Natural language processing (NLP) is being widely used globally for a variety of value-creation tasks ranging from chat-bots and machine translations to sentiment and topic analysis and multilingual large language models (LLMs). However, most of the advances are initially implemented within the English language framework, and it takes time and resources to develop comparable resources in other languages. The advances in machine translations have enabled the rapid and effective conversion of content in global languages into English and vice-versa. This creates potential opportunities to apply English language NLP methods and tools to other languages via machine translations. However, although this idea is powerful, it needs to be validated and processes and best practices need to be developed and kept updated. The present research is an effort to contribute to the development of best practices and an evaluation framework. We present a systematic and repeatable state-of-the-art process to evaluate the viability of applying English language sentiment analysis tools to Italian text by using multiple English language machine translation mechanisms such that it can be easily extended to other languages. hor[RU,RA]{\large Richard Anderson} \address[RU]{\large Rutgers University, USA} \address[RA]{\large [email protected]} \author[RU]{\large Carmela Scala} \author[RU]{\large Jim Samuel} \author[UC]{\large Vivek Kumar} \address[UC]{\large University of Cagliari, Italy} \author[RU]{\large Parth Jain}

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

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

Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than pancreatic ductal adenocarcinoma. We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022. Patient information was extracted from our institutional database with the approval of Institutional Review Board. We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, 1 had borderline resectable disease, and 1 had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (1 patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases which had BostonGene tests was found to have NTRK1 fusion. RNA and TME analysis by BostonGene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74 and MMP1 and higher CDH6 compared with PDAC.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

The interest in random fiber lasers (RFLs), first demonstrated one decade ago, is still growing and their basic characteristics have been studied by several authors. RFLs are open systems that present instabilities in the intensity fluctuations due to the energy exchange among their non-orthogonal quasi-modes. In this work, we present a review of the recent investigations on the output characteristics of a continuous-wave erbium-doped RFL, with emphasis on the statistical behavior of the emitted intensity fluctuations. A progression from the Gaussian to Lévy and back to the Gaussian statistical regime was observed by increasing the excitation laser power from below to above the RFL threshold. By analyzing the RFL output intensity fluctuations, the probability density function of emission intensities was determined, and its correspondence with the experimental results was identified, enabling a clear demonstration of the analogy between the RFL phenomenon and the spin-glass phase transition. A replica-symmetry-breaking phase above the RFL threshold was characterized and the glassy behavior of the emitted light was established. We also discuss perspectives for future investigations on RFL systems.

Anderson-Fabry disease (AFD) results from decreased enzyme activity of lyzosmal enzyme and intralyzosomal storage of its nonhydrolyzed. Cadiovascular complications, mainly in s form of HCM contribute substantially for AFD-patient’s mortality. Here we report three new cases of obstructive HCM (HOCM) due to unclassical presentation of AFD and isolated cardiac involvement. In all three cases the diagnosis of AFD was made postoperative by routine genetic and morphological testing. Together with previously published cases this report illustrates the potential safely and beneficial effect of septal surgical myectomy in patients with AFD-HOCM, as well as underlines the need for more thorough screening for clinical signs of AFD-associated cardiomyopathy and GLA variants among patients with HOCM.

Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The impairment of the nervous system, in addition to the acroparesthesias, is characterized by hypohidrosis and cerebrovascular accidents. Gb3-accumulation supports the hypothesis that Gb3 is not solely responsible for disease manifestation. Overloading of lysosomes with Gb3 may simply lead to the rupture of cytoplasma and in consequence to cell death .Secondary effects of Gb3 accumulation which might be responsible for disease pathology include also inflammatory processes. Perturbed leukocyte function in Fabry disease compared to healthy controls and abnormal numbers of different immune cells, including lymphocytes, monocytes, CD8+ cells, B cells and dendritic cells . Noteworthy other studies reported no correlation between CRP-levels as a global inflammatory marker and the Mainz-Severity-Score-Index (MSSI) as a marker for disease severity . Other authors reported on auto-immunological reactions in α-galactosidase A deficiency. Others researchers found higher expressions of neuronal apoptosis inhibiting protein as a key anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Noteworthy, this upregulation did not change after institution of ERT, whereas apoptosis inducing factor appears to be upregulated under ERT. The authors were not able to explain their observations, but further research has to be directed on this topic. Gb3-accumulation has been reported to induce oxidative stress and/or the formation reactive oxygen species (ROS). Lipids and proteins may be oxidised and may be unable to function. Of note, ERT increased the generation of ROS in vitro, and up-regulated the intracellular adhesion molecule ICAM 1. The authors hypothesized that ERT may enhance endothelial damage, allowing to understand continuously occurring strokes in patients on treatment. Furthermore, Gb3-accumulation has been reported to induce oxidative stress and/or the formation reactive oxygen species (ROS). Lipids and proteins may be oxidised and may be unable to function. Of note, ERT increased the generation of ROS in vitro, and up-regulated the intracellular adhesion molecule ICAM 1. Another gateway into alteration of endothelial function may be given by the Nitric-Oxide-Synthase-3-genotypes. Endothelium-derived nitric oxide is a key regulator of vessel wall function and cardiovascular homeostasis. Thus, neurological complications seem to be linked to different pathogenetic molecular mechanisms.Progressive accumulation of GB3 represent a possible pathogenetic event of peripheral nerve involvement, whereas central nervous involvement in the clinical setting of cerebrovascular ischemic events seem to be due to the endotheliopathy of Anderson-Fabry Disease with lacunar lesions and white matter hyperintensities ( WMHs) . In this review manuscript we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

Multivariate statistical approaches (MSA), such as principal components analysis and multidimensional scaling, seek to uncover meaningful patterns within datasets by considering multiple response variables in a concerted fashion. Although these techniques are readily used by ecologists to visualize and explain differences between study sites, they could theoretically be employed to differentiate organisms within an experimental framework while simultaneously identifying response variables that drive documented experimental differences. Therefore, MSA were used herein to attempt to understand the response of the common, Indo-Pacific reef coral Seriatopora hystrix to temperature changes using data from laboratory-based temperature challenge studies performed in Southern Taiwan. Gene expression and physiological data partitioned experimental specimens by time of sampling, treatment temperature, and site of origin upon employing MSA, signifying that S. hystrix and its dinoflagellate endosymbionts display physiological and molecular signatures that are characteristic of sampling time, site of colony origin, and/or temperature regime. These findings promote the utility of MSA for documenting biologically meaningful shifts in the physiological and/or sub-cellular response of marine invertebrates exposed to environmental change.

The distribution of tiny sensors over a specific area was first proposed in the late 1990s as a concept known as Smart Dust. Several efforts focused primarily on computing and networking capabilities but quickly ran into problems related to power supply, cost, data transmission, and environmental pollution. To overcome these limitations, we propose using paper-based (confetti-like) chemosensors that exploit the inherent selectivity of chemical reagents, such as colorimetric indicators. In this work, cheap and biodegradable passive sensors made from cellulose could successfully indicate the presence of hazardous chemicals, e.g., strong acids, by a significant color change. A conventional color digital camera attached to a drone could easily detect this from a safe distance. The collected data was processed to define the hazardous area. Our work presents a combination of the smart dust concept, chemosensing, paper-based sensor technology, and low-cost drones for flexible, sensitive, economical, and rapid detection of hazardous chemicals in high-risk scenarios.

