This paper describes a new approach that can be used to determine the mechanical properties of unknown materials and complex material systems. The approach uses inverse finite element modelling (FEM) accompanied with a designed algorithm to obtain the modulus of elasticity, yield stress and strain hardening material constants of an isotropic hardening material model, as well as the material constants of the Drucker-Prager material model (modulus of elasticity, cap yield stress and angle of friction). The algorithm automatically feeds the input material properties data to finite element software and automatically runs simulations to establish a convergence between the numerical loading-unloading curve and the target data obtained from continuous indentation tests using common indenter geometries. A further module was developed to optimise convergence using an inverse FEM analysis interfaced with a non-linear MATLAB algorithm. A sensitivity analysis determined that the dual Spherical and Berkovich (S&B) approach delivered better results than other dual indentation methods such as Berkovich and Vickers (B&V) and Vickers and Spherical (V&S). It was found that better convergence values can be achieved despite a large variation in the starting parameter values and / or material constitutive model and such behaviour reflects the uniqueness of the dual S&B indentation in predicting complex material systems. The study has shown that a robust optimization method based on a non-linear least-squares curve fitting function (LSQNONLIN) within MATLAB and ABAQUS can be used to accurately predict a unique set of elastic plastic material properties and Drucker-Prager material properties. This is of benefit to the scientific investigation of properties of new materials or obtaining the material properties at different location of a part which might be not be similar due to manufacturing processes (e.g. different heating and cooling rates at different locations).

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

We are in a new chapter of crop and livestock improvement with the emergence of genome editing. This latest generation of molecular tools can be used to make targeted changes in a genome including insertions, deletions, and mutations. With new advances comes new risks for unintended changes and impacts, thus the need for appropriate risk assessment for product development and to inform regulatory measures. Though CRISPR/Cas has arisen as the predominant technology, there are multiple types of genome editing tools each with pros and cons depending on the organism and desired outcome. Furthermore, each editing tool differs in specificity as they may edit non-intended sites, referred to as off-target edits. The consensus of the agricultural editing community is to avoid off-target editing through design and detection, instead of determining whether off-target editing in each case is detrimental. The design of a targeting component, the tool chosen, and the identification of the edit(s) made are the critical factors in avoiding off-target edits and confirming intended edits in final products that are released commercially. The limited amount of head-to-head comparisons of genome editing tools in diverse crops and livestock make it difficult to develop broad conclusions and best practices, which is further compounded by the diversity of techniques, targets, and processes. Developers and breeders should consult the literature and test as needed to determine which editing technology will be the most effective for their purposes, especially as more tools with altered efficiency and specificity become available. Yet, the lack of off-target edits in studies that employed careful design of targeting components followed by wide testing for on- and off-target edits bodes well for the use of genome editing with proper precautions of target selection and screening.

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Although many small molecules have been proposed as inhibitors of amyloid formation, few have been successful in clinical trials. Amyloid formation is complex and several individual steps could be targeted by small molecules. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light chain dimers, the precursor proteins for AL amyloidosis are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidogenesis.

The issue of workplace toxicity constitutes a major problem for employers, employees and society at large. Toxicity in a workplace context relates to damaging behaviours perpetrated by individuals and organisations that netatively impact on the health and wellbeing of others. Workplace toxicty is habitually associated with activities such as bullying, harrassment, unethical and even illegal acts. In this article, today’s workplace is likenened to a cage where ambition and greed drive people to engage in toxic behaviour to fight for whatever scarce rewards are on offer. Set against a backdrop of continuous demands on employees in a era of constant change and challenge, leadership practice in the 21st century is understandably seeped in complexity. Whilst conditions of scarcity are in fact constructed by employers in today’s lean environments, workplace toxicity has significant implications for organisational leaders in terms of work place disputes, absenteeism and litigation etc. Twentieth century hierarchial and autocratic leadership models are now deemed to be both obsolete and wholly inadedgate to inform leadership practice in the knowledge era. This conceptual article looks at the efficacy of complexity leadership theory (CLT) in empowering today’s leader to better understand and address 21st century workplace toxicity.

There have been several developments in the field of nanopore biosensor development and sequencing applications that address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making these platforms a mainstay in contemporary research labs. Equipped with the ability to provide long and short-read sequencing information with quick turn-around times and simple sample preparation, nanopore sequencers are quickly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We conclude with examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.

The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.

In the wake of the 2008 financial crisis, the Financial Stability Board (FSB) and the Basel Committee on Banking Supervision (BCBS) created a list of Systemically Important Financial Institutions (SIFIs) with the intention of determining which financial institutions were important enough to the global market that their failure would result in systemic collapse. In this work we create a model that modifies the BCBS's five indicators of size, interconnectedness, cross-jurisdictional activities, complexity, and substitutability and applies these measures of systemic stress to governments. The original application of the model is to track the systemic interdependence of the Eurozone, with particular emphasis on the case of Greece. We anticipate this model can be used in regional fiscal situations beyond the Eurozone.

Background: Student-specific stress is pervasive and impairs health and attainment. Experimentally induced self-affirmation can reduce stress, but little is known about the mechanisms underlying this effect, and the role of individual differences. The present study explores the relationship between spontaneous self-affirmation, student-specific stress, and overlapping constructs of positive self-regard during the COVID-19 pandemic. Methods: The study investigated inter-relationships between spontaneous self-affirmation, student-specific perceived stress and potential covariates including self-esteem, self-integrity and habitual positive self-thought. University students (N = 151) aged 18 to 50 responded to an online questionnaire including the Spontaneous Self-Affirmation Measure, College Student Stress Scale, Rosenberg Self-Esteem Scale, Habitual Index of Positive Thinking and Self-Integrity Scale. Results: Unexpectedly, regression analysis revealed that spontaneous self-affirmation was a positive predictor of student-specific stress, seemingly driven by relational affirmations. Self-esteem and habitual self-thought were negative predictors of student-specific stress, whilst self-integrity was not a predictor. Conclusions: Habitual positive self-thought may offer a sustainable solution to student-specific stress, but spontaneous self-affirmation does not. A reduction in defensive responses, elicitation of negative emotions, or use of conditional relationships in relational affirmation

A chiral sodium glicerophosphate is successfully exploited as catalyst in Michael addition of methyl malonate to a number of chalcones. The reactions furnished the target adducts in satisfactory yields and good enantiomeric excesses. A tentative of computational study is presented aiming to understand the reaction mechanism.

E2F4 was initially described as a transcription factor with a key function in the regulation of cell quiescence. Nevertheless, a number of recent studies have established that E2F4 can also play a relevant role in cell and tissue homeostasis as well as tissue regeneration. For these non-canonical functions, E2F4 can also act in the cytoplasm, where it is able to interact with many homeostatic and synaptic regulators. Since E2F4 is expressed in the nervous system, it may fulfill a crucial role in brain function and homeostasis, being a promising multifactorial target for neurodegenerative diseases and brain aging. The regulation of E2F4 is complex as it can be chemically modified through acetylation, from which we present evidence in the brain, as well as methylation, and phosphorylation. The phosphorylation of E2F4 within a conserved threonine motif induces cell cycle re-entry in neurons, while a dominant negative form of E2F4 (E2F4DN), in which the conserved threonines have been substituted by alanines, has been shown to act as a multifactorial therapeutic agent for Alzheimer’s disease (AD). We have generated transgenic mice neuronally expressing E2F4DN. We have recently shown using this mouse strain that expression of E2F4DN in 5xFAD mice, a known murine model of AD, improved cognitive function, reduced neuronal tetraploidization, and induced a transcriptional program consistent with modulation of amyloid-beta (Abeta) peptide proteostasis and brain homeostasis recovery. 5xFAD/E2F4DN mice also showed reduced microgliosis and astrogliosis in both cerebral cortex and hippocampus at 3-6 months of age. Here we have analyzed the immune response in 1 year-old 5xFAD/E2F4DN mice, concluding that reduced microgliosis and astrogliosis is maintained at this late stage. In addition, the expression of E2F4DN also reduced age-associated microgliosis in wild-type mice, thus stressing its role as a brain homeostatic agent. We conclude that E2F4DN transgenic mice represent a promising tool for the evaluation of E2F4 as a therapeutic target in neuropathology and brain aging.

Deep learning techniques are increasingly being recognized as effective image classifiers. Aside from their successful performance in past studies, the accuracies have varied in complex environments in comparison with the popularly applied machine learning classifiers. This study seeks to explore the feasibility for using a U-Net deep learning architecture to classify bi-temporal high resolution county scale aerial images to determine the spatial extent and changes of land cover classes that directly or indirectly impact tidal marsh. The image set used in the analysis is a collection of a 1-m resolution collection of National Agriculture Imagery Program (NAIP) tiles from 2009 and 2019 covering Beaufort County, South Carolina. The U-net CNN classification results were compared with two machine learning classifiers, the Random Trees (RT) and the Support Vector Machine (SVM). The results revealed a significant accuracy advantage in using the U-Net classifier (92.4%) as opposed to the SVM (81.6%) and RT (75.7%) classifiers for overall accuracy. From the perspective of a GIS analyst or coastal manager, the U-Net classifier is now an easily accessible nad powerful tool for mapping large areas. Change detection analysis indicated little areal change on marsh extent, though increased land development throughout the county has the potential to negatively impact the health of the marshes. Future work should explore applying the constructed U-Net classifier to coastal environments in large geographic areas, while also implementing other data sources (e.g., LIDAR, multispectral data) to enhance classification accuracy.

