We report the use of Einstein rings to reveal the quantized and dynamical states of space-time in a region of impressed gravitational field as predicted by the Nexus Paradigm of quantum gravity. This in turn reveals the orbital speeds of objects found therein and the radius of curvature of the quantized space-time. Similarities between the Nexus graviton and the singular isothermal sphere (SIS) in the Cold Dark Matter (CDM) paradigm are highlighted. However unlike the singular isothermal sphere, the Nexus graviton does not contain singularities or divergent integrals. This solves the core cusp problem. In this work, data from a sample of fifteen Einstein rings published on the Cfa-Arizona Space Telescope Lens Survey (CASTLES) website is used to probe the quantized properties of space-time.

Cognitive Computing has become somewhat of a rallying call in the technology world, with the promise of new smart services offered by industry giants like IBM and Microsoft. The recent technological advances in Artificial Intelligence (AI) have thrown into the public sphere some old questions about the relationship between machine computation and human intelligence. Much of the industry and media hype suggests that many traditional challenges have been overcome. On the contrary, our simple examples from language processing demonstrate that present day Cognitive Computing still struggles with fundamental, long-standing problems in AI. An alternative interpretation of cognitive computing is presented, following Licklider's lead in adopting man-computer symbiosis as a metaphor for designing software systems that enhance human cognitive performance. A survey of existing proposals on this view suggests a distinction between weak and strong versions of symbiosis. We propose a Strong Cognitive Symbiosis which dictates an interdependence rather than simply cooperation between human and machine functioning, and introduce new software systems which were designed for cognitive symbiosis. We conclude that strong symbiosis presents a viable new perspective for the design of cognitive computing systems.

BACE1 is involved in the production of beta-amyloid peptides, and inhibiting its activity is a potential therapeutic strategy for managing Alzheimer's disease, as excessive beta-amyloid accumulation is a characteristic feature of the disease.Computational results suggest that hypericin has the potential to act as an inhibitor of BACE1. The Molecular Docking results indicate a high binding affinity between hypericin and BACE1, with a notable binding energy score of -10.3 kcal/mol. Additionally, the formation of various chemical bonds, including hydrogen bonds and hydrophobic bonds, further supports the idea that hypericin may effectively interact with the active site of BACE1. It's important to note that while the in silico Molecular Docking results are promising, further in vitro and in vivo studies would be necessary to validate and better understand the inhibitory potential of hypericin against BACE1. Additionally, the practical application of hypericin as a BACE1 inhibitor in a therapeutic context would require careful consideration of factors such as bioavailability, safety, and efficacy.

Enhancing traffic safety is one of the fundamental objectives of Intelligent Transport Systems (ITS), and it aligns closely with the principles of sustainable transport. Due to specific differences in infrastructure, vehicles, and users’ behaviour, places where different modes of traffic intersect are recognized as critical points of the traffic system, making them crucial aspects of Sustainable Urban Mobility Plans (SUMPs) implementation. The SUMPs aim to create urban mobility that is not only environmentally friendly and efficient but also safe for all users. The continuous development and widespread adoption of innovative ITS technologies have paved the way for a system that could provide drivers with real-time information about both immediate and potential dangers at these critical points. This paper provides an overview of previous research in the field, investigating the impact of information systems on drivers’ behaviour, various detection and communication solutions that can be effectively integrated into such a system, as well as a brief overview of models and solutions that have been developed to warn drivers in a similar context. The reviewed literature offered valuable insights on which a novel driver information system architecture framework is proposed. This framework can contribute to the ongoing safety improvement in multimodal transport networks within the context of sustainable transport.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

The importance of a properly regulated immune response has been explored through various research-oriented methods. It has proved that having an effective and well-regulated immune response helps prevent many minors and serious diseases. Any kind of dysregulation in the working of the immune system may lead to severe consequences. An autoimmune disorder is one such consequence in which the component of the immune system starts targeting self-cells of the body, treating them as self-antigen producing autoantibodies and immune complexes resulting from the failure of immune responses both at a central and peripheral level. Currently, many autoimmune disorders are prevailing across the world, and new diseases need attention.In this review, we have written about the functions of T cell, LncRNAs and also some interactions between the LncRNAs and miRNAs in the pathogenesis of Multiple sclerosis (MS), Systemic lupus erythematosus (SLE), Type 1 diabetes (T1D), Rheumatoid arthritis (RA). To find the functions of these autoimmune disorders we have done intensive literature search during this we also found that GAS5 and MALAT are common in MS, SLE, T1D, RA. And finally, we have also mentioned the therapeutic drugs which neutralizes the different cluster of differentiation (CDs) and also suppresses the T cell differentiation in MS, SLE and RA. For T1D therapeutic strategies and various types of insulin are mentioned.

New setting is introduced to study the alliances. Alliances are about a set of vertices which are applied into the setting of neutrosophic graphs. Neighborhood has the key role to define these notions. Also, neighborhood is defined based on the edges, strong edges and some edges which are coming from connectedness. These three types of edges get a framework as neighborhood and after that, too close vertices have key role to define offensive alliance, defensive alliance, t-offensive alliance, and t-defensive alliance based on three types of edges, common edges, strong edges and some edges which are coming from connectedness. The structure of set is studied and general results are obtained. Also, some classes of neutrosophic graphs containing complete, empty, path, cycle, bipartite, t-partite, star and wheel are investigated in the terms of set, minimal set, number, and neutrosophic number. In this study, there’s an open way to extend these results into the family of these classes of neutrosophic graphs. The family of neutrosophic graphs aren’t study but it seems that analogous results are determined. There’s a question. How can be related to each other, two sets partitioning the vertex set of a graph? The ideas of neighborhood and neighbors based on different edges illustrate open way to get results. A set is alliance when two sets partitioning vertex set have uniform structure. All members of set have different amount of neighbors in the set and out of set. It leads us to the notion of offensive and defensive. New ideas, offensive alliance, defensive alliance, t-offensive alliance, t-defensive alliance, strong offensive alliance, strong defensive alliance, strong t-offensive alliance, strong t-defensive alliance, connected offensive alliance, connected defensive alliance, connected t-offensive alliance, and connected t-defensive alliance are introduced. Two numbers concerning cardinality and neutrosophic cardinality of alliances are introduced. A set is alliance when its complement make a relation in the terms of neighborhood. Different edges make different neighborhoods. Three types of edges are applied to define three styles of neighborhoods. General edges, strong edges and connected edges are used where connected edges are the edges arising from connectedness amid two endpoints of the edges. These notions are applied into neutrosophic graphs as individuals and family of them. Independent set as an alliance is a special set which has no neighbor inside and it implies some drawbacks for this notions. Finding special sets which are well-known, is an open way to purse this study. Special set which its members have only one neighbor inside, characterize the connected components where the cardinality of its complement is the number of connected components. Some problems are proposed to pursue this study. Basic familiarities with graph theory and neutrosophic graph theory are proposed for this article.

In this short communication, we conducted first-principles calculations to explore the stability of boron monochalcogenides (BX, X=S, Se or Te), as a new class of two-dimensional (2D) materials. We predicted BX monolayers with two different atomic stacking sequences of ABBA and ABBC, referred in this work to 2H and 1T, respectively. Analysis of phonon dispersions confirm the dynamical stability of BX nanosheets with the both 2H and 1T atomic lattices. Ab-initio molecular dynamics simulations reveal the outstanding thermal stability of all predicted monolayers at high temperatures over 1500 K. BX structures were found to exhibit high elastic modulus and tensile strengths. It was found that BS and BTe nanosheets can show high stretchability, comparable to that of the graphene. It was found that all predicted monolayers exhibit semiconducting electronic character, in which 2H structures present lower band-gaps as compared with 1T lattices. The band-gap values were found to decrease from BS to BTe. According to the HSE06 results, 1T-BS and 2H-BTe show respectively, the maximum (4.0 eV) and minimum (2.06 eV) electronic band-gaps. This investigation introduces boron monochalcogenides as a novel class of 2D semiconductors with remarkable thermal, dynamical and mechanical stability.

Since 2019, the SARS-CoV-2 virus has caused a global pandemic, resulting in widespread infections and ongoing mutations. Analysing these mutations is essential for predicting future impacts. Unlike influenza mutations, SARS-CoV-2 mutations displayed distinct selective patterns that were concentrated in the spike protein and small ORFs. In contrast to the gradual accumulation seen in influenza mutations, SARS-CoV-2 mutations lead to the abrupt emergence of new variants and subsequent outbreaks. This phenomenon may be attributed to their targeted cellular substances; unlike the influenza virus, which has mutated to evade acquired immunity, SARS-CoV-2 appeared to mutate to target individuals who have not been previously infected. The Omicron variant, which emerged in late 2021, demonstrates significant mutations that set it apart from previous variants. The rapid mutation rate of SARS-CoV-2 has now reached a level comparable to 30 years of influenza variation. The most recent variant, JN.1, exhibits a discernible trajectory of change distinct from previous Omicron variants.

Molecular docking, a computational method predicting how molecules bind to target proteins, is employed in this study to explore Polydatin's interactions with Ras-related protein Rab (Rab) proteins using the Mcule Database. This database validates the docking results and offers insights into the pharmacological properties of Polydatin. Notably, specific Rab proteins like Rab-5A, HRas, and Rab-18 exhibit robust interactions with Polydatin, indicated by favorable binding energies.These findings illuminate the potential roles of Polydatin in therapeutic and biological contexts, emphasizing its interaction with Rab proteins. The Mcule Database enhances the credibility of the study, providing additional perspectives on Polydatin's applications. The observed interactions, particularly with key proteins like HRas, present a promising avenue for modulating cellular signaling pathways. This modulation holds therapeutic potential, potentially addressing conditions associated with pathway overactivity, including specific cancer types.

