There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections and its applicability to human disease.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

The aim of the present study is to investigate themes related to visitors’ perceptions of captive wildlife in particular, attitudes towards non-human primates (henceforth, primates). This research took place in free-roaming, multi-species primate sanctuary, Monkeyland (South Africa), where 400 visitors were interviewed using an anonymous survey both before and after attending a guided tour. The answers were divided into different categories, in order to standardize the motivations behind tourists’ choices. The results of the survey demonstrated that most visitors agree that a primate would not be a good companion animal. Visitors’ desire to touch primates was found to be positively correlated with desire for companion primates and inversely associated with visitor age. In response to: “would you like to touch a monkey?”, the majority of tourists who expressed this desire seemed aware that such interactions are not appropriate, with concern for animal welfare and human health. Of the various primate species present in the sanctuary, visitors preferred the ring-tailed lemur (Lemur catta) and, generally speaking, expressed appreciation for primates’ “cuteness”. Our results indicate a general awareness by the visitors on the importance of animal welfare in the human interactions with captive wildlife, in agreement with the “hands-off” policy of Monkeyland primate sanctuary. We discuss the findings from a general to zooanthropological point of view, proposing some reflections on the attitudes of visitors toward non-human primates.

Besides living as a free-ranging primate in the horn of Africa and the Arabian Peninsula, the hamadryas baboon has an important place in zoos and can be found in biomedical research centers worldwide. To be valuable as a non-human primate laboratory model for man, its anatomy should be portrayed in detail allowing for the correct interpretation and translation of obtained research results. Reviewing the literature on the use of the baboon in biomedical research revealed that very limited anatomical works on this species are available. Anatomical atlases are incomplete, use archaic nomenclature and fail to provide high definition color photographs. Therefore, the skeletons of two male hamadryas baboons were prepared by manually removing as much soft tissues as possible followed by maceration in warm water to which enzyme-containing washing powder was added. The bones were bleached with hydrogen peroxide and degreased by means of methylene chloride. Photographs of the various bones were taken, and the anatomical structures were identified using the latest version of the Nomina Anatomica Veterinaria. As such, the present article shows 31 annotated multipanel figures. The skeleton of the hamadryas baboon generally parallels the human skeleton, but some remarkable differences have been noticed. If these are taken into consideration when evaluating the results of experiments using the hamadryas baboon, justified conclusions can be drawn.

The non-pharmaceutical interventions implemented to prevent the spread of COVID-19 have affected the epidemiology of other respiratory viruses. In South Korea, Human metapneumovirus (HMPV) typically occurs from winter to the following spring; however, it was not detected for two years during the COVID-19 pandemic and re-emerged in the fall of 2022, which is a non-epidemic season. To examine the molecular genetic characteristics of HMPV before and after the COVID-19 pandemic, we analyzed 427 HMPV-positive samples collected in the Gwangju area from 2018 to 2022. Among these, 24 samples were subjected to whole-genome sequencing. The results showed a shift in the predominant genotype from A2b2 before the COVID-19 pandemic to A2b1 in 2022. Furthermore, a significant increase in HMPV cases was observed in the 6–10-year age group. Since the onset of the COVID-19 pandemic, social distancing have reduced the possibility of HMPV exposure and herd immunity due to non-transmission, resulting in the introduction of new HMPV genotypes in different seasons.

In recent years, advances in science, technology, and the way in which we view our world have led to anincreasingly broad use of the term “intelligence”. As we learn more about biological systems, we find more and more examples of complex and precise adaptive behavior in animals and plants. Similarly, as we build more complex computational systems, we recognize the emergence of highly sophisticated structures capable of solving increasingly complex problems. These behaviors show characteristics in common with the sort of complex behaviors and learning capabilities we find in humans, and therefore it is common to see them referred to as “intelligent”. These analogies are problematic as the term "intelligence" is inextricably associated with human-like capabilities. While these issues have been discussed by leading researchers of AI and renowned psychologists and biologists highlighting the commonalities and differences between AI and biological intelligence, there have been few rigorous attempts to create an interdisciplinary approach to the modern problem of intelligence. This article proposes a comparative framework to discuss what we call “purposeful behavior”, a characteristic shared by systems capable of gathering and processing information from their surroundings and modifying their actions in order to fulfill a series of implicit or explicit goals. Our aim is twofold: on the one hand, the term purposeful behavior allows us to describe the behavior of these systems without using the term "intelligence", avoiding the comparison with human capabilities. On the other hand, we hope that our framework encourages interdisciplinary discussion to help advance our understanding of the relationships among different systems and their capabilities.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combat the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Toxoplasmosis is a neglected anthropozoonosis caused by the obligate intracellular protozoan, Toxoplasma gondii. The role of non-human primates in the epidemiology of human toxoplasmosis is not clear. Acute and highly fatal cases of toxoplasmosis are frequently reported in new world monkeys and asymptomatic infections in old world monkeys. Here we report detection of latent natural T. gondii infection in olive baboons during a screening exercise to select animals for an experimental toxoplasmosis study. Archived serum samples from 32 olive baboons (Papio anubis), 23 wild caught and nine colony-born, were screened for T. gondii DNA using nested PCR. Eighteen (56.25%) samples were from females and fourteen (43.75%) from males. Toxoplasma gondii DNA was detected in 21 (65.6%) baboons. 13 females (40. 6%) and eight males (25%). Five baboons (24%) which tested positive were from the Institute of Primate Research colony but there was no statistical significance between them and the wild trapped (p=0.453). There was neither statistical significance (p=0.373) between sex and infection status nor between area of origin and infection status (p>0.05). These results indicate that olive baboons get infected with T. gondii in the wild and during captivity and may be significant reservoirs of human infections, especially where they may be trapped for bushmeat. We recommend a country-wide study to establish true prevalence of toxoplasmosis among non-human primates and identify associated parasite strains.

Leber’s hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease, causing irreversible blindness in young individuals. Current treatments are inadequate, and there is no definitive cure. This study evaluates the effectiveness of delivering wildtype human NADH ubiquinone oxidoreductase subunit 4 (hND4) gene using mito-targeted AAV(MTSAAV) to rescue LHOH mice. We observed declining pattern electroretinograms amplitudes as mice aged across all groups (P< 0.001), with significant differences among groups (P = 0.023, Control vs. LHON, P = 0.008; Control vs. Rescue, P = 0.228). Inner retinal thickness and intraocular pressure do not change significantly with age or groups. Compared to LHON mice, those rescued with wildtype hND4 exhibit improved retinal visual acuity (0.29± 0.1 cy/deg vs.0.15 ± 0.1 cy/deg) and increased functional hyperemia response (effect of flicker, P<0.001, effect of Group, P=0.004; Interaction Flicker x Group, P<0.001). Postmortem analysis shows a marked reduction in retinal ganglion cell density in the LHON group compared to the other groups (Effect of Group, P<0.001, Control vs. LHON, P<0.001, Control vs. Rescue, P=0.106). These results suggest that MTSAAV-delivered wildtype hND4 gene rescues, at least in part, visual impairment in an LHON mouse model and has the therapeutic potential to treat this disease.

Fruits, vegetables, and spices are natural sources of bioactive phytochemicals such as polyphenols, carotenoids, flavonoids, curcuminoids, terpenoids, and capsaicinoids, possessing multiple health benefits and relatively low toxicity. These compounds found in the diet play a central role in organism development and fitness. Given the complexity of the whole-body response to dietary changes, invertebrate model organisms can serve as valuable tools to examine the interplay between genes, signaling pathways, and metabolism. Drosophila melanogaster, an invertebrate model with its extensively studied genome, has more than 70% gene homology to humans and has been used as a model system in biological studies for a long time. The notable advantages of Drosophila as a model system, such as their low maintenance cost, high reproductive rate, short generation time and lifespan, and the high similarity of metabolic pathways between Drosophila and mammals, have encouraged the use of Drosophila in the context of screening and evaluating the impact of phytochemicals present in the diet. In this chapter, we summarize and review the benefits of Drosophila as a model system for use in the study of phytochemical ingestion and describe the previously reported effects of phytochemical consumption in Drosophila.

This paper is referred to a top frontline research in life science, showing that in spite of the large variation of the physiological architecture and behavioral forms of the living systems, the fundamental structure of their informational system is basically the same, allowing the body growth/development by micro to macro-structuration processes, maintaining the same informational configuration and functions like the basic unit of life – the eukaryotic cell. Starting and based on the determination of the special/specific info-operability in living structures and the role of information in structuration and their functionality, there are discussed the informational functions of the eukaryotic/prokaryotic cells, the simplest units of life and is elaborated and presented the Informational Model of the Living Structures, showing that these structures operate on the basis of two main informational systems: one of them defined as the Programmed Informational System, composed by three components, assuring respectively the info-generation, maintenance and the proliferation/reproduction, and another one defined as the Operative Informational System, necessary for the continuous communication with the environment for adaptation, consisting in four main components referred to memory, decision, sentience and info-connection/info-selection. The revealed properties are compared with the Informational System of the Human Body, as a prototype of a living system on the top of the evolutionary scale, showing/demonstrating the compatibility of structuration and functions on the entire scale, from prokaryotic/eukaryotic unit cells to multicellular organisms – plants, animals and human, by means of a continuous adaptation process, which always follows the same line of micro to macro-structuration process based on the same Info-organization and functionality. These models are new and revolutionary in the information and life sciences

Interactome analyses have traditionally been applied to yeast, human and other model organisms due to the availability of protein-protein interactions data for these species. Recently these techniques have been applied to more diverse species using computational interaction prediction from genome sequence and other data types. This review describes the various types of computational interactome networks that can be created and how they have been used in diverse eukaryotic species, highlighting some of the key interactome studies in non-model organisms.