This study highlighted the core and critical tenets that constitute culturally responsive science assessments (CRSciA) for K-12 education and aligned them with the capabilities of generative AI (GenAI). The tenets were identified based on their dominance in the literature, including Indigenous Language, Race and Ethnicity, Religious Beliefs, Family and Community, and Indigenous Knowledge. These tenets were instrumental in developing the GenAI-CRSciA framework and the subsequent prompts to generate CRSciAs aligned with the Next Generation Science Standards (NGSS) while comparing it with standard prompt strategies. The results showed that the GenAI-CRSciA prompting approach outperformed normal prompting strategies in terms of generating CRSciAs, proving its effectiveness in addressing the ongoing challenges in science assessments. Even though the GenAI-CRSciA framework presented assessments that cover a range of the cultural backgrounds, it presents potential challenges such as compromising curricula core competencies and overgeneralization of students’ backgrounds; overlooking subcultural variations within a country or region, for example differences between urban and rural students, or between different ethnic or linguistic groups within the same nation, which can lead to bias and less effective CRSciA outputs. To address this, we recommend that teachers provide comprehensive and specific background information about their students when using the GenAI-CRSciA prompting, ensuring that the generated content is truly reflective of the students’ unique cultural contexts. In larger class settings, teachers could implement comprehensive local data indexing, where detailed student background information is uploaded and retrievable for use in crafting more personalized CRSciAs. We strongly recommend educators to make conscious efforts to validate the generated assessments with input from human experts, including community or family, educators, and even students who are knowledgeable about the cultural nuances. We also suggest continuous professional development would be necessary to enhance teachers’ understanding of the cultural tenets.

This is a study on fractals existing in music. The application case is the composition DIAPHONIES of Michael Paouris. Sliding-window fractal analysis indicate areas of continuous fractality dipped in non-fractal areas of possibly deterministic and stochastic nature. Diverging cases of pronounced non-fractal areas are addressed and also areas of mixed fractality and non-fractality. Many segments exhibit persistency-P (2

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

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives gave significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This means an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

Graph query languages such as Cypher are widely adopted to match and retrieve data in a graph representation, due to their ability of retrieving and transforming information. Despite the most natural way to match and transform information is through rewriting rules, those are scarcely or partially adopted in graph query languages. Their inability of doing so has a major impact on the subsequent way the information is structured, as it might then appear more natural to provide major constraint over the data representation so to consequently constraint the way the information should be represented. On the other hand, recent works are starting to move towards an opposite direction, as the provision of a truly general semistructured model (GSM) allows to both represent all the available data formats (Network-Based, Relational, and Semistructured) as well as support an holistic query language expressing all major queries in such languages. In this paper, we show that the usage of GSM enables the definition of a general rewriting mechanism which can be expressed in current graph query languages only at the cost of adhering the query to the specificity of the underlying data representation. We formalise the proposed query language in terms graph rewriting mechanisms described as a set of production rules $L\to R$ while providing restriction to the characterization of L, while extending it to support structural graph nesting operations, useful to aggregate similar information around an entry-point of interest. We discuss how GSM, by fully supporting index-based data representation, allows for a better physical model implementation leveraging the benefits of columnar database storages. Preliminary benchmarks shows the scalability of this proposed implementation in comparison with state-of-the-art implementations.

The range of rating instruments in depression measurement and the depth of their analytical relevance constitutes a major development in this psychiatric and psychotherapeutic field of mental health. Though the competition is acute amongst these various instruments, the results for the public have been outstandingly positive. A depression rating scale is essentially a psychiatric measuring instrument utilized in the identification and ranking of depression severity within the patient. The scale provides the practitioner, psychiatrist or psychotherapist, with sufficient information to assess the severity of the depression plotted on the scale. Not used as a “diagnostic tool” itself, nevertheless, the depression rating scale does function as an effective device for designating and assigning a behavioral score which may, then, be used in establishing the severity of depression of value in the designation of a diagnosis and treatment formula. In this paper, we will take a close look at the leading depression rating scales and briefly summarize their scope of assessment value in rating depression.

This paper extends our seminal paper on KnoBAB for efficient Conformance Checking computations performed on top of a customised relational model. After defining our proposed temporal algebra for temporal queries (xtLTLf ), we show that this can express existing temporal languages over finite and non-empty traces such as LTLf . This paper also proposes a parallelisation strategy for such queries thus reducing conformance checking into an embarrassingly parallel problem leading to super-linear speed up. This paper also presents how a single xtLTLf operator (or even entire sub-expressions) might be efficiently implemented via different algorithms thus paving the way to future algorithmic improvements. Finally, our benchmarks remark that our proposed implementation of xtLTLf (KnoBAB) outperforms state-of-the-art conformance checking software running on LTLf logic, be it data or dateless.

The structural performance of reinforced concrete relies heavily on the bond between reinforcement and concrete. In nonlinear finite element analyses, bond is either modelled by merged, also called perfect bond, or coincident with slip, also called bond-slip, approaches. Here, the performance of these two approaches for the modelling of failure of reinforced concrete was investigated using a damage-plasticity constitutive model in LS-DYNA. Firstly, the influence of element size on the response of tension-stiffening analyses with the two modelling approaches was investigated. Then, the results of the two approaches were compared for plain and fibre reinforced tension stiffening and a drop weight impact test. It was shown that only the coincident with slip approach provided mesh insensitive results. However, both approaches were capable of reproducing the overall response of the experiments in the form of load and displacements satisfactorily for the meshes used.

Alternative food sources are essential in both low-resource settings or during emergencies like abrupt sunlight reduction scenarios. Seaweed presents a promising option but requires investigation into the viability of unconventionally sourced ropes for harvesting. As such, a low-cost reliable method to test the tensile strength of rope is needed to validate alternative materials for use in harvesting seaweed. Unfortunately, commercial rope testing jigs alone range in price from several thousand to tens of thousands of dollars. To fill this need, this article reports on an open-source design for tensile strength rope testing hardware. The hardware design focuses on using readily available parts that can be both sourced from a hardware store and manufactured with simple tools to provide for the greatest geographic accessibility. The jig design, which can be fabricated for CAD$20 is two to three orders of magnitude less expensive than commercially available solutions. The jig was built and tested using a case study example investigating denim materials (of 1 5/8”, 3 1/4", 4 7/8”, 6 1/2", and 8 1/8” widths) as a potential alternative rope material for seaweed farming. Denim demonstrated strength up to 1.65kN for the widest sample and the jig demonstrated sufficient strength and stiffness for operating at forces below 4kN. The results are discussed and areas for future improvements are outlined to adapt the device to other circumstances and increase the strength of materials that can be tested.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield the Michael type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the reaction. The study of the variation of the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

Coronavirus Disease 2019 (COVID-19) has become a global health threat and has placed an extraordinary demand for healthcare workers around the world. In this study, we aim to examine the prevalence of burnout, its associating factors, and experience among Malaysian healthcare workers through an embedded mixed-method study design. We found that more than half of Malaysian health care workers in this sample experienced burnout. Direct involvement in COVID-19 screening or treatment, having a medical condition, and less psychological support in the workplace emerged to be the significant factors for personal-, work- and patient-related burnout. Participants described workload, uncertainties from the pandemic, challenged work-family balance and stretched workplace relationships as the sources of burnout. Exhaustion appeared to be the major symptom and many participants utilized problem-focused coping to deal with the adversities experienced during the pandemic. Participants reported physical, occupational, psychological, and social-related negative impacts emanating from burnout. As the pandemic trajectory is yet unknown, the findings provide early insight and guidance for possible interventions.

Abstract: Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome and diet influence the diversity, abundance and function of the early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD) and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during the early life stage. In fact, it is critical to explore the role of the human gut microbiota in early life. In this review, we summarize the general understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the relationship between the gut microbiota composition and their metabolites, and immune functions, which could significantly influence long-term health and disease. We then review known pathophysiological interactions of the early gut microbiome with a number of well characterized diseases and pose potential etiological mechanisms.