The assessment of Histone deacetylases in conjunction with Curcumin, conducted through the Mcule Database employing the Autodock Vina algorithm, involves an examination of molecular interactions. This analysis includes the calculation of binding energies, revealing the strength and stability of the interactions between Curcumin and various Histone deacetylase targets. The comparison encompasses diverse aspects such as binding energies, specific binding sites, interactions across different targets, structural details, and potential implications for biological activity. The results imply that Curcumin shows heightened affinity for Histone deacetylase 4 in comparison to other investigated histone deacetylases.

The relationship between perception of anxiety and quality of life in caregivers of children with autism was verified. To verify quality of life, the Short Form Healthy Survey Item was used; perception of anxiety was assessed using the Beck Anxiety Inventory. 80 caregivers of children with autism participated, with 68.7% of caregivers being mothers. Of the total number of caregivers, 68.8% had a severe level of anxiety. Regarding quality of life, they demonstrated greater impairment in Limitation due to physical aspects, Limitation due to emotional aspects, Vitality and Pain. Caregivers with severe anxiety levels had worse quality of life in the domains of pain (p = 0.012), social aspects (p =< 0.001), limitation due to emotional aspects (p = 0.001) and mental health (p =< 0.001). However, in the functional capacity domain, caregivers with a moderate level of anxiety had a better physical capacity score (p = 0.001). There was a negative correlation between the general anxiety score and the general physical (p = 0.029) and general emotional component of quality of life (p =< 0.001). It was found that caregivers of children with ASD present losses related to psychological factors, quality of life and the lack of social support.

We suggest a new solution to the strong CP problem. The solution is based on the proper use of the boundary conditions for the QCD generating functional integral. It obeys the principle of renormalizability of Quantum Field Theory and does not involve new particles like axions.

Abstract In order to reduce the failure accidents of conventional packers, a kind of sealing structure of retrievable packers is designed, which can provide reference for optimizing the sealing performance and pressure capacity of packers. And theoretical calculation and experimental research on its sealing performance and pressure capacity are carries out through the finite element analysis on the contact with large deformation based on Abaqus and experimental. The results show that when the rubber cylinder of retrievable packers in the sealing process, the upper packer is subjected to greater stress and mainly plays a sealing role. In order to improve the sealing performance of packer, the height of upper and lower packer should be preferentially selected about 60 mm, the height of middle rubber cylinders should be about 50 mm, and the thickness of packer should be about 21 mm. The newly designed rubber cylinders can meet 150 ℃. Sealing and pressure-bearing function under the condition of 10000 Psi. The rubber cylinder of newly designed can satisfy the function of sealing and pressure-bearing under 140 ℃ and 10000 Psi. The whole experiment shows that the capacity of bearing pressure and sealing is stable, which can better meet the requirements of field use.

Now-a-days, the thrust area of materials’ research is to develop multifunctional materials, which have multiple properties in a single functional material. We are interested to develop multifunctional polysilanes having special functional properties such as optical activity and photoluminescence (PL) properties. In this investigation, poly(methyl phenyl silane) (PMPS) was integrated with a chiral unit and a photoactive unit by in situ photopolymerization of (R)-N-(1-phenyl ethyl) methacrylamide (R-NPEMAM) and disperse red 1 methacrylate (DR1MA) monomer in the presence of PMPS. PMPS acted as a macrophotoinitiator and by UV exposure it produced macroradicals which initiated polymerization of chiral and photoactive monomers. Thus a block copolymer of PMPS-b-(R-NPEMAM-ran-DR1MA) was synthesized.The synthesized multifunctional organic inorganic hybrid polymer samples were characterized by FTIR and NMR spectroscopy. The molecular weights of the samples were measured by GPC analysis. The optical, chiroptical and photoluminescence properties were studied. The narrow band at about 1638 cm^-1 is due to C=O stretching vibration of -CONH- of the chiral unit. A wide absorption peaks at 3444 cm^-1 is the characteristic of NH trans stretching vibration of secondary amide group. The asymmetric stretching of NO₂ group appeared at 1481 cm^-1 and the characteristic peak at 1427 cm^-1 was observed due to azo (-N=N-) group stretching of DR1MA unit. The Si-Si band of PMPS appeared at about 462 cm^-1 in FTIR spectra. The optical absorbance observed at 272 nm is due to π-π* transition of aromatic ring and at 330 nm corresponds to σ-σ* transition of Si-Si bond. The other electronic absorption observed in the visible region at 475 nm corresponds to the combined contribution of n-π* and π-π* transition of DR1MA unit. The photoluminescence properties of such polymers were studied for the variation of concentration of the polymer solution and variation with excitation energy such as 275 nm, 325 nm and 475 nm in THF solvent. Such synthesized multifunctional photoactive organic-inorganic polymers having unusual optical, chiroptical and photoluminescence property may find novel optoelectronic (friend foe identification and secretive code identification) applications.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

This study investigates the efficiency of BEAM (Biologically Enhanced Agriculture Management) inoculant, derived from compost produced under Dr. David Johnson-Su's composting technique, in promoting plant growth. A winter mix of pasture comprising Oats, Tetila, unhulled Couch, and Haifa was used as the test crop. Seeds were soaked in BEAM inoculant, water (control), and a competitor product 'Companion.' Results revealed significant enhancements in germination rates, foliage growth, and root development in the BEAM-treated group compared to controls. Further research aims to identify the microbial components of BEAM and explore its potential as a suppressant for fusarium species in orchards.

Green economy has emerged as a significant pillar of sustainable development in the current global context, and the unpredictability of economic policy has progressively garnered the interest of businesses and government officials as one of the obstacles they must confront. This paper examines how uncertainty in the green economy impacts the green economy's efficacy. The research concentrates on how changes in a particular region can result in geospatial diffusion (spatial spillover), which is a form of spatial spillover wherein the uncertainty of the green economy can impact its efficacy. This paper examines the policy formulation and current state of the green economy across various regions, as well as the diffusion of economic policy uncertainty across geographical areas and the subsequent impact on the green economy's status quo. There is a negative correlation between economic policy uncertainty and green economy efficacy, according to research. There is a spatial spillover effect between economic policy uncertainty and the efficacy of the green economy. Regional variations exist in the impact of economic policy uncertainty on the efficacy of the green economy. The findings indicate that the implementation of AI has a more substantial beneficial effect on carbon emissions. An increase in carbon dioxide emissions poses a growing challenge for the industrial sector in its pursuit of carbon neutrality.

With reference to our 4G model of final unification, strong coupling constant and strong interaction charge of magnitude $e_s\cong 2.95e$, it is possible to understand the nuclear stability range with a simple power law of the form, $A_s\cong \left(Z+2.95\right)^{1.2\pm0.015}$

This study investigates the effectiveness of a range of timber-based solutions for seismic and energy retrofitting of existing masonry buildings. These solutions are designed not only to prevent structural collapse during earthquakes but also to create integrated interventions that enhance thermo-physical performance and reduce emissions in existing buildings. Various case scenarios were considered and both mechanical and energetic behavior post-intervention were evaluated. Timber-engineered products serve as foundational components for the retrofit approach, encompassing one-dimensional vertical elements (strong-backs) and various types of panels (cross-laminated timber panels, laminated veneer lumber panels, and oriented strand board panels). The analyzed retrofit techniques share a common principle, involving the attachment of these timber-based elements to the building's wall surfaces through mechanical point-to-point connections. The proposed solutions integrate strong-backs and timber panels with membranes and insulation layers, yielding cohesive and highly effective interventions. Finite element modeling was employed to analyze the mechanical and thermal responses of the retrofitted walls. A comprehensive comparative analysis of various techniques was conducted to determine the most effective solution for each specific scenario.

In recent years the yield of fruits and vegetables have been decreasing in Colombia, threatening national food security. Analysis of crop production data may lead to identifying cropping systems that have shown better adaptability to changes in climatic and non-climatic factors associated with agricultural production. The open database AGRONET keeps data of the agricultural activities conducted in Colombia, allowing to find the information organized by crops, regions and years; each row of the database registers farm information in Colombia. Aiming to identify resilient crops systems, agricultural data of fruits and vegetables were analyzed. First, trends in crop production were studied by year and locations, detecting the regions and crops with highest yields in the period from 2006 until 2020. Then, mixed linear regression and principal components analysis were applied to elucidate the relation between non-climatic factors and crop yield. In Colombia, vegetable production was more efficient than fruits, observing yields of 10.23 and 13.33 t ha^-1, respectively. On the other hand, the Colombian central region showed high yields for vegetables, while for fruits this was exhibited in northern and eastern locations. In the present study, yield variation responded to changes in the location of crop systems, while years had no effect on vegetable production. Furthermore, the price of the agricultural product and the cost of fertilizers were associated with the yield of the analyzed crops systems. In Colombia, carrot, cabbage, tomato papaya and pineapple are resilient crops whose yield increases especially by the regions where they are cultivated.

POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).

-- This paper examines the critical role of business analysis in shaping small and medium-sized enterprises’ strategies for better odds of success in the ever-evolving Nigerian economy and within the competitive markets. Business analysis ability, as a knowledge-supporting factor, focuses on understanding consumer needs, planning, data collection, analysis, and presentation to decision-makers. The process begins with strategic planning and meticulous data collection, facilitating a deep understanding of the business and consumer behavior and process potential. Analytical skills unearth the true potential of organizational processes, particularly in product creation, resulting in distinctive and highly valued products. Such products align with theories like the resource-based view or VRIO theory, driving increased sales volume—a key performance metric. By leveraging analytical capabilities, Nigerian SMEs can navigate complex market dynamics, create value-driven businesses, and differentiate themselves from competitors thus increasing the odds of success. This paper sets the stage for further research into the impact of business analysis on organizational success within dynamic market landscapes.

