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

Acute Oak Decline (AOD) is complex syndrome affecting Britain’s keystone native oak species, (Quercus robur L. and Q. petraea L. (Matt.) Liebl.), in some cases causing mortality within five years of symptom development. The most distinguishable symptom is weeping stem lesions, from which four species of bacteria have been isolated: Brenneria goodwinii, Gibbsiella quercinecans, Lonsdalea britannica and Rahnella victoriana. We do not yet know where else these bacteria exist, and little is known about the relationship of the wider oak leaf microbiome (phyllosphere) to acute oak decline. Here we investigate whether incidental evidence from a large oak genome re-sequencing dataset could be used to detect these bacteria in oak foliage, and whether bacterial incidence co-varied with AOD status or location. Oak leaves and buds were sampled from 421 trees at five sites in England. Whole genomic DNA from these samples was shot-gun sequenced with short reads. Non-oak reads were extracted from these data and queried to microbial databases. Reads uniquely matching AOD-associated bacterial genomes were found to be present on trees from all five sites and included trees with active lesions, trees with historic lesions and trees without AOD symptoms. The abundance of the AOD-associated bacteria did not differ between tree health categories but did differ among sites. We conclude that the AOD-associated bacteria may be members of the normal oak microbiome, whose presence on a tree is not sufficient to cause AOD symptoms.

Education on native tree species using indigenous knowledge systems is crucial in elementary school environmental education because it sensitizes learners on the significant roles played by the native trees and their interconnections with their culture and existence. Unfortunately in Ghana, there is no pedagogical model that would aid elementary school teachers in carrying out such education.This study was aimed at developing, implementing and evaluating an indigenous knowledge inspired pedagogical model for native tree education among elementary school learners in Ghana. The convergent parallel mixed methods design that aimed at collecting quantitative and qualitative datasets on the development and evaluation of the developed pedagogical model. The results show that the pedagogical model was deemed very satisfactory in all its aspects for native tree education among elementary school learners in Ghana. The model was able to assist in developing the sustainability consciousness and competence of elementary school learners toward caring for native trees through tree planting, making of nurseries and gardens, and engaging in native tree conservation campaigns. The study recommends that the Ministry of Education should adopt, improve and widely disseminate the pedagogical model and help in its broader implementation in various elementary schools across the country.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

The French-Swiss Professor in inductive philosophy Richard Avenarius (1843-1896), the father of empirio-criticism together with Ernst Mach, is one of the most underrated and misunderstood philosophers ever. It mostly depends upon his terminology, which displays an insurmountable difficulty. However, influenced by the most innovative proposals of his times of transition between the idealistic/rationalist legacies and the new Materialism/scientific interpretation of reality – i.e, by cultural evolutionism, linguistics, biomechanics, entropy/energy and, above all, by the newborn experimental psychology-, he produced a complete system of philosophy and innovative methods of investigation of the laws of knowledge. Hints (chunk, scrap, fragments) of his original ideas can be found not only in philosophers of mind after him - such as Gestalt, phenomenalism, behaviourism, functionalism and cybernetics, autopoiesis, dynamical systems theory, embedded/embodied mind, free-energy principle of the brain – but also in recent neuroscientific theories – nervous transduction, electric spikes, cracking of neural code, multisensory integration -. Our aim is to provide the first chronological English summary of his masterpiece, the “Kritik”, to give the possibility to the (almost) totally unaware English speakers to appreciate such a neglected and innovative thinker.

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

Helmholtz energy of ice VII-X is determined in a pressure regime extending to 450 GPa at 300 K using local basis functions in the form of b splines. The new representation for the equation of state is embedded in a physics-based inverse theory framework of parameter estimation. Selected pressures as a function of volume from 14 prior experimental studies and two theoretical studies constrain the behavior of Helmholtz energy. Separately measured bulk moduli, not used to construct the representation, are accurately replicated below about 20 GPa and above 60 GPa. In the intermediate range of pressure, the experimentally determined moduli are larger and have greater scatter than values predicted using the Helmholtz representation. Although systematic experimental error in the experimental elastic moduli is possible and likely, the alternative hypothesis is a slow relaxation time associated with changes in proton mobility or the ice VII to X transition. A correlation is observed between anomalies in the pressure derivative of the predicted bulk modulus and previously suggested higher-order phase transitions. Improved determinations of elastic properties at high pressure would allow refinement of the current equation of state. More generally, the current method of data assimilation is broadly applicable to other materials in high-pressure studies.

Loyalty is one of the greatest intangible assets that any organization can possess and improving client loyalty is a primary marketing goal that can have a significant financial impact on any business. This quantitative study examined the mediating role of communication on the relationship between satisfaction and loyalty (attitudinal and behavioral) in veterinary clinics, along with the moderating roles of trust, commitment, perceived value, and relational characteristics. Responses collected from 351 pet-owners through social media were analyzed using descriptive and inferential statistics. The results show that attitudinal loyalty (AL) has a strong positive relationship with communication at multiple points in a veterinary clinic whereas the relationship with behavioral loyalty was not as clear. Additional findings suggest that AL, which is influenced by trust in the veterinarian, communication from staff members and commitment, has a strong positive relationship with behavioral intentions, increases the number of products and services that a pet-owner consumes at his or her primary veterinary clinic, and attenuates the role of cost in receiving veterinary care. These findings can help veterinary clinic owners and managers in developing and implementing relationship strategies that improve pet-owner loyalty. The article that follows is a synopsis of the author’s dissertation.

A thorough analysis and comparison of the fatty acid profiles of stipe and blade from Laminaria hyperborea, a kelp species found in the northern Atlantic, is presented. Lipids were extracted and fractionated into neutral lipids, free fatty acids and polar lipids, then derivatized to fatty acid methyl esters prior to GC-MS analysis. A total of 42 fatty acids were identified and quantified, including the n-3 fatty acids α-linolenic acid, stearidonic acid and eicosapentaenoic acid. An n-6/n-3 ratio of 0.8:1 was found in blade and 3.5:1 in stipe, respectively. The ratios vary between the lipid fractions within stipe and blade, with the lowest ratio in the polar lipid fraction of blade. The fatty acid amounts are higher in blade than in stipe, and the highest amounts of n-3 fatty acids are found within the neutral lipid fractions. The amounts of polyunsaturated fatty acids are 3.4 times higher in blade than stipe. This study highlights the compositional differences between the lipid fractions of stipe and blade from L. hyperborea. The amount of polyunsaturated fatty acids, compared to saturated- and monounsaturated fatty acids, as well as the n-6/n-3-ratio, is known to influence human health. In the pharmaceutical, food, and feed industries this can be of importance for production and sale of different health products. Additionally, lipids are today among the unused by products of alginate production, exploiting this material for commercial interest should give both economical and environmental benefits.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

Interferons were the original prototype cytokine system discovered in 20th-century research. As the name implies, they were originally thought to be synthesised and secreted between cells. Thanks to technological advances, the processes involved in protein secretion can be explained comparatively more clearly at both the genetic and biochemical levels. The discovery of interferon (IFN) occurred when genetic research was still in its infancy. Franklin and Wilkins discovered the structure and function of deoxyribonucleic acid (DNA) at the same time as Crick and Watson; however, Isaacs and Lindemann, two scientists, described the first IFN in 1957. Mutations can be caused by inherent genetic protein synthesis and during infection as well as within IFN regulation pathways affecting cell proliferation. This remains central to host cell IFN synthesis and effects through IFN protein receptor subunits defined by 6 protein domains. Type II IFN is key to immune cell function secreted by a variety of immune cells, mainly natural killer (NK) as well as T cells. Single–stranded and/or double–stranded RNA/DNA viruses, as well as bacterial infections (e.g., Escherichia coli) and fungal infections (e.g., Aspergillus), also affect IFN regulation. Pathogenic proteins utilise intra/extracellular proteins that sense foreign antigens like Toll–like Receptors (TLRs), affected by mutations within the human cellular IFN transduction pathways. Since the discovery of the third IFN type in 2003, when immune cell phenotypes were further characterised, questions remain about the immunological mechanisms contributing to the regulation of the innate and adaptive host immune system. Alterations in the synthesis of type I/II/III host IFNs can differentially and beneficially alter homeostatic cellular pathways in pathological disease, with type I IFN being synthesised in cancer as well as by homeostatic cells. Therefore, considered here are the overall IFN molecular, cell regulatory mechanisms in the context of immune cell research developments.

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.

Effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined and the underlying mechanism of PD-L1 expression elucidated. Initial experiments in human melanoma cells (A375) showed PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p

Ebola virus is a zoonotic virus comprised of 6 different species designated within the family Filoviridae and genus Ebolavirus. The first recorded outbreak of an Ebola virus (EBOV) was in Yambuku, Zaire (ZEBOV) in 1976, followed by Sudan Ebola virus (SUBOV) later that year. Outbreaks have been increasing throughout the 21st century, and mortality rates can reach up to 90%. Such extraordinary virulence is evidenced with few pathogens, similarly with Marburg virus (MARV) that originated in Uganda and was first detected in Germany in 1967. The virulent nature of filovirus disease has established these related viruses as a formidable global concern. There are currently four types of Ebolaviridae species known to infect humans, with two more recently identified in other animals that are genomically different with respect to cellular pathogenesis or aetiology of disease. Recent advances into understanding the pathogenesis of filovirus disease infections have been remarkable, yet the immunological response to filovirus infection remains unknown. Scientific analysis of cellular mechanisms can provide insight into virulence factors utilised by other pathogenic viruses that also cause febrile illness with occasional haemorrhagic fever in humans. In this review, we aim to provide a brief summary of EBOV proteins and the role of innate and adaptive immune cells known since 2000. We will consider the relevance and implications of immunological proteins measured by CD marker, alongside cytokine, chemokine and other biologically relevant pathways, as well as genetic research. Thorough understanding of immunological correlates affecting host responses to Ebola viruses will facilitate both clinical and applied research knowledge, contributing towards protection against potential public health threats.

Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the COVID—19 pandemic, an unexpected duality has occurred of SARS–CoV–2 and monkeypox virus (MPXV) infections. Monkeypox virus is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal to human transmission) may occur. The Orthopoxviridae genus includes other Orthopoxviruses (OPXV) present in animal host reservoirs that include cowpox viruses (CPXV), vaccinia virus (VACV) and variola virus (VARV), with the latter being causal agent of smallpox and excessive mortality. The aim in this review is to present facts about MPXV specific pathogenesis, epidemiology, and immunology alongside historical perspectives. Monkeypox virus was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to propagation of MPXV causing MPOX disease requires clarity. Infected hosts display symptoms like extensive cellular initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Anti–viral therapeutic drugs were typically prescribed for smallpox and MPOX disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorised treatment exists for MPOX disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of MPOX resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHV) including Varicella zoster (VZV).