Development of accelerometer-based lameness (mobility) detection has focused on cow behaviors such as lying and walking. Several studies, usually small, have reported levels of accuracy up to 91%. However, there has been limited independent replication of these results. In this study, behavior measures previously identified as being associated with lameness such as lying bouts and walking time are examined in relation to mobility score. On a research farm and a commercial farm, four trials were completed with 65 grazing cows. The cows had differing mobility scores ranging from perfect mobility to impaired mobility. Behavior was monitored using leg worn accelerometers. In general, behavior and mobility associations identified in previous studies were not found. Behavior monitoring with accelerometers as a basis to classify impaired mobility in pasture-based contexts thus remains challenging.

An efficient stereoselective three-component reaction for the synthesis of spiro[4H-chromene-3,3’-oxindole] derivatives was realized through an organocatalyzed cascade Knoevenagel/Michael/cyclization reaction using a quinidine-derived squaramide as the catalyst. Under the optimized conditions, the reactions of isatins, malononitrile, and sesamol yield the desired spirooxindoles in good yields (75–87%) and moderate to high ee values (up to 90% ee). Two pairs of selected enantiomers were subjected to evaluate their antiproliferative activities on three types of human cancer cell lines using the MTT assay. The results indicated that stereoselectivity and electrical effect showed significant impact on activity. Enanotiomer R-3f exhibited optimal cytotoxic activity against U2OS cell line, which was close to the inhibitory activity of positive control, Adriamycin.

This paper introduces an Agent-Based Model (ABM) for investigating the dynamics of the Internet of Things (IoT) ecosystem, specifically focusing on dynamic coalition formation among IoT Service Providers (SPs). Extending our prior work in 5G network modeling, the ABM captures intricate interactions among device, network operator, SP, and customer agents, offering a versatile framework for studying IoT ecosystem dynamics. The simulation portrays the adaptive nature of collaborations, providing insights into the role of dynamic coalition formation in shaping the collaborative landscape of IoT.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, as well as present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have been successful mostly in detecting the presence of these animals in field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored this matter by sampling lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months, attempting to detect differences in eDNA accumulation using a qPCR assay. Only one sample of the highest density pond readily amplified eDNA. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present a “shedding hypothesis”–the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms–as a potential challenge for turtle eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

The Antarctic photopsychrophile, Chlamydomonas priscuii UWO241 is adapted to extreme environmental conditions, including permanent low temperatures, high salt and shade. During long-term exposure to this extreme habitat, UWO241 appears to have lost several short-term mechanisms in favor of constitutive protection against environmental stress. This study investigated physiological and growth responses of UWO241 to high light conditions, evaluating the impacts of long-term acclimation to high light, low temperature, and high salinity on its ability to manage short-term photoinhibition. We found that UWO241 significantly increased its growth rate and photosynthetic activity at growth irradiances far exceeding native light conditions. Furthermore, UWO241 exhibited robust protection against short-term photoinhibition, particularly in photosystem I. Last, pre-acclimation to high light or low temperatures, but not high salinity, enhanced photoinhibition tolerance. These findings extend our understanding for stress tolerance in extremophilic algae. In the past 2 decades climate change-related increasing glacial stream flow has perturbed long-term stable conditions: in the form of has been associated with lake level rise, thinning of ice covers, and expansion of ice-free perimeters. Our findings have implications on phytoplankton survival and response to change scenarios in the light-limited environment of Antarctic ice-covered lakes.

From ancient times to the present, mankind has struggled with infectious diseases that pose a serious threat to people's lives, COVID-19 pandemic has given a huge impact to the human society, which has triggered a lot of thinking. In the future, humans may encounter various unexpected disasters or awful events, therefore, should learn from COVID-19 pandemic incident that need to pay special attention to the emergency supply of manpower and materials, whether a major disaster or not. That is emergency medical management is very important in the event of a sudden outbreak. What’s more, the preparation and scheduling of emergency medical supplies well safeguards people’s lives, health, and safety. However, owing to the sudden onset of an epidemic and given the population trends, the scale of infections and the demand for supplies in the epidemic area are uncertain. The main influencing factors and mechanisms of emergency material demand under the development trend of emergencies can be studied, and materials can be allocated efficiently and effectively, so as to minimize damage. In this study, it improves upon the dynamics model of infectious diseases firstly, by establishing a demand forecasting model for a certain area, taking the Hubei province as an example. Furthermore, this dynamics model is used to predict demand for emergency supplies, such as masks, respirators, and food in the area where the disaster will occur. Experimental results demonstrate the effectiveness and reliability of this prediction model, which supports for the development of emergency material management systems, ulterior, this study provides a framework for the distribution of emergency supplies and a guideline for relief efforts.

Charge-dipole interactions are very common interactions among atoms and molecules, especially materials that can emit light or contain free charges. The second-order charge-dipole interactions, proportional to $\frac{1}{R^4}$, are stronger than the second-order dipole-dipole interactions or van der Waals interactions, proportional to $\frac{1}{R^6}$, at longer distances. In reality, there is more than one atom or charge; therefore, we focus on few-body charge-dipole interactions, such as charge-dipole-dipole interactions. Laser cooling and trapping allow us to study such interactions with much higher precision. In this article, charge-dipole interactions will be investigated in ultracold gases. To increase the interaction strength, we excite the ultracold atoms to highly excited states, Rydberg states. Here, we treat one Rydberg atom as a dipole, the excited electron and the ion core are the two poles of an electric dipole. Specifically, we study charge-atom interactions in ultracold Rydberg gases.

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte Serum-Free Medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12) and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred as DFK. The toxicological effects of electronic cigarette liquids (E-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12 or DFK and cellular morphology, growth, wound healing and gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after E-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24-hours post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, E-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

The philosophy of testing statistical hypothesis is a natural consequence and functional extension of mathematical analysis of Probability. Along with the concept of recurrence when applied to random sequences and functions, it leads to the analysis of a priori and posterior which implies testing statistical hypothesis. Testing statistical hypothesis also involves algebraic, functional and dimensional considerations, which are found in the works of Laplace. Aspects of mathematical analysis such as universality of solutions, Laws of Large Numbers, Entropy, Information, and various functional dependencies are the main factors explained in the five properties that lead to implication of testing statistical hypothesis. Various interesting examples with modern scientific significance from genetics, astrophysics, and other areas give methodological access to answers of different problems and phenomena which are involved in the logic of testing statistical hypothesis.

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

This study introduces a low-cost solution provided by a specialized source measure unit (SMU), offering an alternative to conventional source meter units. Through precise IV curve measurements for graphene-channel FETs, the SMU demonstrates its capability in accurately characterizing these devices with minimal noise and high accuracy. This cost-effective solution presents a promising avenue for researchers and developers seeking reliable tools for sensor development and characterization, providing valuable insights into the behavior of graphene-channel FETs and the effect of surface illumination without the need for expensive equipment. Additionally, the SMU was validated with known passive and active components, along with probe station integration for microscale connection, ensuring its effectiveness in capturing accurate measurements. The SMU’s focus on collecting IV curves, coupled with its ability to identify device defects, such as Schottky junctions, contributes to its utility in quality testing for semiconductor devices. Its low-cost nature makes it accessible for various research endeavors, enabling efficient data collection and analysis for graphene-based sensor applications.

Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-B transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators. To better understand the pleiotropic regulatory function of BRD4, we examine the BRD4 interactome and identify how RSV infection dynamically alters it. To accomplish these goals, we leverage native immunoprecipitation and Parallel Accumulation – Serial Fragmentation (PASEF) mass spectrometry to examine BRD4 complexes isolated from human alveolar epithelial cells in the absence or presence of RSV infection. In addition, we explore the role of BRD4’s acetyl-lysine binding bromodomains in mediating these interactions by using a highly selective competitive bromodomain inhibitor. We identify 101 proteins that are significantly enriched in the BRD4 complex and are responsive to both RSV-infection and BRD4 inhibition. These proteins are highly enriched in transcription factors and transcriptional coactivators. Among them, we identify members of the AP1 transcription factor complex, a complex important in innate signaling and cell stress responses. We independently confirm the BRD4/AP1 interaction in primary human small airway epithelial cells. We conclude that BRD4 recruits multiple transcription factors during RSV infection in a manner dependent on acetyl-lysine binding domain interactions. This data suggests that BRD4 recruits transcription factors to target its RNA processing complex to regulate gene expression in innate immunity and inflammation.

Background: This is a comparative analysis of upgrade to cardiac resynchronisation therapy (CRT) of an existing pacemaker implanted for bradyarrhythmia or an implantable cardioverter defibrillator (ICD). International guidelines recommend an upgrade to CRT for both groups based on the same criteria; this may lead to a hypothesis of whether we are under-treating a population that would otherwise benefit more from a CRT than the other. Methods: So far, this is the largest multicentre retrospective study that includes in total, 151 (93 upgrades to CRT-P and 58 upgrades to CRT-D) participants who had an upgrade to a CRT device between January 2010 and January 2020. Clinical and echocardiographic parameters were analysed both, before and after an upgrade to CRT. Results: EF was greater in patients with PPM, both before and after upgrade. Moreover, the post upgrade increase in EF was significantly greater in patients with PPM. Patients with ICD have, on average, an NYHA class ranking greater than PPM patients, both before and after upgrade. Conclusions: These data show that the PPM group patients have a greater response to upgrade to CRT compared to those from the ICD group. It also demonstrates that patients with non-ischaemic cardiomyopathy are better responders compared to those with ischaemic aetiology.