In standard construction of hyperrational numbers using ultra-power we assume that the ultralter is selective. It makes possible toassign real value to any nite hyperrational number. So, we can consider hyperrational numbers with selective ultralter as extension of traditional real numbers. Also proved the existence of strictly monotonic or stationary representing sequence for any hyperrational number.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

Virtual human body models contribute to designing safe and user-friendly products through virtual prototyping. Anthropometric biomechanical models address different physiques using average dimensions. In designing personal protective equipment, biomechanical models with the correct geometry and shape shall play a role. The presented study shows the variations of subject-specific anthropometric dimensions from the average for the different population groups in the Czech Republic and China as a background for the need for personalized human body models. The study measures a set of clothing industry dimensions of Czech children, Czech teens, Czech adults and Chinese adults and compares them to the corresponding age average, which is represented by a scaled anthropometric human body model. The cumulative variation of clothing industry dimensions increases the farer is the population group from the average. It is smallest for the Czech adults 7.54% ± 6.63%, Czech teens report 7.93% ± 6.25% and Czech children differ 9.52% ± 6.08%. Chinese adults report 10.86% ± 11.11%. As the variations of the particular clothing industry dimensions from the average prove the necessity of having personalized subject-specific models, the personalization of particular body segments using the measured clothing industry dimensions leading to a subject-specific virtual model is addressed. The developed personalization algorithm results in the continuous body surface desired for contact applications for assessing body behavior and injury risk under impact loading.

In this paper we introduce an ODE system to model the interaction between nature resources and human exploitation in a rich consumeristic society. In this model the rate of change of population depends on wealth per capita, and the rate of consumption has a quadratic growth with respect to population and wealth. As in our previous work \cite{BaCra_1}, we distinguish between renewable and non renewable resources, and we introduce a replenishment term for non renewable resources. We first get some information on the asymptotic behaviour of wealth and population, then we compute all the equilibria of the system and we study their stability when the parameter of exploitation of resources is small. Some numerical simulations confirm the theoretical results, and give suggestions for future research.

We summarise contributions made to the computational phase-field modelling of alloy solidification from the University of Leeds spoke of the LiME project. We begin with a general introduction to phase-field, and then reference the numerical issues that arise from solution of the model, before detailing each contribution to the modelling itself. These latter contributions range from controlling and developing interface-width independent modelling; controlling morphology in both single and multiphase settings; generalising from single to multi-phase models; and creating a thermodynamic consistent framework for modelling entropy flow and thereby postulate a temperature field consistent with the concepts of, and applicable in, multiphase and density-dependent settings.

The identification of fetal cells in the blood and tissues of healthy mothers raised questions about the potential alloreactive origins of various diseases, such as autoimmunity, diabetes, arteriosclerosis, and cancer. However, the extent to which alloreactivity contributes to these diseases remains unverified. This study presents a basic mathematical disease model based on the genes’ origin and immunological interactions. This model, grounded in set theory, classifies these immunological interactions based on their intrinsic, extrinsic, and allogeneic nature. Therefore, this model offers an unexpected common theoretical foundation for understanding alloreactivity, genetic diseases, and infections. Furthermore, this model provides a valuable framework for scrutinizing the role of alloreactivity in health and disease.

In this paper we analyze and propose new method and algorithm of selecting the optimal labor time as a function of skills following our main references Mirrlees (1971), Saez (2001) and Stancheva (2014). The optimal labor time is a situation when the utility function of individual reaches a maximum. One of the main differences with Saez (2001) is our algorithm for creation the skill distribution

Climate change, recognized as a global crisis, is not only altering our environment but also significantly impacting human health. Particularly, its influence on non-communicable diseases (NCDs), a leading cause of global mortality, is becoming increasingly evident yet underexplored. This review aims to synthesize current research on the impact of climate change on NCDs, addressing a critical gap in our understanding of how environmental changes affect human health. We examine the complex interplay between climate change and NCDs, drawing insights from recent studies that highlight the adverse effects of climate variables on chronic diseases, such as cardiovascular and kidney diseases, and the role of food and nutrition security in this nexus. Furthermore, the review explores the disproportionate impact on vulnerable regions and populations, particularly in Pacific Island countries and territories, underscoring the urgent need for context-specific solutions and a cross-sectoral approach. By integrating findings from various disciplines, this review aims to inform policy and public health interventions, highlighting the necessity of collaborative efforts to mitigate the burgeoning burden of NCDs in a rapidly changing climate.

This paper presents a critical review and comparison of the results of recently published studies in the fields of human-machine interface and the use of sonomyography (SMG) for the control of upper limb prothesis. For this review paper, a combination of the keywords "Human Machine Interface", "Sonomyography", "Ultrasound", "Upper Limb Prosthesis", "Artificial Intelligence" and "Non-Invasive Sensors" was used to search for articles on Google Scholar and PubMed. Sixty-one articles were found, of which 59 were used in this review. For a comparison of the different ultrasound modes, feature extraction methods, and machine learning algorithms, 16 articles were used. It was found that various modes of ultrasound devices for prosthetic control, various machine learning algorithms for classifying different hand gestures, as well as various feature extraction methods for increasing the accuracy of artificial intelligence used in their controlling systems are reviewed in this article. The results of the review article show that ultrasound sensing has the potential to be used as a viable human-machine interface in order to control bionic hands with multiple degrees of freedom. Moreover, different hand gestures can be classified by different machine learning algorithms trained with extracted features from collected data with an accuracy of around 95%.

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

Chlamydia trachomatis (CT) is an obligate intracellular bacterial pathogen known to cause trachoma, sexually transmitted infections, and reactive arthritis. The more serious sequelae of these diseases, blindness from trachoma and pelvic inflammatory disease from chlamydial STD are immunopathological responses to chronic infections. With the abundance of dendritic cells in CT infection sites and their central importance in immune regulation, the susceptibility of dendritic cells to CT infection was investigated in vitro. CT (serovar F) was grown and extracted from HeLa 229 cells for infection of human dendritic cells (DCs). Human DCs were generated from peripheral blood mononuclear cells in the presence of GM-CSF and IL-4. Infected DCs were harvested at 0, 4, 24, and 48 h after infection and immunostained. Results from fluorescence microscopy showed that DC can be infected and can support the growth of CT in vitro. Intracellular elementary and reticulate bodies of CT were detected, and reticulate bodies were shown to multiply over the 48 h-cycle in DC. At 48 h, intracellular elementary bodies were detected in some DCs. These results may provide new insights into the possible participation of DC in sustaining chronic or latent infection, or even dissemination of CT infection to other sites.

Human motor planning combines such interesting aspects as modular organization in motor primitives and characteristics of stochastic optimality. Motor primitives aided in the description of motor skill learning. In this study, for the first time, an interpretation is proposed to explain how motor primitives are shaped in a stochastic optimality process.To this end, sensory information is assumed to be random variables at each moment. Theoretically, the results confirmed that the variability of a movement increased with passing time. As a result, motor planning should be performed in shorter durations to achieve an accurate movement. It means that a task should be divided into several subtasks at various stages of time. Moreover, theoretically, the results confirmed that motor planning is statistically optimal if the movement is planned in minimum jerk space, which is in accordance with what is reported in the literature. Comparing the proposed mathematical model with the results of experimental data in two different types of motor action (i.e., arm reaching movement and sit-to-stand transfer from a chair) confirmed that the proposed model can be considered a framework to investigate the effect of bottom-up information on human motor planning level. Further experiments need to investigate it more deeply.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

The Human Gut Microbiome is an important host’s component defining its health. These microorganisms are mutualistic symbionts dependent on factors such as host’s age, subsistence models and sociocultural practices, among others. The conjunction of these factors define the microbial ecosystem dynamics. Using a fecal microbiome approach in children, a comparison of two Mexican communities with contrasting lifestyles: “westernized” (Mexico City) and “non-westernized” (Me’phaa indigenous group) was evaluated. The main differences between these two communities are in bacteria associated with different types of diets (high animal protein and refined sugars vs high fiber food, respectively). In addition, the gut microbiome of Me’phaa children showed higher total diversity and the presence of exclusive phyla, such as Deinococcus-Thermus, Chloroflexi, Elusimicrobia, Acidobacteria and Fibrobacteres. In contrast, Mexico City children had less diversity and the exclusive presence of Saccharibacteria phylum which is associated with the degradation of sugar compounds. This comparison allows further exploration of the selective pressures affecting microbial ecosystemic composition over the course of human evolution and the potential consequences of pathophysiological states correlated with westernization lifestyles.

The poor success rate of preclinical drugs which target the nervous system is related to the highly complex nature of brain physiology and pathophysiology. For in vitro drug screening in this field, the two-dimensional (2D) approach - where cells are incubated in a monolayer - is not physiologically relevant. In contrast, in vivo rodent models are very low throughput and expensive. As such, improved, well-characterised three dimensional (3D) in vitro models should be employed to bridge the gap between 2D in vitro primary screening and rodent models by incorporating aspects of the in vivo brain environment. These key features include the extracellular matrix (ECM) and a multidimensional relationship of supporting cells. In this study, a neural progenitor cell line was differentiated into the main types of cells found in brain, including neurons and astrocytes. This model was designed in a 3D extracellular matrix replacement in a minimalised manner. Different culture formats using multi-well plates were explored and a high-throughput cellular imaging platform was applied. Next, we applied this model to assess neural toxicity of a newly synthesised dual-specificity tyrosine-regulated kinase 1 (DYRK1) inhibitor derived from natural compounds, which is structurally related to a natural DYRK1A inhibitor harmine, K04179. Chemical studies have already shown that K04179 has higher specificity to DYRK1A compared with previously reported DYRK1 inhibitors, such as INDY. We have produced the first report of the biological effects of this new compound on the new 3D minimalised mid-brain model with quantification of both neuronal and astrocyte populations in tandem, revealing differential toxic effects of DYRK1 inhibitor compounds K04179 and INDY on neurons and glia.

