Phagosomal escape and intracellular survival, often accompanied by Small Colony Variants (SCVs) formation, are typical features of infections caused by S. aureus. The survival in macro-phages favours S. aureus dissemination and complicates treatment. RAW 264.7 murine macro-phages infected with S. aureus USA300 and treated with erythromycin and 20mM carnosine, alone and in combination, were used as experimental model. SCVs were isolated from all treat-ment conditions, but only those undergoing the pressure of combined erythromycin and carnosine for 48 hours were stable for at least six passages on blood agar. Nucleic acid extraction was car-ried out for S. aureus USA300 wild-type and stable SCVs. Whole Genome Sequencing (WGS) was performed using Illumina DNA Prep and Illumina MiSeq, and quantitative reverse transcription PCR was performed. WGS analysis did not yield mutations pointing to differences between S. au-reus USA300 and stable SCVs, therefore the focus was shifted to evaluating gene expression vari-ations. Genes such as zur, mntR, uhpt, fur, sdrE were shown to be significantly up-regulated in SCVs compared to S. aureus USA300 wild-type, suggesting a global change that allows adapta-tion to intracellular persistence, including protection from inflammatory response and evasion of the immune system.

The DNA methylation profile of breast cancer differs from that in healthy tissue and can be used as a diagnostic and prognostic biomarker. Aim of the study: to compare gene methylation in small malignant breast tumors less than 2 cm and in healthy tissue and fibroadenoma. Methylation of the following 15 genes was studied: MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, TIMP3. Methods: analysis was made by our modified MS-HRM method followed confirmation of the results by pyrosequencing. The genes were selected from publications that studied DNA methylation in breast cancer with high genome coverage. The study group included 48 samples of breast cancer, the control group included 24 samples of fibroadenoma and 24 samples of healthy tissue. Results: significant differences were found in methylation of 8 genes: CCDC181, GSM2, ITPRIPL1, ZNF177, CACNA1E, DLGAP2, TIMP3 (all р<0.001), and PRDM14 (р=0.002). The most accurate diagnostic value, based on logistic regression, was shown with the compound of two genes – CCDC181 and ZNF177 (AUC=0.99) in pyrosequencing analysis. Conclusion: small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissue and benign proliferative lesions.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.

COVID-19 is now a major global health crisis, can lead to severe food crisis unless proper measures are not taken. Though a number of scientific studies have addressed the possible impacts of COVID-19 in Bangladesh on variety of issues, problems and food crises associated with aquatic resources and communities are missing. Therefore, this study aimed at bridging the gap in the existing situation and challenges of COVID-19 by linking its impact on aquatic food sector and small-scale fisheries with dependent population. The study was conducted based on secondary data analysis and primary fieldwork. Secondary data focused on COVID-19 overview and number of confirmed, recovered and death cases in Bangladesh; at the same time its connection with small-scale fisheries, aquatic food production, demand and supply was analyzed. Community perceptions were elicited to present how the changes felt and how they affected aquatic food system and small-scale fisheries and found devastating impact. Sudden illness, reduced income, complication to start production and input collection, labor crisis, transportation abstraction, complexity in food supply, weak value chain, low consumer demand, rising commodity prices, creditor’s pressure were identified as the primary affecting drivers. Dependent people felt the measures taken by the Government should be based on protecting the health and food security, although it could be detrimental to economic growth in the short term. The study provides insight into policies adopted by the policy makers to mitigate the effects of the pandemic on aquatic food sector and small-scale fisheries.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

Here we evaluate the chemistry of mineral soil solutions collected by suction lysimeters in a small mountain catchment that was affected by acidification-related spruce die-back. The aim was to obtain new insights into spatial patterns of nutrient partitioning during acidification recovery. This was achieved by comparing nutrient concentrations in soil solutions, collected along a V-shaped valley, with those in runoff. Five nests of suction lysimeters were installed in the 33-ha UDL catchment at different topographic positions (hilltops, slopes and valley). Following a 1-year equilibration, monthly samples of soil solutions were collected over a 2-year period. In the vicinity of each lysimeter nest, soil pits were excavated for a study of soil chemistry. Soil solutions were analyzed for SO42-, NO3-, DOC, NH4+, Na+, K+, Ca2+, Mg2+, and total dissolved Al concentrations, DOC and pH. For a P release estimation, ammonium oxalate extraction of soil samples was performed. Comparison of soil water data from this study with other European studies indicated that major environmentally relevant chemical species at UDL had concentrations similar to median concentrations across numerous previously acidified sites. CEC (≤ 58 meq kg-1) and BS (≤ 13 %), however, were significantly lower at UDL than at other European sites, documenting incomplete recovery from acidification. Spatial trends and seasonality in soil water chemistry support belowground inputs from mineral-stabilized legacy pollutants and soil nutrients. Seasonal variability of soil water sulfate and nitrate was significant. High nitrate in soil solutions during summer originated during the preceding dormant season, and high sulfate concentrations observed during the winter originating from recycled organic S during the summer. Higher concentrations of SO42-, NO3-, and base cations in runoff than in soil solutions may be explained by lateral surficial runoff leaching pollutants and nutrients from very shallow soil horizons. Nearly 30 years after peak acidification, solutions in mineral subsoil at UDL exhibited similar concentrations of SO42-, Ca2+ and Mg2+ as median values at the Pan-European International Co-operative Program (ICP) Forest sites, yet NO3- concentrations were an order of magnitude higher than the ICP sites. Calcium applied on soil surface by liming 32 to 11 years ago affected runoff more than soil solutions, suggesting contribution of both shallow soil water and groundwater to runoff.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

The increasing use of energy resources recovered from the subsurface environments and the resulting carbon imbalance in the environment has motivated the need to develop thermodynamically downhill pathways to convert and store CO₂ as water insoluble calcium or magnesium carbonates. While previous studies extensively explored aqueous routes to produce calcium and magnesium carbonates from CO₂, there has been a limited scientific understanding of the phase evolution and textural changes during the direct gas-solid conversion routes to produce calcium carbonate from calcium hydroxide, which is one of the abundant constituents of alkaline industrial residues. With increasing interest in developing integrated pathways for capturing, converting and storing CO₂ from dilute flue gases, understanding the compositions of the product phases as they evolve is essential for evaluating the efficacy of a given processing route. Therefore, in this study, we investigate the phase evolution and the corresponding textural changes as calcium hydroxide is converted to calcium carbonate under the continuous flow of CO₂ at an ambient pressure of 1 atm and on heating continuously from 30 °C to 500 °C using in-operando wide angle X-ray scattering (WAXS), small angle X-ray scattering (SAXS), and ultra-small angle X-ray scattering (USAXS) measurements.

This paper delves into the strategic dimensions influencing the adoption of environmental innovations (EIs) in small and medium-sized manufacturing enterprises (SMEs) in Mexico City. Employing a mixed-methods approach combining documentary analysis and expert interviews, the study aims to provide a comprehensive understanding of integrating EI practices in the context of manufacturing SMEs. Qualitative methodology was chosen to explore experiences, perceptions, and practices related to EI adoption, acknowledging its ability to capture the complexity and richness of data. Through systematic literature review and semi-structured interviews with Corporate Social Responsibility experts, causal relationships and key factors influencing EI adoption were identified. The data analysis involved constructing causal maps and applying the Viable System Model to comprehend the interactions and dynamics within the organizational systems.

