The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.

With the recent coronavirus pandemic (Covid-19) online sales of clothing retail have become a necessity to survive in the market. It is for this reason that the objective of the research was to know the purchase intention of clothing by young consumers through the online channel of small and micro companies (MiPyMe) located in the countries of Mexico, Colombia and Peru. To do this, using a structural equations model, it was intended to analyze the relationships between the variables trust, satisfaction, perceived value, quality of interaction and image in the electronic context as antecedent variables of online purchase intention, in accordance with the theoretical framework. 638 surveys were applied to young consumers in Mexico, Colombia and Peru. Sociodemographic characteristics included gender, age, country, and knowledge of a MiPyMe online clothing store. The results reveal that, of the total of young people surveyed, 62.7% stated that they did not know of any online clothing store of a MiPyMe. The contrasting of the hypotheses indicates that the quality of interaction directly and positively influences perceived value, that the image directly and positively influences the satisfaction and purchase intention of the consumer of the MiPyMe of Colombia, Mexico and Peru. These results may be useful for entrepreneurs in this business sector to rethink their online business strategies, as well as for the governments of these nations to promote this sector with training and specialized technical assistance.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

The main obstacle affecting the natural and herbal products industry is the infringement of trade patents. This resulted in losing the opportunity to compete with others in this business. Creating additional value to this business is, therefore, a way of leading to patenting for trade protection for entrepreneurs. This study was conducted to develop the structural equation modeling of guidelines for creating additional value for Thai herbs to support trade patent. The study comprises a mixed method with three parts. In the first part, data comes from interviews with selected 9 specialists. The second part was supported by interviews to create the questionnaire and distributed it to 500 entrepreneurs, the next step was the data analysis using structural equation modeling (SEM). The third part used data from the SEM model to discussion focused on developing the conceptual model by 7 experts. The analysis of the developed model passed the criteria for evaluating consistency and empirical data. All hypotheses proposed in this study were supported, the findings revealed that all factors had a direct effect at a statistically significant level of 0.001. Furthermore, this investigation allows knowing the Brand Identity factor were practically important for creating value of Thai herbs leading to patent protection.

This research aims to analyse the sustainability of retirement system and relevant optimal path to achieve sustainable post-retirement livings in Malaysia context. Focus of this study is put on Employees Provident Fund (EPF) which is mainly constituted by employees from private sector. EPF is a fully funded defined-contribution by both employees and employers. In this research, main variables used are contribution rate and retirement age based on relevant indexation of pension. For a sustainable retirement living, retirement benefits are expected to be in a maximisation function. Attempts to find sustainable retirement fund are via step-by-step mathematical calculation using formulas in Microsoft Excel and verification of the result with Excel Solver via Generalised Reduced Gradient (GRG) algorithm. Eventually, two-third retirement decision model is used to justify the sustainability of retirement fund other than justification using monthly household expenditure.

Due to the increase in the emission of greenhouse gases, the hydrologic cycle is being altered on the daily basis. This has affected the variations in relations of intensity, duration, and frequency of rainfall events. Intensity Duration Frequency (IDF) curves describe the relationship between rainfall intensity, rainfall duration and return period. IDF curves are one of the most often applied implements in water resource engineering, in areas such as for operating, planning and designing of water resource projects, or for numerous engineering projects aimed at controlling floods. In particular, IDF curves for precipitation answer problems of improper drainage systems or conditions and extreme characters of precipitation which are the main cause of floods in Nyabugogo catchment. This study aims to establish Rainfall IDF empirical equations, curves and hydrological discharge (predicted peak rate of runoff (Qlogy)) equations for eight Districts that will be used for designing an appropriate and sustainable hydraulic structures for controlling flood to reduce potential loss of human and aquatic life, degradation of water, air and soil quality and property damage and economic lessen caused by flood in Nyabugogo catchment. However Goodness of Fit tests revealed that Gumbel’s Extreme-Value Distribution method appears to have the most appropriate fit compared with Pearson type III distribution for validating the Intensity-Duration-Frequency curves and equations through the use of daily annual for each meteorological station. The findings of the study show that the intensity of rainfall increases with a decrease in rainfall duration. Additionally, a rainfall of every known duration will have a higher intensity if its return period is high, while the predicted peak rate of runoff (Qlogy) increases also with an increase in the intensity of rainfall.

This work analyzes the severity and risk associated with Automatic Dependent Surveillance-Broadcast (ADS-B) message drop out in Detect and Avoid (DAA) function of Unmanned Aircraft System (UAS). Performance assessment of the Universal Access Transceiver (UAT) ADS-B message implies that in some cases ADS-B fails to update within a specified update interval, which is referred to as drop out in this work. ADS-B is a fundamental surveillance sensor for both class 1 and class 2 DAA systems. Message loss or drop out has been found as one of the common limitations of the ADS-B system. The key feature of this study is incorporating the update rate of real ADS-B data transmitted from the manned aircraft. The data were received from the Grand Forks International Airport, North Dakota. Monte Carlo method has been adopted to resolve encounter scenarios in the presence of drop out. The change in the alert triggered by the UAS DAA in the presence of ADS-B drop out has been investigated. Furthermore, the risk matrices are created to quantify the associated risk with drop out affected alerts. Simulation results depict that both the duration of drop out and DAA look-ahead time affect the alert-triggering function of UAS. With a small look- ahead window and longer duration of drop out, the number of warning alerts increases. Also, alerts are affected more during an overtaking encounter than that of a head-to-head encounter. A system-level analysis is also carried out to recognize the potential reasons behind the ADS-B drop out.

Remotely Piloted Aircraft Systems (RPAS) are increasingly becoming relevant actors flying through the airspace and will assume much more importance in the future perspective. In order to allow their safe integration with manned conventional traffic in non-segregated airspaces, in accordance with the overall Air Traffic Management (ATM) paradigm, specific enabling technologies are needed. As well known, among the enabling technologies identified as crucial for RPAS integration into the overall ATM system, the Detect and Avoid (DAA) technology is fundamental. In the meantime, to support extended surveillance, the universal introduction on-board of aircraft of cooperative Automatic Dependent Surveillance – Broadcast (ADS-B) is increasingly implemented, having the potential to allow coverage of the whole airspace also in remote areas not usually covered by conventional radar surveillance. In this paper, the experimental results are presented and discussed that have been obtained through the real-time validation, with hardware and human in the loop (RTS-HIL) simulations, of an automatic ADS-B based Separation Assurance and Collision Avoidance System aimed to support RPAS automatic operations as well as remote pilot decision making. In the paper, after an introductory outline of the Concept of Operations (ConOps) of the system and of its architectural organization, while also providing basic information about the main system functionalities, the description is reported of the tests that have been carried out and the obtained results are described and discussed, in order to emphasize the performances and limitations of the proposed system. In particular, not only the quantitative performances obtained are reported and commented but also the feedbacks received by the pilots in order to improve the system are described, for instance in terms of preferred typology of conflict resolution manoeuver elaborated by the system.

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

In this note we study the binomial model applied to European, American and Bermudan type of derivatives. Our aim is to give the necessary and sufficient conditions under which we can define a fair value via replicating portfolios for any derivative using simple mathematical arguments and without using no arbitrage techniques. Giving suitable definitions we are able to define rigorously the fair value of any derivative without using concepts from probability theory or stochastic analysis therefore is suitable for students or young researchers. It will be clear in our analysis that if $e^{r \delta} \notin [d,u]$ then we can not define a fair value by any means for any derivative while if $d \leq e^{r \delta} \leq u$ we can. Therefore the definition of the fair value of a derivative is not so closely related with the absence of arbitrage. In the usual probabilistic point of view we assume that $d < e^{r \delta} < u$ in order to define the fair value but it is not clear what we can (or we can not) do in the cases where $e^{r \delta} \leq d$ or $e^{r \delta} \geq u$.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

Infection with the hepatitis B virus (HBV) is a public health problem in many parts of the world, due to its frequency, complications and socio-economic consequences. This study aimed to assess the seroprevalence of hepatitis B virus infection in rural areas and in urban areas. This cross-sectional study assessed the prevalence of HBV infection from 2015-2018 at CHR-Sokodé and USP of Ogaro. Biological data of 3000 participants (500 per year in each zone) enrolled and results of HBsAg were assessed during the study period. Female are represented 60% with average age comprised between [20, 29] years old. The high rate of participants enrolled (45.10%) are come for the monitoring of pregnancy. The prevalence of VHB during the study are 20.33% (610/3000), high prevalence (6.27%) and the means of VHB prevalence are shown in the age range between [30; 39] with 12.17% (365/3000) of female and 8.17% (235/3000) of male are positive after diagnostic detection of HBsAg (antigen of Hepatitis B virus). The prevalence of HBV in rural zone (Ogaro) are 5.23% and 15.07% in urban zone (Sokodé) and the high prevalence (17.50%) are shown in urban zone. The high prevalence of young suggests that some effort will be due to sensibilized young for HBV sexual transmission and the way of prevention. In addition, some research would be done in research of alternative therapy against this infection.

Manufacturing corporations has the acceptance of the Outsourcing Process (OP) to improve industrial activities as well as to archive the revenue objectives, and with this, Risk Analysis (RA) tools are constantly used to assure expected results. Failure Mode and Effect Analysis (FMEA) is one of preferred RA tools, moreover, it is proven that FMEA adds uncertainty because of the human participation at the RA, afterward it is demonstrated that Pythagorean Fuzzy Dimensional Analysis – FMEA – Value Stream Mapping (PFDA-FMEA-VSM) method removes the uncertainty in RA, likewise it aids to the stakeholders for decision making, giving more advantages improving the use of the resources on the project. This document exhibits a real case scenario in a manufacturing firm applying PFDA-FMEA-VSM method adapted for manufacturing OP. The application of PFDA-FMEA-VSM shows solid RA results, removing the human intervention uncertainty added to the risk ranking, gives advantages to the stakeholders for visualize the main risks in detailed diagram, as well as make easier to take better decisions on where to apply resources and mitigate risks during OP.

