Hydrophilic coatings have recently emerged as a new approach to avoid the adhesion of (bio)organisms on surfaces immersed in water. In these coatings the hydrophilic character is crucial for the anti-fouling (AF) performance. However, this property can be rapidly lost due to the inevitable damages which occur at the surface, reducing the long-term effectiveness of the AF functionality. We report hydrophilic polycarbonate-mPEG polyurethane coatings with tunable hydrophilic properties as well as an excellent and long-term stability in water. The coatings exhibit low protein adhesion values and are able to self-replenish their hydrophilicity after damage, due to the existence of a reservoir of hydrophilic dangling chains incorporated in the bulk. The combination of low T_g and sufficient mobility of the mPEG dangling chains (enabled by chains with higher molecular weight) proved to be crucial to ensure autonomous surface hydrophilicity recovery when the coatings were immersed in water. This coatings and design approach offer new possibilities towards high performance AF coatings with an extended service life-time which can be used in several major applications areas, such as marine and biomedical coatings, with major economic and environmental benefits.

The application of machine learning techniques to satellite imagery has been the subject of interest in recent years. The increase in quality and quantity of images, made available by Earth observation programs, such as the Copernicus program, led to the generation of large amounts of data. Among the various applications of this data is the creation of land cover maps. The present work aimed to create machine learning models capable of accurately segment and classify satellite images, to automatically generate a land cover map of the Portuguese territory. Several experiments were carried out with the spectral bands of the Sentinel-2 satellite, with vegetation indices, and with several sets of land cover classes. Three machine learning architectures were evaluated, which adopt two different techniques for image classification. One of the classification techniques follows an object-oriented approach, and in this case the architecture adopted in our models was a U-Net artificial neural network. The other classification technique is pixel-oriented, and the machine learning models tested were random forest and support vector machine. The overall accuracy of the results obtained ranged from 68.6% to 94.75%, depending strongly on the number of classes into which the land cover is classified. The result of 94.75% was obtained when classifying the land cover only into 5 classes. However, a very interesting accuracy of 92.37% was achieved by the model when trained to classify 8 classes. These results are superior to those reported in the related bibliography.

This review focus on a critical analysis of nanocatalysts for Advanced Reductive Processes (ARP) and Oxidation Processes (AOP) designed for the degradation of poly/perfluoroalkyl substances (PFAS) in water. Ozone, ultraviolet and photocatalyzed ARP and/or AOP will be the basic treatment technologies. Besides the review of the nanomaterials with greater potential as catalyst for advanced processes of PFAS in water, the perspectives for its future development considering sustainability considerations will be discussed. Moreover, a brief analysis of the current state of the art of the ARP and AOP for the treatment of PFAS in water will be presented.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

Biomass-derived carbon dots (CDs) are gaining much interest in recent times as it is a sustainable option with abundant availability, low cost, and tunable luminescence. Herein, we report a simple green synthesis method to produce highly fluorescent CDs from Eucalyptus globulus leaves using the one-pot hydrothermal approach. The fabricated CDs exhibit strong blue fluorescence with an excitation and emission maxima of 340 nm and 442 nm respectively. The highest quantum yield (QY) obtained was 60.7%. Due to its promising optical properties and biocompatibility, CDs can be a potential candidate for biosensing applications. Moreover, we employed a life cycle assessment (LCA) cradle-to-gate approach to study the environmental impacts of the synthesis strategy used for the fabrication of CDs. The results point out that citric acid is a main hotspot in CDs synthesis, regarding environmental impacts in most categories. This justifies the introduction of biomass, which reduces the amount of citric acid, thus leading to a more sustainable synthesis strategy for fabricating CDs.

Personal Information Management Systems (PIMS) are acquiring a prominent role in the data economy by promoting services that help individuals to have more control over the processing of their personal data, in line with the European data protection law. One of the highlighted solutions in this area is Solid, a new protocol that is decentralizing the storage of data, through the usage of interoperable Web standards and semantic vocabularies, to empower its users to have more control over the processing of data by agents and applications. However, to fulfill this vision and gather widespread adoption, Solid needs to be aligned with the law governing the processing of personal data in Europe, the main piece of legislation being the General Data Protection Regulation (GDPR). To assist with this process, we analyze the current efforts to introduce a policy layer in the Solid ecosystem, in particular, related to the challenge of obtaining consent for processing personal data, focusing on the GDPR. Furthermore, we investigate if, in the context of using personal data for biomedical research, consent can be expressed in advance, discuss the conditions for valid consent and how it can be obtained in this decentralized setting, namely through the matching of privacy preferences, set by the user, with requests for data and whether this can signify informed consent. Finally, we discuss the technical challenges of an implementation that caters to the previously-identified legal requirements.

Sensing Technology (ST) plays a key role in Structural Health Monitoring (SHM) systems. ST focuses on developing sensors, sensory systems or smart materials that monitor a wide variety of materials properties aiming to create smart structures and smart materials, using Embedded Sensors (ESs), and allowing continuous and permanent measurements of the structural integrity. The integration of ESs is limited to the processing technology to embed the sensor due to its high-temperature sensitivity and the possibility of damage during its insertion into the structure. In addition, the technological process selection is dependent on the base material composition, either metallic or composite parts. The selection of smart sensors or the technology underlying them is fundamental to the monitoring mode. This paper presents a critical review of the fundaments and applications of sensing technologies for SHM employing ESs, focusing on the actual developments and innovation of these, as well as analysing the challenges that these technologies present, to build a path that allows a connected world through distributed measurement systems.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

The global trade and transportation sectors heavily rely on the maritime industry. Still, its dependence on fossil energy sources poses significant environmental challenges and leads to unstable fuel prices that affect the cost of goods transported by sea. This paper aims to evaluate the viability of seaports as energy-intensive entities and explore the feasibility of implementing a Nuclear-Renewable Hybrid Energy System (NRHES). The study presents a case study of the Tanjung Priok Port in Indonesia, focusing on estimating energy consumption, emissions, and the potential impact of carbon taxation on seaport operations. By quantifying these factors, the research provides insights into the energy requirements, environmental effects, and potential costs associated with seaport carbon taxation. A comprehensive analysis of the technical and economic feasibility of implementing an NRHES in the seaport case study is conducted, determining the optimal sizing and composition of components, considering the proportion of nuclear and renewable energy sources. Additionally, the economic analysis considers energy costs, net present cost, cash flow, return on investment, and internal rate of return. The findings aim to inform decision-makers about the benefits and challenges of adopting an NRHES, contributing to a cleaner and more sustainable future for the maritime industry.

The skin acts as a protective barrier, guarding the body against microorganisms, chemicals, and several environmental factors. Accordingly, this all-important organ must be kept healthy to maintain its optimal functionality. One approach to maintain skin health is the application of multifunction bioactive sunscreens containing antioxidant molecule(s). Rosmarinic acid (RA), a phenolic compound, is known for its antioxidant activity. Herein, the safety and efficacy of a multifunction prototype sunscreen were investigated, aiming to probe putative synergies of this polyphenol with two known and widely used UV filters (bemotrizinol and octyl p-methoxycinnamate). Samples protected the DNA fragmentation compared to UV control, by the comet assay, and showed good skin compatibility in subjects. Formulations F1 and F3 were able to increase skin hydration, and, possibly, the RA interfered with this attribute. An increase in transepidermal water loss was observed for formulations F1, F2 and F4, which may be related to vehicle containing or not the RA. No decreases were observed in the inflammatory reaction caused by the ethyl nicotinate with any of the evaluated formulations. As a perspective, we suggest trials with a greater number of subjects or protocol modifications. Altering the vehicle qualitative and quantitative composition is also a pertinent perspective.

