produced thin-films are homogeneous and have low-surface roughness. Furthermore, some other thin-film deposition methods such as physical vapor deposition (PVD) and chemical vapor deposition (CVD) are also discussed. Since CVD is not restricted to line-of-sight deposition, a characteristic shared by sputtering, evaporation, and other PVD processes, many manufacturing methods favor it. However, these techniques require sophisticated equipment and cleanroom facility. We aim to provide the pros and cons of thin-film coating methods and let the readers decide the suitable technique for their specific application.

A Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using Caenorhabditis elegans as a model system to study presenilin function, we found that loss of C. elegans presenilin orthologue, SEL-12, results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in sel-12 mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in sel-12 mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.

As one of the most promising ablative fillers, multi-walled carbon nanotubes (MWCNTs) have been used to improve the ablative resistance of Ethylene-Propylene-Diene Monomer (EPDM) insulators by facilitating the carbothermal reduction reaction of silica. However, the contribution of MWCNTs to char layer structure of the insulators was unclear. In this work, the effects of MWCNTs on char layer structure and ablative resistance were investigated in different EPDM-based insulators with and without silica. The results showed that adding only 3 phr MWCNTs can reduce the linear ablation rate of EPDM-based insulators without silica by 31.7%, while 6 phr MWCNTs are required to obtain similar results in EPDM-based insulators with silica. Both the char layer morphology of the two insulators gradually evolved into dense porous structure as MWCNTs content increasing, but their formation mechanisms are different. The XRD and Raman spectrum showed that different physicochemical reactions occurred around MWCNTs under different charring components. The proposed ablation mechanism was further verified by designing alternating multilayer distribution of MWCNTs and silica. This work can guide the construction of desirable char layer structure for increasing ablative resistance of EPDM-based insulators.

The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting from apoptosis and driving senescence. Thus, understanding the role of autophagy and its underlying signaling pathways is crucial for the development of new therapeutic strategies to overcome chemoresistance. We have previously reported that PKCη is a stress-induced kinase that confers resistance in breast cancer cells against chemotherapy by inducing senescence. Here we show that PKCη promotes autophagy induced by ER and oxidative stress and facilitates the transition from autophagy to senescence. We demonstrate that PKCη knockdown reduces both the autophagic flux and markers of senescence. Additionally, using autophagy inhibitors, such as chloroquine and 3-methyladenine, we show that PKCη and autophagy are required for establishing senescence in MCF-7 in response to oxidative stress. Different drugs used in the clinic are known to induce autophagy and senescence in breast cancer cells. Our study proposes PKCη as a target for therapeutic intervention, acting in synergy with autophagy-inducing drugs, to overcome resistance and enhance cell death in breast cancer.

The development of synthetic biology has enabled us to make massive progress on biotechnology and to approach research questions from a brand new perspective. In particular, the design and study of gene regulatory networks in vitro, in vivo and in silico, have played an increasingly indispensable role in understanding and controlling biological phenomena. Among them, it is of great interest to understand how associative learning is formed at the molecular circuit level. Noticeably, mathematical models have been increasingly used to predict the behaviors of molecular circuits. The Fernando’s model, which is thought to be one of the first works in this line of research using the Hill equation, attempted to design a synthetic circuit that mimics Hebbian learning in the neural network architecture. In this article, we carry out in-depth computational analysis of the model and demonstrate that the reinforcement effect can be achieved by choosing the proper parameter values. We also construct a novel circuit that can demonstrate forced dissociation, which was not observed in the Fernando’s model. Our work can be readily used as reference for synthetic biologists who consider implementing the circuits of this kind in biological systems.

Infectious keratitis (IK) represents a major cause of corneal blindness. This study aims to investigate the demographics, risk factors, microbiological characteristics and antibiotic susceptibility patterns of IK in Taiwan over the past 15 years. A retrospective population-based study was conducted using the Chang Gung Research Database. Patients with IK were identified by diagnostic codes for corneal ulcer from 2004 to 2019. Of 7807 included subjects, 45.2% of patients had positive corneal cultures. The proportion of contact lens-related IK declined, while that of IK related to systemic diseases grew. The percentage of isolated gram-positive bacteria surpassed that of gram-negative bacteria in the 15-year period. The prevalence of Pseudomonas aeruginosa showed a decreasing trend (p = 0.004), whereas coagulase-negative Staphylococcus (CNS) and Propionibacterium species were increasingly detected (p &lt; 0.001). Overall, the trend of antibiotic susceptibility of both gram-positive and gram-negative bacteria did not change throughout the study period. The susceptibility to the test antibiotics maintained over 90% in gram-negative isolates during 15 years. Vancomycin preserved 100% susceptibility to all gram-positive isolates. Since most tested antibiotics exhibited stable susceptibility over decades, this study reinforced that fluoroquinolones and fortified vancomycin continue to be good empiric therapies for treating bacterial keratitis in Taiwan.

Surface water availability is a fundamental environmental variable to implement effective climate adaptation and mitigation plans, as expressed by scientific, financial and political stakeholders. Recently published requirements urge the need for homogenised access to long historical records at a global scale, together with the standardised characterisation of the accuracy of observations. While satellite altimeters offer world coverage measurements, existing initiatives and online platforms provide derived water level data. However, these are sparse, particularly in complex topographies. This study introduces a new methodology in two steps 1) teroVIR, a virtual station extractor for a more comprehensive global and automatic monitoring of water bodies, and 2) teroWAT, a multi-mission, interoperable water level processor, for handling all terrain types. L2 and L1 altimetry products are used, with state-of-the-art retracker algorithms in the methodology. The work presents a benchmark between teroVIR and current platforms in West Africa, Kazakhastan and the Arctic: teroVIR shows an unprecedented increase from 55% to 99% in spatial coverage.A large-scale validation of teroWAT results in an average of unbiased root mean square error ubRMSE of 0.638 m on average for 36 locations in West Africa. Traditional metrics (ubRMSE, median, absolute deviation, Pearson coefficient) disclose significantly better values for teroWAT when compared with existing platforms, of the order of 8 cm and 5% improved respectively in error and correlation. teroWAT shows unprecedented excellent results in the Arctic, using a L1 products based algorithm instead of L2 one, reducing the error of almost 4 m on average. To further compare teroWAT with existing methods, a new scoring option, teroSCO, is presented, measuring the quality of the validation of time series transversally and objectively across different strategies. Finally, teroVIR and teroWAT are implemented as platform-agnostic modules and used by flood forecasting and river discharge methods as relevant examples. A review of various applications for miscellaneous end-users is given, tackling the educational challenge raised by the community.

Glass fibers slowly dissolve and age when exposed to water molecules. Such a phenomenon also occurs when glass fibers are inside fiber-reinforced composites protected by the matrix. This en-vironmental aging results in the deterioration of the mechanical properties of the composite. In structural applications, GFRPs are continuously exposed to water environments for decades (typically design lifetime is around 25 years or even more). During their lifetime, these materials are affected by various temperatures, pH acidity levels, mechanical loads, and the synergy of these factors. The rate of the degradation process depends on the nature of glass, sizing, fiber orientation, and environmental factors such as acidity, temperature, and mechanical stress. In this work, degradation of typical industrial grade R-glass fibers, when inside an epoxy fiber-reinforced composite, is studied experimentally and computationally. A Dissolving Cylinder Zero-Order Kinetic (DCZOK) model was applied and could describe the long-term dissolution of glass composites, considering the influence of fiber orientation (hoop vs transverse), pH (1.7, 4.0, 5.7, 7.0, and 10.0), and temperature (20, 40, 60, and 80 °C). The limitations of the DCZOK model and effects of sizing protection, accumulation of degradation products inside the composite, and water availability were discussed. Experimentally dissolution was measured using ICP-MS. Like for the fibers, for GFRPs also, the temperature showed an Arrhenius-type influence on the ki-netics, increasing the rate of dissolution exponentially with increasing temperature. Similar to fibers, GFRPs showed a hyperbolic dependence on pH. The model was able to capture all of these effects, and the limitations were addressed.

One of the major areas of research in a business setting has been the effect of the transformational leadership style on workplace engagement. Much debate has taken place on the definitions of both constructs but in recent years, general agreement appears to have been reached on the Multi-Factor Leadership Questionnaire (MLQ) (Avolio and Bass, 2004) as the measure of transformational leadership, and on workplace engagement measured by the Utrecht Work Engagement Scale (UWES) (Schaufeli et al, 2006). However, in the education setting, there is much less agreement on the definition of transformational leadership. Furthermore, there is less of a focus on workplace engagement than in the business field even though available evidence suggests that workplace engagement worldwide is in crisis. This study sought to address both the lack of agreement on the transformational leadership definition and the lack of focus on workplace engagement in educational research by means of a meta-analysis. The meta-analysis resulted in a significant pooled effect size although due recognition is given to the endogeneity problem in causal studies. The endogeneity issue together with the results of the meta-analysis are discussed with a view to furthering educational leadership research.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

Antibiotics have been used in various fields such as livestock farm and fish farm as well as hospital in order to treat diseases caused by bacteria. However, the antibiotics that are not completely decomposed, but remains as residue and discharge to aquatic environment, can cause an imbalance in the gut flora of host, as well as regulate abnormal host gene regulatory system. We investigated the effects of chronic exposure with the low concentrations of erythromycin and ampicillin on gut microbiome and immune and stress-related gene expression using Korea native ricefish (Oryzias latipes). As a result of microbiome analysis, the proportion of Proteobacteria was increased in the ricefish when exposed to erythromycin and ampicillin chronically, whereas the proportion of other bacterial phyla decreased. In addition, the immune and stress-related genes were significantly influenced in the ricefish under the chronic antibiotics exposure. These results show that the internal microbial flora and the host gene expression are susceptible even in the low concentration of chronic antibiotic existing environments. This study provides the importance of the appropriate use of antibiotics dose to maintain the sustainable and healthy aquaculture industry and water ecosystem.

The TREX1 exonuclease degrades DNA to prevent aberrant nucleic acid sensing through the cGAS-STING pathway, and dominant Aicardi-Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.A136V and p.R174G TREX1 variants, respectively. Genetic findings, obtained by a customized panel including 183 genes associated with monogenic stroke, were combined with interferon signature testing and biochemical assays to determine the mutations’ effects in vitro. Comprehensive studies revealed no pathological impact on TREX1 enzymatic function for the p.A136V variant. The p.R174G variant modestly altered exonuclease activity consistently with perturbation of substrate interaction rather than catalysis, which represents the first robust enzymological data for a TREX1 variant identified in a CADASIL-like patient. In conclusion, functional analysis allowed us to interpret the impact of TREX1 variants on patients’ phenotypes. Whilst Patient A’s manifestations are not related to p.A136V variant, Patient B’s phenotype is likely related to the p.R174G variant. Further functional investigations of TREX1 variants found in CADASIL-like patients are warranted to establish a causal link and interrogate the molecular disease mechanism.