In two sequential replicates (n=90 and n=96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p&lt;0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin. A similar observed effect was not statistically significant (P &gt; 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. E. faecium isolates were whole-genome sequenced, which yielded sequence types (ST), resistance genes and phylogeny. Samples of the DFM were sequenced and found to contain E. faecium ST296, which was not present on Day 0 of either replicate. This DFM sequence type was found in fecal samples after Day 0, the majority of which were isolated from cattle in one of the DFM-fed pens. Increased prevalence of ST296 occurred with a concomitant decrease in ST240; of importance, the latter typically harbored both ermB and tet(M) genes.

Pronounced differences exist in the biodiversity and structure of coral reef assemblages with increasing distance from shore, which may be expected given marked cross-shelf gradients in environmental conditions. Cross-shelf variation in the abundance of coral reef organisms is likely to be caused, at least in part, by differences in demography (e.g., growth and survival), though this has rarely been tested. This study quantified growth of three distinct coral taxa (Acropora nasuta, Pocillopora spp., and Stylophora pistillata) at 6 sites on Australia’s Great Barrier Reef (GBR), encompassing inshore, mid-shelf and outer-shelf reefs. Replicate colonies (up to 15 colonies per species, per reef) were stained using Alizarin red in December 2015 and retrieved 1-year later to quantify linear extension on replicate branches for each colony. Annual linear extension varied within and among coral taxa, with pronounced differences among reefs. For A. nausta. and S. pistillata, growth rates were highest at Orpheus Island, which is an inner shelf reef. However, inter-reef differences in coral growth were not explained by shelf position. Based on differences in skeletal density, which did vary according to shelf position, branching corals at the inshore sites may actually have higher rates of calcification compared to conspecifics on mid- and outer-shelf reefs. This study shows that growth of branching corals is not lower at inshore sites (and perhaps even higher) compared to sites at mid-shelf and outer reefs, despite generally higher levels of sedimentation and turbidity.

In vitro cancer cell cytotoxicity (IC50 values) of (E)-3-(4’-methylbenzylidene)-4-chromanone (IIIb) showed &gt;50.0 decreases in comparison to those of the respective tetralone derivative (IIIc). On the other hand, such a decrease was not observed in the analogous 4-OCH3 (IIc and IIIc) derivatives. Since the compounds can be considered cyclic chalcone analogs, kinetics and diastereoselectivity of non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of IIIb and IIIc were investigated to assess the possible role of thiol-reactivity in the increased cytotoxicity of IIIb. Reactivity of the compounds and stereochemical outcome of the reactions were evaluated using high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Molecular modeling calculations were performed to rationalize the observed differences in the thiol-reactivities of the chromanones (III) and the previously investigated tetralones (II). The results indicated possible role of spontaneous thiol-reactivity of compounds III in their recorded biological effects.

BK polyomavirus (BKPyV) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein do not propagate to wild-type levels and fail to release from host cells. Despite this, loss of agnoprotein does not impair virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-SNAP is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

We address the problem of finding a unique graph embedding that best describes a graph's "topology". This issue is of particular interest in the chemistry of materials. Graphs that admit a tiling in 3-dimensional Euclidean space are termed tessellate, those that do not decussate. We give examples of decussate and tessellate graphs that are finite and 3-periodic. We conjecture that a graph has at most one tessellate embedding. We give reasons for considering this the default "topology" of periodic graphs.

Computational models of homologous protein groups are essential in sequence bioinformatics. Due to the diversity and rapid evolution of viruses, the grouping of protein sequences from virus genomes is particularly challenging. The low sequence similarities of homologous genes in viruses require specific approaches for sequence- and structure-based clustering. Furthermore, the annotation of virus genomes in public databases is not as consistent and up-to-date as for many cellular genomes. To tackle these problems, we have developed VOGDB, a database of Virus Orthologous Groups. VOGDB is a multi-layer database that progressively groups viral genes into groups connected by increasingly remote homology. The first layer is based on pair-wise sequence similarities, the second layer is based on the sequence profile alignments and the third layer uses predicted protein structures to find the most remote homology. VOGDB groups allow for more sensitive homology searches of novel genes and increase the chance of predicting annotations or inferring phylogeny. VOGDB uses all virus genomes from RefSeq and partially re-annotates them. VOGDB is updated with every RefSeq release. The unique feature of VOGDB is inclusion of both prokaryotic and eukaryotic viruses in the same clustering process which makes it possible to explore old evolutionary relationships of the two groups. VOGDB is freely available at https://vogdb.org under the CC BY 4.0 license.

Starting from acid chlorides, alkynes, tryptamines, and acroyl chloride, 21 densely substituted tetrahydro-beta-carbolines are prepared in a four-component one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones is optimized in the presence of ytterbium triflate. Moreover, apart from acroyl chloride, all reactants can be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationali-zation, the concluding aza-anellation was investigated by DFT calculations on potential inter-mediates and corresponding activation energies, revealing that the aza-anellation rather pro-ceeds via ene-reaction than via electrocyclization.

Class attendance in institutions of higher learning plays a major role in the success of students and as such putting in measures to curb absenteeism of students would go a long way to help improve their grades. This research sought to design a ‘Bring Your Own Device’ System which will be very suitable for the post-COVID era as well as the fast-growing university community. The research results in a mobile-based attendance infrastructure used by students to prove their presence for class sessions. Flutter, a Software Development Kit (SDK) was used to program the mobile platform and Firebase was used for both the authentication and database. This system also comes in as an improvement on most existing systems as it functions on both Android and iOS. After the testing phase, the models achieved high accuracy and the proposed design has proven to have great potential. This solution stands beyond a research model as a ready-to-use platform.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the new Coronavirus disease (COVID-19). The symptoms range from mild to severe with a higher incidence of severe cases seen in patients with risk factors such as older age and comorbidities. COVID-19 is mainly spread through the inhalation of respiratory droplets from coughing or sneezing or via contact with droplet-contaminated surfaces. Paramedics should be aware that some aerosol generating procedures (AGPs) may put them at a higher risk of contracting the virus via possible airborne transmission. The use of remote triage clinical assessment is likely to increase as a result of the pandemic. There is no curative drug treatment for the virus and some medications may exacerbate its effects or make patients more susceptible to it. Paramedics should accept that feeling stressed by the pandemic is a natural response. Official guidelines and advice are evolving continually as the evidence on SARS-CoV-2 and COVID-19 grows. Paramedics should keep up to date with the latest clinical guidance from their employers.

The USDA-FSIS considers mechanically-tenderized beef as ‘non-intact’ and a food safety concern because of the potential for translocation of surface E. coli O157:H7 into the interior of the meat that may be cooked ‘rare or medium-rare’ and consumed. We evaluated 14 potential spray interventions on E. coli O157:H7-inoculated lean beef wafers (~10⁶ CFU/cm² , n=80) passing through a spray system (18 sec dwell time, ~40 PSI) integrated into the front end of a Ross TC-700MC tenderizer. Inoculated and processed beef wafers were stomached with D/E neutralizing broth and plated immediately, or were held in refrigerated storage for 1-, 7-, or 14 days prior to microbial plating. Seven antimicrobials that showed better performance in preliminary screening on beef wafers were selected for further testing on beef subprimals in conjunction with blade tenderization. Boneless top sirloin beef subprimals were inoculated at ~2 x 10⁴ CFU/cm² with a four-strain cocktail of Escherichia coli O157:H7 and passed once, lean side up, through an integrated spray system and blade tenderizer. Core samples obtained from each subprimal were examined for the presence/absence of E. coli O157:H7. Absence of E coli O157:H7 translocated into core samples correlated with the ability of the antimicrobials to reduce bacterial levels on the surface of beef prior to blade tenderization.

Semiconductor technology is the backbone of modern innovations, propelling technological advancements in industries such as electronics, renewable energy, telecommunications, and health-related fields. This review expatiates the fundamental properties and working principles of semiconductor materials that determine device performances, while also tracing the historical trajectory of these technologies from the inception of the transistor to pioneering developments, such as tunnel gate transistors and 2D materials like graphene. Specific challenges such as material constraints, manufacturing complexities, and environmental impacts are highlighted. In response to such challenges, measures for the improvement of sustainability, energy saving, and waste minimization in production are discussed. The research also responds to the extended effects of globalization, including the disruptions like COVID-19 pandemic, on supply chain and emphasizes on the importance of developing resilient production frameworks for future growth. Additionally, this work highlights emerging technologies, including quantum computing, artificial intelligence integration, and nanotechnology, which are poised to redefine data processing and storage. The research vindicates the necessity of innovation and sustainability as the key motivators for enhancing the capabilities of semiconductors and global technology.