Current-voltage characteristics curves of NFinFET are presented and are fitted with the modi-fied current-voltage (I-V) formulas, where the modified term in the triode region is demon-strated to be indispensable. In the as-known I-V formula, important parameters need determin-ing to make both the measured data and the fitting data as close as possible. Those parameters include kN (associated with the sizes of the transistor and mobility), (associated with Early Voltage), and Vth (the threshold voltage). The differences between the measured data and the fit-ting data vary as the applied source-drain bias, proving that the mobility of the carriers is not consistently constant. On the other hand, a modified formula, called kink effect factor, is nega-tively or positively added simulating solitary heat waves, which disturb the propagation of car-riers and thus influence the Source-Drain current (IDS). The new statistical standard deviations () are then found to be effectively suppressed as the kink effect is taken into account.

This article evaluates Europe's building sector's circular economy (CE). This industry is respon-sible for 42% of energy consumption, more than 50% of extracted materials, 30% of Europe's wa-ter and waste generation, and 35% of greenhouse gas (GHG) emissions. This study focuses on peer-reviewed articles from Scopus and Web of Science databases. Of the first 1750 publications, 2.9% were eligible for a full-text reading and analysis. Most of the trending studies, 92%, pro-mote the circular economy concept through construction materials rather than analyzing the im-pact of the construction sector on the environment and finding solutions for better implementa-tion, and 41% promote recycling and reuse as the only options. New Design solutions are in 12% of the studies, six-fold more than Law and Legislation, only 2%. Finding an optimal combination of assessing the life cycle of buildings and components and searching for different ways of man-aging the Construction and Demolition Waste at end-of-life is between 33% and 39%. Ultimately, one evaluated CE proposed frameworks for the building industry based on 10R principles varia-tions. One presents an alternative framework for a circular strategy for the building industry that focuses on Upcycling, replacing the Recover principle.

Somerateofmutationisinevitable,eveningenesthatthemselvesdeterminethemutation rate. Because mutation in these genes can alter the mutation rate, variation in the mutation rate is inevitable. This simple line of reasoning is corroborated by a handful of empirical studies that found mutation-rate variation in natural and laboratory populations. The evolutionary consequences of mutation-rate variation in natural populations can be many and can be difficult to predict, as selection on such variation can be both direct and indirect. For example, lineages with increased mutation rate will have increased adaptability in the long term but decreased overall fitness in the short term because most fitness mutations are immediately deleterious. In spite of its great relevance to basic and applied science, the rate of mutation to mutator phenotype continues to be essentially unknown. The reasons for this gap in our knowledge are largely methodological; in general, a mutator phenotype cannot be observed directly but must instead be inferred from numbers of some neutral “marker” mutation that can be observed directly: different mutation-rate variants will produce this marker mutation at different rates. Here, we derive the expected distribution of numbers of the marker mutants observed, accounting for the fact that some of the mutants will have been produced by a mutator phenotype that itself arose by mutation during the growth of the culture. This development makes possible a novel experimental protocol for estimating the rate of mutation to mutator phenotype. Simulated experiments using biologically-reasonable parameters that employ this protocol show that such experiments in the lab can give us fairly accurate estimates of the rate of mutation to mutator phenotype. Although our ability to estimate mutation-to-mutator rates from simulated experiments is promising, we view this study as a proof-of-concept study and only a first step towards practical empirical estimation.

Left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy (HCM) commonly occur as separate disorders with distinct clinical and pathoanatomical features. However, these cardiomyopathies may have a similar genetic origin with mutations encoding sarcomeric proteins. The described case demonstrates an example, in which phenotypic expression of both diseases occurs in the same patient.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

ABSTRACT Underwater mines may destroy friendly submarines and marine habitats, compromising nonmilitary security. Finding credible information is vital to avoiding scams and spotting hazards. This article employs Supervised Machine literacy models to appropriately categorize subsea items like mines or gems based on Sonar sounds. Python constructs three double classifier models using Gorman and Sejnowski (1988) training data. Through the extraction of key aspects from the Sonar signals, such as spectral components and intensity, the models are able to match newly obtained data with the gemstone order or mine. Delicacy decreases the chance of misidentifications in nonmilitary activities. Machine literacy offers full validation that accommodates real-world Sonar data noise and unpredictability. Based on test results, the highest performing algorithm will deliver the required ratio of accuracy to perceptivity for the bracket task. Central keywords: vaticination model, bracket algorithms, supervised machine literacy, SONAR, and aquatic mining emphasize particular foundations. Improved sophistication in spotting undersea Mines let nonmilitary defence systems respond to proven threats only, preventing friendly submarines or sea life from unnecessary damage owing to false duplicity. This work is a promising start to real-world mine detection devices. Further developments may incorporate greater training data sets, real-time testing on subsea platforms equipped with integrated sonar, and optimization for the discovery of new mine-types. Overall, machine learning and Sonar vision decrease signal fluctuation and noise, making it easier to determine accurate boundaries for non-military applications and environmental protection. The recommended automated discovery technique must balance computational efficiency, generalizability, and delicacy. Prior a real crime, new quality control and verification procedures could boost trust even further.

Plants belonging to the genus Irvingia are widespread across the African and Southeast Asian regions of the world. Irvingia gabonensis, Irvingia malayana, and Irvingia grandifolia are among the commonly used species in ethnomedicine, especially in Africa. Fever, scabies, toothache, inflammation, and liver and gastrointestinal disorders are among the pathological conditions that are reverted by Irvingia plants upon traditional preparations. Modern pharmacological investigations have substantiated the ethnomedicinal uses of Irvingia spp. Reports on the phytochemical analysis of Irvingia plants have revealed the presence of a number of secondary metabolites, such as flavonoids, phenolic compounds, tannins, saponins and alkaloids. Based on the foregoing, the present study provides a comprehensive evaluation of reports on the ethnomedicinal use, phytochemistry, pharmacology, and toxicity of plants from the genus Irvingia. Relevant information on Irvingia plants was mostly obtained from major scientific databases from their inception until July 2023. As a result, more than forty compounds have been identified in Irvingia spp. proving the abundance of secondary metabolites in these plants. Reports have pointed out modern pharmacological activities, such as antiprotozoal, antimicrobial, antioxidant, antidiabetic, anti-inflammatory, and hepatoprotective activities. The present study provides more insights for the successful utilization of Irvingia plants and may guide further research on their therapeutic potential in the treatment of various diseases.

Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lip-idomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

(1) Background: Truing to find a fast and representative method for the approximate calculation of the culture density and the cell content of useful pigments, the examination of the absorption spectra of cultures of the dinoflagellate Amphidinium carterae, the haptophyte Isochrysis galbana, the chlorophyte Nephroselmis sp. and the filamentous cyanobacterium Anabaena sp. were chosen, as representative species of different taxa. (2) Methods: The experimental cultures were made in small volumes with the discontinuous method, under specific conditions each one and during the culture the absorption spectra, the density of the culture and the concentration in the pigments chlorophyll, total carotenoids and phycocyanin was recorded. (3) Results: The algal density can be quite precisely predicted as the regression equation of the correlation of the OD value of 750 nm drawn from each absorption spectrum and the measured algal biomass was very strong. The same applies also for the relevant correlations between OD 750 nm and the recorded pigments. (4) Conclusions: Absorption spectra of microalgal cultures can be an easy, low cost and non-invasive method to get the necessary information for predicting the right time to collect an ideal combination of maximum biomass and useful pigments, provided that the interpretation of the spectra is done considering that they are usefully applicable for that purpose in a case sensitive manner in terms of species and prevailing conditions.

Microsoft has implemented several measures to defend against macro viruses, including the use of Anti-malware Scan Interface (AMSI) and automatic macro blocking. Nevertheless, evidence shows that threat actors have found ways to bypass these mechanisms. As a result, phishing emails continue to apply malicious macros as their essential attack vector. In this paper, we analyze 77 obfuscation features from the attacker’s point of view and extract 46 suspicious keywords in macro. We first combine the above two types of features to train machine learning models on a public dataset. Then, we carry out the same experiment on self-constructed dataset, a collection of newly discovered samples, to see if our proposed method could discover the unseen malicious macros. Experimental results demonstrate that, comparing with the existing researches, our proposed method has a higher detection rate and better consistency. Furthermore, ensemble multi-classifiers with distinct feature selection further improve the detection performance.

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in osteoarthritis pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating some protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with osteoarthritis, and possible therapeutic approaches to target neutrophils for the treatment of osteoarthritis are described. Understanding neutrophil heterogeneity and their mechanisms of action in joint inflammation, provides a potential strategy for OA management.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Proteins are considered to be the main carriers of antigenic properties of Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis, the most serious infectious disease. Neutrophils, following resident macrophages, are among the first to attack the mycobacteria in defense of the organism. Neutrophils themselves are also the target of mycobacterial products; and their effect on neutrophil functions has been less studied. We have obtained about 70 protein fractions from M. bovis lysate; among them four protein fractions (10, 22, 24, and 40 kDa) had high serological activity against the serum of a rabbit immunized with M. bovis cells. We studied the effect of the serologically active proteins isolated from M. bovis on the generation of reactive oxygen species by bone marrow granulocytes of the Balb/c mouse, evaluated by luminol-dependent chemiluminescence. For comparison, two synthetic peptides (both 3 kDa) carrying immunogenic epitopes of MPB 70 protein (M. bovis) were taken. Proteins of 10, 22, and 24 kDa at concentrations of 83, 80, and 59 ng/mL, respectively, were found to activate ROS generation by mouse granulocytes. The 10- and 40-kDa antigens inhibited the receptor-mediated respiratory responses to opsonized zymosan (OZ) and N-formyl-MLF peptide (fMLF) but significantly enhanced the response to the phorbol ester PMA, which directly activates protein kinase C. Antigens with molecular weights of 22 and 24 kDa enhanced the fMLF-induced response and had no effect on the response activated by PMA. The response to OZ was suppressed in the presence of the 22 kDa protein. Synthetic peptides over a wide range of concentrations showed no activity in any case. All M. bovis proteins examined did not affect both proliferation and cell viability of the A549 and THP-1 cells; therefore, they have no cytotoxic or proliferative effects. Thus, serologically active proteins with molecular weights of 10, 22, 24, and 40 kDa isolated from M. bovis modulated the respiratory responses of mouse granulocytes induced by the formyl peptide, while proteins of 10, 22, and 40 kDa inhibited the responses induced by OZ.