Abstract Universities have the potential, and the responsibility, to take on more ecological and relational approaches to facilitating learning-based change in times of interconnected socio-ecological crises. Signs for a transition towards these more regenerative approaches of higher education (RHE) that include more place-based, ecological, and relational, ways of educating can already be found in niches across Europe (see for example the proliferation of education-based living labs, field labs, challenge labs). In this paper, the results of a podcast-based inquiry into the design practices and barriers of enacting such forms of RHE are shown. This study revealed seven educational practices that occurred across the innovation niches. It is important to note these practices are enacted in different ways, or are locally nested in unique expressions, For example, while the ‘practice’ of Cultivating Personal Transformations was represented across the included cases, the way these transformations were cultivated were unique expressions of each context. These RHE-design practices are derived from twenty-six narrative-based podcasts as interviews recorded in the April through June 2021 period. The resulting podcast (The Regenerative Education Podcast) was published on all major streaming platforms from October 2021 and included 21 participants active in Dutch Universities, 1 in Sweden, 1 in Germany, 1 in France, and 3 primarily online. Each episode engages with a leading practitioner, professor, teacher, and/or activist that is trying to connect their educational practice to making the world a more equitable, sustainable, and regenerative place. The episodes ranged from 30 to 70 minutes in total length and included both English (14) and Dutch (12) interviews. These episodes were analyzed through transition mapping a method based on story analysis and transition design. The results include seven design practices such as Cultivating Personal Transformations, Nurturing Ecosystems of Support, and Tackling Relevant and Urgent Transition Challenges, as well as a preliminary design tool that educational teams can use together with students and local agents in (re)designing their own RHE to connect their educational praxis with transition challenges.

In recent years, natural polymers have replaced synthetic polymers for antibacterial orthopedic applications owing to their excellent biocompatibility and biodegradability. Zein is a biopolymer found in corn. The lacking mechanical stability of zein is overcome by incorporating bioceramics e.g. mesoporous bioactive glass nanoparticles (MBGNs). In present study, pure zein and zein/Zn-Mn MBGNs composite coatings were deposited via electrophoretic deposition (EPD) on 316L stainless steel (SS). Zn and Mn were co-doped in MBGNs in order to make use of their antibacterial and osteogenic potential, respectively. A Taguchi design of experiment (DoE) study was established to evaluate the effect of various working parameters on the morphology of the coatings. It was observed that coatings deposited at 20 V for 5 min with 4 g/L concentration (conc.) of Zn-Mn MBGNs showed highest deposition yield. Uniform coatings with highly dispersed MBGNs were obtained adopting these optimized parameters. Scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-Ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR) were employed to investigate the morphology and elemental composition of zein/Zn-Mn MBGNs composite coating. Surface properties i.e. coating roughness and wettability analysis concluded that composite coatings were appropriate for cell attachment and proliferation. For adhesion strength various techniques including tape test, bend test, pencil hardness test, and tensile test were performed. Wear and corrosion analysis highlighted the mechanical and chemical stability of coatings. Colony forming unit (CFU) test showed that zein/Zn-Mn MBGNs composite coating was highly effective against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) due to the presence of Zn. The formation of hydroxyapatite (HA) like structure upon immersion in simulated body fluid (SBF) validated the in vitro bioactivity of the coating. It was concluded that zein/Zn-Mn MBGNs coating synthesized in this work can be used for bioactive and antibacterial orthopedic applications.

The present paper deals with the investigation, at conceptual level, of the performance of short-medium-range aircraft with hydrogen propulsion. The attention is focused on the relationship between figures of merit related to transport capability, such as passenger capacity and flight range, and the parameters which drive the design of liquid hydrogen tanks and their integration with a given aircraft geometry. The reference aircraft chosen for such purpose is a box-wing short-medium-range airplane, object of study within a previous European research project called PARSIFAL, capable to cut the fuel consumption per passenger-kilometre up to 22%. By adopting a retrofitting approach, non-integral pressure vessels are sized to fit into the fuselage of the reference aircraft, under the assumption that the main aerodynamic, flight mechanic and structural characteristics are not affected. A parametric model is introduced to generate a wide variety of fuselage-tank cross-section layouts, from a single tank with the maximum diameter compatible with a catwalk corridor to multiple tanks located in the cargo deck , and an assessment work-flow is implemented to perform the structural sizing of the tanks and analyse their thermodynamic behaviour during the mission. This latter is simulated with a time-marching approach that couples the fuel request from engines with the thermodynamics of the hydrogen in the tanks, which is constantly subject to evaporation and, depending on the internal pressure, vent-ed-out in gas form. Each model is presented in detail in the paper and results are provided through sensitivity analyses to both the technology parameters of the tanks and the geometric parameters influencing their integration. The guidelines resulting from the analyses indicate that light materials, such as the Aluminium alloy AA2219 for tanks’ structure and polystyrene foam for the insulation, should be selected. Preferred values are also indicted for the aspect ratios of the vessel components, i.e. central tube and endcaps, as well as suggestions for the integration layout to be adopted depending on the desired trade-off between passenger capacity, as for the case of multiple tanks in the cargo deck, and achievable flight ranges, as for the single tank in the section.

With the ever-increasing popularity of unmanned aerial vehicles and other platforms providing dense point clouds, universal filters for accurate identification of ground points in such dense clouds are needed. Many filters have been proposed and are widely used, usually based on the determination of an original surface approximation and subsequent identification of points within a predefined distance from such surface. In this paper, we present a new filter. This Multi-view and shift rasterization algorithm (MVSR) is based on an entirely different principle, i.e., on the identification of just the lowest points in individual grid cells, shifting the grid along both planar axis and subsequent tilting of the entire grid – after each of these steps, one lowest point per cell is detected. The principle is presented in detail and compared both visually and numerically to other commonly used ground filters (PMF, SMRF, CSF, ATIN) on three sites with different ruggedness and vegetation density. Visually, the MVSR filter showed the smoothest and thinnest ground profiles, with ATIN the only filter performing comparably (although the profiles were somewhat thicker and not as complete as MVSR-acquired ground). The same was confirmed when comparing ground filtered by other filters with the MVSR-based surface. The goodness of fit with the original cloud is demonstrated by the root mean square deviations (RMSD) of the points from the original cloud found below the MVSR-generated surface (ranging, depending on site, between 0.6-2.5 cm). ATIN again performed closest to MVSR, with RMSDs of ground filtered points found above MVSR-based surface at individual sites ranging between 4.5-7.4 cm. The remaining filters performed comparable in the simplest flat area but poorly in rugged and much-vegetated sites, with RMSDs above the MVSR surface ranging at such sites from 21 to 95 cm. In conclusion, the novel filter presented in this paper performed outstandingly at all sites, identifying the ground points with great accuracy while filtering out the maximum of vegetation/above-ground points. The filter dilutes the cloud somewhat; in such dense point clouds, however, this can be perceived rather as a benefit than as a disadvantage.

Comparing sonification with visualization is like comparing apples and oranges. While visualizations are ubiquitous to the public and have established names, principles, application areas, and sophisticated designs, sonifications tend to be unique, self-made and completely new to users. In this study we developed a rudimentary visualization that is related closely to the principle of the sonification designs that we want to evaluate. In addition, we implemented a prototypical sonification that uses the most common mapping principles. Experiment results show that participants perform similarly well using the rudimentary visualization and the prototypical sonification, which is much better than chance but significantly worse than using our new sonification results. We therefore argue that both rudimentary visualization and prototypical sonifications can serve as a suitable benchmark to evaluate new sonifications designs against.

The fault diagnosis of the gearbox is primarily based on the analysis of the harmonic response. However, the generation mechanism of the harmonic response of the gear pair is still not distinctly explained in a healthy gearbox. Therefore, this paper is dedicated to establishing a dynamic model of the gearbox for this issue. In this model, the contact force of the bearing and the meshing stiffness of the gear pair are determined by the Hertz theory and the potential energy method, then the shaft motion is used as the connection to establish the coupling relationship between the gear pair and the bearing. After this dynamic model is confirmed by experiments and existing models, the coupling relationship inside the gearbox and the harmonic response of the gear pair are studied using this model. The result demonstrates that a closed control loop is formed due to the vibration transmission between the gear pair, the bearing and the shaft, and there is a strong coupled vibration between the gear pair and the bearing in the gearbox. Due to the generation of the center distance error, misalignment angle and disorganized meshing process of the gear pair, the meshing stiffness is altered, which excites the harmonic response of the gear pair. When the speed of the gearbox is increased, although the vibration amplitude of the gearbox is increased, the system predominantly vibrates at the fundamental frequency, and the harmonic of the gear pair is also shifted to the low frequency band.

Exploration practices have proven that over mature shale gas exhibits a feature of carbon isotope reversal. The geochemical statistics indicate that the wetness (C2-C5/C1-C5) of shale gas with carbon isotope reversal is less than 1.8%. In addition, the magnitude of carbon isotope reversal (δ13C1- δ13C2) for the over mature shale gas presents a parabolic variation with decreasing wetness. δ13C1-δ13C2 increases with decreasing wetness within a wetness range of 0.9% ~1.8% and then decreases with decreasing wetness at wetness < 0.9%. The CH4 cracking experiment demonstrates that CH4 polymerization occurring in the early stage of CH4 cracking is an important factor involved in isotope reversal of over mature shale gas. Moreover, δ13C1- δ13C2 decreases with an increase in experimental temperature prior to CH4 substantial cracking. The values of δ13C1 and δ13C2 tend to equalize during CH4 substantial cracking. The δ13C1-δ13C2 of mud gas present at different depths during shale gas drilling in Sichuan Basin increases initially, then decreases with further increase in the depth and finally tends to zero, with only a trace hydrocarbon gas being detectable. Statistical data suggests that the shale gas production in Sichuan Basin decreases with the decreasing δ13C1-δ13C2 value and wetness. Thus, δ13C1-δ13C2 and wetness could potentially serve as useful criteria to screen CH4 cracking degree and to determine the largest depth of natural gas exploration. Great care should be taken during shale gas exploration in deeper layers, with wetness and δ13C1-δ13C2 less than 0.2% and 1%, respectively, since very low wetness (<0.2%) and δ13C1-δ13C2 (<1%) might be indicative of CH4 substantial cracking in a geological setting.

The geographic variability of the dorsal pattern (DP) of the Italian wall lizard, Podarcis siculus, across its native range was studied with the aim to understand whether the distributions of this phenotypic trait were more shaped by allopatric differentiation rather than adaptive processes. A total of 1298 georeferenced observations scattered across the Italian peninsula and the main islands (Sicily, Corsica and Sardinia) were obtained from citizen science databases and five DPs were characterized by different shapes of the dark pattern (“reticulated”, “campestris”, “reticulated/campestris” and “striped”) or by absence of it (“concolor”). Frequencies of different DP phenotypes differ between the two main mtDNA lineages settled in central-northern and in southern Italy respectively. This pattern may be indicative of a role of long-term allopatric historical processes in determining the observed pattern. The analysis also identified a putative wide area of secondary contact, in central southern Italy, characterized by high diversity of the DP. Generalized Linear Models (GLMs), used to estimate a possible association between bioclimatic variables and the observed phenotypic variation, showed that each of the five DPs is correlated to different environmental factors and show different distribution of areas with high probability of occurrence. However, for all but one of the DPs, the area with the greatest probability does not correspond exactly to the real distribution of the DP. Conversely, the “concolor” phenotype does not seem related to any particular mtDNA lineage and it shows a preference for areas with high temperature and low rainfall. This is in agreement with the expectation of low amount of melanin of the dorsal pattern that, in the study areas, is characterized by a light uniform coloration which could confer a better thermoregulation ability in high temperatures environments avoiding overheating.