Excessive vibration of temporary grandstand owing to crowd has lateral rhythmic motions can cause human in panic, which attracted increasing attention in recent years. This paper focuses on experiments that a temporary grandstand occupied 20 participants is oscillated by a shaking table with a series of random waves and induced by crowd with rhythmic swaying motions at lateral direction, respectively. And then a series of vibration perception questionnaires about crowd reaction are obtained. Evaluation of annoying level derives in concept of degree of membership and annoying rate method is proposed, then the human health risk of vibration serviceability of temporary grandstand is assessed with acceleration vibration dose value(VDV). From these results it is clear that standing crowd is more tolerant to vibration than seated crowd. The measured vibrations generated by crowd activities on temporary grandstand can cause panic in crowd. New relationship between the annoyance rate and structural acceleration VDV at logarithmic coordinate is proposed. The findings of this study can be utilized to manage the vibration of temporary grandstand and assess the human health risk.

1) Background: In service business areas, design enhances the customer experience through the elements which anticipate specific emotional responses of customers. Many service companies are keen to develop and examine design elements from the customer perspective. Furthermore, recently, having considered the significance of customers’ emotional responses by design elements, categorising design elements into manageable dimensions can facilitate the evaluation of design elements. However, design elements and dimensions of design value are not defined in the current service marketing literature, and companies need a measurement tool and managerial guideline to their innovative value creation and compelling service delivery. For these reasons, this research aims to categorise the design value dimensions and propose the managerial implication for the innovative use of design; 2) Methods: This study used the mixed methodology; two stages of interviews and SEM (Structural Equation Modelling); 3) Results: Interview analyses facilitate the identification of design elements in the service delivery process. SEM results underpin the relevance of the categorised design elements and their impact on customer loyalty by comparing different groups (country and time elapsed from experience); and 4) Conclusions: Findings are the fundamentals of developing measuring tool for design and trigger future studies for conceptualising intangible assets.

In the present paper, Co-B/SiC composite coatings were obtained via electrodeposition from colloidal suspensions with different concentrations of SiC particles and subsequent heat treatments at 350 °C. The composition, morphology and structure of the Co-B/SiC composite coatings were analyzed using glow discharge spectrometry (GDS), scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD). Hardness and tribological properties were also studied. The results showed that an increase in the SiC concentration in the colloidal suspensions resulted in both an increase in the SiC content and a decrease in the B content in the obtained Co-B/SiC coatings. The Co-B/SiC coatings were adherent, glossy and soft and exhibited a homogeneous composition in all thicknesses. By contrast, an increase in the SiC particle content of the Co-B/SiC composite coating from 0 to 2.56 at.% SiC reduced the hardness of the film from 680 to 360 HV and decreased the wear volume values from 1180 to 23 mm³ N^-1 m^-1, respectively (that is, the wear resistance increased). Moreover, when the Co-B/SiC coatings with SiC content ranging from 0 to 2.56 at.% SiC were subjected to a heat treatment process, the obtained coating hardness values were in the range of 1200 to 1500 HV and the wear volume values were in the range of 382 to 19 mm³ N^-1 m^-1.

Urban areas face daunting economic challenges that have increased in scope in recent years. At the same time, cities provide for opportunities for growth and value creation. The interplay of these challenges and opportunities represents the area of intervention for policymakers and researchers. However, the traditional approach to urban policy, deriving from the managerial and economic policy theories, shows difficulties mainly related to the capacity to counterbalance the interests and expectations of a multitude of stakeholders participating to the value co-creation process and to bring all different components to synergically contribute to the sustainability of the system. The Author proposes an innovative approach to urban public policy, by adopting the theoretical corpus of the Viable Systems Approach ("VSA"). Urban planning will be particularly analysed, as systemic components of urban areas, with the aim to investigate the decision-making processes for an integrated, efficient, effective and sustainable management of the territory as a multidimensional, multisectoral and multi-stakeholder entity. By recovering different settings, the VSA intends the co-creation of value as the capacity of the viable systems to increase its surviving chances in its own context. The value derives, first of all, from the strategic decisions aimed at finding both dyadic and context consonance. Through its strategic decisions, the Governing Body of the territory develops a specific system as the overall synthesis of all possible systems organised within a specific area, identifying pattern of development agreed by the several stakeholders of the territory. In the dynamics of value co-creation in systemic multi-subjective organizations, where the level of complexity is particularly significant, the research for consonance among different stakeholders is particular important in order to achieve the most value for the territory. In this respect, the VSA may constitute a valid tool, helping to find the necessary capacities to imagine evolutionary paths towards new competencies.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Growing evidence has revealed the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of putatively disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment of 26 genes in germline protein truncating variants (PTVs), affecting cell signaling (MET, JAK2, ANGPT2), energy metabolism (ACO1) and nucleic acid metabolism and repair pathways (NT5E, DCK). Interestingly, some of these variants were restricted to either chronic lymphocytic leukemia (CLL) (i.e., ANGPT2 and AKR1C3) or B-cell lymphoma cases (PNMT, TPT1 and IGHMBP2). Additionally, we detected 1,675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were PTVs. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A and TSC2. Homozygous or compound heterozygous variants were detected in 28 cases; and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D and MYC. Finally, we observed that variants in the helicase gene WRN were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis, clinical presentation and disease outcome of B-cell lymphoid neoplasms.

This paper investigates the dynamic tail dependence risk between BRICS economies and world energy market in the context of the COVID-19 financial crisis of 2020, to determine optimal investment decisions based on risk metrics. For this purpose, the study employs a combination of novel statistical techniques ranging from Markov Switching, GARCH and Vine copula. Using a dataset consisting of daily stock and world crude oil prices; we find high probability of transition between lower and higher volatility regimes. Furthermore, our results based on the C-Vine copula confirm the existence of two types of tail dependence: - symmetric tail dependence between South Africa and China; South Africa and Russia; and lower tail dependence between South Africa and India; South Africa and Brazil; South Africa and Oil. For the purpose of diversification in these markets, we formulate an asset allocation problem using C-vine copula-based returns and optimize it using Particle Swarm algorithm with a rebalancing strategy. The results show an inverse relationship between the risk contribution and asset allocation of South Africa and oil market supporting the existence of lower tail dependence between them. This suggests that when South African stocks are in distress, investors tend to shift their holdings in oil market. Similar results are found between China and oil. In the upper tail, South African asset allocation is found to have an inverse relationship with that of Brazil, Russia and India suggesting that these three markets might be good investment destinations when things are not good in South Africa and vice-versa.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

Botulinum neurotoxin (BoNT) intoxication can lead to the disease botulism, characterized by flaccid muscle paralysis that can cause respiratory failure and death. Due to the significant morbidity and mortality costs associated with BoNTs high toxicity, developing highly sensitive, rapid, and field-deployable assays are critically important to protect the nation’s food supply against either accidental or intentional contamination. We report here that the B-cell based biosensor assay (CANARY^® Zephyr) detects BoNT/A in buffer and various food matrices rapidly in ≤ 40 min, in small volumes ≈ 50 μL, with minimal processing of samples, and is extremely portable (suitcase-sized equipment). BoNT/A was detected at limits of detection (LOD) < 0.075 ng ± 0.02 in assay buffer while milk matrices (non-fat, 2 %, whole milk) increased the LOD to < 0.175 – 0.314 ng. Limits of detection for the assay in complex foods were < 1 ng ± 0.0 (neutralized acidic juices-carrot, orange and apple); < 16.7 ng ± 7.7 (liquid egg); and varied from < 0. 39 – 3.125 ng for solid complex foods (ground beef, green bean baby puree, smoked salmon). These results show that the CANARY^® Zephyr assay can be a highly useful tool in clinical, environmental, and food safety surveillance programs.

The class of A-stable symmetric one-step Hermite-Obrechkoff (HO) methods introduced in [1] for dealing with Initial Value Problems is analyzed. Such schemes have the peculiarity of admitting a multiple knot spline extension collocating the differential equation at the mesh points. As a new result, it is shown that these maximal order schemes are conjugate symplectic which is a benefit when the methods have to be applied to Hamiltonian problems. Furthermore a new efficient approach for the computation of the spline extension is introduced, adopting the same strategy developed in [2] for the BS linear multistep methods. The performances of the schemes are tested in particular on some Hamiltonian benchmarks and compared with those of the Gauss Runge-Kutta schemes and Euler-Maclaurin formulas of the same order.

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

Total Nigeria Plc is a Marketing and Services subsidiary of Total; a multinational energy company operating in more than 130 countries and committed to providing sustainable products and services for its customers. For over 50 years, Total Nigeria Plc has remained the leader in the downstream sector of the Nigerian oil and gas industry. This study investigated the volatility of the stock price of Total Petroleum Nigeria plc using nine (9) GARCH models namely sGARCH, gjrGARCH, eGARCH, iGARCH, aPARCH, TGARCH, NGARCH, NAGARCH and AVGARCH. We also investigated the Value-at-Risk (VaR) and Backtesting of the Models. The aim actually of this study is to boost the confidence of the shareholders and investors of the Total Nigeria plc. To achieve this, daily stock price for Total petroleum Nigeria plc from secondary was collected from January 2^nd 2001 to May 8^th 2017. . The study used both normal and student t innovations, using Akaike Information Criterion (AIC) to select the best model, for normal innovations for log returns and cleansed log returns of Total plc, the eGARCH and sGARCH models performed best respectively, while NGARCH model performed best for student t innovation for both log returns and cleansed returns of Total plc. The persistence of the models are stable except in few cases where iGARCH, eGARCH where not stable. Also for student t innovation, the sGARCH and gjrGARCH fails to converge. The mean-reverting number of day for the returns of Total Nigeria plc differs from model to model. Evidence from the VaR Analysis revealed from the selected models revealed that the Risk of VaR losses is high at 99% confidence level, slightly high at 95% confidence level and better at 90% confidence level. Although The Duration-Based Tests of independence conducted revealed that the models are correctly specified since in all cases the null hypotheses were accepted. This means that the probability of an exception on any day did not depends on the outcome of the previous day. Finally, both the unconditional (Kupiec) and conditional (Christoffersen) coverage tests for the correct number of exceedances for both Total stock returns and cleansed returns. The tests revealed rejection of the models at 1% level of significance. This confirms that unconditional (Kupiec) and conditional (Christoffersen) coverage tests for the correct number of exceedances are reliable compared to the Duration-Based Tests of independence. Therefore we recommend that shareholders and investors in Total Nigeria plc are to remain and continue to investment in Total Nigeria plc because if there is any form of losses, the price of the stock has the potentials to improve in the future. Again, though the risk is high at 99% confidence level, this in line with the financial theory that states that an asset with high expected risk would pay higher return on the average.