We propose the traditional goal of cancer therapists to develop a single drug or drug combination that can, by itself, eliminate all cancer cells within a host has neglected potential treatments that may achieve curative outcomes by strategically combining agents that are individually effective but non-curative. We derive basic principles for such an approach from the eco-evolutionary dynamics of background extinctions in which a “first strike” reduces the size and heterogeneity of the initial population and is followed immediately by demographic and ecological “second strikes” that push the population below an extinction threshold. This proposed strategy appears identical to the empirically-derived curative therapy in childhood Acute Lymphocytic Leukemia.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

Decisions affecting the COVID-19 pandemic, by the individual and those with highest authority, are being made on the basis of unreliable data. Data about cases and deaths are collected daily but represent only a sample of reality. Statistics convert sample data into more reliable estimates. However, statistics have no magical powers; reliability requires dependable data. It is futile to rail against this darkness; COVID-19 is not a scientific experiment. However, we must do better both with data collection and data analysis. In this review, I focus on one element of the data, the asymptomatic case of COVID-19. Without reliable information about this number, decision makers are significantly blinded. By its nature, the asymptomatic case is hidden but contaminating to understanding COVID-19. The true case rate and death rate per case are unknowable without knowing the fraction of cases that are asymptomatic. The best estimate of asymptomatic cases is in the CDC document: COVID-19 Pandemic Planning Scenarios. For four different scenarios the estimates range from 10% to 70%, with the best estimate of 40% for asymptomatic cases. However, even the definition of the asymptomatic case is problematic. In simplest terms, two elements are required: an infection and no symptoms. How is “no symptoms” to be usefully defined? It appears to be analogous to pontificating about black swans from studying only white swans. It implies infection, but how is infection defined? Is it presence of the virus, replication of the virus, or presence of antibodies? Is asymptomatic disease an oxymoron? Without extensive, purposeful screening for specifically defined, essential symptoms and appropriate virus and antibody testing over time, the class of asymptomatic cases remains unknown. Current estimates range from <20% to ˃80%. If low, it can be ignored; if high, it dramatically and proportionately lowers the case rate and the death rate per case. Consequentially, the asymptomatic rate dramatically affects our societal and political responses. In this focused review, we assess the limitations of the published estimates, bring attention to the importance of obtaining accurate data, and exhort that high priority be given in the scientific community to understanding the issue, asymptomatic COVID-19 cases.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Obesity-associated metabolic abnormalities comprise of a cluster of conditions including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. Variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. Substantially decreased BAT activity in individuals with obesity indicates a role for BAT in setting of human obesity. On the other hand, BAT mass and its prevalence has been reported to correlate with lower body mass index (BMI), decreased age and glucose levels, leading to lower incidence of cardio metabolic diseases. Increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. Deeper understanding of the role of BAT in human metabolic health and its inter-relationship with body fat distribution and deciphering proper strategies to increase energy expenditure by either increasing functional BAT mass, or inducing white adipose browning holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

Tubulin superfamily (TSF) proteins are widespread and known for multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. Functions of the lesser-known archaeal TSF proteins are beginning to be identified, and show surprising diversity, including homologs of tubulin and FtsZ, and a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we defined sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identified CetZ groups and diversity amongst archaea, and identified potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. At least three subfamilies of orthologous CetZ proteins were identified in the archaeal class Halobacteria, including CetZ1 and CetZ2 and a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another and to cell shape and motility phenotypes across diverse Halobacteria. Amongst other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales affiliated strongly with Halobacteria CetZs, suggesting they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting a potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods included nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. The findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis and motility.

Conservation history of D614 residue is valuable in predicting the consequences of D614G mutation in the SARS-CoV-2 spike glycoprotein (SGP). We report here that the D614 belonged to an extraordinarily conserved, densely hydrophobic eleven amino acid peptide-motif vavlyqdvnct (11-aa), in the Sarbecovirus group and the variant carrying vavlyqdvnct had appeared in Chinese samples and became predominant in several geographical hotspots in late March, 2020. Interestingly a 2009 annotation of SARS-CoV contained the same mutation.

Matter grows and self-assembles to produce complex structures such as virus capsids, carbon fullerenes, proteins, glasses, etc. Due to its complexity, performing pen-and-paper calculations to explain and describe such assemblies is cumbersome. Many years ago, Richard Kerner presented a pen-and-paper path integral approach to understand self-organized matter. Although successfully addressed many important problems including the yield of fullerene formation, the glass transition temperature of doped chalcogenide glasses, the fraction of boroxol rings in B2O3 glasses, the first theoretical explanation for the empirical recipe of window and Pyrex glass and the understanding of virus capsid self-assembly, still is not the primary choice when tackling similar problems. The reason lies in the fact that it diverges from mainstream approaches based on the energy landscape paradigm and non-equilibrium thermodynamics. In this context, a critical review is presented, demonstrating that the Richard Kerner method is, in fact, a clever way to identify relevant configurations. Its equations are simplified, common physical sense versions to those found in the energy landscape kinetic equations. Subsequently, the utilization of equilibrium Boltzmann factors in the transition Markov chain probabilities is analyzed within the context of local two-level energy landscape models kinetics. This analysis demonstrates that their use remains valid when the local energy barrier between reaction coordinate states is small compared to the thermal energy. This finding places the Richard Kerner model on par with other more sophisticated methods and, hopefully, will promote its adoption as an initial and useful choice for describing the self-agglomeration of matter.

The effect of varying concentrations of crude oil pollution on the germination and growth parameters of Mucuna pruriens (Var. cochinchinenesis) was investigated. The following treatments were used; 0ml, 100ml, 200ml, 400ml, 800ml 1600ml respectively. The germination of velvet bean was 100% but growth was found to be inhibited by a wide range of treatments (800ml and 1600ml). the lag phase of proceeding growth is also reduced at this treatment. Growth inhibition is attributed primarily to the characteristics of oil, which acts as a physical barrier to water and oxygen uptake. Reduction in the growth and development of plants was observed in the polluted treatments as against the control (non–polluted treatment) because of the deleterious effect of the petroleum products on the morphological parameters (plant height, number of leaves and leaf area) tested for. Velvet beans treated with lower treatment (100ml and 200ml) were observed to be more productive when compared to the control experiment. Consequently, as the crude oil exceeds the plant absorbing capacity at 800ml and 1600ml respectively, the growth retards, chlorosis, presence of tough apical meristem, and defoliation from the base of the plant.

The brown pelican (Pelecanus occidentalis) is a species often affected by natural and man-made disasters such as hurricanes and oil spills as well as general human activities; that subsequently receives medical care and rehabilitation. During rehabilitation, blood may be collected for various testing to help with diagnosis, treatment, and monitoring. Reference intervals for this species are limited, dated, and typically from small sample sizes. Seventy one presumed healthy brown pelicans were sampled as a part of their pre-release examination from rehabilitation at the Wildlife Center of Texas after a large volume stranding in December 2014 to January 2015, and various venous analytes were measured to establish updated reference intervals for Brown Pelicans. Fibrinogen was measured via heat precipitation and the Abaxis VSPro equine Fibrinogen cartridge to determine reference intervals, and in an attempt to validate the VSPro for use in avian species. Abaxis VS2 Avian/Reptile Chemistry panel, iSTAT CG4+, and iSTAT Chem8+ results in addition to body condition score, spun PCV, cloacal temperature and fibrinogen were measured. Proposed reference intervals for brown pelicans are presented. Fibrinogen results were not comparable between the gold standard method and the VSPro, indicating that the VSPro is not appropriate for use in brown pelicans.

The dimorphic, soil-dwelling fungus Coccidioides is the causative agent of coccidioidomycosis and is a reemerging pathogen of human health concern. Despite increasing incidence and isolations of the organism outside of its theoretical environmental range, much of Coccidioides epidemiology, including complete host range, remains unknown. Feral swine (Sus scrofa) are an invasive species distributed throughout the United States that may play a role in fungal ecology due to their behavioral associations with soil. To address this, we evaluated seven feral swine for susceptibility to Coccidioides. After intranasal inoculation with 106.2 arthroconidia of C. posadasii, no pigs displayed signs of clinical disease, nor did any exhibit antibodies by AGID testing. Histopathologic evaluation did not reveal the presence granulomatous lesions, and fungal spherules or endospores were not observed in any of the tissue sections examined, although individuals had significant comorbidities, most notably Metastrongylus nematodes in the lungs. Despite the absence of lesions and organisms histologically, C. posadasii was isolated by culture from the lung and mediastinal lymph node of two pigs, indicating active infection. These results suggest that feral swine are mildly susceptible to acute Coccidioides infection and may aid in fungal dispersal due to the presence of spherules in tissues post-mortem.

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

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from from northeastern India to eastern China. Genomics research can help provide much insight in understanding venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China, producing a highly continuous reference genome, with the length of 1.53 Gb and 41.18% repeat element content. From this 24,799 genes were identified, and 97.97% genes could be annotated. Nuclear genome single-copy genes phylogenetic tree including 6 species verified the validity of our genome assembly and annotation process. This research will contribute to further study on Protobothrops biology and the genetic basis of the snake venom.

Brown-Séquard Syndrome (BSS) is a rare spinal cord injury characterized by asymmetrical motor and sensory dysfunction. Trauma to the spinal cord, particularly the hemi section, is the primary cause. Diagnosis involves a thorough medical history, physical examination, and imaging studies. Treatment focuses on stabilization, rehabilitation, and potential emerging therapies. This article provides a comprehensive overview of BSS, including its causes, symptoms, diagnosis, and treatment.

With an increasing adoption of Battery Electric Bus (BEB) fleets, developing a reliable charging schedule is vital to a successful migration from their fossil fuel counterparts. In this paper, a Simulated Annealing (SA) implementation is developed for a charge scheduling framework for a fixed-schedule fleet of BEBs that utilizes a proportional battery dynamics model, accounts for multiple charger types, allows partial charging, and further considers the total energy consumed by the schedule as well as peak power use. Two generation mechanisms are implemented for the SA algorithm denoted as the "quick" and "heuristic" implementations, respectively. The model validity is demonstrated by utilizing a set of routes sampled from the Utah Transit Authority (UTA) and comparing the results against two other models: the BPAP and the Qin-Modified. The results presented show that both SA techniques offer a means of generating operationally feasible schedules quickly while minimizing the cost of operation and considering battery health.