A digital text abstract presents the essential information of an article, and we can find the trend and value of the research by analyzing it rigorously and digging up knowledge. Therefore, this study focuses on the abstracts of index journals in China and Taiwan from July 2010 to June 2020 (a total of 3,283 abstracts). Through the concepts of text mining and natural language processing (NLP), it constructs processes such as text retrieval, text segmentation and word cloud analysis, TF-IDF weight analysis, co-word analysis, network analysis, and trend analysis, and analyses a large amount of text data. The results show that the scope of research in China covers the fields of social sports and sports science, and research in Taiwan covers both natural and social sciences. The network diagram highlights the richness of sports-related research fields in the two regions, but research on sports philosophy is relatively rare. It is suggested that all disci-plines/departments should re-allocate the same resources, so as to show a balanced development trend and help expand a new chapter in the sports academic field.

COVID-19 vaccine hesitancy is considered responsible for the lower rate of acceptance of vaccines in many parts of the world. However, sources of this hesitancy are rooted in many social, political, and economic factors. This paper strives to find the most important variables in predicting the COVID-19 vaccination uptake. We introduce an explainable machine learning (ML) framework to understand the COVID-19 vaccination uptake around the world. To predict vaccination uptake, we have trained a random forest (RF) regression model using a number of sociodemographic and socioeconomic data. The traditional decision tree (DT) regression model is also implemented as the baseline model. We found that the RF model performed better than the DT model since RF is more robust to handle nonlinearity and multi-collinearity. Also, we have presented feature importance based on impurity measure, permutation, and Shapley values to provide the most significant unbiased features. It is found that electrification coverage and Gross Domestic Product are the strongest predictors for higher vaccination uptake, whereas the Fragile state index (FI) contributed to lower vaccination uptake. These findings suggest addressing issues that are found responsible for lower vaccination uptake to combat any future public health crisis.

In West Africa, research on the hepatitis E virus (HEV) is barely covered despite the recorded outbreaks. The still low level of access to safe water and adequate sanitation is one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Here, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A total of 1,227 consenting participants attending antenatal clinics responded to our questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. HEV global seroprevalence was 7.9% with 0.5% and 7.4% for HEV IgM and HEV IgG, respectively. One participant's sample was IgM/IgG positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p&lt;0.0001), by the regularity of income (p=0.0043) and by access to sanitation services (p=0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental and behavioral aspects for a better management of HEV infection in Senegal.

Important current limitations of the implementation of Evidence-Based Practice (EBP) in the rehabilitation field are related to the validation process of new technologies and interventions. Indeed, most of the strict guidelines that have been developed for the validation of new drugs (i.e., double or triple blinded, strict control of the doses and intensity) cannot – or only partially – be applied in rehabilitation. Well powered high quality randomized controlled trials are more difficult to organize in rehabilitation (e.g., longer duration of the intervention in rehabilitation, more difficult to standardize the intervention compared to drugs’ validation studies, limited funding’s since not sponsorized by big pharma companies), which reduces the possibility of conducting systematic reviews and meta-analyses, as currently high level of evidence is sparse. The current limitations of EBP in rehabilitation are presented in this paper and innovative solutions are suggested such as: technology-supported rehabilitation systems, continuous assessment, pragmatic trials, rehabilitation treatment specification systems, and advanced statistical methods, to tackle the limitations to increase the quality of the research in rehabilitation. The development and implementation of new technologies should increase the quality of research and the level of evidence supporting rehabilitation provided some adaptation in our research methodology.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

This work deals with the performance evaluation of novel flat photovoltaic-thermal (PV-T) modules under vacuum. Through a 1D (dimensional) steady-state-energy-balance numerical model developed in MATLAB, two different layouts are studied: the first consisting of a photovoltaic (PV) cell installed just below the glass encapsulating the flat panel, and the second where the PV cell is placed on the selective solar absorber (SSA). In both cases the thermal and electrical efficiencies have been evaluated at different SSA operating temperatures, in the range of 323 K to 423 K. The analysis has been conducted at different energy bandgap (E_bg) of the PV cell and assuming a variable transmittance or emittance of the PV cell, depending on the design. The two systems efficiency comparison has been carried out at the same operating temperature. Overall, this work highlights the importance of high vacuum insulation, which guarantees the reduction of convective thermal losses, and shows that the maximum energy is produced for PV cells with E_bg ≈1.5-1.7 eV, depending on layout and operating temperature, by including the thermal output in the PV-T optimization. The energy and exergy efficiencies obtainable using the proposed PV-T systems are considerably improved compared to the results previously reported in the literature.

This study quantified effluents generated during processing in three industry types, estimated the energy potential from the quantified effluents in form of biogas generation, and determined the economic viability of the biogas recovered. Data were procured from relevant scientific publications to quantify the effluents generated from the production processes in the industry types examined using industrial process calculations. The effluent data generated was used on the 2-module biogas energy recovery model to estimate the bioenergy recovery potential within it. Economic and financial analysis was based on cash flow comparison of all costs and benefits resulting from its activities. The effluents generated average daily biogas of 2559 Nm³/gVS, having a daily potential combined heat and power of 0.52 GWh and 0.11 GWh respectively. The Life Cycle Analysis and cost-benefit analysis show the quantity of avoided emissions from using the effluents to generate heat and power for processes, and also the profitability of the approach. Conclusively, the study shows the use of biomass effluents to generate biogas for CHP is a viable one based on the technologies of a reciprocating engine, gas turbine, microturbine, and fuel cell. However, it is recommended that the theoretical estimation be validated using a field-scale project.

Issues related to safe and abundant energy production have been prominent in recent years. This is particularly tr ue when society considers how to increase the quality of life by providing low-cost energy to citizens. A significant concern of the Gulf Cooperation Council (GCC) relates to the environmental effects of energy production and energy use associated with climate change. Efforts to reduce fossil fuel use and increase the use of renewable energy, together with the price volatility of fossil fuels, have seriously impacted the economics of many of the oil-producing countries, particularly the Gulf States, which has led to efforts to make their economies more diverse and less dependent on oil production.

The neuroglial extracellular matrix (ECM) provides critical support and physiological cues for the proper growth, differentiation, and function of neuronal cells in the brain. However, in most in vitro settings that study neural physiology, cells are grown as monolayers on stiff surfaces that maximize adhesion and proliferation, and therefore lack the physiological cues that ECM in native neuronal tissues provides. Macromolecular crowding (MMC) is a biophysical phenomenon based on the principle of excluded volume that can be harnessed to induce native ECM deposition by cells in culture. Here, we show that MMC using two species of Ficoll with vitamin C supplementation significantly boosts deposition of relevant brain ECM by cultured human astrocytes. Dopaminergic neurons co-cultured on this astrocyte-ECM bed prepared under MMC treatment showed longer and denser neuronal extensions, a higher number of pre ad post synaptic contacts, and increased physiological activity as evidenced by higher frequency calcium oscillation, compared to standard co-culture conditions. When the pharmacological activity of various compounds was tested on MMC-treated co-cultures, their responses were enhanced, and for apomorphine, a D2-receptor agonist, it was inverted in comparison to control cell culture conditions, thus emulating responses observed in in vivo settings. These results indicate that macromolecular crowding can harness the ECM-building potential of human astrocytes in vitro forming an ultra-flat 3D microenvironment that makes neural cultures more physiological and pharmacological relevant.

Japan Aerospace Exploration Agency (JAXA) is going to launch Advanced Land Observing Satellite 3 (ALOS-3) after 2022. ALOS-3 satellite is capable of observing global land areas with wide swath (4000 km along-track direction and 70 km cross-track direction) at high spatial resolution (panchromatic: 0.8m, multispectral: 3.2m). Maintenance and updating of land cover and vegetation information at national level is one of the major goals of the ALOS-3 mission. This paper presents the potential of simulated ALOS-3 images for the classification and mapping of land cover and vegetation types at Genus-Physiognomy-Ecosystem (GPE) level. We acquired and simulated WorldView-3 images according to the configuration of the ALOS-3 satellite sensor and the simulated ALOS-3 images were utilized for the classification and mapping of land cover and vegetation types in three sites (Hakkoda, Zao, and Shiranuka) in northern Japan. This research dealt with 17 land cover and vegetation types in Hakkoda site, 25 land cover and vegetation types in Zao site, and 12 land cover and vegetation types in Shiranuka site. Ground truth data were newly collected in three sites, and we employed eXtreme Gradient Boosting (XGBoost) classifier with the implementation of 10-fold cross-validation method for assessing the potential of ALOS-3S images. The classification accuracies obtained in Hakkoda, Zao, and Shiranuka sites in terms of f1-score were 0.810, 0.729, and 0.805 respectively. The fine scale (3.2m) land cover and vegetation maps produced in the study sites showed clear and detailed view of the distribution of plant communities. Regardless of the limited number of the temporal images, ALOS-3S images showed high potential (at least 0.729 F1-score) for the land cover and vegetation classification in all three sites. The availability of more cloud free temporal scenes is expected for improved classification and mapping in the future.

This transdisciplinary review of research about international cooperation on social and environmental change builds the case for replacing Sustainable Development as the dominant framework for an era of increasing crises and disasters. The review is the output of an intentional exploration of recent studies in multiple subject areas, based on the authors’ decades of work in related fields since the Rio Earth Summit 30 years ago (rather than a keyword search of databases). It summarizes the research which documents failure to progress towards the Sustainable Development Goals (SDGs). Consequently, the extensive scholarship critiquing the conceptual framework behind those ‘Global Goals’, and the economic ideology they arose from and support, is used to explain that failure. Although the pandemic set back the SDGs, it further revealed the inappropriate strategy behind those goals. This suggests the Global Goals constitute an ‘own-goal’ scored against people and nature. From this conclusion, alternative frameworks for organizing action on social and environmental issues become more important and are therefore briefly reviewed. It is argued that such a future framework must relate a new eco-social contract between citizen and state, and engage existing organizations and capabilities that are relevant to an increasingly disrupted world. Therefore, the case is made for considering an upgraded form of Disaster Risk Management (DRM) as an overarching framework. The proposed upgrades include detaching from economic ideologies, and recognizing that a wider metadisaster from climate chaos may reduce the future availability of external support. Therefore, self-reliant resilience and locally-led adaptation are identified as important to the future of DRM. Some options for professionals continuing to use the term sustainability, such as this journal, are discussed.

Despite significant advances in metallurgy and the potential to create high and very high-strength steel, all international specifications for steel design provided little information about the limits of slenderness for high-strength steel sections (HSSs) and didn’t give anything about the design of very high-strength steel sections (VHSSs). The American structural steel design specification covers circular hollow sections (CHS) of steel grades up to S690, while it isn't in ANSI/AISC 360-16 and ASTM A514/A514M. Euro code EN 1993-1-1 can be applicable only to steel grades up to S460. EN 1993-1-3 and EN 1993-1-12 contain supplementary rules for cold-formed members and HSS (S460- S700), respectively. Though ductility requirements for (HSS) are specifically established in EN 1993-1-12, it is largely a continuation of the normal-strength-steel design procedures standardized in EN 1993-1-1, where (HSSs) are largely treated as normal-strength steels in these rules, and the same design approaches are used. The behavior of high and very high-strength steel circular hollow sections under axial compression load is studied in this research. A total of 16 nonlinear finite-element (FE) models were generated to replicate stub column tests that were experimentally tested by others in previous research. Hence, a parametric study is conducted using forty FE models developed to investigate the local buckling behavior under various slenderness ratios comprehensively. The developed models cover slenderness ratios ranging from 20 to 1226 and steel grades S460 and S1100 with yield stress equal 460 MPa and 1152 MPa, respectively. The FE results were combined with 105 previously collected experimental results to assess the applicability of existing codified design methodologies in the Euro code and the North American codes of cold-formed CHS. Based on the results of this study, new cross-sectional slenderness limits and new design equations for more efficient simple designs were presented for high and very-high strength steel circular hollow sections and Compared with the results of experimental tests and FE models.