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data which highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked resource for advancing therapies and management of HIV/AIDS.

During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca2+oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction ability.

Most studies modelling population mobility and the spread of infectious diseases, particularly using meta-population-multi-patched models, tend to focus on theoretical properties and numerical simulations of such models. There is relatively scanty literature published on fit, inference and uncertainty quantification on epidemic models with population mobility. In this research, we have used three estimation techniques to solve an inverse problem and quantify its uncertainty on a human mobility-based multi-patched epidemic model, using mobile phone sensing data and COVID-19 confirmed positive cases in Hermosillo, Mexico. First, we have utilized a Brownian bridge model using mobile phone GPS data to estimate residence and mobility parameters of the epidemic model. In the second step, we have estimated the optimal model epidemiological parameters by deterministically inverting the model using a Darwinian inspired evolutionary algorithm (EA) known as the genetic algorithm (GA). The third part of the analysis involves performing inference and uncertainty quantification on the epidemic model using two Bayesian Monte Carlo sampling methods: t-walk and Hamiltonian Monte Carlo (HMC). The results show that the estimated model parameters and incidence adequately fit the observed daily COVID-19 incidence in Hermosillo. Moreover, the estimated parameters from HMC result into large credible intervals, improving their coverage for the observed and predicted daily incidences. We also observe improved predictions when using multi-patch model with mobility against the single-patch model.

In this study, the generality and prediction accuracy of a generalised series model for large eddy simulation of premixed and non-premixed turbulent combustion is explored. The model is based on Taylor series expansion of the chemical source term in scalar space and implemented into OpenFOAM. The mathematical model does not depend on the combustion regimes, and has the correct limiting behaviour. The numerical error sources are outlined and analysed. The model is first applied to a piloted methane/air non-premixed jet flame (Sandia Flame D). The statistical (time-averaged and RMS) results agree well with experimental measurements, particularly with regard to the mixture fraction, velocity, temperature, and concentrations of major species CH4, CO2, H2O, and O2. The concentrations of intermediates CO and H2 are over-predicted, due to the limitations of the reduced reaction mechanism employed. Then, a Bunsen piloted flame is simulated. Most of the statistical properties of both reactive species and progress variable are well reproduced. The only major discrepancy evident is in the temperature, which is attributed to the experimental uncertainties of temperature fields in the pilot stream. These findings have demonstrated the model`s generality for both premixed and non-premixed combustion simulation, as well as the accuracy of prediction of reactive species distribution.

Tuberculosis (TB) is still a worldwide major health problem and models using non-human primates (NHP) provide the most relevant approach for vaccine testing. In this study we have analysed CT images collected from cynomolgus and rhesus macaques, following exposure to ultra-low dose Mycobacterium tuberculosis (Mtb) aerosols, and monitored them for 16 weeks to evaluate the impact of prior intradermal or inhaled BCG-vaccination on the progression of lung disease. All lesions found (2553) have been classified according to their size and we have subclassified small micronodules (<4.4 mm) as ‘isolated’, or as ‘daughter’ when they are in contact with consolidation (described as lesions ≥ 4.5 mm). Our data links the higher capacity to contain Mtb infection in cynomolgus with the reduced incidence of daughter micronodules, thus avoiding the development of consolidated lesions and their consequent enlargement and evolution to cavitation. In the case of rhesus, intradermal vaccination has a higher capacity to reduce the formation of daughter. This study supports the ‘Bubble Model’ defined with the C3HBe/FeJ mice and proposes a new method to evaluate outcome in experimental models of TB in NHP based on CT images, which would fit a future machine learning approach to evaluate new vaccines.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

We have implemented quantum modeling mainly based on Bohmian Mechanics to study time series that contain strong coupling between their events. Compared to time series with normal densities, such time series are associated with rare events. Hence, employing Gaussian statistics drastically underestimates the occurrence of their rare events. The central objective of this study is to investigate the effects of rare events in the probability densities of time series from the point of view of quantum measurements. For this purpose, we first model the non-Gaussian behavior of time series using the multifractal random walk (MRW) approach. Then, we examine the role of the key parameter of MRW, λ, which controls the degree of non-Gaussianity, in quantum potentials derived for time series. Our Bohmian quantum analysis shows that the derived potential takes some negative values in high frequencies (its mean values), then substantially increases, and the value drops again for rare events. Thus, rare events can generate a potential barrier in the high-frequency region of the quantum potential, and the effect of such a barrier becomes prominent when the system transverses it. Finally, as an example of applying quantum potential beyond the microscopic world, we compute quantum potentials for the S&amp;P financial market time series to verify the presence of rare events in the non-Gaussian densities and demonstrate deviation from the Gaussian case.

We describe a new approach for integrating multiple views of data into a common latent space using non-negative tensor factorization (NTF). This approach, which we refer to as the "Integrated Sources Model" (ISM), consists of two main steps: embedding and analysis. In the embedding step, each view is transformed into a matrix with common non-negative components. In the analysis step, the transformed views are combined into a tensor and decomposed using NTF. Noteworthy, ISM can be extended to process multi-view data sets with missing views. We illustrate the new approach using two examples: the UCI digit dataset and a public cell type gene signatures dataset, to show that multi-view clustering of digits or marker genes by their respective cell type is better achieved with ISM than with other latent space approaches. We also show how the non-negativity and sparsity of the ISM model components enable straightforward interpretations, in contrast to latent factors of mixed signs. Finally, we present potential applications to single-cell multi-omics and spatial mapping, including spatial imaging and spatial transcriptomics, and computational biology, which are currently under evaluation. ISM relies on state-of-the-art algorithms invoked via a simple workflow implemented in a Jupyter Python notebook.

This paper presents ConF, a novel deep learning model designed for accurate and efficient prediction of non-coding RNA families. NcRNAs are essential functional RNA molecules involved in various cellular processes, including replication, transcription, and gene expression. Identifying ncRNA families is crucial for comprehensive RNA research, as ncRNAs within the same family often exhibit similar functionalities. Traditional experimental methods for identifying ncRNA fam-ilies are time-consuming and labor-intensive. Computational approaches relying on annotated secondary structure data face limitations in handling complex structures like pseudoknots and have restricted applicability, resulting in suboptimal prediction performance. To overcome these chal-lenges, ConF integrates mainstream techniques such as residual networks with dilated convolutions and cross multi-head attention mechanisms. By employing a combination of dual-layer convolu-tional networks and BiLSTM, ConF effectively captures intricate features embedded within RNA sequences. This feature extraction process leads to significantly improved prediction accuracy compared to existing methods. Experimental evaluations conducted on a ten-fold publicly available dataset demonstrate the superiority of ConF in terms of accuracy, sensitivity, and other perfor-mance metrics. Overall, ConF represents a promising solution for accurate and efficient ncRNA family prediction, addressing the limitations of traditional experimental and computational methods.

When analyzing user geospatial information through deep learning methods, it is typically necessary to annotate existing geospatial data. Currently, manual annotation methods are commonly employed, suffering from issues related to low efficiency and accuracy. This design is based on the TensorFlow deep learning framework and first realizes the BiLSTM+CRF+AGG deep learning model. Among the models, AGG is the aggregation layer, which is introduced to solve the problem of solid particle size equilibrium. Secondly, based on the characteristics of original data and professional data, an automatic labeling algorithm is proposed. The algorithm first preprocesses the acquired original data set and professional data set, The most valuable unlabeled data set which can make the training model converge quickly is selected from the original data set as the target data set. Sort the target data set based on preset rules and set annotation parameters for the sorted target data set. Based on the set annotation parameters, the corpus is synthesized and used as the annotation result. Thirdly, based on the active learning strategy, a manual annotation auxiliary scheme is proposed, and an Excel generation module that is convenient for manual annotation correction is designed and developed to further improve the efficiency and quality of annotation through iterative processing. The combination of the BiLSTM+CRF+AGG deep learning model and high-quality annotation can accurately identify non-standard, incomplete, or even incorrect geographical information entities. This annotation method has found successful practical application within the context of the research project and has been granted an invention patent.

This paper considers a non-mixture cure model for right censored data. It utilizes the maximum likelihood method to estimate model parameters in the non-mixture cure model. The simulation study is based on Fréchet susceptible distribution to evaluate the performance of the method. Comparing with Weibull and exponentiated exponential distributions, the non-mixture Fréchet distribution is shown to be the best in modeling a real data on allogeneic marrow HLA-matched donors and ECOG phase III clinical trial e1684 data.