Urban wind energy has emerged as an attractive source of distributed generation in cities to achieve sustainable development goals. The advance in technologies for the use of urban wind energy has turned this source into an attractive alternative for the decarbonization of cities and the energy transition. The objectives of this work are (1) to identify the potential of wind energy through numerical weather prediction (NWP) data tools and (2) to identify the roles and responsibilities of the stakeholders involved in the decision-making process. A methodology was developed in two phases and applied to a case study in the Dominican Republic. The first phase consisted of estimating the wind energy potential for the 32 provinces at a height of 10 m using open-access geographic reference systems tools provided by NASA. In the second phase, 28 stakeholders were identified through snowball sampling. The Responsible, Accountable, Consult, and Informed (RACI) matrix tool was applied to identify the roles of the 28 institutions addressed at the country level as relevant in the decision-making process for the energy sector. The annual average wind speed and energy potential for each province were determined. It was found 24 provinces have poor potential, below &lt;4.5 m/s. In the northwest and east is where there is the greatest potential, between 4.83 - 6.63 m/s. The population density was established and was observed that the provinces with greater potential are less densely populated. Through 59 interviews 28 institutions were identified and evaluated due to their relevance in decision-making for the implementation of energy projects. The MEM has strongly categorized as “A”, electricity distribution companies as “R”, energy associations and universities as “C”, and educational and justice institutions as “I”.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcome. In this study we evaluated whether Naples Prognostic Score, a novel index which considers both inflammatory and nutritional values, was associated with long-term survival. The study is a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered four pre-operative parameters: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, serum albumin and total cholesterol. Kaplan-Meier method and Cox regression analysis were performed to evaluate the relation between the score and disease-free survival, overall survival and cancer-related survival. A total of 260 patients were selected for the study, reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between Naples Prognostic Score and overall survival (p=0.018) and cancer-related survival (p=0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both these survivals (p=0.007 and p=0.010 respectively). Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

The residual content of the only carbon source increases at the end of the exponential growth phase when P. putida BS3701 cells are cultured under nitrogen deficiency. Moreover, the mRNA quantity of some genes involved in carbon catabolism decreases. There are no available data on regulators capable of stimulating the target mRNA degradation in pseudomonads under nitrogen deficiency in the literature. We have applied both comparative genomics methods and a number of biomolecular ones to identify new small P. putida BS3701 RNAs. This is due to the fact that the formation of ncRNA-mRNA duplexes, recognized by RNases, is one of the main mechanisms for reducing the number of transcripts in a cell. We have used the following selection criteria: 1) the presence of the interest gene of the NtrC binding site and a sigma54-dependent promoter in the upstream area, 2) the conservative location of the interest gene in the P. putida and P. aeruginosa genomes, 3) increase in the product quantity of the interest gene in a cell under nitrogen deficiency on two different carbon sources (succinate and naphthalene), 4) the product detection of the interest gene in a fraction enriched with small RNAs. The expression of two new small RNAs has increased twice or more times under nitrogen deficiency on both succinate and naphthalene: expression of ng171 and ng379. ng379 contains narK RNA motif.

In recent years, the high-frequency abnormal price fluctuations of small-scale agricultural products have been detrimental to market stability. The traditional method based on statistical data of production factors can no longer accurately predict abnormal price fluctuations. Taking scallions as a case, the paper identifies price influencing factors from massive network information, and analyzes the causes and changing characteristics of price fluctuations from four perspectives: market supply, economic environment and market sentiment, and attention. Initially, the study employs an LDA topic model to extract factors from online sentiment data over the past four years, including market supply and demand, economic conditions, related agricultural prices, and market attention. Subsequently, using the SO-PMI algorithm to expand domain-specific lexicons and employing semantic and sentiment analysis with syntactic parsing, the study aims to improve the accuracy of sentiment quantification in text analysis. Furthermore, cointegration and Granger causality tests validate the significant impact of these factors on scallion price fluctuations, mitigating spurious regression issues. Finally, by employing a TVP-VAR model, the study compares the impulse responses and shock magnitudes of various factors in different time and spatial dimensions. It also delves into the mechanisms of heterogeneous impacts and trends in scallion prices, considering the corresponding socio-economic context and public sentiment events within specific time windows, thereby providing valuable decision-making insights for the healthy development of agricultural markets.

Concatemeric viral DNA is packaged into Bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme. Both native mass spectrometry and transmission electron microscopy reveal that the P22 terminase complex adopts three main assemblies, which include a nonameric S-terminase bound to two L-terminase 1(gp3)9:2(gp2), two nonameric S-terminase bound to five L-terminase 2(gp3)9:5(gp2), and three nonameric S-terminase bound to seven L-terminase 3(gp3)9:7(gp2). Native agarose gel electrophoresis shows that the terminase complex interacts with procapsid with mild crosslinking. These results herein illustrate the P22 terminase complex can adopt a variety of confirmations and assembly states.

Autoantibodies against specific lung cancer-associated antigens have been suggested for lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of anti-gen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, NGAL, and NSE in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9G DNA chip method. The ratios of AICs to their antigens and combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than their free antigens in all participants. The levels of each free antigen distinguished patients with NSCLC from HCs. The ratios of AIC to its antigen and seven combinations consisting of two to four ratios were significantly higher in patients with NSCLC than those in HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at cutoff 3.51. Higher sensitivity was observed in the very early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. The combination of all ratios of AICs and their antigens for all four markers is useful in the diagnosis of NSCLC.

Phylogenetic tree analysis is commonly used to understand the evolutionary distance between different species or strains of the same species. This work originally aimed to gain an understanding and visual depiction of the evolutionary distance in 23S rRNA gene of different Helicobacter pylori strains. Using an in-house MATLAB multiple sequence alignment and phylogenetic tree analysis software, the phylogenetic tree constructed for 23S rRNA gene reveals two major lineages with further subdivisions in each cluster. This suggests two major evolutionary forces driving the evolution of the 23S rRNA gene. In comparison, there is relatively short evolutionary distance in the 16S rRNA gene phylogenetic tree of H. pylori, suggesting lack of major evolutionary forces driving mutational changes of the gene. Overall, the data suggests that the large ribosome subunit which houses the 23S rRNA of H. pylori is undergoing significant conformational changes that may be a response to the frequent use of various antibiotics that target the ribosome of H. pylori.

Abstract: Pericyte(s) (Pcs) and resident perivascular macrophages (rPVMΦs) are positioned perfectly in the neurovascular unit (NVU) and perivascular spaces to facilitate metainflammation that results in brain endothelial cell activation and dysfunction and neuroinflammation. Their positions within the NVU allow intimate contact with one another as follows: Brain endothelial cells (BECs) and the Pcs via their shared basement membrane and physical contact peg-socket junctions with N cadherins and gap junctions Cx43; Pcs and rPVMΦs intimate contacts. Additionally, rPVMΦs have intimate contact with the astrocyte endfeet (ACef) that form the outermost membrane of perivascular spaces. Importantly, ACef have intimate contact with BECs that have intimate physical contact with neuronal axons and dendrites to complete NVU coupling. The multiplicity of intimate contacts of NVU cells allow for continuous crosstalk communications to provide brain homeostasis. While each of the cells of the NVU play important roles in the development of enlarged perivascular spaces (EPVS), this review focuses on the Pcs and rPVMΦs and discusses each of the intimate contacts and their functional significance in detail with numerous illustrations and transition electron microscopic images to demonstrate their role in the development of EPVS. EPVS are known to be biomarkers for cerebral small vessel disease and impaired glymphatic system waste clearance. Additionally, EPVS associate with mixed dementias of vascular dementia, vascular contributions to cognitive impairment and dementia, and Alzheimer’s disease that results in high economic and psychosocial cost to the global community.

In the vaginal ecosystem there is a symbiotic relationship between the microbiota and the host, particularly Candida spp., which are considered commensals of the vaginal mucosa. During pregnancy there is an increase in hormonal secretion that alters the vaginal microbiota and favors the development of Candida infection. Several studies have shown the increased prevalence of Candida during pregnancy, as well as its association with perinatal complications and current clinical practice guidelines recommend fluconazole as the treatment of choice during pregnancy in case of infection by Candida albicans and non-albicans Candida. However, in the Mexican population, this association has not been studied. So in this study, an intentional search for colonization by Candida spp. in pregnant women who attended the obstetric triage of the Hospital Regional de Alta Especialidad de Ixtapaluca during the period from May to October 2019, and they were followed up until the end of the pregnancy. Data on age, number of pregnancies, gestational age, body mass index, and perinatal outcomes were analyzed. Of 83 patients included in the study, yeasts corre-sponding to C. albicans (12) and C. glabrata (4) were isolated in 16. In the group of patients with Candida, the maternal age range was from 15 to 36 years old, of which 7 were adolescents and 2 with advanced maternal age, with an average of 2 gestations, the range of body mass index was from 19.3 to 42.4, of which 4 were overweight and 7 obese. Perinatal complications were observed in three patients, one presented chorioamnionitis and in two the neonates were small for gestational age. No association was found between colonization by Candida spp. and the number of preg-nancies, gestational age, body mass index or perinatal results. However, it was found that age (adolescence) may be a risk factor for the development of vulvovaginitis during pregnancy.

Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ribosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We investigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.

Abstract Kidney transplant recipients, because of a weak immune response due to the assumption of immunosuppressant are exposed to the risk of COVID-19 infection. This fact realize the problem on how to treat the severe infection without carrying the risk of acute rejection due to the reduction of the immunosuppressive drugs. The best are the prophylactic measures to be taken before transplantation as vaccination. If the patient is already transplanted, three measures may be undertaken: Vaccination, use of monoclonal antibodies, use of therapeutic antiviral small molecules. Concerning vaccination is still debated which one is the best and how many doses should be given. The surge of new virus variant is the major problem and invites to find new active vaccines. In addition, not all the transplanted patients develop antibodies. The other measure is the use of monoclonal antibodies. They may be used as prophylaxis or in the early stage of the disease. Finally, the antiviral small molecules may be used again as prophylaxis or treatment. Their major drawback are the interference with the immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

One of the most important challenges in the Machine and Deep Learning areas today is to build good models using small datasets, because sometimes it is not possible to have large ones. Several techniques have been proposed in the literature to address this challenge. This paper aims at studying the different available Deep Learning techniques and performing a thorough experimentation to analyze which technique or combination thereof improves the performance and effectiveness of the models. A complete comparison with classical Machine Learning techniques was carried out, to contrast the results obtained using both techniques when working with small datasets. Thirteen algorithms were implemented and trained using three different small datasets (MNIST, Fashion MNIST, and CIFAR-10). Each experiment was evaluated using a well-established set of metrics (Accuracy, Precision, Recall, F1, and the Matthews correlation coefficient). The experimentation allowed concluding that it is possible to find a technique or combination of them to mitigate a lack of data, but this depends on the nature of the dataset, the amount of data, and the metrics used to evaluate them.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.

To address the severe distresses of asphalt pavement, a new type of pavement maintenance treatment, porous ultra-thin overlay (PUTO) with small particle size was proposed. The PUTO has a thickness of 1.5~2.5 cm and a large void ratio of 18~25%. As a newly asphalt mixture, the structure characteristics differ from traditional pavement. Therefore, it is necessary to investigated the fabrication schemes in laboratory and on-site, respectively. In this study, the optimal fabrication schemes, including compaction temperature and number of blows of PUTO were determined based on Cantabro test and volumetric parameters. Then, the corresponding relationship between laboratory and on-site compaction work was then established based on the energy equivalent principle. On this basis, the numbers of on-site rolling passes and the combination method were calculated. The results show that increased compaction temperature and number of blows reduce the height and enhance the compactness of the Marshall sample. With the same temperature and number of blows, the scattering resistance of coarse gradation (PAC-1) is better than that of fine gradation (PAC-2), and the increased asphalt viscosity significantly improves the scattering resistance of the asphalt mixture. To ensure the scattering resistance and volumetric characteristic, the initial compaction temperature of the PAC-1 and PAC-2 should not be lower than 150 °C and 165 °C, respectively. Then, the laboratory compaction work and on-site compaction work were calculated and converted based on the principle of energy equivalence. Consequently, the on-site compaction combination of rolling machines for four asphalt mixtures was determined. According to the volumetric parameters, the paving test section proved that the construction temperature and the on-site rolling combination determined by laboratory tests are reasonable, and ultra-thin overlay has good structural stability, drainage and skid resistance.

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and caused by members of the Filoviridae family. The recent large outbreak of EVD in West Africa (2013-2016), highlighted the worldwide danger of this disease and its impact on global public health and economy. The development of highly needed anti-Filoviridae antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, and therefore screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to in vitro study of Filoviridae entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus like particles, tremendously boosted both our knowledge on viral life cycle and the identification of promising anti-Filoviridae compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

The properties of rubber are strongly influenced by the distribution of filler within the polymer matrix. Here we introduce a Monte Carlo-based morphology generator. The basic elements of our model are cubic cells, which, in the current version, can be either silica filler particles or rubber volume elements in adjustable proportion. The model allows the assignment of surface free energies to the particles according to whether a surface represents, for instance, 'naked' silica or silanised silica. The amount of silanisation is variable. We use a nearest-neighbour site-exchange Monte Carlo algorithm to generate filler morphologies, mimicking flocculation. Transmission electron micrographs (TEM) as well as small angle scattering (SAS) intensities can be calculated along the Monte Carlo trajectory. In this work we demonstrate the application of our morphology generator in terms of selected examples. We illustrate its potential as a tool for screening studies, relating interface tensions between the components to filler network structure as characterized by TEM and SAS.

This article concerns the adoption of small-scale irrigation farming as a climate-smart agriculture practice and its influence on household income in the Chinyanja Triangle. Chinyanja Triangle is a region that experiences mid-season dry spells and an increase in occurrences of drought due to low and erratic rainfall patterns which is attributed largely to climate variability and change. This poses high agricultural production risks, which aggravate poverty and food insecurity. For this region, adoption of small-scale irrigation farming as a climate-smart agriculture practice is very important. Through a binary logistic and ordinary least squares regression, the article determines factors that influence the adoption of small-scale irrigation farming as a climate-smart agriculture practice and its influence on income among smallholder farmers. The results show that off-farm employment, access to irrigation equipment, access to reliable water sources and awareness of water conservation practices, such as rainwater harvesting have a significant influence on the adoption of small-scale irrigation farming. On the other hand, the farmer’s age, distance travelled to the nearest market and nature of employment negatively influenced the adoption of small-scale irrigation farming decisions. Ordinary least squares regression results showed that the adoption of small-scale irrigation farming as a climate-smart agriculture practice has a significant positive influence on agricultural income. We therefore conclude that to empower smallholder farmers to quickly respond to climate variability and change, practices that will enhance adoption of small-scale irrigation farming in the Chinyanja Triangle are critical as this will significantly impact on agricultural income.

Besides the Lagrangian and the Eulerian descriptions, the motion of a body can also be expressed relative to the present configuration of the body, known as the relative motion description. It is interesting to consider such a relative motion description in general to formulate the basic system of field equations for solid bodies. In doing so, when the time increment from the present state is small enough, the nonlinear constitutive equations can be linearized relative to the present state so that the resulting system becomes linear. This will be done for thermoelastic materials with a brief comment on the exploitation of entropy principle in general. Relative Lagrangian formulation is based on the well-known ``small-on-large'' idea, and can be implemented for solving problems with large deformation in successive incremental manner. Some applications of such a formulation in numerical simulations are briefly reviewed.

The question of the relevance of human and natural capital, as well as the potential adverse effect of natural capital on economic growth, has gained increased attention in development economics. The aim of this paper is to theoretically and empirically assess the relevance of several forms of capital on economic growth in small economies that are dependent upon tourism or natural resources. The empirical framework is based on Impulse Response Functions obtained from Vector Autoregressive models in which we focus on the model where economic growth is the dependent variable for ten small economies that are dependent upon either tourism or natural resources. We find that there is evidence of the ‘’natural resource curse’’, especially in the economies that have a strong dependence on resources that are easily substitutable and whose prices constantly fluctuate. We further find that in the majority of observed cases the type of capital these small economies are most dependent on for their economic growth causes negative impulses in the majority of the observed periods. The main policy recommendation should be to assure that even these small economies should strive towards further diversification and avoid dependence on only one segment of their economy.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

Pinus squamata is one of the most threatened conifer endemic to northeastern Yunnan Province, China, and it is prioritized as one of the Plant Species with Extremely Small Populations (PSESP) for urgent protection in China. However, we lack a comprehensive consideration of the protection effect and the endangered mechanism, especially based on the underground growth status of endangered plants. The integrated study of soil properties and rhizosphere bacteria can assist conservation to understand therequired conditions for the protection and survival of rare and endangered species. In our study, bacterial communities in wild, ex-situ, and reintroduced P. squamata rhizosphere were compared using Illumina sequencing of the V3-V4 region of the 16S rRNA genes. We determined the soil physicochemical properties, analyzed the relationships between the bacterial communities and soil physicochemical factors, and predicted the potential bacterial ecological functions. The reintroduced site Qiaojia (RQ) had the highest richness and diversity. Samples were scattered (R = 0.93, P = 0.001), indicating significant difference between the different conservation sites. Soil total potassium (TK) and available nitrogen (AN) were the main factors driving bacterial community (0.01 &lt; P ≤ 0.05). The low abundance of Plant growth-promoting rhizobacteria (PGPR) may be a biotic factor contributing to the endangerment of P. squamata. This study provides a foundation to assess the effect of conservation based on bacterial diversity and plant growth-promoting rhizobacteria (PGPR) to guide future research into the conservation of P. squamata.