On February 24, 2022 Russia started the full-scale invasion of Ukraine, which created an unprecedented number of refugees. To estimate the influence of this humanitarian disaster on the COVID-19 pandemic dynamics, the averaged daily numbers of cases and reproduction numbers in Ukraine, the UK, Poland, Germany, the Republic of Moldova, and in the whole world were calculated for the period February-April 2022. The registered numbers of cases were compared with ones calculated with the use of the generalized SIR-model and corresponding parameter identification procedure for the previous epidemic waves in Ukraine, Poland, Germany, and the world. Since before February 24, 2022 the estimation of the number of infectious persons per capita in Ukraine 3.6 times exceeded the global figure, the increase of the number the new cases and the pandemic duration was expected. In March 2022 the increase of the averaged number of new cases in the UK, Germany, and worldwide was visible. A simple formula to estimate the effective reproduction number based on the smoothed accumulated numbers of cases is proposed. The results of calculations agree with the figures presented by John Hopkins University and demonstrate a short-term growth of the reproduction number in the UK, Poland, Germany, Moldova, and worldwide in March 2022.

Ukiyo-e is a traditional Japanese painting style most commonly printed using wood blocks. Ukiyo-e prints feature distinct line work, bright colours, and a non-perspective projection. Most previous research on ukiyo-e styled computer graphics has been focused on creation of 2D images. In this paper we propose a framework for rendering interactive 3D scenes with ukiyo-e style. The rendering techniques use standard 3D models as input and require minimal additional information to automatically render scenes in a ukiyo-e style. The described techniques are evaluated based on their ability to emulate ukiyo-e prints, performance, and temporal coherence.

In this note, I analyze the data generated by M. Fodje's (2013) simulation programs "epr-simple" and "epr-clocked". They were written in Python and published on Github. Inspection of the program descriptions shows that they make use of the detection-loophole and the coincidence-loophole respectively. I evaluate them with appropriate modified Bell-CHSH type inequalities: the Larsson detection-loophole adjusted CHSH, and the Larsson-Gill coincidence-loophole adjusted CHSH (NB: its correctness is conjecture, we do not have proof). The experimental efficiencies turn out to be approximately eta = 81% (close to optimal) and gamma = 55% (far from optimal). The observed values of CHSH are, as they should be, within the appropriately adjusted bounds. Fodjes' detection-loophole model turns out to be very, very close to Pearle's famous 1970 model, so the efficiency is close to optimal. The model has the same defect as Pearle's: the joint detection rates exhibit signaling. Fodje's coincidence-loophole model is actually a clever modification of his detection-loophole model. Because of this, however, it cannot lead to optimal efficiency.

This article reevaluates the Woesean concept of crossing a ‘Darwinian threshold’ from pre-genomic communality, as prevailing in an ancestral ‘progenote’ state, to vertically stable lineages of autonomous and self-similar cells. This transition from collective trunk-line evolution to Darwinian speciation is dependent on the generation of modular organismal genomes. The same general principle should be valid at subcellular levels, allowing the emergence of semi-autonomous genomic agents, such as viruses and plasmid-carrying endogenous vesicles with organelle-like properties. As compartmentalized agents of endogenous nature could start with smaller genomes than those required for fully autonomous cells, it is conjectured that stable subcellular lineages emerged earlier than their cellular counterparts. Referring to the recent ‘pre-endosymbiont hypothesis’, it is proposed that free-living bacteria (the first ‘prokaryote’ cells) arose by ‘lineage escape’ from plasmid-bearing organelle-like compartments, evolving inside the internally complexifying ‘paracells’ of the progenote community. The double-membrane envelopes of diderm bacteria may have resulted from cell-biological processes facilitating cellular lineage escape. The later emergence of archaeal cells (resembling bacteria in ‘prokaryote’ appearance with unichromosomal genomes) and eukaryotic organisms (with compartmented cells and multichromosal genomes) can also be interpreted in terms of this modified progenote hypothesis. Conceivably, the multichromosomal genomes of eukaryotes were bundled in endogenous nuclear compartments to organize a ‘nuclear-cytoplasmic lineage’, which became vertically stable by perfecting mitosis/meiosis-like divisions and yet retained some intra-species population confluence by sexual division-fusion cycles.

Driven by the proliferation of DC energy sources and DC end-use devices (e.g., photovoltaics, battery storage, solid-state lighting, and consumer electronics), DC power distribution in buildings has recently emerged as a path to improved efficiency, resilience, and cost savings in the transitioning building sector. Despite these important benefits, there are several technological and market barriers impeding the development of DC distribution, which have kept this technology at the demonstration phase. This paper identifies specific end-use cases for which DC distribution in buildings is viable today. We evaluate their technology and market readiness, as well as their efficiency, cost, and resiliency benefits while addressing implementation barriers. The paper starts with a technology review, followed by a comprehensive market assessment, in which we analyze DC distribution field deployments and their end-use characteristics. We also conduct a survey of DC power and building professionals through on-site visits and phone interviews and summarize lessons learned and recommendations. In addition, the paper includes a novel efficiency analysis, in which we quantify energy savings from DC distribution for different end-use categories. Based on our findings, we present specific adoption pathways for DC in buildings that can be implemented today, and for each pathway we identify challenges and offer recommendations for the research and building community.

The present study provides new insights into the growth of brown algal cell wall by showing that cell wall polysaccharide plays an important role in the process of growth consider- ing the physicochemical characteristic of young and old Cladosiphon okamuranus. To determine its structural variation in detail, the cell wall was sequentially fractionated into five fractions: hot water (HW), ammonium oxalate, hemicellulose-I (HC–I), HC-II, and cellulose, and analyzed physicochemically. Results showed that almost 80% of the total recovery cell wall from both young and old thalli was HW and HC-I contained mainly fucoidan composed of Fuc, GlcA, and sulfate in molar ratios of 1.0: 0.3: 0.6~0.7 and 1.0: 0.3: 0.2~0.3, respectively. Fucoidan in HW was a highly sulfated matrix polysaccharide abundance in young thalli, while fucoidan in HC-I was rich in old thalli and functions as hemicellulose in land plants, crosslink with cellulose and strengthen the cell wall. We found that HW and HC-I were particularly involved in the growth and strength of old thalli appeared to be due to the deposition of HC-I and reducing of water content during the growth process.

Members of the genus Mycoplasma and related organisms impose a substantial burden of infectious diseases on humans and animals, but the last comprehensive review of mycoplasmal pathogenicity was published 20 years ago. Post-genomic analyses have now begun to support the discovery and detailed molecular biological characterization of a number of specific mycoplasmal virulence factors. This review covers three categories of defined mycoplasmal virulence effectors: 1) specific macromolecules including the superantigen MAM, the ADP-ribosylating CARDS toxin, sialidase, cytotoxic nucleases, cell-activating diacylated lipopeptides, and phosphocholine-containing glycoglycerolipids; 2) the small molecule effectors hydrogen peroxide, hydrogen sulfide, and ammonia; and 3) several putative mycoplasmal orthologs of virulence effectors documented in other bacteria. Understanding such effectors and their mechanisms of action at the molecular level connects the biology of the bacteria to direct effects on the host and host responses they elicit, and is expected to translate into new interventions for human and veterinary mycoplasmosis.

Transition metal complexes have historically played a pivotal role in creating vibrant pigments utilized across artistic mediums such as ceramics, paintings, and glass mosaics. Despite their extensive historical use, our understanding of the mechanisms governing transition metal complex behavior has predominantly emerged in recent times, leaving numerous aspects of this process ripe for exploration. These complexes exhibit striking color variations under diverse conditions when employed in pigment formulations. This review utilizes a bottom-up scientific approach, spanning from microscopic to macroscopic scales, to unravel the molecular origins of the colors generated by transition metal complexes in pigments and ceramic glazes. Advanced spectroscopy techniques and computational chemistry play pivotal roles in this endeavor, highlighting the significance of understanding and utilizing analytical data effectively, with careful consideration of each technique's specific application. Furthermore, the review investigates the influence of processing conditions on color variations, providing valuable insights for artists and manufacturers aiming to enhance the precision and quality of their creations while mitigating environmental impact.

This article explores the intricate dynamics of complexity and emergence through the lens of a graphical model representing hippocampal functions. Utilizing a series of overlapping curves that intersect at varying degrees and frequencies, we create a visual metaphor for the sophisticated processes to store information observed in the hippocampus. This model not only depicts the spatial and frequency-related interactions of these curves but also illustrates the emergent patterns that arise from these interactions. These patterns exemplify the principles of complexity and emergence, where the collective behavior of simple elements results in intricate and unexpected outcomes. This graphical representation serves as a bridge between the abstract mathematical concepts of complexity theory and the tangible biological processes observed in neuroscience. By drawing parallels to the hippocampus, known for its role in memory formation and spatial navigation, the article sheds light on how complex systems, such as neural networks, exhibit properties that are more than just the sum of their parts. The model thus offers a unique perspective on understanding complex systems, not only in neuroscience but in broader scientific inquiries where complexity and emergent phenomena are pivotal.

Does the choice of proxy for stock market development matter? This paper suggests that the growth effect of stock market development is sensitive to the choice of proxy and using alternative financial development indicators have practically no influence on the results. We found that using either the stock market capitalization to GDP ratio or the stock market returns; have a positive and significant effect on growth. However, we cannot make same conclusion when one uses either the ratio of total value of trades on the major stock exchanges to GDP or stock market turnover ratio to proxy for stock market development as the coefficient on these variables were found to be statistically insignificant. The indexes extracted from principal component analysis confirm the sensitivity of the effect to the choice of proxy. This finding suggest that stock market development is a conceptual terms, thus, representing it with single indicators make it impossible to identify which stock market development indicators have a significant positive growth effects.