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

It's a method to achieve energy savings in single-phase active power greater than that obtained with the "Fan Law" in electric machines applied to ventilation. Quantitative analysis methods were based on electrotechnical techniques, practiced with the corresponding laboratory equipment on the working materials (three prototypes of electric machines). The results obtained from experimentation on the test bench were recorded in tables that collect data of formulas, values, and physical units. The discussion provides a comprehensive comparative study, mainly between power (watts), active energy consumption (kWh), and rotational speed (revolutions per minute). The permanent magnet synchronous motor (PMSM) with the coupling of an RL circuit design does mechanical work at its maximum speed of 3000 (RPM) with only 6.3 (Watts), which is equivalent to 25.2% of the active power required by the single-phase induction asynchronous motor (or shaded pole motor), which required 25 (Watts) to rotate at 1690 (RPM). This translates to 75% lower active power with a 44% superiority in speed, resulting in a 75% savings in single-phase active energy (measured in kWh). The same occurs when comparing it to the universal AC motor (with brushes and wound rotor) to maintain a speed of 3000 (RPM); since it consumes 64.8 (Watts), which is 90.3% more single-phase active energy than that required to achieve the same rotational speed as the permanent magnet synchronous motor (PMSM). The study was conducted on all motors with the same impeller blade diameter and under identical air temperature and atmospheric pressure conditions.

From 1964 to the early 1970s, Orson Anderson led a research program at the Lamont Geological Observatory in the newly-emerging field of “mineral physics”. In collaboration with colleagues Edward Schreiber and Naohiro Soga, Orson exploited the techniques of physical acoustics to study the behavior of the sound velocities of minerals at elevated pressures and temperatures. This research program also included semi-empirical studies of relationships between the bulk modulus and the molar volume of solids and the use of lattice dynamics to calculate the elastic moduli of cubic structures as a function of pressure to predict instabilities, as well as theoretical investigations of the Lagrangian vs. Eulerian formulations of finite strain equations of state.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

This study focuses on the design, development, and evaluation of an educational mobile robot, named Robot-T2, to be used in educational activities within a technical school. The primary objective was to create a versatile platform that allows students to explore programming, engineering, and science concepts in a practical and collaborative manner. The methodology included an iterative design and testing approach, incorporating feedback from students and teachers to continuously improve the robot's functionality. The tests covered autonomous navigation, line following, and object manipulation, using the OnBotJava programming software and the Control Hub as the main interface. The results demonstrated that Robot-T2 is highly efficient and adaptable in various educational contexts, showing remarkable precision in navigation and object manipulation. The design iterations significantly improved the robot's performance, enriching the educational experience and promoting active learning. In conclusion, educational robotics, represented by Robot-T2, has great potential to enhance the teaching and learning process in technical schools, fostering teamwork, problem-solving, and the integration of technology in the classroom. This project is expected to inspire future developments in educational robotics.

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

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

First, an introductory essay is carried out to build a historical, economic-productive and legal theoretical framework of the origin and formation of Secondary Technical Schools in Europe, North America and the Argentine Republic. Then a normative introduction to Technical Education is carried out at the Technical School No. 2 “Independencia” of Concordia, Entre Ríos, Argentine Republic. Its regulations and Laws that govern technical education. We continue analyzing the development of five (5) case studies generated in the E.E.T. No. 2 “Independence” of the city of Concordia, Province of Entre Ríos, Argentine Republic. Case study No. 1: Face masks for Covid-19, designed with CAD-STL software and printed in polylactic acid (PLA) with 3D printers, for protection from SARS-CoV-2 (Coronavirus) or Covid-19. Case study No. 2: TURBO: air extractor/blower for environments contaminated by COVID-19. Case study No. 3: ROBOT-T2: Educational Robot Made by Students and Teachers of the Technical School No. 2 (E.E.T. No. 2) “Independencia”, Concordia, Entre Ríos, Argentine Republic. Case study No. 4: Self-construction EcoBlock, for social housing. Case study No. 5: Relationships of all sciences with abductive thinking, creativity, design, art and the main relationships between Social Sciences (philosophy, logic, hermeneutic research methodology, etc.) with Exact and Natural Sciences (mathematics, physics, chemistry, biology, genetics), other sciences and disciplines such as engineering, medicine, etc. We obtain the conclusions of the development. Bibliography.

This paper proposes how to reduce the consumption of active electrical energy (kwh) by 90.3% while maintaining the same mechanical work speed (RPM) at variable torque loads (fans or air-fluid blowers, centrifugal pumps are not included). of water and similar fluids), by using the “Fan Law” in an innovative way in PMSM-type synchronous motors (a comparative study never before carried out on the Fan Law). The work is carried out comparatively between brushless a-synchronous motors with starting loop (or motor with a short-circuited loop) versus brushed a-synchronous motors and PMSM-type synchronous motors without the need to use VDF (variable frequency drives), simplifying technology (electronics) and saving costs in an innovative way (R+D+i). The case study was developed on a design applied to a centrifugal air extractor/blower with PMSM/IPM type synchronous motor. Applying one of the fan affinity laws –with the impeller diameter 10.5 (mm) constant- the electrical power absorbed by the blower motor is proportional to the cube of the shaft speed: . Being “P” power (Watts) and “N” speed (RPM). Carrying out a comparative study between power (watts), active energy consumption (kwh) and rotational speed (RPM). This has a direct impact on the costs of residential and commercial single-phase active electrical energy consumption, measured in kilowatt-hours (kwh). Carrying out a comparative study between three (3) types of alternating current (AC) electrical machines, according to the NEMA (National Electrical Manufacturers Association); AC motors fall into three (3) categories. One (1), synchronous motors (Syncrhonous Motor) of three types: (1a) excitation by DC (DC Excited Motor), (1b) permanent magnet (Permanent Magnet Motor) and (1c) reluctance motor (Reluctance Motor) or motor Step by Step. Two (2), asynchronous induction motors of two types: (2a) Squirrel-Cage Induction Motor and (2b) Wound-Rotor Induction Motor. Three (3) series-wound motor (Series-Wound Motor) also called universal motor (they have carbons).

Recent years have seen a rapid uptake in distributed energy resources (DER). Such technologies pose a number of challenges to network operators, which can ultimately limit the amount of rooftop solar photovoltaics (PV) systems that can be connected to a network. The objective of this industry-based research was to determine the potential network effects of forecast levels of customer owned rooftop solar PV on Energy Queensland’s distribution network and formulate functions that can be used to determine such effects without the requirement for detailed network modeling and analysis. In this research, many of Energy Queensland’s distribution feeders were modelled using DIgSILENT PowerFactory and analyzed with forecast levels of solar PV and customer load. Python scripts were used to automate this process and quasi dynamic simulation (QDSL) models were used to represent the dynamic volt-watt and volt-var response of inverters, as mandated by the Australian Standard AS/NZS 4777. In analyzing the results, linear regression was used to form trend equations that represent various network characteristics against the number of PV connections. The trend equations provide a way of approximating network characteristics for other feeders under various levels of customer owned rooftop solar PV without the need for detail modeling.