The study of angular correlations of heavy-flavor particles in hadronic collisions can provide crucial insight into the heavy-quark production, showering and hadronization processes. The comparison with model predictions allows us to discriminate among different approaches for heavy-quark production and hadronization, as well as different treatments of the underlying event employed by the models to reproduce correlation observables. In ultra-relativistic heavy-ion collisions, where a deconfined state of matter, the quark-gluon plasma (QGP), is created, heavy-flavor correlations can shed light on the modification of the heavy-quark fragmentation due to interaction of charm and beauty quarks with the QGP constituents, as well as characterize their energy loss processes while traversing the medium. Insight into possible emergence of collective-like mechanisms in smaller systems, resembling those observed in heavy-ion collisions, can also be obtained by performing correlation studies in high-multiplicity proton-proton and proton-nucleus collisions. In this review, the most recent and relevant measurements of heavy-flavor correlations performed in all collision systems at the LHC and RHIC will be presented, and the new understandings that they provide will be discussed.

The detection and analysis of small molecules, typically defined as molecules under 1000 Da, is of growing interest ranging from the development of small molecule drugs and inhibitors to the sensing of toxins and biomarkers. However, due to challenges such as their small size and low mass, many biosensing technologies struggle to have the sensitivity and selectivity for the detection of small molecules. Notably, their small size limits the usage of labeled techniques that can change the properties of small molecule analytes. Furthermore, the capability of real-time detection is highly desired for small molecule biosensors’ application in diagnostics or screening. This review highlights recent advances in label-free real-time biosensing technologies utilizing different types of transducers to meet the growing demand for small molecule detection.

The article presents a technology for producing nitrogen-containing nanoporous biocarbon with high degree of elemental composition homogeneity, confirmed by electron spectroscopy. The research explores the relationship among the electronic characteristics of supramolecular nanoporous carbon, its porous structure, and the capacitance at its interface with the electrolyte. The obtained biocarbon is characterized by micro and mesopores, as evidenced by the results of studies by the method of nitrogen adsorption/desorption. The specific area of the available porous surface was found to be 1247 m2/g. Comparing this result with the data of small-angle X-ray scattering, we conclude that micropores are open while mesopores remain closed. This material was found to have a saturation magnetization σs of 1.4 A∙m2∙kg-1 and a coercive force Hc of 10 kA/m. The impedance studies of electrochemical cells of supercapacitors made of the experimental biocarbon were carried out. Equivalent electrical circuits of the studied electrochemical processes were constructed and characterized.

In this work,the wave behaviour propagation of single-walled fluid conveying carbon nanotubes (SWCNT) under longitudinal magnetic fields and elastic foundations is studied, based on the nonlocal strain gradients theory(NSGT). With considertion of surface effect, the governing differential equation are obtained utilising Timoshenko beam theory and Hamilton's variational principle. The influence of small-scale parameters, fluid density, magnetic flux, surrounding elastic medium and surface effects on wave behaviour characteristics of carbon nanotubes are discussed in detail. The numerical results illustrated that with the magnetic flux increase，the phase velocities of the carbon nanotube will increase. When the fluid effects inside the carbon nanotube, the wave frequencies of the system reduces with increase in the non-local coefficient, while promotes with increase in the strain gradient coefficient. In addition, fluid density, surrounding elastic medium and surface effects have meaningful influence on the phase velocity of the system.

BACKGROUND: diabetic foot ulcers (DFU) represent the main cause of major amputations and hospitalizations in diabetic patients. Aim of this study was to assess safety and cost-efficacy of intramuscular injection of peripheral blood mononuclear cells (PBMNCs), in diabetic patients with no-option chronic limb-threatening ischemia (CLTI) and small artery disease (SAD). METHODS: a retrospective study was carried out on a series of types 2 diabetic patients with DFU grade Texas 3 and no-option CLTI and SAD. All patients had undergone at least a previous revascularization and were allocated in a surgery waiting-list for major amputation. The principal endpoint evaluated at 90 days was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoint were individual components of the primary endpoint, any serious and non-serious adverse events, direct costs at one year. RESULTS: the composite endpoint was achieved in 9 patients (60.0 %); one patient (6.7%) healed within 90 days and 26.7% and 46.7% showed TcPO2 ≥30 mmHg and a TcPO2 increase of at least 50% at 90 days, respectively. At 1-year, three (20.0%) patients underwent a major amputation (all diagnosed SAD grade III). One patient died after seven months, and seven patients (46.7%) healed. The overall median and mean cost per patient were 8,238±7,798€ and 4,426[3,798;8,262]€, respectively. CONCLUSIONS: the use of PBMNCs implants in no-option CLTI diabetic patients with SAD seems to be of help in reducing the risk of major amputation.

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.

In the leading/trailing edge’s adaptive machining of the near-net-shaped blade, a small portion of the theoretical part is retained for securing aerodynamic performance by manual work. However, this procedure is time-consuming and depends on the human experience. In this paper, we defined retained theoretical leading/trailing edge as the reconstruction area. To accelerate the reconstruction process, an anchor-free neural network model based on Transformer was proposed, named LETR (Leading/trailing Edge Transformer). LETR extracts image features from an aspect of mixed frequency and channel domain. We also integrated LETR with the newest meta-Acon activation function. We tested our model on the self-made dataset LDEG2021 on a single GPU and got an mAP of 91.9\%, which surpassed our baseline model, Deformable DETR by 1.1\%. Furthermore, we modified LETR’s convolution layer and named the new model after GLETR (Ghost Leading/trailing Edge Transformer) as a lightweight model for real-time detection. It is proved that GLETR has fewer weight parameters and converges faster than LETR with an acceptable decrease in mAP (0.1\%) by test results.

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites (e.g., exosites, ectosites) through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches such as proteomics and N-terminomics to identify new MMP substrates and achieve a better understanding of the roles of these proteases in diseases.

As early as February 2020, many countries have started imposing measures to curb the spread of Covid-19. Despite the right intention, it is a challenging moment for the people, especially the rural population living in the coastal areas. The document presents the preliminary findings on the impacts of Covid-19 on the small scale fisheries in Tun Mustapha Park, Sabah, Malaysia.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.

Social customer relationship management (SCRM) is a new philosophy influencing the relationship between customer and organization, where the customer gets opportunity to control relationship through social media. The paper aims on (a) identification of current level of SCRM and also on (b) influence of basic organizational characteristics on SCRM level. The data were gathered through the questionnaire distributed in 362 organization headquartered in the Czech Republic. The questionnaire comprised 54 questions focusing on the significance of marketing and CRM practices, establishing a relationship with the customer, online communities, the use of social media in marketing, and acquiring and managing information. The majority of questions were scalable and used typical five-level Likert scale. Results showed that larger firms more often set up their own online communities and manage them strategically, moreover they are able to manage information better. Contrariwise, small sized organizations use social networks as a way to establish communication with the customer more than large sized entities. Use of social media for marketing purposes is significantly higher in organizations oriented on consumer markets than on business markets.