It has often been said that Gaelic football (GF) and Australian Rules Football (ARF) are similar sports, and amateur Gaelic footballers have been recruited to play in the professional Australian Football League. Using Wilcoxons’s test, the significant (p < 0.05) factors differentiating winning and losing performance in ARF were indirectly compared to the differentiating factors between winning and losing in GF. Of the 15 key performance indicators (KPIs) that were seen to be significant between ARF teams, six (40 %) were also seen to be significant in discriminating between winning and losing GF teams. A Mann-Whitney U test was then completed to directly compare ARF and GF, twenty-six of the 30 KPIs were seen to be significantly different to each other (p < 0.05). The findings suggest that recruiting a Gaelic footballer based on the belief that their Gaelic background will aid their transition to ARF is not an appropriate decision. Instead, staying with more traditional methods of talent identification – for example anthropometric measurements – is advocated until further research is undertaken in this area.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

The main objective is to offer a functionally coherent counter-narrative to the polarized views prevailing now about the complex ‘Eukaryogenesis problem’ versus the “primitive” nature ascribed to so-called “Prokaryotes” (termed Akaryotes herein). The paradigm shift presented aims at bridging the conceptual gap between the rudimentary beginnings of biomolecular cooperativity on a pristine Earth (the Origins of Life or OoL) and the beginnings of lineage-wise diversification toward Darwinean speciation in the Tree of Life (or ToL). Although the research field as a whole is not aware of a corresponding ‘Prokaryogenesis problem’, the evolutionary process resulting in the partly independent archaeal and bacterial cell types is not fully understood. The present paper provides an explanation for these problems based on coevolutionary complementarity at multiple levels. The unconventional model connects various stages from “neighborhood selection” in film-like layers of unbounded “surface protoplasm” based on short “statistical proteins”, via a closely knit “peptide/RNA partnership” in the “making of genes”, toward the “making of genomes” in several RNA-to-DNA transitions. Three virus-related plasmids carrying different DNA replicases may have initiated the vertical stability of hereditable lineages that led to the three “domains” of organismal life, with a fourth lineage ending in eukaryotic organelles. These partly independent transitions established DNA as a late-comer of fundamental biomolecules.

Attention-Deficit/Hyperactivity Disorder (ADHD) exhibits a notable prevalence across diverse populations, with estimates ranging from 4% to 6%. This wide range prompts an investigation into the evolutionary and genetic underpinnings of ADHD, especially considering the markedly different environments faced by ancestral human populations compared to today's structured societies. This study examines the potential adaptive advantages of ADHD-associated traits in hunter-gatherer contexts, where hyperactivity, impulsivity, and novelty-seeking behaviors may have conferred survival benefits. We employ the principles of population genetics, including Hardy-Weinberg equilibrium, selection coefficients, and genetic drift, to model the dynamics of ADHD allele frequencies over time. Additionally, we discuss balancing selection as a mechanism for maintaining genetic diversity and how gene-environment interactions (GxE) contribute to the expression of ADHD in contemporary settings. Our analysis suggests that traits associated with ADHD, while potentially maladaptive in modern structured environments, could have been preserved through evolutionary processes due to their adaptive value in ancestral contexts. Understanding these dynamics provides a comprehensive view of ADHD's prevalence and highlights the significance of genetic and environmental interplay in shaping human behavior.

To show that underlying Schmitt's account of fascist politics lies a Gnostic-like metaphysical dualism separating the realms of value and power. Contrary to the normative political tradition of the West, which defends an ethical politics, Schmitt - jurist and theorist of the Nazis - aligns himself with Machiavelli and Hobbes to defend realpolitik: where sovereignty is ultimately a function of the Dictator's will alone. This paper shows the contradiction within such a position, which criticizes values in politics but by its advocacy, and its defense of the Dictator's willing, relies on valuation, choice, and hence the ethical.

Invasive weeds cause significant crop yield and economic losses in agriculture. The highest in-direct impact may be attributed to the role of invasive weeds as virus reservoirs especially within the commercial growing areas. The new tobamovirus tomato brown rugose fruit virus (ToBRFV), recently identified in the Middle-East, overcomes the Tm-22 resistance allele in the cultivated tomato varieties grown in greenhouses. In this study, we determined the role of invasive weed species as potential hosts for ToBRFV and pepino mosaic virus (PepMV). Out of all tested weed species, the invasive species So-lanum elaeagnifolium and S. rostratum, mechanically inoculated with ToBRFV, were positive for To-BRFV in both enzyme linked immunosorbent assay (ELISA) and RT-PCR tests. S. rostratum was also positive for PepMV. No conspicuous phenotype was observed on ToBRFV infected S. elaeagnifolium plants suggesting a hostplant associated defense response. S. rostratum plants inoculated with either ToBRFV alone or a mixture of ToBRFV and PepMV-IL, contained high ToBRFV levels. In addition, when inoculated with ToBRFV or PepMV-IL disease symptom manifestations were observed in S. rostratum plants and the symptoms were exacerbated upon mixed infections with both viruses. The distribution and abundance of both Solanaceae species increase the risks of virus transmission between species.

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

This study presents a computational simulation to explore the distinctive patterns of neural connectivity in Autism Spectrum Disorder (ASD), focusing on the concepts of spatial and topological proximities. ASD is characterized by unique cognitive and behavioral profiles, often attributed to atypical neural development and connectivity. Our simulation employs a two-pronged approach: first, by modeling spatial proximity through the generation of clustered 3D node positions, we mimic the observed over-connectivity in localized brain regions in ASD. Second, we construct a topological network to represent the complex interplay of under-connectivity and over-connectivity in functional brain networks, a hallmark of ASD's neural landscape. The spatial model demonstrates pronounced clustering, reflecting the structural brain differences and atypical growth patterns reported in neuroimaging studies of individuals with ASD. In contrast, the topological model reveals a network with a mix of sparse and dense connections, simulating the diverse and often contradictory findings of functional connectivity in ASD, such as reduced long-range connections and increased local connections. Our simulation provides a visual and conceptual framework for understanding the altered neural connectivity in ASD. It underscores the importance of considering both physical (spatial) and functional (topological) aspects of brain connectivity to grasp the full extent of neurodevelopmental deviations in ASD. This approach not only aids in elucidating the neural underpinnings of ASD's core symptoms but also offers a foundation for developing targeted interventions. Future research, integrating more complex and individual-specific data, could further refine this model, enhancing our understanding of ASD's neural dynamics and contributing to personalized therapeutic strategies.

Sociality in animal populations is a continuum, and interactions between conspecifics are meaningful for all vertebrates. Ignorance of social structures can lead to misunderstanding their ecology and, consequently, to unsuccessful species management. Here, we combined genetic and spatial data on radio-collated brown bears (Ursus arctos) to investigate kin-related home range overlap and kin-related centroid distance within central and eastern Finland. We found that the extent of overlap of home ranges was positively linked with relatedness among adult females. A similar positive correlation could be detected between home range centroid distance and relatedness among adult females. Moreover, there were significant differences between the two studied regions: female brown bears in central Finland were more closely related to each other, and the sizes of their home ranges were larger than those in eastern Finland. The smaller home ranges and lower degree of relatedness among bears in eastern Finland might be a result of the substantially higher hunting pressure in the area, combined with immigration of new unrelated individuals from Russia.

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

The complex dynamics of the neocortex, the outermost layer of the brain, have been a subject of intense research in neuroscience. Recent studies have suggested that magnetic fields generated by neuronal activity may play a significant role in neocortical dynamics. This paper presents a simplified mathematical model that explores the hypothesized interactions between magnetic dynamos, nondissipative systems, Hamiltonian equations, and the Lorenz force in the context of neocortical dynamics. The proposed model is based on a set of coupled Hamiltonian equations inspired by the Lorenz system, a well-known chaotic dynamical system. The generalized coordinates in the model represent the magnetic field components, while the generalized momenta are related to the electric field components or other relevant quantities. The Hamiltonian equations describe the conservative dynamics of the system, and the coupling terms in the equations are interpreted as representing the interactions between the magnetic and electric field components, analogous to the Lorenz force in electromagnetism. The model is implemented using Python, and the Hamiltonian equations are numerically solved using the odeint function from the scipy.integrate module. The resulting dynamics of the magnetic field components are visualized using matplotlib. While the model is highly simplified and does not capture the full complexity of neocortical dynamics, it serves as a starting point for investigating the potential role of magnetic dynamos and Lorenz force interactions in the brain. The paper discusses the limitations of the current model and highlights the need for further refinements, such as incorporating more realistic biological constraints, considering energy dissipation and compensation mechanisms, and validating the model against experimental data. Future work should focus on developing a more comprehensive and biologically plausible model that integrates the latest findings from neuroscience, physics, and computational modeling. By presenting this simplified Hamiltonian model, the paper aims to stimulate further research and discussion on the potential significance of magnetic dynamos and Lorenz force interactions in neocortical dynamics. The model provides a framework for exploring these hypothesized mechanisms and may guide future experimental and theoretical investigations in this emerging field of neuroscience

This paper presents data supporting the IC Regimen for potentiating the effectiveness of lorlatinib in treating ALK positive cancers, and specifically non-small cell lung cancer. Lorlatinib is an effective treatment for ALK driven non-small cell lung cancer and other ALK driven cancers. Lorlatinib inhibits ALK kinase and achieves good brain tissue levels, a common site for metastases in lung cancers. However, resistance to lorlatinib usually supervenes and the cancer awakens and starts growing again, resistant to lorlatinib. This paper analyses data indicating that adding two common generic drugs, itraconazole and cilostazol, to lorlatinib treatment may delay resistance development. Itraconazole is marketed worldwide as a generic antifungal drug that also inhibits Hedgehog signaling, CYP3A4, and the p-gp efflux pump. Cilostazol is a generic anti-thrombosis, phosphodiesterase 3 inhibiting drug that carries minimal bleeding risk. Cilostazol may enhance lorlatinib by deprivation of trophic growth factors supplied by platelets. Itraconazole may enhance lorlatinib effectiveness by reducing or stopping a Hedgehog centered amplifying feedback loop with ALK kinase. The combination of metastatic non-small cell lung cancer being a low-survival disease and the general safety itraconazole plus cilostazol augmentation, make a clinical trial of this trio worthwhile.