The product is a centrifugal air extractor, whose objective is to extract the stale air of SARS-CoV-2 or Covid-19 (Coronavirus); designed for civil and commercial use, it works with a single-phase alternating current (AC) motor of 220 (V) and 50 (Hz), with high energy efficiency (EE). Developed under the Design Thinking methodology, by electromechanical simulation using NI Multisim 14.0 software, case design using Cfturbo 2020 R2.0 CAD software, and rapid 3D prototyping with the OverLord Pro printer; with a prototype of the conventional stator winding of a synchronous motor with a two-pole PMSM/IPM single-phase alternating current (AC) field winding and a 4000 (Gauss) ferromagnetic ceramic magnet rotor. Innovating online nº 15 of invention patent nº 381968 by Nikola Tesla, 5/1/1888.One of the objectives is to link the middle level or Technical Schools with the University system (and careers with a Technological profile) through Project B374 located in the Secretariat of Science and Technology (SCyT) of the National University of La Plata ( UNLP), whose title is: “Integrated Management of Design and Innovation. Contributions for a theoretical-conceptual and methodological review” by the Director: Mg. Federico del Giorgio Solfa. Just as links were sought with the Research and Development Laboratory of the Department of Industrial Design (LIDDI-FBA-UNLP) through its Director D.I. Pablo Ungaro and D.I. Ana Bocos. In 2021, the project participated in the INNOVAR National Contest of the Ministry of Science, Technology and Productive Innovation of the Nation (MINCYT), Argentine Republic; in the "Covid-19 Projects" category, having been selected in the catalog of innovative products, won the 1st. "Covid-19 Projects" position of the National Agency for Research and Technological Development and local innovation (R+D+i) dependent on MINCYT.The results showed, according to the analysis of the test bench, that the PMSM/IPM type synchronous motor used in the centrifugal fan, with the innovation of the reactance-inductive control in series plus the capacitor in parallel, reduces the power by 67% (Watts) and active energy consumption (kWh), performing 56% more mechanical work (Joules) on the fluid air (with a 50% reduction in carbon footprint). Which leads us to the following conclusion: it is possible to develop centrifugal fans that save electricity (kWh) without the need to resort to (1) the "Fan Affinity Law", nor (2) the use of variable speed drives (VDF) or frequency (which are devices with complex and expensive electronics). Which would bring an enormous saving of the cost of electrical energy.

Iodide is an essential micronutrient present in very small quantities in the human body, with a fundamental action for the adequate synthesis of thyroid hormones, which are critical for cell differentiation, growth and metabolism. In the form of iodide, iodine is widely distributed in the environment, although in an irregular manner, occurring in abundant amounts in the oceans and in coastal areas and scarcely found on islands and mountains. The diet is the main source of iodine, whose intake varies according to the amount present in soil and water and according to eating habits. Governmental policies have been adopted to satisfy and guarantee the necessary daily supply of iodine, such as fortification of industrialized salt for domestic iodine consumption or addition to the bread commonly consumed in a given region, or the offer of iodized oil to the population, or even iodine supplementation through medications. Iodide deficiency is the main avoidable cause of brain damage to fetuses and children, as well as retardation of psychomotor development. Thyroid hormones are almost universally involved in the development and proliferation of fetal neural tissue. Permanent lesions of the cerebral cortex, hippocampus and cerebellum may occur, with loss of, or damage to the brainstem or spinal cord, affecting cortical areas that integrate highly specialized stimuli, which become poorly defined on an anatomical basis, including silent areas of the associative cortex. One of the more significant metabolic problems due to dietary iodine deficiency is the presence of goiter (increased volume of the thyroid gland). Thyroid carcinoma is the most frequent endocrine neoplasia affecting the human species and plasma iodine concentration is related to the development of specific subtypes of this neoplasia. An increased prevalence of follicular carcinoma, a more aggressive tumor, has been observed in areas of iodine deficiency, while the correction of this deficiency is associated with a higher prevalence of papilliferous carcinoma, a less aggressive form. CONCLUSION: An ideal plasma iodide concentration is necessary to insure the proper mental development of fetuses and young children and to minimize the aggressiveness of thyroid cancer from follicular cells in humans.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

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

From the mid-19th century, Collegiate Gothic architecture gained prominence among American universities. Subsequently, through the efforts of American missionaries, the Collegiate Gothic style spread to Christian universities in Asia. Specifically, this study concentrates on the nuanced relationship between the transnational missionary routes and adopting the Collegiate Gothic style, primarily focusing on Anderson Hall at Soochow University, China. The investigation meticulously dissects the multifaceted factors influencing the choice of architectural styles, considering the perspectives of missionaries, architects, and other key stakeholders. Through an intricate analysis of Anderson Hall, this research illuminates the unique characteristics of Collegiate Gothic architecture. By unraveling the complex layers of East Asian campus heritage, this study enriches our comprehension of its origins. It establishes a robust foundation for guiding the preservation and revitalization of architectural styles within university campuses. This scholarly inquiry holds particular significance for experts in academic heritage conservation.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

The present work titled QRGB consists of the development of a Python application for generating QR codes using the additive color generation method (RGB). This innovative method increases the information density stored in QR codes by using three color layers (red, green, and blue), each representing a different data set. QRGB offers an efficient and secure solution for storing and transmitting large amounts of information in limited spaces, significantly improving the capabilities of traditional black-and-white QR codes.By using three color layers (red, green, and blue), QRGB codes can store up to three times more information in the same space. This technique not only increases storage capacity but also enhances information security, making it more difficult to counterfeit or manipulate the code. The superposition of multiple data layers allows for redundancy implementation, increasing the code's robustness against damage or reading errors.QRGB codes are especially useful in applications that require the transmission of large amounts of data in limited spaces, such as in the packaging industry, digital business cards, and interactive advertising. Additionally, they have great potential in areas such as document and ticket security, where the authenticity and integrity of information are crucial.These points provide a solid foundation for understanding the innovation and advantages of colored QR codes (QRGB) compared to traditional QR codes, highlighting their applicability and potential in various sectors.The Python application developed for QRGB utilizes advanced color image processing techniques, applying models and methods to generate and decode QR codes using the RGB color system, thus enhancing information density and security through the innovative use of additive color layers.

We evaluated progress towards animal biodiversity research in Georgia, a key area in the Caucasus biodiversity hotspot. By reviewing recently (1990-2018) published articles in all areas of animal diversity research, we unmasked the trends in biodiversity inventory, ecological and biogeographical studies, and conservation issues in Georgia. We concluded that species inventory and biodiversity research in Georgia has significantly increased during the last ten years, however the rate and extent of investigation is far from satisfactory. Major gaps remain in all branches of animal diversity research in Georgia, and consequently existing knowledge is inadequate to address modern challenges related to species and ecosystem conservation. We urge local governmental authorities and international scientific societies to support development of stronger research facilities and cultivate interest in biodiversity inventory and research in Georgia as an important step towards maintaining globally important biodiversity in the Caucasus.