In this article the possible impact on the present state of particle physics theory is discussed of two unrecognized theoretical elements. These elements are the awareness that (a) the quark is a Dirac particle with a polarisable dipole moment in a scalar field and that (b) Dirac’s wave equation for fermions, if derived from Einstein’s geodesic equation, reveals a scaling theorem for quarks. It is shown that recognition of these elements proves by theory quite some relationships that are up to now only empirically assessed, such as for instance, the mass relationships between the elementary quarks, the relationship between the bare mass and the constituent mass of quarks, the mass spectrum of hadrons and the mass values of the Z boson and the Higgs boson.

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. This study examined the clinical characteristics, genetic basis, and arrhythmic outcomes of CPVT patients from China. Methods: PubMed and EMBASE were systematically searched for case reports or series reporting on CPVT patients from China until February 19th, 2022 using the keyword “Catecholaminergic Polymorphic Ventricular Tachycardia” OR “CPVT”, with the location limited to “China” OR “Hong Kong” or “Macau” in EMBASE, with no language or publication type restriction. Clinical characteristics, genetic findings, and primary outcome of spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) were analyzed. Results: A systematic search of the PubMed and Embase databases yielded 1049 and 47 articles, respectively. After the exclusion of overlapping cohorts, a total of 58 unique cases from 15 studies (median presentation age: 8 [5.0-11.8] years old) were included. All patients except for one presented at or before 19 years of age. 56 patients (96.6%) were initially symptomatic. Premature ventricular complexes (PVCs) were present in 44 of 51 patients (86.3%) and VT in 52 of 58 patients (89.7%). Genetic tests were performed on 54 patients (93.1%) with a yield of 87%. RyR2, CASQ2, TERCL, and SCN10A mutations were found in 35 (71.4%), 12 (24.5%), one (0.02%) patient, and one patient (0.02%) respectively. 54 patients were treated with beta-blockers, eight received flecainide, five received amiodarone, two received verapamil and one received propafenone. Sympathectomy (n=10) and implantable-cardioverter defibrillator implantation (n=8) were performed. On follow-up, 13 patients developed VT/VF. Conclusion: This is the first systematic review of CPVT patients from China. Most patients had symptoms on initial presentation, with syncope as the presenting complaint. RyR2 mutation accounts for more than half of the CPVT cases, followed by CASQ2, TERCL and SCN10A mutations.

We present improvements in n-best rescoring of code-switched speech achieved by n-gram augmentation as well as optimised pretraining of long short-term memory (LSTM) language models with larger corpora of out-of-domain monolingual text. In addition, we consider the application of large pretrained transformer-based architectures. Our experimental evaluation is performed on an under-resourced corpus of code-switched speech comprising four bilingual code-switched sub-corpora, each containing a Bantu language (isiZulu, isiXhosa, Sesotho, or Setswana) and English. We find in our experiments that, by combining n-gram augmentation with the optimised pretraining strategy, speech recognition errors are reduced for each individual bilingual pair by 3.51% absolute on average over the four corpora. Importantly, we find that even speech recognition at language boundaries improves by 1.14% even though the additional data is monolingual. Utilising the augmented n-grams for lattice generation, we then contrast these improvements with those achieved after fine-tuning pretrained transformer-based models such as distilled GPT-2 and M-BERT. We find that, even though these language models have not been trained on any of our target languages, they can improve speech recognition performance even in zero-shot settings. After fine-tuning on in-domain data, these large architectures offer further improvements, achieving a 4.45% absolute decrease in overall speech recognition errors and a 3.52% improvement over language boundaries. Finally, a combination of the optimised LSTM and fine-tuned BERT models achieves a further gain of 0.47% absolute on average for three of the four language pairs compared to M-BERT. We conclude that the careful optimisation of the pretraining strategy used for neural network language models can offer worthwhile improvements in speech recognition accuracy even at language switches, and that much larger state-of-the-art architectures such as GPT-2 and M-BERT promise even further gains.

The Circular Economy is matter of recent discussions and quite popular, however the meaning has not been understood by most Business stakeholders. This Case study proposes to illustrate the Circular Economy importance and its status now. The contribution that UAE education sector can make to the Circular Economy is immense and is the focus of this study. Circular Economy awareness and its inner meaning can be only spread by the education sector and the author emphasizes the role of the education can play in implementing the Circular Economy. The study shows the way for the future Managers and Business stakeholders to participate in this crucial endeavor of Businesses to follow the Circular Economy. The ADKAR change management can be adopted to inspire the CE initiatives of the UAE Education sector.

Platelets are a uniquely mammalian physiologic attribute. As the only non-marine vertebrate class to experience menopause, humans have a substantial post-reproductive lifespan and are believed to have a limited, non-renewable oocyte supply. Ovarian reserve typically declines after about age 35yrs, marking losses which cannot be recovered by available fertility medications. When in vitro fertilization fails due to low or absent ovarian response, gonadotropin adjustments are often ineffectual and if additional oocytes are occasionally harvested, egg quality is usually poor. This problem was confronted by Greek researchers who developed a new surgical method to insert autologous platelet-rich plasma (PRP) into ovaries; the first ovarian PRP success to improve reproductive outcomes was published from Athens in 2016. This innovation influenced later research with condensed platelet-derived growth factors, leading to correction of oocyte ploidy error, normal blastocyst development, and additional term livebirths. Yet women’s health was among the last clinical domains to explore PRP, and its role in ‘ovarian rejuvenation’ remains unsettled. One critical aspect in this procedure is platelet activation, a commonly overlooked step in the cytokine release cascade considered essential for successful transition of undifferentiated ovarian stem cells to an oocyte lineage. Poor activation of platelets thus becomes an unforced error, potentially diminishing or even negating post-treatment ovarian follicular response. To answer this query, relevant theory, current disagreements, and new data on platelet activation are presented, along with clinical challenges for regenerative fertility practice.

The presence of bubbles near the sea surface under certain conditions leads to abnormal sound scattering and a significant change in the acoustic properties of the upper layer of the sea. The article presents some results of sound scattering studies under various sea conditions, up to stormy conditions, when extensive bubble clouds arise. By the method of unsteady acoustic spectroscopy, data on the size distribution of bubbles at various depths have been obtained, which can be described by a power function with exponential decay at small bubble sizes of the order of 10 microns. Estimates of the gas content in bubble clouds and their influence on the acoustic characteristics of the upper layer of the sea have been carried out. It is shown that at sufficiently high concentrations, sharp increases in absorption and dispersion of the sound velocity are observed. Modeling of sound propagation in the presence of a quasi-homogeneous bubble layer shows that it leads both to a change in the laws of the average decay of the sound field along the sound propagation path and to a change in the shallow spatial structure of the field.

This study aims to comparatively analyse the importance and performance of the health of Korean and Japanese adolescents during the prolonged coronavirus disease 2019 (COVID-19) pandemic. Data were collected from 1,341 sampled Korean and Japanese adolescents in September 2021 through online and offline surveys. The collected data were analysed with frequency analysis, reliability testing, t-test, and importance-performance analysis (IPA). The following results were obtained. First, adolescents in the two countries perceive various factors about health as important during the COVID-19 pandemic, but their performance is weak compared to their perceived importance. Second, Korean adolescents had greater perceived importance for all factors of health perception compared to their Japanese counterparts. Third, the difference in performance between Korean and Japanese adolescents was especially evident for ‘hygiene management’, and there were significant differences in performance in ‘disease management’ and ‘physical activity’. Fourth, in quadrant 4 of the IPA matrix, there were similarities and differences in a particular factor of health perception between Korean and Japanese adolescents. Based on these results, we proposed measures to emphasise the importance of health and enhance performance among Korean and Japanese adolescents.

Background: As coronavirus (COVID-19) continues to pose a threat to the entire world, it is critical to developing strategies for containing its spread. The purpose of this study was to assess the demographic characteristics, brain tomography characteristics, and diffusion magnetic resonance findings of COVID-19 positive individuals. Material and Method: Between January 1 and December 31, 2021, 317 patients over the age of 18 were admitted to the emergency department with symptoms consistent with COVID-19. Three groups were formed based on clinical findings in patients, divided into light, medium, and severe, and four groups were formed based on radiological imaging findings. Results: The mean age of the 317 patients included in the study was 67.28±12.06 years, with a range of 28-91 years. The clinical classification of the patients was based on laboratory parameters and radiological imaging, not on their age or gender. Mild cases were classified as CO-RADS 0-4; moderate and severe cases were classified as CO-RADS 5-6 (p=0.001). While 60 (18.9%) of patients were followed outpatient, 144 (45.4%) were admitted to the hospital, 73 (23%) were admitted to the intensive care unit, and 40 (12.7%) died (p=0.001). Direct radiographs revealed bilateral involvement in 224 (70.7%) cases, peripheral involvement in 259 (81.7%) cases, and mid-lower lobe lung involvement in 194 (61.2%) cases (p=0.001). Brain tomography revealed infarction in 42 (13.2%) of the patients who were followed and hospitalized and hemorrhage in 22 (6.9%) of the patients. Magnetic resonance imaging revealed diffusion involvement in 68 (21.5%) of the cases (p=0.001). Conclusion: A standardized reporting system for COVID-19 data is required, and it must be simple to use, quick to understand, and focused on determining the risk of pneumonia. Additionally, the diagnostic role of radiological imaging, prognosis prediction, and severity scoring of lung involvement should be included.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon^® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Quantitative dynamic strain measurements of the ground would be useful for engineering scale problems such as monitoring for natural hazards, soil-structure interaction studies and non-invasive site investigation using full waveform inversion (FWI). Distributed Acoustic Sensing (DAS), a promising technology for these purposes, needs to be better understood in terms of its directional sensitivity, spatial position, and amplitude for application to engineering-scale problems. This study investigates whether the physical measurements made using DAS are consistent with the theoretical reception patterns and experimental measurements of ground strain made by geophones. Results show that DAS and geophone measurements are consistent in both phase and amplitude for broadband (10s of Hz), high amplitude (10s of microstrain) and complex wavefields originating from different positions around the array when: (1) the DAS channels and geophone locations are properly aligned, (2) the DAS cable provides good deformation coupling to the internal optical fiber, (3) the cable is coupled to the ground through direct burial and compaction, and (4) laser phase noise is mitigated in the DAS measurements. The theoretical relationship between DAS-measured and point-wise strain for vertical and horizontal active sources is introduced using 3D elastic finite-difference simulations. The implications of using DAS strain measurements are discussed including directionality and magnitude differences between the actual and DAS-measured strain fields. A method for spatially aligning the DAS channels with the geophone locations at tolerances less than the spatial resolution of the DAS system is proposed.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

This study focused on the level of Phonological awareness and Word Decoding ability among second year BSED English students in the University of Southeastern Philippines in terms of critical sound. Moreover, it aimed to recognize the significant relationship between the two variables. To verify, there were tests being employed to gather the necessary data. These were: listening test for measuring the respondents' level of awareness to words with critical sounds; phonetic transcription test to identify the respondents' level of awareness to sound-symbol relationship; and spelling test to know the respondents' level of ability for transcriptions to be translated to its Standard English spelling. After the data have been gathered, it was interpreted that the students have a moderate Phonological awareness. On the other hand, their Word Decoding ability resulted to high level. As being correlated, it is being found that there is a great significant relationship between the two variables. With these marks, the researchers encourage the schools in enhancing the students' sound-word relationship knowledge by primarily utilizing speech laboratory and establishing a speech club in the school for extending their exposure about these concepts.