The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

The main purpose of this paper is to propose a novel optimization model with a new machine learning approach in the first section to achieve the best results in financial institutions in the second section. Since the constancy of efficacy derived from parametric and non-parametric is not significant, this paper provides a scientific assessment at the optimization section and proposes a novel combined parametric and non-parametric model which will be a new experiment in literature perception. A scientific assessment of banks based on a combination of the efficiency measurement method of CCR(Charnes, Cooper and Rhodes model) or CRS(Constant Return to Scale) BCC(Banker, Charnes, and Cooper model) or VRS (Variable Return to Scale) in Data Envelopment Analysis (DEA), as well as Stochastic Frontier Approach (SFA) for 65 banks during Feb to July 2020, are introduced. For analyzing the performance of the parametric and non-parametric approaches we have considered the linear regression and Unreplicated Linear Functional Relationship (ULFR). At the machine learning section, a novel four-layers data mining filtering pre-processes for selected supervised classification as well as unsupervised clustering algorithms to increase the accuracy and to remove unrelated attributes and data are applied. For the four kinds of preprocessing approaches of unsupervised attributes, supervised attributes, supervised instances, and unsupervised instances, we have chosen discretization, attribute selection, stratified remove folds, and resample filters respectively. Based on the nature of the suggested financial institution's dataset and attributes, the most appropriate preprocessing filter in each layer to achieve the highest performance is suggested. Finally, the superior bank, best performance model, and the most accurate algorithm are introduced. The results indicate that the bank number 56 is the superior bank. Among the proposed techniques, the novel recommended CVS compared with CCR-BCC and SFA models, has a more positive correlation with profit risk, and show a higher coefficient of determination values. Sequential Minimal Optimization(SMO) algorithm receives the highest accuracy in all four suggested filtering layers.

We present an any-to-one voice conversion (VC) system, using an autoregressive model and LPCNet vocoder, aimed to enhance the converted speech in terms of naturalness, intelligibility, and speaker similarity. As the name implies, non-parallel any-to-one voice conversion does not require paired source and target speeches and can be employed for arbitrary speech conversion tasks. Recent advancements in neural-based vocoders, such as WaveNet, have improved the efficiency of speech synthesis. However, in practice, we find that the trajectory of some generated waveforms is not consistently smooth, leading to occasional voice errors. To address this issue, we propose to use an autoregressive (AR) conversion model along with the high-fidelity LPCNet vocoder. This combination not only solves the problems of waveform fluidity but also produces more natural and clear speech, with the added capability of real-time speech generation. To precisely represent the linguistic content of a given utterance, we use speaker-independent PPG features (SI-PPG) computed from an automatic speech recognition (ASR) model trained on a multi-speaker corpus. Next, a conversion model maps the SI-PPG to the acoustic representations used as input features for the LPCNet. The proposed autoregressive structure enables our system to produce the following prediction step outputs from the acoustic features predicted in the previous step. We evaluate the effectiveness of our system by performing any-to-one conversion pairs between native English speakers. Experimental results show that the proposed method outperforms state-of-the-art systems, producing higher speech quality and greater speaker similarity.

The main focus when developing software is to improve the reliability and stability of a software system. When software systems are introduced, these systems are used in field environments that are the same as or close to those used in the development-testing environment; however, they may also be used in many different locations that may differ from the environment in which they were developed and tested. In this paper, we propose a new software reliability model that takes into account the uncertainty of operating environments. The explicit mean value function solution for the proposed model is presented. Examples are presented to illustrate the goodness-of-fit of the proposed model and several existing non-homogeneous Poisson process (NHPP) models and confidence intervals of all models based on two sets of failure data collected from software applications. The results show that the proposed model fits the data more closely than other existing NHPP models to a significant extent.

We report the characterization of phenotype, genotype, and functional parameters such as CD4+ T cell, viral load, HIV-1 genotype, class I HLA genotype, CCR5 polymorphism, and IFN-γ producing cells from a cohort of 37 people living with HIV-1 (PLWH) (viremic controllers, were compared those on antiretroviral therapy (ART) from two sites in São Paulo, Brazil. Half the PLWH (51.4%) were classified as viremic controllers (Controller group - CG), compared to 48.6% were on ART. As expected, controllers showed baseline higher levels of CD4+ T cells and nadir compared to those under ART, confirming the ability of HIV-1 controllers to preserve these cells even in the absence of ART. IFN-γ-producing cells showed greater magnitude to the HIV peptides Gag in controllers (p<0.03). Our results demonstrated that HLA protective alleles are associated with strong production of IFN-γ to Gag, Nef and RT epitopes in people living with HIV controllers.

MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.

The evolution of integrable classical systems leads to conserved quantities and vanishing Poisson brackets. In contrast, such invariants do not exist in the dynamics of non-integrable systems, which include (but are not limited to) deterministic models with long-term chaotic behavior. The object of this review is to briefly survey the mathematical background of nonintegrability and its role in the physics unfolding well-above the Standard Model (SM) scale.

Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission dynamics model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV in-fections are persistent in the MSM population, with sustained circulation of the virus among un-vaccinated individuals. Coverage around 75% of both sexes would be necessary to eradicate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV eradication maybe achieved if men’s coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.

We present a mixing length based algebraic turbulence model calibrated to pipe flow; the main purpose of the model is to capture the increasing turbulence production-to-dissipation ratio observed in connection with the high Reynolds number transition region. The model includes the mixing length description by Gersten and Herwig which takes the observed variation of the von Kármán number with Reynolds number into account. Pipe wall roughness effects are included in the model. Results are presented for area-averaged (integral) quantities which can be used both as a self-contained model and as initial inlet boundary conditions for computational fluid dynamics simulations.

Along with the economic growth, the companies must contribute to social progress and promote environmental sustainability in equal harmony. Sustainable human resource management (SHRM) strategies make it possible to attain the economic, social and environmental goals of a firm. In this regard, a survey method is discussed using the literature review and online questionnaire to identify the main factors/indicators during the SHRM evaluation of manufacturing firms in India. Uncertainty is commonly occurred in the assessment of SHRM factors. As a generalized version of fuzzy sets, single-valued neutrosophic set (SVNS) has been demonstrated as a valuable tool to illustrate the indeterminate, inconsistent and uncertain data of realistic decision-making problems. Considering the idea of SVNSs, this study develops a hybrid multi-criteria group decision-making (MCGDM) approach for assessing the SHRM of manufacturing firms under uncertainty settings. For this purpose, an SVN-alternative ranking order method accounting for two-step normalization (AROMAN) is proposed based on VIFI-score function-based decision experts’ (DEs’) weighting tool and integrated criteria weight-determining model to solve the MCGDM problems with fully unknown DEs and criteria weights. In this regard, we develop new SVN-distance measure to compute the degree of difference between SVNSs. Some examples are presented to demonstrate the efficacy of developed measure over the existing ones. In addition, new criteria weight-determination model is presented with the integration of objective weights through IVIF-distance measure-based model and subjective weights through ranking comparison (RANCOM) tool on SVNSs. The proposed ranking method is applied to an empirical study of SHRM assessment for manufacturing firms in India, which shows its applicability and feasibility. In this study, the evaluation criteria are characterized into social, environmental and economic aspects with DE’s opinions. Comparative and sensitivity analyses are made to show the strength and steadiness of presented approach. This study provides an innovative MCGDM analysis framework, which makes a significant contribution to the SHRM assessment problem under indeterminate, inconsistent and uncertain setting.

In this work, we incorporate a thixotropic-viscoelastic model into the widely used Computational Fluid Dynamics (CFD) software OpenFOAM, along with the rheoTool library. The model we implement is known as the Modified-Bautista-Manero (MBM), and effectively describes the rheological behavior of worm-like micellar solutions in extensional flows. We provide a detailed explanation of the numerical implementation of the model, specifically using the log-conformation tensor approach. Unlike previous works focused on this kind of fluids, we simulate inertial flows while considering convective terms in the governing equations, thus obtaining a more realistic behavior on the calculated results. The MBM model implementation is validated through numerical simulations on two different industrial-relevant geometries: the planar 4:1 contraction and the 4:1:4 contraction-expansion configurations. Furthermore, we investigate the influence of inertial, viscoelastic, and thixotropic effects on various flow field variables. These variables include velocity, viscosity, normal stresses, and corner vortex size. Our analysis encompasses both transient and steady solutions of corner vortexes across a range of Deborah and Reynolds numbers. Our results are also directly compared with simulations obtained using the non-thixotropic rubber network-based exponential Phan-Thien-Tanner (EPTT) model. From our planar 4:1 contraction results, we found that vortex-enhancement is seen when high elasticity is coupled with quick structural reformation and very low inertial effects. From our planar 4:1:4 contraction-expansion simulations, we show that an increase in inertia leads both to vortex-inhibition in the upstream channel and slight vortex-enhancement in the downstream channel. Lastly, we show the strong effect of the convection of fluidity into the fluidity profiles and into the upstream/downstream corner vortex sizes.

The human capital index is a multivariate variable used to measure the assessment of human resource productivity in the future. Human capital has a connection with economic development. Moreover, the study looks to analyses the relationship between Human Capital and Economic Growth indicators such as HCI and GDP. Human Capital relates to the development of individual skills to make them function more profitable for the national economy. The study was aimed at investigating the effect of population, the number of people engaged and the average annual hours worked by engaged persons on the human capital index. The analysis was in SPSS for the findings. Correlation tests were used for analysis. The study revealed that population, the number of people engaged and the average annual hours worked by engaged persons had a significant positive effect on the human capital index.