The primary purpose of this article is to present a maturity model dealing with environmental manufacturing processes in a company. First, a theoretical approach is presented where evolution from the first industrial revolution to the present (Industry 4.0.) is outlined with a need to implement environmental initiatives. Chapter two contains a detailed literature review, which resulted in the creation of our own maturity model presented in the next chapter. According to some authors, Industry 4.0 is based on characteristics that have already been the focus of “lean and green” concepts. The practical part of the article is a case study that shows which areas of the manufacturing process have “environmental” potential. The goal was to move from resource consumption, pollutant emissions and more extensive manufacturing towards environmentally responsible manufacturing (ERM). Using environmental materials and methods reduces energy consumption, which generates cost savings and higher profits. Here, VSM (Value Stream Mapping) was applied to identify core processes with environmental potential. The final part of the article summarizes the work and presents future possibilities. This paper provides an understanding of the role of environmental manufacturing in the era of the 4th industrial revolution.

The construction industry is one of the most fatal industries, so it is important to pay more attention to safety solutions. Even though work-related accidents are known as major waste in construction projects, little attention has been paid so far to incorporating safety into the lean construction framework. In this research, lean construction theory is reviewed through the lens of safety. That being so, the identified challenges in previous research on improving safety in construction projects are categorized and those related to the concept of lean project delivery are introduced. Then, the principles of the lean construction framework are explained and the relevant changes for incorporating safety into the framework are introduced and discussed. It is expected that this hybrid model would further enrich the lean construction framework. The careful attention of project executives to this model may improve the safety situation in construction projects.

Land and property development process include a series of multifaceted activities ranging from purchasing to converting it for development purposes and everything in between. The process itself encompasses multiple stakeholders, drivers, and contributions from diversified public and private actors and transaction cost arises out of their complex interaction. Transaction costs incurred during any kind of human interactions (i.e. transactions). Every actor involved in the process wishes to maximize his achievement under various constraints and hence institutional arrangement (i.e. set of humanly devised rules to administer the constraints) is necessary for efficient management of the development process. Therefore, to devise an optimum outcome out of economic and social transactions in the property development process, cooperative and competitive relationships between individuals should be understood from a broader socio-political and governance structure. In this research, it is critically argued that land and property development process should implicate a multifaceted set of formal and informal rules or institutional arrangement to govern the intrinsic interaction, action and thereby reducing the related transaction cost. The argument is further reproachfully evaluated and implicated in the urban development process through the myopic lens of Transit-oriented development (TOD) pathway. A vigilant combination of descriptive and explanatory research approach is adopted to analyze the connection between theory and practice.

An analysis of the performance of Automatic Dependent Surveillance-Broadcast (ADS-B) data received from the Grand Forks, North Dakota International Airport was carried out in this study. The purpose was to understand the vulnerabilities of Universal Access Transceiver (UAT) ADS-B system and recognize the effects on present and future Air Traffic Control (ATC) operation. The Federal Aviation Administration (FAA) mandated all the General Aviation aircraft to be equipped with ADS-B. The aircraft flying within United States and below the transition altitude (18,000 feet) are more likely to install an UAT ADS-B. At present unmanned aircraft systems (UAS) and autonomous air traffic control (ATC) towers are being integrated into the aviation industry and UAT ADS-B is a basic sensor for both class 1 and class 2 Detect and Avoid (DAA) systems. As a fundamental component of future surveillance system, the anomalies and vulnerabilities of ADS-B system need to be identified to enable a fully utilized airspace with enhanced situational awareness. The data received was archived in GDL-90 format, which was parsed into readable data. The anomaly detection of ADS-B messages was based on the FAA ADS-B performance assessment report. The data investigation revealed ADS-B message suffered from different anomalies including drop out; missing payload; data jump; low confident data and altitude discrepancy. Among those studied, the most severe was drop out and 32.49% of messages suffered from this anomaly. Dropout is an incident where ADS-B failed to update within a specified rate. Considering the potential danger being imposed, an in-depth analysis was carried out to characterize message dropout. Three flight parameters were selected to investigate their effect on drop out. Statistical analysis was carried out and Friedman Statistical Test identified that altitude affected drop out more than any other flight parameters.

The complete-lattice approach to optimization problems with a vector- or even set-valued objective already produced a variety of new concepts and results and was successfully applied in finance, statistics and game theory. For example, the duality issue for multi-criteria and vector optimization problems could be solved using the complete-lattice approach, compare [11]. So far, it has been applied to set-valued dynamic risk measures (in the stochastic case), as discussed in Feinstein, Rudloff etc. (see [11], for example), but it has not been applied to deterministic calculus of variations and optimal control problems. In this paper, the following problem of set-valued optimization is considered: minimize the functional $$ \overline J_t[y]=\int_0^t \overline L(s,y(s),\dot y(s))\ ds + U_0(y(0)) $$ over all admissible arcs $y$, where $\overline L$ is the associated multifunction to a vector-valued Lagrangian $L$, the integral is in the Aumann sense and $U_0$ is the initial cost. A new concept of \emph{value function}, for which a Bellman's optimality principle holds, is introduced. Also the classical result of the Hopf-Lax formula holds for the generalized value function. Finally, a derivative with respect to the time $t$ and a directional derivative with respect to $x$ of the value function are defined, based on ideas close to the concepts in [12]. The value function is proved to be solution of a suitable Hamilton-Jacobi equation.

Two sets of initial conditions are used in the investigation of capital return rate and carbon storage in boreal forests. Firstly, a growth model is applied in young stands as early as the inventory-based model is applicable. Secondly, the growth model is applied to observed wooded stands. Four sets of thinning schedules are investigated in either case. First, the capital return rate is aspired without any restriction. Second, the number of thinnings is restricted to at most one. Third, thinnings are restricted to the removal of only trees thicker than 237 mm. Fourth, commercial thinnings are omitted. The two sets of initial conditions yield similar results. The capital return rate is a weak function of rotation age, which results in variability in the optimal number of thinnings. Reducing the number of thinnings to one increases timber stock but induces a capital return rate deficiency. The deficiency per excess volume unit is smaller if the severity of any thinning is restricted by the removal of large trees only. Omission of thinnings best applies to spruce-dominated stands with stem count less than 2000/ha. Restricted thinning intensity applies to deciduous stands and dense pine stands. The albedo effect increases the benefits of restricted thinnings and increased clearcuttings instead of contradicting the carbon storage.

Diffuse large B cell lymphoma (DLBCL), the most frequent type of non-Hodgkin lymphoma in adulthood, remains challenging clinical issues. Despite enhanced remission rates can be achieved, there are one-third of patients who will not respond to current treatment or will relapse with resistant disease, necessitating ongoing efforts on effective treatment strategies and agents. The vacuole H+-ATPase inhibitor bafilomycin A1 is broadly used to block late stage of autophagy flux at high concentration. In this study, we show that, to our surprise, bafilomycin A1 effectively inhibited and killed DLBCL cells at nanomolar concentrations (5nM). Bafilomycin A1 targeted cell cycle regulators cyclin D1 and cyclin E2 to induce cell cycle arrest in G0/G1 phase. Meanwhile, it induced caspase-dependent apoptosis with concomitant cleaved caspase-3 and Parp. Furthermore, we found that bafilomycin A1 inhibited autophagy flux at both early and late stages of the autophagy flux through activating ERK and mammalian target of rapamycin signaling, as well as by inhibiting the degradation of autolysosomes. We speculated that bafilomycin A1 as autophagy inhibitor might enhance the effect of DLBCL chemotherapeutic drug rituximab. Accordingly, our results provided evidence that the combination of bafilomycin A1 with rituximab enhanced the inhibition of DLBCL cells notably. Taken together, our data suggest that bafilomycin A1 may be a promising candidate drug in the therapy of diffuse large B cell lymphoma.

In Europe, the recent application of regulations oriented to zero-energy buildings and climate neutrality in 2050 has led to a reduction in energy consumption for heating and cooling in the construction sector. The thermal insulation of the building envelope plays a key role in this process and the requirements about the maximum allowable thermal transmittance are defined by country-specific guidelines. Typically, high insulation values provide low energy consumption for heating, however, they may paradoxically imply the risk of overheating in summer period and thus negatively affect the overall performance of the building. In addition, the embodied energy and related emissions caused by the manufacturing and transportation processes of thermal insulation cannot be further neglected in the evaluation of the best optimal solution. Therefore, this paper aims to evaluate the influence in terms of embodied and operational energy of various walls’ thermal insulation thicknesses on residential buildings in Europe. To this end, the EnergyPlus engine was used for the energy simulation within Ladybug &amp; Honeybee tools, by parametrically conducting multiple iterations; 53 variations of external wall U-value, considering high and low thermal mass scenarios, were simulated for 100 reference cities of the European context, using a representative multifamily building as a reference. The results demonstrate that massive walls generally perform better than lightweight structures and, of course, the best solution in terms of energy varies according to each climate. The optimal values are graphically reported on the map of Europe according to specific climatic features, providing a guidance for new constructions and building retrofit.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

Cash holding is important for Chinese manufacturing firms coping with the increasing cost of financing and stiff market conditions. This study examines the impact of cash holding on the firm value of Chinese manufacturing firms. We find evidence that a non-linear relationship exists between cash holding and firm value in manufacturing firms of China. The study reveals that financially constrained firms having a higher level of cash holding negatively affects the firm value, while the unconstrained firms having a lower level of cash holding positively influences the firm value. Finally, this research is enriched by adopting the novel measure of managerial op-timism and reveals the interactive role of cash holding and optimism on firm value. The study concludes that managerial optimism influences the firm’s cash holding decisions and this is more costly for unconstrained firms.