Introduction of exotic species in new areas through anthropic action is one of the major problems that can affect biodiversity. Branchiomma luctuosum is known for its highly invasive potential and the actual occurrence of species commonly associated with port activity areas is an extra evidence that this anthropogenic activity should not be underestimated. In order to develop suitable molecular markers for future studies on colonization routes and population dynamics of the invading individuals of B. luctuosum, nine highly polymorphic microsatellite loci were isolated and their polymorphism levels were evaluated. These loci showed a range of number of alleles per locus from five to ten and all loci had a high level of genetic diversity, and exhibited significant heterozygote deficiencies probably due to the presence of null alleles. Significant deviations from the Hardy-Weinberg equilibrium were detected at several loci and most of them were related to a heterozygous deficit. Heterozygous deficiency can be expected in this case due to the biology and history of this invasive species, in relation to its recent introduction in Brazilian coast and possible action of multiple introductory events.

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

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

The Anderson insulating states in Au nanoparticle assembly are identified and studied under the application of magnetic fields and gate voltages. When the inter-nanoparticle tunneling resistance is smaller than the quantum resistance, the system showing zero Mott gap can be insulating at very low temperature. In contrast to Mott insulators, Anderson insulators exhibit great negative magnetoresistance, inferring charge de-localization in a strong magnetic field. When probed by the electrodes spaced by ~200 nm, they also exhibit interesting gate-modulated current similar to the multi-dot single electron transistors. These results reveal the formation of charge puddles due to interplay of disorder and quantum interference at low temperatures.

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

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

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

Autism spectrum disorder (ASD) is characterized by diverse patterns of social interaction, communication, and behavior. This study explores the application of clustering and stochastic migration models to visualize and understand the social and neural connectivity patterns associated with autism. The clustering model, with its strong internal connections and limited external connections, mirrors the tight-knit social groups and communication barriers often observed in individuals with autism. In contrast, the stochastic model, characterized by more dispersed connections and greater adaptability, represents the variability and flexibility seen in social interactions across typical individuals. By comparing these models, we can gain deeper insights into the unique challenges and strengths of individuals with autism, highlighting the importance of personalized interventions. Additionally, these models provide a visual framework for understanding the differences in brain connectivity patterns observed in autism, with implications for both behavioral and neural correlates. This study underscores the value of computational models in advancing our understanding of autism and guiding effective support strategies.

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

Glioblastoma is a highly aggressive brain tumor characterized by rapid growth, extensive infiltration, and poor prognosis. Understanding the complex interplay of biological processes driving glioblastoma progression is crucial for developing effective therapeutic strategies. In this study, we present a comprehensive mathematical model that incorporates key aspects of glioblastoma growth and dissemination, including tumor cell diffusion, angiogenesis, nutrient availability, molecular signaling pathways, and blood-brain barrier (BBB) interactions. The model is based on a system of coupled partial differential equations (PDEs) and ordinary differential equations (ODEs) that capture the spatiotemporal dynamics of tumor cell density, nutrient concentration, signaling molecule concentrations, and BBB integrity. We employ numerical simulation techniques, such as the finite difference method and the Runge-Kutta method, to solve the model equations and visualize the evolution of tumor growth and its associated biological processes. The model parameters are estimated using experimental data from the literature, and the model is validated against clinical observations. Furthermore, we perform a comprehensive sensitivity analysis to identify the key parameters that significantly influence tumor growth, diffusion, and dissemination. The sensitivity analysis reveals the relative importance of each parameter in driving glioblastoma progression and highlights potential targets for therapeutic interventions. Our computational framework provides a powerful tool for understanding the complex dynamics of glioblastoma growth and offers valuable insights into the underlying biological mechanisms. The model can be used to test hypotheses, predict tumor response to various treatment strategies, and guide the design of targeted therapies. The findings from this study contribute to the ongoing efforts in developing personalized treatment approaches for glioblastoma patients and improving their clinical outcomes.

Frailty syndrome is a complex and multifaceted condition that significantly impacts the health and well-being of older adults. This article provides a comprehensive overview of frailty syndrome, including its definitions, evolution, and the rising role of biomarkers and electroencephalography (EEG) in its diagnosis. The discussion explores the reasons behind the rise of frailty syndrome, the difficulties in managing it, and the global research efforts aimed at understanding and addressing this condition. The economic costs associated with frailty syndrome are highlighted, along with the countries that are currently and will be more affected in the near future. Strategies to postpone or avoid frailty syndrome are discussed, with an emphasis on the importance of muscle strength exercises over aerobic exercises to combat sarcopenia. The article concludes by emphasizing the need for a multidisciplinary approach to frailty management and the importance of social support and engagement in preventing and managing frailty.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are prevalent neurodevelopmental disorders with distinct diagnostic criteria but significant overlap in symptoms and comorbidity. This article explores the relationship between ADHD and ASD, examining their common neurodevelopmental origins, shared features, and distinct trajectories. Both disorders are highly heritable, with genetic studies identifying shared genetic variants and neurobiological abnormalities. Environmental factors, including prenatal and perinatal exposures, also contribute to their etiology. Despite these commonalities, ADHD and ASD exhibit distinct developmental trajectories, cognitive profiles, and long-term outcomes. Understanding the interplay between these disorders is crucial for developing effective diagnostic and treatment strategies. Future research should focus on elucidating the underlying mechanisms and developing targeted interventions for individuals with comorbid ADHD and ASD.

Myelination, the process of forming a myelin sheath around nerve fibers, is critical not only during early development but also throughout adulthood. This article explores the multifaceted impacts of myelination on the adult brain, highlighting its importance in cognitive functions, neurological health, and overall brain efficiency. In adults, efficient myelination enhances information processing speed, supports memory consolidation, and contributes to cognitive reserve, potentially delaying the onset of neurodegenerative diseases. Myelination ensures synchronized neural activity and energy-efficient brain function, playing a key role in complex cognitive tasks and coordination. Despite a slower rate of plasticity compared to early development, the adult brain retains the ability to adapt and learn, with myelination facilitating these processes. This article also draws parallels between myelination in the brain and learning curves in deep learning Perceptrons, emphasizing how reduced stimulation and experience can significantly slow down cognitive and learning processes. Additionally, the clinical implications of myelination are discussed, including its role in multiple sclerosis and age-related cognitive decline, along with strategies to maintain and enhance myelin health through lifestyle choices and emerging pharmacological interventions. Understanding the ongoing significance of myelination in the adult brain, and its comparison to artificial neural networks, is crucial for developing interventions to support cognitive health and mitigate neurological disorders.

This study presents two interconnected mathematical models: one describing the stability and bifurcation dynamics of ecological biomes, and another simulating the progressive deformation and structural failure of a toroidal object. Both models explore topological changes in complex systems, bridging concepts from ecology, materials science, and mathematical physics. The first part introduces a dynamic model of ecological biomes, incorporating seasonal oscillations and external pressures. We define equations for topology updates, seasonal effects, and pressure impacts, culminating in a bifurcation condition that represents a critical shift in the biome's equilibrium state. This model provides insights into the resilience and tipping points of ecological systems under varying environmental stresses.The second part extends these concepts to a three-dimensional toroidal structure. We present parametric equations describing the torus geometry and develop a time-dependent deformation model that includes both stochastic and deterministic elements. A novel twisting deformation component enhances the realism of the structural changes. We define a critical threshold for maximum displacement, beyond which the torus undergoes structural failure, analogous to the bifurcation point in the biome model. Both models are implemented computationally, providing visual representations of the systems' evolution over time. The biome model illustrates the path to and consequences of bifurcation, while the torus simulation depicts the stages of deformation leading to structural break. This work contributes to the understanding of topological changes and critical transitions in both ecological and physical systems. By presenting these models in parallel, we highlight the universal nature of stability, bifurcation, and failure across different domains. The methodologies presented here have potential applications in ecology, materials science, structural engineering, and theoretical physics, offering a framework for studying the limits of system integrity under stress.