Horizontal transfer of transposons (HTT) is an important source of genomic evolution in eukaryotes. The HTT dynamics is well characterized in eukaryotes including insects however, but there is a huge gap of knowledge about HTT regarding many eukaryotes’ species. In this study we analyzed the events of the HTT between Rhus gall aphids (Hemiptera) and other insects. We analyzed the Mariner-like transposable elements (MLEs) belongs to Rhus gall aphids for the possible HT events. The MLEs have patchy distribution and have high similarity over the entire length of element with insects MLEs from different orders. We selected representative sequences from the Rhus gall MLEs and identified five events of HT between MLEs of Rhus gall aphids and other insects from five different orders. We also found multiple HTT events among the MLEs of insects from the five orders which demonstrate that these Mariner elements have been involved in recurrent HT between these six order of insects. Our current study closed the knowledge gap of HTT and reported the events between Rhus gall aphids and other insects for the first time. We believe that this study about HTT events will help to understand the evolution and spread of transposable elements in the genomes of Rhus gall aphids.

The purpose of this work was to evaluate the suitability of recent US Food and Drug Administration (US-FDA) approved and marketed oral liquid, powder, or granule products for children in North America, to identify the next group of Active Pharmaceutical Ingredients (APIs) that have high potential for development as commercially available FDA-approved finished liquid dosage forms , and to propose lists of compounded nonsterile preparations (CNSPs) that should developed as commercially available FDA-approved finished liquid dosage forms as well as those that pharmacists should continue to compound extemporaneously. Through this identification and categorization process, the pharmaceutical industry, government, and the professions are encouraged to continue to work together to improve the likelihood that patients will receive high quality standardized extemporaneous CNSPs and US-FDA-approved products.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

Particle deposition on the surface of the drying chamber poses the main drawback in the spray drying process, which reduces the product recovery and affects the quality of the product. In view of this, the potential application of chemical surface modification to produce a hydrophobic surface that reduces the powder adhesion (biofouling) on the wall of the drying chamber was investigated in this study. The hydrophobic Polydimethylsiloxane (PDMS) solution was used in the vertical dipping method at room temperature to determine the optimum coating parameters on borosilicate glass and stainless-steel substrates, which were used to mimick the wall surface of the drying chamber, to achieve highly hydrophobic surfaces. A single-factor experiment was used to define the range of the PDMS concentration and treatment duration using the Response Surface Methodology (RSM). The Central Composite Rotatable Design (CCRD) was used to study the effects of the concentration of the PDMS solution (X1, %) and the treatment duration (X2, hr) on the contact angle of the substrate (°), which reflected the hydrophobicity of the surface. A three-dimensional (3D) response surface was constructed to examine the influence of the PDMS concentration and treatment duration on the contact angle readings, which serve as an indicator of the surface's hydrophobic characteristic. Based on the optimisation study, the PDMS coating for the borosilicate glass achieved an optimum contact angle of 99.33° through the combination PDMS concentration: X1 = 1% (w/v) and treatment time X2 = 4.94 hr, while the PDMS coating for the stainless-steel substrate achieved an optimum contact angle of 98.31° with PDMS concentration: X1 = 1% (w/v) and treatment time X2 = 1 hr. Additionally, the infrared spectra identified several new peaks that appeared on the PDMS-treated surfaces, which represented the presence of Si-O-Si, Si-CH3, CH2, and CH3 functional groups for the substrates coated with PDMS. Furthermore, the surface morphology analysis using the Field Emission Scanning Electron Microscopy (FESEM) showed the presence of significant roughness and uniform nanostructure on the surface of PDMS-treated substrates, which indicated the reduction of wettability and the potential effect on unwanted biofouling on the spray drying chamber.

COVID-19, a global health crisis, occurred unexpectedly and has led to global transformation over all countries in the world today. While COVID-19 had claimed lives and led to an economic crisis, the impacts on the financial market cannot be overemphasized. Considering the previous financial crisis, which occurred due to poor regulations and unchecked misconduct by financial market stakeholders, COVID-19 is the first to mention an indirect crisis that almost has no direct relationship to the financial system. Thus, this paper explores the impacts of COVID-19 from a stochastic approach on Local markets by applying the GARCH model to measure the level of volatility of two (2) US stock indexes (NASDAQ and NYSE) and a Europe index (EURONEXT). Our results show that volatility existed before COVID-19, but the volatility rate increased after COVID-19, possibly due to the COVID-19 shock. We also explore the Markov-Switching Dynamic Regression (MSDR) model to corroborate our findings. We validated that there is a very high persistent volatility for all the considered local markets at the early stage COVID-19 period.

Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.

There is a growing need for an area-wide knowledge of SOC contents in agricultural soils at field scale for food security, monitoring long-term changes related to soil health and climate change. In Germany, large-scale SOC maps are mostly available with a spatial resolution of 250 m to 1 km2. The nationwide availability of both digital elevation models at various spatial resolutions and multi-temporal satellite imagery enables the derivation of multi-scale terrain attributes and Landsat-based multi-temporal soil reflectance composites (SRC) as explanatory variables. On the example of an Bavarian test of about 8000 km2, the scale-specific dependencies between the representativeness of 220 soil samples and different aggregation levels of the explanatory variables were analyzed for their scale-specific predictive power. The aggregation levels were generated by applying a region-growing segmentation procedure, the SOC content prediction was realized by the Random Forest algorithm. In doing so, established approaches of (geographic) object-based image analysis (GEOBIA) and machine learning were combined. The modeling results revealed scale-specific differences. Compared to terrain attributes, the use of SRC parameters lead to a significant model improvement at large field-related scale levels. The joint use of both terrain attributes and SRC parameters resulted in further model improvements. The best modeling variant is characterized by an accuracy of R2=0.84 and RMSE=1.99.

The impacts of climate change on shrimp aquaculture can vary widely and can have environmental and socioeconomic consequences. This study assessed the vulnerability to climate change impacts of selected small-scale shrimp farms of Penaeus vannamei and shrimpfish market vendors in Davao region, Philippines using a modified Fisheries Vulnerability Assessment Tool (FishVool). Shrimp farmers and vendors were interviewed using two separate semi-structured questionnaires. A total of thirty-nine (N=39) shrimp farmers and forty-eight (N=48) market vendors from various market areas within the region were interviewed. Data regarding exposure (E), sensitivity (S), and adaptive capacity (AC) were collected following the FishVool parameters with modifications. Results revealed that overall climate change vulnerability of the shrimp farmers was medium (M), where both exposure and adaptive capacity were low (L) while sensitivity was medium (M). In addition, the shrimp market vulnerability of the various sites examined revealed medium (M) scores for markets in Pantukan, Mabini, Tagum, Maco, Lupon, Davao City, and Digos. But high (H) vulnerability scores for the markets in Panabo and Sta Cruz. Overall, the study provided a better understanding about shrimp farming in relation to climate change impacts and vulnerability and provided information for future shrimp farm management, marketing and climate change adapation in the region.

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using the mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England from March 2020 to March 2021. The research proposed the time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risk based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population's dynamic risk perceptions and lockdown duration. The case study at Leeds fits data well and shows that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results prove that simulated risk perceptions and policy decay could explain urban mobility behaviour during the mobility well during lockdown periods, which could be a reference for future decision-making processes.

Cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a Thoracic Pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and 15 culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p=0.19), a history of hematopoietic cell transplant (80% vs. 53%, p=0.31), severe lymphopenia (absolute lymphocyte count ≤500/µL, 100% vs. 73%, p=0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p=0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p=0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.

SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated February 22, 2022, of the in vitro activity of authorized mAbs against the Omicron variants. Thirty-three studies were eligible including 33 containing Omicron BA.1 susceptibility data and five that also contained Omicron BA.2 susceptibility data. The first two authorized mAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were inactive against the Omicron BA.1 and BA.2 variants. In 24 studies, sotrovimab (third authorized mAb) displayed a median 4.1-fold (IQR: 2.4-7.6) reduced activity against Omicron BA.1 and, in four studies, a median 26-fold (IQR:16-35) reduced activity against Omicron BA.2. In 18 studies, cilgavimab and tixagevimab independently displayed median reductions in activity of >300-fold against Omicron BA.1, while in ten studies, the cilgavimab/tixagevimab combination (fourth authorized mAb preparation) displayed a median 63-fold (IQR: 26-145) reduced activity against Omicron BA.1. In two studies, cilgavimab was approximately 100-fold more susceptible to BA.2 than to BA.1. In two studies, bebtelovimab, the most recently authorized mAb, was fully active against both the Omicron variants. Disparate results between assays were common as evidenced by a median 42-fold range (IQR: 25-625) in IC50 between assays for the eight authorized individual mAbs and three authorized mAb combinations. Highly disparate results between published assays indicates a need for improved mAb susceptibility test standardization or inter-assay calibration.

Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.

Tourism may not sustainably support territories with limited natural resource stock as islands. The volume in visitor arrivals and the industry investments can increase the pressure even beyond sustainable levels. There is an evident and unresolved tension between these two great polarities, sustainability and economic growth driven by tourism. The aim for policymakers is to find an acceptable equilibrium between these two dimensions. This paper investigates the tourism evolution between 2007 and 2019 in 15 Mediterranean islands, comparing the tourism pressures through statistical indicators. The analysis will compare tourism demand and supply trends in these contexts. The performances will be evaluated to identify the Islands positioning between sustainability needs and tourism development opportunities considering post-covid-19 challenges.

Obesity is linked to an inflammatory process, with adipocyte release triggering insulin resistance (IR) and autonomic imbalance. A cardiovagal trainning protocol has shown favorable results in autonomic balance and decrease of inflammatory markers. The aim of this study was to analyze the autonomic behavior related to inflammatory and metabolic parameters in obese people after a cardiovagal exercise protocol. Twenty people with obesity, were distributed by their HOMA-IR value: obese without IR (n/IR) (n=8) and obese with IR (y/IR) (n=12). The cardiovagal training program was carried out in both groups for 8 weeks at a frequency of 5 times per week. A blood sample was obtained to determine insulin, leptin, TNF alpha and IL6 levels, in addition to determining the HOMA-IR index and autonomic function was measured by heart rate variability. Changes were recorded in the OB-IR group, a decrease in inflammatory markers, glycemia and a reduction of sympathetic activity after the cardiovagal training intervention. In addition, significant differences between the y/IR and n/IR groups were shown in insulin, leptin, TNFa and IL6 values. It can be concluded that after 4 weeks of intervention with a cardiovagal trainning protocol, parasympathetic modulation increased and inflammatory markers decreased in obese subjects.