Compared to tin lead alloys, lead-free tin alloys have lower toxicity, making them more widely used. In this study, Sn-20Bi-0.3Al-xY solders alloys were prepared. The effects of the addition of Y on its microstructure, micro-hardness, wettability and mechanical properties was investigated. The result showed that the addition of Y had significant effect on the refinement of Sn-20Bi-0.3Al-xY. From the spreading tests results, Y increased the wettability of the solders, however when the fraction of Y gradually increased, the wettability reduced. The ultimate tensile and hardness of Sn-20Bi-0.3Al-xY solders alloys were increased as the content of Y increasing.

Insect meal as a protein source has been considered a sustainable way to feed animals. H. illucens and T. molitor larvae meal are considered high protein sources for poultry, also presenting considerable amounts of fatty acids, vitamins, and minerals. However, other potential components in insect meal and insect oil have been more studied nowadays. Chitin, lauric acid, and antimicrobial peptides can present antimicrobial and prebiotic functions, indicating that low inclusions of insect meal can beneficially affect broilers` health and immune responses. This systematic review was developed to study the impact of insect products on health parameters of broilers, and a metanalysis was conducted to evaluate the effects on performance. A database was obtained based on a selection of manuscripts from 2016 to January 2023, following the mentioned parameters. There were positive effects of both H. illucens and T. molitor meal or oil products on poultry health status, especially in microbiota population, immune responses, and antimicrobial properties. The average daily gain was greater in broilers fed T. molitor meal compared to H. illucens meal (p = 0.002). The results suggest that low levels of insect meal were suitable for broilers, without result in negative effects on performance, while the insect oil can totally replace soybean oil without negative impacts.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Lymphedema refers to a group of disorders characterized by the accumulation of protein-rich fluid in the interstitial tissues, resulting from an imbalance between lymph production and it’s drainage via lymphatic vessels. More than 10 types of isolated primary LD is described, and among them CELSR1-associated lymphedema are one of the less studied. A family with two sibs, a 17-year-old boy and an 8-year-old girl, both diagnosed with primary LD, presented to the clinic. Both patients were observed with primary symptoms of LD at 2-3 months of age, presented by the swelling of right foot. Lymphatic pathologies were not diagnosed in parents or close relatives. The rare c.7664A>C variant, resulting in the H2555P missense mutation in the intracellular loop of CELSR1 transmembrane domain, was discovered in a patients. The clinical signs, MRL scanning data, in silico predictors and the absence of known pathogenic mutations or rare variants of unknown significance in other genes, associated with the development of primary lymphedema, allow us to assume that c.7664A>C variant of CELSR1 may be responsible for pathogenesis of the disease in the presented family case.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

LASER cladding is a technique which has as main purpose to improve mechanical properties of materials surface with the addition of thin layers of other materials. Cladding/coating/addition material can be transferred to the substrate by powder injection, wire feeding or paste feeding and by the method of pre-placing the powders on the substrate. LASER cladding as a technique has only about 40 years. Is not yet a current technology and more work is needed, namely in the characterization of mechanical properties of new alloys used as base or cladding materials in this process. In this paper will be done initially an historical approach, followed by a description of the principles of the LASER cladding, a description of the applicability of the process and its advantages and limitations and the paper will end with a state of the art about the advances in new metallic alloys. So, this paper presents a review and the state of the art of the technological process and will be a contribution for the divulgation of this recent technique.

Modified nucleobases are potentially useful building blocks when containing catalytically active functionalities and could be introduced in chiral tridimensional molecules such as nucleic acids, which creates the premises for the development of novel catalytic species. Herein we describe the synthesis of a novel β-C-nucleoside bearing a diol group at anomeric position, amenable as metal ligand or as organo-catalyst. The abasic ligand was successfully prepared and inserted into complementary DNA strand.

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

We present a very computationally light and fast approximation algorithm and then verify it with genetic algorithm and simulated annealing. We show that our algorithm is on par with GA and SA in terms of output produced while having a tightly bounded time complexity. Our algorithm works best when there is a strong positive correlation between the reliability of a component and its cost. We present two algorithms with the same essence. One of them is system cost bounded and the other is target reliability bounded. Our proposed algorithm works on a subsystem level redundancy instead of component level redundancy.

Introduction: The aim of the present systematic review was to evaluate the clinical and radiographic success of partial pulpotomies in deep caries processes or post-eruptive defects in young, vital permanent teeth. Methods: Electronic databases, PubMed, Scopus, and Embase, were searched, followed by a manual search. Randomized controlled trials evaluating partial pulpo-tomy with a follow-up period of ≥12 months were included. Meta-analyses using a random effect model were performed. Results: A total of 3.127 articles were retrieved, and after duplicate re-moval, 2.642 were screened by title and abstract; 1 additional article was found during the manual search in the reference lists, and 79 were identified. Finally, 6 papers were included in the review. Regardless of the partial pulpotomy modalities or material used, there were no signifi-cant differences between clinical and radiographic success rates (cumulative success rate 91,8%-92,3%, respectively). Five studies were included in the meta-analysis that did not indicate any statistically significant differences in success rates when Mineral Trioxide Aggregate was compared to other materials (95% CI 0,239 to 1,016 p=0.055). Conclusion: This research system-atically evaluates the evidence and summarises the available data on partial pulpotomy in young permanent teeth. Given its high clinical and radiographic success rate, partial pulpotomy should be considered when vital pulpal therapy needs to be performed in highly damaged young per-manent teeth, as this procedure provides a biological benefit and allows more invasive endodon-tic treatments to be postponed.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

The transportation sector is a significant source of greenhouse gas emissions. Electric vehicles (EVs) have gained popularity as a solution to reduce emissions, but the high load of charging stations poses a challenge to the power grid. Nuclear-Renewable Hybrid Energy Systems (N-RHES) present a promising alternative to support fast charging stations, reduce grid dependency, and decrease emissions. However, the intermittent problem of renewable energy sources (RESs) limits their application, and the synergies among different technologies have not been fully exploited. This paper proposes a predictive and adaptive control strategy to optimize the energy management of N-RHES for fast charging stations, considering the integration of nuclear, photovoltaics, and wind turbine energy with a hydrogen storage fuel cell system. The proposed dynamic model of a fast-charging station predicts electricity consumption behavior during charging processes, generating probabilistic forecasting of electricity consumption time-series profiling. Key performance indicators and sensitivity analyses illustrate the practicability of the suggested system, which offers a comprehensive solution to provide reliable, sustainable, and low-emission energy to fast-charging stations while reducing emissions and dependency on the power grid.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