This small article examines the pivotal roles of redundant and degenerate neural networks in the brain across three critical dimensions: evolutionary development, early childhood neural formation, and their implications in neurological diseases. Redundant networks, characterized by parallel neural pathways with similar functions, provide a foundation for cognitive resilience, ensuring continuity of brain functions despite damage or developmental anomalies. Degenerate networks, comprising structurally varied but functionally equivalent pathways, contribute to cognitive flexibility and adaptability, essential for innovative problem-solving and learning. From an evolutionary perspective, these networks have been instrumental in the brain's adaptation to diverse environmental challenges, facilitating cognitive maximization and the development of complex behaviors. The genetic underpinnings and environmental influences that shaped these networks are explored, highlighting their contribution to the evolutionary success of the human species. In the realm of early childhood development, the formation and reinforcement of these networks are crucial. The brain's plasticity during this period leads to the establishment of robust redundant networks and versatile degenerate networks, shaped significantly by environmental stimuli and learning experiences. This developmental phase lays the groundwork for cognitive abilities and resilience to neurological challenges later in life. Furthermore, the paper delves into the implications of these networks in the context of brain diseases. The disruption of the equilibrium between redundancy and degeneracy is linked to various neurological conditions, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke and Huntington's disease. Understanding the roles and balances of these networks offers insights into the pathophysiology of these diseases and potential therapeutic approaches. This review underscores the significance of redundant and degenerate neural networks in the evolutionary context, their critical formation during early childhood, and their profound impact on brain health and disease. It highlights the need for further research into these networks to enhance our understanding of brain function and to develop targeted interventions for neurological disorders.

This paper explores a novel approach to establishing the topological equivalence of manifolds embedded in ℝ

This study aims to refine our understanding of evolutionary processes, particularly as they apply to complex organisms, using an innovative graph-based simulation approach. We model the topological evolution of simple (5-node ring graph) and complex (20-node dense random graph) organisms over 10 generations, applying different mutation rates to reflect biological realities. Our results provide intriguing insights into the potentially different evolutionary dynamics at play in simple versus complex organisms. While simple organisms demonstrate high topological flexibility and rapid adaptability, aligning with classical evolutionary models, complex organisms exhibit a surprising degree of structural stability. This stability persists even under mutation rates that would typically drive significant changes in simpler systems. The simulation highlights an important consideration: the intricate, interdependent networks characteristic of complex organisms may create a form of evolutionary buffering. This buffering could modulate the impact of random mutations and natural selection – processes that are cornerstones of evolutionary theory. Our findings suggest that the high degree of complexity in advanced life forms may necessitate a more nuanced view of how evolutionary processes operate across different levels of biological organization. Furthermore, the emergence of new structural motifs in simple organisms, contrasted with the relative conservation in complex topologies, indicates that evolutionary mechanisms may manifest differently across the spectrum of biological complexity. This observation invites a more detailed exploration of how evolutionary principles apply to diverse life forms.These results contribute to the ongoing refinement of evolutionary theory, especially in its application to complex organisms. They suggest that additional mechanisms, such as constrained mutations, epigenetic changes, or higher-order organizational principles, may play significant roles alongside random mutations and natural selection in the evolution of complex life forms.

Recent developments in microfluidics and biomaterials have enabled the creation of organs-on-chips (OoCs), which provide a controlled and lifelike in vitro microenvironment resembling an actual organ. Organ-on-a-chip technology offers a tremendous opportunity for efficient, cost-effective, and ethical drug testing and research. However, the high throughput and large quantities of data these complex microenvironments produce make it difficult for researchers to effectively analyze the data and draw valuable conclusions. Convolutional Neural Networks (CNNs) are most aptly positioned to address many of OoC’s challenges because of their ability to interpret microscopic images and facilitate the analytical process. Despite the growing field of AI, there have been a limited number of studies summarizing the various applications of CNNs in OoCs. This review aims to provide 1) an overview of the technology involved with CNNs and OoCs 2) an insight into the state-of-the-art applications of CNNs in OoCs including device parameters, predicting and tracking cell trajectories, super-resolution image segmentation, and image classification, and 3) an overview of existing challenges and opportunities ahead for clinical translation of this technology. Various applications of CNNs have been classified by the type of task. Different CNN models such as Faster R-CNNs, fully convolutional networks (FCNs), and Mask R-CNNs are explained and highlighted. This review article can be used as a resource for a better understanding of the potential of CNNs in biomedical research and clinical applications, particularly OoCs.

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

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by the demyelination of neural fibers in the central nervous system. Understanding the impact of demyelination on neural network efficiency is crucial for elucidating the pathophysiological mechanisms underlying MS. This study aims to model the effects of demyelination on neural network efficiency, specifically focusing on how increased resistance and path lengths due to demyelination correlate with the clinical symptoms of MS. We employed a graph-theoretical approach to simulate neural networks, introducing varying degrees of demyelination. The demyelination was represented by increasing the resistance (weights) of selected edges within the network, affecting both random and clustered distributions of network connections. The primary metric analyzed was the average shortest path length, indicative of network efficiency. The models demonstrated a significant increase in the average shortest path length in demyelinated networks compared to intact ones. Specifically, networks with clustered demyelination exhibited localized inefficiencies, correlating with the focal nature of MS lesions. The increase in path length was associated with reduced signal transmission efficiency, providing insights into a range of MS symptoms including motor and sensory impairments, cognitive dysfunction, visual disturbances, and fatigue. The graph-theoretical model of neural network demyelination offers a novel perspective on how structural changes in the brain's connectivity due to MS can lead to diverse clinical manifestations. While the model simplifies the complexity of neural networks, it underscores the potential of computational approaches in understanding and predicting the course of neurological disorders like MS.

This study explores the intriguing phenomenon of action potentials reverberating and propagating in high-resistance tissues, such as gliosis, leading to the emergence of short circuits within the brain. Gliosis, characterized by increased tissue resistance, presents a unique environment for electrical signals. My research investigates the possible mechanisms behind these reverberations and their role in the creation of self-empowering short circuits that can potentially affect the entire brain's functionality. Understanding these processes may have significant implications for the treatment and management of neurological disorders associated with gliosis and abnormal electrical activity in the brain.

This review article provides a comprehensive overview of the anatomical structure of the human brain, highlighting its key components and their functional significance. The brain is the central organ of the nervous system, responsible for controlling and coordinating various bodily functions. The article begins with an introduction to the brain's gross anatomy, including the cerebrum, cerebellum, brainstem, and diencephalon. It then delves into the detailed microstructure of the brain, discussing neurons, glial cells, and the complex network of neural connections. The review also explores the functional organization of the brain, emphasizing the roles of different regions such as the frontal, parietal, temporal, and occipital lobes. It discusses the importance of the limbic system in emotional processing and the basal ganglia in motor control. Additionally, the article covers the brain's vascular system and the blood-brain barrier, which are crucial for maintaining the brain's homeostasis. Recent advancements in neuroimaging techniques, such as magnetic resonance imaging (MRI) and functional MRI (fMRI), have significantly enhanced our understanding of brain anatomy and function. These techniques have enabled researchers to map brain activity in real-time, providing insights into cognitive processes and neurological disorders. The article concludes by discussing the implications of understanding brain anatomy for clinical practice, including the diagnosis and treatment of neurological conditions. It also highlights areas for future research, emphasizing the need for further exploration of the brain's structural and functional complexity.