High temperature Ni-superalloys are limited by reliance on critical elements and complex processing steps. High entropy alloys (HEAs) have demonstrated stable single/dual phase microstructures with strong ordering tendencies. A dual phase (FCC+BCC) Al0.5Co0.5CrFeNi1.5Ti0.25 alloy (developed using CALPHAD) was tested for room and high temperature compression behavior. The microstructure mainly comprises of coarse ordered FCC(L12) surrounding decomposed lamellae of ordered FCC(L12) and BCC(L21) phases, which coarsened upon annealing at high temperature (1100 °C) into a bi-continuous structure of disordered FCC+BCC(B2). Additionally, cold rollability of the cast alloy increased from &lt;5% to ~40% after annealing, with a corresponding softening observed in room temperature compression mainly due to disordering of FCC and BCC phases. Peak flow stresses of 793.45MPa, 535.12MPa, and 324.40MPa were achieved at 800oC, 900oC, and 1000oC respectively for the high temperature annealed alloy.

Influenza virus imprinting is now understood to significantly the influence immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year to subsequently build a complex influenza virus immune history but very little is known about how the imprinting strain influences vaccine responses. To investigate the imprinted host immune responses to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60 day recovery period was given to build immune memory, ferrets were immunized and the challenge at Day 123. Samples were collected throughout the time course and immunological assays were performed to investigate recall mechanisms. The preimmune-vaccinated ferrets did not experience significant disease during challenge while naïve-vaccinated ferrets had severe disease. Hemagglutination inhibition assays showed preimmune ferrets had a more robust antibody response post vaccination, increased virus neutralization activity. Virus specific immunoglobulins were of predominantly the IgG isotype suggesting B cell maturity and plasticity at vaccination. These results are important and should be considered for vaccine design.

Group IV alloys of GeSn have been extensively investigated as a competing material alternative in short-wave to mid-infrared photodetectors (PDs). The relatively large defect densities present in GeSn alloys are the major challenge in developing practical devices, owing to the low-temperature growth and lattice mismatch with Si or Ge substrates. In this paper, we comprehensively analyze the impact of defects on the performance of GeSn p-i-n homojunction PDs. We first present our theoretical models to calculate various contributing components of the dark current including minority carrier diffusion in p- and n-regions, carrier generation-recombination in the active intrinsic region, as well as the tunneling effect. We then analyze the effect of defect density in the GeSn active region on carrier mobilities, scattering times and the dark current. A higher defect density increases the dark current, resulting in reduction in detectivity of GeSn p-i-n PDs. In addition, at low Sn concentrations, defect-related dark current density is dominant, while the generation dark current becomes dominant at a higher Sn content. These results point to the importance of minimizing defect densities in the GeSn material growth and device processing, particularly for higher Sn compositions necessary to expand the cutoff wavelength to mid- and long-wave infrared regime. The study provides more of realistic expectations and guidelines for evaluating GeSn p-i-n PDs as a competitor to the III-V and II-VI-based infrared PDs currently on the commercial market.

Gonorrhea is a major global public health problem with emergence of multiple drug-resistant strains with no effective vaccine. This retrospective cohort study aimed to estimate the effectiveness of the New Zealand meningococcal B vaccine against gonorrhea associated hospitalization. The cohort consisted of individuals born 1984-1999 residing in New Zealand, therefore eligible for meningococcal B vaccination during 2004-2008. Administrative datasets of demographics, customs, hospitalization, education, income tax and immunization, were linked using the national Integrated Data Infrastructure. The primary outcome was hospitalization with a primary diagnosis of gonorrhea. Cox’s proportional hazards models were applied with a Firth correction for rare outcomes to generate estimates of hazard ratios. Vaccine effectiveness estimates were calculated as 1-Hazard Ratio expressed as percent. There were 1,143,897 eligible cohort members, with 135 missing information on gender, 16,245 missing ethnicity and/or 197,502 missing deprivation hence 935,496 were included in the analysis. After adjustment for gender, ethnicity and deprivation, vaccine effectiveness (MeNZB™) against hospitalization caused by gonorrhea was estimated to be 24% (95% CI 1-42%). In conclusion, vaccination with MeNZB™ significantly reduced the rate of hospitalization from gonorrhea. This supports prior research indicating possible cross protection of this vaccine against gonorrhea acquisition and disease in the outpatient setting.

Smart manufacturing encompasses a category of manufacturing that employs computer-integrated capabilities and technologies to enhance supply chain optimization, production efficiency, and recyclability. Yet limited studies have been conducted to optimize these prospects from the perspective of low resource countries where such innovative studies have not been adequately explored. This paper aims to examine the implications of smart manufacturing practices (Smart Procurement, Smart Supply Chain, Smart Production Planning and Control, Automation and Industrial Robot, and Supply Chain Configuration) on pro-environmental behaviour and develop a baseline moderated mediation model to explain the relationship between smart manufacturing and pro-environmental behaviour with a role of green dynamic capability, and environmental orientation. This study is anchored on quantitative research approach, deductive reasoning, and explanatory design. Cross – sectional survey data have been obtained from 382 manufacturing companies in Ghana. Our hypotheses have been tested using Structural Equation Modelling and SMART-PLS version 3.8.9. The study has revealed that smart manufacturing practices significantly and positively relate to pro-environmental behaviour. Moreover, green dynamic capability and environmental orientation moderate the relationship between smart manufacturing and pro-environmental behaviour. The implications of the study include the emergence of a baseline model to guide policymakers, practitioners, and academicians to explain the relationship between smart manufacturing and sustainable manufacturing in the context of developing countries. Again, the social implication of the study includes the realisation of decent job and economic growth, responsible consumption and production as well as actions taken to combat climate change.

This paper will discuss Data, Information, Knowledge, and Wisdom, which is commonly referred to as DIKW. The DIKW Pyramid Model that is often referenced in both academics and practitioner circles will be discussed and shown to be faulty on several levels, including. a lack of definitional agreement. A new DIKW framework will be proposed that focuses on what the DIKW elements do in the way humans think, not what they are by definition. Information as a replacement for wasted physical resources in goal-oriented tasks will be a central organizing point. The paper will move the DIKW discussion to the computer-based concept of Digital Twins (DTs) and its augmentation of how we can use DIKW to be more effective and efficient. This will especially be the case as we move to Intelligent Digital Twins (IDT) with Artificial Intelligence (AI).

By using a systems biological perspective and available literature on human social interaction, grouping, and cohesiveness, a new coherent model is proposed that integrates existing social integration and neurobiological research into a theoretical neurobiological framework of personality and social interaction. This model allows for the coherent analysis of complex social systems and interactions within them, and proposes a framework for estimating group cohesiveness and evaluating group structures in order to build and organize optimized social groups. This „Neurobiological-Associative“ model proposes two primary feedback loops, with environmental conditioning (learning) being sorted into an associative model that modulates interaction with the social environment, and which impacts the second feedback loop involving the individuals' neurobiological capacity. In this paper, the concept of neurobiological capacity is developed and based upon contemporary research on intelligence, personality, and social behavior with a focus on the oxytocin, serotonin, and dopamine systems. The basis of social exclusion and group structure is thus, expressed in the very most simple terms, neurobiological compatibility and risk assessment modulated by an internal associative model.

Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago. Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids (aldosterone, cortisol), and sex steroids (estrogen, progesterone, testosterone) also are young, with an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. Through gene duplication and divergence of the 3-ketosteroid receptor, receptors that respond to androgens, glucocorticoids, mineralocorticoids and progestins evolved in vertebrates. Thus, an ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, evolved in jawless vertebrates (cyclostomes: lampreys, hagfish). This was followed by evolution of an androgen receptor, distinct glucocorticoid and mineralocorticoid receptors and estrogen receptor-α and -β in cartilaginous fishes (gnathostomes: sharks). Further evolution of mineralocorticoid signaling occurred with the evolution of aldosterone synthase in lungfish, a forerunner of terrestrial vertebrates. Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The evolution of steroid receptors at key nodes in the evolution of vertebrates, in which steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for an important role for steroid receptors in the evolutionary success of vertebrates, considering that the human genome contains about 22,000 genes, which is not much larger than genomes of invertebrates, such as Caenorhabditis elegans (~18,000 genes) and Drosophila (~14,000 genes).