The intricate architecture of dendritic arborization is fundamental to the formation and functionality of neural networks, serving as the primary site for synaptic integration and signal propagation. This study presents a pioneering computational model that simulates dendritic growth dynamics, employing exponential and logarithmic scaling over an extended developmental period of 720 days. This model offers a valuable tool for investigating the implications of diverse dendritic growth patterns on neural development, synaptic connectivity, and ultimately, cognitive functions. The computational framework incorporates biologically plausible parameters, allowing for the systematic exploration of dendritic branching patterns and their potential impact on neuronal information processing. By simulating exponential and logarithmic growth scales, the model captures the inherent complexity and diversity of dendritic morphologies observed in various neuronal populations across different brain regions. The findings from this study hold significant implications for our understanding of neural circuit assembly, synaptic integration, and the potential functional consequences of aberrant dendritic growth patterns observed in neurodevelopmental disorders. Furthermore, the model's ability to simulate extended developmental trajectories over a prolonged period of 720 days offers insights into the dynamic interplay between dendritic growth and synaptic pruning, which is crucial for the refinement and optimization of neural networks.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

The SARS–CoV-2 infection has caused both acute and chronic COVID–19 disease during the recent pandemic with emerging more transmissible SARS–CoV–2 Omicron variants (BQ1 and XBB1) that have increased demands for more effective immunogens and therapeutic approaches to protect the lives of numerous SARS–CoV-2 affected individuals and reduce overall disease burden that could be affected by concurrent other pathogens causing diseases. Following a worldwide campaign of mass vaccination, there is still a significant demand to quell the harmful effects of novel SARS–CoV–2 infections due to higher mutation rates within specific areas of the SARS–CoV-2 domain, leading to enhanced viral entry, especially within individuals with one or more significant comorbidities, and there is still a dilemma of how prevention of future pandemics will occur as within host animal mutations and cross species transfer naturally occurs. Concerns intersect at a specific point; a gained evolutionary ability of several viruses over the previous centuries to remain undetected during the first stages of infection by means of capping the 5' end of their DNA and RNA genes respectively. This may occur by reducing the rate of host Type I and Type III Interferons (IFN) cellular synthesis, that would usually occur and affect both apoptotic pathways, that facilitate viral replication and clearance, as well as immune cells, that process and present pathogenic antigen epitopes. Furthermore, although methods of vaccination exist, other methods in clinical development remain that could evoke an immune response in different cellular, serum or mucosal compartments being cellular, serum and mucosal that evoke differential antibody responses. Antibodies are classed as natural and synthetic. Natural antibodies are further classified into neutralizing and non-neutralizing, whilst synthetic antibodies are also further classified into monoclonal and polyclonal. As a result of single cell study transcriptome research, viruses do utilize an array of protein receptors for receptor-mediated cellular entry. This, therefore suggests that potential differential production of antibody immunoglobulins (Ig) within serum and mucosal areas remains affected by cytokines, adhesion molecules and chemokines that can be upregulated or downregulated upon host viral infection. Serum plasma antibodies can be multimeric that may not efficiently cross the nasal epithelium cell layer, therefore offering less protection against mucosal inflammation due to mucin proteins. On the other hand, antibodies produced by mucosal plasma cells at epithelial surfaces are known to provide effective immune responses in some viral infections. The existence of developments that stimulate mucosal immune responses has so far only been seen with influenza nasal immunogens. Nevertheless, scientists developed ways of immunization and early treatment worldwide that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration. For example, the administration of human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can stimulate cellular activity to train the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Recently, it was discovered that specific plants secrete proteins that also stimulate the production of Type I Interferons. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. Naturally-selected polymorphic viruses through genetic recombination pose challenges to traditional concepts of cellular and molecular immune system neutralization of these viruses during the first stages of cellular infection. It is until the scientific community realizes this potentially crucial aspect that we will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently monkeypox. Type I IFNs tend to be produced faster than Type III IFNs, and the first induce slightly more abundant pro-inflammatory signals than the latter, meaning that type III IFNs, if produced early, may further decrease the extent of excessive proinflammatory signals. Hence, we believe that nasal sprays containing a low dosage of Type I and Type III IFNs not only represent a relevant COVID-19 therapeutic, but also a potential unknown modulatory therapy of the future. Of note, it has been indicated that IFN I and / or III display significant immunizing and early therapeutic effects for other viral evoked diseases like Influenza (Influenza (A)H1N1), rabies (Rabies lyssavirus), measles (Measles virus), rubella (Rubivirus rubellae), Hepatitis B, HIV-induced AIDS, Ebola, Marburg, as well as bacterial diseases, such as lower respiratory tract infectious diseases induced by Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus, and a number of oncological diseases, like hepatic melanoma.

Temperature is the abiotic factors that strongly influence the biology and behavior of insects. Thus, we assessed the development of the egg parasitoids, Ooencyrtus submetallicus and Telenomus podisi, parasitizing eggs of the brown stinkbug, Euschistus heros, at different temperatures, in addition to estimating the average number of generations using temperature records for seven representative soybean producing regions in Brazil. The comparative biology study conducted evidenced that O. submetallicus and T. podisi had similar percentages of parasitism and emergence, life cycle duration (egg-adult), and longevity. The sex ratio and the number of adult parasitoid emerged per parasitized egg was superior for O. submetallicus. The study of thermal requirements evaluated temperatures of 16, 19, 22, 25, 28, 31, and 33 °C. Ooencyrtus submetallicus and T. podisi developed at temperatures between 16 and 31°C. The lower temperature (Tb) threshold for O. submetallicus and T. podisi was 9.3° and 6.7°C, while the thermal constant (K) was 336.9 and 272.7 degree days, respectively. The estimated average number of generations per year for both parasitoids was greater than the pest E. heros. Ooencyrtus submetallicus and T. podisi exhibited the same biological capacity to parasitize and to develop parasitizing E. heros eggs under laboratory studied conditions. The temperature range between 16° and 33 °C was favourable for the development of both parasitoids parasitizing E. heros eggs.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

Adaptive bitrate (ABR) algorithms optimize the quality of streaming experiences for users in client-side video players especially in unreliable or slow mobile networks. Several rule-based heuristic algorithms can achieve stable performance, but they sometimes fail to adapt properly to changing network conditions. Fluctuating bandwidth may cause algorithms to default to behavior that creates a negative experience for the user. ABR algorithms can be generated with reinforcement learning, a decision-making paradigm in which an agent learns to make optimal choices through interactions with an environment. Training reinforcement learning algorithms for bitrate streaming requires building a simulator for an agent to experience interactions quickly; training an agent in the real environment is infeasible due to the long step times in real environments. This project explores using supervised learning to construct a world-model, or a learned simulator, from recorded interactions. A reinforcement learning agent trained inside of the learned model, rather than a simulator, can outperform rule-based heuristics. Furthermore, agents trained inside the learned world-model can outperform model-free agents in low sample regimes. This work highlights the potential for world-models to quickly learn simulators, and to be used to generate optimal policies.

Global coverage and scale up of interventions to reduce newborn mortality remains low, though progress has been achieved in improving newborn survival in many low-income settings. An important factor in the success of newborn health interventions, and moving to scale, is appropriate design of community-based programs and strategies for local implementation. We report the results of formative research undertaken to inform the design of a newborn health intervention in Cambodia. Information was gathered on newborn care practices over a period of three months using multiple qualitative methods of data collection in the primary health facility and home setting. Analysis of the data indicated important gaps, both at home and facility level, between recommended newborn care practices and those typical in the study area. The results of this formative research have informed strategies for behavior change and improving referral of sick infants in the subsequent implementation study. Collection and dissemination of data on newborn care practices from settings such as these can contribute to efforts to advance survival, growth and development of newborns for intervention research, and for future newborn health programming.

We describe electron temperature measurements in the SSX MHD wind tunnel using two different methods. First, we estimate T_e along a chord by measuring the ratio of the C__III 97.7 nm to C_IV 155 nm line intensities using a vacuum ultraviolet monochrometer. Second, we record a biasing scan to a double Langmuir probe to obtain a local measurement of T_e. The aim of these studies is to increase the Taylor state lifetime, primarily by increasing the electron temperature. Also, a model is proposed to predict magnetic lifetime of relaxed states and is found of predict the lifetime satisfactorily. Furthermore, we find that proton cooling can be explained by equilibration with the electrons.

Urban lakes, especially those of natural origin, provide ecosystem services, recreation being one of the most important and highly valued by the city dwellers. Fulfilling the needs of city residents to relax and have contact with nature has become a priority in urbanized areas and has been proved to positively affect people’s health and well-being. The recreational potential of water bodies was identified to be most important aspect of ecosystem services to the residents of the neighboring areas. An assessment of recreational ecosystem services (RES) provisioning to society based on the real time spent by the citizens and housing values in the rural-urban gradient revealed that the economic benefits of lakes differ in urbanized, suburban and rural landscapes. The growth of cities has led to an increased population density in the surroundings of ecologically valuable areas, resulting in higher pressure from visitors seeking recreational areas. Along with urbanization, the impoverishment of ecosystem functions takes place, limiting their capability to provide ecosystem services. In this work provisioning of recreational ecosystem services of 28 floodplain lakes located along the urban-rural gradient of the Warsaw agglomeration was assessed. The relationship between the ecological value of the water bodies, measured using naturalness indices, and the recreational ecosystem services they can provide was assessed. The results showed that the floodplain lakes located along the urban-rural gradient are of a great importance to the citizens due to their recreational potential. The provisioning of recreational ecosystem services is poorly connected with the ecological characteristics of the floodplain lakes. Only hemeroby, was significantly correlated with provisioning, and there was no relationship with factors such as naturalness of vegetation or water quality, demonstrating that public preference was not generally influenced by high ecological quality. These data should be available to potential buyers and be integrated in spatial planning management plans in order to shape future housing policy.

Unnatural diet composition and frequent feeding regimes may play an aetiological role in the multiple diseases prevalent in captive cheetahs. This study investigated the responses of captive-born (hand-reared) cheetahs (n = 6) to a reduced feeding frequency schedule. During the 3-week treatment period, the study cheetahs were fed four once-daily meals per week and two daily rations six days a week, subsequently, during the control period of equal duration. Total weekly food intake was maintained throughout the study. Variations in body temperature (Tb), heart rate (HR), locomotor activity (LA), behaviour, faecal glucocorticoid metabolite concentration, and faecal consistency score (FCS) were measured. Less frequent feeding resulted in higher FCS (p < 0.01) and LA (p < 0.0001) and lower HR (p < 0.0001) among the studied cheetahs. The study found that their HR was higher when the cheetahs were fed (p < 0.0001) than on days when they were not. Additionally, Tb (p < 0.0001) and HR (p < 0.05) were higher during feeding, suggesting a psychological excitation to food consumption. The results of the FCS analysis indicate that the more natural feeding pattern could have benefited the studied cheetahs’ GI health without a significant behavioural or physiological stress response to the change in feeding frequency.