Neuroinflammatory responses are implicated in the pathogenesis of neurodegenerative diseases. In neurodegenerative diseases, neuroinflammatory reactions to neuronal injury are modulated by microglial cells, which are vital innate immune cells in the central nervous system. Activated microglial cells release proinflammatory cytokines, mediators, and neurotoxic factors that induce fatal neuronal injury. The present study investigated the anti-neuroinflammatory effects of cudratricusxanthone L (1), which was isolated from Cudrania tricuspidata. This compound reduced the levels of lipopolysaccharide-stimulated inflammatory mediators and cytokines, including nitric oxide, prostaglandin E2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12. These effects suggested that cudratricusxanthone L (1) suppressed the nuclear factor-kappa B (NF-κB) signaling pathway. Specifically, cudratricusxanthone L (1) also attenuated the phosphorylation of Jun kinase and inhibited p38 mitogen-activated protein kinase (MAPK) signaling in BV2 and rat primary microglial cells. These results indicated that cudratricusxanthone L (1) effectively repressed neuroinflammatory processes in BV2 and rat primary microglial cells by inhibiting NF-κB and the MAPK signaling pathway.

Cardiovascular disease (CVD) places a heavy burden on older patients and the global healthcare system. A large body of evidence suggests that exercise training is essential in preventing and treating cardiovascular disease, but the underlying mechanisms are not well understood. Here, we used the Drosophila melanogaster animal model to study the effects of early-life exercise training (ELET) on the aging heart and lifespan. We found in flies that age-induced arrhythmias are conserved across different genetic backgrounds. The fat body is the primary source of circulating lipoproteins in flies. Inhibition of fat body apoLpp (the flies apoB homolog) demonstrated that low expression of apoLpp reduced the development of arrhythmias in aged flies but did not affect average lifespan. At the same time, ELET can also reduce the expression of apoLpp mRNA in aged flies and have a protective effect on the heart, which is similar to the inhibition of apoLpp mRNA. Although treatment of apoLppRNAi and ELET alone had no significant effect on lifespan, the combination of apoLppRNAi and ELET extended the average lifespan of flies. Therefore, we conclude that apoLppRNAi and ELET are sufficient to resist age-induced arrhythmias, which may be related to the decreased expression of apoLpp mRNA, and that apoLppRNAi and ELET have a combined effect on prolonging the average lifespan.

Starting from early 2020, the COVID-19 pandemic has caused a morbidity and mortality excess worldwide. Containment strategies rely firstly on rapid and sensitive laboratory diagnosis with molecular detection of the viral genome in respiratory samples being the gold standard. Reliability of diagnostic protocols could be affected by SARS-CoV-2 genetic variability. In fact, mutations occurring during SARS-CoV-2 genomic evolution can involve the regions targeted by the diagnostic probes. Following a review of the literature and an in silico analysis of the most recently described virus variants (including the UK B 1.1.7 and the South Africa 501Y.V2 variants), we conclude that the described genetic variability should have minimal or no effect on the sensitivity of existing diagnostic protocols for SARS-CoV-2 genome detection. However, given the continuous emergence of new variants, the situation should be monitored in the future, and protocols including multiple targets should be preferred.

In this paper we present a review of recent developments in AI towards the possibility of an artificial intelligence equals that of human intelligence. AI technology has always shown a stepwise increase in its capacity and complexity. The last step took place several years ago, with the increased progress in deep neural network technology. Each such step goes hand in hand with our understanding of ourselves and our understanding of human cognition. Indeed, AI was always about the question of understanding human nature. AI percolates into our lives, changing our environment. We believe that the next few steps in AI technology, and in our understanding of human behavior, will bring about much more powerful machines, flexible enough to resemble human behavior. In this context, there are two research fields: Artificial Social Intelligence (ASI) and General Artificial Intelligence (AGI). The authors also allude to one of the main challenges for AI, embodied cognition, and explain how it can viewed as an opportunity for further progress in AI research.

The research was carried out in southern Ethiopia to determine farmers' preferences for indigenous legume, fodder trees and shrubs (ILFTS), as well as the relationship between local feed valuation and scientific parameters. A focus group discussion (FGD) was conducted with ten farmers in each agro-ecological zone to determine the benchmarks for the preference ratings. The respondent farmers used the preference score sheet to rate all ILFTS on an individual basis. Twenty farmers with extensive experience in ILFTS took part in the preference score rating of each plant species in each agroecosystems. Dry matter (DM), organic matter (OM), Ash, crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), and metabolizable energy (ME) content of the samples were determined. The standard two-stage in vitro approach was used to measure the in vitro dry matter digestibility (IVDMD) of samples. ANOVA was used to analyze the variation among the species in agroecosystems. Farmers evaluated the ILFTS using a variety of parameters, according to the study (feed value, growth rate, biomass output, compatibility, and multifunctionality). The farmers ILFTS preference score on the evaluation criteria differed considerably (P<0.05) with species in agroecosystems. The nutritive value of ILFTS was in the acceptable range for feeding ruminants although exhibited a wide variation among the species in agroecosystems. The CP content was above the minimum requirement (8%) to support the normal function of rumen microorganisms. Moreover, CP exhibited positive significant correlation with IVDMD, IVOMD, and DOMD unlike CT and ADL which exhibited negative significant correlation. Thus, ADL and CT were identified as feed fractions that inhibit IVDMD either by depressing the activity of rumen microorganisms or restricting enzyme access to cell wall components. Conversely, the DM, OM, CP, IVDMD, IVOMD, DOMD, and ME were shown a positive significant correlation with farmers feed preference score, unlike the ADL and CT which exhibited a negative significant correlation. In conclusion, Farmers' indigenous knowledge of feed value is therefore relevant to some extent for judging the nutritive value of the ILFTS and could complement the scientific indicators.

Objective: Taiwan Government’s organizations have endeavored to promote the applications of big data and open data. The “My Health Bank” is one of the measures promoted by the National Health Administration, Ministry of Health and Welfare. This study proposes the perspective of the “value co-creation” with the attempt to extend the concept of service ecosystem and apply it on the platform of My Health Bank to examine whether people (patients, families, and caregivers) can promote their health literacy? Method: This cross-sectional study, with people that have registered at “My Health Bank” as subjects. Complying with the inclusion criteria, 401 questionnaires were delivered, with 391 valid ones, excluding those incompletely and inaccurately filled. Result: That the affecting factors of the co-creation of values: age, education level, annual income, and platform operation show to be significant ( p＜0.05); and gender, occupation, and resource exchange do not reach the significant level (p＞0.1). Conclusion: We found My Health Bank changed the inertia of “value creation” in the traditional medical value, it allows the traditional medical and healthcare industry to expose to the impacts of the mega trend of the internet, the transformation of the platform in a necessary trend.

The differential transformation, an approach based on Taylor's theorem, is proposed as convenient for finding exact or approximate solution to the initial value problem with multiple Caputo fractional derivatives of generally non-commensurate orders. The multi-term differential equation is first transformed into a multi-order system and then into a system of recurrence relations for coefficients of formal fractional power series. The order of the fractional power series is discussed in relation to orders of derivatives appearing in the original equation. Application of the algorithm to an initial value problem results in a reliable and expected outcome.

Biofuels have many environmental and practical benefits as a transportation fuel. They are among the best alternatives to fossil fuels due to their capacity for negative carbon emissions, which is vital for archiving the global ambition of a Net-Zero Economy. However, conventional biofuel production takes place on inland sites and relies on freshwater and edible crops (or land suitable for edible crop production), which has led to the food vs fuel debate. It also suffers technical and economical barriers due to the energy balance and the cost of production compared to fossil fuels. Establishing a coastal integrated marine biorefinery (CIMB) system for the simultaneous production of biofuels, high-value chemicals, and other co-products could be the ultimate solution. The proposed system is based on coastal sites and relies on marine resources including seawater, marine biomass (seaweed) and marine microorganisms (marine yeasts and marine microalgae). The system will not require the use of arable land and freshwater in any part of the production chain and will be linked to offshore renewable energy sources to increase its economic and environmental value. This article aims to introduce the CIMB system as a potential vehicle for addressing global warming and speeding the global effort on climate change mitigation as well as increasing global water, food and energy security. I hope this perspective may serve to draw attention into research funding for this approach.

In this study, it was aimed to analyze the multi-cultural characteristics of the pre-service teachers and the values they have in terms of various variables, to determine the relationship between these values. Descriptive survey model, one of the quantitative research methods, was used in the study. The population of the study consisted of the pre-service teachers studying in different departments in the Faculty of Education, İbrahim Çeçen University of Ağrı in 2017-2018 academic years. The sample of the study consisted of 341 pre-service teachers selected with random sampling method. According to the results obtained from the study, it was determined that the value preferences of the pre-service teachers and their multicultural personality characteristics showed a significant difference in terms of gender, undergraduate program, educational background of the mother, having social media account and daily internet use variables; however, there was not a significant difference in terms of family structure, the place s/he grew up, educational background of the father and monthly income variables. The abstract does not include information about which groups are favored for the difference in the variables and in which sub-dimensions, but detailed information is given in the following sections of the study.

The changes in consumer preferences and the increasingly competitive global market have demanded that food entrepreneurs engage in innovative value-added activities. The date is a delicatessen fruit known by its content of active compounds (e.g., dietary fiber and antioxidants) and its biological activity which has a vast potential in the design of new products such as bioactive ingredients, sugar substitutes, dietary supplements, functional foods, among others. In the current paper, innovative approaches to the value addition to date fruits and their processing by-products have been reviewed from recent high-quality scientific works. New processes such as ultrafiltration and hydrothermal treatments are shown as a useful alternative to obtain differentiated date-based ingredients (e.g., fiber concentrates, sap syrups, and date powders). Moreover, the use of date fruits and their byproducts as natural sources of value-added active compounds in the preparation of dairy, meat, and bakery and cereal products is also presented.