There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals, such as bisphenol A, and pesticides, such as DDT. These endocrine-disrupting chemicals influence steroid-mediated physiology in humans and other vertebrates by competing with steroids for receptor binding sites, disrupting diverse responses involved in reproduction, development and differentiation. Here I discuss that due to evolution of the progesterone receptor (PR) and mineralocorticoid receptor (MR) after ray-finned fish and terrestrial vertebrates diverged from a common ancestor, each receptor evolved to respond to different steroids in ray-finned fish and terrestrial vertebrates. In elephant shark, a cartilaginous fish, ancestral to ray-finned fish and terrestrial vertebrates, both progesterone and 17,20-beta-dihydroxy-progesterone activate the PR. During the evolution of ray-finned fish and terrestrial vertebrates, the PR in terrestrial vertebrates continued responding to progesterone and evolved to weakly respond to 17,20-beta-dihydroxy-progesterone. In contrast, the physiological progestin for the PR in zebrafish and other ray-finned fish is 17,20-beta-dihydroxy-progesterone, and ray-finned fish PR responds weakly to progesterone. The MR in fish and terrestrial vertebrates also diverged to have different responses to progesterone. Progesterone is a potent agonist for elephant shark MR, zebrafish MR and other fish MRs, in contrast to progesterone’s opposite activity as an antagonist for aldosterone, the physiological mineralocorticoid for human MR. These different physiological ligands for fish and terrestrial vertebrate PR and MR need to be considered in applying data for their disruption by chemicals in fish and terrestrial vertebrates to each other.

Industrial fires at facilities including waste management sites, warehouses, factories, chemical works and fuel storage depots are relatively frequent occurrences. Often, these fires occur adjacent to urban communities and result in ground-level airborne pollutant concentrations that are well above guideline values. Land, water, livestock and crops may also be contaminated by the emissions and by firefighting activities. Moreover, impacted communities tend to have a higher proportion of minority ethnic populations, individuals with underlying health vulnerabilities, as well as those of lower socio-economic status. Nevertheless, this is an aspect of air quality that is under-researched, and so this review aims to highlight the public health hazards associated with industrial fires and the need for an effective, coordinated, public health response. We also review the range of monitoring techniques that have been utilised in such fires and highlight the role of dispersion modelling in predicting plume trajectories and in estimating population exposure. We recommend establishing 1-h guideline values for particulate matter to facilitate timely public health interventions and we highlight the need to review regulatory and technical controls for sites prone to fires, particularly in the waste sector.

Rehabilitation following anterior cruciate ligament reconstruction with hamstring graft allows the patient to regain his functional capacities and to support him in the resumption of sports activities. Rehabilitation also aims to minimize the risk of recurrence, which is why it ensures that the patient's muscular capacities develop properly until they return to sport. Isokinetics helps strengthen and assess the strength of muscle groups in the thigh, but controversy exists as to its use by resistance to the open kinetic chain knee extension that would cause the transplant to distend. The objective of this study is to determine the influence of isokinetic muscle strengthening on the possible laxity of the anterior cruciate ligament and to be able to determine risk factors. The study relates to a population having benefited from anterior cruciate ligament reconstruction with hamstring graft from 3 to 6 months after surgery. Two groups are differentiated, one group exposed to isokinetism during rehabilitation, the other group, named unexposed, undergoes rehabilitation without the use of isokinetism. An anterior knee laxity test is performed 6 months postoperatively using the GNRB® machine for all subjects according to the same protocol. The test results were statistically analyzed to determine a relative risk of transplant distension for each group in the study. Comparison of the results of each group by univariate analysis did not reveal any significant result. Multivariate analysis showed interactions in the two strata of the study. It was argued that the use of isokinetics seems to have no effect on the risk of developing distension for the majority of subjects in the exposed group. A tendency towards transplant protection was perceived for each variable except the age under 25 years (RRa = 1.07). The use of isokinetics does not appear to be a cause of transplant distension in patients undergoing an anterior cruciate ligament reconstruction when this method is introduced 3 months postoperatively.

The spillover of the terrorist activities of Boko Haram, a Nigerian jihadi group, into Cameroon’s northern region has resulted in security challenges and humanitarian activity opportunities for Christian churches. The insurgents have attacked and destroyed churches, abducted Christians, worsened Muslim-Christian relations, and caused a humanitarian crisis. Aggregately, these ensuing phenomena have adversely affected Christian churches in this region, triggering an aura of responses: coping strategies, humanitarian work among refugees, and inter-faith dialogue. These responses are predicated on Christianity’s potential as a resource for peace, compassion, and love. In this study we emphasize the role of Christian churches in dealing with the Boko Haram insurgency. It opens up with a contextualization of Boko Haram in Cameroon’s north. This is followed by an examination of the brutality meted out on Christians and church property. The final section is an examination of the spiritual, humanitarian and relief services provided by Christian churches. The paper argues that although Christian churches have suffered at the hands of Boko Haram insurgents, they have engaged in various beneficial responses underpinned by the Christian values of peace and love.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

Problem solving is one of the most important components of the human cognition that affects for ages the progress of the human society. Mathematical modelling is a special type of problem solving concerning problems related to science or everyday life situations. The present study is a review of the author’s earlier works on problem solving and mathematical modelling from the scope of Education. Its real goal is that it presents in a systematic way and in a few pages only the results of many years research on the subject. This helps the reader to get a comprehensive idea about a very important topic belonging to the core of Mathematics Education, which is very useful to those wanting to study deeper the subject and get directions for further research in the area.

Statistical modeling lies at the heart of product design and development throughout numerous engineering disciplines, especially since processing large amounts of data has become increasingly ubiquitous. While mathematical statistics provide elegant guidance pertaining to the question of whether or not some particular underlying modeling assumptions are justified and appropriate, when pursuing a more comprehensive assessment of product design and development other considerations often increase in significance. Therefore, we will examine and analyze the tedious interactions and implications of statistical modeling choices and product liability exposure. To the best of our knowledge, this paper is the first to draw attention to and explore some often overlooked or oversimplified dangers and pitfalls that enter the equation when product design heavily relies on statistical modeling. In particular, through a diligent analysis of both statistical and legal aspects we will explore how statistically optimal procedures may yield far from optimal outcomes in terms of product liability when applied to actual real life problems and why suboptimal nonparametric or robust approaches may constitute better alternatives.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

The conventional explanation of delayed-choice experiments seems to violate our causal intuition. This apparent violation is caused by a misinterpretation of the conventional formulation of quantum mechanics. I reanalyze these experiments using advanced and time-symmetric formulations of quantum mechanics. All three formulations give the same experimental predictions, but the advanced and time-symmetric formulations violate our causal intuition that effects only happen after causes. I explore reasons why our causal intuition may be wrong at the quantum level. I also suggest how conventional causation might be recovered in the classical limit, and speculate on cosmological boundary conditions.

Stellar heated gas and dust makes a significant entropic/information energy contribution to the universe. At temperatures ~10⁷ the ~10⁸⁶ bits are equivalent to ~10⁷⁰J, equivalent to the energy equivalence of the universe’s ~10⁵³ kg ordinary baryon matter. A survey of stellar mass density measurements shows this dark energy contribution has a constant energy density that effectively mimics a cosmological constant over the redshift range z<1.35. The measurable difference between this information energy and a true cosmological constant is small, with a maximum difference of <2% in Hubble parameter at z~2. As information energy is significant and co-located with hot baryons it produces gravitational effects that resemble dark matter. Information energy is shown to be consistent with the dark matter effects observed in clusters of colliding galaxies (e.g. Bullet Cluster), with dark matter location specified by baryon location and strongest in regions of highest luminosity / temperature. The dark matter fraction measured in galaxy surveys more closely fits an information energy explanation than the fraction expected in the standard ɅCDM model. Information energy provides a solution to the cosmological coincidence problem and also would allow the cosmological constant to take the preferred zero value.

SETMAR is a protein lysine methyltransferase that is involved in several DNA processes, including DNA repair via the non-homologous end joining (NHEJ) pathway, regulation of gene expression, illegitimate DNA integration, and DNA decatenation. However, SETMAR is an atypical protein lysine methyltransferase since in anthropoid primates, the SET domain is fused to an inactive DNA transposase. The presence of the DNA transposase domain confers to SETMAR a DNA binding activity towards the remnants of its transposable element, which has resulted in the emergence of a gene regulatory function. Both the SET and the DNA transposase domains are involved in the different cellular roles of SETMAR, indicating the presence of novel and specific functions in anthropoid primates. In addition, SETMAR is dysregulated in different types of cancer, indicating a potential pathological role. While some light has been shed on SETMAR functions, more research and new tools are needed to better understand the cellular activities of SETMAR and to investigate the therapeutic potential of SETMAR.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

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

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Here we present a fast and highly scalable community structure preserving network module detection that recursively integrates graph sparsification and clustering. Our algorithm, called SparseClust, participated in the most recent DREAM community challenge on disease module identification, an open competition to comprehensively assess module identification methods across a wide range of biological networks.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions. It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models. The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Several methods of processing wood into strong, durable products for the construction industry provide transformative opportunities to substitute for less sustainable building materials. Carbon storage is a further advantage, with the added possibility of combustion for bioenergy at end of life. Intense research activity in this area is expected to open up new markets for wood fiber during the lifetime of trees now being planted. Here, wood-derived materials are classified according to the particle size, from metres to nanometres, into which the wood is fragmented before reconstitution. Materials made by densifying or chemically modifying solid wood with no fragmentation are already in production for exterior doors, window frames and cladding, with improved uniformity and stability compared with unmodified wood. Pre-commercial developments promise further gains in durability and strength. Emerging developments extend these process technologies to wood that has been chipped or stranded or pulped, retaining the above advantages over raw timber for weather-facing applications and adding processability by moulding or extrusion. Crucially, the raw material does not then need to be sawn timber but can be bioenergy-grade wood biomass. This will facilitate afforestation strategies that combine the aims of carbon sequestration and biodiversity.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