Heat stress affects the granulosa cells (GCs) and ovarian follicular microenvironment, causing poor oocyte developmental competence and fertility. This study aimed to investigate the physical responses and global transcriptomic changes in bovine GCs to acute heat stress (43 ℃ for 2 h) in-vitro and gave essential insights into the general interaction at cell–stress nexus. Heat-stressed GCs exhibited transient proliferation senescence, resumed proliferation at 48 h post-stress. While post-stress immediate culture-media change had a relatively positive effect on proliferation resumption. Increased accumulation of reactive oxygen species and apoptosis was observed in heat stress group. In spite of the upregulation of pro-apoptotic and caspase executioner genes, antioxidants and anti-apoptotic genes were also upregulated in heat-stressed GCs. Progesterone and Estrogen hormones along with steroidogenic genes expression, declined significantly, in spite of the upregulation of genes involved in cholesterol synthesis. Out of 12385 differentially expressed genes (DEGs), 330 significant DEGs (75 upregulated, 225 downregulated) were subjected to KEGG functional pathway annotation, gene ontology enrichment, and STRING network analyses. Based on the manual query of DEGs, pathway and enrichment analyses, a vast interplay observed among all major signaling pathways strongly evidence the repression of cellular transcriptional and proliferation activity, averting the effects of heat stress through remodeling of cellular structural proteins and energetic-homeostasis. This study presents detailed responses of acute heat-stressed GCs at physical, transcriptional, and pathway levels and presents interesting insights into future studies regarding GCs adaptation and their interaction with oocyte and reproductive system at ovarian level.

Dams have made great contributions to human society, facilitating flood control, power generation, shipping, agriculture and industry. However, the construction of dams greatly impacts downstream ecological environments and nearby marine areas. To summarize these impacts, this review used recent research to comprehensively analyze how dam construction has affected river hydrology, geomorphology, and ecosystem of downstream reaches globally. Effects of dams on ecosystems occur through reduced river flow, reduced sediment flux, altered water temperature, changed estuary delta, altered composition and distribution of nutrients, altered structure and distribution of phytoplankton populations, caused habitat fragmentation, and blocked migration routes in river sections and adjacent seas. Besides, exploring new reservoir management strategies (including targeted control of dam storage and flushing sediment operations), banning fishing activities, and removing unnecessary dams (obsolete or small dams) are becoming crucial tools for ecosystem restoration.

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.

Validation of satellite sea surface salinity (SSS) products is typically based on comparisons with in-situ measurements at a few meters depth, that are mostly done at a single location and time. The difference in term of spatio-temporal resolution between the in-situ near-surface salinity and the two-dimensional satellite SSS results in a sampling mismatch uncertainty. The Climate Change Initiative (CCI) project has merged SSS from three satellite missions. Using an optimal interpolation, weekly and monthly SSS and their uncertainties are estimated at a 50 km spatial resolution over the global ocean. Over the 2016-2018 period the mean uncertainty on weekly CCI SSS is 0.13, whereas the standard deviation of weekly CCI minus in-situ Argo salinities is 0.24. Using high resolution SSS simulations, we estimate the expected uncertainty due to the CCI versus Argo sampling mismatch. Most of the largest spatial variability of the satellite minus Argo salinity are observed in regions with large mismatch. A quantitative validation is performed by considering the statistical distribution of the CCI minus Argo salinity normalized by the sampling and retrieval uncertainties. This quantity should follow a Gaussian distribution with a standard deviation of 1, if all uncertainty contributions are properly considered. We find that 1) the sampling mismatch can explain most of the observed differences between Argo and CCI data, especially for monthly products and in dynamical regions (river plumes, fronts), 2) overall, the uncertainties are well estimated in CCI version 3, much better compared to CCI version 2. There are a few dynamical regions where discrepancies remain, and where the satellite SSS, their associated uncertainties and the sampling mismatch estimates should be further validated.

Influence of the volute design parameters on the stable operating range and the performance of a centrifugal compressor was investigated experimentally for the following design conditions. The volute casing surface roughness was changed from 0 to 200 µm in five steps and tested. The axial distance between the casing and the diffuser cascades (clearance) was varied in five steps as C/b₂ = 1.2, 2.4%, 3.6%, 4.8%, and 6% relative to the impeller exit width. The radial distance from the impeller blade exit to the diffuser vane inlet in (vaneless space radius) in six steps as C/r₂ = 1.03, 1.05, 1.07, 1.09, 1.11, and 1. 13 relatives to the rotor outlet radius. The volute outlet geometry of a symmetric and tangent with different area ratios from 0.4 to 0.9. Finally, the compressor has been tested experimentally with different pinched vaned diffuser distances relative to the impeller exit width of bp/b2 =1, 0.98, 0.96, 0.94, 0.92, and 0.9. These testes were carried at different compressor operating conditions, and the time variations of the static pressure were recorded using five high-frequency response pressure transducers. A hot-wire anemometer is used to measure the compressor flow rate. The rotating stall and surge at the vaneless zone after the impeller exit can be detected by analyzing the fluctuations of pressure signals and the power spectrum density by using the Fast Fourier Transformation analysis. The experimental results indicated that the compressor with volute casing surface roughness of 100mm gives about 10.9% enhancements in the stable operating and 1% in pressure rise coefficient. The best axial distance between the diffuser vanes and the casing is 2.4% of the impeller blade height and the compressor in this design gives about 12.4% improvements in the stable working range. The compressor with radial vaneless distance of 1.056 gives improvements of about 16.6% in the surge margin, 2% in the pressure recovery and 4% in pressure rise coefficients. The compressor with a pinched diffuser of b/bp of 0.98 gives an improvement of 20.8% in surge point.

Cytochrome P450 monooxygenases (P450s) are promising versatile oxidative biocatalysts. However, the practical use of P450s in vitro is limited by their dependence on the co-enzyme NAD(P)H and the complex electron transport system. Using H2O2 simplifies the catalytic cycle of P450s; however, most P450s are inactive in the presence of H2O2. By mimicking the molecular structure and catalytic mechanism of natural peroxygenases and peroxidases, an artificial P450 peroxygenase system has been designed with the assistance of a dual-functional small molecule (DFSM). DFSMs, such as N-(ω-imidazolyl fatty acyl)-l-amino acids, use an acyl amino acid as an anchoring group to bind the enzyme, and the imidazolyl group at the other end functions as a general acid-base catalyst in the activation of H2O2. In combination with protein engineering, the DFSM-facilitated P450 peroxygenase system has been used in various oxidation reactions of non-native substrates, such as alkene epoxidation, thioanisole sulfoxidation, and alkanes and aromatic hydroxylation, which showed unique activities, and regio- and enantioselectivities when compared with native P450s. Moreover, the DFSM-facilitated P450 peroxygenase system can switch to the peroxidase mode by mechanism-guided protein engineering. In this short review, the design, mechanism, evolution, application, and perspective of these novel non-natural P450 peroxygenases for the oxidation of non-native substrates are discussed.

Background: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous cardiomyopathy characterized by a two-layered myocardium consisting of compacted and noncompacted segments, prominent ventricular trabeculations, and intertrabecular recesses. Patients with LVNC are at increased risk to develop heart failure, atrial and ventricular arrhythmias, and/or systemic thromboembolic events. Familial forms of primary sinus bradycardia have been attributed to mutations in HCN4. There are very few reports about the association between HCN4 mutations and LVNC. The aim of our study was to characterize the clinical phenotype of families with LVNC and sinus bradycardia caused by mutation of the HCN4 gene. Methods: From March 2008 to July 2021 we prospectively enrolled 6 patients from 4 families with diagnosed isolated LVNC based on the clinical presentation, family history and echocardiographic and cardiovascular magnetic resonance (CMR) evidence of LVNC. Next generation sequencing (NGS) analysis was undertaken for evaluation of the molecular basis of the disease in each family. Results: A total of 6 children (median age 11 years) were enrolled and followed prospectively for the median of 12 years. All 6 patients were diagnosed with LVNC by echocardiography and 5 participants additionally by CMR. The presence of LGE was found in 3 children. Sinus bradycardia and dilation of the ascending aorta occurred in 5 studied patients. In 4 patients from 3 families the molecular studies demonstrated the presence of rare heterozygous HCN4 mutations. Conclusion: (1) The HCN4 mutation influences the presence of a complex LVNC phenotype, sinus bradycardia and dilation of the ascending aorta. (2) HCN4 mutation may be associated with the early presentation of clinical symptoms and the severe course of the disease. (3) It is particularly important to assess myocardial fibrosis not only within the ventricles, but also in the atria in patients with LVNC and sinus bradycardia.

Growing evidence suggests that healthcare provider advice may increase tobacco cessation, reduce alcohol use, and improve the adoption of desirable lifestyle behaviors among patients. However, how brief interventions and other provider-patient interactions can shape cumulative adoption of multiple modifiable behaviors is less well studied for diabetes prevention and control. Using weighted internet panel survey data from a large socio-demographically diverse urban population in the United States (n=1,003), the present study describes differences in group characteristics among those who had been “ever diagnosed” with prediabetes/diabetes versus those who had not. It also examines the associations between the cumulative adoption of lifestyle behaviors and each of the following: a) lifetime prediabetes/diabetes diagnosis; b) brief lifestyle intervention exposure (i.e., received provider advice/encouragement); and c) recent provider-patient communication about diabetes. There were several group differences in “ever diagnosed” prediabetes/diabetes status by age, employment status, health status, nutrition knowledge, blood pressure/hypertension diagnosis, and diabetes-related health behaviors (p<0.05). Each of the three provider-patient interactions of interest were positively associated with a higher cumulative sum of adopted modifiable lifestyle behaviors for diabetes prevention and management. Results suggest that provider advice/provider-patient interactions of any type can have a salutary impact on whether individuals with prediabetes or type 2 diabetes will engage in recommended lifestyle behavior modifications.

The concept of distributed generation has made photovoltaic an integral source of energy in smart grid systems, especially in peer-to-peer energy trading frameworks that exploit excess power to fulfill the energy requirements of consumers in cost-efficient and eco-friendly manner. It is believed that P2P energy trading will dominate a significant portion of research in forthcoming power generation systems due to the excessive rise of energy demands across the globe. Despite a plethora of studies on energy optimization solutions in P2P trading, minimizing nanogrid energy trading cost and efficient energy sharing between consumers and prosumers are deemed among the challenging problems. This study overcomes essential issues overlooked by the contemporary P2P energy trading models by introducing a predictive optimization-oriented nanogrid energy trading model. The proposed study encompasses two stages: (1) predictive optimization model which harnesses BD-LSTM-based forecasted energy parameters (energy load, energy consumption, and PV generation) that are later incorporated in PSO-enabled objective function to reduce nanogrid trading cost, (2) optimal energy sharing plan is devised to decide the role of nanogrids as prosumers or consumers by emphasizing the use of PV-produced energy. The proposed model is validated on the case study containing nanogrid houses data. The simulation provides detailed experiments by comparing the energy demand and response using the proposed energy sharing model. The outcomes yield that the energy sharing plan holds a significant potential to fulfill maximum energy requirements of nanogrid house in P2P cluster and significantly reduces the energy cost compared to grid.

Acetaminophen use during pregnancy and early childhood was accepted in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on false assumptions and ignorance of the impact of the drug on brain development. Fourteen studies now indicate that prenatal exposure to acetaminophen is associated with neurodevelopmental problems. Based on corrections for confounding factors applied to the analyses of available data, it can be concluded that prenatal exposure to acetaminophen causes statistically significant risks of one subtype of autism spectrum disorder (ASD), developmental delays, and attention deficit hyperactivity disorder. In contrast, data regarding postnatal exposure to acetaminophen are limited, and several factors impede a classic multivariate analysis of data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and it can be concluded beyond a reasonable doubt that postnatal exposure to acetaminophen in susceptible children is responsible for many if not most cases of ASD. Circumstantial evidence includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and the lack of alternative suspects that fit the evidence-derived profile.