(1) Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. (2) Methods: One hundred twelve 15-mer peptides covering the entire sequence of DTx protein were prepared by Spot-synthesis. Membrane-bound peptides immunoreactivity with sera from mice immunized with triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, MAPs synthesis, and ELISA development. (3) Results: Twenty epitopes were identified, being 2 in the signal peptide, 5 in the CD, 7 in the HBFT domain, and 5 in the RBD. Two 17-mer (CB/Tx-2/12 and CB/DTx-4-13) derived bi-epitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccined sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) either for huVS and miVS and when compared with a commercial ELISA test, demonstrate high performance. (4) Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated the specificity and eligibility to enter phase IIB studies of some epitopes to develop new and fast diagnostic assays.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

During the COVID-19 pandemic, WIC increased the Cash Value Benefit (CVB) for fruits and vegetables by roughly $25/month/person. We sought to understand WIC participant perceptions of this change and barriers and facilitators to using the CVB. We conducted 10 virtual focus groups (5 rural, 5 urban/suburban) with WIC participants (n=55) in North Carolina in March 2022. Focus groups were recorded and transcribed. We open coded the content and used thematic analysis to uncover consistencies within and between sampled groups. Participants expressed favorable perceptions of the CVB increase and stated the pre-pandemic CVB amount was insufficient. Barriers to using the increased CVB were identifying WIC approved fruits and vegetables in stores and insufficient supply of fruits and vegetables. Barriers were more pronounced in rural groups. CVB use facilitators were existing household preferences for fruits and vegetables and the variety of products that can be purchased with the CVB relative to other components of the WIC food package. Participants felt the CVB increase allowed their families to eat a wider variety of fruits and vegetables. The CVB increase may improve fruit and vegetable intake, particularly if made permanent, but barriers to CVB and WIC benefit use may be limiting the potential impact.

Investments in digital infrastructure in marginalised communities are set to increase in the next decade. These are premised on the potential of digital technologies to contribute towards solving societal problems, including the fragility of food value chains in rural areas. Although there are mixed empirical findings on the impact of these digital infrastructure investments, huge investments are continuing amid changing ICT policies in most developing countries. This paper, using a case study of a local livestock value chain in a rural community in Zimbabwe, argues for the application of non-conventional approaches towards digital infrastructure transformation impact assessment. Using selected theories and frameworks (socio-ecological systems framework, choice framework and technology affordances theory) as well as empirical data from a project in a rural community, the paper shows that real-time impact assessment using context-specific metrics may reveal hidden digital infrastructure transformation impacts, positive and negative, that are often overlooked when traditional impact assessment approaches are employed. The findings of this study contribute towards improving approaches towards ICT impact assessment. Practitioners engaging in impact assessment are challenged to move beyond dependence on traditional metrics (e.g. access) to the adoption of participatory processes to decipher context-appropriate metrics.

AAs the global energy market undergoes a wholesale transformation accelerated by the need to decarbonise, a rapid transition to renewable energy and the mass deployment of distributed energy resources, autonomous energy networks or microgrids are emerging as an attractive mechanism for the delivery of electricity to end users. Yet in Australia, at least, relatively little is known about key aspects of microgrids that are fundamental to their successful deployment, not least the more commercial and economic elements rather than the purely technical. Drawing on the extant global literature on microgrids, this paper explores the most important of these aspects including business models, ownership and investment. Identifying the ambiguity, inconsistency and uncertainty evident in many of the feasibility studies currently in train across Australia, this paper highlights specific areas for future research that need to be addressed if the full potential of microgrids is to be realised in the context of a global energy transition both domestically and internationally.

Deep learning has been applied in many areas that have had a significant impact on applications that improves real-life challenges. The success of deep learning in a wide range of areas is due in part to the use of activation functions, which are particularly effective at solving non-linear problems. Activation functions are a key focus for researchers in artificial intelligence who aim to improve the performance of neural networks. This article provides a comprehensive explanation and comparison of different activation functions, with a focus on the arc tangent and its variations specifically. The paper presents experimental results that show that variations of the arc tangent using irrational numbers such as pi, the golden ratio, and Euler’s number, as well as a self-arctan function, produce promising results. Since we experimented with promising activation functions on two different problems, and datasets, we reached a result that different irrationals work well for different problems. In other words, arctan ϕ gives the best results mostly for multiclass classification and arctan e gives the best results for time series prediction problems. The paper focuses on a multi-class classification problem applied to the Reuters Newswire dataset and a time-series prediction problem on Türkiye energy trade value to show the impacts of activation functions.

This work analyzes the visibility and scientific impact of publications related to agricultural value chains. The incidence of bibliometric indicators allows for the interpretation of bibliographic information generated worldwide. Objective: The objective of this research is to analyze the published literature and bibliometric indicators on agricultural value chains. The Web of Science database was used to extract value chains data. The study analyzed articles published between 2010 and 2020. The keywords used are "agricultural value chains'' and articles from journals or studies related to the subject were selected for bibliometric analysis and methodological review. In the search for the keyword, a total of 4208 results were extracted, of which 1,669 records were considered for analysis. The bibliometric analysis of the data reveals that Wageningen University (55) has the highest number of publications, followed by Chinese Acad Sci (26). The author Klerkx L (9) has the highest number of records, followed by Hellin J (7). With respect to the countries with the greatest contributions on the subject are: the People's Republic of China, Germany, Italy, France and the United States. The study contributes to the analysis of bibliometrics and provides a methodological review of published journal articles on agricultural value chains. This bibliographic study presents the history of research development in agricultural value chains.

The bivalve mollusk, Anadara tuberculosa (Black Shell, in Spanish Concha prieta, "CP"), is found on America's Pacific coast, where it is harvested for subsistence and commercial markets. This paper aims to diagnose the performance of the black shell's value chain. We also identify several challenges that must be addressed to improve the sustainability of the black shell fishery in Ecuador. The descriptive methodology was quantitative, with a non-experimental, field, cross-sectional, and ex post facto design. Similar questionnaires were designed, validated, and applied to each link in the production chain to collect information. The performance of the value chain was diagnosed in the dimensions of productivity, competitiveness, and quality of life, reaching a 75.1% index, a result that indicates that the value chain has a moderate to good performance level. However, the value chain can be improved if the following challenges are met: 1) Restoration of the mangrove ecosystem, 2) Promotion of low-intensity shellfish aquaculture, 3) Good sanitary management and purification, 4) Promotion of value-focused ventures, 5) Strengthening of organizations and agreements for the use and custody of mangroves, and 6) Strengthening of institutions that contribute to the advancement of these challenges.

High concentrations of Na⁺ or [Co(NH₃)₆]³⁺ can induce the B to Z conformational transition in alternating (dC-dG) oligo and polynucleotides. The use of short DNA oligomers (dC-dG)₄ and (dm⁵C-dG)₄ as models can allow a thermodynamic characterization of the transition. Both form right handed double helical structures (B-DNA) in standard phosphate buffer with 115 mM Na⁺ at 25 ^oC. However, at 2.0 M Na⁺ or 200 mM [Co(NH₃)₆]³⁺, (dm⁵C-dG)₄ assumes a left handed double helical structure (Z-DNA) while the unmethylated (dC-dG)₄ analogue remains right handed under those conditions. We have previously demonstrated that the enthalpy of the transition at 25 ^oC for either inducer can be determined using isothermal titration calorimetry (ITC) [Ferreira, J. M. & Sheardy, R. D., Biophys. J. 2006, 91, 1–7]. Here, ITC is used to investigate the linkages between temperature, water activity and DNA conformation. We found that the determined enthalpy for each titration varied linearly with temperature allowing determination of the heat capacity change (DC_p) between the initial and final states. As expected, the DC_p values were dependent upon the cation (i.e. Na⁺ vs [Co(NH₃)₆]³⁺) as well as the sequence of the DNA oligomer (i. e., methylated vs unmethylated). Osmotic stress experiments were carried out to determine the gain or loss of water by the oligomer induced by the titration. The results are discussed in terms of solvent accessible surface areas, electrostatic interactions and the role of water.

Artificial general intelligence (AGI) progression metrics indicate AGI will occur within decades. No proof exists that AGI will benefit humans and not harm or eliminate humans. I propose a set of logically distinct conceptual components that are necessary and sufficient to 1) ensure various AGI scenarios will not harm humanity and 2) robustly align AGI and human values and goals. By systematically addressing pathways to malevolent AI we can induce the methods/axioms required to redress them. Distributed ledger technology (DLT, ‘blockchain’) is integral to this proposal, e.g. ‘smart contracts’ are necessary to address evolution of AI that will be too fast for human monitoring and intervention. The proposed axioms: 1) Access to technology by market license. 2) Transparent ethics embodied in DLT. 3) Morality encrypted via DLT. 4) Behavior control structure with values at roots. 5) Individual bar-code identification of critical components. 6) Configuration Item (from business continuity/disaster recovery planning). 7) Identity verification secured via DLT. 8) ‘Smart’ automated contracts based on DLT. 9) Decentralized applications - AI software modules encrypted via DLT. 10) Audit trail of component usage stored via DLT. 11) Social ostracism (denial of resources) augmented by DLT petitions. 12) Game theory and mechanism design.

This paper investigates the photocatalytic characteristics of Ag Nanowire (AgNW)/TiO2 and AgNW/TiO2/Graphene oxide (GO) nanocomposites. Samples were synthesized by the direct coating of TiO2 particles on the surface of silver nanowires. As-prepared AgNW/TiO2 and AgNW/TiO2/GO nanocomposites were characterized by electron microscopy, X-ray diffraction, UV/visible absorption spectroscopy, and infrared spectroscopy. Transmission electron microscope (TEM) images confirmed the successful deposition of TiO2 nanoparticles on the surface of AgNWs. The photocatalytic activity of synthesized nanocomposites was evaluated using Rhodamine B (RhB) in an aqueous solution as the model organic dye. Results showed that synthesized AgNW/TiO2/GO nanocomposite has superior photocatalytic activities when it comes to the decomposition of RhB.