The effects of the coolant pulsation and the film cooling with the plasma aerodynamic actuation (PAA) could be herein explored via large eddy simulations. The electrohydrodynamic force derived from the PAA was solved through the phenomenological plasma model. The Strouhal number of the sinusoidal coolant pulsation and the averaged pulsation blowing ratio were 0.25 and 1.0, respectively. Comprehensive analyses were carried out on the time-averaged flow fields, and the results revealed that the pulsed cooling jet might cause a deeper penetration into the crossflow, and this phenomenon could be remarkably mitigated by the downward force of the PAA. Furthermore, because of the coolant pulsation, the counter rotating vortex pair (CRVP) expanded to lifted off the wall less well, and the PAA lessened the negative lift-off impact and entrapment from the CRVP. Then, the spatial-temporal development of the coherent structures was figured out by the alterations of the centerline temperature, reflecting formation of the intermittent coherent structures rather than hairpin vortices due to the coolant pulsation, and their size and upcast behaviors were reduced by the PAA. Consequently, there was a basic suppression of the turbulent mixing of the cooling fluid with the crossflow. Finally, the three-dimensional streamlines confirmed that the coherent structure dynamic behaviors were significantly regulated by the PAA for alleviating the adverse influences of the coolant pulsation. In summary, through controlling how the dominating coherent structures evolve throughout time and space, the PAA can effectively increase the pulsed film cooling efficiency.

Infectious illnesses have always posed a threat to human health, with tuberculosis (TB) being a major concern. The use of various medications and antibiotics in the fight against such illnesses has led to the emergence of drug-resistant infectious diseases, which have become increasingly dif-ficult to manage as medical and scientific research has advanced. Inadequate medical infrastruc-ture, incorrect treatment practices that exacerbate resistance patterns, and transmission within communities and healthcare facilities are the main factors contributing to the spread of drug-resistant TB. Though treating individuals with multiple drug resistance (MDR) and extreme drug resistance (XDR) strains is challenging, early identification of resistance and the imple-mentation of a well-designed treatment regimen can result in a cure. Community-based inter-ventions that address socioeconomic barriers to adherence can also enhance treatment outcomes. While there have been few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations has been developed. This paradigm seeks to bridge the gap by facilitating the exchange of knowledge among healthcare professionals (HCP) in healthcare facilities (HCF), diagnostic laboratories (DL), and research institutes (RI), particularly for underprivileged communities in the Eastern Cape. The model guide will also monitor and evaluate TB management plans

The paper presents a new type of hydraulic clutch operating with magnetorheological (MR) fluids and the results achieved from both theoretical analysis and experimental measurement. The hy-draulic clutch system of its own design with MR working fluid and a rotating magnetic field lo-cated is designed. The principle of this clutch is to use a rotating magnetic field created by an al-ternating current electromagnet to set the MR fluid in motion. In the tests of the hydraulic clutch with a rotating magnetic field, MR fluid produced on their own, consisting of solid iron particles of various diameters mixed with a silicone oil, are used as working fluids. The rheological properties of MR fluids are assessed on the basis of tests carried out with a Brookfield DV2T rheometer equipped with a magnetic device for generating the magnetic field of its own design. The char-acteristics of the hydraulic clutch with MR working fluid and the rotating magnetic field are tested on a specially built test stand. As a result of the research, it has been found that the torque transmitted by the clutch is the greater, the higher the rotational speed of the magnetic field and the lower the rotational speed of the beaker in which the working fluid is placed, and that the greatest torque occurs for the working fluid with the highest iron content. Based on the analysis of the structure and characteristics of the clutch in which the magnetic field is used, it has been shown that the design of the developed clutch is similar to that of an induction clutch, and its characteristics correspond to the characteristics of the eddy current clutch. Therefore, the proposed new clutch working with MR fluid and the rotating magnetic field can be applied to stationary power transmission system similarly to an eddy current clutch.

Studies have shown that STK11 mutation plays a critical role in affecting the lung adenocarcinoma (LUAD) tumor immune environment. By training an Inception-Resnet-v2 deep convolutional neural network model, we were able to classify STK11-mutated and wild type LUAD tumor histopathology images with a promising accuracy (per slide AUROC=0.795). Dimensional reduction of the activation maps before the output layer of the test set images revealed that fewer immune cells were accumulated around cancer cells in STK11-mutation cases. Our study demonstrated that deep convolutional network model can automatically identify STK11 mutations based on histopathology slides and confirmed that the immune cell density was the main feature used by the model to distinguish STK11-mutated cases.

Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. BRAFV600E mutation is a highly specific target for papillary thyroid carcinoma (PTC) and may have a reciprocal causative relationship with iodide-metabolizing genes. Here, we performed a review of studies published in the past 10 years to determine the relationship between iodine intake and BRAFV600E mutation in patients with PTC. We searched the MEDLINE, PubMed, and EMBASE databases for studies published from 2009 to 2019; seven partially matched the selection criteria and were suitable for review, and five passed all selection criteria. We divided the patients into three groups by iodine intake: low (urinary iodine concentration [UIC] &lt;100 μg/L), adequate (UIC 100–200 μg/L), and high iodine intake groups (UIC ≥200 μg/L). Between-group analysis revealed no significant differences in the odds ratio of the prevalence of BRAFV600E mutation between the high and adequate/low iodine intake groups and between the adequate and low iodine intake groups. To further analyzed the results of studies, they exhibited U-shaped curves in the relation of deficient and excessive dietary iodine intake in BRAFV600E mutation. The results might suggest that iodine intake slightly influences the prevalence of BRAFV600E mutation in patients with PTC despite the heterogeneity of studies. Further research should explore potential mechanisms underlying the associations between iodine intake and BRAF mutation in PTC. The systematic review was registered in PROSPERO (CRD42021279462).

Data on the KIT mutation rate in skin melanoma in the central European region is missing. Accordingly, in a cohort of 79 double wild type (BRAF/NRAS) skin melanoma KIT mutation was assessed by Sanger sequencing of exons 9,11,13,17 and 18. In this skin melanoma cohort KIT mutation frequency was found to be 34/79 (43%) with a significantly higher rate in acrolentiginous melanoma (ALM) as compared to UV-induced common variants (20/34, 58.8% versus 14/45, 31.1%, p=0.014). Exon 11 was the most frequent mutation site (44.7%) followed by exon 9 (21.1%) equally characterizing UV-induced common histotypes and ALM tumors. KIT mutation hotspots were identified in exon 9 (c491/492), in exon 11 (c559,c572, c570), in exon 13 (c642), in exon 17 (c822) and in exon 18 (c853). The relatively high KIT mutation rate in skin melanoma in this central-European cohort justifies regular testing of this molecular target.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

Climate change is affecting the planet, compromising survival and altering forest ecosystems. Investigating climatic variations in all regions is important. The aim of this research was to assess such variations in the W and Pendjari Biosphere Reserves in Benin from 1985 to 2015 and predict climate up to 2045. Drought frequency was assessed by using the Standardized Precipitation and Evapotranspiration Index (SPEI) and correlation was performed between climatic variables. Then a predictive analysis was computed. From 1985 to 2015, there was change in the climate with few severe dry and wet years while no extreme climatic condition was noticed. Most of the years showed nearly normal climatic conditions. The predicted climate indicates an absence of extreme conditions up to 2045 but an increase in the annual humidity is expected. A low decrease in annual mean temperature with high confidence is expected. Decision-makers can better organize adaptation programs and sensitize people in the reserves on their role in environmental conservation and mitigation of climate change using these outputs.

Introduction: Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process.Methods: We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022.Results: Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8⁺ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45⁺ cells, total lymphocytes, CD4⁺ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs.Conclusions: These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Optical power splitters play a crucial role as the fundamental building blocks for many integrated optical devices. They should have low losses, broad bandwidth, and a high tolerance to fabrication errors. Adiabatic optical power splitters inherently possess these qualities while being compatible with foundry processes well-suited for mass-production. The long device lengths of adiabatic power splitters, however, are a limiting factor to achieve compact device sizes, which must be reduced. Here, we use a polynomial taper profile optimization algorithm to design 1×2 and 2×2 adiabatic power splitters with significantly shorter lengths than their adiabatic counterparts. The best performing 1×2 and 2×2 power splitters have 20 μm and 16 μm coupling lengths, respectively. Our designs have minimum feature sizes ranging from 140 nm to 200 nm, and our measurements averaged across 9 different chips show excellent consistency in performance for devices with 180 nm and 200 nm minimum features. Both the 1×2 and 2×2 adiabatic optical power splitters have excess losses less than 0.7 dB over a 100 nm bandwidth, with a standard deviation lower than 0.3 dB. Furthermore, our measurements show greater than 20 dB extinction ratios over 130 nm bandwidth. We also demonstrate the design of 1×2 power splitters with arbitrary splitting ratios, where splitting ratios ranging from 50:50 to 94:6 were achieved with standard deviations between 2% and 6%.

Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor. Furthermore, the prediction of glycosylation points has revealed that there are about 20 N-glycosylation potential sites on spike protein. We believe that the information present here would not only help in thorough understanding of infectivity but also enhance the knowledge of the scientific community in developing prophylactics and/or therapeutics for SARS-CoV19-2 virus.

In flowering plants with dry stigmas, pollen hydration involves water movement, which may be facilitated by aquaporins. To explore the possibility underlying this biological process, we identified and characterized a mutant with a T-DNA insertion in PIP2;5, which encodes an aquaporin with water channel activity in the PIP2 subfamily. We monitored the pollination process (pollen hydration, germination, and pollen tube growth) of wild type pollen on stigmas of the mutant and wild type. Pollen hydration was postponed on the stigmas of the mutant, compared with that on wild type stigmas. However, pollen tube germination and growth was unaffected in the mutant. The PIP2;5 protein was located in the cell plasma membrane and was preferentially expressed in the stigma. Based on our results, we concluded that PIP2;5 might play an important role in water movement during pollen hydration.