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

This project aims to simulate and analyze population dynamics in evolutionary systems, using stochastic differential equations and probabilistic rules for crossbreeding and benefits. The study employs advanced computational techniques to model the evolution of populations over an extended period. Specifically, we explore a scenario with ten distinct groups, each starting with an equal population and evolving under defined genetic and cooperative behaviors. The simulation spans 1000 years, incorporating individual lifespans, stochastic updates, and probabilistic interactions. To ensure robustness and reliability, the study includes detailed statistical analysis, encompassing descriptive statistics, confidence intervals, and ANOVA tests. We further visualize the temporal behavior of populations and subpopulations, providing insights into the evolutionary dynamics and stability of the system. The results demonstrate the effectiveness of balanced cooperation and genetic diversity in maintaining stable population distributions. The project showcases the integration of mathematical modeling, statistical analysis, and computational simulations, contributing valuable insights into evolutionary biology and complex systems. It highlights the importance of interdisciplinary approaches in understanding and predicting population behaviors, with implications for both theoretical research and practical applications in fields such as ecology, genetics, probability and social sciences.

Psychiatric disorders, characterized by complex and fluctuating patterns of thoughts, emotions, and behaviors, can be effectively modeled and visualized using mathematical wave equations. This study explores the representation of three major psychiatric conditions— Psychosis, Bipolar Disorder and Obsessive Compulsive Disorder (OCD)—through the application of differential equations, damping factors, and noise perturbations. Psychosis is modeled using Lissajous figures with high-frequency components, damping, and noise, symbolizing the irregular and erratic thought patterns characteristic of this condition. The inclusion of random perturbations and varying frequencies illustrates the chaotic and unpredictable nature of psychotic episodes, while damping effects reflect the temporary reductions in symptom intensity. For bipolar disorder, a system of partial differential equations simulates the cyclical nature of manic and depressive episodes. The model captures high-energy manic phases with periodic disturbances and the subsequent transition to lower-energy depressive states through damping effects. This representation highlights the oscillatory behavior and recurring episodes inherent to bipolar disorder. OCD is represented with Circumferential Complex Equations in Mult directions. The resulting graphical representations provide intuitive visual insights into the dynamics of these psychiatric disorders. By leveraging wave equations and mathematical modeling, this approach offers a novel perspective on understanding and analyzing the complex behaviors associated with OCD, bipolar disorder and psychosis. This method not only aids in the conceptualization of psychiatric phenomena but also underscores the potential of mathematical tools in the study of mental health conditions.

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

This study presents a novel approach to understanding evolutionary dynamics through topological analysis of genotypic structures. We model the genome of a simple organism as a topological torus undergoing mutations at a constant rate of 1% per generation. Employing persistent homology and other topological data analysis techniques, we investigate how these mutations influence the overall topology of the genomic structure over time. Our simulations reveal that specific critical mutations lead to significant changes in the homotopic and homologic properties of the torus. We interpret these topological shifts as potential markers for the formation of new subspecies. By identifying the precise points of topological "breaks" within the toroidal genomic representation, our model provides a quantitative framework for observing the incremental transformations that underpin major evolutionary developments. The results offer new insights into the thresholds of speciation and adaptation, demonstrating how gradual genetic changes can accumulate to produce qualitative shifts in organismal traits. This approach bridges the gap between microscopic genetic mutations and macroscopic evolutionary outcomes, potentially revolutionizing our understanding of evolutionary processes. Our findings have implications for various fields, including theoretical biology, genetic engineering, and conservation biology. The model provides a novel perspective on genetic resilience and adaptability, offering a foundation for future research on the relationship between genomic topology and evolutionary trajectories. It also emphasizes the innovative nature of the research and its potential impact on multiple fields of study.

Borrelia miyamotoi is an emerging tick-borne pathogen in the Northern hemisphere and is the causative agent of Borrelia miyamotoi disease (BMD). B. miyamotoi is vectored by the same hard-bodied ticks as Lyme disease Borrelia, yet phylogenetically groups with relapsing fever Borrelia, and thus has been uniquely labeled a hard tick-borne relapsing fever Borrelia. Burgeoning research has uncovered new aspects of B. miyamotoi in human patients, nature, and the lab. Of particular interest are novel findings on disease pathology, prevalence, diagnostic methods, ecological maintenance, transmission, and genetic characteristics. Herein we review recent literature on B. miyamotoi, discuss how findings adapt to current Borrelia doctrines, and briefly consider what remains unknown about B. miyamotoi.

Ultraviolet (UV) light with a wavelength of 254 nm has proven to be effective at inactivating microorganisms, and thus has been increasingly employed as a method of disinfection for indoor environments. Solar UV wavelengths (300 to 400 nm) are known to initiate the formation of secondary organic aerosol (SOA) particles from photo-oxidation of volatile organic compounds in the atmosphere, but germicidal wavelengths have not been extensively studied for indoor environments. In this work, toluene was exposed to 254 nm UV light in a laboratory photoreactor, with varying conditions of the air, the duration of UV exposure, and the duration of post-UV time. The number of particles formed in the fine particulate matter (PM2.5) size range was measured, and significant levels of particle formation were observed for UV exposure periods of as short as 5 minutes. The particle formation ranged from 2.4x10⁶ particles/m³ for 5 minutes of UV exposure, to 1449.8x10⁶ particles/m³ for 15 minutes of UV exposure. Particle formation was found to increase with increasing concentrations of gas phase toluene, and at relative humidity of approximately 20% and higher. Variations in the initial number of particles present did not appear to have a significant effect on the particle formation, suggesting that nucleation was not a controlling factor. However, tests in a commercial environment showed no significant detectable PM2.5 formation, indicating that SOA formation during the intermittent use of germicidal UV may not significantly affect indoor air quality.

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

Comparative analysis of mortality rates between public and private healthcare systems remains a critical yet complex area of study. This article synthesizes findings from extensive academic literature and empirical studies to examine the relationship between healthcare system type and patient outcomes across various countries. By focusing on mortality rates as a key indicator, we elucidate the nuanced impacts of public versus private healthcare delivery. Our analysis reveals the multifaceted challenges inherent in both systems and their implications for patient survival. We conclude by identifying crucial gaps in current research and proposing policy recommendations to optimize healthcare outcomes in diverse global contexts.This revised abstract:Starts with a strong opening statement that immediately captures the topic's importance. Clarifies the article's methodology (synthesizing existing literature and studies).Specifies the focus on mortality rates as the primary outcome measure.Hints at the complexity of the findings, avoiding oversimplification.Ends with a clear statement about the article's contributions to both research and policy.

