Gout is at least 3 times more prevalent in men than in women. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet and lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in women, and mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters, and higher hypertension and chronic kidney disease prevalence in women compared to men, may help explain why gout incidence rises robustly after menopause in women to approach that in men. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, and diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes and outcomes of gout and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flare, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in women. Significantly, women with gout also have poorer COVID-19 outcomes than do men. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex.

Infectious diseases are one of the leading causes of death among children under the age of 5 with 60% of those deaths preventable with prophylaxis. Vaccinations prove to be the most succesfull and effective public health tool of infectious dieases preventions. Poland first implemented a program of mandatory childhood vaccinations in 1960. The program is updated each year and provides parents with a clear schedule to follow. The program includes vaccinations against 12 diseases (tuberculosis, hepatitis B, rotaviral disease, diphtheria, pertussis, tetanus, Haemophilus influenzae, Streptococcus pneumoniae, poliomyelitis, measles, mumps and rubella) mandatory for all children and funded by the government. It also includes recommended vaccinations which costs are covered by a patient. Immunization rates are monitored nationwide and reported to the Chief Sanitary Inspector. With recent outbreaks of infectious diseases among young children the obligation lies on the government to provide childhood immunizations, and largely on the physicians to provide reliable education about infectious diseases in children and safety of vaccinations to the parents.

The Individual Work Performance Questionnaire (IWPQ) can be defined as the individual be-haviour capable of generating value and competitive advantage for the organization. It is a mul-ti-dimensional construct, consisting of task performance, contextual performance and counter-productive work behavior. Albeit important, a comprehensive measure of individual job per-formance is still lacking in the Italian context. This paper describes the validation of an Italian adaptation of the IWPQ. A back translation procedure was used. To investigate the psychometric properties of the 18-item Italian IWPQ, 1053 participants (502 men, 47.7%; 551 women, 52.3%) were enrolled; the age of participants ranged between 19 and 69 (Mage=34.6, SD= 11.8), and for the oc-cupation, the sample is classified in blue collar 32.5%, pink collar 33% and white collar 34.5%. Exploratory and confirmatory factor analyses and multigroup confirmatory factor analyses were performed to test the structural factor of the IWPQ. The results supported the goodness of the IWPQ in the Italian context and the scales were found consistent with the original structure. One item was omitted due to a low factor loading, resulting in a final 17-item structure. Multigroup confirmatory factor analysis showed that the factor solution was invariant across both gender and occupational category and found evidence of metric invariance, uniqueness and scalar invariance, and structural invariance. Convergent and discriminant validity were also tested and showed.

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, a carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses. RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

The paper proposes an approach to determine the optimal number of medical specialists in the region. According to the author's theoretical model, in order to maximize public welfare, the marginal contribution of the last physician recruited to the growth of the public utility function should be equal to the marginal cost of attracting him and providing conditions for his work. To empirically assess the contribution of physicians to the number of lives saved, the CVD mortality rate is modeled using the instrumental variable method. On average, a 1% increase in the number of cardiologists is associated with a 0.6% decrease in cardiovascular mortality. At the level of provision with cardiologists in the amount of 1 per 100 thousand people, their marginal contribution to the number of lives saved is not less than 129 per 100 thousand people, with a further decrease by 5 people with the increase in the level of provision by 1 unit. The use of the obtained results will increase the validity of managerial decisions and in determining the optimal level of doctors when choosing between alternative possibilities of spending money on hiring doctors of different profiles or other expenses, especially in the case of limited resources.

By using the Black-Derman-Toy (BDT) model, we predict the future trend of the riskless rate, and then we build an equation that relates the market price of zero-coupon bonds and the theoretical price of zero-coupon bonds calculated using a binomial option pricing model. Based on this, we can find the implied daily return μ, implied natural upturn probability p, and implied daily volatility σ with respect to different time-to-maturity values of zero-coupon bonds. With these results, we can give some suggestions to bond traders.

Rheocasting is getting more and more attention from the electronics and automotive industries. Mechanical properties and thermophysical properties such as thermal and electrical conductivity are affected by the amount of solid phase generated in the slurry process. The RheoMetal process specifically has a significant deviation from the expected solid fraction. This deviation is discussed, explained and a way to control the excess generation of solid phase is proposed.

As a matter of course, the first gene must be formed in the absence of gene. On the other hand, many biopolymers including gene are produced under the genetic system in extant organisms. Thus far, no idea explaining how the first gene was formed in the absence of gene, has been proposed except the idea based on the GADV hypothesis. GADV means four amino acids; Gly [G], Ala [A], Asp [D] and Val [V]. In this article, a reliable answer to the question, how the first gene was generated, is provided. The idea is as follows. The first gene (genetic information) was formed by random joining of anticodons, GNCs, which were carried by primeval anticodon stem-loop (AntiC-SL) tRNAs produced during repeated cycles of random joining of nucleotides and degradation of oligonucleotides. However, it might be difficult for many persons to accept the idea, because tRNAs and metabolic pathways using various proteins, which are produced under genetic functions, must be used to form the first gene. Then, it is reconsidered based on definition of genetic information and minimum necessary things to generate the first gene in this article, how the first gene was generated. Consequently, it could be reconfirmed that five prototypes of members (genetic code, tRNA, metabolism, cell structure and protein) composing the fundamental life system, except gene, are certainly necessary to generate the first gene. Namely, it can be concluded that the first gene was formed through nucleotide metabolism with immature [GADV]-proteins, primeval AntiC-SL tRNA formation with immature [GADV]-proteins, formations of single-stranded (GNC)n codon sequence by random joining of anticodons, GNCs, carried by AntiC-SL tRNAs, double-stranded (ds)-(GNC)n RNA and maturation of an immature [GADV]-protein, which was produced from one strand of the ds-RNA. Thus, the first gene was formed using the five primitive or prototypes of members, which were produced in the absence of gene. There would be no other way for generating the first gene.

The perturbations of DNA methyltransferase 3 alpha (DNMT3A) may cause uncontrolled gene expression, resulting in cancers and tumors. The DNMT inhibitors Azacytidine (AZA) and Zebu-larine (ZEB) inhibit the DNMT family with no specificities and consequently would bring side effects during the treatment. Therefore, it is vital to understand their inhibitory mechanisms in DNMT3A to inform the new inhibitor design for DNMTs. Herein, we carried out molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations to investigate the inhibitory mechanisms of AZA and ZEB. The results were compared to the methyl transfer of cytosine. We showed AZA might stop the methyl transfer process, whereas the ZEB might be stuck in a me-thyl-transferred intermediate (IM3). Such IM3 state then fails the elimination due to the unique protein dynamics that result in missing the catalytic water chain. Our results brought atomic-level insights into the mechanisms of the two drugs in DNMT3A, which could benefit the new generation of drug design for the DNMTs.

The paper proves a theorem about the structure of the distribution function on which the extremum of fractionally linear functional is reached in the presence of an uncountable number of linear constraints. The problem of finding an extremal distribution function arises when determining the optimal control strategy in a class of Markov homogeneous randomized control strategies. The structure of extremal functions is described by a finite number of parameters, hence the problem is greatly simplified since it is reduced to the search for an extremum of some function.

The orthogonal matrix with cube be symmetric is a common class of matrices with important properties. We pay attention to this kind of matrices. By using the close relationship between the eigenvalues of a matrix and the trace of its power, we obtain the algorithm for its all possible different eigenvalues and multiplicities. The calculation formula is expressed only by the trace of a matrix and its power, avoiding solving the characteristic polynomial. The method is simple and practical. Furthermore, a new essential characterization for the sum of orthogonal matrix pairs being orthogonal is given as well.

Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas is a characteristic feature of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.

Solid asperity interactions are common and inevitable under severe loading conditions for any lubricated contact. Heavy-duty machine components (gear, bearings etc.) generally operate under Mixed Lubrication, where uneven surface features contact each other when generated fluid pressure is not enough to support the external load. The Reynolds equation is commonly used to simulate smooth lubricated contacts numerically. In rough lubricated interfaces where opposite surface asperities make contact, the Reynolds equation alone cannot accurately predict pressure using the traditional numerical simulation method. In this paper, Lubrication-Contact interface conditions (LCICs) have been implemented and extended to solve the multiple asperity contact problem using the full-multigrid approach. The developed novel algorithm has significantly accelerated the solution process and improved the accuracy and efficiency of pressure calculation for fluid-solid sub-interactions that can occur under ML regions. The Finite Difference Method (FDM) results have been compared with Computational Fluid Dynamics (CFD) simulation to validate the newly developed model. Hence, the proposed optimized solution method will provide valuable insight to researchers and industry engineers interested in simulating the ML problem where the effect of the fluid-solid interface can be captured effectively to improve reliability in the calculation of the life expectancy of the lubricated parts.

The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. But research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and four RNA mononucleotides in three charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the -1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least one of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomized assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology.

Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

The aim of this work is to study the zonally asymmetric stratopause that occurred in the Arctic winter of 2019/2020, when the polar vortex was particularly strong and there was no sudden stratospheric warming. Aura Microwave Limb Sounder temperature data were used to analyze the evolution of the stratopause with a particular focus on its zonally asymmetric wave 1 pattern. There was a rapid descent of the stratopause height below 50 km in the anticyclone region in mid-December 2019. The descended stratopause persisted until mid-January 2020 and was accompanied by a slow descent of the higher stratopause in the vortex region. The results show that the stratopause in this event was inclined and lowered from the mesosphere in the polar vortex to the stratosphere in the anticyclone. It was found that the vertical amplification of wave 1 between 50 km and 60 km closely coincides in time with the rapid stratopause descent in the anticyclone. Overall, the behavior contrasts with the situation during sudden stratospheric warmings when the stratopause reforms at higher altitudes following wave amplification events. We link the mechanism responsible for coupling between the vertical wave 1 amplification and this form of zonally asymmetric stratopause descent to the unusual disruption of the quasi-biennial oscillation that occurred in late 2019.