Taking four of the United Nations Development Goals as reference, this overview describes the need to see from a systemic perspective, the food certifications programs along the food chain in Mexico as today food certifications are voluntary. Using secondary data, the main objectives were: a) there is a fall short in food safety policies and those federal agencies responsible for food safety, to guarantee safe food along the whole domestic food chain, especially in that for low income players; b) the amount of the Mexican Federal Budget Expenses devoted to safety food issues is really low, considering the health, well- being, and food security consequences; and c) due the structural heterogeneity of the Mexican food market, there is a lack of coordination in food regulations along all agents of the food supply chain, bringing to alternate informal markets that put at risk peoples´ health, increasing poverty and inequalities. According to this exercise, only 0.7- 8.7% of producers, 12.5% of supermarkets as well as 42.8% of restaurants would have some type of certifications. Public policies must attend this issue in order to improve food safety and security for the whole population, reducing inequalities, poverty and ensuring them a healthy live.

Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

The effectiveness of simple weirs and the ability of rural farmers to construct durable weirs are still areas of concern in rural areas in Zambia. The objective of this study is to investigate the factors contributing to the varying levels of durability of the simple weir structures used for the diversion of river flows. This study was conducted in 5 districts where 33 SWs located in similar geographical zones were analyzed for their longevity. The research delved into catchment and climatic variables, and the social and psychological perception of simple weirs. The study conducted interviews with key informants who were familiar with the use of SWs in 5 districts in Muchinga provinces between 26 December 2023 and 15 January 2024 using semi-structured questions. The findings of this study indicated that simple weirs constructed on relatively square-shaped catchments and narrow-shaped catchment areas were less vulnerable to damage and easy to operate and maintain. The study also found that climatic factors such as storm rainfall events had little impact on the operation and maintenance of these weirs in Muchinga province, as most sites are in the rainfall shadow while farmers` views about the structures varied from site to site. Overly, planning is necessary for implementing small or large irrigation structures.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Electrospun fiber scaffolds are widely used in small diameter vascular tissue engineering because they mimick organizational structure and biological function of natural extracellular matrix. However, there is still one problem of low patency rate in the long term. The main reasons are the mismatch of compliance and the easy formation of thrombus. Therefore, it is very important to promote the rapid endothelialization of small diameter tissue engineering blood vessels by regulating the topological structure and biological properties of electrospun fiber scaffolds. Firstly, crimped polylactic acid (PLA) fibers were prepared by heat treatment to mimick the crimped structure and nonlinear mechanical properties of the elastic membrane of blood vessel wall. It improved effectively the aspect ratio of human umbilical vein endothelial cells (HUVECs) and promoted lateral alignment and growth. Then, crimped PLA fibers with three levels of pore structure were prepared by thermal induced phase separation, vapor induced phase separation and laser ablation to enhance the degree of HUVECs infiltrarion and realize patterned cell growth. Crimped PLA fibers with three levels of pore structure promote rapid endothelialization of blood vessels, which is of great significance to achieve long term patency rate of small diameter tissue engineering blood vessels.

Energy transition is one of the greatest challenges facing humanity today. All micro, small, medium and large enterprises in operation will have to face it, and some can al-ready boast the first successes in this regard. This paper focuses on the involvement of these smallest players in energy transition. Micro and small entities are the largest part of the economy, having a great influence on its development. Looking at the wide scale of their activities, these entities are distinguished by a specific owner-manager relationship. This means that the final decision-making is influenced by business goals, but also by the manager's approach, their awareness of changes, and personal and other factors. Based on a structured and standardized survey questionnaire, the research was carried out using the Computer-Assisted Telephone Interviewing technique between April and May 2022 among owners of micro and small enterprises operating in Poland. The survey showed that active engagement of micro and small enterprises in energy efficiency initiatives is related to their market success and financial health.

Small-scale fisheries are significant sources of nutrition and livelihood globally. However, increasing anthropogenic activities in coastal areas of developing countries have threatened the sustainability of artisanal fisheries and species. Fisheries of Sardinella maderensis (Lowe, 1838), to which Nigeria contributes 9% of the global stock and is a significant livelihood source in the coastal communities of Ibeju-Lekki, Lagos, face sustainability threats. This research investigated the effects of anthropogenic activities on S. maderensis fishery in the coastal areas of Ibeju-Lekki, Lagos, Nigeria. The study adopted a mixed-method approach involving qualitative and quantitative research methods. These include species identification, water quality analysis, land use change analysis, field surveys, focus group discussions and interviews. Results show genetic analysis of the fish samples from six stations revealed that the species had a mean of 98% similarity to Sardinella maderensis in NCBI. Multiple linear regression indicates that anthropogenic variables explained approximately 4.62% of the variance in the fish catch (p &lt; .001, R2 = .05). Water samples showed heavy metal levels were above international limits, high total petroleum hydrocarbon (TPH) pollution in all stations (27.56 mg/L- 3985.40 mg/L). Physiochemical analysis of water samples indicated TDS higher than acceptable limits (Mean = 24971.1 mg/L) and inadequate chlorophyll-a level (Mean = 0.01 µg/L). Hence, urgent strategies are required to mitigate anthropogenic threats through inclusive coastal management policies supporting resilient artisanal fisheries and marine spatial planning.

The authors of the article analyze the existing methods and models of technological preparation of machine-building industries. The structure of a three-level simulation model with network-centric control, the structures of individual elements of the simulation model and the process of simulation modeling are described. The criteria for choosing a rational option for the processing technological route have been determined. During the research, a simulation program was implemented in C++. It allows you to select the optimal scenario for the operation of a production site based on two criteria: time and cost. The volume of implementation is about 2x103 lines of code. A diagram of the modeling algorithm for the implemented program, a description of the classes and their interactions are given in the article. The developed simulation model was tested at a machine-building enterprise using the example of the “Pusher” part, manufactured under single-unit production condi-tions. The technological equipment used for the manufacture of this part was formed in the form of input data of the simulation model. The results of simulation modeling for the selected part are described. For each variant of the technological processing route, the values of variable costs and the duration of the production cycle were determined.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

In the realm of modern drug discovery, the integration of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structural-activity relationships (SARs), play a pivotal role in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. By embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.

Compared to wide-field telescopes, small-field detection systems have higher spatial resolution, resulting in stronger detection capabilities and higher positioning accuracy. When detecting by small-field in synchronous orbit, both space debris and fixed stars are imaged as point targets, making it difficult to distinguish them. In addition, with the improvement of detection capabilities, the number of stars in the background rapidly increases, which puts higher requirements on recognition algorithms. Therefore, star detection is indispensable for identifying and locating space debris in complex backgrounds. To address these difficulties, this paper proposes a real-time star extraction method based on adaptive filtering and multi frame projection. We use bad point repair and background suppression algorithms to preprocess star image. Afterwards, we analyze and enhance the target signal-to-noise ratio(SNR). Then, we use multi frame projection to fuse information. Subsequently, adaptive filtering, adaptive morphology, and adaptive median filtering algorithms are proposed to detect trajectories. Finally, the projection is released to locate the target. Our recognition algorithm has been verified by real star images, and the images were captured using small-field telescope. The experimental results demonstrate the effectiveness of the algorithm proposed in this paper. We successfully extracted hip-27066 star, which has magnitudes about 12 and SNR about 1.5. Compared with existing methods, our algorithm has advantages in both recognition rate and false-alarm rate, and can be used as real time target recognition algorithm for space-based synchronous orbit detection payload.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO’s performance does not deteriorate as PVS volume increases. Second, the performance of all “vesselness” filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

Potato is among one of the most important food crops, yet maintaining plant productivity in this drought-sensitive crop has become a challenge. Competition for scarce water resources and the continued effects of global warming exacerbate current constraints on crop production. While plants’ response to drought in above-ground tissues has been well documented, the regulatory cascades in developing tubers have been largely unexplored. Using the commercial Canadian cultivar ‘Vigor’, plants were subjected to a drought treatment under high-tunnels causing a 4 ℃ increase in canopy temperature when compared to the well-watered control. Tubers were sampled for RNAseq and metabolite analysis. Approximately 2600 genes and 3898 transcripts were differentially expressed by at least four-fold in drought-stressed potato tubers, with 75 % and 69 % being down-regulated respectively. A further 229 small RNAs were implicated in gene regulation during drought. The comparison of protein homologues between Solanum tuberosum L. and Arabidopsis thaliana L. indicates that downregulated genes are associated with phenylpropanoid, carotenoid, and patatin biosynthesis. This suggests that there may be nutritive implications to drought stress occurring during the potato tuber bulking phase in sensitive cultivars.

Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.

The alignment of nanostructures in materials such as lyotropic liquid crystals (LLCs) templated materials has the potential to signicantly improve their performances. However, accurately characterising and quantifying the alignement of such fine structures remains very challenging. In situ small angle X-ray scattering (SAXS) and molecular dynamics were employed for the first time to understand the hexagonal LLC alignment process with magnetic nanoparticles under a magnetic field. The enhanced alignment has been illustrated from the distribution of azimuthal intensity in the samples exposed to magnetic field. Molecular dynamics simulations reveal the relationship between the imposed force of the magenetic nanoparticles under magnetic field and the force transferred to the LLC cylinders which leads to the LLC alignment. The combinational study with experimental measurement and computational simulation will enable the development and control of nanostructures in novel materials for various applications.

Currently, companies and SMEs (small and medium enterprises) are looking to be more competitive. In order to achieve this, they are adopting new business models and strategies that allow them to move towards sustainability. Strategies such as CSR (Corporate social responsibility) and supply chain management have become essential for ensuring a company’s permanence and financial consolidation. The literature has stated that the theories of Stakeholders and Sustainability are fundamental pillars for the development and sustained growth of business. The purpose of this article is to examine the effects of CSR and the SC (supply chain) on innovation, image and reputation, and in turn, their influences on profitability in SMEs. This research is based on a sample of 143 companies in the city of Guaymas Sonora, in Mexico. For the analysis and validation of the results, we used the SEM (Structural Equation Modeling) statistical technique based on the variance, through PLS (Partial Least Squares) (using SmartPLS version 3.2.6 Professional). The findings show that SMEs that develop social and sustainable practices increase their level of innovation, and improve their image, their reputation, and their financial profitability. This work contributes mainly to the development of Stakeholders and Sustainability.

The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transactivity of each other. Mttp mRNA and protein levels of Shp^/– mice were similar to those of wild-type; however, those of Chrebp^–/–Shp^–/– and Chrebp^–/– mice were much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp^–/–- mice were similar to wild-type, but were much lower in Chrebp^–/– and Chrebp^–/–Shp^–/–- mice. These findings suggested that ChREBP rather than SHP regulates VLDL secretion and that ChREBP and SHP do not affect the transactivities of each other.

The development of small scale hydroelectric power plants in Norway is determined by natural conditions, policies, attitudes and property rights. The owner of the river is the central decision maker. It is he who decides whether he will develop the power plant himself, Whether he wants to enter into a contract with an external investor and let him develop the power plant, whether he will sell his property rights or postpone the decisions. All available choices will involve risk. In order for him to make the best choice he must find the certainty equivalent to each of the choices and choose the one with the highest certainty equivalent. This is the first time the utility theory of John von Neumann and Oskar Morgenstern has been applied to decision makers in the hydro power industry in Norway.

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

The EU’s energy targets are to achieve at least 32% renewables in the energy mix by 2030. Part of the solution is strengthening consumer rights by empowering individuals to generate their own electricity. The study aimed to identify the most suitable energy system for electricity generation of up to 50 kW in the EU residential sector. The Multi-Criteria Decision Analysis was used to compare four systems: proton exchange membrane fuel cell with photovoltaic panels, photovoltaic panels, biomass powered Stirling engine, and solar powered Stirling engine. Based on the results, the most beneficial system for household electricity generation is the Biomass-fueled Stirling engine system due to its affordability, reliability, and low environmental impact. Governments and businesses can use these findings to improve information for the residential sector and enable the transition to renewable energy.

Simple weir irrigation was recently introduced in rural areas of Zambia. This irrigation technique is based on gravity diversion of the river flow using simple weirs. This study was conducted between November 2022 to January 2023 in 3 northern region provinces (Luapula, Copperbelt, and North-western) of Zambia to perform a diagnostic assessment on simple weirs during the dry and the wet seasons. In this study, 15 single-line simple weirs were selected. The objective of the study is to assess the physical status, identify problems and extent, and estimate water diversion potential by each single-line weir. The findings of this study showed that 67% of weirs were in excellent status (recently maintained and repaired), and 26% of the weirs were partially damaged (leakages, decayed thatch grass). The study revealed that single-line weirs were able to raise a flood height of 0.1m at low flow and 0.5m at medium flow. It was found that single-line weirs in excellent condition diverted more than 90% of the river flow while poorly maintained weirs diverted below 45% of the river discharge. Based on the findings, Single-line weirs have the potential to assist small-scale farmers in accessing river water for irrigation purposes through diversion.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

During two decades back, the growth of the fisheries sector in Indonesia was showing increasing trend, however, behind the rapid development of the sector, small-scale fisheries role is often neglected as one of the main actors to support the whole sector. They remain poor and doing fishing activities traditionally. Therefore, this study aims to describe the real situation of small-scale fishers, analyzing fishers’ ownership of the boat, analyzing their income level to reveal their poverty condition, to analyze the factors affecting their income. The regression analysis results indicate that fishing days, boat category, sea fish catch, fish selling price, variable cost, and secondary job have significant affect to fishers’ net income.

Ral-interacting protein 76 (RLIP76) is a potential factor with vascular endothelial growth factor (VEGF) in the corpus luteum and tumor angiogenesis. RLIP76, VEGF, and hypoxia-inducible factor-1 (HIF-1) are proteins that activate angiogenic functions in tumor and endothelial cells. RLIP76 is a main factor in tumor growth, and VEGF is a major endothelial cell protein for angiogenesis. Also, RLIP76 regulates a small GTPase (R-Ras, oncogene) in cell survival, spreading, and migration. HIF-1 is important in the corpus luteum, tumor angiogenesis, and tumor growth. VEGF and HIF-1 regulate the angiogenic function of RLIP76, and RLIP76 controls vascular growth in endothelial and tumor cells. RLIP76, R-Ras, VEGF, and HIF-1 may be useful in the research of corpus luteum and cancer therapy and the study of mechanisms of tumor angiogenesis. This review will help to elucidate the roles of RLIP76/R-Ras and VEGF via HIF-1 in corpus luteum and tumor angiogenesis, tumorigenesis, and the specific regulation of RLIP76 in luteal, tumor, and endothelial cells. Thus, we reviewed the angiogenesis of the corpus luteum and tumor in the ovarian and tumor microenvironment.

The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining &gt;10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Besides the increase in global energy demand, access to clean energy, reduction in greenhouse gas emissions caused by conventional power generation sources, energy security, and availability of electricity in remote villages in emerging nations are some of the factors that foster the use of renewable energy sources (RESs) in generating electricity. One of the aims of initiating microgrids (MGs) is to maximize the benefits of RES and alleviate the associated grid integration issues. Microgrids are made up of RES connected to electrical loads within clearly delineated electrical limits that operate as individual controllable units on the electrical network. It can operate in-dependently as well as in connection with the grid. The paper presents an overview of microgrids and investigates the system's performance when connected to and disconnected from the grid. Furthermore, in both modes of operation, the functioning and behavior of system components such as the bidirectional DC-DC converter and energy storage system (ESS) were evaluated. The architecture of the proposed microgrid consists of a small hydropower plant, a wind farm, and a battery energy storage system (BESS). The microgrid under investigation is modeled and simu-lated using MATLAB and Simulink.