ND1 subunit possesses the majority of the inhibitor binding domain of the human MRC-I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, some metabolites from Annona muricata called acetogenins have important biological activities such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine MRC-I by bis-THF acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human MRC-I. In this work, we evaluate the molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, QM optimizations, MD simulations and MM/PBSA analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known MRC-I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger BFE compared to the rotenone complex. Detailed analysis of the BFE shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of MRC-I.

Climate adaptation is a major challenge. Chasing the sufficient amount of hay is getting in higher priority. Distant mass hay producers give favourable offers despite long distances. Quality is also gaining position and indicators like RFQ (Relative Forage Quality) is highlighting the marketing language. Hay market as we knew no longer exists in Hungary. Most farmers produce their own hay and do not spend extra cents to buy bales. Climate change however, force them to adapt and store more bales for the future. Horse owners and dairy farmers are the main driver to convince hay producers to provide high quality forage. We gathered Hungarian regional hay-price information and evaluated the trends in this sector. The demand-driven hay-price is in contradiction with premium quality timothy grass hay.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

A generalization of $\eta$-Ricci solitons is considered involving an additional metric and functions as soliton coefficients. The soliton potential is torse-forming and orthogonal to the contact distribution of the almost contact B-metric manifold. Then such a manifold can also be considered as an almost Einstein-like manifold, a generalization of an $\eta$-Einstein manifold with respect to both B-metrics and functions as coefficients. Necessary and sufficient conditions are found for a number of properties of the curvature tensor and its Ricci tensor of the studied manifolds. Finally, an explicit example of an arbitrary dimension is given and some of the results are illustrated.

Twenty-first century infrastructure needs to respond to changing demographics, becoming climate neutral, resilient, and economically affordable, while remaining a driver for development and shared prosperity. However, the infrastructure sector remains one of the least innovative and digitalized, plagued by delays, cost overruns, and benefit shortfalls [1-4]. The root cause is the prevailing fragmentation of the infrastructure value chain [5]. To support overcoming the shortcomings, an integration of the value chain is needed. This could be achieved through a use-cased-based creation of federated digital platforms applied to infrastructure projects. Such digital platforms enable full-lifecycle participation and responsible governance guided by a shared infrastructure vision.

Herewith we report a facile synthesis of zinc oxide doped with (5, 10, 15, and 20 wt%) titanium oxide nanocomposites in gelatin under ultra-sonication. The X-ray diffraction (XRD) data revealed ZnO the formation in addition to a rutile phase TiO2. The ZnO phase size decreased, and the rutile TiO2 phase increased with a TiO2 loading increment. The scanning electron microscopy (SEM) displayed a combination of spherical and hexagonal particles with a 60 – 80 nm size distribution. The prepared nanostructures photocatalytic activity was assisted using Rhodamine B dye, where they showed enhanced photodegradation competence under visible light irradiation. The kinetics of photodegradation followed the first-order kinetics with the 20 % wt sample having the maximum activity. The mechanistic investigation revealed the dominance of h+ and •O2- species during the dye photodegradation. The results indicate the potential application of such gelatin stabilized nanostructures for dye illumination from aqueous solutions under sunlight.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

Land consolidation engineering inevitably interferes with terrestrial ecosystems, leading to natural capital loss. Therefore, conducting an ecological sensitivity evaluation of a project area before consolidation engineering is very important for reducing unnecessary human interference. Conservation of terrestrial ecosystems and the biodiversity therein to the greatest possible extent is urgently needed. This research analyzes the interference by human activities caused by land consolidation engineering in terrestrial ecosystems. GIS technology, ecological values, landscape pattern indexes, and an ecological risk evaluation were used to construct an ecological sensitivity evaluation index. The coefficient of variation method and a comprehensive sensitivity rating evaluation were used to calculate the weights and results. The project area was divided into sensitivity zones according to the results, and the results and suggestions are as follows: In the highly eco-sensitive zone, where bare rocks, gravel, and grass-covered areas compose the main landscape type, vegetation should be restored, and forests should be planted. In the medium eco-sensitivity zone, where irrigated paddy fields and arid land compose the main landscape type, land parcels should be merged, and agricultural infrastructure should be constructed or improved. In the low eco-sensitivity zone, where forests compose the main landscape type, roads should be closed, natural habitat should be restored, and buffer zones should be created. This study provides suggestions for future land management decisions.

Though innovations for sustainable management of natural resources have emerged over time, the rising demand for nature based health solutions and integration of endemic flora into global value chains could have adverse impacts on ecosystems. The ecological risks in the exploitation of wild medicinal plant resources are exacerbated by a myriad of agrotechnological risks and challenges that highly constrain their domestication. Successful exploitation and commercialization of medicinal plants thus require a clear understanding of their demand and production systems or value chain analysis. Accordingly there is need for innovative approaches towards their integration into global value chains. Since quality and safety, traceability, certification, as well as, consumer tastes and preferences are critical drivers in purchasing decisions by global consumers, they are inadvertently exploited to weaken Indigenous knowledge (IK), undermine common property rights and entrench value chains that favour a few elite buyers. This tend to create pervasive incentives for overexploitation of medicinal plant resources and environmental degradation. Potential solution lies in the recognition of drivers of vulnerability to environmental degradation and the innovative use of policy bricolage, feedback loops and interactions between knowledge, power and agency on one hand, and collective action and property rights institutions on the other hand. We conceptualise a framework that can mediate a transformational agenda and enhance systematic understanding of sustainability lenses in endemic medicinal plant resources value chains. This could in turn strengthen IK, enhance collective action and promote participation of local actors with positive impact on the utilisation and integration of endemic medicinal plant resources into global value chains.

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host-genome integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription, and their impact on the stability of viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA, small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA and small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrant templates. These antivirals mediate their effects by reducing viral transcripts abundance, eventually leading to loss of surface antigen expression, and can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.

The objective of this study is to determine the type of governance of the four main agricultural value chains in Tamaulipas, northeast of Mexico. For the preparation of this research used a qualitative design, using a questionnaire and semi-structured interviews to a sample of representatives of the four selected chains. The results showed that in all the studied networks, control and coordination capacity is limited by the influence that has a link on the rest of the chain. In all cases, was that the industrial link is who leads the chains and exert control over the rest of the links. The results showed that, when the industrial link is located close geographically to the rest of the links (chains of rice and sugar cane), the chains showed a hierarchical type, where the industrial exercised dominion over the rest of the links and captures most of the income. On the other hand, in chains where control is exercised by links that are outside the territory (chains of soybeans and sorghum), they function as captive chains, putting the rest of the chain to its influence and control.

The annual budget for the United States National Park Service was roughly three billion dollars in 2016. This is distributed amongst 405 National Parks, 23 national scenic and historic trails, and 60 wild and scenic rivers. Entrance fees and concessions generate millions of dollars in income for the National Park Service; however, this metric fails to account for the total value of the National Parks. In failing to consider the value of the ecosystem services provided by the National Parks we fail to quantify and appreciate the contributions our parks make to society. This oversight allows us to continue to underfund a valuable part of our natural capital and consequently damage our supporting environment, national heritage, monetary economy, and many of our diverse cultures. We explore a simple benefits transfer valuation of the United States national parks using National Land Cover Data from 2011 and ecosystem service values determined by Costanza (et al). This produces an estimate suggesting the parks provide $84 billion / year in ecosystem service value. If the natural infrastructure 'asset' that is our national park system had a budget comparable to a piece of commercial real estate of this value, the annual budget of the National Park Service would be roughly an order of magnitude larger at something closer to $30 billion rather than $3 billion.

The finding of important explanatory variables for the location parameter and the scale parameter of the generalized extreme value (GEV) distribution, when the latter is used for the modelling of annual streamflow maxima, is known to have reduced the uncertainties in inferences, as estimated through regional flood frequency analysis frameworks. However, important explanatory variables have not been found for the GEV shape parameter, despite its critical significance, which stems from the fact that it determines the behaviour of the upper tail of the distribution. Here we examine the nature of the shape parameter by revealing its relationships with basin attributes. We use a dataset that comprises information about daily streamflow and forcing, climatic indices, topographic, land cover, soil and geological characteristics of 591 basins with minimal human influence in the contiguous United States. We propose a framework that uses random forests and linear models to find (a) important predictor variables of the shape parameter and (b) an interpretable model with high predictive performance. The process of study comprises of assessing the predictive performance of the models, selecting a parsimonious predicting model and interpreting the results in an ad-hoc manner. The findings suggest that the shape parameter mostly depends on climatic indices, while the selected prediction model results in more than 20% higher accuracy in terms of RMSE compared to a naïve approach. The implications are important, since incorporating the regression model into regional flood frequency analysis frameworks can considerably reduce the predictive uncertainties.

Pharmacogenomics (PGx) is the study of how variations of the patient genetic makeup could influence the selection and dosing of medications, including urate-lowering therapies (ULTs). Patients with gout present with several comorbidities, warranting the use of several long-term medications that increase their pill burden and the risk of adverse drug events. PGx testing can identify individuals who are more or less likely to benefit from a given treatment and ultimately improve adherence and reduce polypharmacy. Gout management involves using various ULTs associated with specific genetic variations that could modulate medication safety and efficacy. Individuals carrying the HLA-B*58:01 variant are at a higher risk of serious and life-threatening skin reactions from taking allopurinol. Besides, racial disparities in HLA-B distribution warrant testing for its status in high-risk populations, specifically some Asian subgroups and African Americans. G6PD-deficient individuals are prone to develop hemolytic anemia and methemoglobinemia with pegloticase and probenecid use. Patients with the less active form of the drug-metabolizing CYP2C9 are at higher risk for NSAID-related upper gastrointestinal (GI) bleeding. The drug-gene pair interactions among various gout therapies were also reviewed. Allopurinol-related genes included AOX, ABCG2, and SLC22A12. Febuxostat-related genes included UGT1A1. Benzbromarone- and probenecid- related genes included SLC22A12 and ABCB1. Colchicine-related genes included CYP2D6, ABCB1, rs6916345 G>A, and SEPHS1. Finally, the corticosteroid-related gene included HCG22; and the anakinra-related gene included IL1RA. This review synthesizes the most contemporary level of evidence for using PGx in gout pharmacotherapy, as referenced in the CPIC guidelines, FDA, PharmGKB, and current literature.