Unification based upon the generalisation of proper time is proposed as a comprehensive framework to account for the fundamental structure of matter, in a manner contrasting with the more familiar approach based on extra dimensions of space. The elementary properties of matter to be incorporated include the Standard Model of particle physics together with a source for the dark sector and a coherent formalism for quantum gravity. We elaborate upon the manner in which all such material phenomena and empirical properties as distributed in an extended 4-dimensional spacetime can be encompassed within, and derived from, the continuous flow of time alone via a generalised arithmetic form for infinitesimal intervals of proper time. This approach will also be compared and contrasted with the basic structure of causal set theory as a means of demonstrating how it is possible to construct a full physical theory essentially from elements of time alone, as explicitly developed from the most elementary level. The conception of time as utilised and elucidated in this theory, with emphasis upon the causal continuum properties and as the basis for unification, will be clarified.

Legal research is an indispensable skill for lawyers. Therefore, it is always necessary for lawyers to engage in legal research in due course of trying to alleviate various legal problems. Although the purpose and methodology of the research may vary from lawyer to lawyer, doing research is a common activity. As a result, the quest to assess the impacts of artificial intelligence (hereinafter ‘AI’) on legal research allows one to measure the influence of AI on the legal profession in general. Moreover, with the advent of Legal AI, it is now evident that the legal profession is not immune from disruption. According to the above, this article discusses the impacts of AI on research in the legal profession in general in accomplishing various lawyerly tasks by different legal professionals.

The process of senescence (aging) is largely determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function of senescence, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood’s disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is described.

Recent research has shown that the sensorimotor system plays a significant role in a variety of cognitive processes. In this paper, we will review recent studies performed in our lab (Body Action Language Lab, BALLAB) or in labs with which we collaborate, showing the involvement of the sensorimotor system at different levels. With the purpose of expounding on this aspect, we focus on studies that highlight two main characteristics of the involvement of the sensorimotor systems. First, we concentrate on the flexibility of sensorimotor grounding during interaction with objects. We report evidence showing how social context and current situations influence affordance activation. We then focus on the tactile and kinesthetic involvement in body-object interaction. Second, we illustrate flexible sensorimotor grounding in word use. We review studies showing that not only concrete words, like “bottle,” but also abstract words, like “freedom,” “thinking,” and “perhaps,” are grounded in the sensorimotor system. We report evidence showing that abstract words activate sensory modalities and involve the mouth effector more than concrete words due to their privileged relationship with language, both outer and inner speech. We discuss the activation of the mouth sensorimotor system in light of studies on adults (e.g., studies employing articulatory suppression), children (e.g., studies on the effects of pacifier use on word acquisition and processing), and infants (e.g. studies on emergence of new words). Finally, we pinpoint possible mechanisms at play in the acquisition and use of abstract concepts. We argue that with abstract concepts, we rely more on other people to learn or negotiate the meaning of words; we have called this mechanism social metacognition.Social metacognition is bidirectionally linked to our sensorimotor system. On the one hand, linguistic explanations constitute a primary source of grounding that may be re-enacted when retrieving a concept, for example through inner speech. On the other hand, it leads us to feel closer and be more synchronous in movement with others, who can help us understand the meaning of very complex words. Overall, we show that the sensorimotor system provides a grounding basis not only for objects and concrete words but also for more abstract and concrete ones. We conclude by arguing that future research should address and deepen two different and interrelated aspects concerning the involvement of the sensorimotor system during object and word processing. First, the sensorimotor system is flexibly modulated by the context, as studies on affordances reveal. Second, the sensorimotor system can be involved at different levels, and its role can be integrated and flanked by that of other systems, like the linguistic one, as studies on abstract concepts clearly show. We urge future research aimed at unravelling the role of the sensorimotor system in cognition to fully explore the complexity of this intricate-and sometimes slippery-relation.

Introduction: Pancasila was born as the ideology of the Indonesian nation, which reflects the values cultural values, ethics, morals, and the spirit of the nation. Pancasila was born as a form of national character, which reflects divinity, nationality, unity, togetherness, and justice. The purpose of this research is to know the practice of Pancasila values ​​in the life of the nation and the state. Especially, the implementation of the life of the younger generation in the 21st century today. Methods: This study is literature research where data is collected using keywords in the database. Literature source search carried out with the help of Boolean operators and using the PICOS format. The results of selecting articles, using PRISMA Flow Diagrams. The search results found 125 articles that match the research theme. After checking for duplication, 82 articles were excluded because of the similarity in the results of the discussion. In the end, there were 43 articles used as a literature source. Results: Based on the analysis of research findings, which are supported by literature sources, it shows that the current values ​​of Pancasila are worrying. This can be seen, where people's behavior has been contaminated by external cultures due to technological sophistication. At present, it can be said that the ethics and morals of society do not reflect the values ​​of Pancasila. Conclusion: In order to re-install the values ​​of Pancasila in people's lives, the participation of all parties is necessary. This is especially so, for today's younger generation. Therefore, it is necessary to develop a model for teaching Pancasila to be carried out by schools and colleges. So that later, it can produce a generation of ethics and morals who love the country.

Authors such as Schnoebelen (2012: 12) suggest that in some languages (cf. Navajo) certain dependent clauses are frequently used independently to “mark emotional evaluation and background information”. Evans (2007) uses the term insubordination to refer to this phenomenon. Our study focuses on a particular insubordinate construction introduced by the sequence ni que in Spanish, as in the example [¡Una carta cada día!] Ni que yo fuese Umbral. (CORPES 100), used as an independent clause with a sociopragmatic meaning which is different from that of its subordinate counterpart (cf. No escribiría una carta cada día ni que yo fuese Umbral). Our research questions ask about the potential for ni que to be used as a discourse marker fulfilling an expressive function when it introduces this type of construction, and the derived hypothesis is then oriented to test whether Schnoebelen's (2012) observation about insubordinate constructions applies also to this Spanish construction. In order to test this hypothesis, we performed a functional-discourse analysis of more than 2000 concordances (and their extended contexts) in Mark Davies' Corpus del Español and the Real Academia CORPES XXI. Our findings show that the insubordinate construction differs in function and meaning from its subordinate counterpart, the former fulfilling a stronger emotive function, often combined with other discourse-pragmatic functions, such as evaluation or the organization of discourse.

Alphaviruses are positive-sense RNA arboviruses that are capable of causing severe disease in otherwise healthy individuals. There are many aspects of viral infection that determine pathogenesis and major efforts regarding the identification and characterization of virulence determinants have largely focused on the roles of the nonstructural and structural proteins. Nonetheless, the viral RNAs of the alphaviruses themselves play important roles in regard to virulence and pathogenesis. In particular, many sequences and secondary structures within the viral RNAs play an important part in the development of disease and may be considered important determinants of virulence. In this review article, we summarize the known RNA-based virulence traits and host:RNA interactions that influence alphaviral pathogenesis for each of the viral RNA species produced during infection. Overall, the viral RNAs produced during infection are important contributors to alphaviral pathogenesis and more research is needed to fully understand how each RNA species impacts the host response to infection as well as the development of disease.

Three genera of very large volant birds existed for most of the Pliocene: the Pelagornithidae seabirds; the large North American Teratornithidae and the stork Leptoptilos falconeri in Africa and Asia. All became extinct around 3 Ma. The reasons for their demise are puzzling, as the Pelagornithidae had a world-wide evolutionary history of more than 50 Ma, smaller teratorns were still extant in the Holocene and smaller stork species are still globally extant. Extant large birds have a common critical takeoff airspeed suggesting a biomechanical limit in terms of power, risk and launch speed, and simulations of the flight of these extinct species suggest that at 1 bar they would have exceeded this value. Estimates for the Late Pliocene atmospheric density are derived from marine and terrestrial isotopes as well as resin chemistry, both approaches suggesting a value of about 1.2 bar, which drops to present levels during the period 3.3 to 2.6 Ma, thus a loss in atmospheric density may have caused biomechanical and ecological stress contributing to their extinction and/or development of smaller forms. This hypothesis is examined in terms of a possible mechanism of atmospheric mass loss and how this would be seen in the geological record. At 1.2 bar all the extinct species present takeoff airspeeds similar to large extant volant birds and which match the expected power and kinetic energy levels.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.

The meaning and evolution of the notion of “temperature” (which is a key concept for the condensed and gaseous matter theories) is addressed from the different points of view. The concept of temperature turns out to be much more fundamental than it is conventionally thought. In particular, the temperature may be introduced for the systems built of “small” number of particles and particles in rest. The Kelvin temperature scale may be introduced into the quantum and relativistic physics due to the fact, that the efficiency of the quantum and relativistic Carnot cycles coincides with that of the classical one. The relation of the temperature to the metrics of the configurational space describing the behavior of system built from non-interacting particles is demonstrated. The Landauer principle asserts that the temperature of the system is the only physical value defining the energy cost of isothermal erasing of the single bit of information. The role of the temperature the cosmic microwave background in the modern cosmology is discussed.