The integration of genetic technologies into neurological diagnostics has significantly enhanced our ability to understand and manage neurological disorders. This article discusses the functional analysis of key genetic tests, including microarray analysis, variant sequencing, exome sequencing, RNA sequencing, and whole genome sequencing. Each of these technologies offers unique advantages and challenges, providing a comprehensive toolkit for diagnosing and understanding the genetic basis of neurological conditions. The functional insights gained from these tests not only detect genetic abnormalities but also elucidate their functional consequences, aiding in the diagnosis, prognosis, and management of neurological disorders. As these technologies continue to evolve, they are expected to play an increasingly important role in the field of neurological diagnostics, paving the way for personalized medicine and improved patient outcomes.

Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the DNA sequence, is revolutionizing our understanding of psychiatric disorders. This article provides a comprehensive overview of the role of epigenetics in psychiatry, discussing its implications for genomics, evolution, inheritance patterns, and the development of biomarkers. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, are explored in the context of psychiatric conditions such as depression, schizophrenia, and post-traumatic stress disorder (PTSD). The discussion highlights how epigenetic modifications can influence brain dynamics, as measured by electroencephalography (EEG), and how artificial intelligence (AI) can accelerate the development of treatment options. The potential for epigenetic biomarkers to improve diagnosis, prognosis, and treatment is emphasized, along with the role of behavioral interventions in inducing beneficial epigenetic modifications. Future directions in epigenetic research, including the development of epigenetic therapies and the elucidation of molecular mechanisms underlying epigenetic inheritance, are also discussed. This article underscores the transformative potential of epigenetics in advancing our understanding of mental health and disease, paving the way for novel therapeutic interventions.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

Telehealth is the delivery of many health care services and technologies to individuals at different geographical areas and is categorized as asynchronously or synchronously. The coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions in health care delivery to breast cancer (BCa) patients and there is increasing demand for telehealth services. Globally, telehealth has become an essential means of communication between patient and health care provider. The application of telehealth to the treatment of BCa patients is evolving and increasingly research has demonstrated its feasibility and effectiveness in improving clinical, psychological and social outcomes. Two areas of telehealth that have significantly grown in the past decade and particularly since the beginning of the COVID-19 pandemic are telerehabilitation and teleoncology. There two technological systems provides opportunities at every stage of the cancer care continuum for BCa patients. We conducted a systematic literature review that examined the use of telehealth services via its various modes of delivery among BCa patients particularly in areas of screening, diagnosis, treatment modalities, as well as satisfaction among patients and health care professionals. The advantages of telehealth models of service and delivery challenges in delivery to patients in remote arears are discussed.

Attention-Deficit/Hyperactivity Disorder (ADHD) is traditionally conceptualized within a framework emphasizing deficits in attention regulation and executive function. However, emerging evidence from the fields of predictive coding and active inference offers a novel lens through which to understand ADHD not merely as a disorder of attention but as a distinctive mode of neurodevelopmental variation. This article synthesizes current research and theoretical models to propose a redefined understanding of ADHD. By integrating insights from Ryan Smith, Paul B. Badcock, and Karl J. Friston (2020), we explore the premise that individuals with ADHD exhibit unique differences in how their brains generate and update predictions about the environment, leading to the characteristic behavioral patterns observed in ADHD. We argue that ADHD involves a divergence in the brain's predictive models and its ability to minimize prediction error, impacting sensory processing, attention allocation, and motor control. This perspective illuminates the adaptive aspects of ADHD, suggesting that what are often labeled as deficits could also reflect an adaptive fit to certain environmental contexts, underscoring the role of neurodiversity in human evolution. Furthermore, we discuss the implications of this reconceptualization for clinical practice, including diagnosis, treatment, and support for individuals with ADHD, emphasizing approaches that align with their unique neurocognitive profiles. This article calls for a shift in the narrative surrounding ADHD, advocating for a model that appreciates the complexity and adaptiveness of neurodevelopmental diversity.

Computational neuroscience has undergone a significant transformation in recent years, driven by the exponential growth of neural data and advancements in data science and machine learning. While traditional theoretical models remain valuable, there is a growing emphasis on integrating data-driven approaches to develop more accurate, biologically plausible, and predictive models of neural function. This shift has led to a new equilibrium in the field, where data-driven model development, machine learning techniques, and hybrid approaches that combine data and theory are increasingly prevalent. In this article, we discuss the evolving landscape of computational neuroscience, highlighting the importance of data-driven methods and the emergence of a more integrative approach that leverages both data and theory to unlock the mysteries of the brain. We also explore the implications of this shift for future research and clinical applications, emphasizing the potential for data-driven computational neuroscience to revolutionize our understanding of neural function and pave the way for new treatments for neurological disorders.

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

The global landscape of health and disease has undergone significant transformations over the past several decades. While infectious diseases once dominated the morbidity and mortality statistics, non-communicable diseases (NCDs) have emerged as the leading cause of death and disability worldwide. This shift has profound implications for public health systems, healthcare delivery, and global health policies. This introduction aims to explore the main tendencies of disease burden, morbidity, and mortality in the world, with a special emphasis on NCDs and the Implications of Emerging AI Technologies. By examining the current trends and underlying factors, we can better understand the challenges and opportunities for improving global health outcomes.

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

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

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

This paper presents a novel game-theoretic model simulating the global artificial intelligence (AI) development race among nations. We introduce a dynamic system of equations that captures the complex interplay between a country's development level, investment strategies, market share, and the possibility of technological domination. The model incorporates key features of technological races, including returns subject to diminishing marginal utility, exponentially increasing costs, market dynamics, and strategic investment decisions based on relative market positions. Through Monte Carlo simulations, we analyze various scenarios of the AI race, focusing on the emergence of dominant players and the challenges faced by countries attempting to catch up. Our results indicate a tendency towards oligopolistic market structures, with a few countries achieving technological domination while others struggle to close the gap. The model provides insights into the potential trajectories of global AI development and the conditions under which technological leapfrogging might occur. These findings have implications for policymakers and researchers in understanding the dynamics of technological races and formulating strategies for national AI development.

Bipolar disorder (BD) is a complex mental health condition characterized by alternating periods of mania and depression. This review provides a comprehensive overview of BD, focusing on its genetics, causal hypotheses, clinical signs and evolution, potential biomarkers with an emphasis on electroencephalography (EEG), and treatment options. Genetic studies have identified several susceptibility genes and polygenic risk scores, highlighting the heritable nature of BD. Various causal hypotheses, including monoamine dysregulation, kindling, circadian rhythm disruptions, and neuroinflammation, have been proposed to explain its pathophysiology. The clinical course of BD is characterized by recurrent episodes of mania/hypomania and depression, with significant heterogeneity among individuals. EEG and other biomarkers hold promise for improving diagnosis, predicting treatment response, and elucidating the neurobiological underpinnings of BD. Current treatment options include pharmacotherapy, psychotherapy, and neuromodulation techniques, which can be tailored to individual needs based on clinical presentation and response to treatment. Future research should focus on identifying more specific biomarkers, developing novel treatments, and optimizing existing therapies to improve outcomes for individuals with BD.