Accurate evaluation of thermo-fluid dynamic characteristics in tank are critically important for designing liquid hydrogen tank of small-scale hydrogen liquefier to minimize heat in-leak into the liquid and ullage. Due to the huge cost, most future liquid hydrogen storage tank designs will have to rely on predictive computational models for storage tank pressurization and heat-leak minimization. Thus, reliable on predictive numerical models to aid design process of tank design have been required. Therefore, in this study, in order to improve the storage efficiency of the small-scale hydrogen liquefier, a three-dimensional CFD model that can predict the boil-off rate and the thermo-fluid characteristics due to heat penetration has been developed. The prediction performance and accuracy of the CFD model is validated on the basis of the comparisons between its results and previous experimental data and a good agreement is obtained. To evaluate insulation performance of polyurethane foam according to thickness, the pressure change and thermo-fluid characteristics in a partially liquid hydrogen tank, subject to fixed ambient temperature and wind velocity, has been investigated numerically. Three different insulation thickness were considered to investigate not only interfacial characteristics between liquid and ullage but thermo-fluid dynamics in hydrogen storage tank for various heat-leak situation. The results indicate that as the insulation thickness becomes thinner and more heat penetration exists, natural convection by buoyancy develops stronger, so strong vortices are created near the interfacial zone by upward flow driven by buoyancy. In particular, as the amount of heat in-leak increased, wider and stronger heat accumulation was found in the top dished head area of the ullage area. In addition, it was confirmed that the CFD model developed in this study could well describe the phenomenon in which the temperature of the tank wall and the insulation mat increased at a faster rate due to faster heat transfer from the vapor and interface. In the future, the numerical model developed in this study will be used for optimizing insulation system of storage tank for small-scale hydrogen which is cost-effective and highly efficient.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

To contribute to small and medium enterprises (SMEs) sustainable transition into the circular economy, the study proposes the activation of organizational learning (OL) processes – denoted here as multi-level knowledge creation, transfer, and retention processes – as a key phase in introducing circular business models (CBMs) at SME and supply chain (SC) level. The research employs a mixed-method approach, using the focus group methodology to identify contextual elements impacting on CBM-related OL processes, and a survey-based evaluation to single out the most frequently used OL processes inside Italian construction SMEs. As main result, a CBM-oriented OL multi-level model offers a fine-grained understanding of contextual elements acting mutually as barriers and drivers for OL processes, as possible OL dynamics among them. The multi-level culture construct – composed of external stakeholders’, SC stakeholders’, and organizational culture – identify the key element to activate CBM-oriented OL processes. Main implications are related to the identification of cultural, structural, regulatory, and process contextual elements across the external, SC, and organizational levels, and their interrelation with applicable intraorganizational and interorganizational learning processes. The proposed model would contribute to an improved implementation of transitioning into the circular economy utilizing sustainable business models in the construction SMEs.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

Although the spanwise periodicity within the gap between two tandem circular cylinders has been observed by some researchers, there is a lack of systematic study on the properties of this pe-riodicity. For the spanwise periodicity within the gap, this study aims to ascertain its characteris-tics, its influences on the flow field, and its variation trend with increasing spacing ratio. By nu-merically simulating the flow around two tandem circular cylinders with a diameter ratio of d/D=0.6 and seventeen spacing ratios (L/D=1.00~6.00) at Re=3900, this study shows four flow re-gimes: Reattachment Flow (L/D=1.00~3.15), Bi-stable Flow (L/D=3.24), Intermittent Lock-in Co-shedding (L/D= 3.30~3.50) and Subharmonic Lock-in Co-shedding (L/D=4.00~6.00). Further, de-pending on the spanwise periodicity length of the time-averaged flow structures (i.e. Pz) within the gap, Reattachment Flow is, for the first time, subdivided into three new sub-flow regimes: Small-scale Periodic Reattachment (L/D=1.00~1.50, Pz/D=(0, 4]), Large-scale Periodic Reattachment (L/D=2.00~2.25, Pz/D>4) and Non-periodic Reattachment (L/D=2.50~3.15, no spanwise periodicity). The formation mechanisms are elaborated by analyzing the combined effect of both the L/D value and the spanwise-averaged time-averaged reattachment angle of the downstream cylinder. Moreover, this study proves that the newly-defined Small-scale Periodic Reattachment and Large-scale Periodic Reattachment are responsible for the pronounced asymmetry of the flow along the transverse direction within the gap. In addition, detailed flow properties and statistical pa-rameters are provided for each flow regime, such as velocity, vorticity, force coefficient, separa-tion/reattachment angle, Strouhal number and Q-criterion.

The variability of the material properties of steel from different suppliers causes problems in achieving the required surface quality after turning. Therefore, the manufacturer needs to be able to estimate the resulting quality before starting production, especially if it is an expensive, small-batch production from stainless steel. Predictive models will make it possible to estimate the surface roughness from the mechanical properties of steel in the Mill Test Certificate (MTC) and thus support decision-making about the supplier selection or the acceptance of a material supply. Multivariate second-order polynomial model and feedforward back-propagation Artificial Neural Network (ANN) model were used to enhance the methodological robustness in formulating the decision if the predicted surface roughness is outside the required range, even before accepting the delivery. Both models can accurately predict surface roughness, while the ANN model is more accurate than the polynomial model; however, the predictive model is sensitive to the accuracy of the input data, and the model’s prediction is valid only under precisely defined conditions. The prediction model is used in a step-by-step decision-making procedure, which enables the trained staff to make a quick decision.

Abstract: Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components in NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background of NSCLC is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin. We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the effect of transcription factor (TF) LRF, a known epigenetic silencer, was examined on the epigenome modulation. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060-109,747,960 mouse chromosomal region to micro-RNA upregulated species. Fur-thermore, the novel epigenetic miR-148b-3p/PVT1/ZBTB7A axis was identified, which differentiates lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes. The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease and patient-tailored treatments.

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

Researchers have reported various impacts of the COVID-19 outbreak on small-scale fishers, such as stagnating market demands, reduction of market price and income, etc. While literature have heeded to these impacts in a relatively short time frame, scant evidence exists on the changing impacts over time and on the detailed processes of how fishers have been coping with the challenges in a longer time period. Furthermore, few studies have comprehensively analysed the impacts and strategies from multiple perspectives. This study aims to explore the perceived impacts of the COVID-19 outbreak on small-scale fishing communities and to highlight the coping strategies adopted by fishers over a year since the initial outbreak, through a case study in Trang Province, Thailand. Analysis of both qualitative and quantitative data obtained through semi-structured interviews indicated that fishers wisely utilised natural, financial and social capitals at the early stages of the outbreak, while human capitals were essential for recovering from the impacts in the later stages. Our findings suggest that the adaptive capacity to flexibly change livelihood strategies are crucial, while alternative income source may not necessarily help small-scale fishers under stagnating global economy.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

Abstract Aim of the study: Presentation of ophthalmic symptoms of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infracts and Leucoencephalopathy (CADASIL). Material and methods: Clinical presentation of female patient with diagnosed CADASIL, manifested by transient loss of vision, migraine, convergence insufficiency, diplopia, increased deep tendon reflexes of upper left limb, subcortical infarcts, mood disturbances and dementia. Results: Confirmed NOTCH3 gene mutation (p.Cys212Gly), and presence of granular osmiophilic material (GOM) in cutaneous small vessel wall in immunohistochemistry laboratory test (IHC). Magnetic resonance imaging (MRI) revealed bilateral focal vasogenic lesions in white matter of cerebral hemisphere with single micro-focal infarct in the left external capsule. Furthermore, a left eye exophoria, a bilateral peripheral visual field loss of 20 degrees and a loss of nasolabial fold was confirmed during ophthalmic tests. An eye fundus examination as well as a fluorescein angiography (FA) revealed vessel constriction of retinal arteries and a peripheral retinal pigment epithelium (RPE) atrophy with focal drusen in the left eye. The doppler ultrasonography (USG) confirmed a decreased blood flow and an increased vascular resistance of the extraocular vessels. The pattern electroretinogram (PERG) revealed a reduced P50 wave amplitude in the patient’s left eye. Conclusions: intermittent blindness, migraine, convergence failure, diplopia with specific MRI signs, NOTCH3 mutation, and the presence of GOM in the skin of small blood vessels in a young or middle-aged patient suggests CADASIL. New observations include: atrophic changes in the RPE, hemodynamic disturbances in blood flow in the short posterior ciliary arteries and in the central retinal artery, single drusen in the retina, and a reduced amplitude of the P50 wave in PERG.