The notion that there is a one to one mapping from genotype to phenotype was overturned a long time ago. Along with genotype and environment, ‘non-genetic changes’ orchestrated by altered RNA and protein molecules also guide the development of phenotype. The idea that there is a route through which changes in phenotype can lead to changes in genotype impinges on several phenomena of molecular, developmental, evolutionary and applied interest. Phenotypic changes that do not alter the underlying DNA sequence have been studied across model systems (eg: DNA and histone modifications, RNA editing, prion formation) and are known to play an important role in short term adaptation. However, because of their transient nature and unstable inheritance, the role of such changes in long term evolution has remained controversial. I classify and review three ways in which non-genetic changes can influence genotype and impact cellular fitness across generations, with an emphasis on the enticing idea that they may act as stepping stones for genetic adaptation. I focus on work from microbial systems and attempt to highlight recent experiments and models that bear on this idea. Overall, I review evidence which suggests that non-genetic changes can impact phenotype via their influence on the genotype, and thus play a role in evolutionary change.

The key premise of translational studies is that knowledge gained in one animal species can be transposed to other animals. So far translational bridges have mainly relied on genetic and physiological similarities, in experimental setups where behaviours and environment are often oversimplified. These simplifications were recently criticised for decreasing the intrinsic value of the published results. The inclusion of wild behaviour and rich environments in neuroscience experimental designs is difficult to achieve because no animal model has it all. As an example, the genetic toolkit of moths species is virtually non-existent when compared to C. elegans, rats, mice, or zebrafish, however the balance is reversed for wild behaviours. The ethological knowledge gathered about the moth was instrumental for designing natural-like auditory stimuli, that were used in association with electrophysiology in order to understand how moths use these variable sounds produced by their predators in order to trump death. Conversely, we are still stuck with understanding how male moths make sense of their complex and diffuse olfactory landscape in order to locate conspecific females up to several hundred meters away, and precisely identify a conspecific in a sympatric swarm in order to reproduce. This systemic review articulates the ethological knowledge pertaining to this unresolved problem and leverages the paradigm to gain insight into how male moths process sparse and uncertain environmental sensory information.

For the solution existence condition of the Navier-Stokes equation, we propose a conjecture as follows: "\emph{The Navier-Stokes equation has a solution if and only if the determinant of flow velocity gradient is not zero, namely $\det (\bm \nabla \bm v)\neq 0$.}"

: As antibiotic resistance undermines efforts to treat bacterial infections, phage therapy is being increasingly considered as an alternative in clinical settings and agriculture. However, a major concern in using phages is that pathogens will develop resistance to the phage. Due to the constant evolutionary pressure by phages, bacteria have evolved numerous mechanisms to block infection. If we determine the most common among them, we could use this knowledge to guide phage therapeutics. Here we compile data from 88 peer-reviewed studies where phage resistance was experimentally observed and linked to a bacterial gene, then assessed these data for patterns. In total, 141 host genes were identified to block infection against one or more of 80 phages (representing five families of the Caudovirales) across 16 microbial host genera. These data suggest that bacterial phage resistance is diverse, but even well-studied systems are understudied, and there are gaping holes in our knowledge of phage resistance across lesser-studied regions of microbial and viral sequence space. Fortunately, scalable approaches are newly available that, if broadly adopted, can provide data to power ecosystem-aware models that will guide harvesting natural variation towards designing effective, broadly applicable phage therapy cocktails as an alternative to antibiotics.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

Health information and communication are key elements that allow patients and family members to make decisions about end-of-life process and guarantee a death with dignity. Objective: To understand carers’ experiences regarding health information and communication during the illness and death of family members. Methods: This qualitative study was conducted in Andalusia based on the paradigm of hermeneutic phenomenology. Participants were carers who had accompanied a family member at the end of life for over 2 months and less than 2 years. Five nominal groups and 5 discussion groups were established, and 41 in-depth interviews with 123 participants were conducted. Atlas.ti 7.0 software was used to analyse the discourses. Results: Four dimensions of the dying process emerged: differences in carers’ perceptions of information and communication, a conspiracy of silence, consequences of the absence or presence of information, and the need for a culture change. Conclusions: Poor management of health information and communication at the end of life suffering and discomfort patients and their families. The culture of denying and avoiding death is still present today. A change in education about death would better enable health professionals to care for patients at the end of life.

The striving for sustainable development has become the goal of actions undertaken not only by representatives of public authorities and institutions representing this sector, but also representatives of private entities who are increasingly recognizing the benefits and sources of long-term development based on the principles and objectives of sustainable development. These are mainly based on the pursuit of synergy in the three basic areas of activities, i.e., in the economic, social, and environmental dimensions as well as in the maintenance of natural resources. The implementation of these activities is connected with the necessity of incurring financial expenditures, which the government (public sector) does not have in the required value. Therefore, in the process of sustainable development for which the government is responsible, the active participation of the financial sector (banks) is necessary. Achieving results within the alliance of the concept of sustainable development requires the setting of a kind of contract, the parties of which are the government, society, and financial institutions. The purpose of the conducted research is to indicate by which means the government can stimulate economic growth towards its sustainable development.

The competitiveness of domestic products at the regional or global market is one of the cornerstones of a country’s internationalcompetitiveness. In this regard, the assessment and analysis of the competitiveness of a country’s international trade becomes an important issue. Thus, development and diversification of the export potential of the country is viewed as one of the most important directions of the international trade policy of the given country. Therefore, another important task is the specialization of the country in the most efficient and competitive segments of the economy. The above-mentioned circumstances embody the fact, that the role of quantitative assessment of potential competitive advantages is important, as it allows determining to what extent certain factors influence on the formation of export capacity in the country. The main objective of the study is to determine the role of export competitiveness in the process of competitive advantages formation of a country. This study mainly focuses on quantitative analysis based on the calculation of Balassa index, determining the extent to which a country has a comparative advantage in producing and exporting certain goods. The study presents the example of the Republic of Armenia, the study covers the period between 2002- 2016. Based on the index calculation, it can be determined whether the country has "revealed" comparative advantage or not. The practical significance of the study lies in the fact that its main findings and conclusions arising from it can be used in assessing the export competitiveness of not only Armenia, but also for other countries or groups of countries.The outcomes and implication of the research can be used to improve the competitiveness of goods and services in the global market.

There is increasing interdisciplinary interest in phytoplankton community dynamics as the growing environmental problems of water quality (particularly eutrophication) and climate change demand attention. This has led to a pressing need for improved biophysical and causal understanding of Phytoplankton Functional Type (PFT) optical signals, in order that satellite radiometry may be used to detect ecologically relevant phytoplankton assemblage changes. This understanding can best be achieved with biophysically and biogeochemically consistent phytoplankton Inherent Optical Property (IOP) models, as it is only via modelling that phytoplankton assemblage characteristics can be examined systematically in relation to the bulk optical waterleaving signal. The Equivalent Algal Populations (EAP) model is used here to investigate the source and magnitude of size- and pigment- driven PFT signals in the water-leaving reflectance, as well as the potential to detect these using satellite radiometry. This model places emphasis on explicit biophysical modelling of the phytoplankton population as a holistic determinant of IOPs, and a distinctive attribute is its comprehensive handling of the spectral and angular character of phytoplankton scattering. Selected case studies and sensitivity analyses reveal that phytoplankton spectral scattering is the primary driver of the PFT-related signal. Key findings are that the backscattering-driven signal in the 520 to 600 nm region is the critical PFT identifier at marginal biomass, and that while PFT information does appear at blue and red wavelengths, it is compromised by biomass/gelbstoff ambiguity in the blue and low signal in the red, due primarily to absorption by water. These findings are hoped to provide considerable insight into the next generation of PFT algorithms.

In this paper, the effect of an exterior shading element (Iwan) on energy consumption in four different climatic regions, and for different geographical directions, has been investigated numerically and experimentally. By applying different materials and techniques and creating various elements and spaces, architects make hard climatic conditions more tolerable for residents. Iwan is one of the cooling elements which is used in different forms and dimensions in the Islamic architecture. In the present research, Iwan has been introduced as a climatic element in traditional and contemporary architectures and its role in reducing the energy consumption in buildings has been studied. In this respect, first, the thermal loads of a building without Iwan are computed by means of EnergyPlus software. Then, four different forms of Iwan are added to the above-mentioned structure along the four principal geographical directions, and the effect of Iwan on the reduction of thermal loads is analyzed for four different climates. Finally, the design parameters of Iwan, in terms of depth and form, that can help reduce the thermal loads in different climatic conditions are presented. The results show that the best position for using an Iwan is the south direction and the use of Iwan in temperate & humid, hot & humid, cold & mountainous and hot & dry climates could reduce the energy consumption in buildings by 32%, 26%, 14%, and 29%, respectively.