Simulating the non-perturbative and non-Markovian dynamics of open quantum systems is a very challenging many body problem, due to the need to evolve both the system and its environments on an equal footing. Tensor network and matrix product states (MPS) have emerged as powerful tools for open system models, but the numerical resources required to treat finite temperature environments grow extremely rapidly and limit their applications. In this study we use time-dependent variational evolution of MPS to expore the striking theory of Tamescelli et al. that shows how finite temperture open dyanmics can be obtained from zero temperature, i.e. pure wave function, simulations. Using this approach, we produce a benchmark data set for the dynamics of the Ohmic spin-boson model across a wide range of coupling and temperatures, and also present detailed analysis of the numerical costs of simulating non-equilibrium steady states, such as those emerging from the non-perturbative coupling of a qubit to baths at different temperatures. Despite ever growing resource requirements, we find that converged non-perturbative results can be obtained, and we discuss a number of recent ideas and numerical techniques that should allow wide application of MPS to complex open quantum systems.

Deep neural network (DNN) watermarking is a potential approach for protecting the intellectual property rights of DNN models. Similar to classical watermarking techniques for multimedia content, the requirements for DNN watermarking include capacity, robustness, and transparency, and other factors. Studies have focused on robustness against retraining and fine-tuning. However, less important neurons in the DNN model may be pruned. Moreover, although the encoding approach in renders DNN watermarking robust against pruning attacks, the watermark is assumed to be embedded only into the fully connected layer in the fine-tuning model. In this study, we extended the method such that the model can be applied to any convolution layer of the DNN model and designed a watermark detector based on a statistical analysis of the extracted weight parameters to evaluate whether the model is watermarked. Using a nonfungible token mitigates the overwriting of the watermark and enables checking when the DNN model with the watermark was created.

Generative models for images, audio, text and other low-dimension data have achieved great success in recent years. Generating artificial human movements can also be useful for many applications, including improvement of data augmentation methods for human gesture recognition. The object of this research is to develop a generative model for skeletal human movement, allowing to control the action type of generated motion while keeping the authenticity of the result and the natural style variability of gesture execution. We propose to use a conditional Deep Convolutional Generative Adversarial Network (DC-GAN) applied to pseudo-images representing skeletal pose sequences using Tree Structure Skeleton Image format. We evaluate our approach on the 3D-skeleton data provided in the large NTU RGB+D public dataset. Our generative model can output qualitatively correct skeletal human movements for any of its 60 action classes. We also quantitatively evaluate the performance of our model by computing Frechet Inception Distances, which shows strong correlation to human judgement. Up to our knowledge, our work is the first successful class-conditioned generative model for human skeletal motions based on pseudo-image representation of skeletal pose sequences.

New modied Hayward metric of magnetically charged non-singular black hole spacetime in the framework of nonlinear electrodynamics is constructed. When the fundamental length introduced, characterising quantum gravity effects, vanishes one comes to the general relativity coupled with the Bronnikov model of nonlinear electrodynamics. The metric can have one (an extreme) horizon, two horizons of black holes, or no horizons corresponding to the particle-like solution. Corrections to the Reissner-Nordström solution are found as the radius approaches to innity. As r -> 0 the metric has a de Sitter core showing the absence of singularities. The asymptotic of the Ricci and Kretschmann scalars are obtained and they are nite everywhere. The thermodynamics of black holes, by calculating the Hawking temperature and the heat capacity, is studied. It is demonstrated that phase transitions take place when the Hawking temperature possesses the maximum. Black holes are thermodynamically stable at some range of parameters.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

In this review, our goal is to design and test quantum-like algorithms for Artificial Intelligence (AI) in open systems to structure a human-machine team to be able to reach its maximum performance. Unlike the laboratory, in open systems, teams face complexity, uncertainty and conflict. All task domains have complexity levels, some have low, and others high levels. Complexity in this new domain is affected by the environment and the task, which are both affected by uncertainty and conflict. We contrast the individual and interdependence approaches to teams. The traditional and individual approach focuses on building teams and systems by aggregating the best available information for individuals, their thoughts, behaviors and skills. Its concepts are characterized chiefly by one-to-one relations between mind and body, a summation of disembodied individual mental and physical attributes, and degrees of freedom corresponding to the number of members in a team; however, this approach is characterized by the many researchers who have invested in it for almost a century with few effects that can be generalized to human-machine interactions; by the replication crisis of today (e.g., the invalid scales for self-esteem, implicit racism, and honesty); and by its many disembodied concepts. In contrast, our approach is based on the quantum-like nature of interdependence. It allows us to theorize about the bistability of mind and body, but it proposes a measurement problem and a non-factorable nature. Bistability addresses team structure and performance; the measurement problem solves the replication crisis; and the non-factorable aspect of teams reduces the degrees of freedom and the information derivable from teammates to match findings by the National Academies of Science. We begin with a review of the science of teams and a focus on human-machine team research in the laboratory versus the open; justifications for rejecting traditional social science while supporting our approach; a full understand of the complexity of the domain, tasks in the domain, and how teams address both; the mathematics involved; a review of results from our model versus the open field; a discussion of the results; conclusions; and the path forward to successfully advance the science of interdependence and autonomy.

For the soil in different regions, the nutrient fertility contained in it is different, and the detection and zoning management of soil nutrients before tillage every year can improve grain yield. In this paper, an integrated learning strategy model based on black soil hyperspectral data is designed for rapid classification of organic matter content classification of black soil. Soil hyperspectral image dataset of Xiangyang Experimental Base was collected; by changing the internal structure of the stacking model, an LSVM-stacking model with (MLP, SVC, DTree, XGBl, kNN) five classifiers as the L1 layer was built, and the simulated annealing algorithm was used for hyperparameter optimization. Compared to other stacking models, the LSVM-stacking metrics are significantly improved. The accuracy rate of hyperparameter optimization is improved by 38.6515%, the accuracy rate of the independent test data set is 0.9488, and the comparison of individual learners can improve the recognition classification accuracy of label"1" to 1.0.

The rapid advancements in gene therapy have opened up new possibilities for the treatment of genetic disorders, including Duchenne muscular dystrophy, Thalassemia, cystic fibrosis, Hemophilia, and Familial hypercholesterolemia. The utilization of the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases, necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation, while ensuring safety and effectiveness. This review aims to explore the biomedical potential of non-viral vector-explore CRISPR/Cas9 systems for the treatment of genetic diseases. Furthermore, it provides a comprehensive overview of recent research advances in viral and non-viral vector-based gene therapy for genetic disorders, including insights from preclinical and clinical studies. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for the development of novel nano-delivery platforms.

Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be infected more frequently with flaviviruses due to their arboreal and diurnal habits, their genetic similarity to humans and their relative closeness to humans. However, the only known flavivirus in America that is maintained by sylvatic cycles involving NPs is Yellow Fever virus (YFV), and the NPs role as potential hosts of flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 free range and captive NPs of Costa Rica to evaluate their involvement in flavivirus transmission cycles and their potential as flavivirus hosts. We used a highly-specific micro plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, Dengue virus 1-4 (DENV), Zika virus, West Nile Virus (WNV) and Saint Louis Encephalitis virus (SLEV). We found evidence of seropositive NPs to DENV-1 8.2% (homotypic –3/86, heterotypic – 4/86), SLEV 15.1% (homotypic – 10/86, heterotypic – 2/86), WNV 2.3% (homotypic – 2/86) and 8.1% (7/86) undetermined Flavivirus species. No antibodies against YFV or ZIKV were found. This work provides compelling serological evidence of exposure in NPs of flaviviruses associated with urban cycles, i.e. DENV, and confirms decades of circulation of SLEV in the same environments. Also, the range of years of sampling and the socioeconomic region was statistically significant for the presence of Dengue and Flavivirus undetermined seropositive individuals, respectively. Both the years and socioeconomic regions with greater seroprevalence coincide with the years and socioeconomic regions with high numbers of Dengue human cases for the country. Our work suggests bidirectional? circulation of different flaviviruses between humans and wildlife with public health importance and underscores the necessity of further surveillance for flaviviruses in the humans/wildlife interface in Central America.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Easter Island (Rapa Nui) deforestation has traditionally been viewed as a single event, synchronous in time and space across the island and caused by Polynesian settlers. However, recent studies have challenged this idea introducing the concept of spatio-temporal heterogeneity and suggesting a role for climate change. This paper presents a continuous paleovegetation record of the last millennium (~960 to ~1710 CE), based on palynological analysis of a peat core from Lake Kao. During this time interval, deforestation was gradual, with three main pulses at ~1070 CE, ~1410 CE and ~1600 CE, likely driven by drought, anthropogenic practices (mostly fire) or the coupling of both. Some forest regeneration trends have been documented after the first and the second deforestation pulses. Forests were totally removed by 1600 CE, coinciding with the full permanent human settlement of the Kao area. Comparison with other continuous palynological records available for the last millennium (Aroi marsh and Lake Raraku), confirms that forest clearing was heterogeneous in time and space, rather than synchronous island-wide.