Sorghum grain processing can improve the nutritional content by promoting dietary properties that contribute to food security and economic development. The quality, nutritional content, and processing properties of sorghum bicolor grain can greatly affected by the inbred line races and variance in pericarp colour.The current study assessed the influence of the Husking Fraction Time Units (HFTU) process, which employed set time units per second (S), on the variation in the nutritional profile of fifty-one inbred line sorghum varieties based on distinct pericarp colours. When the assessment of the nutritional profile was involved: dry matter, total protein besides, namely mineral (P, K, S, Ca, Mg, Na, Fe, Zn, and Mn). The variety groups showed a significance value of (P < 0.05), indicating the study hypothesis's truth.The results demonstrated substantial impacts implied by the Husking Fraction Time Unit (HFTU) technique. This occurrence was noted when the dry matter percentage was increased in the husked products, specifically the endosperm (grits) and bran. The protein percentage redistributed by 19.2% compared to the whole grain and bran content. In comparison, the ratio of N/S was 14:1 in the S. bicolor and 12:1 in the kafirin in the bran part. Moreover, a strong correlation was observed among the examined minerals of S.bicolor and kafirin, such as the correlation between Ca: P, K: Na, and Fe: Zn attributed 80 (S) time unit, with correlation coefficients of R = 0.784 and R = 0.586, R= 517, R= 0.884, R= 0.745, and R = 0.893, respectively. At the same time, the 80 (S) time unit showed a significant effect on the colour property profile.The study results could benefit breeders and nutrition specialists in developing genotypes and processing sorghum grains, promoting research, and aiding several industrial sectors owing to the grain's adaptability and nutritional properties.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

In an age of market liberalization, globalization, and expanding agribusiness, there is a danger that small-scale farmers will find difficulty in fully participating in the market economy. One of the solutions to solve the above situation is to strengthen linkages between farmers and firms through contract farming. The purpose of this study is to assess the factors affecting the level of linkages between businesses and farmers in crop development in Thai Binh province, Vietnam. The two main research methods used were exploratory factor analysis (EFA) and regression analysis with survey data which was conducted from 300 farmers, 10 firms, and 15 factors related to contract-farming. The results indicated that there are 5 factors that significantly affect the level of participation of farmers in the linking process, the order of impacts from strong to weak is as follows: (1) Commitment and sharing of benefits and risks between farmers and firms in the linking process, (2) Issues related to management skills and enterprises capacity of link firms, (3) Price issues that farmers are interested in in the process of implementing links with firms, (4) Policy environment - Institutions related to farmer contracts between firms and farmers, (5) Household awareness about the benefits brought about by farmer contracts with firms. Based on results, a number of specific solutions have been proposed to enhance the efficiency of farming contracts between firms and farmers in cultivation production.

The abundant use of lithium-ion batteries (LIBs) in a wide variety of electric devices and vehicles will generate a large number of depleted batteries, which contain several valuable metals such as Li, Co, Mn, and Ni present in the structure of the cathode material (LiMO2). The present work investigates chemical, technological, and environmental aspects in the treatment of such wastes, development of a methodology for the extraction of lithium, cobalt, nickel, manganese, and graphite by a carbochlorination pyrometallurgical process. Mixtures of cathode and anode materials (called black mass, mixed oxides of Li, Co, Ni, Mn, and graphite) from different LIBs, carbon black (as reducing agent), and CaCl2 (as chlorinating agent) were used. Non-isothermal thermogravimetric tests up to 850°C and isothermal tests at 700°C of the mixtures in an inert atmosphere were carried out. It was experimentally observed that the LiMO2-C-CaCl2 reaction takes place at 700°C. LiCl, Ni, and Co were obtained as final products, and to a lesser extent, CoO, NiO, and MnO2. CaCO3 was also obtained as a by-product. The obtained results show that carbochlorination is an efficient and effective alternative route for the extraction and recovery of metals from different LIBs, focused on the sustainability and circular economy

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

This research aims to examine the level of readiness of the community to carry out sustainable tourism development, especially community-based tourism on small islands, such as Lombok Island, Indonesia. More specifically, the objectives of this study are as follows: (1) Knowing the level of community readiness in carrying out sustainable tourism development. (2) Knowing the various dimensions that influence sustainable tourism development. (3) Knowing the role of stakeholders in sustainable tourism development. The method applied in this research is mixed methods, a combination of quantitative and qualitative approaches. Quantitative methods are used to determine community readiness for sustainable tourism development. A qualitative approach is used to determine the various factors that influence the development of community-based tourism and to determine the role of stakeholders in the development of community-based tourism. The level of community readiness for sustainable tourism development is high in terms of economic, social, cultural, environmental, and symbolic capital aspects. Aspects that influence the development of sustainable tourism are economic, social, and cultural. Stakeholders who play a role in developing sustainable tourism in the research area are the government, the private sector, universities, non-governmental organizations, and the media.

Background: Hypertension is a condition of a person's blood pressure being at a level above normal, hypertension treatment can be done herbally using avocado leaves. Avocado leaves can lower blood pressure because they contain active substances, namely flavonoids and quercetin. This research was conducted in the working area of the Tilango Health Center. Objective: This study aims to determine the effect of giving boiled water of avocado leaves on reducing blood pressure in the elderly with hypertension. Methods: Design This study used a two-group quasi-experimental pre-test - post-test design. The sample is the elderly who have hypertension, amounting to 125 people with purposive sampling technique. The research instrument used a questionnaire. Results: Statistical test using T-Test on blood pressure before and after the intervention was given a significance value of 0.000 (p-value < 0.05 ). Conclusion : This study concludes that there is a significant effect between giving avocado leaf boiled water on reducing blood pressure in the elderly with hypertension in the working area of the Tilango Health Center.

Enteroaggregative Escherichia coli (EAEC) are highly heterogeneous in virulence; we wanted to understand the pathogenic potential of EAEC isolated various clinical and non-clinical sources in an animal model. We infected male BALB/c mice in six mice/group with 50 EAEC isolates, isolated from clinical and non-clinical sources. We studied colonization, weight loss, stool shedding, inflammatory markers and its relationship with 21 virulence genes and phylogroups, EAEC organ burden and histopathological changes. We detected significantly more inflammatory changes and fecal lactoferrin and calprotectin levels in mice infected with EAEC isolated from symptomatic cases. In clinical EAEC isolates, the presence of chromosomal genes {(aap (46%), aaiC (23.3%), and SPATEs (pet (13.3%), sat (20%), sigA and pic (6.6%)}, adhesive variants {(agg4A (53.3%), aggA (53.3%), aafA (36.6%), agg3A (40%)} of EAEC, and master regulator gene aggR (66.6%) were associated with higher levels of lactoferrin and calprotectin. Also, 70% (9/13) of EAEC isolated from acute diarrheal cases bearing chuA (70%) in our study were assigned to group B2 (4 isolates) and D (5 isolates). Real-time PCR analysis revealed that colonization by EAEC strains from different clinical and non-clinical sources occurs up to 10-15 days of life. Even from non-diarrhoeal stools and non-clinical sources, had the potential to cause prolonged colonization, weight loss, and inflammation in the intestine though the degree varied. Moreover, better understanding of EAEC pathogenic pathways is desperately needed in different clinical scenarios.

Physics of high-Tc superconducting cuprates is obscured by the effect of strong electronic correlations. One way to overcome the problem is to seek for an exact solution at least within the small cluster and expand it to the whole crystal. Such an approach is in the heart of the cluster perturbation theory (CPT). Here we develop CPT for the dynamic charge and spin susceptibilities (spin-CPT), within which the correlation effects are explicitly taken into account by the exact diagonalization. We apply spin-CPT to the effective two-band Hubbard model for the cuprates obtained from the three-band Emery model and calculate one- and two-particle correlation functions, namely, spectral function and spin and charge susceptibilities. Doping dependence of the spin susceptibility was studied within spin-CPT and CPT-RPA that is the CPT generalization of the random phase approximation (RPA). Both methods produce the low energy response at four incommensurate wave vectors in qualitative agreement to the results of the inelastic neutron scattering on overdoped cuprates.

This work is a natural extension of the author’s previous work: “Multiple scattering theory for heterogeneous elastic continua with strong property fluctuation: theoretical fundamentals and applications” (arXiv:1706.09137 [physics.geo-ph]), which established the foundation for developing multiple scattering model for heterogeneous elastic continua with either weak or strong fluctuations in mass density and elastic stiffness. Polycrystalline material is another type of heterogeneous materials that widely exists in nature and extensively used in industry. In this work, the corresponding multiple scattering theory for polycrystalline materials with randomly oriented anisotropic crystallites is developed. To validate the theory, the theoretical results for a series of materials such as OFHC copper, 304 stainless steel, and Inconel 600 are compared to experimental measurements and the numerical results obtained using finite element simulations. Detailed analysis shows that the new theory is capable of predicting the dispersion and attenuation of polycrystals with satisfactory accuracy. The results also show the new model can give an estimate on the average grain size with a relative error equal to or less than ten percent. As applications in ultrasonic nondestructive evaluation, we calculated the dispersion and attenuation coefficient of one of the most important polycrystalline materials in aeronautics engineering: high-temperature titanium alloys. The effects of grain symmetry, grain size, and alloying elements on the dispersion and attenuation behaviors are examined. Key information is obtained which has significant implications for quantitatively evaluating the average grain size, monitoring the phase transition, and even estimating gradual change in chemical composition of titanium components in gas turbine engines. For applications in seismology, the velocities and Q-factors for both hexagonal and cubic polycrystalline iron models for the Earth’s uppermost inner core are obtained in the whole frequency range. Using the realistic material parameters of iron under the high temperature and high-pressure conditions calculated from ab initio simulations, the numerical results show that the Q-factors range from 0.001 to 0.05, which shows good agreement with that inferred from real seismic data. The new model predicts the velocity of longitudinal waves varies between ± 1% to ± 5 % relative to the Voight average velocity, while the velocity of transverse waves varies from ± 10% to ± 20%, which gives promising explanation to the abnormally slow transverse velocity observed in practical measurements. The numerical results support the conjecture that the Earth’s uppermost inner core is a solid polycrystalline medium. The comprehensive numerical examples show the new model is capable of capturing the most important scattering features of both ultrasonic and seismic waves with satisfactory accuracy. This work provides a universal, quantitative model for characterization of a large variety of polycrystalline materials. It also can be extended to incorporate more complicated microstructures, including ellipsoidal grains with or without textures, and even multi-phase polycrystalline materials. The new model demonstrates great potential of applications in ultrasonic nondestructive evaluation and inspection of aerospace and aeronautic structures. It also provides a theoretical framework for quantitative seismic data explanation and inversion for the material composition and structural formations of the Earth’s inner core.