Tomato is one of the most important vegetable crops grown worldwide. Tomato brown rugose fruit virus (ToBRFV), a seed-borne tobamovirus, poses a serious threat to tomato productions due to its ability to break the resistant genes (Tm-1, Tm-2, Tm-22) in tomato. The objective of this work was to identify new resistance source(s) of tomato germplasm against ToBRFV. To achieve this aim, a total of 476 accessions from 12 Solanum species were tested with the ToBRFV US isolate for their resistance and susceptibility. As a result, a total of 44 asymptomatic accessions were identified as resistance/tolerance, including 31 accessions of S. pimpinellifolium, one accession of S. corneliomulleri, four accessions of S. habrochaites, three accessions of S. peruvianum and five accessions of S. subsection lycopersicon hybrid. Further analysis using serological tests identified four highly resistant S. pimpinellifolium lines, PI 390713, PI 390714, PI 390716 and PI 390717. The inheritance of resistance in the selected lines was verified in next generation and confirmed by RT-qPCR. To our knowledge, this is a first report of high resistance to ToBRFV in S. pimpinellifolium. These new genetic resources will expand the genetic pool available for breeders to develop new resistant cultivars of tomato against ToBRFV.

Of the documented tick-borne diseases infecting humans in Mexico, Rocky Mountain spotted fever (RMSF), caused by the gram-negative bacterium Rickettsia rickettsia, is responsible for most fatalities. Given recent evidence of brown dog tick, Rhipicephalus sanguineus sensu lato, as an emerging vector of human RMSF, we aimed to evaluate dogs and their ticks for rickettsiae infections as an initial step in assessing the establishment of this pathosystem in a poorly studied region of northeastern Mexico while evaluating the use of dogs as sentinels for transmission/human disease risk. We sampled owned dogs living in six disadvantaged neighborhoods of Reynosa, Northern Mexico to collect whole blood and ticks. Of 168 dogs assessed, tick infestation prevalence was 53%, comprised of exclusively R. sanguineus s. l. (n=2,170 ticks). Using PCR and sequencing, we identified an overall rickettsiae infection prevalence of 4.1% (n=12/292) in ticks, in which eight dogs harbored at least one infected tick. Rickettsiae infections included R. amblyommatis and R. parkeri, both of which are emerging human pathogens, as well as candidatus R. andeanae. This is the first documentation of pathogenic Rickettsia in R. sanguineus s.l. collected on dogs from northeastern Mexico. Domestic dog infestation with Rickettsia-infected ticks indicates ongoing transmission, thus humans are at risk for exposure and underscores the importance of public and veterinary health surveillance for these pathogens.

The COVID-19 pandemic caused significant training disruptions during the 2020-21 season due to lockdowns, quarantines, and strict adherence to pandemic protocols. The main purpose of this study was to determine how pandemic training restrictions affected training volume and performance in one collegiate swim team. Cumulative training volume data, across a 28-week season, were compared between a pandemic (2020-2021) versus non-pandemic (2019-2020) season. Swimmers were categorized into three groups (Sprinters, Mid-Distance, and Long-Distance) based on training group. Performance times in 25 swimmers who competed in Regional Championships, during both the non-pandemic and pandemic year, were compared via 1-way ANOVA. 26 male and 22 female swimmers commenced the 2020-21 (pandemic) season, with 23% of swimmers voluntarily opting out. Three COVID-19 cases were confirmed (2%) by the medical staff with no long-term effects. Significant reductions in average swim volume were verified in Sprinters (32,867±10,135 vs.14,800±7,995yards;p<0.001), Mid-Distance (26,457±10,692 vs.17,054±9.923yards;p<0.001), and Long-Distance (37,600±14,430 vs.22,254±14,418yards;p<0.001) swimmers (non-pandemic vs. pandemic season, respectively). In the Regional performance analyses, the Sprinters swam faster (n=8;-0.5±0.6secs), while Mid-Distance (n=10;0.17±2.1secs) and Long-Distance (n=7;6.0±4.9secs) swimmers swam slower (F=11.76;p=0.0003;r²=0.52). Thus, the pandemic caused significant reductions in swim training volume, with Sprinters performing better and Long-Distance swimmers performing worse at Regional Championships.

Type 2 diabetes mellitus (T2DM) poses a significant public health challenge. Prioritising its prevention is essential. With the growing interest in wearable health technologies continuous glucose monitoring systems (CGMs) have expanded their scope, transitioning from exclusive use in diabetes management to lifestyle enhancement for individuals without diabetes. While CGMs primarily target glycaemic stabilization, their potential role in mitigating noncommunicable conditions, including T2DM, warrants exploration. This review examines the regulation of CGMs and critically assesses the purported benefits of CGMs for individuals without diabetes, as presented in the 'health and wellness' sector: (1) early dysglycaemia detection through glucose variability observation; (2) refining glycaemic control by tailoring nutrition according to postprandial glucose response; and (3) promoting and fine-tuning physical activity based on instantaneous data feedback. We find a lack of compelling evidence for the utility of CGMs in PNLD, including accuracy, data analysis and interpretation metrics, and user acceptability markedly under-researched. A paucity of research exists on the unanticipated negative consequences of CGM usage, such as obsessive symptom tracking and potential onset of disordered eating, like orthorexia. Given the increasing adoption of CGMs by individuals without diabetes, this review underscores the need of addressing these research gaps to ensure safety and reliability of CGMs in novel contexts. We emphasise the importance of refining CGM regulation in the UK, particularly when considering its ‘off-label’ use. Marrying robust scientific evidence with effective regulation is pivotal in fortifying the coherence, equity, and effectiveness of diabetes prevention initiatives, while protecting the wellbeing of CGM users.

Osteitis fibrosa cystica (OFC) and Brown Tumour are two related but distinct types of bone lesions that result from overactivity of osteoclasts most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions placing them in the spectrum of RAS-MAPK-driven neoplasms, while until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumour such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumour includes clinical symptoms involving chronic bone pain and laboratory finding of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically both lesions are characterized by clustered osteoclast in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumour.

Tendon injuries, while prevalent, present a significant challenge in fully restoring their structural and functional integrity. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored Met's effects on tendon healing and repair and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met -administered before or after injury, as well as both - effectively prevent the release of HMGB1 into the tendon matrix and reduce circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-β1 levels within the healing tendon. These interventions also improved tendon healing by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III, and enhancing the presence of collagen type I. These outcomes highlight Met's anti-fibrotic properties on acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.

Rice blast and brown planthopper (BPH) are two of the most destructive diseases and pests in rice (Oryza sativa L.) production in China. The development of multi-resistant varieties is widely recognized as the most efficient and environmentally friendly approach to controlling crop diseases and pests. Functional molecular markers (FMMs) have been developed from functional variants in the genic region associated with trait variation, greatly enhancing the efficiency of identifying and pyramiding valuable genes in crop breeding. In this study, two FMMs and a multiplex PCR amplification system were developed for two major broad-spectrum BPH resistance genes, Bph6 and Bph9. By assistance of FMMs in multi-resistant rice restorer line development pipeline, two lines (Huahui7713 and Huahui3006) with blast and BPH resistance were developed by pyramiding three resistance genes Pigm, Bph6 and Bph9. Huahui7713 and Huahui3006 as male lines, two new hybrid rice varieties (WeiLiangYou7713 and Xuanliangyou3006) were certificated and commercial released in China. WeiLiangYou7713 and Xuanliangyou3006 showed improved blast and BPH resistance, and no penalty on yield and grain-quality. Annual promotion area of WeiLiangYou7713 has exceeded 53.3 thousand hectares, indicating its widespread adoption and success in the market. Huahui7713 and Huahui3006 could have great potential for utilization in blast and BPH resistance rice breeding.

Cardiac amyloidosis (CA) results mainly from infiltration of myocardium by either immunoglobulin light chain fibrils (AL) or transthyretin fibrils (ATTR), causing restrictive cardiomyopathy and eventually death if untreated (3). AL derives from monoclonal immunoglobulin light chain produced by plasma cell clone in the bone marrow, while ATTR is the misfolded form of hepatically-derived transthyretin (TTR) protein, and could be hereditary (hATTR) or wild-type (wtATTR). Over the last decade, improvement in diagnostic imaging and better clinical awareness has unleashed a notable presence of CA in the community, especially ATTR in the elderly population. These multimodality imaging modalities include echocardiography, cardiac magnetic resonance and radionuclide scintigraphy with bone-avid tracers. There has been remarkable progress in the therapeutic landscape as well, and there are disease-modifying therapies available now that can alter the course of the disease and improve survival if initiated at an early stage in the disease. There remains an unmet need for detecting this disease accurately and early, so that these patients could benefit the most from newly-emerging therapies.

The 55-million-year history of equine phylogeny has been well documented from the skeletal record, however not the soft tissue structures that are now vestigial in modern horse. A recent study reported 2 ligamentous structures resembling functional 3^rd and 4^th interosseous muscles were evident in Dutch Konik horses. The current study investigates this finding and compares it to members of the genus Equus to identify either a breed anomaly or functional primitive trait. Distal limbs (n=571) were dissected from 4 species of Equus; E. caballus, E. asinus, E. przewalskii and E. burchelli beohmi. Breed representatives of E.caballus (n=18) included the primitive Dutch Konik. The 2^nd and or 4^th interosseous muscle was evident in all 4 species, but only 2 breeds of E.caballus expressed this trait - the Dutch Konik and Bosnian Mountain Horse. These 2 breeds were the only close descendants of the extinct Tarpan (Equus ferus ferus) represented in this study. In conclusion, the 2^nd and 4^th interosseous muscles originated from the distal nodule of respective splint bones and inserted into the corresponding branches of the 3^rd interosseous muscle proximal to the sesamoids. Suggesting a functional role in medial and lateral joint stability and a primitive trait in modern equids.

The proportion of adults aged over 60 years in the world is expected to reach 20% by the year 2050. Ageing is associated with several physiological changes that increase the risk of malnutrition among this population. Malnutrition is characterized by deficiencies or insufficiencies of macro- and micronutrients. Malnutrition has detrimental effects on the health, wellbeing and quality of life of older adults. Nuts are rich in energy, unsaturated fats, protein, as well as other nutrients that provide a range of health benefits. While the effects of nuts on overnutrition have been studied extensively, very few studies have been specifically designed to understand the role of nuts in mitigating undernutrition in the elderly. Therefore, this review explores the potential role of nuts in improving the nutritional status of older adults who are at risk of undernutrition. Several properties of whole nuts, some of which appear important for addressing overnutrition, (e.g. hardness, lower-than-expected nutrient availability, satiety-enhancing effects) may limit their effectiveness as a food to combat undernutrition. However, we propose that modifications such as transforming the physical form of nuts, addressing the timing of nut ingestion, and introducing variety may overcome these barriers. This review also discusses the feasibility of using nuts to prevent and reverse undernutrition among older adults. We conclude with a recommendation to conduct clinical studies in the future to test this conceptual framework.