In this paper, we present an extended version of the Hadi-Vencheh model for multiple criteria ABC inventory classification. The proposed model is a nonlinear weighted product model (WPM) which determines a common set of weights for all the items. Our proposed nonlinear WPM incorporates multiple criteria with different measure units, without converting the performance of each inventory item in terms of each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification, and demonstrates an efficient algorithm for solving nonlinear programming problems in which the feasible solution set does not have to be convex. The algorithm presented in this study improves the solution efficiency of the Canonical Coordinates Method (CCM) algorithm substantially when applied to large scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm's efficacy. The practical implications of the study are to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

We find at least 4 quantum properties that are indeed universal in some number systems; and we can use them for quantum consciousness. Using the sets B={0,1}, N, Z, or Q has the +4 quantum properties that one can trust, as archetypes of easy communication to friends and foes, to ignoranti or cognoscenti, and for quantum computing. This paper proposes the use of Bayesian geometry to reduce the space of possible results, reducing or increasing initial beliefs by successive experimentation. This is exemplified in biology and mathematics, and can be applied to physics and other sciences. The conclusion is that an experimental fact can be absolutely verified. Any mathematical choice (as verified by computers) militating against R=Q, is under an absolutely low chance to succeed. Infinitesimals are denied based on 3^16 independent factors. This is not a probabilistic result, but based on reduction of the Bayes geometry for updating beliefs. This work applies to non-probabilistic and unknown phenomena, such as those found in oscillations (neutrino, health), evolution, and quantum computing, denies Gödel's uncertainty, and solves the liar's paradox by reflection. This connects different scientific fields with one another, in an internet, i.e., in a network of connections of multiple open networks, using the set Q, resembling a hologram, and includes entanglement.

The zero-catch problem is a key issue in CPUE(Catch Per Unit Effort) standardization, and previous studies have treated all zero-catch data uniformly, but this actually loses some correctly-labeled samples. On the other hand, for the main catches with few zero-catch samples, the problem of low performance of fisheries forecasting remains unsolved even though the forecasting model structure is updating constantly, since we cannot know whether the samples are correctly recorded. In this paper, we propose a method based on confident learning theory to detect anomalous samples in the datasets and unify zero-catch and non-zero samples as noise through an overarching framework of learning with noisy labels, which reveals the heterogeneity among zero-catch samples (as well as among non-zero samples) and the homogeneity between zero-catch samples and non-zero samples. Using three species of tuna in the tropical Atlantic Ocean with the spatial resolution of 0.5 ◦ × 0.5 ◦ and time resolution of days from 2016 to 2019 as experimental material, performance on all three classical machine learning models(Random forest, Support Vector Machine and XGBoost) is significantly improved compared to each baseline.This confirms that we propose a self-adaptive, effective method for detecting and repairing anomalous samples in the fishery dataset.

The role of human resource management practices and organizational loyalty dealing with employee retention has been widely explored and examined in the existing literature. The majority of human resource management researchers have focused on the role of policies and practices in different sectors related to employee retention. However, less attention has been given to identifying the practices and procedures common across all industries and sectors. The present study attempts to determine and examine the most important constructs like HR practices and organizational loyalty of employee retention management and proposes a comprehensive structural equation model to measure the impact of these constructs on employee retention. After an extensive review of the literature, organizational loyalty, and human resources management practices like recruitment and selection, compensation and benefit, training and development, supervision and evaluation have been identified as four essential practices dealing with employee retention and are common across all industries. These practices constitute the component factors of an employee retention management predicting employee’s turnover intentions. The survey method was adopted, and the original data obtained through the self-administered questionnaire. The valid one hundred and eighty-nine (189) respondents analyzed by using Lisrel 8.7, Structural equation model (SEM) analysis results shows that human resource management practices and organizational loyalty have strong positive impact on employee retention. This study tends to assist human resource managers and decision makers in selecting the appropriate motivating factors to retain and satisfy their employees

Based on the Generalized bracket, or Beris-Edwards, formalism of non-equilibrium thermodynamics, we have recently proposed [Stephanou et al. Materials, 13, 2867 (2020)] a new differential constitutive model for the rheology of entangled polymer melts and solutions. It has amended the shortcomings of a previous model that was too strict in the values of the convective constraint release parameter for the model not to violate the second law of thermodynamics and has been shown capable of predicting a transient stress undershoot (following the overshoot) at high shear rates. In this work, we wish to further examine this model’s capability of predicting the rheological response of industrial polymer systems by extending it to its multiple-mode version. The comparison against industrial rheological data (High-Density Polyethylene resins), as compared against available experimental data in (a) Small Amplitude Oscillatory shear, (b) start-up shear, and (c) start-up uniaxial elongation, is noted to be good.

A vast majority of the countries is under the economic and health crises due to the current epidemic of coronavirus disease 2019 (COVID-19). The present study analyzes the COVID-19 using time series, which is an essential gizmo for knowing the enlargement of infection and its changing behavior, especially the trending model. We have considered an autoregressive model with a non-linear time trend component that approximately converted into the linear trend using the spline function. The spline function split the COVID-19 series into different piecewise segments between respective knots and fitted the linear time trend. First, we obtain the number of knots with its locations in the COVID-19 series and then the estimation of the best-fitted model parameters are determined under Bayesian setup. The results advocate that the proposed model/methodology is a useful procedure to convert the non-linear time trend into a linear pattern of newly coronavirus case for various countries in the pandemic situation of COVID-19.

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

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

Human-Robot Interaction (HRI) for collaborative robots has become an active research topic recently. Collaborative robots assist the human workers in their tasks and improve their efficiency. But the worker should also feel safe and comfortable while interacting with the robot. In this paper, we propose a human-following motion planning and control scheme for a collaborative robot which supplies the necessary parts and tools to a worker in an assembly process in a factory. In our proposed scheme, a 3-D sensing system is employed to measure the skeletal data of the worker. At each sampling time of the sensing system, an optimal delivery position is estimated using the real-time worker data. At the same time, the future positions of the worker are predicted as probabilistic distributions. A Model Predictive Control (MPC) based trajectory planner is used to calculate a robot trajectory that supplies the required parts and tools to the worker and follows the predicted future positions of the worker. We have installed our proposed scheme in a collaborative robot system with a 2-DOF planar manipulator. Experimental results show that the proposed scheme enables the robot to provide anytime assistance to a worker who is moving around in the workspace while ensuring the safety and comfort of the worker.

Rotational jumps are crucial techniques in sports competitions. Estimating ground reaction forces (GRFs), one of the components constituting jumps, through a biomechanical model-based approach enables analysis even in environments where force plates or machine learning training data cannot be utilized. In this study, rotational jump movements involving twists on land were measured using inertial measurement units (IMUs) and estimated GRFs and body loads using a 3D forward dynamics model. Our estimation method, based on forward dynamics and optimization calculations, generated and optimized body movements using cost functions defined by motion measurements and internal body loads. To reduce the influence of the dynamic acceleration in the optimization calculation, the 3D orientation using sensor fusion composed of acceleration and angular velocity data obtained from IMUs and an extended Kalman filter was estimated. As a result, by generating movements based on the cost function, it was possible to calculate biomechanically valid GRFs while following the measured movements even if not all joints are covered by IMUs. This estimation method allows for 3D motion analysis independent of measurement conditions or training data.

Porous coatings on prosthetic implants encourage implant fixation. Enhanced fixation may be achieved using a magneto-active porous coating that can deform elastically in vivo on application of an external magnetic field, straining in-growing bone. Such coating, made of 444 ferritic stainless steel fibres, was previously characterised in terms of its mechanical and cellular responses. In this work, co-cultures of human osteoblasts and endothelial cells were seeded into a novel fibrin-based hydrogel embedded in a 444 ferritic stainless steel fibre network. Albumin was successfully incorporated into fibrin hydrogels improving the specific permeability and the diffusion of fluorescently-tagged dextrans without affecting their Young’s modulus. The beneficial effect of albumin was demonstrated by upregulation of osteogenic and angiogenic gene expression. Furthermore, mineralisation, extracellular matrix production and formation of vessel-like structures were enhanced in albumin-enriched fibrin hydrogels compared to fibrin hydrogels. Collectively, the results indicate that the albumin-enriched fibrin hydrogel is a promising bio-matrix for bone tissue engineering and orthopaedic applications.

Predicting the growth response of seedlings from the environmental responses of photosynthesis and metabolism may be improved by considering the dynamics of non-structural carbohydrate, NSC, over a diurnal cycle. Attenuation of growth metabolism when NSC content is low could explain why some NSC is conserved through the night. A dynamic model, incorporating diurnal variation in NSC, was developed to simulate growth of seedlings hour-by-hour. I compared predictions of this model to published growth and NSC data for seedlings that varied according to temperature, light, day length, or CO₂. Prolonged-darkness experiments showed a temperature dependent upper limit on the respiration capacity. Respiration was attenuated as NSC was depleted. Furthermore, when NSC was high at dawn, inhibition of photosynthesis could attenuate the accumulation of NSC under low temperature, or high light, or high CO₂. These concepts were used to simulate plant metabolism and growth rates and diurnal variation of NSC in tomato seedlings under two light levels and various temperatures. Comparison of other results using the same model parameters showed the dynamic model could predict results for starch and starch-less plants, and when growth was affected by CO₂ enrichment and day length.

Recruitment is a fundamental aspect of Human Resource Management to drive organizational performance. Traditional recruitment processes, with manual stages, are time-consuming and inefficient. Artificial Intelligence (AI), which demonstrates its potential in various sectors such as healthcare, education and notable cases of ChatGPT, is currently reshaping recruitment by automating tasks to improve efficiency. However, in Thailand, where there is a growing demand for talents, the application of AI in recruitment remains relatively limited. This research focuses on human resources (HR) and recruitment professionals in Thailand, aiming to understand their perspectives on the integration of AI in recruitment. It extended the Unified Theory for Acceptance and Use of Technology (UTAUT) model, customized to suit the specific requirements of Thai recruitment practices. The study explores the factors influencing users' intention to adopt AI in recruitment. Survey questionnaire items were created based on prior literatures and refined with insights from HR and recruitment experts to ensure applicability in the context of recruitment in Thailand. A survey involving 364 HR and recruiting professionals in Bangkok metropolitan area supplied comprehensive responses. The research reveals that several factors, including Perceived Value, Perceived Autonomy, Effort Expectancy, and Facilitating Conditions, significantly impact the intention to adopt AI for recruitment. While Social Influence and Trust in AI Technology do not have a direct influence on intention, Social Influence directly affects Perceived Value. Trust in AI Technology positively influences Effort Expectancy. This study provides valuable benefits for HR and recruitment professionals, organizations and AI developers by offering insights into AI adoption and sustainability, enhancing recruitment processes and promoting the effective use of AI tools in this sector.