The popular appreciation of dry white wines is most frequently directed to young wines. However, present consumption trends comprise the valorisation of aged dry white wines. Therefore, the present work was aimed at the sensory analysis of these wines with different ages to define their sensory space and to understand which factors drive their quality evaluation by experienced tasters (critics, oenologists and students). Individuals were asked to evaluate several synthetic and aesthetic attributes and to characterise the analytic sensory profile through a Check-All-That-Apply (CATA) methodology. The quality evaluations were differently correlated with wine synthetic parameters according to the taster group. For both critics and oenologists, overall quality scores were driven by persistence and complexity. Moreover, quality was also highly correlated with power for critics and with balance for oenologists. Quality scores were highly correlated with wine browning (absorbance at 420 nm) for critics. The tasting panel showed a homogeneous analytic description of aroma, taste and mouthfeel consistent with wine age. The different ages could be associated to a continuous sensory space characterised by a decreasing perception of freshness and increase in mature and mellowed descriptors. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. The age prediction showed that most tasters failed to guess the age wines with more than roughly 13 years old, indicating that tasters were not familiar with the sensory features of white wines with 17 to 46 years old. In conclusion, experienced tasters consistently described the sensory space and recognised the high quality of aged dry white wines. Education programs may use the defined sensory spaces according to aging and to expand the range of quality perception by consumers.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Meat loss and waste are estimated at each stage along the food chain, but the methods used are complex and the data needed often fragmented. We, therefore, evaluated the feasibility of estimating meat loss and waste using a simpler method comparing meat availability and consumption, using Swiss meat consumption according to a national nutrition survey and Swiss meat availability according to food balance sheets. As availability is reported at the fresh meat level and consumption as consumed, items of the latter were converted to fresh meat equivalents before comparing consumption with availability. Consumed unprocessed meat was directly converted to fresh meat equivalents and consumed meat products after having identified their meat ingredients. Meat availability, meat consumption as consumed and as fresh meat equivalent were 138.4 g/d, 105.5 g/d, and 112.1 g/d, respectively. The resulting total meat loss and waste was 19% and varied from −36% to 38% for the different meat types. Estimating meat loss and waste based on meat availability and consumption derived from a national nutrition survey yielded results varying to such an extent that the evaluated method to estimate meat loss and waste cannot be recommended.

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

Agriculture is the main economic activity of Mozambique and there is lack of information about the quality of agricultural soils. In this paper, five soils from the Manica and Sussudenga districts (Manica province) were sampled in the years 2021/2022 and 2022/2023 (before and after the rainy seasons), were subjected to an agronomical and environmental chemical analysis to assess its quality, either from the fertility and environmental contamination point of view. Standard analytical methodologies from external certified laboratories and local X-ray fluorescence measurements were used. All the studied soils are acidic (pH ranging from 4.5 and 5.4), have no salinity problems (conductivity ranging from 4.2 to 11.8 mS/m), have low amount of soil organic matter (0.90% to 1.81%), and soils from the Sussudenga district have a very low cation exchange capacity (CEC) (average of 3.33 cmolc/kg), while those from Manica district ranges from very low to average CEC (3.59 to 13.11 cmolc/kg). Also, Sussudenga soils have a phosphorous deficiency (values ranging from <20 to 38.5 mg/kg) and there are deficiencies and/or excesses of some macro and micronutrients in all soil samples. Manica soils are contaminated, apparently from geogenic origin, with Cr (280 to 1400 mg/kg), Co (80 mg/kg), Ni (78 to 680 mg/kg) and V (86 mg/kg). Agricultural soils monitoring must be fostered in Mozambique in order to improve food quality and quantity to assure economic and environmental sustainability.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca²⁺/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca²⁺/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca²⁺] changes. I suggest here that that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation is by translocation of the β-arrestin from the sarcoplasm to the PM thus reducing its kinase inhibition action in the sarcoplasm, this reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

Mozambique is one of the poorest countries of the world. However, it has natural resources and if they are managed under sustainable development principles, Mozambique can overcome the current problems. In the present socio-economic status, soil is one of its most important resources and must be protected from pollution and from degradation. This review focuses on the identification and discussion of the main soil quality stressors, namely: soil fertility; deforestation and its sources: agriculture, timber harvesting, charcoal production and uncontrolled fires; mining activities, manly gold artisanal explorations and industrial open-pit coal mining. The sustainable use of the natural resources is mandatory to allow future generations to continue profiting for this nature-based wealth.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

This study employed the Fully Modified Ordinary Least Squares (FMOLS) and the Error Correction Model (ECM) to investigate the long-run and short-run determinants of unemployment rate in Nigeria. To achieve this annual data on unemployment rate, inflation rate, interest rate, exchange rate and population growth from 1981 to 2016 was collected from Central Bank Statistical Bulletins and the World Bank website. The ADF test revealed that the macroeconomic variables are stationary at first difference while the Cointegration test revealed that the variables are cointegrated. Using unemployment rate as dependent variable, the FMOLS model revealed that exchange rate and population growth are positively significantly related to unemployment rate, interest rate and inflation rate were negatively related to unemployment rate but only interest rate was significant. The short run relationship revealed that the coefficient of the ecm(-1) is negative and statistically significant at 5% level indicating that the system corrects its previous period disequilibrium at the speed of 48.93% yearly. This study concludes that high exchange rate and population growth can lead to increase in unemployment rate in Nigeria while the government should develop the industrial sector and non-oil sector in order to generate employment and boost export in Nigeria.

Acute myeloid leukemia (AML) is a rare subtype of acute leukemia in the pediatric and adolescent population but causes disproportionate morbidity and mortality in this age group. Standard chemotherapeutic regimens for AML have changed very little in the past 3-4 decades, but addition of targeted agents in recent years have led to improved survival in select subsets of patients as well as a better biologic understanding of the disease. One key paradigm of bench-to-bedside practice in the context of adult AML currently is the focus on leukemia stem cell (LSC)-targeted therapies. Here we review current and emerging immunotherapies and other targeted agents that are in clinical use for pediatric AML, through the lens of what is known (and not known) about their LSC-targeting capability. Based on a growing understanding of pediatric LSC biology, we also briefly discuss potential future agents on the horizon.

Type 2 Diabetes Mellitus is a chronic metabolic disease that poses a significant long-term health risk due to its debilitating complications. While the diagnosis and monitoring of diabetes are well-established, the monitoring of its numerous complications presents a challenge, which can compromise patients' prognosis and quality of life. We analyzed the proteome of ten saliva samples, five from healthy individuals and five from patients with Type 2 Diabetes Mellitus. The aim was to identify potential biomarkers of Type 2 Diabetes Mellitus and its complications. We used PANTHER and FUNRICH tools to conduct a functional analysis and enrichment approach. Our findings revealed 622 proteins involved in 16 disrupted biological processes, which are linked to Type 2 Diabetes Mellitus. Metabolic processes, response to stimuli, processes of the immune system, and signaling are notable due to their known relation with Type 2 Diabetes Mellitus. Enrichment analysis has revealed that there are eleven biological processes that have been deregulated. These processes involve twenty different salivary proteins that are associated with multiple complications in diabetes. Our findings demonstrate that saliva is a dependable source of possible biomarkers that can be used to monitor diabetes and its complications.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

Hepatitis C virus (HCV) is a major medical health burden and leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations making a vaccine a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered to be the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

Currently, in a context of biorefinery and bioeconomy, lignocellulosic biomass is increasingly used to produce biofuels, biochemicals and value-added products. Microwaves and ultrasounds are emerging techniques that enable efficient and environmentally more sustainable routes in the transformation of lignocellulosic biomass. This review is divided into four parts. In Part I, the theoretical foundations of microwaves and ultrasounds are revisited. Dielectric constants for biomass, factors that influence pre-treatment, are some of the subjects addressed. In Part II, the effects that these technologies have on lignocellulosic biomass (on the size and surface area of the particle; on the content of lignin, hemicellulose and cellulose; on the crystallinity index of cellulose; on the effect of solubilization of organic matter; on hydrolysis and reduction of sugars) are analyzed. In Part III, emphasis is given on how microwaves and ultrasounds can contribute to the achievement of value-added products. In this context, several examples of liquefactions and extractions are presented. Part IV describes examples of sonocatalysis of lignocellulosic biomass to obtain value-added products such as for instancethe production of furfural, which is significantly reduced by ultrasound.