The parts obtained by FFF technology are anisotropic in any direction; while the whole part constitutes out of layers, each of the layers include one or more perimeters of shell and the infill with density from 0 to 100%. Mechanical performance of FFF parts depends on its shape, orientation, constitution and 3D printing parameters. A classification for shapes of parts obtained by FFF and stressed during its operation is provided. For the most questionable class (parts with interrupted shell critically stressed on interlayer boundaries) a representative sample and testing apparatus is developed. Different approaches to the sample shape modification were applied and tested. The part shape optimization resulted in increment of the force, required to fracture the part from 483 to 1096 N.

Although global life expectancy has increased over the past 20 years due to improvements in managing infectious diseases, one in five people still succumbs to infections. Humanity is tirelessly working towards developing vaccines and antimicrobial agents in response to this ongoing threat. However, pathogens continue to acquire numerous resistance mechanisms and proliferate. Meanwhile, the COVID-19 pandemic has prompted us to recognize that focusing solely on the killing strategies of immunology and microbiology in complex and multisystemic infectious diseases is insufficient for understanding survival. In essence, there is a need for a treatment approach centered on disease tolerance, capable of alleviating pathology and/or promoting physiological functions in conjunction with the existing strategies of host immune response and pathogen destruction. Against this backdrop, this narrative review comprehends and introduces microbiome therapeutics, which recently garnered attention as next-generation treatments regarding two defense strategies against infectious diseases. First, we delineate the application of existing probiotics and then the microbiome in infectious diseases. Subsequently, we expand this concept to encompass host microbiome crosstalk and present related microbiome therapeutics' current status and direction. Ultimately, the review presents a fresh perspective on understanding microbiome therapeutics in infectious diseases based on a cooperative defense system.

The sustainable management of Land - Water - Energy - Food (LWEF) nexus requires an envi-ronmental characterization that allows the comparison of complex interlinkages between nexus resources and livelihoods. This complexity makes this characterization difficult coupled with limited study in quantifying sustainability of LWEF nexus and its linkage with livelihood. Therefore, the present study aimed to investigate the link between sustainable LWEF nexus and livelihoods. We used analytical hierarchy process and pairwise comparison matrix in combina-tion with weighting model. The result of composite LWEF nexus index was 0.083 representing, low sustainability. This could be linked with nexus resources consumption, use, and manage-ment. From the analysis of the weight of land, water, energy and food nexus resources, the highest weight was observed for food. The focus of on food production only shows no clear synergy on provisioning, supporting or regulating nexus resources to address livelihoods. The result further showed that LWEF nexus resources have strong correlation with livelihoods. This was evidenced by social (r>0.8, P<0.01), natural (r>0.3, P<0.05) and physical (r>0.6, P<0.01) liveli-hood indicators showed strong positive correlation with LWEF nexus resources. From this re-sults, it was observed that managing nexus resources not only provide a significant contribution to achieve sustainable LWEF nexus, but also be effective for enhancing livelihood through food security. This could be attained by strong evidence based policy to ensure sustainable use of nexus resources. The results provided by this study would serve as the foundation for future study, policy formulation and implementation.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

Abstract Background Fatigue Syndrome (FS) is described as extreme exhaustion following ordinary activities. Sleep deprivation, the use of antidepressants, autoimmune illnesses, and anemia are also risk factors for FS. Symptoms of FS include headache, dizziness, and dyspnea, among others. Objective: This study focused on assessing the prevalence of fatigue syndrome (FS) and its association with depression and anxiety, among the medical students in Saudi Arabia. Methodology In this cross-sectional investigation conducted in 2023, 740 medical students participated. Data were gathered using an online survey, which encompassed four key sections: Sociodemographic details, the 11-item Chalder Fatigue Questionnaire (CFQ), the 9-item Primary Health Questionnaire (PHQ) assessing depression, and the Generalized Anxiety Disorder 7-item (GAD-7) scale. Analyses were performed by the use of SPSS version 25. Results A total of 740 students were surveyed, 417 (56.4%) satisfied the diagnostic requirements for fatigue syndrome (FS), with most of them being females. Furthermore, 234 (31.2%) and 296 (40.8%) of the participants reported having significant anxiety symptoms and depressive symptoms, respectively. FS was positively correlated with symptoms of anxiety and depression (P

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

Purpose: To investigate the molecular basis of congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome. Methods: We report ocular features of 3 girls with GAPO syndrome born of consanguineous marriage in a multi- generation consanguineous family. The proband (4year old girl) and her younger sibling (1 year old girl) were operated for bilateral congenital glaucoma in both eyes. The elder sibling (10year old female) had features of GAPO syndrome but did not manifest features of glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a homozygous ANTXR1 mutation in all 3 affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense mutation in TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome.Conclusions: Mutations in TGFBI gene could have a role in the pathogenesis of congenital glaucoma.

It has been more than a year since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found. This coronavirus has infected more than 110 million people worldwide by the end of February, 2021, and several virulent as well as more spreadable mutant forms of SARS-CoV-2 have emerged subsequently. In the latter group, three variants B.1.1.7, B.1.351, and P1 lineages, have been reported. Using computer simulation, the present paper investigates the structural differences between the wild type SARS-CoV-2 spike protein and its Asn501Tyr (N501Y) mutant variant. Time-based structural changes between the receptor binding domains of these two species are also examined. The N501Y mutation is common to all the three aforesaid mutant variants.

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed murine thrombocytosis in the absence of functional TRPV4, but no prior reports have described platelet count abnormalities in the context of human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.

Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LEM-domain, emerin interacts with the DNA-binding protein Barrier-to-Autointegration (BAF). Emerin also binds to members of the Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss Muscular Dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, ∆K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas DK37 mutation impairs correct folding of the LEM-domain, P22L and T43I have no impact on the 3D structure of emerin. Surprisingly, all three mutants bind to BAF, albeit with a weaker affinity in the case of DK37. In human myofibroblasts derived from a patient’s fibroblasts, emerin ∆K37 is correctly localized at the inner nuclear membrane, but is present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 is reduced, and cells are defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation DK37 is to perturb emerin function within the LINC complex in response to a mechanical stress.

Controllable, quantum-strong correlations of polarization states can be implemented with multi-photon independent states. Polarization-based photonic quantum correlations can be traced back to the overlap of the polarization Stokes vectors on the Poincaré sphere between two polarization filters. The quantum Rayleigh scattering prevents a single photon from propagating in a straight line inside a dielectric medium, and it also provides a mechanism for the projective measurement of polarization. Complexities associated with single-photon sources and detectors can be eliminated because the quantum Rayleigh scattering in a dielectric medium destroys entangled photons. Entanglement-free, identical sources and processing devices give rise to correlations rather than these being caused by “quantum nonlocality”. These analytic developments were prompted by the vanishing expectation values of the Pauli spin vector for a single photon of maximally entangled photonic Bell states.

Chess is an interesting game for artificial intelligence research and an entertaining hobby and sport for a growing number of people. However, humans differ greatly in their ability to play. Typically, the Elo rating is used to determine a player's skill and to predict who will win. When differences in Elo are too great the weaker player is almost guaranteed to lose. While on one hand, the Elo rating allows players to be matched to equally well-playing opponents, it also to some degree restricts the games to be played between equally strong opponents since otherwise the result is known beforehand. Here a handicap system where stronger players remove pieces at the start of the game is evaluated. Specifically, the effect each removed piece or combination of pieces have on a player. Interestingly, pieces do not always reduce the Elo of a player by a predefined amount, but their effect depends strongly on the player's current Elo. The results presented here are from playing the computer engine Stockfish because data about humans playing this scheme is limited. However, the results make direct predictions about the effect of piece removal on Elo.

The chemistry and electrochemistry basic fields have been active since the last two decades of the past century studying how surface modification of electrodes by coating with conductive films enhances their activity and performance. In the light of the development of alternative sustainable ways of energy storage and carbon dioxide conversion by electrochemical processes, these research studies have jumped in the 21st century to more applied fields such as chemical engineering, energy and environmental science and engineering. The huge amount of literature on experimental works dealing with the development of CO2 electroreduction processes addresses electrocatalyst development. Membranes can help understanding and controlling the mass transport limitations of current electrodes and reactors designs. The present bibliometric review addresses the papers published in the 21st century regarding membrane coated electrodes and electrocatalysts to enhance electrochemical reactor performance and viability with a special focus on the urgent issue of carbon dioxide capture and utilization.