Despite great technical capabilities, the theory of non-contact temperature measurement is usually not fully applicable to the use of measuring instruments in practice. While black body calibrations are in practice well established and easy to accomplish, this calibration protocol is never fully applicable to measurements of real objects under real conditions. Currently, the best approximation to real world radiation thermometry is grey body radiation thermometry, which is supported by most measuring instruments to date. Nevertheless, the metrological requirements necessitate traceability, therefore real body radiation thermometry is required for temperature measurements of real bodies. This article documents the current state of temperature calculation algorithms for radiation-thermometers and the creation of a traceable model for radiation thermometry of real bodies that uses a digital twin model of the system of measurement to compensate for the loss of data, caused by spectral integration, which occurs when thermal radiation is absorbed on the active surface of the sensor. To solve this problem, a hybrid model with variable scalar inputs is proposed, in which the scalar input parameters are calculated to correspond to the system of measurement. The method for calculating the effective parameters is proposed and verified with the theoretical model of non-contact thermometry. The sum of effective instrumental parameters is presented for different temperatures to show that the rule of radiation thermometry of grey bodies, according to which the sum of instrumental emissivity and instrumental reflectivity equals to 1, does not hold in radiation thermometry for real bodies. Using the derived models of radiation thermometry, the uncertainty of radiation thermometry due to the uncertainty of spectral emissivity is analysed by simulated measurements along the temperature ranges of various radiation thermometers, enabling traceable non-contact temperature measurements with known measurement uncertainty under any known conditions.

Requirements Engineering (RE) is an important step in the whole software development lifecycle. The problem in RE is to determine the class of the software requirements as functional and non-functional. Proper and early identification of these requirements is vital for the entire development cycle. On the other hand, manual government of requirement classes is a timewasting task, and it needs intensive effort. Automatic requirement classification techniques through advanced Machine Learning (ML) strategies are started to be developed to address this problem. Basically, software requirements are generated as natural language explanations and therefore requirement classification may be handled as a particular Natural Language Processing (NLP) problem. From ML point of view, classification strategies require dataset to be used in the training/learning phase. For this goal, we generated a unique Turkish dataset having collected the requiremenst from real-world software projects with 4600 samples. Of these requirements, 3000 and 1600 were labeled as functional and non-functional, respectively. The data set has been evaluated using (i) traditional machine learning algorithms, (ii) deep learning algorithms, and (iii) transformer models respectively. As a result BERTurk was found to be the most successful algorithm to discriminate functional and non-functional requirements in terms of 95% f-score metric.

As the global population rapidly ages with longer life expectancy and declining birth rates, the need for healthcare services and caregivers for older adults is increasing. Current research envisions addressing this shortage by introducing domestic service robots to assist with daily activities. The successful integration of robots as domestic service providers in our lives requires them to possess efficient manipulation capabilities, provide effective physical assistance, and have adaptive control frameworks that enable them to develop social understanding during human-robot interaction. In this context, human factors, especially quantifiable ones, represent a necessary component. The objective of this paper is to conduct an unbiased review encompassing studies on human factors studied in research involving physical interactions and strong manipulation capabilities. We identified the prevalent human factors in physical human-robot interaction (pHRI), noted the factors typically addressed together and determined the frequently utilized assessment approaches. Additionally, we gathered and categorized proposed quantification approaches based on measurable data for each human factor. We also formed a map of common contexts and applications addressed in pHRI for a comprehensive understanding and easier navigation of the field. We found out that most of the studies in direct pHRI (when there is direct physical contact) focus on social behaviors with belief being the most commonly addressed human factor type. Task collaboration is moderately investigated, while physical assistance is rarely studied. In contrast, indirect pHRI (when the physical contact is mediated via a third item) studies often involve industrial settings, with physical ergonomics being the most frequently investigated human factor. More research is needed on human factors in direct and indirect physical assistance applications, including studies that combine physical social behaviors with physical assistance tasks. We also found that while the predominant approach in most studies involves the use of questionnaires as the main method of quantification, there is a recent trend that seeks to address quantification approaches based on measurable data.

Of the roughly 20,000 canonical human protein sequences, as of September 15, 2020, 6,937 proteins have had their full or partial, medium- to high-resolution structures determined by x-ray crystallography or other methods. Which of these proteins dominate the Protein Data Bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top-10 soluble and membrane proteins are all well-known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 yrs for proteins from all organisms). Growth in human protein structures is slightly faster (at 5.9 yrs, while E.Coli and Mouse+Rat protein structures accumulate more slowly, Zebrafish protein structures are growing most, at a doubling every 3.7 years, albeit starting from only approx. 100 structure entries in 2010). The information may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2020 snap-shot for the state of protein structural biology.

It has been a challenge to visualize in nature some concepts from abstract subjects such as mathematics and philosophy. Irrationality is certainly among the least comprehensive. This essay aimed to propose that irrationality is simply an illusion resulting from the human inability to grasp the full nature of reality, rather than actual continuity flaws in the fabric of existence. There are three major arguments: (1) human senses have limitations and these are likely to be extended to the intellect, (2) there are no observable existential discontinuities in everyday experience, and (3) some rational phenomena have irrational components. These arguments point towards the existence of a physical existence of irrational quantities or distances, visible to the human eye but not fully comprehended through arithmetic abstraction.

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

In this study, we propose a radiomics-clinical probability weighted model for the prediction of prognosis for NSCLC. The model combines radiomics features extracted from RT planning images with clinical factors such as age, gender, histology, and tumor stage. CT images with radiotherapy structures of 422 NSCLC patients were retrieved from The Cancer Imaging Archive (TCIA). Radiomic features were extracted from gross tumor volume (GTV). Five machine learning algorithms, namely decision trees (DT), random forests (RF), extreme boost (EB), support vector machine (SVM) and generalized linear model (GLM), were optimized by a voted ensemble machine learning (VEML) model. A probabilistic weighted approach is used to incorporate the uncertainty associated with both radiomic and clinical features and to generate a probabilistic risk score for each patient. The performance of the model is evaluated using a receiver operating characteristic (ROC). Radiomic model, clinical factors model and combined radiomic-clinical probability weighted model demonstrated good performance in predicting NSCLC survival with AUC of 0.941, 0.856 and 0.949 respectively. The combined radiomics-clinical probability weighted enhanced model achieved significantly better performance than radiomic model in 1-year survival prediction (chi-square test, p<0.05). The proposed model has the potential to improve NSCLC prognosis and facilitate personalized treatment decisions.

We live in the world that is completely entangled on energy and thus, Humankind can no longer do without it, power. With electricity being the main form of energy today, this has increased the complexity of our life today. In Uganda, electricity generation is mainly through hydropower which put the country in the bottleneck of over dependence on one source of energy. Yet, there are many energy systems out there that country can diversify its electricity generation. Therefore, the need to understand, the level of development and utilization of various energy systems has been the underlying question for this present study. Comprehensive literature survey was conducted from the electronic databases including ScienceDirect, Wiley, Sage, Scopus, Taylor & Francis, and Google Scholar. The publications in form of reports, conference papers, working papers, discussion papers, journal articles, book sections and textbooks were considered in this study. In total, 11 energy systems including human and animal energy, solid biomass (firewood), hydropower, wind, geothermal, solar, nuclear, peat, coal, petroleum, and non-solid biomass (methanol, hydrogen, ethanol, biodiesel, and biogas) are described. The current and the future development and utilization of these energy systems has been described. The challenges with their development and utilization were elaborated and the solution the challenges were presented. The hydropower with River Nile being the main river for large hydropower plant construction is the dominance energy system in Uganda. Nuclear energy will be the salvation for the country’s electric energy supply in the near future. Therefore, Uganda needs to bet big on nuclear energy.

Propolis, or bee glue, is a complex mixture of resins from plant buds and flowers, wax, pollen and bee saliva. It also contains various vitamins, essential oils, mineral salts, trace elements, hormones and enzymes. It has been found that propolis possesses antimicrobial, antiviral and anti-inflammatory properties. We have studied the antiviral activity of six extracts of Bulgarian propolis collected from six districts of Bulgaria. The study was conducted against structurally different viruses: Human coronavirus strain OC-43 (HCoV OC-43) and Human respiratory syncytial virus type 5 (HRSV-5) (enveloped RNA viruses), Human herpes simplex virus type 1 (HSV-1) (enveloped DNA virus), Human rhinovirus type 14 (HRV-14) (non-enveloped RNA virus) and Human adenovirus type 2 (HadV-2) (non-enveloped DNA virus). The influence of the extracts on the internal replicative cycle of viruses was determined using the cytopathic effect (CPE) inhibition test. The virucidal capacity, their influence on the adsorption stage and their protective effect on uninfected cells were also determined by the end-point dilution method. Residual viral infectivity in propolis samples was compared to untreated controls and Δlgs were calculated. When administered during viral replication, most propolis extracts demonstrated the strongest activity against HCoV OC-43. The influence of propolis extracts on the viability of extracellular virions was expressed to a different degree in the various viruses studied, and the effect was significantly stronger in those with an envelope. Almost all extracts significantly inhibited the step of herpes virus adsorption to the host cell, and some of them showed a protective effect on healthy cells before they were subjected to herpes infection. Our results enlarge the knowledge about the action of propolis and could open new perspectives for its application in viral infections treatment.