Deoxynivalenol (DON) is a mycotoxin produced by Fusarium spp. that causes Fusarium head blight (FHB) disease in cereal crops. Ingestion of food contaminated with DON poses serious human health complications. However, the DON cytotoxicity has been mostly deduced from animal studies. In this study, we used the nematode Caenorhabditis elegans (C. elegans) as a tractable animal model to dissect the toxic effect of DON. Our results indicate that DON reduces the fecundity and lifespan of C. elegans. The real-time RT-PCR analysis showed that DON upregulates innate immunity-related genes including C17H12.8 and K08D8.5 encoding PMK-1 (mitogen activated protein kinase-1)-regulated immune effectors, and F35E12.5 encoding a CUB-like domain-containing protein. Furthermore, our RNAseq data demonstrate that out of ~ 17,000 C. elegans genes, 313 are upregulated and 166 were downregulated by DON treatment. Among the DON-upregulated genes, several are ugt genes encoding UDP-glucuronosyl transferase (UGTs) which are known to be involved in chemical detoxification. The three upregulated genes, F52F10.4 (oac-32), C10H11.6 (ugt-26) and C10H11.4 (ugt-28) encoding the O-acyltransferase homolog, UGT26 and UGT 28, respectively, are shown to contribute to DON tolerance by RNAi bacterial feeding experiment. The results of this study provide insights to the targets of DON cytotoxicity and potential mitigation measures.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Groundwater vulnerability assessment has become a useful tool for groundwater pollution pre-vention. Groundwater vulnerability maps provide useful data to protect groundwater resources. The identification of agricultural patterns is an important issue for optimized land management. The Tagus river watershed is the backbone of this survey. Naturtejo UNESCO Global Geopark, in central inland Portugal, corresponds to a rural territory. Intensive agricultural practices showed a rising tendency in the last decades. The most internationally used method for vulnerability evaluation is the DRASTIC index. In this survey, the DRASTICAI index is introduced. A new at-tribute - Anthropogenic Influence - is here added. Five levels of growing vulnerability, from low to high, can be here acknowledged. Idanha-a-Nova municipality is the most affected by intensive farming activities. A robust assessment of groundwater quality has a key role. Climate change scenarios and water scarcity are important issues in years to come. Therefore, optimized groundwater management is essential to consider in policy-making strategies.

Intracranial and extracranial large artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients´ risk of stroke. We performed a narrative review of the literature mainly published in the last five years with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA mainly related to lipid pathways and inflammation have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with prognosis of LAA stroke as evaluated by the modified Rankin score. Increased levels of IL-6 and have been associated with the risk of progression of the atherosclerotic disease. Overall, in most studies, the results were not externally validated. External validation of these results is needed. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice we will need robust multicentric studies proving their reproduci-bility and a clear practical applicability for their use.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase of saturated fatty acids in the membrane. The C. elegans homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated 13C stable isotopes into the diet of nematodes and quantified the 13C-labelled fatty acid by GC-MS and HPLC/MS-MS to track the metabolic response to various concentrations of glucose. Previous work has analyzed membrane composition of C. elegans when responding to mild glucose stress and showed few alterations in overall fatty acid composition in the membrane. Here, in nematodes exposed to higher concentrations of glucose, a specific reduction of oleic acid and linoleic acid was observed. Using time courses and stable isotope tracing, the response of fatty acid me-tabolism to increasing levels of glucose stress has been characterized, revealing a funneling of monounsaturated fatty acids to preserve polyunsaturated fatty acid abundance. Taken together, higher levels of glucose unveil a specific reduction of oleic and linolenic acid in the metabolic re-wiring required to survive glucose stress.

Resistance training increases myofiber hypertrophy, but the morphological adaptations that occur within myofibers remain largely unresolved. Fifteen males with minimal training experience (24±4 years, 17.9±1.4 kg/m2 lean body mass index) performed 10 weeks of conventional, full-body resistance training (2x weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained one week prior to and 72 hours following the last training bout. Fiber typing and the quantification of myofibril and mitochondrial areas per fiber were performed using histology/immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, various strength metrics, and mean and type II fiber cross sectional areas (fCSA) (p<0.05). Myofibril areas in type I or II fibers were not altered with training, suggesting a proportional expansion with fCSA increases. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018). However, CS activity levels remained unaltered with training. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in type I+II myofibril areas (r=0.600, p=0.018). Shorter-term resistance training seemingly involves a proportional expansion of myofibrils and an accelerated expansion of mitochondria in type I and II fibers. Additionally, histological and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes in muscle tissue.

Climate change may cause organisms to seek thermal refuge from rising temperatures, either by shifting their ranges or seeking microrefugia within their existing ranges. We evaluate the potential for thermal stratification to provide refuge for two fish species in the San Francisco Estuary (SFE): Chinook Salmon (Oncorhynchus tshawytscha) and Delta Smelt (Hypomesus transpacificus). We compiled water temperature data from multiple monitoring programs to evaluate spatial, daily, hourly, intra-annual, and inter-annual trends in stratification using generalized additive models. We used our data and models to predict the locations and periods of time that the bottom of the water column could function as thermal refuge for salmon and smelt. Periods in which the bottom was cooler than surface primarily occurred during the peak of summer and during the afternoons, with more prominent stratification during warmer years. Although the SFE is often exceedingly warm for fish species and well-mixed overall, we identified potential for thermal refugia in a long and deep terminal channel for Delta Smelt, and in the periods bordering summer for Chinook Salmon. Thermal stratification may increase as the climate warms, and pockets of cooler water at depth, though limited, may become more important for at-risk fishes in the future.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Nowadays, the most advanced micromachined microphones on the market are based on a capacitive coupling principle. Capacitive micro-electro-mechanical systems-based (MEMS) microphones resemble their millimetric counterparts, both in function and in performances. The most advanced MEMS microphones reached a competitive level compared to commonly used measuring microphones in most of the key performance parameters except the acoustic overload point (AOP). In an effort to find a solution for measurement of high-level acoustic fields, microphones with piezoelectric coupling principle have been proposed. Such novel microphones exploit the piezoelectric effect of a thin layer of aluminum nitride, which is incorporated in their diaphragm structure. In these microphones fabricated with micromachining technology, no fixed electrode is necessary, in contrast to capacitive microphones. This specificity significantly simplifies both the design and the fabrication and opens the door for a new improvement of the acoustic overload point as well as harsh environmental applications. Several variations of piezoelectric structures together with an idea leading to electrically controlled sensitivity of MEMS piezoelectric microphone are discussed in the paper.

The ability to control the temperature distribution T(t,r) and the rate of temperature change Rt,r inside glasses is important for their microstructuring. The lattice temperature is considered at time t, exceeding the electron-phonon thermalization time, and at a distance r from the center of the model spherical heating zone. In order to describe thermal excitations, the heat capacity of glasses must be considered as a function of time due to its long-term relaxation. A method for analytical calculation of T(t,r) and R(t,r) for glasses with dynamic heat capacity cdyn(t) is proposed. It is shown that during laser microstructuring the local cooling rate -R(t,r) significantly depends on the time dispersion of cdyn(t). It has been established that at the periphery of the model heating zone of the laser beam focus, the local cooling rate can reach more than 1011 K/s. Strong cooling rate gradients were found at the periphery of the heating zone, affecting the microstructure of the material. This effect is significantly enhanced by the time dispersion of cdyn(t). The effect associated with this time dispersion is significant even well above the glass transition temperature Tg, since even short relaxation times of the dynamic heat capacity cdyn(t) are significant.