The Delaware River has made a marked recovery in the half-century since the adoption of the Delaware River Basin Commission (DRBC) Compact in 1961 and passage of the Federal Clean Water Act amendments during the 1970s. During the 1960s, the DRBC set a 3.5 mg/l dissolved oxygen criteria for the river based on an economic analysis that concluded a waste load abatement program designed to meet fishable water quality goals would generate significant recreation and environmental benefits. Scientists with the Delaware Estuary Program have recently called for raising the 1960s DO criteria along the Delaware River from 3.5 mg/l to 5.0 mg/l to protect anadromous American shad and Atlantic sturgeon and address the prospect of rising temperatures, sea levels, and salinity in the estuary. This research concludes through a marginal abatement cost (MAC) analysis that it would be cost effective to raise DO levels to meet a more stringent standard by prioritizing agricultural conservation and wastewater treatment investments in the Delaware River watershed to reduce 90% of the pollutant load 13.6 million kg/year of nitrogen (30 million lb/year) for $160 million at 35% of the $449 million annual cost. The annual least cost to reduce nitrogen loads and raise dissolved oxygen levels to meet more stringent water quality standards in the Delaware River totals $45 million for atmospheric NOX reduction, $130 million for wastewater treatment, $132 million for agriculture conservation, and $141 million for urban stormwater retrofitting. This 21st century least cost analysis estimates that $50 million/year is needed to reduce pollutant loads in the Delaware River to raise dissolved oxygen levels to 4.0 mg/l, $150 million/year is needed to reach 4.5 mg/l, and $449 million/year is needed to reach 5.0 mg/l.

Decomposed fuzzy sets are the resent extension of intuitionistic fuzzy sets by incorporating functional and dysfunctional points of views to the definition of membership functions. This paper extends the Technique of Order Preference Similarity to the Ideal Solution (TOPSIS) method to the Decomposed Fuzzy TOPSIS (DF TOPSIS) method and applies it to a multi-criteria risk-based supplier selection problem under fuzziness. DF TOPSIS involves finding a positive ideal solution and a negative ideal solution and measuring the distance of each alternative to these solutions. The final ranking is obtained based on the proportion of distances to the positive and negative ideal solutions. The developed DF TOPSIS method incorporates the accuracy and consistency of expert judgments, enhancing the decision-making process. A sensitivity analysis is also presented in order to show the robustness of the obtained rankings by DF TOPSIS.

This paper reviews the ethical issues involved and argues that each of the usual policies for handling conscientious refusals faces serious challenges. Healthcare providers who refuse to provide medical services should be expected to explain their reasons, make prompt referrals, and bear some of the resulting costs or burdens.

In this article it is shown, first, that a change of basis in Minkowski space is equivalent to a change of basis in Euclidean space if a basis element is replaced by its dual element, constituting a mixed basis set. Second, that such mixed bases can be interpreted as a measurement system used by local, flat observers whose direct distance measurements are restricted to an (n−1)-dimensional submanifold in an n-dimensional Euclidean space. Combining these steps, it is concluded that a local, flat observer in a four-dimensional Euclidean space measures a Minkowski spacetime. This interpretation could be useful for theories in special relativity and related fields that rely on spacetime concepts, as it offers a more intuitive geometric understanding of the Minkowski metric.

This study explored factors influencing the adoption of blockchain technology in US educational settings using the UTAUT2 model. Results from 160 IT officers via an online survey and PLS-SEM analysis showed that performance expectancy and social influence significantly predict behavioral intentions towards blockchain adoption, impacting actual utilization. While some factors like effort expectancy, facilitating conditions, hedonic motivation, price value, and habit did not show significant relationships, this research underscores UTAUT2's relevance in blockchain acceptance in education. Future studies should address limitations and explore diverse stakeholder perspectives for strategic implementation approaches.

Physical laws manifest themselves through the amalgamation of mathematical symbols, numbers, functions, geometries, and relationships. These intricate combinations unfold within a mathematical model devised to capture and represent the ``objective reality'' of the system under examination. In this symbiotic relationship between physics and mathematics, the language of mathematics becomes a powerful tool for describing and predicting the behavior of the physical world. The language used and the associated concepts are in a perpetual state of evolution, mirroring the ongoing expansion of the phenomena accessible to our scientific understanding. In this contribution, written in honor of Richard Kerner, we delve into fundamental, at times seemingly elementary, elements of the mathematical language inherent to the physical sciences, guided by the overarching principles of symmetry and group theory. Our focus turns to the captivating realm of spheres, those strikingly symmetric entities that manifest prominently within our geometric landscape. By exploring the interplay between mathematical abstraction and the tangible beauty of symmetry, we seek to deepen our understanding of the underlying structures that govern our interpretation of the physical world.

The extent to which projects are established as an organizational form in society to cope with various challenges has been analyzed extensively in research under the term ‘projectification.’ However, it remains unclear how the projectification at the level of society begins and which actors are involved in its institutionalization. Drawing on an explanatory case study in post-Soviet Kyrgyzstan, responses are provided to these questions and propositions for further research. The country is undertaking reforms as part of its ongoing transformation, which includes professional implementation of projects, particularly in the public sector. These activities are, to some extent, based on the developments in project management in neighboring Kazakhstan, where a presidential decree also constituted a first step towards the institutionalization of projectification. It later found its way into relevant sectors and to key actors via the presidential administration, primarily through regulative and normative institutions. Due to increased international cooperation, the number and importance of projects in Kyrgyzstan will continue to increase in the coming years, requiring greater emphasis on projectification. The results are informative for research into projectification and for those involved in countries with comparable situations.

A compositional data vector is a special type of multivariate observation in which the elements of the vector are non-negative and sum to a constant, usually taken to be unity. A compositional data does not have zero and only retains relative information. Furthermore, comparisons can only be made between compositional data of the same component. The relevant sample space is the standard simplex. A simplex space is a space that is a generalized form of a triangle. For compositional data, many of the operations defined in Euclidean space are meaningless. Microbiome analyzes have become popular in recent years. Operational Taxonomic Units (OTU) and Amplicon Sequence Variants (ASVs) used in microbiome analysis are one type of compositional data. The microbiome data are counts of different species within a sample and it is compositional. Although there is an order of bacterial abundance within a sample, there is no order of bacterial abundance between samples. Firmicutes and Bacteroidetes, the major phyla in the colon, have been observed in humans worldwide. Gut microbiome analyses often use the Firmicutes/Bacteroidetes ratio and principal coordinates analysis (PCoA). Alpha and beta diversities are used as indicators of bacterial flora diversity. However, misinformation is pervasive in the human microbiome literature and analysis. There is a lot of misunderstanding regarding compositional data and its analysis. An attempt was made to demonstrate how to analyze using the “National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN JMD) (Public Data).” The results showed that PCoA did not work, and principal component analysis (PCA) was useful for analyzing the gut microbiome relative diversity.

Homochirality is an obvious feature of life on Earth. On the other hand, extraterrestrial samples contain largely racemic compounds. The same is true for any common organic synthesis. Therefore, it has been a perplexing puzzle for decades how these racemates could have formed enantiomerically enriched fractions as a basis for the origin of homochiral life forms. Numerous hypotheses have been put forward as to how preferentially homochiral molecules could have formed and accumulated on Earth. In this article, it is shown that homochirality of the abiotic organic pool at the time of formation of the first self-replicating molecules is not necessary and not even probable. It is proposed to abandon the notion of a molecular ensemble and to focus on the level of individual molecules. Although the formation of the first self-replicating, most likely homochiral molecule is a seemingly improbable event, on a closer look, it is almost inevitable that homochiral molecules have formed simply on a statistical basis. In this case, the non-selective leap to homochirality would be one of the first steps in chemical evolution directly out of a racemic “ocean”. Moreover, most studies focus on the chirality of the primordial monomers with respect to an asymmetric carbon atom. However, any polymer with a minimal size that allows folding to a secondary structure, would spontaneously lead to asymmetric higher structures (conformations). Most of the functions of these polymers would be influenced by this inherently asymmetric folding. To summarize, simple and universal mechanisms may have led to homochiral self-replicating systems in the context of chemical evolution. A homochiral monomer pool is deemed unnecessary and probably never existed on primordial Earth.

Claudins are a family of 27 proteins that have an important role in the formation of tight junc-tions. They also have an important function in ions exchange, cell mobility, and in in the epitheli-al-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evi-dence shows improved outcomes when combining monoclonal antibodies against Claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently Chimeric anti-gen receptor T-cells targeting Claudin 18 are under investigation.

Brain models present a viewpoint on the fundamental structural components of the brain and their mutual organization, generally relative to a particular concept of the brain axis. A model may be based on adult brain structure or on developmental morphogenetic aspects. Brain models usually have functional implications, depending on which functional properties derive from the postulated organization. This essay examines the present scenario about brain models, emphasizing the contrast between columnar or other longitudinal models and transverse subdivisional neuromeric models. In each case, the main functional implications and apparent problems are explored and commented. Particular attention is given to the modern molecularly based ‘prosomeric model’, which postulates a set of 20 transverse prosomeres as the developmental units that serve to construct all the cerebral parts and the particular typology of many different neuronal populations within the forebrain and the hindbrain, plus a number of additional spinal cord units. These metameric developmental units (serially repeated, but with unique molecular profiles) confer to this model remarkable functional properties based mainly on its multiplicity and modularity. Many important brain functions can be decomposed into subfunctions attended to by combined sets of neuronal elements derived from different neuromeres. Each neuromere may participate in multiple functions. Most aspects related to creation of precise order in neural connections (axonal navigation and synaptogenesis) and function is due to the influence of neuromeric anteroposterior and dorsoventral positional information. Research on neuromeric functionality aspects is increasing significantly in recent times.