The morphological aspects of urban growth on wetlands in Africa are under-researched. Using the Densu Delta Ramsar site in Accra, Ghana, as a case study, this paper analyses the morphological patterns and drivers of urban growth and its impact on wetlands. Data were obtained through remote-sensing, ground truthing and limited key informant interviews. The analysis combined land use/land cover, building coverage and multiple regression techniques, with the aid of GIS and STATA software. The findings reveal that urban growth at the Ramsar site follows discernible spatial patterns consistent with the spreading pancake, village magnet and ribbon development models. However, the primary force behind these patterns is growing demand for land to meet housing needs, aided by the failure of state institutions to perform their land use control and wetland protection functions. To achieve sustainable urban development, there is an urgent need to ensure effective wetland management by enforcing existing land use, development control and wetland protection measures. This calls for the strengthening, resourcing and closer collaboration between the various state agencies responsible for urban planning and wetland management. There is also the need to engage and sensitise political leaders to increase their commitment to implementing wetland protection and pro-environmental policies.

This article challenges the assumption that journals and peer review are essential for developing, evaluating and disseminating scientific and other academic knowledge. It suggests a more flexible ecosystem, and examines some of the possibilities this might facilitate. The market for academic outputs should be opened up by encouraging the separation of the dissemination service from the evaluation service. Publishing research in subject-specific journals encourages compartmentalising research into rigid categories. The dissemination of knowledge would be better served by an open access, web-based repository system encompassing all disciplines. There would then be a role for organisations to assess the items in this repository to help users find relevant, high-quality work. There could be a variety of such organisations which could enable reviews from peers to be supplemented with evaluation by non-peers from a variety of different perspectives: user reviews, statistical reviews, reviews from the perspective of different disciplines, and so on. This should reduce the inevitably conservative influence of relying on two or three peers, and make the evaluation system more critical, multi-dimensional and responsive to the requirements of different audience groups, changing circumstances, and new ideas. Non-peer review might make it easier to challenge dominant paradigms, and expanding the potential audience beyond a narrow group of peers might encourage the criterion of simplicity to be taken more seriously - which is essential if human knowledge is to continue to progress.

This study aims to systematically review and meta-analyze the nitro-oxidative stress (O&NS)/antioxidant (ANTIOX) ratio in the peripheral blood of people with mild cognitive impairment (MCI). We searched PubMed, Scopus, Google Scholar, and Web of Science for articles published from inception until July 31, 2021. Forty-six studies on 3.798 MCI individuals and 6.063 healthy controls were included. The O&NS/ANTIOX ratio was significantly higher in MCI than in controls with a Standardized Mean Difference (SMD)=0.378 (95% CI: 0.250; 0.506). MCI individuals showed increased lipid peroxidation (SMD=0.774, 95%CI: 4.416; 1.132) and O&NS-associated toxicity (SMD=0.621, CI: 0.377; 0.865) and reduced glutathione (GSH) defenses (SMD=0.725, 95%CI: 0.269; 1.182) as compared with controls. MCI was also accompanied by significantly increased homocysteine (SMD=0.320, CI: 0.059; 0.581), but not protein oxidation, and lowered non-vitamin (SMD=0.347, CI: 0.168; 0.527) and vitamin (SMD=0.564, CI: 0.129; 0.999) antioxidant defenses. The results show that MCI is at least in part due to increased neuro-oxidative toxicity and suggest that treatments targeting lipid peroxidation and the GSH system may be used to treat or prevent MCI.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

This paper discusses recent developments in creep, over a wide range of temperature, that mqy change our understanding of creep. The five-power law creep exponent (3.5 to 7) has never been explained in fundamental terms. The best the scientific community has done is to develop a natural three power-law creep equation that falls short of rationalizing the higher stress exponents that are typically five. This inability has persisted for many decades. Computational work examining the stress-dependence of the climb rate of edge dislocations we may rationalize the phenomenological creep equations. Harper-Dorn creep, “discovered” over 60 years ago has been immersed in controversy. Some investigators have insisted that a stress exponent of one is reasonable. Others believe that the observation of a stress exponent of one is a consequence of dislocation network frustration. Others believe the stress exponent is artificial due to the inclusion of restoration mechanisms such as dynamic recrystallization or grain growth that is not of any consequence in the five power-law regime. Also, the experiments in the Harper-Dorn regime, which accumulate strain very slowly (sometimes over a year) may not have attained a true steady state. New theories suggest that absence or presence of Harper-Dorn may be a consequence of the initial dislocation density. Novel experimental work suggests that power-law breakdown may be a consequence of a supersaturation of vacancies which increase self-diffusion.

Involving local people in natural area management is very important to address the complexity of environmental management issues for sustainable use of local resources. Participatory methods require the contribution of local stakeholders in decision making. Mapping the environmental views of local communities allows for detecting aspects that could facilitate management efforts. This research – in the frame of the Skyros LIFE project and the PAMNATURA project - measures local acceptability of the conservation actions proposed by the LIFE project in Skyros Island (Greece) in relation with recording local people’s environmental orientation using the 15-item revised New Ecological Paradigm (NEP) scale. The research was carried out by means of questionnaires. The LIFE project proposed actions were grouped into three categories according to their theme, i.e. promoting (a) Nature protection, (b) Agro-pastoralism and (c) Ecotourism. The sample seems to largely agree with the LIFE project proposals, while the results showed high scores for most of the NEP scale items, implying pro-environmental beliefs, though there appears disagreement or neutrality regarding a few items. Local acceptability of the proposed actions was found to correlate to local people’s environmental concern measured through the NEP scale. Drawing on the results, implementation of actions related directly or indirectly to economic activities, preservation of traditional activities, as well as environmental education, interactive informing and consultation could enhance local participation. Skyros island seems to offer an appropriate social background for applying participatory and adaptive management and implementing conservation programs.

Objective: The goal of this review is to provide a succinct, yet comprehensive, guide to the an-tepartum management of multiple gestations. Methods: This narrative review on twins and multiple gestation provides a concise guide for providers with this ever-growing patient population. PubMED was utilized for literature search. Each reference was evaluated and graded for quality of evidence by US Preventative Services Task Force and Cochrane Review guidelines. Screening, surveillance, and management strategies are delineated succinctly and organized by type of multiple gestation being managed from the lowest risk dichorionic twin pair to the increasingly escalating risks of twins and higher order multiples sharing a placenta and/or amniotic sac. Results: The incidence of twin pregnancies has grown over the past several years, due in large part to delayed reproductive timing and surge in assisted reproductive technologies. Twin pregnancies are associated with higher morbidity for both gravidas and offspring, warranting evidence-based approach in counseling and management. Conclusions: We note the important differences among multiples in chorionicity and amnionicity, in the importance of close surveillance and early delivery. Graded clinical pearls and evi-dence-based recommendations are presented to guide obstetric providers.

With LiDAR (Light Detection and Ranging) time series being used for various applications, optimal realisation of a common geodetic datum over many epochs is a highly important prerequisite with direct impact on accuracy and reliability of derived measures. In our work, we develop and define several approaches to the adjustment of multi-temporal LiDAR data in a given software framework. These approaches ranging from pragmatic to more rigorous solutions are applied to an 8 year time series with 21 individual epochs. The analysis of the respective results suggests that a sequence of bi-temporal adjustments brings the best results while being more flexible and computationally viable than the most extensive approach of using all epochs in one single multi-temporal adjustment. With a combination of sparse control patches measured in the field and one selected reference block, we obtain relative datum discrepancies in the range of 1-2 cm for the complete time series. Based on our findings, we formulate design criteria for setting up and adjusting future time series with the proposed method.