The post-2007 crisis-induced an agricultural expansion across Africa, but local level production and marketing experiences remain understudied. This study assesses the dynamics of agricultural expansion and small-scale farmers’ experiences in rural Zambia. Using a mixed research design, data were drawn from surveys, multi-level interviews, group discussions policy reviews and observations. Results show an agriculture expansion among small-scale farmers is underway due to favourable climatic conditions, land, and water availability, enabled by state subsidies, and an emerging market in commercial and supermarket outlets. However, farmers encounter production and marketing challenges related to poor tenure security, late delivery of inputs, and low financing. They face low and fluctuating prices, poor infrastructure, including low levels of mechanisation necessary to expand the production. Overall, despite an agricultural and land-use expansion taking shape, actual benefits for real transformation are largely missing – and currently over their heads. An argument is made that whilst policy actors continue to impress farmers to organise themselves to maximise benefits of an agricultural expansion, actual processes on how farmers can achieve this are missing in policy and practice. This necessitates a focus on multi-level processes aimed at addressing production, storage and marketing dynamics within a progressive coordination arrangement that centralizes small producers. Until that is addressed, the prospects for local development and poverty reduction for small-scale farmers under an agricultural expansion will be slender but continue to centrally reside in the state efforts to create enabling local and community environment that addresses real challenges. Overall, this study helps to extend the debate on diverse processes shaping rural transformation in Zambia and across sub-Saharan Africa, including the role and importance of agricultural expansion.

Attackers are perpetually modifying their tactics to avoid detection and frequently leverage legitimate credentials with trusted tools already deployed in a network environment, making it difficult for organizations to proactively identify critical security risks. Network traffic analysis products have emerged in response to attackers’ relentless innovation, offering organizations a realistic path forward for combatting creative attackers. Additionally, thanks to the widespread adoption of cloud computing, Device Operators (DevOps) processes, and the Internet of Things (IoT), maintaining effective network visibility has become a highly complex and overwhelming process. What makes network traffic analysis technology particularly meaningful is its ability to combine its core capabilities to deliver malicious intent detection. In this paper, we propose a novel darknet traffic analysis and network management framework to real-time automating the malicious intent detection process, using a weight agnostic neural networks architecture. It is an effective and accurate computational intelligent forensics tool for network traffic analysis, the demystification of malware traffic, and encrypted traffic identification in real-time. Based on Weight Agnostic Neural Networks (WANNs) methodology, we propose an automated searching neural net architectures strategy that can perform various tasks such as identify zero-day attacks. By automating the malicious intent detection process from the darknet, the advanced proposed solution is reducing the skills and effort barrier that prevents many organizations from effectively protecting their most critical assets.

Planning and implementation of construction projects are difficult processes and are burdened with many risk elements. The budget spread over time, which is developed on the basis of the schedule, presents the expected distribution of costs throughout the duration of the works, which during the implementation of the project is subject to constant changes resulting from time, cost and organizational factors. Managing construction contracts requires managers to be able to analyze on an ongoing basis the variances of production costs - from the values calculated in the offer cost estimate and assumed in the Budgeted Cost of Work Scheduled. The article attempts to analyze the emerging time and cost variances using proprietary C-S and S-C monitoring, based on simple indicators of the EVM method. An example of construction of a multi-family housing development was used to study the variances of planned and incurred costs.

Based on the key molecule of humoral adaptive immunity, the antibody, evolution of the system comprises molecular genetic, cell biologic and immunologic mechanisms, and as a network the system is likely governed and can be characterized by physical rules as well. While deep sequencing can provide vast amounts of data related primarily to clonal relationships, functional interpretation of such data is hampered by the inherent limitations of converting sequence to structure to function. In this paper a novel model of structural interaction space, termed radial adjustment of system resolution, or RADARS, is proposed. The model is based on the radial growth of resolution of structural recognition, corresponding to increasing affinity of immune reactivity, and the virtual infinity of directions of growth, corresponding to the ability to respond to almost any molecular structure. Levels of interaction strength appear as shells of the sphere representing the system. B-cell development and immune responses can be readily interpreted in the model and quantitative properties of the antibody network can be inferred from the physical properties of a quasi-spherical system growing multi-radially. The system is described by double-Pareto distribution, sampling the lognormally distributed equilibrium constants at a rate of phi square. Finally, general strategies for merging antibody sequence space into structural space are outlined.

Supermarkets in Port Harcourt (PH) city, Nigeria, predominantly rely on diesel electricity generation due to grid instability, leading to high cost of electricity prices. Although solar photovoltaic (PV) systems have been proposed as an alternative, these supermarkets have yet to adopt them, mainly due to high investment costs and a lack of awareness of the long-term financial and environmental benefits. This paper examines the technical and economic practicality of a PV system for these supermarkets using the PVsyst software and a spreadsheet model. Solar resources showed that PH has a daily average solar radiation and temperature of 4.21 kWh/m2/day and 25.73℃, respectively. Market Square, the supermarket with the highest peak power demand of 59.8 kW, and a 561 kWh/day load profile, was chosen as a case study. A proposed PV system with a power capacity of 232 kW, battery storage capacity of 34,021 Ah, a charge controller size of 100 A/560V, and an inverter with a power rating of 60V/75 kW has been designed to meet the load demand. The economic analysis showed a $266,936 life cycle cost, $0.12 per kWh levelized cost of electricity (LCOE), 4-year simple payback time, and a 20.5% internal rate of return (IRR). The PV system is feasible due to its positive net present value (NPV) of $165,322 and carbon savings of 582 tCO2/year.

Myocardium transcriptomes of mouse left and right atria and ventricles were profiled separately to identify the differences that might be responsible for the distinct functional roles of the four heart chambers. In total, 16,886 distinct unigenes have been quantified in all 16 samples collected from four adult male mice from the same litter. 15.76% of the quantified genes on the left and 16.5% on the right exhibited differential expression between the corresponding atrium and ventricle of the same side, while 5.8% in atria and 1.2% in ventricles were differently expressed between the left and the right. Beyond the differentially expressed genes, the study revealed distinct expression control and coordination of ion channels and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/glucogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 (encoding ankyrin-B) oscillates in phase with all its binding partners in the left ventricle, the percentage of synergistically expressed partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis revealed also the high interventricular synchrony of the expression of ion channels.

In this article, we establish the existence of and then compare smallest eigenvalues for nabla fractional boundary value problems involving a fractional difference boundary condition, using the theory of u0-positive operators with respect to a cone in a Banach space.

The objective of this study was to evaluate the efficacy of fungal treatment (Pleurotus ostreatus) of urea-treated rice stubble on growth performance in slow-growing goats. Eighteen crossbred Thai native x Anglo-Nubian male goats (average body weight: 20.4 ± 2.0 kg) were randomly assigned to three experimental total mixed rations containing 35% rice stubble (RS) that was either untreated (URS), urea treated (UTRS) or treated with urea and fungi (UFTRS). URS and UTRS were cultivated and harvested from aseptically fungal spawn, incubated at 25-30 °C for 25 days. Indicators of growth performance were monitored and faeces were collected quantitatively to assess nutrient digestibility, during a 12-week feeding trial. All goats remained healthy throughout experiment. The goats fed UFTRS had a lower feed conversion ratio (kg feed/kg growth) compared to goats fed URS or UTRS. Compared to URS, dietary UFTRS increased nutrient digestibility of slow-growing goats, such as OM (+8.5%), CP (+5.5%), NDF (+39.2%), and ADF (+27.4%). Likewise, dietary UFTRS tended to increase rumen ammonia concentrations but rumen pH and volatile fatty acids were not affected by UFTRS. In conclusion, the present study indicates that the fungal treatment of RS is an effective tool to improve the growth performance of slow-growing goats.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

Methods are currently lacking to prove artificial general intelligence (AGI) safety. An AGI ‘hard takeoff’ is possible, in which first generation AGI1 rapidly triggers a succession of more powerful AGIn that differ dramatically in their computational capabilities (AGIn≪AGIn+1). No proof exists that AGI will benefit humans or of a sound value-alignment method. Numerous paths toward human extinction or subjugation have been identified. We suggest that probabilistic proof methods are the fundamental paradigm for proving safety and value-alignment between disparately powerful autonomous agents. Interactive proof systems (IPS) describe mathematical communication protocols wherein a Verifier queries a computationally more powerful Prover and reduces the probability of the Prover deceiving the Verifier to any specified low probability (e.g., 2-100). IPS procedures can test AGI behavior control systems that incorporate hard-coded ethics or value-learning methods. Mapping the axioms and transformation rules of a behavior control system to a finite set of prime numbers allows validation of ‘safe’ behavior via IPS number-theoretic methods. Many other representations are needed for proving various AGI properties. Multi-prover IPS, program-checking IPS, and probabilistically checkable proofs further extend the paradigm. In toto, IPS provides a way to reduce AGIn↔AGIn+1 interaction hazards to an acceptably low level.

In this study, we introduce a new type curve in 3-dimensional space which called B-lift curve and we obtain the Frenet operators of the B-lift curve. Moreover, we consider the correpondence of Frenet operators between the Blift curve and the natural lift curve. Finally, we investigate the B-lift curve according to the main curve is slant helix or darboux helix.

Over time, the agricultural sector's contribution to the nation's Gross Domestic Product and revenue is declining exponentially; the decline may be attributed to varying problems affecting the agricultural value chain resulting in low productivity. The agricultural value chain comprises a series of activities and value addition processes required to transform raw materials into useable products to maximize the final consumers' utility.¹ The agricultural value chain's marketing activities have been skewed with challenges, thus affecting agricultural productivity and agricultural sector contribution to the economy. The paper critically examines and discuss the impact of agricultural marketing to economic development, a historical review of agricultural marketing in Nigeria, challenges undermining the impact of agricultural marketing, measures to reposition agricultural marketing potential to build back better, policy recommendations to reposition the future of Nigeria's agricultural productivity. The paper aims to promote concerted efforts through knowledge dissemination to build back better through market research and facilitation and boost economic prosperity.