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Fungal infection of grape berries (Vitis vinifera) by Botrytis cinerea frequently coincides with harvest, impacting both the yield and quality of grape and wine products. A rapid and non-destructive method for identifying B. cinerea infection in grapes at an early stage prior to harvest is critical to manage loss. In this study, zeolitic imidazolate framework-8 (ZIF-8) crystal was applied as an absorbent material for volatile extraction from B. cinerea-infected and healthy grapes in a vineyard followed by thermal desorption gas chromatography-mass spectrometry. The performance of ZIF-8 to absorb and trap targeted volatiles was evaluated with a standard solution of compounds and with a whole bunch of grapes enclosed in a glass container to maintain standard sampling conditions. Results from sampling methods were then correlated to B. cinerea infection in grapes as measured and determined by Genus specific antigen quantification. Trace levels of targeted compounds reported as markers of grape B. cinerea infection were successfully detected with in-field sampling. Peak area counts for volatiles 3-octanone, 1-octen-3-one, 3-octanol, and 1-octen-3-ol extracted using ZIF-8 were significantly higher than values achieved using Tenax®-TA from field testing and demonstrated good correlation with B. cinerea infection severities determined by B. cinerea antigen detection.

Institutionalized older adults often face complex medication regimens, increasing their risk of adverse drug events due to polypharmacy, overprescribing, medication interactions or the use of Potentially Inappropriate Medications (PIM). However, data on medication use and associated risks in this population remain scarce. This pilot study aimed to characterize the sociodemographic, clinical and pharmacotherapeutic profiles and the use of PIM among institutionalized elders residing in Residential Structures for Elderly People (ERPI) in the Faro municipality, located in the Portuguese region of the Algarve. We conducted a cross-sectional study in a non-randomized sample of 96 participants (mean age: 86.6 ±7.86 years) where trained researchers reviewed medication profiles and identified potentially inappropriate medications using the EU(7)-PIM list. Over 90% of participants exhibited polypharmacy (≥5 medications), with an average of 9.1 ± 4.15 medications per person. About 92% had potential drug interactions, including major and moderate interactions. More than 86% used at least one potentially inappropriate medication, most commonly central nervous system drugs. This pilot study demonstrates that institutionalized older adults may be at high risk of potential medication-related problems. Implementing comprehensive medication review programs and promoting adapted prescribing practices are crucial to optimize medication use and improve the well-being of this vulnerable population.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Electroluminescence (EL) is an innovative technology in the lighting area. The EL device's main structure consists of a phosphor layer sandwiched by two electrodes. In this work, several alternating current EL devices have been developed by applying a set of sequential layers with combinations of in-house prepared inks and commercially available ink as a phosphor layer. A flexible polyester textile substrate was functionalized with inks by spray coating technique, after knife-coated an interfacial layer directly on the surface. A thorough study was carried out on the phosphor layer composition to optimize the EL device performance, more precisely the illuminance intensity and the illuminance homogeneity. The developed phosphor layer was composed of zinc sulphide doped with copper (between 30.0 to 38.1 wt%) and diluted by using a diluent at different ratios (28.0 to 35.5 wt%). The best peak illuminance intensity of 61 lux was obtained when the phosphor ink presented 35.4% ZnS:Cu and was diluted with 33.0% diluent. The aim of this study to determine the best formulation of the phosphor layer, which can be highly promising for further developments of EL devices, taking in account different applications in market.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of two weeks front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n= 13) and experimental (EXP, n=17) subjects completed pre and post testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction and force steadiness computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects supports development of training implements for a more clinical population to help improve force steadiness.

We investigate the determinants of U.S. bilateral imports of olive oil and their dynamics from shocks in foreign supplies and changes in U.S. olive oil demand, using an augmented gravity framework that leads to an equilibrium of bilateral trade flows from olive oil exporters to the U.S. market. The empirical specification is applied at the disaggregated HS-6 level in a panel dataset, and three estimation techniques (truncated OLS, PPML, Heckman), for which the latter two account for zero trade flows, the extensive margin of trade and the potential censored distribution of exports with zero trade flows. We run Reset and HPC tests to qualify our results. On the supply side, exporters’ capacity to exports, multilateral trade resistance, and immigrants’ networks into the US are strong determinants of the bilateral trade flows for both aggregate olive oil exports and for virgin olive oil exports, On the consumer side, U.S. GDP, the import unit value, and immigrant network effects are robust determinants of bilateral flows as well for aggregate and virgin olive oil trade flows. Migrants’ stock, exporters’ GDP and population, and total exports revenues increase the probability of an exporter entering the U.S. market. We could not find robust evidence of consumer behavior being influenced by popular press measures of the emergence of Mediterranean diet and olive oil, or measures of cultural globalization of U.S. consumers.

Genomic analysis indicates that SARS-CoV-2 is most related to RaTG13, a beta corona virus derived from bats by 96% ¹. At present, RaTG13 is only available on the public database in the form of a genome sequence. The genome of RaTG13 (MN996532.1) was sequenced from the RNA of a bat faecal swab collected in 2013 from Yunnan, China, however the exact location is not mentioned. Since RaTG13 is one of the main supports for SARS-CoV-2 to have a natural origin, it is of utmost importance to understand the sample location. RNA dependent RNA polymerase (RdRp) sequence of RaTG13 shows that it is 100% similar to that of bat corona virus BtCoV/4991 and 98.7-98.9% similar to SARS-CoV-2 RdRp ². BtCoV/4991 was described to be a SARS-like (SL-) corona virus from bat faeces sampled in an abandoned mine from Mojiang ². Both the publications ^1,2 are authored by Dr. Zheng-li Shi (Z-L Shi), who is described as the bat woman of China ³. However, BtCoV/4991 has not been mentioned by Zhou et al 2020 ¹ where novel corona virus was first described. Based on the RdRp sequence similarities, similarities in sample collection dates, sample locations, and the fact that RaTG13 is mentioned synonymous to BtCoV/4991 on the Chinese bat database, it is predicted that RaTG13 and BtCoV/4991 originate from the same sample. The sample, bat faecal swab was collected in 2013 from an abandoned mineshaft in Mojiang by Dr. Shi and her work group. In 2012, in a Mojiang mineshaft, six mine workers suffered from atypical pneumonia and three of them died. These workers were engaged in the work of clearing debris from a mineshaft which had a lot of bats and bat faeces ^3,4. A detailed health investigation indicated that the miners suffered from atypical pneumonia mostly of the viral origin ⁴. Therefore, in the light of the present Covid-19 caused by SARS-CoV-2, the fact that its phylogenetic neighbour RaTG13 originated from bat faeces collected from a mineshaft, which was also the origin of pneumonia-like disease in miners in 2012, should be noted.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

Nuʻupia Ponds, a traditional Hawaiian fishpond system, are located at Marine Corps Base Hawaii (MCBH) and part of the Nuʻupia Ponds Wildlife Management Area, a wetland refuge for native, endangered, and protected birds and Hawaiian green sea turtles, as well as many native fish species. Currently, there is uncertainty regarding the ecological status and condition of the fishponds following prior modification of wetland habitats in and around the ponds. This study examines circulation dynamics and characterizes water exchange, pond volume, and residence time across the full tidal spectrum at Nuʻupia fishponds. Our results indicate a general west to east gradient in current flow; with higher flushing rates and lower residence times of fishponds in the western ponds of the Nu’upia system compared to the eastern ponds. We further found low flushing rates at several sites causing limited water exchange with Kāne’ohe Bay, as well as within Nu’upia Pond system. Sufficient water circulation plays a fundamental role in maintaining a healthy balance of fishpond flora and fauna and preserve ecosystem health. The results from this study provide a baseline of current physical water circulation dynamics and implications for ecosystem health, as well as inform science-based conservation and management strategies moving forward.