MicroRNAs act as the cardinal post-transcriptional monitors of gene regulatory networks sculpturing the developmental plasticity and stress responses in plants. Single miRNA target several genes and how the transcriptional regulation of miRNA impacts its pool of targets in different tissues and stress conditions is still elusive. The present study investigated the highly conserved and evolving MIR408 family comprehensively by redefining its evolutionary conservation and diversification in plants followed by detailed functional analysis in rice. MIR408 family comprises three dominant mature forms (21 nt) including a distinct monocot variant. Plant MIR408 family can be divided into six groups. miR408 majorly cleave genes belonging to blue copper protein in addition to several other species-specific targets in plants. Screening of 4726 rice accessions identified 22 sequence variants in 1 Kb upstream (15) and MIR408 region leading to the identification of 8 haplotypes (3: Japonica-specific and 5: Indica-specific). miR408-3p follows flag leaf preferential and drought upregulated expression profile in flag leaf and roots of N22 which seems to be regulated by differential fraction of mCs in the precursor region. The active pool of miR408 regulated targets under control and drought conditions is impacted by the tissue type. Comparative expression analysis of miR408/target module under different sets of conditions features 83 targets exhibiting antagonistic expression in rice. Twelve high confidence targets including 4 plantacyanins (OsUCL6, 7, 9 and 30), pirin, OsLPR1, OsCHUP1, OsDOF12, OsBGLU1, glycine rich cell wall, deoxyuridine 5-triphosphate nucleotidohydrolaseand OsERF7 with antagonistic expression under most conditions. Further, over-expression of osa-MIR408 in drought sensitive rice cultivar leads to the massive enhancement of vegetative growth in rice with improved ETR and Y(II) and enhanced the dehydration stress tolerance at seedling stage.

Machine learning has become widely adopted as a strategy for dealing with a variety of cybersecurity issues, ranging from insider threat detection to intrusion and malware detection. However, by their very nature, machine learning systems can introduce vulnerabilities to a security defence whereby a learnt model is unaware of so-called adversarial examples that may intentionally result in mis-classification and therefore bypass a system. Adversarial machine learning has been a research topic for over a decade and is now an accepted but open problem. Much of the early research on adversarial examples has addressed issues related to computer vision, yet as machine learning continues to be adopted in other domains, then likewise it is important to assess the potential vulnerabilities that may occur. A key part of transferring to new domains relates to functionality-preservation, such that any crafted attack can still execute the original intended functionality when inspected by a human and/or a machine. In this literature survey, our main objective is to address the domain of adversarial machine learning attacks and examine the robustness of machine learning models in the cybersecurity and intrusion detection domains. We identify the key trends in current work observed in the literature, and explore how these relate to the research challenges that remain open for future works. Inclusion criteria were: articles related to functionality-preservation in adversarial machine learning for cybersecurity or intrusion detection with insight into robust classification. Generally, we excluded works that are not yet peer-reviewed; however, the authors include some significant papers that make a clear contribution to the domain. There is a risk of subjective bias in the selection of non-peer reviewed articles; however, this is mitigated by co-author review. We selected the following databases with a sizeable computer science element to search and retrieve literature: IEEE Xplore, ACM Digital Library, ScienceDirect, Scopus, SpringerLink,Google Scholar. The literature search was conducted upto January 2022. We have striven to ensure a comprehensive coverage of the domain to the best of our knowledge. We have performed systematic searches of the literature, noting our search terms and results, and following up on all materials that appear relevant and fit within the topic domains of this review. This research was funded by the Partnership PhD scheme at the University of the West of England in collaboration with Techmodal Ltd.

Stemming from the Bulgarian case study developed within a European research project (ECHOES, Horizon 2020), the paper discusses the links between: (a) the urgent need to operationalize EU energy transition policy in the housing domain; (b) the complexity of factors influencing the policy implementation in different contexts – geographical, economic, and technical but also social and cultural; and (c) the important role of the urban level in policy implementation. Under the specific spatial planning context of Bulgaria, the local collective energy-related decision-making in the housing field evolves through the interaction – formal (at the municipal level of governance) and informal (individuals, households and homeowners’ associations taking decisions on self-organization and collective action). The authors claim that interdisciplinary context-sensitive research would contribute to a better understanding for the ongoing energy-related decision-making processes at the local level and would enable the development and implementation of effective and efficient policy instruments in support of energy transition in the housing sector in Europe.

Background: In Switzerland, Aedes albopictus is well established in Ticino, south of the Alps, where surveillance and control are implemented. The mosquito has also been observed in Swiss cities north of the Alps. Decision-making tools are urgently needed by the local authorities in order to optimize surveillance and control. Methods: A regularized logistic regression was used to link the long-term dataset of Ae. albopictus occurrence in Ticino with socio-environmental predictors. The probability of establishment of Ae. albopictus was extrapolated to Switzerland and more finely to the cities of Basel and Zurich. Results: The model performed well, with an AUC of 0.86. Ten so-cio-environmental predictors were selected as informative, including the road-based distance in minutes of travel by car from the nearest cell established in the previous year. The risk maps showed high suitability for Ae. albopictus establishment in the Central Plateau, the area of Basel and the lower Rhone Valley in the Canton of Valais. Conclusions: The areas identified as suitable for Ae. albopictus establishment are consistent with the actual current findings of tiger mosquito. Our approach provides a useful tool to prompt authorities’ intervention in the areas where there is higher risk of introduction and establishment of Ae. albopictus.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

This study aims to explore the link between public investment and private investment in South Africa, using time series data spanning 40 years (1980–2020). Private investment is subdivided into credit to private sector (CPS) and foreign direct investment (FDI). Several econometric methodologies were used in the study, including the unit root test, cointegration test, and Error Correction Method (ECM). The Phillips-Perron (PP) test results point out that all the variables are stationary at levels with the exception of public investment (PI) which is stationary at first difference. The co-integration test reveals that the variables have a long-run equilibrium relationship. According to the findings of the ECM, public investment has a negative relationship with private investment (as measured by credit to private sector and foreign direct investment). The conclusion implies that in South Africa, public investment crowds out private investment. Other results revealed that, RGDP crowds in credit to private sector while crowding out foreign direct investment. Finally, the ECM findings show that government consumption expenditure crowds out credit to private sector and foreign direct investment. The residuals are homoskedastic and show no serial correlation, indicating that the model is adequate, according to the test for adequacy.

In this review, we provide an overview of the most common majority and minority charge carrier traps in n-type 4H-SiC material. We focus on the results obtained by different applications of junction spectroscopy techniques. The basic principles behind the most common junction spectroscopy techniques are given. These techniques, namely, deep level transient spectroscopy (DLTS), Laplace DLTS (L-DLTS) and minority carrier transient spectroscopy (MCTS) have led to recent progress in identifying and better understanding of the charge carrier traps in n-type 4H-SiC material.

In recent years, excessive heat in the urban texture has become the main problem in the humid and calm wind city of Babolsar with high density, especially in high-rise areas. Therefore, in order to create comfort in this region, it is necessary to establish and continue the wind circulation in space with an environmentally compatible and optimal configuration. The study applies combination of literature, field measurement, experimental validation of CFD simulation output, and comparative analysis. After field measurement and validation of FLOW-3D simulation software (V11.2.2), the relationship between these parameters (height, the width of passages, enclosure between buildings, and buildings' orientation) will be studied which affects the wind’s velocity and direction. The factors of the buildings' orientation and enclosure based on the passages' width have opposite reactions in the direction of the prevailing wind especially from perpendicular side. In this study, two effective factors are on wind velocity: 1- The orientation of the buildings towards the wind flow by creating permeability 2- Reducing the enclosure by increasing the width of the passage's perpendicular to the wind flow (w '= 3w, E' = 0.33E). According to the theoretical and practical study, first, the creation of permeability in the body of the block and the separation of buildings instead of aggregation has been studied, and then reducing the confinement of streets perpendicular to the wind flow has been discussed as effective solutions to improve the wind velocity and circulation between the urban environment.

This paper proposes a new structure of the dual-rotor hybrid-excited axial-flux permanent magnet vernier machine (DR-HEAFPMVM) with the modular stator and the consequent-pole PM (CPM) rotor for low-speed, high torque density applications such as in-wheel electric vehicles. The tooth-wound non-overlapping armature windings and direct current (DC) excitation windings are respectively arranged in stator main-teeth and split-teeth to obtain the modulated and adjustable air-gap flux densities, which result in the high torque density and outstanding flux-weakening capability. First, the design consideration, operation principle, and the air-gap flux density distributions of the proposed machine are elaborated based on the air-gap permeance function. Then, the influence of the pole ratios (PRs) and the DC excitation currents on the main electromagnetic performances of the DR-HEAFPMVM, such as the flux-weakening capability, back-electromotive force (back-EMF), on-load electromagnetic torque, loss distribution, and efficiencies, is investigated using the 3-D finite-element method (FEM). Results verify the feasibility of the flux adjustment of the DC excitation windings equipped in the split-tooth, and the design with a pole ratio of 8/1 tends to have higher torque density, higher machine efficiency, and considerable flux-weakening capability compared with the other two PRs.

Hyperactivation of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling is an attractive therapeutic target for tumor therapy. Herein, forty-eight novel meridianin derivatives were designed and synthesized, and their anti-tumor activity were evaluated in vitro both for activity optimization and structure-activity relationship (SAR) study. The results indicated that most derivatives exhibited significantly improved anti-tumor activity, especially for compound 6e. The compound 6e contains an isothiouronium linked by an alkyl chain consisting of 6 carbon atoms with IC50 ranging from 1.11 to 2.80 μM on various cancer cell lines. Consistently, 6e dose dependently induced the apoptosis of A549 and DU145 cells, in which STAT3 are constitutively active. Western blotting assays indicated that the phosphorylation levels of JAK1, JAK2 and STAT3 were inhibited by 6e at 5 μM without significant change in total STAT3 level. Moreover, 6e also suppressed the expressions of STAT3 downstream genes, including c-Myc, Cyclin D1 and Bcl-XL at 10 μM. An additional in vivo study revealed that 6e at the dose of 10 mg/kg could potently inhibit the DU145 xenograft tumor without obvious body-weight loss. These results clearly indicate that 6e could be a potential anti-tumor agent by targeting JAK/STAT3 signaling pathway.

Long-term changes in nanoparticles of copper-silver bimetallic systems on natural clinoptilolite obtained by ion exchange of Cu2+ and Ag+, and then reduced at different temperatures, have been studied. Even after storage under ambient conditions, XRD and UV-Vis diffuse reflectance spectra indicate the presence of nanospecies of reduced copper and silver. Scanning Electron Microscopy of aged bimetallic samples, reduced at the highest temperature (450oC) and the primary samples for their preparation, also aged, showed the presence of silver nanoparticles with a size of about 100 nm. They are formed in the initial ion-exchanged sample (without reduction) due to the degradation of Ag+ ions. The nanoparticles in the reduced sample are larger; in both samples they are evenly distributed over the surface. The presence of silver affects the stability and the mechanism of decomposition/oxidation of reduced copper nanospecies, and this stability is higher in bimetallic systems. The decomposition pattern of recently reduced species includes the formation of smaller nanoparticles and few-atomic clusters. This can occur, preceding the complete oxidation of Cu to ions. Quasi-colloidal silver, which is present in fresh bimetallic samples reduced at lower temperatures, transforms after aging into Ag8 clusters, which indicates the stability of these nanospecies on natural clinoptilolite.