This research paper examines the effects, advantages, challenges, and economic aspects of a research town. The study concludes that inclusion and diversity not only constitute fundamental values but also serve as crucial drivers of business success and sustained competitiveness. Universities play a central role in shaping the prosperity of the research town by functioning as knowledge hubs, fostering collaboration, nurturing talent, and contributing to the broader innovation ecosystem. The symbiotic relationship between universities and industries within the cluster establishes a dynamic and resilient environment for research and development. The presence of startups within the research cluster introduces novel ideas, enhancing the overall vibrancy and competitiveness of the local economy. In an era where social media algorithms increasingly influence people's choices, the potential for foreign interference emerges as a significant threat.

In this article, it is demonstrated that if the zeta function does not have a sequence of zeros whose real part converges to 1, then it cannot have any zeros in the critical strip, showing that the Riemann Hypothesis is false.

Pseudoxanthoma Elasticum (PXE) is an inherited disease characterized by elastic fibers calcification in the eyes, the skin and the cardiovascular system. PXE results from mutations ABCC6 that encodes an ABC transporter primarily expressed in liver and kidneys. It took nearly 15 years after identifying the gene to better understand the etiology of PXE. the ABCC6 functions facilitates the efflux of ATP (and other nucleotides) which is sequentially hydrolyzed by the ectonucleotidases ENPP1 and CD73 into pyrophosphate (PPi) and adenosine, both inhibitors of calcification. PXE, together with General Arterial Calcification of Infancy (GACI caused by ENPP1 mutations) as well as Calcification of Joints and Arteries (CALJA caused by NT5E/CD73 mutations) form a disease continuum with overlapping phenotypes and sharing steps of the same molecular pathway. The explanation of these phenotypes places ABCC6 as an upstream regulator of a purinergic pathway (ABCC6 → ENPP1 → CD73) that notably inhibits mineralization by maintaining a physiological Pi/PPi ratio in connective tissues. Based on a review of the literature and our recent experimental data, we suggest that PXE (and GACI/CALJA) be considered as an authentic “purinergic disease”. In this article, we recapitulate the pathobiology of PXE, review molecular and physiological data showing that, beyond PPi deficiency and ectopic calcification, PXE is associated with wide and complex alterations of purinergic systems. Finally, we speculate on future prospects regarding purinergic signaling and other aspects of this disease.

Optical networks, characterized by using optical fibers as a transmission medium, constitute the fundamental infrastructure employed today by network operators to deliver services to users. As network capacity is one of the key factors influencing optical network performance, it is important to comprehend its limitations and have the capability to estimate its value. In this context, we revisit the concept of capacity from various perspectives, including channel capacity, link capacity, and network capacity, thus providing an integrated view of the problem. Hence, we review the fundamental concepts behind optical networks, along with the basic physical phenomena present in optical fiber transmission and provide methodologies for estimating the different types of capacities, mainly using simple formulations. In particular, we propose a method to evaluate the network capacity that relies on the optical reach to account for physical layer aspects, in conjunction with capacitated routing techniques for traffic routing. We apply this method to three reference networks and obtain capacities ranging from tens to hundreds of Terabits/s. Whenever possible, we also compare our results with published experimental data to understand how they relate.

Scientists, politicians, and practitioners are debating the current structure of pig farms in Lithuania, as medium and small farms have almost disappeared over the past decade. The debated problem is whether the revitalization of medium and small pig farms would sustainably contribute to self-sufficiency in pork? Therefore, this research aims to determine which farms in terms of size could be the most perspective. In order to achieve this aim the multi-criteria evaluation method TOPSIS was used. The economic, production and environmental indicators of Lithuanian pig farms and pig farming sector in Lithuania and selected EU countries: Latvia, Estonia, Poland, Germany, and Denmark were analyzed in this research. The multi-criteria evaluation led to the conclusion that Danish pig farms were the best managed. Germany occupied the second place. The industrial large farms were found as dominated in those countries. Large pig farms (approximately two thousand sows) appeared most perspective in Lithuania: they took the first place in the years examined (2016–2021). The criterion estimate of their assessed indicators was much higher than of the medium (100 sows) and small (20 sows) farms. The main reasons: significantly higher labour productivity, lower cost, lower price, and better production indicators.

A (2,6)-fullerene F is a 2-connected cubic planar graph whose faces are only 2-length and 6-length. Furthermore, it consists of exactly three 2-length faces by Euler's formula. The (2,6)-fullerene comes from Do\v{s}li\'{c}'s (k,6)-fullerene, a 2-connected 3-regular plane graph with only k-length faces and hexagons. Do\v{s}li\'{c} showed that the (k,6)-fullerenes only exist for k = 2, 3, 4 or 5, and some of the structural properties of (k,6)-fullerene for k = 3, 4 or 5 are studied. In this paper, we study the properties of (2,6)-fullerene. We obtain that the edge-connectivity of (2,6)-fullerenes is 2. Every (2,6)-fullerene is 1-extendable, but not 2-extendable. F is said to be k- resonant (k>0) if the deleting of any i (0=< i<= k) disjoint even faces of F results in a graph with at least one perfect matching. We have that every (2,6)-fullerene is 1-resonant. An edge set S of F is called an anti-Kekule set if F-S is connected and has no perfect matchings, where F-S denotes the subgraph obtained by deleting all edges in S from F. The anti-Kekule number of F, denoted by ak(F), is the cardinality of a smallest anti-Kekule set of F. We have that every (2,6)-fullerene F with |V(F)|>6 has anti-Kekule number 4. Further we mainly prove that there exists a (2,6)-fullerene F having f_{F} hexagonal faces, where f_{F} is related to the two parameters n, m.

Growing incidence of myopia worldwide justifies the search for efficient methods of myopia prevention. Numerous pharmacological, optical, and lifestyle measures have already been utilized, but there remains a need to explore more practical and predictable methods for myopia control. This paper presents a review of the latest literature on preventing the progression of myopia using Defocus Incorporated Multiple Segments Spectacle Lenses (DIMSsl), Repeated Low-level Red-Light Therapy (RLRL), and the combination of low-dose atropine (0.01%) with orthokeratology lenses.

In 1911, A. Einstein suggested that gravity affects at the electromagnetic radiation originating from the distant sources, namely, it shifts the spectral lines in the red side of the spectrum and derived the gravitational redshift formula. A modern science claims that Einstein’s formula is mathematically immaculate. We show that this is not true: in fact, this formula is approximate. Using the law of conservation of mechanical energy, we derived two exact formulas оf the gravitational redshift.

Microalgae are a source of carotenoids, phycocyanin, phenol, amino acids, polyunsaturated fatty acids, sulfated polysaccharides, pigments, and other bioactive molecules with antimicrobial, antioxidant, antiviral, antitumor, anti-inflammatory, and fat-burning properties. The increasing incidence of infectious processes, including tuberculosis, caused by antimicrobial resistant strains of microorganisms necessitates the search for alternative sources of compounds with antimicrobial activity, including microalgae. In this study, the antimicrobial properties of marine and freshwater microalgae extracts were evaluated against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa), Mycobacterium tuberculosis strain H37Rv and Mycobacterium smegmatis. Water, dimethyl sulfoxide, and ethanol were used as extractants. The obtained microalgae extract exhibited cytotoxicity against splenocytes and, to a lesser extent, against peritoneal macrophages of CBA mice. The bacteriostatic effect of the microalgae extracts against bacteria and mycobacteria was demonstrated by MTT test. In addition, activation of bacterial and mycobacterial growth was observed in a number of cases with high levels of microalgae extracts in the medium. In an expression model of tuberculosis in mice, a decrease in mycobacterial load in the lungs and spleen was observed. Thus, microalgae have moderate to weak antimicrobial activity.

GS provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. But there are good reasons to remain cautious about the broad implementation of these strategies in babies and children. At best, rapid GS leads to diagnoses in many infants in highly selected populations. It sometimes leads to beneficial and changes in management. Parents and physicians both often find these results useful. We don’t know how useful such testing will be in the general population. It is almost inevitable that genetic counseling will be more challenging in a more general population. We don’t know how often GS helps improve outcome and survival or reduce symptoms in babies who receive a molecular diagnosis. We don’t know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We don’t know the relative contribution of a molecular diagnosis to the decision to withdraw life support. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. In the meantime, parents should know that genetic results sometimes confirm an already suspected dismal prognosis and sometimes yield only ambiguous findings. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Both doctors and parents should recognize that the clinical usefulness of diagnostic genomic testing in newborns is a work in progress. We are only a decade into the age of true genomic medicine. We still have much to learn.

Although ChatGPT promises wide-ranging applications, there is a concern that it is politically biased; in particular, it has a left-libertarian orientation. Nevertheless, in light of recent trends in attempts to reduce such biases, this study re-evaluated the political biases of ChatGPT using political orientation tests and the application programming interface. Moreover, the effects of the languages used in the system as well as gender and race settings were evaluated. The results indicated that ChatGPT had less political bias than previously thought; however, they did not entirely discount the political bias. The languages used in the system and the gender and race settings may induce political biases. These findings enhance our understanding of the political biases of ChatGPT and may be useful for bias evaluation and designing ChatGPT’s operational strategy.