Nutrient estimation in forest ecosystems through satellite images allows us to obtain accurate data, starting with data transformation from forest stands and the existing relationship with the spectral information of the image through modeling. The objective of the study was to quantify and validate the content of C, N, H in aboveground tree biomass in managed stands using spatial modeling and satellite images. This study was conducted during 2017-2018 in managed forest stands in San Juan Lachao, Oaxaca, Mexico. Fifteen 400 m2 experimental sites were selectively established, using a completely randomized experimental design of five silvicultural treatments with three replications. As part of data preprocessing, normality and homogeneity of variances assumptions were checked using the Shapiro-Wilk and Bartlett tests, respectively. From the pixels, data of the average of Normalized Difference Vegetation Index (NDVI) that surrounded the sampling sites were contrasted against the data obtained from forest inventory and the regression models to estimate C, N, H and biomass were generated. Models were validated by NDVI. With the models we estimated 0.95 t ha-1 biomass, which contains between 0.61 and 0.63 of C, 0.44-0.46 of N and 0.24 of H. The models generated had coefficients of determination (R2) of 0.85 to 0.87, which are significant parameters (p ≤ 0.0001). These results confirm that the use of Sentinel satellite images in the estimation of these elements in forest ecosystems based on the relationship between data inventory and the NDVI is highly reliable.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

This research emphasizes a meta-heuristic Modified Ant Lion Optimizer (MALO) optimization approach for simultaneous utilization of DSTATCOM devices and distributed Photovoltaic (PV) sources with network reconfiguration in a radial power distribution scheme. In a radial power distribution network with network reconfiguration majority of the research is based on Constant Power model analysis. However, it is noticed that load models have a substantial impact on the distributed PV sources and the D-STATCOM device's optimal size and position. The effect of the Constant Power (CP) and Polynomial (ZIP) with load growth load models for the simultaneous insertion of distributed PV sources and DSTATCOM devices with network reconfiguration examined in this research work for power system planning. The penetration levels of distributed PV sources considered for the investigation are 25%, 50%, 75%, and 100%. The principal objective of this research is to reduce network total power losses, enhance the voltage magnitude profile at all buses, and reduce the overall operating cost while adhering to equality and inequality constraints. The proposed algorithm verified on 118-node test systems. The investigation is carried out for planning network upgradation to a High Voltage Distribution System(HVDS) on 317 nodes in the rural Bangalore Electricity Supply Company Limited(BESCOM) radial distribution scheme. Simulated results obtained by this method are validated with the BAT algorithm and available techniques in the literature.

Knowledge is not merely the characteristic of certain pieces of information being deemed true and justifiable, but rather a process. Within an axiomatic system, the set of information that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the process of justification (exchange of information), if it consistently justifies a particular piece of information, it elevates it to knowledge. In this paper, we provide a framework for knowledge within an axiomatic model where we define the fundamental elements of communication and grammar. As a result, the structure dictates that knowledge, to be considered as such, must be investigateable by anyone who utilizes it in its entirety, both in form and content. Ultimately, the development of knowledge processing, referred to as \emph{knowmatics}, represents a clear evolution of the computer science that processes information (subset of knowledge).

Residential dust is recognized as a major source of environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs). To characterize the thoracic dust fraction (PM10), a sampling campaign was carried out with an in-situ resuspension chamber in three rooms (kitchen, living room and bedroom) of four Spanish houses. Two samples per room were collected with, at least, a one-week interval. The PM₁₀ samples were analyzed for their carbonaceous content by a thermo-optical technique and, after solvent extraction, for 20 PAHs, 8 phthalate plasticizers (PAEs) and one non-phthalate plasticizer (DEHA) by gas chromatography-mass spectrometry. In general, higher dust loads were observed for parquet flooring compared with tile. The highest dust loads were obtained for rugs. Total carbon accounted for 9.3 to 51%wt of the PM₁₀ mass. Plasticizer mass fractions varied from 5 µg g-1 to 17 mg g^-1 PM₁₀, whereas lower contributions were registered for PAHs (0.98–116 µg g^-1). The plasticizer and PAH daily intakes for children and adults via dust ingestion were estimated to be 3–4 orders of magnitude higher than those via inhalation and dermal contact. Potential carcinogenic and negligible non-carcinogenic risks arising from exposure to PAHs were found.

Responding to the substantial finance gap for achieving Sustainable Development Goal 6.1 and 6.2, the Water and Sanitation sector has mobilized to launch new blended finance vehicles with increasing frequency. The sustainability and scale-up of financial solutions is intended to support increased access to unserved, marginalized populations. However, without addressing foundational issues in the sector, any finance mechanism, whether public, private or blended, will be a short-term, band-aid solution and the sector will continue the cycle of dependency on external assistance. This paper presents the results of a collaborative effort of Water.org, IRC WASH and the World Bank Water Global Practice. Drawing from the latest research on effective public financial management and based on evidence from the countries where these organizations work, the paper demonstrates that sustainable success in mobilising finance at large scale is dependent on a reasonable level of performance across 10 foundational areas. The paper presents evidence on the 10 foundational areas and discusses why other aspects of finance and governance while necessary are not sufficient. Better coordination amongst all development partners and governments, including a collective commitment to and prioritization of working on these foundational issues, is a necessary first step.

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

Polyalcohol liquefaction can be done by acid or basic catalysis producing polyols with different properties. This study compared the mechanical properties of foams produced using polyols from liquefied Cytisus scoparius obtained by acid and basic catalysis and using two different foam catalysts. The differences were monitored using FTIR analysis. Acid-catalyzed liquefaction yielded 95.1 %, with the resultant polyol having an OH index of 1081 mg KOH/g while basic catalysis yielded 82.5 %, with a similar OH index of 1070 mg KOH/g. Generally, compressive strength with dibutyltin dilaurate (DBTDL) ranged from 16 - 31 kPa (acid-liquefied polyol) and 12 -21 kPa (base-liquefied polyol), while with stannous octoate (TIN), it ranged from 17 - 42 kPa (acid) and 29 - 68 kPa (base). Increasing water content generally decreased the compressive modulus and strength of foams. Higher water content led to a higher absorption at 1670 cm-1 in the FTIR spectrum due to the formation of urea. Higher isocyanate indices generally improved compressive strength, but high amounts led to unreacted isocyanate that could be seen by a higher absorption at 2265 cm-1 and 3290 cm-1. DBTL was shown to be the best foam catalyst due to higher trimer conversion seen in the spectra by a higher absorption at 1410 cm-1. Acid and base-derived polyols lead to different polyurethane foams with different FTIR spectra, particularly with a higher absorption at 1670 cm-1 for foams from acid-derived liquefaction.

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).