Influence of Joule heating on magnetic properties, giant magnetoimpedance (GMI) effect and domain wall (DW) dynamics of Fe75B9Si12C4 glass-coated microwires was studied. A remarkable increase in GMI ratio is observed in Joule heated samples. The hysteresis loops of Joule heated samples maintain a rectangular shape, while a slight decrease in coercivity after Joule heating is observed. On the other hand, a modification of MOKE hysteresis loops is observed upon Joule heating. Additionally, DW dynamics improvement after Joule heating is observed. The observed GMI ratio improvement along with the change in MOKE loops and DW dynamics improvement has been discussed considering magnetic anisotropy induced by Oersted magnetic field in the surface layer during Joule heating and the internal stress relaxation. A remarkable GMI ratio im-provement observed in Fe-rich Joule-heated microwires with a rectangular hysteresis loop and fast DW propagation, together with the fact that Fe is a more common and less expensive metal than Co, makes them suitable for use in magnetic sensors.

Demographic change is leading to the aging of German society. As long as the baby boom co-horts are still of working age, the working population will also age - and decline as soon as this baby boom generation gradually reaches retirement age. At the same time, there has been a trend towards increasing absenteeism (times of inability to work) in companies since the zero years, with the number of days of absence increasing with age. We present a novel stochastic forecast approach that combines population forecasting with forecasts of labor force participation trends, considering epidemiological aspects. For this, we combine a stochastic Monte Carlo-based cohort-component forecast of the population with projections of labor force participation rates and morbidity rates. This article examines the purely demographic effect on the economic costs associated with such absenteeism due to the inability to work. Under expected future employment patterns and constant morbidity patterns, absenteeism is expected by close to 5 percent by 2050 relative to 2020, associated with increasing economic costs of almost 3 percent. Our results illustrate how strongly the pronounced baby boom/ baby bust phenomenon determines demographic development in Germany in the midterm.

Mesothelin is a protein that is expressed in the mesothelial cell lining in the pleura, peritoneum, and pericardium. The gene of mesothelin encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycophosphatidylinositol linkage and a shred fragment named the megakaryocytic-potentiating factor. The biological functions of this substance in normal cells are still unknown. Experimental studies on knockout mice suggest that this substance does not play an important role in development and reproduction. In contrast, it has been observed that mesothelin is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered a tumour marker or an antigenic target for many malignancies. Many molecular studies also have demonstrated that mesothelin is overexpressed in serous ovarian carcinomas and may bind to ovarian cancer antigen Ca-125, favouring the spread of the tumour in the abdominal cavity. 3 Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses as well as its impact on the prognosis in serous ovarian carcinomas. We also briefly discuss the latest progress of mesothelin-targeting therapies for this aggressive and lethal neoplasm.

A structure-based view on mesons is given, based upon the concept of an archetype quark, described as a pointlike source producing an energy flux, the spatial description of which is derived from Dirac’s second dipole moment. This enables to conceive the archetype meson (pion) as a structure that behaves as a one-body anharmonic quantum mechanical oscillator. All mesons appear being excitations of the archetype, thereby allowing a calculation of the mass spectrum without the use of empirical parameters for the masses of the quark flavors. This includes a physically comprehensible analysis of the spin-spin interaction between quarks. It also provides a solution for the eta-etaprime puzzle. Next to this, it is shown that quite some particles that are presently regarded as elementary, have a common root and can be traced back to a few archetypes only.

Recently it was found from Cassini data that the mean recession speed of Titan from Saturn is v = 11.3 ± 2.0 cm/yr which corresponds to a tidal quality factor of Saturn Q ≈ 100 while the standard estimate yields Q ≥ 6 · 10⁴ . It was assumed that such a large speed v is due to a resonance locking mechanism of five inner mid-sized moons of Saturn. In this paper, we show that an essential part of v may come from a local Hubble expansion, where the Hubble-Lemaˆıtre constant H0 recalculated to the Saturn-Titan distance D is 8.15 cm/(yrD). Our hypothesis is based on many other observations showing a slight expansion of the Solar system and also of our Galaxy at a rate comparable with H0. We demonstrate that the large disproportion in estimating the Q factor can be just caused by the local expansion effect. [Accepted for publication in "Gravitation and Cosmology". The paper is to appear in Vol. 28, Issue 2 (2022) of the journal Gravitation and Cosmology.]

Every day around 93% of children under the age of 15 (1.8 billion children) breathe outdoor air that is so polluted it puts their health and development at serious risk. Due to the pandemic, however, ventilation of buildings using outdoor air has become an important safety technique to prevent the spread of COVID-19. With the mounting ev-idence suggesting that air pollution is impactful to human health and educational out-comes, this contradictory guidance may be problematic in schools with higher air pol-lution levels, but keeping kids COVID-19 free and in school to receive their education is now more pressing than ever. To understand if all schools in an urban area are ex-posed to similar outdoor air quality and if school infrastructure protects children equally indoors, we installed research grade sensors to observe PM2.5 concentrations in indoor and outdoor settings to understand how unequal exposure to indoor and out-door air pollution impacts indoor air quality among high- and low-income schools in Salt Lake City, Utah. Based on this approach, we found that during atmospheric inver-sions and dust events, there was a lag ranging between 35 to 73 minutes for the out-door PM2.5 concentrations to follow a similar temporal pattern as the indoor PM2.5. This lag has policy and health implications and may help to explain the rising concerns re-garding reduced educational outcomes related to air pollution in urban areas. These data and resulting analysis show that poor air quality may impact school settings, and the potential implications with respect to environmental inequality.

This study examined the link between tax revenue components and economic growth in South Africa, utilizing time series data for the period of 22 years. The stationarity of the variables was established using the Phillips-Perron (PP) unit root test, and the existence of long-run and short-run equilibrium conditions was tested using the Autoregressive Distributed Lag (ARDL) model. As a proxy for economic growth, the study used the real GDP growth rate as the dependent variable, with company income tax, personal income tax, taxes on international trade and transactions, taxes on income, profits, and capital gains tax, foreign direct investment, inflation, and gross savings as the independent variables. According to the PP findings, none of the variables are integrated at a higher order than one, i.e. (1). All variables are found to be cointegrated, and all explanatory variables have a long-run link with economic growth. According to the ARDL findings, company income tax, personal income tax, and taxes on international trade and transactions all have a positive long-run and short-run link with economic growth, whereas capital gain tax, foreign direct investment, and gross savings all have a negative long-run and short-run link with economic growth. The long-run coefficient is negatively related to RGDP, while the short-run coefficient revealed a positive link between inflation and economic growth, among other findings. Heteroskedasticity and autocorrelation are not present in our model, according to diagnostic tests. The CUSUM and CUSUMSQ values indicate that the model is structurally sound.

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, to establish laboratory reference ranges in SCD at steady-state. Patients were grouped into five age groups with respects to their sex. Aggregate functions were used to handle repeated measures within the indi-vidual level in each age group. A nonparametric approach was used to smooth the curves and a parametric approach was used to determine SCD normal ranges. Comparison between males and females and against the general population was documented. Data from 4,422 patients collected from 2004-2015 were analyzed. The majority of the patients (35.41%) were children aged between 5-11 years. There were no significant differences (p≥0.05) in mean corpuscular hemoglobin concentration (MCHC), lymphocytes, basophils and bilirubin direct observed between males and females. Significant differences (p<0.05) were observed in all selected parameters across age groups except neutrophils and MCHC in adults, as well as platelets and alkaline phosphatase in infants when SCD estimates were compared to the general population. Laboratory reference ranges in SCD at steady-state were different from those of the general population and varied with sex and age. The established reference ranges for SCD at steady-state will be a helpful in the management and monitoring of the progress of SCD.

This study provides a novel method to prepare metal-ceramic composites from magnetically selected iron ore using microwave heating. By introducing three different microwave susceptors (Activated Carbon, SiC, and a mixture of Activated Carbon and SiC) during the microwave process, effective control of the ratio of metallic and ceramic phases has been achieved easily. The effects of the three susceptors on the microstructure of the metal-ceramics and the related reaction mechanisms were also investigated in detail. The results show that the metal phase (Fe) and ceramic phase (Fe2SiO4, FeAl2O4) can be maintained, but the metal phase to ceramic phase changed significantly. In particular, the microstructures appeared as well-distributed nanosheet structures with diameters of ~400 nm and thicknesses of ~20 nm when SiC was used as the microwave susceptor.

Among many research areas to which Ron Yager contributed are decision making under uncertainty (in particular, under interval and fuzzy uncertainty) and aggregation – where he proposed, analyzed, and utilized the use of Ordered Weighted Averaging (OWA). The OWA algorithm itself provides only a specific type of data aggregation. However, it turns out that if we allows several OWA stages one after another, we get a scheme with a universal approximation property – moreover, a scheme which is perfectly equivalent to deep neural networks. In this sense, Ron Yager can be viewed as a (grand)father of deep learning. We also show that the existing schemes for decision making under uncertainty are also naturally interpretable in OWA terms.

Background: Smoking is disproportionately prevalent among Aboriginal and Torres Strait Islander Australian peoples, with 39% of Indigenous Australians aged over 15 years smoking daily. Efforts to reduce this high prevalence include culturally focused media campaigns, designed using community consultation, highlighting the need to determine how such health messaging is received by smokers. This study aimed to examine Indigenous Australian smokers’ reactions to a culturally focused anti-smoking mass media campaign—'Give up Smokes’. Methods: Intercept surveying across health services and events used recorded demographics, smoking status, quit attempts, smoking health effects, anti-smoking campaign recall, social support, and campaign reactions. Participants rated campaign images in five domains: 1) whether it made them stop and think; 2) personal relevance; 3) believability of design and message; 4) prompting concern about smoking; and 5) motivation towards quitting. Cluster analysis was used to segment smoker types. Results: Smoking health effects knowledge was high, and did not differ by quit readiness, attempts, or social support. Cessation support access was higher among those with greater readiness to quit. Social smoking behaviour and confidence to support others quitting did not significantly differ between participants, however importance of others quitting did. Quit readiness, attempts, and social support were associated with reaction to campaign design, but not message recall. Four types of smokers were described, using smoking characteristics, who differed in campaign message reactions. Conclusions: Strategies using campaign-exposed smoker characteristics to inform culturally focused health promotion are discussed in relation to four identified types of smokers.

A model for parasitic motility has been proposed in which parasite filamentous actin (F-actin) is attached to surface adhesins by a large component of the glideosome, known as the glideosome-associated connector protein (GAC). This large 286 kDa protein interacts at the cytoplasmic face of the plasma membrane with the phosphatidic acid-enriched inner leaflet and cytosolic tails of surface adhesins to connect them to the parasite actomyosin system. GAC is observed initially to the conoid at the apical pole and re-localised with the glideosome to the basal pole in gliding parasite. GAC presumably functions in force transmission to surface adhesins in the plasma membrane and not in force generation. Proper connection between F-actin and the adhesins is as important for motility and invasion as motor operation itself. This notion highlights the need for new structural information on GAC interactions, which has eluded the field since its discovery. We have obtained crystals that diffracted to 2.6-2.9 Å for full-length GAC from Toxoplasma gondii in native and selenomethionine-labelled forms. These crystals belong to space group P212121, cell dimensions are roughly a=119 Å, b=123Å, c=221Å, α=90, β=90, γ=90 with 1 molecule per asymmetric unit, suggesting a more compact conformation than previously proposed.