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

The texture properties of cooked rice are a dominant property which can indicate the eating quality. Evaluation of back extrusion (BE) test precision and sensitivity for cooked germinated brown rice (GBR) texture in production process was investigated in this study. BE test on texture properties of cooked GBR rice show high precision of measurement of hardness, toughness and stickiness tests which indicated by the repeatability and reproductivity test but the sensitivity indicated by coefficient of variation of the texture properties. The findings of the study of the effect of different soaking and aging duration in the production of Khao Dawk Mali 105 (KDML 105) GBR on cooked GBR texture measured by BE test confirmed the developed protocol for evaluation of high precision and sensitivity of the texture measurement method. Repeatability and reproducibility of reliable measurements have a low standard deviation of the farthest different between replicates, which is considered high precision. High coefficient of variation where the relative wide variation of the absolute value of the property can be detected indicate high sensitivity which even small resolution can be detected or vice versa. But the correlation coefficient among the texture properties by BE were not related to the precision or sensitivity of the test. By these results, the original protocol for determination of precision and sensitivity of food texture measurement was successfully verified as the usable evaluation protocol for GBR texture measurement.

To get a better knowledge of the effects of residual chlorothalonil on soil characteristics and soil microbial communities, we evaluated the dissipation of chlorothalonil and the effects of different chlorothalonil concentrations on soil respiration, enzyme activities, and microbial community structure in yellow-brown loam soils. Bacterial and fungal soil communities were examined using traditional plate counting and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR–DGGE) methods. Soil properties and the results of DGGE band analysis were both used to estimate the status of the soil microbial ecosystem. The results show that residual chlorothalonil has considerable effects on soil respiration, enzymatic activities, and microbial community structure. In particular, soil respiration and phosphatase activities were increased, while saccharase activity, microbial biomass, and microbial community diversity were decreased by increasing levels of chlorothalonil treatment. Correlation analyses revealed that the application of chlorothalonil was significantly correlated with the change of the soil respiration, urease activity, sucrase activity, soil culturable bacteria and culturable fungi biomass. We conclude that residual chlorothalonil is directly related to soil respiration, enzyme activities, and microbial community structure.

Animals in human care are affected by stressors that can ultimately reduce fitness. When reproduction is affected, endangered species’ conservation programmes can be severely compromised. Thus, understanding factors related to stress and reproduction, and measures of related hormones, are important to ensure captive breeding success. Red pandas are endangered and populations in the wild are threatened with extinction. A global captive breeding programme has been launched to conserve the species with the goal of reintroduction. However there is little informaiton on how stressors impact reproductive aspects of the species. This study measured fecal glucocorticoid (fGCM), fecal progestagen (fPM) and fecal androgen (fAM) metabolite concentrations in 12 female and 8 male red pandas (Ailurus fulgens fulgens) at three zoos in northeastern India to determine predictors of adrenal and gonadal steroid activity and the influence of fGCM on reproduction. Results indicated that fGCM concentrations were higher in males than females, and positively correlated with number of visitors, while negatively related to frequency of feedings and enclosure area. Sex, visitor number, frequency of feeding, and enclosure area explained 67% of the variations in fGCM concentrations in the study population. Concentrations of fPM were positively associated with tree density in the enclosure, explaining 47% of the variation among females. For fAM, positive associations were found with frequency of feeding, but concentrations were negatively related to age and number of visitors; these three covariates explained 45% of the variation in fAM concentration among males. Comparison of fGCM with fPM showed a negative trend, indicating increasing adrenal hormones may decrease reproductive function among female red pandas. The study thus suggests that zoo management should consider increasing feeding frequency, providing larger enclosures with more trees, and regulating visitor numbers to reduce stress and increase reproductive fitness among red pandas.

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. It’s elegantly simplicity was an inspired development by Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty.

Simulated crime scene investigation is an essential component of forensic science education, but its implementation poses challenges relating to cost, accessibility and breadth of experience. Virtual reality (VR) is an emerging technology which offers exciting prospects for teaching and learning, especially for imparting practical skills. We document here a multidisciplinary experimental study in which a bespoke VR crime scene app was designed and implemented, after which it was tested by both undergraduate student and staff/postgraduate student cohorts. Through both qualitative and quantitative analyses, we demonstrate that VR applications support learning of practical crime scene processing skills. VR-based practical sessions have the potential to add value to forensic science courses through offering cost-effective practical experience and the ability to work in isolation, in a variety of different scenarios. Both user groups reported high levels of satisfaction with the process and reports of adverse effects (motion sickness) were minimal. With reference to user feedback, we proceed to evaluate the scalability and development challenges associated with large-scale implementation of VR as an adjunct to forensic science education.

The irradiation biology of the brown marmorated stink bug (BMSB, Halyomorpha halys Stål) treated at the nymphal stage was investigated to determine its application for sterile insect technique (SIT). Fifth instar males of BMSB were exposed to gamma-radiation 60Co at different doses of 12, 16, 20, 24 and 64 Gy. Irradiated males were mated with non-irradiated virgin females to assess the longevity of both sexes, female fecundity and fertility of their offspring until the egg stage of the F2 generation. The mortality of each of the developmental stages of the F1 and eggs of the F2 generation was observed to determine whether negative effects from exposure to radiation was inherited. The data indicated that irradiation significantly reduced the lifespan of male insects at doses above 20Gy. Irradiated males did not affect the longevity and fecundity of their female partners, nor either sex of their resulting progeny, but it did reduce the hatch rate of the eggs at all doses tested. The sterility rates of F1 eggs were 55.6%, 73.3%, 74.1% and 74.1% at doses of 12Gy, 16Gy, 20Gy and 24Gy respectively. Eggs were completely sterile (100%) at a dose of 64Gy with no egg hatch recorded. A low hatch rate of F2 eggs illustrated that negative effects from radiation was inherited by the subsequent generation. The results support the potential for the use of SIT for BMSB management by irradiating the fifth instar male nymphs at 16-64Gy.

Credit rationing, especially prevalent for smaller firms, impedes economic growth. A Central Bank aligned “not for profit” managed business to business “Stable-Coin” (“Synthetic Central Bank Digital Currency”) providing trade debt liquidity can lower small firm credit rationing. It raises growth by reducing monetary transmission imperfections consequent upon asymmetric information, commercial bank underwriting restrictions, market power dynamics and regulatory distortion. A simple framework is developed to contextualise small firm credit rationing and associated monetary transmission imperfections with broader credit flows into both the real and monetary sectors. Evidence is presented regarding US monetary transmission efficacy to firms, paving the way to proposing a trade debt business to business focused stable-coin to help close credit rationing gaps. Designed to minimise “moral hazard”, the proposed stable-coin provides an additional monetary transmission channel that supplies interest free trade debt funding to firms to support economic activity and raise growth. In addition to helping close the small firm financing gap, the stable-coin provides policy makers with an additional contra-cyclical monetary transmission instrument to minimise real economic disruption consequent upon financial system crises and liquidity events.

This article presents a novel computational approach to visualizing memristor dynamics within a simulated neural network. Memristors, known for their ability to emulate synaptic plasticity due to their variable resistance characteristics, are key components in neuromorphic computing and hold potential for advancing our understanding of neural processes. Our study introduces a sophisticated memristor model that incorporates non-linear resistance changes, simulating the complex behavior of synaptic connections in a neural network.The neural network, consisting of multiple interconnected neurons with memristor-based synapses, is subjected to a series of electrical stimuli. Each memristor's resistance is modulated in response to the applied voltage, mimicking the synaptic weight adjustments that occur during learning and memory formation in biological neural networks. To effectively illustrate these changes, we employ a high-contrast color mapping scheme, where the varying resistance of each memristor is represented by distinct colors, providing a clear and intuitive visualization of synaptic modifications over time.Our simulation runs through multiple iterations, demonstrating how synaptic weights evolve in response to different input patterns. The use of an extended voltage range and increased scaling factors ensures pronounced changes in memristance, enhancing the visibility of synaptic adaptations. The resulting visualizations offer a compelling representation of how memristors can mimic the dynamic nature of biological synapses, contributing to the field of neuromorphic engineering and deepening our comprehension of neural mechanisms underlying learning and memory.This work not only showcases the potential of memristors in simulating neural behavior but also provides a valuable educational tool for illustrating complex concepts in neuroscience and neuromorphic computing. The insights gained from this study pave the way for further exploration into the development of advanced neural network models and the design of memristor-based computing systems.

This article explores the intricate journey of neural progenitor cells from the ventricular zones of the embryonic brain, focusing on their pivotal role in the formation of rich club networks, which are integral to the brain's functional architecture. Initially, the ventricular zones, particularly the cerebral ventricular zone, serve as the primary sites for the proliferation and differentiation of neural progenitors, giving rise to various types of neurons and glial cells. We delve into the sequential migration patterns of these cells, emphasizing how early-migrating neurons, destined to form deeper cortical layers, establish extensive and robust connections, potentially evolving into rich club nodes. These nodes are characterized by their high-degree connectivity and serve as crucial hubs for integrating and disseminating information across disparate brain regions.The article further discusses the implications of this developmental pathway in the context of brain network efficiency, resilience, and cognitive function. We highlight how disruptions in early cell migration can lead to anomalies in rich club formation, drawing connections to various neurodevelopmental disorders such as autism, ADHD and schizophrenia. Additionally, the significance of rich club nodes in maintaining efficient information transfer and network resilience is elucidated, underscoring their role in supporting complex cognitive processes and overall brain dynamics.In summary, this article offers a comprehensive overview of the developmental trajectory from the ventricular zones to the establishment of rich club networks, providing insights into the fundamental processes that shape the brain's intricate connectivity and functional capabilities. Ric

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

Detailed evaluation is provided for the likelihood statistics intrinsic to interlocking Sequential Bayes analysis, which allows estimation of evidential support for dendrograms charting the macroevolution of taxa. It involves complexity functions, such as fractal evolution, to generate well-supported evolutionary trees. Required are data on trait changes from ancestral species to descendant species, which is facilitated by reduction of large genera to monothetic groups (one ancestral species each), most conveniently named as separate genera. Assigning each species one Shannon informational bit per new trait, then adding the traits as sequential Bayesian analysis (each posterior probability used as the prior for the next iteration of Bayes Formula), then interpretation with an odds chart, provides a posterior probability that the ancestor-descendant order is correct, that is, entirely follows evolutionary theory involving adaptation and rarity of total trait reversals. The key fact is that the most recently acquired traits of the ancestral species are selectively inviolate and passed on without change to each descendant species. The details of sequential Bayesian analysis were clarified by calculation of likelihood ratios and Bayes factors that compare optimal models with the next most likely model. Such analysis demonstrated that the optimum arrangement of ancestor and descendant species leads to high support values for fitting evolutionary theory, comparable to statistical support levels reported for molecular evolutionary trees. The fact that phylogenetic analysis does not offer an ancestor-descendant model in is found to be conducive of precision at the expense of accuracy, and leads to wrong ancestor-free models with likelihoods explaining data at high credible levels. The number of advanced traits in the outgroup as a Bayesian prior greatly enhances posterior probability. The method is simple, free of special computer analysis, and well-suited to standard taxonomic practice.