Electrical properties of the thin films of poly(arylene ether ketone) copolymers (co-PAEKs) with the fraction of phthalide-containing units of 3, 5 and 50 mol% in the main chain were investigated by using radiation induced conductivity (RIC) measurements. Transient current signals and current-voltage (I-V) characteristics were obtained under exposing 20÷25 thick films of the co-PAEKs to monoenergetic electron pulses of the energy ranged from 3 to 50 keV in the electric field ranged from 5 to 40 V/μm. The Rose-Fowler-Vaisberg semi-empirical model based on a multiple trapping formalism was used for an analysis of the RIC data and the parameters of the highly dispersive charge carrier transport were evaluated. The analysis revealed that charge carriers moved in isolation from each other and the applied electric fields were below the threshold field triggering the switching effect (a reversible high-to-low resistivity transition) in the co-PAEK films. It was also found that the co-PAEK films due to the super-linear I-V characteristics are highly resistant to electrostatic discharges arising from the effects of ionizing radiation. This property is important for the development of protective coatings for electronic devices.

This study demonstrates a global, non-parametric, non-iterative optimization of time-mean value of a kind of index vibrated by time-varying forcing. It is based on the fact that the (steady) forced vibration of non-autonomous ordinary differential equation systems is well approximated by an analytical solution when the amplitude of forcing is sufficiently small and its base state without forcing is linearly stable and steady. It is applied to optimize a time-averaged heat-transfer rate on a two-dimensional thermal convection field in a square cavity with horizontal temperature difference, and the globally optimal way of vibrational forcing, i.e. the globally optimal, spatial distribution of vibrational heat and vorticity sources, is first obtained. The maximized vibrational thermal convection corresponds well to the state of internal gravity wave resonance. In contrast, the minimized thermal convection is weak, keeping the boundary layers on both sidewalls thick.

Statistical denoising techniques have been well studied, however many challenges still remain. This 9 article focuses on determining the least necessary number of significant samples in a statistical pop-10 ulation sampling, while minimizing the impact on the statistical detection of the fiber Bragg grating 11 (FBG) power spectra. This is achieved by using Bayesian decision making, small population statis-12 tics while excluding false detection. First, we investigate the impact of two-sided sliding window 13 technique applied near the cell under the test. The window size varies from 8 to 60 samples. The 14 considered maximum size of population sampling is connected with the number of wavelength 15 samples within the bandwidth of the symmetrical FBG power spectra peaks. Regarding the sym-16 metry of FBG power spectra peaks and the possible reduction of computational demands, we inves-17 tigate the impact of a one-sided sliding window. This enables to achieve less processing latency for 18 real time applications thus brings benefits to FBG-based fiber optical sensing. Both, two- and one-19 sided small population sampling techniques are then experimentally verified. Detection results are 20 analyzed in depth via calculating detection thresholds by using the small size window sliding along-21 side the waveband. From results achieved, it was found that the normality three-sigma rule does 22 not need to be followed while using the small population sampling. Experimental demonstrations 23 and analyses showed that the proposed concept of denoising and statistical threshold detection 24 based on the sliding window does not depend on the prior knowledge of probability distribution 25 functions of the FBG power spectra peaks level and background noise. We have also found that the 26 thresholds’ adaptability mainly depends on the statistical numerical characteristics of the above ad-27 ditive mixture of the FBG power spectra peaks signals and background noise.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Small-scale facilities play a significant role in the landscape of nuclear physics research in Europe. They address a wide range of fundamental questions and are essential for teaching and training personnel in accelerator technology and science, providing them with diverse skill sets, complementary to large projects. The current status and perspectives of nuclear physics research at small-scale facilities in Europe will be given.

Maternal and child nutrition has been a critical component of health, sustainable development, and progress in low- and middle-income countries (LMIC). While a decrement in maternal mortality is an important indicator, simply surviving pregnancy and childbirth does not imply better maternal health. One of the fundamental obligations of nations under international human rights law is to enable mothers and teenage girls to endure pregnancy and delivery as an aspect of their enjoyment of reproductive and sexual health and rights and live a dignified life. The aim of this study was to discover the correlation between the Maternal Observation and Motivation (MOM) program and m-Health support for maternal and newborn health. A Comparative study was done among 109 pregnant mothers (study group-94; control group-102 mothers) with not less than 20 weeks of gestation. Maternal outcomes such as Hb, weight gain and newborn results like birth weight and crown- heel length was obtained on the baseline, 28 and 36 weeks of gestation. Other secondary data collected were abortion, stillbirth, low birth weight, major congenital malformations, twin or triplet pregnancies, physical activity and maternal wellbeing. The MOM intervention included initial face to face education, three in-person visits and eight virtual health coaching by WhatsApp. The baseline data on Hb of the mothers show that 31(32.98%) vs 27(28.72%) of the study and control group had anaemia, which improved to 27.66% and 14.98% among study group mothers at 28 and 36 weeks of gestation (p<0.001). The weight gain (p< 0.001), level of physical activity (p< 0.001), and maternal wellbeing (p< 0.01) also had significant differences after the Intervention. Even after controlling for potentially confounding variables, the maternal food practices regression model revealed that birth weight was directly correlated with consumption of milk (p 0.001), fruits (p 0.01), and green vegetables (p 0.05).As per the physical activity and maternal wellbeing regression model, the birth weight and crown heel length were strongly related with the physical activity and maternal wellbeing of mothers at 36 weeks of gestation (p <0.05). Combining the MOM intervention with standard antenatal care is a safe and effective way to improve maternal welfare while upholding pregnant mothers' human rights.

This paper presents a robust and efficient fault detection and diagnosis framework for handling small faults and oscillations in synchronous generator (SG) systems. The proposed framework utilizes the Brunovsky form representation of nonlinear systems to mathematically formulate the fault detection problem. A differential-flatness model of SG systems is provided to meet the conditions of the Brunovsky form representation. A combination of high-gain observer and group method of data handling neural network is employed to estimate the trajectory of the system and to learn/ approximate the fault and uncertainties associated functions. The fault detection mechanism is developed based on output residual generation and monitoring so that any unfavourable oscillation and/or fault occurrence can be detected rapidly. Accordingly, an average L1-norm criterion is proposed for rapid decision making of faulty situations. The performance of the proposed framework is investigated for two benchmark scenarios which are actuation fault and fault impact on system dynamics. The simulation results demonstrate the capacity and effectiveness of the proposed solution for rapid fault detection and diagnosis in SG systems in practice, and thus enhancing service maintenance, protection, and life cycle of SGs.

Market turbulence with fiscal investment influences has altered IT infrastructure performance as business pursue extravagant new technology adoption. Yet, few studies have examined how shareware solution goes beyond Medium Size Enterprise that pushes efficiency and sustainability. This PLS-SEM integrated with dual primary compilation approach lessens shallow perceptions coupled with outlooks that streamline each phenomenal activity that is worthy of the necessity for competitive innovation. This unified model was applied to sampling respondents and analyzed using an ordinal regression relationship that generates a robust association that triggers the hypothesis acceptance. The adopting of BOINC shareware mesh network towards unified processing designs that were employed to build the yield by promising financial possibility using coordinated interworks hence improved group accomplishment and establishing greater esteem. This paper showcases a flexible inner IT infrastructure alongside the economic uncertainty with the framework advancement for Exostructure as a Service. Associated theoretical and practical implications were discussed.

Recent studies on seafloor mapping have presented different modelling methods for the automatic classification of seafloor sediments. However, most of these studies have applied these models to seafloor data with appropriate number of ground-truth samples, which raises the question whether these methods are applicable to studies with smaller numbers of ground-truth data. In this study, we aim to address this issue by conducting sediment class-specific predictions using ensemble modelling to map areas with limited or without ground-truth data and combined with hydro-acoustic datasets. The resulting class-specific maps were then assembled into one map, where the most probable class was assigned to the appropriate location. Our approach was able to predict sediment classes without bias to the class with more ground-truth data and produced reliable seafloor sediment distributions maps that can be used for seafloor monitoring. Sediment shifts of a heterogenous seafloor in the Sylt Outer Reef, German North Sea were also assessed to understand the sediment dynamics in the area. The analyses of sediment shifts showed that the western area of the Sylt Outer Reef is highly active, and the results of the analyses assisted in providing recommendations on future seafloor monitoring activities.

To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.