In this paper, by using the variational method, a sufficient condition for the unique existence of the stationary solution of the reaction-diffusion ecosystem is obtained, which directly leads to the global asymptotic stability of the unique equilibrium point. Moreover, delayed feedback ecosystem with reaction-diffusion item is considered, and utilizing impulse control results in the globally exponential stability criterion of the delayed ecosystem. It is worth mentioning that the Neumann zero-boundary value that the infected and the susceptible people or animals should be controlled in the epidemic prevention area and not allowed to cross the border, which is a good simulation of the actual situation of epidemic prevention. And numerical examples illuminate the effectiveness of impulse control, which has a certain enlightening effect on the actual epidemic prevention work . That is, in the face of the epidemic situation, taking a certain frequency of positive and effective epidemic prevention measures is conducive to the stability and control of the epidemic situation. Particularly, the newly-obtained theorems quantifies this feasible step. Besides, utilizing Laplacian semigroup derives the $p$th moment stability criterion for the impulsive ecosystem.

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of a HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation for stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations along with attenuating mutations E580G and S660A in PB1 of B/Bris (B/Bris PB1att 4M). Serial passage of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

This study assesses the pursued impacts of Tulsi value chain development intervention on the livelihoods of rural poor in Uttarakhand state of India. Tulsi as an alternative livelihood, particularly for the rural poor, is less explored. With increased crop depredation of major cereal crops grown in the district by wild animals and pests, and decreasing availability of water agriculture, attempts were made to improve earnings from Tulsi as an alternative livelihood. Findings suggest that the average households’ gross profit from Tulsi farming increases by more than double within a span of two years. Total crop income of beneficiary farmers’ increases by 0.8 percent for every 1 percent increase in Tulsi income. Intervention helped enhance productivity of Tulsi, thereby enhancing earnings from Tulsi farming. Most importantly, intervention has shown a tremendous adoption rate. Towards the end of the intervention, the value chain work was out-scaled to another 19 villages in Chamoli district, thereby reaching out to more than 400 households.

In this study, a mixed rule of degree of precision nine has been developed and implemented in the field of electrical sciences to obtain the instantaneous current in the RLC- circuit for particular value .The linearity has been performed with the Volterra’s integral equation of second kind with particular kernel . Then the definite integral has been evaluated through the mixed quadrature to obtain the numerical result which is very effective. A polynomial has been used to evaluate Volterra’s integral equation in the place of unknown functions. The accuracy of the proposed method has been tested taking different electromotive force in the circuit and absolute error has been estimated.

This is the first study to provide a systematic monetary benefit matrix, including greenhouse gas (GHG) emissions reduction benefits and air pollution reduction health co-benefits, for a change in on-the-road transport to low-carbon types. The benefit transfer method is employed to estimate the social cost of carbon and the health co-benefits via impact pathway analysis in Taiwan. Specifically, the total emissions reduction benefits from changing all internal combustion vehicles to either hybrid electric vehicles, plug-in hybrid electric vehicles, or electric vehicles would generate an average of US$760 million from GHG emissions reduction and US$2,091 million from health co-benefits based on air pollution reduction, for a total benefit of US$2,851 million annually. For a change from combustion scooters to light- or heavy-duty electric scooters, the average GHG emissions reduction benefits would be US$96.02 million, and the health co-benefits from air pollution reduction would be US$1,008.83 million, for total benefits of US$1,104.85 million annually.

With the Paris Agreement, countries are obliged to report greenhouse gas (GHG) emission reduc-tions, which will ensure that the global temperature increase is maintained well below 2C. The Parties will report their Nationally Determined Contributions in terms of plans and progress to-wards these targets during the postponed COP26 in Glasgow in November 2021. These commit-ments however do not take significant portions of the consumption related emissions related to countries imports in to account. Similarly, the majority of companies that report their emissions to CDP also do not account for their embodied value-chain related emissions. Municipalities, on the path towards carbon neutrality in accordance with the methods outlined by C40, also do not in-clude imported and embodied CO2e in their total emission tallies. So, who is responsible for these emissions - the producer or the consumer? How can we ensure that the NDC's, municipalities and companies reduction targets share the responsibility of the emissions in the value-chain thus en-suring that targets and plans become, sustainable, climate fair, and just in global value chains? Today the responsibility lays with the producer, which is not sustainable. We have the outline for the tools needed to quantify and transparently share the responsibility between producers and consumers at corporate, municipal and national level based on an improved understanding of the attendant sources, causes, flows and risks og GHG emissions globally. Hybrid LCA/EEIO models can for example be further developed. This will, in the end, enable everyday consumption to support a more sustainable, green and low carbon transition of our economy.

In this work, we studied the Green’s functions of the second order differential operators with involution. Uniform equiconvergence of spectral expansions related to the second-order differential operators with involution is obtained. Basicity of eigenfunctions of the second-order differential operator operator with complex-valued coefficient is established.

The increasing demand for higher inclusion cleanliness levels motivates the control over the formation and evolution of inclusions in the steel production process. In this work, the evolution of the chemical composition and size distribution of inclusions throughout a slab production process of Al-killed steel, including ladle furnace (LF) treatment and continuous casting (CC), was followed. The initial solid Al2O3 and Al2O3-MgO inclusions were modified to liquid Al2O3-CaO-MgO inclusions during LF treatment. The evolution of the size distributions during LF treatment was associated with the growth and removal of inclusions, as new inclusions were not created after the deoxidation process, according to a population density function (PDF) analysis. Additionally, the size distributions tended to be similar as the LF treatment progressed regardless of their initial features, whereas they differed during CC. Analysis of the upper tails of the distributions through generalized extreme values theory showed that inclusion distributions shifted from larger to smaller sizes as the process progressed. There were great changes in the distributions of large inclusions throughout the LF treatment and between the end of the LF treatment and the start of the CC process. Additionally, distributions of large inclusions differed at the end of the LF treatment, whereas such differences decreased as CC progressed.

The connection of two phenomena - non-conservative friction forces and dissipation-induced instability can lead to many interesting engineering problems. The paper studies general material-dependent damping influence on dynamical instability of disc brake systems leading to brake squeal. The effect of general damping is demonstrated on a minimal and complex model of a disc brake. A complex system including material-dependent damping is defined in the commercial finite element software. The finite element model validated by experimental data on the brake-disc test bench is used to compute the influence of a pad and a disc damping variations on system stability by complex eigenvalue analysis. Analyzes show a significant sensitivity of the experimentally verified unstable mode of the system to the ratio of the damping between the disc and the friction material components.

Growing acreage and changing consumer preferences cause increasing interest in the cereal products originating from organic farming. Lack of results of objective test, however, does not allow drawing conclusions about the effects of cultivation in the organic system and comparison to currently preferred conventional system. Field experiment was conducted in organic and conventional fields. Thirty modern cultivars of winter wheat were sown. They were characterized for disease infection including Fusarium head blight, seed sowing value, the amount of DNA of the six species of Fusarium fungi as well as concentration of ergosterol and trichothecenes in grain. The intensity Fusarium head blight was at a similar level in both systems. However, Fusarium colonization of kernels expressed as ergosterol level or DNA concentration was higher for the organic system. It did not reflect in an increased accumulation of trichothecenes in grain, which was similar in both systems, but sowing value of organically produced seeds was lower. Significant differences between analyzed cropping systems and experimental variants were found. The selection of the individual cultivars for organic growing in terms of resistance to diseases and contamination of grain with Fusarium toxins was possible. Effects of organic growing differ significantly from the conventional and grain obtained such way can be recommended to consumers. There are indications for use of particular cultivars bred for conventional agriculture in the case of organic farming, and the growing organic decreases plant stress resulting from intense fertilization and chemical plant protection.

In this present work, we are reporting a novel route for the synthesis of the tetracyclic ring systems, which is a common core of crinipellin via oxidative dearomatization, cycloaddition and oxa- di-pi-methane rearrangement. We considered to exploring a route to tetracyclic core (1e) of Crinipellin and tricyclic core (1g) of Allicaol B through intermolecular diels alder reaction and photochemically 1,2 acyl shift. Moreover, docking study of compound 13 and 16has been investigated against AcrB multidrug efflux pump of Escherichia coli (PDB ID: 1T9U), main protease of SARS COV-2 (PDB ID: 6W63), DNA gyrase of Streptococcus pneumonia (PDB ID: 4Z2C), human estrogen receptor alpha (PDB ID: 3ERT), human lanosterol 14-alpha-demethylase (CYP51)(PDB ID: 3JUS) and cyclooxygenase-2 (Prostaglandin Synthase-2) (PDB ID: 1CX2). The obtained results herein are important for the exploitation of the therapeutic potential of these derivatives as antimicrobial, antiviral, anticancer, antifungal or anti-inflammatory agents.

Using a theorem of Ulam and Hyers, we will prove the Hyers-Ulam stability of two-dimensional Lagrange's mean value points $(\eta, \xi)$ which satisfy the equation, $f(u, v) - f(p, q) = (u-p) f_x(\eta, \xi) + (v-q) f_y(\eta, \xi)$, where $(p, q)$ and $(u, v)$ are distinct points in the plane. Moreover, we introduce an efficient algorithm for applying our main result in practical use.

Introduction: Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb and analyze how enrolment in obligatory and supplemental courses affects knowledge and needlestick injury reporting practice. Materials and methods: The knowledge was assessed by our questionnaires based on Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data was analyzed by descriptive statistical analysis, independent-samples t-tests, proportion analyses and combined factor analyses of categorical and quantitative variables in SPSS and R. Results: In total, 206 students participated. The overall level of HBV and HCV-related knowledge was poor with average scores being 61.90% and 51.35% respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants 18.2% sustained a needlestick injury, and majority of them (78.95%) never reported the injury. Conclusion: In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form failed to significantly improve competence of students and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.