Glioma accounts for 80% of all malignant brain tumors and is the most common adult primary brain tumor. Age is an important factor affecting the development of cancer as somatic mutations accumulate with age. In this study, we aimed to analyze the significance of age-related non-silent somatic mutations in glioma prognosis. Histological tumor grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wildtype counterpart. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. In conclusion, among the many somatic mutations, those in IDH1, TP53, ATRX, and EGFR are important for glioma classification based on histological grade. Patients with EGFR mutation had the poorest prognosis, whereas those with only IDH1 mutation showed the best prognosis.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

Abstract This study investigates the assessment literacy, perceived practice, and observed practice of CBA practices among TVET teachers and assessors in private TVET colleges in South Gonder Zone, Ethiopia. The participants included 49 teachers and 14 assessors. Data collection utilized a modified four-option multiple-choice test, the Teacher Assessment Competency Inventory Questionnaire, a five-point Likert scale for perceived and observed practices, a semi-structured observation checklist, and interviews. Descriptive analysis, including mean scores, standard deviation, one-sample t-test, and proportions (%), was employed to analyze the data. Pearson correlation test was used to explore relationships between teacher assessment test scores, observed practices, and perceived practices. Findings revealed that private TVET teachers in the Amhara National Regional State lacked competence in assessing students' competence, falling short of overall and specific standards in both the assessment competence test and real classroom practice. Despite this, teachers modestly perceived their assessment practices across competency domains. Consequently, there were significant differences between teachers' actual competence and practice in educational assessments and their self-perceived practice. Qualitative approaches, employing theme analysis of assessment practice from semi-structured observations and interviews, highlighted poor performance among teachers on most assessment criteria. A small percentage demonstrated competence in specific concepts. Overall, the majority of teachers exhibited low levels of assessment literacy, suggesting a need for professional support in educational assessment approaches to enhance competence among TVET teachers.

COVID-19 pandemic in first seven months has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19 has proved a great challenge for its ability to spread in asymptomatic stages and a diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8, predict upon its protein features and review current available literature regarding its function. We have also undertaken review of ORF8 homolog ORF8ab from SARS-CoV with a purpose of developing holistic understanding of these proteins for reason that coronaviruses have been infecting humans repeatedly and might continue to do so. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

Background: Oral squamous cell carcinoma (OSCC), with poor prognosis and high mortality rates, is one of the most diagnosed head and neck cancers. Cancer stem cells (CSCs) - epithelial-to-mesenchymal transition (EMT) loop is increasingly implicated in the therapy-resistance, relapse, and metastasis of OSCC patients. Accumulating evidence indicate that aberrantly expressed CD47 is associated with cell-death evasion, invasion and cancer metastasis; however, the role of CD47 in the modulation of CSCs-like phenotypes, including therapy-resistance and metastasis, with its underlying mechanism in OSCC remains largely underexplored. Methods: This study investigated the CSCs- modulating potential of CD47 in OSCC cell lines SAS, TW2.6, HSC-3 and FaDu using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony and orosphere formation, as well as radiosensitivity assays. Results: We demonstrated that the characteristic ectopic expression of CD47 in OSCC patients was associated with ~ 20% 2-year survival disadvantage (p = 0.01) and positively correlated with the expression of pluripotency factors; while shRNA silencing of CD47 significantly suppressed cell viability and markedly inhibited orosphere formation, resulting in smaller and fewer orospheres, and downregulated CD133, SOX2, OCT4 and c-Myc mRNA and protein expression levels. We also showed that CD47 downregulation attenuates EMT, migration and clonogenicity of OSCC cells, with associated E-cadherin upregulation and suppression of Vimentin, Slug, Snail, and N-cadherin expression. Conclusion: Of therapeutic relevance, combined with radiotherapy, CD47 knockdown enhanced the anti-OSCC effect of radiotherapy. Thus, we demonstrate the therapeutic feasibility of a CD47-mediated anti-CSCs strategy, and suggest a role for CD47 suppression in potentiating the therapeutic efficacy of radiation therapy in OSCC patients.

The evidence is presented for the long-range previtreous changes of two static properties: dielectric constant ( ) and its strong electric field related counterpart - the nonlinear dielectric effect (NDE). Notable is the evidence for the functional characterizations of (T) temperature changes by the ‘Mossotti Catastrophe’ formula, and NDE vs. T evolution by the relations resembling one developed for critical liquids. The analysis of dynamic properties based on the activation energy index excluded the Vogel-Fulcher-Tammann (VFT) relation as a validated tool for portraying the evolution of the primary relaxation time. Such a result questions the commonly applied ‘Stickel operator’ routine as the reliable tool for determining the dynamic crossover temperature. It is worth stressing that the strong electric field radically affects the distribution of relaxation times, the form of the evolution of the primary relaxation time as well as the fragility. Obtained results support the concept of a possible semi-continuous phase transition hidden below Tg. Studies were carried out in supercooled squalene, the material with extremely low electric conductivity, strongly elongated molecule, and vitally important for biology and medicine related issues.

Scattering of elastic waves in heterogeneous media has become one of the most important problems in the field of wave propagation due to its broad applications in seismology, natural resource exploration, ultrasonic nondestructive evaluation and biomedical ultrasound. Nevertheless, it is one of the most challenging problems because of the complicated medium inhomogeneity and the complexity of the elastodynamic equations. A widely accepted model for the propagation and scattering of elastic waves, which properly incorporates the multiple scattering phenomenon and the statistical information of the inhomogeneities is still missing. In this work, the author developed a multiple scattering model for heterogeneous elastic continua with strong property fluctuation and obtained the exact solution to the dispersion equation under the first-order smoothing approximation. The model establishes an accurate quantitative relation between the microstructural properties and the coherent wave propagation parameters and can be used for characterization or inversion of microstructures. Starting from the elastodynamic differential equations, a system of integral equation for the Green functions of the heterogeneous medium was developed by using Green’s functions of a homogeneous reference medium. After properly eliminating the singularity of the Green tensor and introducing a new set of renormalized field variables, the original integral equation is reformulated into a system of renormalized integral equations. Dyson’s equation and its first-order smoothing approximation, describing the ensemble averaged response of the heterogeneous system, are then derived with the aid of Feynman’s diagram technique. The dispersion equations for the longitudinal and transverse coherent waves are then obtained by applying Fourier transform to the Dyson equation. The exact solution to the dispersion equations are obtained numerically. To validate the new model, the results for weak-property-fluctuation materials are compared to the predictions given by an improved weak-fluctuation multiple scattering theory. It is shown that the new model is capable of giving a more robust and accurate prediction of the dispersion behavior of weak-property-fluctuation materials. Numerical results further show that the new model is still able to provide accurate results for strong-property-fluctuation materials while the weak-fluctuation model is completely failed. As applications of the new model, dispersion and attenuation curves for coherent waves in the Earth’s lithosphere, the porous and two-phase alloys, and human cortical bone are calculated. Detailed analysis shows the model can capture the major dispersion and attenuation characteristics, such as the longitudinal and transverse wave Q-factors and their ratios, existence of two propagation modes, anomalous negative dispersion, nonlinear attenuation-frequency relation, and even the disappearance of coherent waves. Additionally, it helps gain new insights into a series of longstanding problems, such as the dominant mechanism of seismic attenuation and the existence of the Mohorovičić discontinuity. This work provides a general and accurate theoretical framework for quantitative characterization of microstructures in a broad spectrum of heterogeneous materials and it is anticipated to have vital applications in seismology, ultrasonic nondestructive evaluation and biomedical ultrasound.

Abstract: Chloroplast is a new hotspot in the field of plant transformation system of plant genetic engineering. Initially developed in Chlamydomonas and tobacco, it is now feasible in a broad range of species. They exploit the homologous recombination and segregation pathways acting on chloroplast genomes and are based on direct repeats, transient co-integration or co-transformation and segregation of trait and marker genes. Foreign site-specific recombinases and their target sites provide an alternative and effective method for removing marker genes from plastids.Chloroplast genetic engineering has many advantages over nuclear genetic enginering, especially site-specific introduction of foreign genes ,leading to the absence of gene siliency and positon effect,which providing the available to explore the regulation and mechanism of chloroplast genes`expression in vitro .It also can identify the structure and function of the chloroplast genome , the expression of chloroplast affect the nulear genome. In this paper, the basic methodology of chloroplast transformation, the current techniques and applications, and the future possibilities for Chloroplast genetic engineering was reviewed[1-3].

.Background: Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) showed promising results in patients with colorectal carcinoma at high risk of recurrence but still without clinically and radiologically evident signs of peritoneal spread. This study aims to analyze the feasibility of this proactive, early phase, multimodality approach. Methods: A mono-institutional, prospective, parallel, two-stage phase II trial enrolled 49 patients to standard surgery or surgery plus intraoperative HIPEC. Before the procedure and during surgery, patients received intravenous fluorouracil (and leucovorin to potentiate oxaliplatin activity. Data analysis included length of hospital stay, surgery duration, type of surgery and chemotherapy-related complications risk score. Results: No significant difference was seen in the median time spent in the hospital with a median stay of 7 days in both groups (p=0.5720). The surgical procedure's median duration was longer in the HIPEC group than in the control one. Side-effects and surgical complications did not cross at any time the Pocock-type boundary for side/effect monitoring (p=0.80, N.S.). Conclusions: The present prospective study results demonstrate the feasibility and safety of the colorectal surgery plus HIPEC treatment in patients with colorectal cancer patients at high-risk for peritoneal invasion, although clinically and radiologically undetectable.

To investigate whether the ech42 gene in Clonostachys rosea can improve the biocontrol efficacy of Bacillus amyloliquefaciens and its molecular mechanism.Compared to the wild type, the B. amyloliquefaciens transformed with the ech42 gene exhibited a higher chitinase activity. The B. amyloliquefaciens-ech42 also showed a significantly higher biocontrol efficiency against B. cinerea when tomato plants were pre-treated with amyloliquefaciens-ech42. No significant difference of control efficiency was observed between the wild type and amyloliquefaciens-ech42 when tomato plants were first infected by B. cinerea. In addition, the activity of the defense-related enzyme polyphenol oxidase, but not superoxide dismutase was significantly higher in amyloliquefaciens-ech42 than in the wild type.The ech42 enhances the Bacillus amyloliquefaciens biocontrol efficiency by increasing the capacity of protection/prevention to plants, rather treating/killing the pathogens.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

This article is devoted to the problem of genetically coding of inherited cyclic structures in biological bodies, whose life activity is based on a great inherited set of mutually coordinated cyclic processes. The author puts forward and arguments the idea that the genetic coding system is capable of encoding inherited cyclic processes because it itself is a system of cyclic codes connected with Boolean algebra of logic. In other words, the physiological processes in question are cyclical because they are genetically encoded by cyclic codes. In support of this idea, the author presents a set of his results on the connection of the genetic coding system with cyclic Gray codes, which are one of many known types of cyclic codes. This opens up the possibility of using for modeling inherited cyclic biostructures those algebraic and logical theories and constructions that are associated with Gray codes and have long been used in engineering technologies: Karnaugh maps, Hilbert curve, Hadamard matrices, Walsh functions, dyadic analysis, etc. Additionally, the connections of these constructions with statistical rules of genomic DNAs and binary-genomic numbers are considered.