Given the broad and intense use of plastic, society is being increasingly affected by its degradation and by-products, particularly by microplastics (MPs) -fragments smaller than 5 mm in size-, and nanoplastics (NPs) -with sizes less than 1 µm. MPs and NPs may enter the body primarily through inhalation, consumption, and skin contact. Once ingested, MPs can penetrate tissues, deviating to other parts of the body, and hence potentially affecting important cellular pathways such as nonconforming chemokine receptors that control the communication between the fetus and the mother. Consequently, the potential health harm induced by MP internalization is a major issue, evidenced by multiple studies demonstrating harmful consequences in diverse animal models and human cells. Here, an overview of the various modes of exposure to MPs and NPs is presented, including inhalation, placental transfer, ingestion, breastmilk consumption, and skin absorption, as well as placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Though MPs in our environment are becoming more recognized, their developmental toxicity is still scarcely known. Besides negatively affecting pregnancy, MPs and NPs have been shown to potentially harm the developing fetus, given their ability to cross the placental barrier. Still, considerable gaps remain in our understanding of the dispersion and toxicity of these particles in the environment, as well as the precise types of NPs and MPs bearing the greatest dangers. As a result, we advocate for larger-scale epidemiological investigations, the development of novel approaches for measuring NP and MP exposures, and the necessity of understanding the toxicity of various kinds of NPs to guide future research efforts.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

In a recent reformulation of the Marrucci-Ianniruberto constitutive equation for the rheology of entangled polymer melts in the context of non-equilibrium thermodynamics, rather large values of the convective constraint release parameter \beta_{ccr} had to be used in order not to violate the second law of thermodynamics. In this work, we present an appropriate modification of the model which avoids the splitting of the evolution equation for the conformation tensor into an orientation and a stretching part. Then, thermodynamic admissibility dictates simply that \beta_{ccr}≥ 0, thus allowing for more realistic values of \beta_{ccr} to be chosen. Moreover, and in view of recent experimental evidence for a transient stress undershoot (following the overshoot) at high shear rates whose origin may be traced back to molecular tumbling, we have incorporated in the model additional terms accounting, at least in an approximate way, for non-affine deformation through a slip parameter \xi. Use of the new model to describe available experimental data for the transient and steady-state shear and elongational rheology of entangled polystyrene melts and solutions shows close agreement. Overall, the modified model proposed here combines simplicity with accuracy, which renders it an excellent choice for managing complex viscoelastic fluid flows in large-scale numerical calculations.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Ancient DNA has given a new vision to the recent history of human evolution. However, by always relying on the information provided by whole genome sequencing, some relevant relationships between modern humans and its archaic relatives have been misinterpreted by hybridization and recombination causes. In contrast, the congruent phylogeny, obtained from non-recombinant uniparental markers, indicates that humans and Neanderthals are sister subspecies, and that the most recent common ancestor of modern humans was not of African origin but Eurasian.

In the framework of 2D circular membrane Micro-Electric-Mechanical-Systems (MEMS), a new non-linear second-order differential model with singularity in the steady-state case is presented in this paper. In particular, starting from the fact that the electric field magnitude is locally proportional to the curvature of the membrane, the problem is formalized in terms of the mean curvature. Then, a result of existence of at least one solution is achieved. Finally, two different approaches prove that the uniqueness of the solutions is not ensured.

The pathophysiology of Nonketotic Hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neuronal model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance and protein analyses. The study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology and offer new perspectives for therapeutic options.

In the wake of the rapid deployment of Small Modular Reactors (SMRs), this study aims to enhance the efficiency, reliability, and safety of SMR operations through a deeper understanding of human factors in their interaction within digital control room systems. Recognizing the pivotal role of human understanding in this new era of nuclear power, we employed electroencephalogram (EEG)-based monitoring to provide an unparalleled real-time view into operators' cognitive states. By interfacing detailed human models, informed by EEG metrics, with specific operational tasks, we recreate potential operational scenarios using an SMR simulator and capture intricate human responses therein. Our results elucidated the intricate relationship between EEG-derived data and human performance shaping factors, indicating a marked correlation between certain EEG patterns and operational efficiencies. Conclusively, these findings underscore the potential of EEG monitoring not only as a diagnostic tool but as an instrumental aid in the design and operation of future SMR digital control rooms. The insights derived offer a roadmap for the development of practical strategies, ensuring more effective and safer SMR operations.

Multimodal user interfaces promise a natural and intuitive human machine interactions. But is the extra effort for the development of a complex multi-sensor system justified, or can users also be satisfied with one input modality already? This study investigates interactions in an industrial weld inspection workstation. Three unimodal interfaces, including spatial interaction with buttons augmented on a workpiece or a worktable, and speech commands, were tested individually and in a multimodal combination. Within the unimodal conditions, users preferred the augmented worktable, but overall, the interindividual usage of all input technologies in the multimodal condition was ranked best. Our findings indicate that the implementation and use of multiple input modalities is valuable, and that it is difficult to predict the usability of individual input modalities for complex systems.

Proteins are the primary effectors of function in biology, and thus complete knowledge of their structure and properties is fundamental to deciphering function in basic and translational research. The chemical diversity of proteins is expressed in their many proteoforms, which result from combinations of genetic polymorphisms, RNA splice variants and post-translational modifications. This knowledge is foundational for the biological complexes and networks that control biology, yet remains largely unknown. We propose here an ambitious initiative to define the human proteome; that is to generate a definitive reference set of the proteoforms produced from the genome. Several examples of the power and importance of proteoform-level knowledge in disease-based research are presented, along with a call for improved technologies in a two-pronged strategy to accomplish the Human Proteoform Project.

Soybean with insignificant differences in appearance have large differences in their internal physical and chemical components, therefore follow-up storage, transportation and processing require targeted differential treatment. A fast and effective machine learning method based on hyperspectral data of soybean for pattern recognition of categories is designed as a non-destructive testing method in this paper. A hyperspectral-image dataset with 2299 soybean seeds in 4 categories is collected; Ten features is selected by extreme gradient boosting algorithm from 203 hyperspectral bands in range 400 to 1000 nm; A Gaussian radial basis kernel function support vector machine with optimization by the Tree-structured Parzen Estimator algorithm is built as TPE-RBF-SVM model for pattern recognition of soybean categories. The metrics of TPE-RBF-SVM are significantly improved compared with other machine learning algorithms. The accuracy is 0.9165 in the independent test dataset which is 9.786% higher for vanilla RBF-SVM model and 10.02% higher than the extreme gradient boosting model.

Reporting on CSR activities has become the essence of reporting for modern business entities. In this regard, particular attention is paid to public interest companies. Therefore, the following paper aims to answer the question of whether there are differences in the linguistic structure of the studied CSR reports in three selected industry indices on the Warsaw Stock Exchange (WSE) in Poland, i.e. WIG-energy index, WIG-fuel index, WIG-mining index and their relationship with the performance of selected companies. The study was conducted on a purposely selected sample of companies between 2013 and 2018. A total of 138 CSR reports and 138 annual separate financial statements prepared in accordance with international balance sheet law were collected. The study was carried out based on a panel regression model. It was found that CSR reports contained similar average percentages of parts of speech such as nouns and adjectives. When linking the economic performance of companies, expressed with selected indices, to the information on the implementation of CSR concepts, it was revealed that the results are more likely to describe business performance when it is satisfactory.

The use of new assistive technologies in general, and Socially Assistive Robots (SAR) in particular is becoming increasingly common for supporting people’s health and well-being. However, it still faces many issues regarding long-term adherence, acceptability and utility. Most of these issues are due to design processes that insufficiently take into account the needs, preferences and values of intended users. Other issues are related to the currently very limited amount of long-term evaluations, performed in real world settings, for SAR. This study presents the results of two regional projects that consider as a starting hypothesis that the assessment in controlled environments and/or with short exposures may not be enough in the design of a SAR deployed in a retirement home and the necessity of designing for and with users. Thus, the proposed methodology has focused in use cases definitions that follow a human-centred and participatory design approach. The main goals have been facilitating system acceptance and attachment by involving stakeholders in the robots design and evaluation, overcoming usage barriers and considering user’s needs integration. The implementation of the first use case deployed and the two-phase pilot test performed in the retirement home are presented. In particular, a detailed description of the interface re-design process based on improving a basic prototype with users’ feedback and recommendations is presented together with main results of a formal evaluation that has highlighted the impact of changes and improvements addressed in the first redesign loop of the system.

Collaborative robotics is a major topic in current robotics research posing new challenges, especially in Human-Robot Interaction. The crucial aspect in this area of research focuses on understanding the behavior of robots when engaging with humans, where reinforcement learning is a key discipline that allows us to explore sophisticated emerging reactions. This review aims to delve into the relevance of different sensors and techniques, with special attention to EEG (electroencephalography data on brain activity) and its influence on the behavior of robots interacting with humans. In addition, mechanisms available to mitigate potential risks during the experimentation process such as virtual reality will also be addressed. In the final part of the paper, future lines of research combining the areas of collaborative robotics, reinforcement learning, virtual reality and human factors will be explored, as this last aspect is vital to ensure safe and effective Human-Robot Interactions.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.