Differences between the quantum mechanical and relativistic concepts of time observed in GPS satellites are accounted for by applying the equivalence principle to the transitioning electron of an atomic clock. It allows a differential equation of motion to be derived for the electron in the Minkowski space between electron shells. Using Hamilton’s principle we transform the differential equation relativistically into an integral equation of motion, the time integral of a Lagrangian. This newly derived equation accounts for the abstract mathematics of the more familiar non-relativistic model by means of a physical interpretation. Abstract rotations in Hilbert space are replaced by the rotations of real particle field geometries in Minkowski space. Because the properties of energy are universal the same equations are then used to describe the field geometry of galaxies despite vast differences in lifetime. They reveal a symmetry between the electromagnetic fields of atoms and the gravitational fields of galaxies due to similarities in the exchange of energy by radial and transverse fields. Our analysis reveals that the conjugate variables energy and time permit differences between atomic and galactic structure to be compared in a more intuitive way than by means of the differential equations of motion which use the conjugate variables position and momentum.

During glioblastoma treatment, the pharmaceutical monoclonal antibody to VEGF, bevacizumab, has improved quality of life and delayed progression for several months but has not, or only marginally prolonged overall survival. In 2017 several dramatic research papers appeared that are crucial to our understanding of glioblastoma vis a vis the mode of action of bevacizumab. As a consequence of these papers, a new, potentially more effective, treatment protocol can be built around bevacizumab. This is the ADZT Regimen where four old drugs are added to bevacizumab. These four are apremilast, marketed to treat psoriasis, dapsone, marketed to treat Hansen’s disease, zonisamide, marketed to treat seizures, and telmisartan, marketed to treat hypertension. The ancillary attributes of each of these drugs has been shown to augment bevacizumab. This paper will detail the research data supporting that contention.

Hash tables are widely used. They rely on good quality hash functions. Popular data structure libraries either provide no hash functions or weak hash functions for sets or maps, making it impossible or impractical to use them as keys in other tables. This article presents three algorithms for hashing a set, two of which are simple to implement, practically fast, and can be combined. The quality evaluations follow the method of [1, chapter 2]. The insight that we are looking for commutative semigroups suggests that even better methods than symmetric polynomials may be found.

In the early decades of the 19th century, the deaf population in the eastern US and Canada was distributed across a vast area. After the 1817 founding of the American School for the Deaf (ASD) in Hartford, CT and the subsequent establishment of schools for the deaf in New York City (NYSD), Philadelphia, and many other US states, hundreds of deaf students called these schools home for several years. After leaving school, the early American Deaf community faced a challenge: How would the community maintain its social and linguistic ties across a vast geographical area once community members had dispersed to their hometowns? In this paper we analyze the attendance registries of two large gatherings of deaf individuals in Hartford in the years 1850 and 1854. These were among the largest and earliest known gatherings of deaf adults. The demographic data included in these registries open a window onto the evolving American Deaf community of the mid-19th century. Our analyses of the attendees’ school affiliations, ages, and marital status show that the signing community that had taken root among students at schools in Hartford and New York persisted among the adult graduates of those schools in towns across the northeastern US. We compare the places of residence of ASD and NYSD alumni in 1850 and 1854 to their hometowns when they first enrolled at school. Our comparisons suggest the mid-19th-century signing community had become more urban; it was centered to a greater extent in populous cities such as New York, Boston, and Hartford than had been true when the attendees had enrolled in school. We consider how the geography of deafness in the 19th century might inform our understanding of the sources of regional variation in ASL. We also consider how early cross-regional interactions may have inhibited such regional variation.

Cardiovascular diseases (CVDs) are the leading cause of death in the globally. Morbidity and disability related to non-fatal events are increasing exponentially. There are several symptoms that may arise after invasive therapeutic approaches such as coronary artery bypass graft (CABG), including chronic pain in anatomical areas connected to the mediastinum; these pains can be found not only initially after surgery, but also years later. We present a case where non-specific neck pain (NNP), in a patient undergoing CABG five years earlier, was approached with an osteopathic technique, working the pericardial area. To the knowledge of the Authors, it is the first case report where osteopathy is associated with a gentle treatment on the pericardial area to resolve a NNP.

At 2.3 megabases in length, the dystrophin gene is enormous: transcription of a single mRNA requires approximately 16 hours. Principally expressed in skeletal muscle, the dystrophin protein product protects the muscle sarcolemma against contraction-induced injury, and dystrophin deficiency results in the fatal muscle-wasting disease, Duchenne muscular dystrophy. This gene is thus of key clinical interest, and therapeutic strategies aimed at eliciting dystrophin restoration require quantitative analysis of its expression. Approaches for quantifying dystrophin at the protein level are well established, however study at the mRNA level warrants closer scrutiny: measured expression values differ in a sequence-dependent fashion, with significant consequences for data interpretation. In this manuscript we discuss these nuances of expression and present evidence to support a transcriptional model whereby the long transcription time is coupled to a short mature mRNA half-life, with dystrophin transcripts being predominantly nascent as consequence. We explore the effects of such a model on cellular transcriptional dynamics, and then discuss key implications for the study of dystrophin gene expression, focussing both on conventional (qPCR) and next-gen (RNAseq) approaches.

Three soybean field trials were conducted in Indiana to evaluate the integration of seed treatment, cultivar selection, and seeding rate on sudden death syndrome (SDS) root infection, foliar symptoms, yield and net return. Two soybean cultivars, one moderately resistant and one susceptible to SDS were planted at three seeding rates (272,277 seeds/ha, 346,535 seeds/ha, and 420,792 seeds/ha). Fluopyram and pydiflumetofen seed treatments were applied to both cultivars and were compared to a control. Low foliar SDS disease pressure was observed in our study. Seed treatment of either fluopyram or pydiflumetofen, and use of a moderately resistant cultivar decreased root infection relative to the control and the use of a susceptible cultivar. Fluopyram significantly reduced root rot severity by 8.8% and increased yield by 105 kg/ha relative to the control, but was not different from pydiflumetofen. However, pydiflumetofen performed the same as the control with respect to root rot severity and yield. Findings from this study support the use of a seed treatment to protect roots from infection and the use of a moderately resistant cultivar planted at a seeding rate of 346,535 seeds/ha to protect yield and maximize on net returns when a field has low foliar SDS pressure.

The savings behavior of individuals has been a topic of both macroeconomic and policy importance throughout history. Theoretical and empirical research offers strong evidence that savings are the result of a number of demographic and economic factors working together to produce long-term, sustainable economic growth. This study therefore looked at how domestic savings affected South Africa's economic growth between 1970 and 2022. The ARDL framework was used to analyze data that came from the World Bank and the South African Reserve Bank. The results of the study demonstrate that corporate savings have a major effect on economic growth, especially over the long term. When corporate savings rise by 1%, the economy expands by 3.12%. On the other hand, savings by the government and the general public, especially in the long run, have no appreciable impact on economic growth. Given that domestic savings mobilization is the most suitable channel for financing capital accumulation to support economic growth and development, the study suggests reviewing current policies to encourage domestic savings mobilization.

The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for directly and simply obtaining surfactant compositions of mixtures of D-mannuronic acid and L-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in derived compounds and in compositions having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.

The endeavor to decode the brain's intricate architecture and its multifaceted functions has propelled scientists into the domain of complex differential equations, aiming to construct a computational framework capable of representing its uncountable intricacies. This article delves into the sophisticated and daunting task of modeling the brain, a system of seemingly uncountable coupled differential equations, each symbolizing the vast array of interconnected neural pathways and processes. We discuss the current limitations of computational resources and the significant challenges faced in accurately capturing the non-linear, high-dimensional, and plastic nature of neural dynamics. Despite these challenges, we explore the progressive strides in computational neuroscience that lay the groundwork for partial models, offering insights into the brain's localized circuits and broader network interactions. These models serve as pivotal stepping stones towards a more comprehensive understanding, which is incrementally built upon by interdisciplinary approaches, leveraging advancements in neuroimaging, data analysis, and theoretical biology. Looking ahead, the article speculates on the potential paradigm shifts that could arise from breakthroughs in computational technology, such as quantum computing, that may one day enable the simulation of the brain in its entirety. The article ultimately paints a picture of cautious optimism, where each incremental discovery is a valuable piece of the grand puzzle, bringing us closer to the epochal goal of comprehensively modeling the human brain.

In this study, we develop a stochastic partial differential equation (SPDE) model to assess the regional severity of temperature increases due to global warming. The model incorporates various stochastic processes to account for uncertainties such as solar explosions, economic upheavals, rising emissions, and irreversible changes in the climate system. Our base temperature model, influenced by latitude, is enhanced by these random factors to simulate realistic and diverse outcomes of climate change. Numerical simulations on a global grid provide a heatmap representing potential temperature increase severity across different regions. The results highlight the significant impact on tropical and polar regions, demonstrating the utility of SPDE models in understanding and predicting the complex dynamics of climate change. This approach offers valuable insights for policymakers and researchers aiming to develop adaptive strategies for mitigating the adverse effects of global warming.

Repetitive elements, often referred to as selfish genes, pose significant challenges to genome assembly and read mapping in bioinformatics. These elements can replicate within the genome without providing functional benefits to the host organism, leading to complexities in accurate genome analysis. This study presents a simulation-based approach to illustrate the impact of repetitive elements on read mapping accuracy. By comparing genome sequences with and without repetitive elements, we demonstrate how these selfish genes create ambiguities and errors in read alignment. The findings underscore the importance of developing advanced bioinformatics tools aligned with artificial intelligence to mitigate the effects of repetitive sequences and improve the reliability of genomic analyses.