UV-A (ca. 365 nm wavelength, a.k.a. 'black light') photocatalysis has been investigated to comprehensively mitigate odor and selected air pollutants in the livestock environment. This study was conducted to confirm the performance of UV-A photocatalysis on the swine farm. The objectives of this research were to (1) scale-up of the UV-A photocatalysis treatment, (2) evaluate the mitigation of odorous gases from swine slurry pit, and (3) test different UV sources, (4) evaluate the effect of suspended particulate matter (PM), and (5) conduct preliminary economic analyses. We tested UV-A photocatalysis at a mobile laboratory-scale capable of treating ~0.2 - 0.8 m3·s-1 of barn exhaust air. The targeted gaseous emissions of barn exhaust air were significantly mitigated (p < 0.05) up to 40% reduction of measured odor; 63%, 44%, 32%, 40%, 66%, and 49% reduction of dimethyl disulfide, isobutyric acid, butanoic acid, p-cresol, indole, and skatole, respectively; 40% reduction of H2S; 100% reduction of O3; and 13% reduction of N2O. The PM mitigation effect was not significant. Formaldehyde levels did not change, and a 21% generation of CO2 was observed. The percent reduction of targeted gases decreased as the airborne PM increased. Simultaneous chemical and sensory analysis confirmed that UV-A treatment changed the overall nuisance odor character of swine barn emissions into weaker manure odor with 'toothpaste and 'mint' notes. The smell of benzoic acid generated in UV-A treatment was likely one of the compounds responsible for the less-offensive overall odor character of the UV-treated emissions. Results are needed to inform the design of a farm-scale trial, where the interior barn walls can be treated with the photocatalyst, and foul air will be passively treated as it moves through the barn.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca²⁺ replaces Mg²⁺ in the excitation pathway. Here I revisit the studies on [Ca²⁺] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

Investments in wind and solar power are driven by the aim to maximize the utilization of renewable energy (RE). This results in an increased concentration of wind farms at locations with higher average wind speeds and of solar panel installations at sites with higher average solar insolation. This is unfavourable for energy suppliers and for the overall economy when large power output fluctuations occur. Thus, when evaluating investment options for spatially distributed RE systems, it is necessary to model resource fluctuations and power output correlations between locations. In this paper, we propose a methodology for analyzing the spatial dependence, accurate modeling, and forecasting of wind power systems with special consideration to spatial dispersion of installation sites. We combine vine-copulas with the Kumaraswamy distribution to improve accuracy in forecasting wind power from spatially dispersed wind turbines and to model solar power generated at each location. We then integrate these methods to formulate an optimization model for allocating wind turbines and solar panels spatially, with an end goal of maximizing overall power generation while minimizing the variability in power output. A case study of wind and solar power systems in Central Ontario, Canada is also presented.

Anthropogenic activities have increased the amount of urban wastewater discharged into natural aquatic reservoirs confining in them a high amount of nutrients and organics contaminants. Several studies have reported that an alternative to reduce those contaminants is using consortiums of microalgae and endogenous bacteria. In this research, a genome-scale biochemical reaction network is reconstructed for the co-culture between the microalga Chlorella vulgaris and the bacterium Pesudomonas aeruginosa. Metabolic Pathway Analysis (MPA), is applied to understand the metabolic capabilities of the co-culture and to elucidate the best conditions in removing nutrients such as Phosphorus (inorganic phosphorous and phosphate) and Nitrogen (nitrates and ammonia). Theoretical yields for Phosphorus removal under photoheterotrophic conditions are calculated, determining their values as 0.042 mmol of PO₄/ g DW of C. vulgaris, 19.53 mmol of inorganic Phosphorus /g DW of C. vulgaris and 4.90 mmol of inorganic Phosphorus/ g DW of P. aeruginosa. Similarly, according to the genome-scale biochemical reaction network the theoretical yields for Nitrogen removal are 10.3 mmol of NH₃/g DW of P. aeruginosa and 7.19 mmol of NO₃ /g DW of C. vulgaris. Thus, this research proves the metabolic capacity of these microorganisms in removing nutrients and their theoretical yields are calculated.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of (two or more) random variables (the sources) has about another variable (the target) into three types of information: unique, redundant, and synergistic. Classical information theory alone does not provide a unique way to decompose information in this manner and additional assumptions have to be made. One often overlooked way to do this decomposition is using a so-called measure of union information – which quantifies the information that is present in at least one of the sources – from which a synergy measure stems. In this paper, we introduce a new measure of union information based on adopting a communication channel perspective, compare it with existing measures, and study some of its properties. We also include a comprehensive critical review of characterizations of union information and synergy measures that have been proposed in the literature.

Disposing pollutants into water sources has posed risks to human health and the environment, and biosorption has emerged as an eco-friendly, cost-effective, and green alternative for wastewater treatment. This work shows banana peel powder (BPP) biosorbents for efficient sorption of methylene blue (MB), atrazine, and glyphosate pollutants. The biosorbent highlights several surface chemical functional groups and morphology containing agglomerated microsized particles and microporous structures. BPP showed 66% elimination of MB in 60 min, with an adsorption capacity (qe) of ~33 mg g-1, where a combination of film diffusion and chemisorption governed the sorption process. Besides, the biosorbent removed 91% and 97% of atrazine and glyphosate pesticides after 120 min, with qe of 3.26 and 3.02 mg g-1, respectively. The glyphosate and atrazine uptake best followed the Elovich and pseudo-first-order kinetic, respectively, revealing different sorption mechanisms. Our results suggest that BPP are low-cost biomaterials for green and environmentally friendly wastewater treatment.

Globally, noncommunicable diseases (NCDs) were responsible for 41 million deaths in 2016, with the majority of these occurring in low and middle-income countries. These diseases were on the rise as a result of unhealthy, low-quality, and unbalanced diets, which resulted in overweight and obesity. The National School Nutrition Programme (NSNP) was created to regulate the foods sold to schoolchildren. To ascertain school management teams' perspectives on the relationship between the NSNP and the development of lifestyle diseases. A phenomenological qualitative study using Focus Group Discussions among 16 purposively selected members of the School Management Teams were conducted in Mt Frere, Eastern Cape in 2016. The narrative data was analyzed using Tesch's eight-phase thematic analysis approach. The data analysis revealed two themes (NSNP and the vendor system) and six sub-themes. The NSNP was viewed as making a significant contribution to children's food security, thereby improving academic output. However, reengineering of the NSNP was need through improved budgeting and inclusion of breakfast in the menu to control NCDs risk factors. The current implementation of the vendor system did not support reduction of NCDs risk factors. Improved implementation of the guide to vendor system is needed.

In this paper, we introduce the application of Type-I fuzzy inference systems (FIS) as an alternative to improve the prioritization in the FMECA analysis applied in cyber-power grids. Classical FMECA assesses the risk level through the Risk Priority Number (RPN). The multiplication between three integer numbers computes this, called risk factors, representing the severity, occurrence, and detectability of each failure mode and are defined by a team of experts. The RPN does not consider any relative importance between the risk factors and may not necessarily represent the real risk perception of the FMECA team members, usually expressed by natural language; this is the main FMECA shortcoming criticized in the literature. Our approach considers fuzzy variables defined by FMECA experts to represent the uncertainty associated with the human language and a rule base consisting of 125 fuzzy rules to represent the risk perception of the experts. To test our approach, we select a cyber-power grid previously analyzed by the authors using the classical FMECA. The results reveal our proposed fuzzy approach as promissory to represent the uncertainty associated with expert knowledge and to perform an accurate prioritization of failure modes in the context of electrical power systems.