We consider the role information energy can play as a source of dark energy. Firstly, we note that, if stars and structure had not formed in the universe, elemental bits of information describing the attributes of particles would have exhibited properties similar to the cosmological constant. The Landauer equivalent energy of such elemental bits would be defined identical in form and value to the characteristic energy of the cosmological constant. But, with the formation of stars and structure, stellar heated gas and dust now provides the dominant contribution to information energy with the characteristics of a dynamic, transitional, dark energy. At low redshift, z<~1.35, this dark energy emulates the cosmological constant with a near constant energy density, w=−1.03±0.05, and an energy total similar to the mc² of the universe's ∼10⁵³ kg of baryons. At earlier times, z>~1.35, information energy was phantom, differing from the cosmological constant, Λ, by a CPL parameter difference of ∆w_o=−0.03±0.05 and ∆w_a=−0.79±0.08, values sufficient to account for the H₀ Tension. Information dark energy agrees with most phenomena as well as Λ, while exhibiting characteristics that resolve many tensions and problems of ΛCDM: the cosmological constant problem; the cosmological coincidence problem; the H₀ and σ₈ tensions. As this proposed dark energy source is not usually considered, we identify the expected signature in H(a) that will enable the role of information dark energy to be falsified by experimental observation.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

Jamoytius kerwoodi, is a primitive, eel-like jawless vertebrate found uniquely in an Early Silurian (Llandovery epoch; 444-433 Ma) horizon near Lesmahagow, Scotland. This species is a rare component of a low-diversity dominantly nektonic detritus and herbivorous fauna living over an anoxic bottom and is found at the transition from a marine-influenced, probably brackish-water, deep-water basin to a shallower-water, less saline and likely freshwater basin. In the absence of true teeth, Jamoytius was probably a detritivore or herbivore feeding on Ceratiocaris. Jamoytius may be a direct ancestor of living lampreys, especially as their ectoparasitic mode of life might have evolved from ancestral microphagous filterers or herbivores.

An immune-inflammatory response is accompanied by increased nitro-oxidative stress. The aims of this mechanistic review are to review: a) the role of redox sensitive transcription factors and enzymes, ROS/RNS production and the activity of cellular antioxidants on the activation and performance of macrophages, dendritic cells, neutrophils, T cells, B cells and natural killer cells; b) the involvement of high-density lipoprotein (HDL), apolipoprotein (Apo)A1, paraoxonase (PON)-1, and oxidized phospholipids in the regulation of the immune response; and c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor (NF)-κB, HIF1alpha, the mechanistic target of rapamycin (mTor), the phosphatidylinositol 3‑kinase (PI3K) / protein kinase B (AKT) signalling pathway, mitogen-activated protein (MAP) kinases, 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR). The performance and survival of individual immune cells is under redox control and sensitive to intracellular and extracellular levels of ROS/RNS and is heavily influenced by cellular anti-oxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2 (Nrf-2), and the HDL complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, those redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.

Adeno-associated viral (AAV) vectors can be used for gene delivery. AAV.CAP-Mac was recently developed; it can cross the blood-brain barrier and transduce cells throughout the CNS. However, some brain regions were not transduced in adult rhesus monkeys. Additionally, AAV vectors can only package 5 kb of DNA. Also, AAV vectors may be genotoxic and cytotoxic, especially at high doses. Finally, AAV vectors are very expensive to produce at sufficiently high titers for treatment. Off-the-shelf cell-based delivery systems wherein the cells can infiltrate the target tissue and be hyper-motile would be ideal. Also, mRNA-based gene editing would be a transient treatment, and thus be much safer.

The current report represents a case of a 77-year-old man with Parkinson’s disease who died three weeks after receiving his third COVID-19 vaccination in January 2022. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov- 19 vector vaccine, followed by two more doses with the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to the ambivalent clinical features noted before death. The underlying illness (Parkinson’s disease) was confirmed by autopsy. However, no sign of a florid COVID-19 was discovered. Meanwhile, the immunohistochemical staining of the brain and heart revealed previously undiagnosed conditions. The brain, in distinctive, revealed multifocal necrotizing encephalitis with massive inflammatory lymphocyte infiltrates. In addition, the heart showed signs of serious myocarditis. Finally, immunohistochemical staining revealed that the SARS-CoV-2 spike protein was evident in the tissues investigated. Based on these immunohistochemical findings, it appears that the inflammatory changes in the patient's brain tissues are most likely the result of immunological processes. Concurrently, the absence of SARS-CoV-2 nucleocapsid-protein was evidenced, indicating that the detected spike-protein is unrelated to a SARS-CoV-2 infection. If such an infection was the cause of the spike protein, the SARS-CoV-2 nucleocapsid protein would also be detectable. As a consequence, the confirmed presence of the spike protein had to be attributed to the previous vaccination with the BNT162b2 mRNA vaccine that the deceased patient had received.

While the importance of continuous monitoring of electrocardiographic (ECG) or photoplethysmographic (PPG) signals to detect cardiac anomalies is generally accepted in preventative medicine, there remain major barriers to its actual widespread adoption. Most notably, current approaches tend to lack real-time capability, exhibit high computational cost, and be based on restrictive modeling assumptions or require large amounts of training data. We propose a lightweight and model-free approach for the online detection of cardiac anomalies such as ectopic beats in ECG or PPG signals based on the change detection capabilities of Singular Spectrum Analysis (SSA) and nonparametric rank-based cumulative sum (CUSUM) control charts. The procedure is able to quickly detect anomalies without requiring the identification of fiducial points such as R-peaks and is computationally significantly less demanding than previously proposed SSA-based approaches. Therefore, the proposed procedure is equally well suited for standalone use and as an add-on to complement existing (e.g. heart rate (HR) estimation) procedures.

Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors, nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss management of older adults and transplant-ineligible patients who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.

Background: Over the past two decades, the Copenhagen Psychosocial Questionnaire (COPSOQ) has been established as a valid instrument to measure psychosocial stress at work. Currently, the COPSOQ international network is responsible for monitoring and improving COPSOQ. In 2019, a new questionnaire was published, and the Greek version is now being validated. Methods: The measurement qualities of the Greek COPSOQ III have been explored in accordance with the usual requirements of a validation study as defined by DIN EN ISO 10075-3. A sample of observations from 2,189 participants surveyed with the COPSOQ in Greece was used to validate the current version with appropriate statistical analyses. Exploratory factor analysis was used to assess the statistical relationships for many scales. Results: With its 108 items and 40 scales, the Greek COPSOQ III includes all psychosocial work factors that have been internationally validated and remain compatible with approximately 72% of the COPSOQ III German version content. In addition to the primary results, congruence with widely used theoretical approaches such as the demand-control (−support) model (DCM) or the job demands-resources model (JDR) is generally satisfactory. In summary, our validation study for the Greek COPSOQ III version showed adequate reliability and validity, which is in line with the findings of the COPSOQ III questionnaire from other European countries, and it is also compatible with the validation of the German COPSOQ III (Lincke, 2021). Our regression analysis revealed that 34 psychosocial work factors (34 “context” scales) could adequately predict the scores of the satisfactory and health scales (6 “outcome” scales). The analysis also revealed the top five (5) predictors (context variables) for each of the six (6) “effect” scales (outcome variables). Conclusions: With the launch of COPSOQ III in Greece, current and new workplace psychosocial aspects could be explored. COPSOQ III (GR) is a beneficial instrument for enterprise research and risk assessment.

A deterministic compartment model for the transmission dynamics of onchocerciasis with nonlinear incidence functions in two interacting populations is studied. The model is quantitatively analyzed to investigate it's local asymptotic behavior with respect to disease-free and endemic equilibria. It is shown, using Routh-Hurwitz criteria, that the disease-free equilibrium is locally asymptotically stable when the basic reproduction number is less than the unity. When the reproduction number is greater than the unity, we prove the existence of a locally asymptotically stable endemic equilibrium. Furthermore, bifurcation analysis was done by investigating the possibility of the co-existence of the equilibria of the model at R0<0 but near R0=0 by Center Manifold Theory.

This is a case study of a 55-year-old patient who died four months after receiving the mRNA-vaccine BNT162b2 (Pfizer-BioNTech) against COVID-19 as a second dose, following an initial vaccination with the ChAdOx1 nCov-19 vector vaccine (AstraZeneca) two months earlier. The autopsy diagnosis revealed general atherosclerosis. The histopathologic analyses of cardiac tissue demonstrated the presence of a thrombus occluding the right coronary artery (RCA) without evidence of plaque rupture. As a substitute trigger of clotting, the RCA presented with characteristics of acute lymphocytic vasculitis that extended to vasa vasorum in the adventitia and vessels in adjacent adipose tissue. Microthrombi were occasionally detected in these small vessels. It was obvious that lymphocytic myocarditis had been a chronic ongoing process temporally distinct from acute myocardial infarction. The myocardium contained patchworks of fibrotic areas alongside foci of displaying acute inflammation and fresh myocyte damage. SARS-CoV-2 Spike protein, but not nucleocapsid protein was sporadically detected in vessel walls by immunohistochemical assay. The cause of death was determined to be acute myocardial infarction and lymphocytic myocarditis. These findings indicate that myocarditis, as well as thrombo-embolic events following injection of spike-inducing gene-based vaccines, are causally associated with a injurious immunological response to the encoded agent. Because of the fact that the immune response to a first gene-based vaccination is very low in comparison with the immune response to the second vaccination, the found adverse events has rather to be attributed to the mRNA-based second vaccination as to the initial vector-based one.