This primer provides an overview of the rapidly evolving field of generative artificial intelligence, specifically focusing on large language models like ChatGPT (OpenAI) and Bard (Google). Large language models have demonstrated unprecedented capabilities in responding to natural language prompts. The aim of this primer is to demystify the underlying theory and architecture of large language models, providing intuitive explanations for a broader audience. Learners seeking to gain insight into the technical underpinnings of large language models must sift through rapidly growing and fragmented literature on the topic. This primer brings all the main concepts into a single digestible document. Topics covered include text tokenization, vocabulary construction, token embedding, context embedding with attention mechanisms, artificial neural networks, and objective functions in model training. The primer also explores state-of-the-art methods in training large language models to generalize on specific applications and to align with human intentions. Finally, an introduction to the concept of prompt engineering highlights the importance of effective human-machine interaction through natural language in harnessing the full potential of artificial intelligence chatbots. This comprehensive yet accessible primer will benefit students and researchers seeking foundational knowledge and a deeper understanding of the inner workings of existing and emerging artificial intelligence models. The author hopes that the primer will encourage further responsible innovation and informed discussions about these increasingly powerful tools.

An extensive review of literature simulations of polymer melts is given, considering results that test aspects of the Rouse model in the melt. We focus on the mean-square amplitudes < (X_p(0))^{2} > and time correlation functions < X_p(0) X_p(t) > of the Rouse modes $X_p(t)$. Contrary to the Rouse model: (i) Mean-square Rouse mode amplitudes < (X_p(0))^2> do not scale as sin^{-2}(p \pi/2N), N being the number of beads in the polymer. For small p (say, p <= 3) < (X_p(0))^2> scales with p as p^{-2}$; for larger p it scales as p^{-3}. (ii) Rouse mode time correlation functions < X_p(t) X_p(0) > do not decay with time as exponentials; they instead decay as stretched exponentials exp(-a t^b)$. b depends on p, typically with a minimum near N/2 or N/4. (iii) Polymer bead displacements are not described by independent Gaussian random processes. (iv) For p not equal to q, < X_p(t) X_{q}(0) > is sometimes non-zero. (v) The response of a polymer coil to a shear flow is a rotation, not the affine deformation predicted by Rouse. Simulations thus conclusively demonstrate that the Rouse model is invalid in polymer melts. We also briefly consider the Kirkwood-Riseman polymer model.

Recent developments, begun by the ascending spiral of the anticipated endless prospects of ChatGPT, promote artificial intelligence (AI) as an indispensable tool and commodity whose time has come. Yet the sinister specter of a technology that has hidden and unmanageable attributes that might be harmful to society looms in the background. As well as the likelihood that it will never deliver on the purported promise of artificial general intelligence (AGI). Currently the prospects for the development of AI and AGI are more a matter of opinion than based on a consistent methodological approach. Thus the need to take a step back to develop a general framework from which to evaluate current AI efforts, which also permits the determination of the limits to its future prospects as AGI. To gain insight into the development of a general framework, a key question that needs resolution is, what is the connection between human intelligence and machine intelligence? This is the question that needs a response because humans are at the center of AI creation and realize that without an understanding of how we become what we become, we have no chance of finding a solution. This work proposes infoautopoiesis, the self-referential, recursive and interactive process of self-production of information, as the needed general framework. Infoautopoiesis shows how the key ingredient of information is fundamental to an insightful resolution to this crucial question and allows predictions as to the present and future of AGI.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

The standard Cosmological model (LCDM) assumes that the expanding spacetime around us is infinite, which is inconsistent with the observed cosmic acceleration unless we include Dark Energy (DE) or a Cosmological Constant ($\Lambda$). But the observed cosmic expansion can also be explained with a finite mass $M$, inside a uniform expanding sphere, with empty space outside. An object with mass $M$ has a gravitation radius $r_S=2GM$. When $M$ is all contained within $r_S$, this is a Black Hole (BH). Nothing can escape from $r_S$, which becomes a boundary for the inside dynamics. In the limit where there is nothing outside, the inside corresponds to a local isolated Universe. The $r_S$ boundary condition corresponds to an effective force which is mathematically equivalent to $\Lambda=3/r_S^2$. We can therefore interpret cosmic acceleration as a measurement of the gravitational boundary of our Universe, with a mass $M = \frac{c^2}{2G}\sqrt{3/\Lambda} \simeq 6 \times 10^{22} M_{\odot}$. Such BH Universe (BHU) is observationally very similar to the LCDM, except for the very large scale perturbations, which are bounded by $r_S$.

This paper discusses and reviews the current taxonomic status and zoogeographical distribution of the mammals of Yemen. Data were collected from previous literature in addition to field observations during 2017–2018. This checklist includes 100 species of wild (terrestrial and marine) mammals currently occurring and those that went extinct within the last century in Yemen. Only wild mammals were included and domesticated species were excluded. These 100 species belong to 11 orders, 28 families, and 64 genera. In this paper, the current status and distribution of three Erinaceomorphs, seven Soricomorphs, 34 Bats, 16 Carnivores, seven Artiodactyls, one Lagomorph, 20 Rodents, one Hyracoidea, nine Cetaceans, one Sirenia, and one Primate were reported. According to the evaluation of the International Union for the Conservation of Nature and Natural Resources (IUCN): 70 species were listed as Least Concern (LC), two as Extinct (EX), one as Critically Endangered (CR), two as Endangered (EN), eight as Vulnerable (VU), five as Near Threatened (NT), and 12 as Data Deficient (DD). This paper also discusses the current main threats to the wild mammals in Yemen.

Natural systems of units $\{U_i\}$ need to be overhauled to include the dimensionless coupling constants $\{\upalpha_{U_i}\}$ of the natural forces. Otherwise, they cannot quantify all forces in a unified manner. Thus, each force must furnish a system with at least one dimensional and one dimensionless constant. We revisit three natural systems of units (atomic, cosmological, and Planck). The Planck system is easier to rectify, and we do so in this work. The atomic system discounts $\{ G, \upalpha_G \}$, thus it cannot account for gravitation. The cosmological system discounts $\{ \slashed{h}, \upalpha_\slashed{h} \}$, thus it cannot account for quantum physics. Here, the symbols have their usual meanings; in particular, $\upalpha_G$ is the gravitational coupling constant and $\upalpha_\slashed{h}$ is the fine-structure constant. The speed of light $c$ and the impedance of free space $Z_0$ are resistive properties of the vacuum, thus they must be present in all systems of units. The upgraded Planck system $${\rm UPS} \,:=\,\{ c, Z_0, G, \upalpha_G, \slashed{h}, \upalpha_\slashed{h}, \,\dots\,\!\},$$ describes all physical scales in the universe---it is nature's system of units. As such, it reveals a number of properties, most of which have been encountered previously in seemingly disjoint parts of physics, and some of which have been designated as mere coincidences. Based on the UPS results, that relate (sub)atomic scales to the Planck scale and the fine-structure constant to the Higgs field, we can state with confidence that no observed/measured physical properties are coincidental in this universe.

Morinda citrifolia (noni) fruit juice has the potential to influence immune system function. This review discusses results from several human and animal studies that provide insight into the potential mechanisms of action by which noni juice exerts its immunomodulatory effects. Increased natural killer cell activity is a likely a major contributor to the improved health outcomes and increased survival times described in case reports and as observed in LLC and S180 tumor bearing mice. Increased interferon-gamma (IFN-γ) production is also an important mechanism of action through which noni improves immune function. IFN-γ promotes natural killer cell activity and phagocytosis, activities both seen in human and bovine studies as well as in rodents. Noni promotes regulatory cytokine expression, such as IL-2 which stimulates CD4+ T cell differentiation. Noni juice appears to influence this process via kinase 1/2 (ERK1/2) protein kinase B (Akt) and nuclear factor-kappa-beta signaling. As oxidative status is known to influence immune function, this review also discusses the notable antioxidant properties of noni juice that have been demonstrated in human trials.

We present a pragmatic analysis of the different meanings assigned to the term "local realism'' in the context of the empirical violations of Bell-type inequalities since its inception in the late 1970s. We point out that most of them are inconsistent and arise from a deeply ingrained prejudice that originated in the celebrated 1935 paper by Einstein-Podolski-Rosen. We highlight the correct connotation that arises once we discard unnecessary metaphysics.

The geodesics on a relativistic manifold are given by the well-known equation involving the Christoffel coefficients. This equation can be solved numerically step by step and transposed into a quantization. We study here the effect of this quantization on the Schwarzschild spacetime, more precisely in the Kruskal-Szekeres map.

Analytical study presents the evolution and change in content over time and the emergence of different sustainable tourism (ST) concepts in tourism and hospitality. For this purpose, a Comparative Automated Content Analysis (ACA) analyses scientific articles published between 1990, when the first article in this field was published in the Web of Science (WOS), and the end of 2020. With the ACA for analysis papers research, this research helps explain why and how changing business models cross the time, organizational processes, importance of information and communication technologies in sustainable tourism strategies, green investments, sustainable standards in tourism and hospitality, and sustainable reporting.

The Mobius function is commonly used to define Euler's totient function and the Mangoldt function. Similarly, the summatory Mobius function (the Mertens function) can be used to define the summatory totient function and the summatory Mangoldt function (the second Chebyshev function).