It is essential to consider the factors that affect early childhood development because doing so can help identify potential risks and window of opportunity for intervention to improve outcomes for children. However, identifying risk and protective factors in early childhood requires careful consideration of several challenges and an integrated approach that recognises the complex and dynamic nature of development. The purpose of this study was to identify and describe the prevalent psychosocial risk and protective factors in the early childhood development phase, using an ecological perspective. The study employed a quantitative cross-sectional study using a random sampling technique. The final sample consisted of 505 caregivers of children aged 5 years old and younger. This study revealed that the most prevalent protective factors include child self-regulation, parent-child warmth, family management and collective efficacy but more importantly social support. While risk factors may exist this is mitigated by social support as it moderates and buffers against the effects of risk factors, as indicated by the various research studies cited.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) implies increased absolute risk also for other malignancies such as cholangiocarcinoma (CCA). However, even if somatic mutations in CCA have been reported, there are no data on its utilization as predisposing genetic factor in a family. For the first time, we utilized CCA somatic BRCA mutation to individualize a family with HBOC. A 47-year-old woman (daughter of a patient died for CCA) accessed to our Genetic Councelling to evaluate her personal cancer risk. We performed a somatic BRCA1/2 NGS analysis on DNA extracted from formalin-fixed, paraffin-embedded CCA-tissue of her mother. After demonstration of pathogenic variant c.6468_6469delTC in BRCA2 gene mutation, the same germline pathogenic variant was found in DNA blood of one of two daugthers. So far, CCA tissue can be utilized, in addition to patient’s selection to specific therapeutic strategies, also to individualize families belonging to HBOC syndrome.

Potassium inwardly-rectifying channel, subfamily J, member 12 (KCNJ12) gene is one promising candidate for economic traits because of its crucial roles in myoblast development. Here, a missense mutation (Cys>Arg), was firstly detected to locate in exon 3 of KCNJ12 from three Chinese cattle breeds by DNA-pool sequencing. Then, we performed the association analysis of this SNP with stature in three Chinese cattle populations (n = 820). Significantly positive correlation was revealed by reduced animal general linear model and the genotype of CC is the most excellent genotype in three breeds. Further, we measured the expression profiling of the KCNJ12 gene in various cattle tissues and primary bovine skeletal muscle cells. Ubiquitous expression with high abundance in muscle was observed. Further, in primary bovine skeletal muscle cells, the KCNJ12 mRNA expression was gradually up-regulated in differentiation medium (DM) compared with that in growth medium (GM), suggesting that KCNJ12 gene is involved in bovine myocyte differentiation. Conclusively, KCNJ12 gene is a functional candidate gene which can be used as molecular marker for beef cattle breeding.

Abstract: Assessing infection by a parasite, such as Haemonchus contortus, requires time and experienced personnel. Field-based diagnostics using metagenomic species-specific targeting methods would be beneficial. Here, we examine two helminth control methods, zoledronic acid (ZA), an activator of γ δ T cells, and a neutralizing antibody (AB) against γ δ T cells. We conducted a randomized complete block designed investigation for the effects of Haemonchus contortus (Hc) infection on Alpine wethers (young castrated male goats) to identify if metagenomic methods will provide strong evidence for diagnostics. Different tissues were collected from wethers and the microbiome compositions were identified. The relative proportion of microbial community members in the environments; the richness of the microbial community; and the evenness of distribution in microbial community members were determined. It was hypothesized that numerous parameters that include many data points will provide a more precise means to identify infection or health based on similarity to uninfected control data parameters. We found that samples did not sequence well, when multiplexed with high concentration libraries, giving taxonomic numbers that had residual and unmeasured confounding bias related to analysis or selection that define significance of OTUs in the tissue samples at the phylum or species level.

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

The aim of this expository article is to present recent developments in the centuries-old discussion on the interrelations between several types of domination in graphs. However, the novelty even more prominent in the newly discovered simplified presentations of several older results. Domination can be seen as arising from real-world application and extracting classical results as first described by this article.The main part of this article, concerning a new domination and older one, is presented in a narrative that answers two classical questions: (i) To what extend must closing set be dominating? (ii) How strong is the assumption of domination of a closing set? In a addition, we give an overview of the results concerning domination. The problem asks how small can a subset of vertices be and contain no edges or, more generally how can small a subset of vertices be and contain other ones. Our work was as elegant as it was unexpected being a departure from the tried and true methods of this theory that had dominated the field for one fifth a century. This expository article covers all previous definitions. The inability of previous definitions in solving even one case of real-world problems due to the lack of simultaneous attentions to the worthy both of vertices and edges causing us to make the new one. The concept of domination in a variety of graphs models such as crisp, weighted and fuzzy, has been in a spotlight. We turn our attention to sets of vertices in a fuzzy graph that are so close to all vertices, in a variety of ways, and study minimum such sets and their cardinality. A natural way to introduce and motivate our subject is to view it as a real-world problem. In its most elementary form, we consider the problem of reducing waste of time in transport planning. Our goal here is to first describe the previous definitions and the results, and then to provide an overview of the flows ideas in their articles. The final outcome of this article is twofold: (i) Solving the problem of reducing waste of time in transport planning at static state; (ii) Solving and having a gentle discussions on problem of reducing waste of time in transport planning at dynamic state. Finally, we discuss the results concerning holding domination that are independent of fuzzy graphs. We close with a list of currently open problems related to this subject. Most of our exposition assumes only familiarity with basic linear algebra, polynomials, fuzzy graph theory and graph theory.

Weight thresholding (WT) is a method intended to decrease the number of links within weighted networks that may otherwise be excessively dense for network science applications. WT aims to remove links to simplify the networks by holding most of the features of the original network. Here, we test the robustness and the efficacy of the node attack strategies on real-world networks subjected to WT that remove links of higher weight (strong links). We measure the network robustness along node removal with the largest connected component (LCC). We find that the real-world networks under study are generally stable in terms of robustness when subjected to WT. Nonetheless, WT by strong link removal changes the efficacy of the attack strategies and the rank of node centralities. Also, WT by strong link removal may trigger a greater change in node centrality rank than WT by removing weak links. Network science research finding important/influential nodes in the network has to consider that simplifying the network with WT methodologies may change the node centrality.

We show that the compound samarium hexaboride is a strong topological insulator using the eigenvalues of the space inversion operator in the low-energy limit of the periodic Anderson model. Additionally, we assume the presence of the ferromagnetic exchange interaction (M). A Dirac cone like feature in the surface state energy spectra is observed for M equals zero in a certain parameter range. For M not equal to zero, there is no Kramers degeneracy. We have been able to show that this phase corresponds to the quantum anomalous Hall state by calculating Berry curvature and the Chern number. Using Floquet theory, we further show that the access to a novel state with broken time reversal symmetry is possible due to the normal incidence of circularly polarized optical field on the surface of the compound despite M being absent.

Chan and colleagues in their paper titled “Human origins in a southern African palaeo-wetland and first migrations” (https://www.nature.com/articles/s41586-019-1714-1) report 198 novel whole mitochondrial DNA (mtDNA) sequences and infer that ‘anatomically modern humans’ originated in the Makgadikgadi–Okavango palaeo-wetland of southern Africa around 200 thousand years ago. This claim relies on weakly informative data. In addition to flawed logic and questionable assumptions, the authors surprisingly disregard recent evidence and debate on human origins in Africa. As a result, the emphatic and high profile conclusions of the paper are unjustified.

Current study aims to evaluate the possibilities to increase part strength by optimizing the FFF process parameters. Five different CAD models of parts with same coupling dimensions but different shape inherited from a recent study were converted into test samples with Ultimaker 2 3D printer. The main measure of success was the sample strength, defined as the load at which the first crack in the stressed area of the part appeared. Three different modifications to the FFF process with verified positive effect on interlayer bonding were applied. First modification included raising the extrusion temperature and disabling printed part cooling. Second modification consisted in reduction of the layer thickness. Third modification combined the effects of the first and the second ones. For four out of five shapes tested applied process modifications resulted in significant strengthening of the part. The shape that exhibited the best results was subject to further research by creating special printing mode. The mode included fine-tuning of three technological parameters on different stages of the part fabrication. As result it was possible to increase the part strength by 108% only by tuning printing parameters of the best shape designed with increasing its weight by 8%.

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10^-5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10^-4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.

it has been just over three years since SARS-CoV-2 viral infection was first known as causing severe acute and highly transmissible respiratory syndrome coronavirus. During one of the worst global pandemics of the last century, caused by the COVID-19 disease, under the persistent immune pressure exerted by the newest vaccines, the SARS-CoV-2 virus is fastly mutating and becoming less severe, but more contagious. On the other hand, some studies [1,2,3] indicate that the elderly COVID-19 patients or those who have reported a virulent episode of this infection, experience some long-lasting neurological complications, including encephalopathy, encephalitis, cerebrovascular disease, Parkinson’s disease (PD), Alzheimer’s disease (AD) and prion disease (PrD). So, there are several recent reports of patients [4,5] developing PrD following the SARS-CoV-2 infection, but, to the best of our knowledge, this is the first case reported in Italy on an association of the PRNP E200K somatic mutation with gCJD. The rising global prevalence neurodegenerative complications following COVID-19 disease adds urgency to the study of this potential relationship.