Microalgae are highly attractive to various industrial sectors and can serve as indicators of aquatic environmental health. An essential step for cultivating microalgae is assessing the cell density, which is traditionally performed through viable cell counting by optical microscopy (OM). However, this method has some limitations, such as the time involved in the process of counting, and the need for specialized training of laboratory personnel. Spectrophotometry is an affordable alternative, especially when applied to culture growth and toxicological tests. We chose the wavelength of 680 nm to detect the optical density (OD) of the green freshwater microalga Desmodesmus subspicatus and green the marine microalga Tetraselmis sp. The correlation between the number of cells and OD was suitable for both microalgae and accuracy was comparable to traditional OM counting. In toxicological tests, the OD technique allowed the monitoring of microalgal growth in the presence of the chemicals potassium dichromate, potassium chloride and sodium dodecyl sulfate (SDS), with results very close to those reported in the scientific literature. This study sheds light on this well-known technique, which is an important contribution since few articles have explored its potentialities and fragilities, showing the successful application to monitoring green microalgal cultures and toxicological assays.

An 8-months old male American Staffordshire terrier was referred for a no weightbearing lameness of the right pelvic limb, hyperthermia, lethargy and inappetence caused by hematogenous osteomyelitis. Orthopedic, radiographic and tomographic examinations revealed a bone sequestrum of 4 x 1.4 cm and active periosteal reaction of the caudo-lateral cortical in the metaphysis and the distal third of the right femoral diaphysis, medullary osteolysis and interruption of the cranio-medial cortical profile, with involvement of the femoral trochlea leading to a secondary medial patella luxation. Once skeletally mature, after 4 months from surgical debridement and aggressive antibiotic therapy against Klebsiella oxytoca revealed by bacteriological exam, the patient underwent prosthetic surgery for the application of a custom-made patellar groove replacement (PGR) to fill the bone defect and restore the femoral trochlea surface. Despite the serious injury that afflicted the right pelvic limb, the surgery had satisfactory outcomes until the last 18-months postoperative follow up.

This paper proposes a method based on genetic algorithm (GA) for the security-constrained optimal dispatch of integrated natural gas and electricity networks, considering operating scenarios in both energy systems. The mathematical formulation of the optimization problem consists of a multi-objective function which aims to minimize both cost of thermal generation (diesel and natural gas) as well as the production and transportation of natural gas. The joint gas-electricity system is modeled by two separate groups of nonlinear equation, which are solved by the combination of Newton's method with the GA. The applicability of the proposed method is tested in the Belgian gas network integrated with the IEEE 14-bus test system and a 15-node natural gas network integrated with the IEEE 118-bus test system. The results demonstrate that the proposed method provides efficient and secure solutions for different operating scenarios in both energy systems.

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4 butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. The PU made with polycarbonate diol polyol (YCD) was the only showing intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis and dynamic mechanical thermal analysis was carried out. It was concluded that the self-healing at 20 °C of YCD was due to non-covalent dynamic exchange interactions among the carbonate groups of the soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

This study addresses the problem of accurately predicting azimuth and elevation angles of signals impinging on an antenna array employing Machine Learning (ML). Using the information obtained at a receiving system when a transmitter’s signal hits it, a Decision Tree (DT) model is trained to estimate azimuth and elevation angles simultaneously. Simulation results demonstrate the robustness of the proposed DT-based method, showcasing its ability to predict the Direction of Arrival (DOA) in diverse conditions beyond the ones present in the training dataset, i.e., the results display the model’s generalization capability. Additionally, the comparative analysis reveals that DT-based DOA estimation outperforms the state-of-the-art MUltiple SIgnal Classification (MUSIC) algorithm, establishing DTs as competitive alternatives for DOA estimation in signal reception systems.

Keywords: Wood residuals; Forest biomass; Wood composite; Wood floor; Life Cycle Assessment.

Fungal keratitis (FK) is an invasive infection of the cornea primarily associated with Aspergillus and Fusarium species. FK is treated empirically with a limited selection of topical antifungals with varying levels of success. Though clinical infections are typically characterized by a dense network of mature mycelium, traditional models used to test antifungal susceptibility of FK isolates exclusively evaluate susceptibility in fungal cultures derived from asexual spores known as conidia. The purpose of this study was to characterize differences in fungal response when topical antifungal treatment is initiated at progressive phases of fungal development. We compared efficacy of voriconazole and luliconazole against in vitro cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. A porcine cadaver corneal model was used to compare antifungal efficacy of voriconazole and luliconazole in ex vivo tissue cultures of A. flavus and F. keratoplasticum at 0, 24, and 48 h of fungal development. Our results demonstrate phase-dependent susceptibility of both A. flavus and F. keratoplasticum to both azoles in vitro as well as ex vivo. We conclude that traditional antifungal susceptibility testing with conidial suspensions does not correlate with fungal susceptibility in cultures of a more advanced developmental phase. A revised method of antifungal susceptibility testing that evaluates hyphal susceptibility may better predict fungal response in the clinical setting where treatment is often delayed until days after the initial insult.

Mangoes have a unique nutrient profile (carotenoids, polyphenols, sugars, vitamins) that we hypothesized would mitigate post-exercise inflammation. This study examined the effects of mango ingestion in moderating exercise-induced inflammation in a randomized crossover trial with 22 cyclists. In random order with trials separated by a 2-week washout period, the cyclists ingested 330 g/day mangoes with 0.5 liters water or 0.5 liters water alone for 2 weeks, followed by a 2.25-h cycling bout challenge. Blood and urine samples were collected pre- and post-2 weeks supplementation, with additional blood samples collected immediately post-exercise, and then 1.5-h, 3-h, and 24-h post-exercise. Urine samples were analyzed for targeted mango-related metabolites. The blood samples were analyzed for 67 oxylipins that are upstream regulators of inflammation and other physiological processes. After 2-weeks mango ingestion, three targeted urine mango-related phenolic metabolites were significantly elevated compared to water alone (interaction effects, p≤0.003). Significant post-exercise increases were measured for 49 oxylipins, but various subgroup analyses showed no differences in the pattern of change between trials (all interaction effects, p&gt;0.150). The 2.25-h cycling bouts induced significant inflammation but no countermeasure effect was found after 2-weeks mango ingestion despite the elevation of mango gut-derived phenolic metabolites.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (&gt; 90%); the compounds were able to inhibit HCV replication without significant side effects, even in pediatric populations. The management of coinfected patients HBV-HCV and HCV-HIV has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research focuses on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection to different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

Concept Knowledge (C-K) theory has been used in engineering and science-based research for more than a decade. Design of an Information Technology (IT) artefact is mostly pragmatic in nature. Design Science Research (DSR) methodology applied and studied in many Information Systems (IS) research. Many sub design decisions involved through the design of an IT artefact from a concept (idea) to a working prototype. A DSR artefact is based on a combination of decisions made during several sub-design stages. Artefacts are built based on the selection of elements in each sub-design space. Recording the design decisions on each sub-design space would be beneficial for future researchers. By knowing the design decisions on each sub-design space, researchers would be able to try different combinations of the design. C-K theory provides the ability to capture the design processes’ several sub-design spaces. In this paper, we discuss the DSR research methodology by looking at the stages proposed in the literature, and the application of C-K theory in an IT-based DSR. This paper also proposed a C-K theory-based protocol called Concept Tree for tracking and reporting artefact design steps. The application of C-K theory in DSR is exhibited using the implementation of the Concept Tree for a prototype design IT artefact.