Background: This study was conducted to investigate medical students' lifestyle habits, including sleep quality, eating and drinking pattern, physical activity, and social status. Method: This research project is part two of a multi-institutional cross-sectional observational study conducted among medical students from six medical colleges in Saudi Arabia between September and December 2019. Results: 675 medical students were enrolled electively into the lifestyle study. About half of this number were male students, and the majority aged 18-24 years. Most students (87.6%) slept between 4-8 hours a day, and over 44% were dissatisfied with their sleep. Only 28.1% had three meals a day; about 40% of them usually or always skipped breakfast. While 44% usually or always eat fast food, 44.7% drink 2 liters of water per day. Moreover, male students were significantly consuming fast foods than females, p<0.001. The majority (63.3%) revealed they usually or always drink black coffee daily. Females were significantly more inclined to regular coffee consumption than males, p<0.001. Only 4.3% exercising for 30 minutes or more daily. The majority (65%) of the students were introverted; they had few close friends. Yet, 81% were somewhat satisfied or satisfied with their social life. Male students were predicted to be significantly more satisfied with their social life than females, p=0.001. Only 4.6% smoked cigarettes daily. Whereas 7.1% smoke e-cigarette daily. In contrast, only 0.3% use shisha (hookah) daily. Male medical students were substantially more predicted to be inclined to e-cigarette use than females (p <0.001. The top five leisure activities of a medical student are surfing social media (75.9%), watching movies (61.3%), hanging out with friends (58.1%), spent time with their family (55.4%), and browsing the internet (53.6%). Female medical students were significantly more inclined to surfing social media than male medical students, p=0.022; also, watching movies was preferred for females compared to males, p=0.006. Conclusion: This study revealed that the majority of medical students in Saudi Arabia exhibited healthy lifestyles to some extent, and these health-promoting behaviors differed based on gender, especially concerning physical activity and eating patterns. The findings of this study provide relevant information for future actions that will be geared towards effectively decreasing the occurrence of chronic illnesses and improving future doctor’s well-being.

Precipitation plays vital role in the economy of agricultural country like Pakistan. Baluchistan being the largest province of Pakistan in term of land is facing reoccurring droughts as well as flashflood due unprecedent torrential precipitation pattern.

This paper extends previous research on the influence of social media and digital channels on customer purchase behaviour by presenting a new omnichannel purchasing model. We characterise that model as a “virtuous circle” as it centres around customer use of social media and has potential to benefit both customers and companies. We illustrate that model with a worked example, discuss approaches to its implementation and evaluate its use in the context of a business case study. The model creates a framework that combines elements of digital marketing, social CRM, omnichannel CRM, and customer experience and engagement. This paper bridges academic and industry practitioner communities across those fields.

We study various properties of the polygonal numbers; such as their recurrence relations; fundamental identities; weighted binomial and ordinary sums; partial sums and generating functions of their powers; and a continued fraction representation for them. A feature of our results is that they are presented naturally in terms of the polygonal numbers themselves and not in terms of arbitrary integers; unlike what obtains in most literature.

We show that the quaternion quantum mechanics has well-founded mathematical roots and can be derived from the model of elastic continuum by French mathematician Augustin Cauchy, i.e., it can be regarded as representing physical reality of elastic continuum. Starting from the Cauchy theory (classical balance equations for isotropic Cauchy-elastic material) and using the Hamilton quaternion algebra we present a rigorous derivation of the quaternion form of the non- and relativistic wave equations. The family of the wave equations and the Poisson equation are a straightforward consequence of the quaternion representation of the Cauchy model of the elastic continuum. This is the most general kind of quantum mechanics possessing the same kind of calculus of assertions as conventional quantum mechanics. The problem of the Schrödinger equation, where imaginary ‘i’ should emerge, is solved. This interpretation is a serious attempt to describe the ontology of quantum mechanics, and demonstrates that, besides Bohmian mechanics, the complete ontological interpretations of quantum theory exists. The model can be generalized and falsified. To ensure this theory to be true, we specified problems allowing exposing its falsity.

Active galactic nuclei (AGNs) are throwing in the interstellar space huge jets of energy in the form of elementary particles. The calculation of the energy density of space in the centre of the black hole with the mass of the Sun shows that in the space-time singularity of such a black hole energy density of space there is so low that atoms become unstable and fall apart into elementary particles. In this sense, AGN is a rejuvenating system of the universe. It transforms its own old matter into fresh energy in the form of jets.

COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection with the virus retaining viability for over 5 days at temperatures between 22–25^oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38^oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50^◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.

Planck’s constant and the gravitational constant are comprised of more fundamental quantities of length, mass, and time. Reformulating traditional equations in terms of these fundamental units offers a more granular view of the physical transformations encoded in the equations of physics. The composite structure of h and G conceals a simple model in which maximum unit potentials are reduced by dimensionless proportionality operators. Natural symmetries correlate the three unit dimensions, yielding predictable quantities of physical dynamics. Insights are organized into a New Foundations Model of physics that reformulates traditional constants and equations in elementary form. The New Foundations Model offers a common language for describing quantum mechanical, gravitational, and electromagnetic phenomena.

How, if at all, consciousness can be part of the physical universe remains a baffling problem. This article outlines a new, developing philosophical theory of how it could do so, and offers a preliminary mathematical formulation of a physical grounding for key aspects of the theory. Because the philosophical side has radical elements, so does the physical-theory side. The philosophical side is radical, first, in proposing that the productivity or dynamism in the universe that many believe to be responsible for its systematic regularities is actually itself a physical constituent of the universe, along with more familiar entities. Indeed, it proposes that instances of dynamism can themselves take part in physical interactions with other entities, this interaction then being “meta-dynamism” (a type of meta-causation). Secondly, the theory is radical, and unique, in arguing that consciousness is necessarily partly constituted of meta-dynamic auto-sensitivity, in other words it must react via meta-dynamism to its own dynamism, and also in conjecturing that some specific form of this sensitivity is sufficient for and indeed constitutive of consciousness. The article proposes a way for physical laws to be modified to accommodate meta-dynamism, via the radical step of including elements that explicitly refer to dynamism itself. Additionally, laws become, explicitly, temporally non-local in referring directly to quantity values holding at times prior to a given instant of application of the law. The approach therefore implicitly brings in considerations about what information determines states. Because of the temporal non-locality, and also because of the deep connections between dynamism and time-flow, the approach also implicitly connects to the topic of entropy insofar as this is related to time.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

Covid-19 disease is caused by SARS Cov-2 virus. Despite its high transmissibility, the CFR (Case Fatality Rate) of COVID-19 seems to be lower than the SARS (9,5%) and MERS (34,4%) ones⁹³ , but higher than the influenza one (0-1%)^94,95 . The disease is asymptomatic or paucisymptomatic in most of the patients, although in few cases it can be characterized by serious complications. The main causes of hospitalization in intensive care are represented by ALI (Acute Lung Injury), ARDS (Acute Respiratory Distress Syndrome), cardiovascular problems and coagulopathies (diffuse thrombosis, microthrombosis, embolisms, myocarditis, arrhytmias, heart failure, stroke)^96-98, acute nephropathy^99,100 and encephalopathies¹⁰¹. The virus presence in the vascular wall can cause endotheliitis, which triggers the process of diffuse coagulation that can lead to a worsening of the systemic inflammation. The exaggerated inflammatory response seems to be connected with the development of ARDS, MOF (Multiple Organ Failure) and coagulopathies^102-107.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

The complex color patterns on the wings and body of Drosophila guttifera (D. guttifera) are emerging as model systems for studying evolutionary and developmental processes. Studies regarding these processes depend on overexpression and down-regulation of developmental genes, which ultimately rely upon an effective transgenic system. Methods describing transgenesis in Drosophila melanogaster (D. melanogaster) have been extensively reported in several studies. However, these methods cannot be directly applied to D. guttifera due to the low egg production rate and very delicate embryos’ pre-injection treatment requirements. In this protocol, we describe extensively a comprehensive method used for generating transgenic D. guttifera. Using the protocol described here, we are able to establish transgenic lines, identifiable by the expression of Enhanced Green Fluorescent Protein (EGFP) in the eye disks of D. guttifera larvae. The entire procedure, from injection to screening for transgenic larvae, can be completed in approximately 30 days and should be relatively easy to adapt to other non-model Drosophila species, for which no white-eyed mutants exist.

If a clear and valid no-go for Einsteinian hidden parameters is real, it must in no way be possible to violate the CHSH with a local hidden variables based computer simulation. In the paper we show that with the use of a modied Glauber-Sudarshan method it is possible to violate the CHSH.The criterion value comes close to the quantum value and is approximately 2.4. The proof (POC) is presented with the use of an R computer program. The important snippets of the code are discussed and the complete code is presented in an appendix.

Financial literacy is a path to sustainability and has an important role in ensuring the financial sustainability of individuals, families, enterprises and national economies. The level of these economic indicators such as debt, payment discipline, savings and financial management all translate into prosperity or insolvency and bankruptcy and result partially from financial literacy. The higher the level of financial literacy, especially of young people, the more favorable the level of economic indicators, which translates into the economy and sustainable development. However, despite many years of research, there is still a lack of a uniform and coherent definition of financial literacy, as well as methods for measuring it. This study offers a small step forward, presenting the authors’ own view of the concept of financial literacy, the conceptualizations of financial literacy and methods used for investigating. Moreover, they present the results of a survey conducted on the financial behaviour, financial attitudes, and financial knowledge of the Polish youth and compare this to a PISA study on 15-year-old students. Results demonstrate a good, and partially very good, level of financial literacy among young Poles, showing that they are rational in their financial decision making.

Visual imagery, i.e., the mental experience of an object occurring in the absence of external visual stimulus, might encompass diverse content according to different observers. Further, subjectively experienced time is encoded in the later entorhinal cortex. Starting from these two observations, and considering Einstein’s account of spacetime, we show how, in terms of special relativity, the content of visual imagery is not stationary and fixed, rather depends on the standpoint of the observer. We elucidate how the subjective definition of time (perceived by our mind as static) might give rise to modifications in the length of the imagined object which are experimentally assessable and quantifiable. In particular, based on recent neuroscientific literature, we show how changes in our mental time windows are able to squeeze the visual content of mental imagery.

We examine the extensions of the basic arithmetical operations of addition and multiplication on the natural numbers into higher-rank hyper-operations also on the natural numbers. We go on to define the concepts of prime and composite numbers under these hyper-operations and derive some results about factorisation, resulting in fundamental theorems analogous to the Fundamental Theorem of Arithmetic.

Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system. This rare tumor in duodenum is seen 5%. The diagnosis and treatment is hard because of its rarity and location. Case: A 63-year-old man with a solid mass at the third part of the duodenum, and local segmental resection of the tumor was performed. The histopathology was reported as gastrointestinal stromal tumor of the duodenum with negative surgical margins. Discussion: Gastrointestinal stromal tumors at the duodenum are seen rarely. They can be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumors less than 2 cm can be followed by endoscopic ultrasound. Local segmental resection with 1cm clear margin is the treatment choice.

We reelaborate on the basic properties of PT symmetry from a geometrical Perspective. The transfer matrix associated with these systems induces a Möbius transformation in the complex plane. The trace of this matrix classifies the actions into three types that represent rotations, translations, and parallel displacements. We find that a PT invariant system can be pictured as a complex conjugation followed by an inversion in a circle. We elucidate the physical meaning of these geometrical operations and link them with measurable properties of the system.

The rapidly evolving field of additive manufacturing requires a periodic assessment of the progress made in understanding the properties of metallic components. Although extensive research has been undertaken by many investigators, the data on properties such as hardness from individual publications are often fragmented. When these published data are critically reviewed, several important insights that cannot be obtained from individual papers become apparent. We examine the role of cooling rate, microstructure, alloy composition, and post process heat treatment on the hardness of additively manufactured components. Hardness data for steels and aluminum alloys processed by additive manufacturing and welding are compared to understand the relative roles of manufacturing processes. Furthermore, the findings are useful to determine if a target hardness is easily attainable either by adjusting AM process variables or through appropriate alloy selection.

Friction is an important subject for sustainability due to problems associated with energy loss. Recent years, surface micro- and nanostructures have attracted much attention to reduce friction; however, suitable structures are still under consideration. Many functional surfaces are present in nature, such as the friction reduction surfaces of snake skins. In this study, we focused on firebrats, Thermobia domestica, living in narrow spaces such as under bark, so their surface frequently contacts with surrounding surfaces. We speculate that their body surface would be adapted to reduce friction. To investigate the firebrat surface functions, firebrat surfaces were observed by using a field-emission scanning electron microscope (FE-SEM) and a colloidal probe atomic force microscope (AFM), respectively. Results of surface observations by the FE-SEM revealed that firebrats are entirely covered with scales, whose surfaces have micro groove structures. Scale groove periods around the firebrat's head are almost uniform within a scale but vary between scales. AFM friction force measurements revealed that firebrat scale reduces friction by decreasing contact area between scales and a colloidal probe. The heterogeneity of groove periods of the scales suggest that it is difficult to fix the whole body in particular rough surfaces and that lead to be "fail-safe".

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

Euglena gracilis is an alga of great biotechnological interest and extensive metabolic capacity, able to make high levels of bioactive compounds, such as polyunsaturated fatty acids, vitamins and β-glucan. Previous work has shown that Euglena expresses a wide range of carbohydrate-active enzymes, suggesting an unexpectedly high capacity for the synthesis of complex carbohydrates for a single-celled organism. Here, we present an analysis of some of the carbohydrates synthesised by Euglena gracilis. Analysis of the sugar nucleotide pool showed that there are the substrates necessary for synthesis of complex polysaccharides, including the unusual sugar galactofuranose. Lectin- and antibody-based profiling of whole cells and extracted carbohydrates revealed a complex galactan, xylan and aminosugar based surface. Protein N-glycan profiling, however, indicated that just simple high mannose-type glycans are present and that they are partially modified with putative aminoethylphosphonate moieties. Together, these data indicate that Euglena possesses a complex glycan surface, unrelated to plant cell walls, while its protein glycosylation is simple. Taken together, these findings suggest that Euglena gracilis may lend itself to the production of pharmaceutical glycoproteins.

In the paper, the author (1) presents an explicit formula and its inversion formula for higher order derivatives of generating functions of the Bell polynomials, with the help of the Faà di Bruno formula, properties of the Bell polynomials of the second kind, and the inversion theorem for the Stirling numbers of the first and second kinds; (2) recovers an explicit formula and its inversion formula for the Bell polynomials in terms of the Stirling numbers of the first and second kinds, with the aid of the above explicit formula and its inversion formula for higher order derivatives of generating functions of the Bell polynomials; (3) constructs some determinantal and product inequalities and deduces the logarithmic convexity of the Bell polynomials, with the assistance of the complete monotonicity of generating functions of the Bell polynomials. These inequalities are main results of the paper.

Models come in different forms: visual, arithmetic, mental, physical. The most common type of model is arguably the mental model, which people use to view and interpret the world. A model can be described as a representation of a problem or a situation – a simplified representation. The process of building or developing a model is called modeling. A model once developed by the modeller, can be ‘owned’ by a manager or decision maker. The ideal is to make the model an extension of the user’s ability to think about and analyse problems or situations. When used properly – taking into consideration its limitations – an economic model for a project can provide insight for decision makers, when making the crucial decision to approve a project. An economic model for a liquefied natural gas (LNG) project is shown as an example.

The manufacturing method influences the properties of the produced components. This work investigates the influence of manufacturing methods such as fused filament fabrication (3D printing) and injection molding on water absorption, mechanical and thermal properties of the specimens produced from neat biobased poly(lactic acid) (PLA) polymer and poly(lactic acid)/wood composites. Acrylonitrile butadiene styrene (ABS) acts as the reference material due to its low water absorption and good functional properties. The printing layer thickness is one of the factors that affects the properties of a 3D printed specimen. The investigation includes two different layer thicknesses (0.2 mm and 0.3 mm) while maintaining uniform overall thickness of the specimens across two manufacturing methods. 3D printed specimens absorb significantly higher amounts of water than the injection molded specimens, and the increase in the layer thickness of the 3D printed specimens contributes to further increased water absorption. However, the swelling due to water absorption in 3D printed specimens decreases on increased layer thickness. Tensile, flexural and impact properties of all the specimens decrease after water absorption while the properties improve on decreasing the layer thickness. Higher porosity on increasing the layer thickness is the predominant factor. The results from dynamic mechanical analysis and microscopy validate the outcomes.

Background: Health-related knowledge is among the essential factors to enable women to be aware of their rights to seek health services. However, little is known about knowledge of safe abortion care services among women of reproductive age in Ethiopia. The main purpose of the study was to assess knowledge of safe abortion care services and associated factors among women of reproductive age in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted from April-June 2019 among 432 respondents. Bivariate statistics including correlation coefficients, student t-test, one-way analysis of variance, and linear regressions, and multiple linear regression analyses were used. A significant statistical test was determined at a 95% confidence interval and p-value <0.05. Results: About 65.5% had heard about safe abortion care services; media being the main source of information for 79.5%. The finding from an independent-sample t-test shows that the place where the respondents grew up (p< 0.006), history of past miscarriage, and previous information of abortion care service were significantly associated with the knowledge about safe abortion care services (p< 0.001). Conclusions: Women without prior health experiences and those with rural origin could be targeted for reproductive health information interventions including safe abortion care provision.

Geographic Information Systems (GIS) played an important role in understanding the dynamics of the territorial spread of COVID-19 during the pandemic. Even today, it is important to understand such dynamics in view of the imminent risk of new epidemics and pandemics. This study aimed to identify space-time clusters of incidence and mortality due to COVID-19 during the pandemic, analyzing socioeconomic and demographic characteristics in order to highlight the priority areas for control and surveillance actions. This study was conducted in the Metropolitan Region of São Paulo (MRSP) from March 2020 to February 2022. To detect the clusters, a multidimensional punctual process was created to perform multiple tests for every geographic point using the SaTScan™ software. Socioeconomic and demographic differences were analyzed using nonparametric Mann-Whitney and Kruskal-Wallis tests. High-risk clusters of incidences were observed in May 2020 (RR=2; p-value <0.001) and March to June 2021 (RR=2.6; p-value <0.001) in the capital of São Paulo and neighboring municipalities, with statistically significant differences between the socioeconomic variables analyzed. No low-risk cluster of COVID-19 incidence was found, but low-risk clusters of mortality from COVID-19 were found in the period from July to December 2020 in the central region of the capital (RR=0.33; p-value <0.001), which concentrates the highest incomes and the lowest percentages of Black, Brown (Mixed-race), and Indigenous people in the MRSP.

The prevalence of depression and anxiety among healthcare workers (HCWs) during the Covid-19 pandemics is high. The aim of the study is to identify the importance of self-esteem and occupational factors in association with the incidence of depression and anxiety among HCWs through a longitudinal cohort study during the Covid-19 pandemics in Latvia. Participants were interviewed repeatedly seven times during the Covid-19 pandemics. 322 participants were included in the data analysis for depression and 352 for anxiety. Low self-esteem and working in the general practitioner's office is associated with the incidence of depression and anxiety. Undergraduate education and direct contact with Covid-19 patients are associated with the incidence of depression. The risk of anxiety decreases by 1% each year among HCWs. Our study shows the importance of personality factors of HCWs during the Covid-19 pandemics.