The intricate relationship between genomic mutations and proteomic network topology represents a frontier in understanding cellular resilience and disease mechanisms. This study presents a novel approach to analyzing how proteomic topological structures evolve and potentially break down in response to accumulating genomic mutations, offering insights into the complex interplay between genetic alterations and protein interaction networks. We developed a computational model simulating a network of ten key proteins (A-J) over 20 discrete time points, each representing a state of increasing genomic mutation load. Our model incorporates dynamic protein interaction strengths that fluctuate in response to simulated genomic alterations and a topological representation of the protein network, allowing for visualization of structural changes. Not forgetting a quantitative measure of network integrity, correlating with the system's ability to maintain function under mutational stress. Our Key findings include: visualization of proteomic network evolution through a series of topological graphs, revealing how genomic mutations progressively alter protein interaction patterns and identification of a critical "breakage point" in the network topology, signifying a threshold where genomic mutations overwhelm the protein network's ability to maintain its functional structure. And also quantification of network properties, including interaction strengths and overall network density, demonstrating the non-linear relationship between genomic mutations and proteomic topological integrity.The observed breakage point may represent a critical threshold in disease progression, where the accumulation of genomic mutations leads to a collapse in the proteomic interaction network, potentially triggering pathological states. This methodology offers a new perspective on the genotype-phenotype relationship, viewing it through the lens of protein network topology. Our approach provides a framework for future studies to analyze how specific genomic mutations might impact proteomic structures, potentially leading to new insights in cancer research, neurodegenerative disorders, and other mutation-driven diseases. It also suggests that maintaining proteomic topological integrity could be a key factor in cellular resilience against genomic instability.

The annual budget for the United States National Park Service was roughly three billion dollars in 2016. This is distributed amongst 405 National Parks, 23 national scenic and historic trails, and 60 wild and scenic rivers. Entrance fees and concessions generate millions of dollars in income for the National Park Service; however, this metric fails to account for the total value of the National Parks. In failing to consider the value of the ecosystem services provided by the National Parks we fail to quantify and appreciate the contributions our parks make to society. This oversight allows us to continue to underfund a valuable part of our natural capital and consequently damage our supporting environment, national heritage, monetary economy, and many of our diverse cultures. We explore a simple benefits transfer valuation of the United States national parks using National Land Cover Data from 2011 and ecosystem service values determined by Costanza (et al). This produces an estimate suggesting the parks provide $84 billion / year in ecosystem service value. If the natural infrastructure 'asset' that is our national park system had a budget comparable to a piece of commercial real estate of this value, the annual budget of the National Park Service would be roughly an order of magnitude larger at something closer to $30 billion rather than $3 billion.

Frailty syndrome, a significant contributor to morbidity and mortality in older adults, has traditionally been addressed through aerobic exercises. However, recent research has highlighted the importance of anaerobic and strength training activities in mitigating frailty. This article explores the shift from aerobic to anaerobic/strength training exercises, emphasizing the benefits of the latter in improving muscle strength, balance, and overall physical function. The discussion includes the physiological mechanisms underlying this shift, the evidence supporting strength training, and practical recommendations for implementation.

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

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

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

Electric vehicles offer a means to reduce greenhouse gas emissions in passenger transport. The availability of reliable charging infrastructure is crucial for the successful uptake of electric vehicles in dense urban areas. In a pilot project in the city of Hamburg, Germany, public charging infrastructure is equipped with a reservation option providing exclusive access for local residents and businesses. The present paper combines quantitative and qualitative methods to investigate the effects of the newly introduced neighborhood charging concept. We use a methodology combining a quantitative questionnaire survey and qualitative focus group discussions as well as the analyses of charging infrastructure utilization data. Results show that inner-city charging and parking options are of key importance for (potential) users of electric vehicles. Hence, the neighborhood concept is rated very positively. Providing guaranteed charging and parking facilities are therefore likely to increase the stock of EVs. On the other hand, these could to a large extent be additional cars with consequential disadvantages. The study shows that openly accessible infrastructure is presently utilized much more intense than the exclusive option. Consequentially, the concept evaluated should be part of an integrated approach managing parking and supporting efficient concepts like car sharing.

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

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

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

Differences between the quantum mechanical and relativistic concepts of time observed in GPS satellites are accounted for by applying the equivalence principle to the transitioning electron of an atomic clock. This allows a differential equation of motion to be derived for the electron in the Minkowski space between electron shells. By applying Hamilton’s principle we transform the differential equation into a relativistically correct integral equation of motion, the time integral of a Lagrangian. This newly derived equation accounts for the abstract mathematics of the more familiar non-relativistic model by means of a physical interpretation. Abstract rotations in Hilbert space are replaced by real rotations of particle field geometries in Minkowki space that describe the electron transition and emission of a photon. Because the properties of energy are universal the same integral equations are able to be used to describe the time evolution of galaxies despite vast differences in lifetime. The comparison of gravitational and electromagnetic energy exchanges by means of radial and transverse fields leads to an alternative to the standard model that is based on a field model. It explains the observed properties of galaxies as a superposition of neutrinos localized within the horizon of a black hole with spins aligned. The particle properties of free neutrinos are accounted by means of a classical field geometry; specifically, a spin that is oriented in space with rotational inertia due to energy. A test of the standard model is proposed based on differing views for flavor oscillation.

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

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

In this study, ignition delay and burning rate are experimentally investigated in relation to the effect of pristine carbon nanotubes (CNTs), sodium dodecylbenzene sulfonate (SDBS), and diesel blends. Single droplet combustion tests were conducted in a combustion system for 21 days using CNTs at concentrations of 50 ppm and 100 ppm, that were dispersed in Colombian commercial diesel and stabilized by SDBS. Additionally, recordings of the combustion were collected, and the Shadowgraph optical method was utilized for monitoring the evolution of droplet size during combustion. The measurements were done over a four-week period. The results demonstrated that the temporal stability has a direct impact on the single droplet combustion tests because a concentration of CNTs of 100 ppm showed higher stability than those achieved by 50 ppm. Consequently, improvements were found with a concentration of 100 ppm, for instance, thermal conductivity increased by about 20%, ignition delay time by 16.2%, and burning rate by 30.5%.

Recent advances in microscopy imaging and image analysis motivate more and more institutes world-wide to establish dedicated core-facilities for bio-image analysis. To maximize the benefits research groups at these institutes gain from their core-facilities, they should be established to fit well into their respective environment. In this article, we introduce common collaborator requests and corresponding potential services core-facilities can offer. We also discuss potential conflicts of interests between the targeted missions and implementations of services to guide decision makers and core-facility founders to circumvent common pitfalls.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

A pixel-based segmentation method was demonstrated to be confounded by developmental stage in estimation of flowering of mango. Categorization of panicles into three developmental stages was undertaken with a single and a two-stage deep learning framework (YOLO and R2CNN), using either upright or rotated bounding boxes. For a validation image set and for total panicle count, the models MangoYOLO(-upright), MangoYOLO-rotated, YOLOv3-rotated, R2CNN(-rotated) and R2CNN-upright achieved: (i) RMSEs of 25.6, 16.0, 15.4, 25.8 and 32.3 panicles per tree image, (ii) Mean average precision (mAP) scores of 72.2, 69.1, 65.0, 62.5 and 70.9% and (iii) weighted F1-scores of 76.5, 76.1, 74.9, 74.0 and 82.0, respectively. For a test set of images involving a different orchard and cultivar and use of a different camera, the R2 for machine vision to human count of panicles per tree was 0.86, 0.80, 0.83, 0.81 and 0.76 for the same models, respectively. Thus, models generalised well, but with no consistent benefit from use of rotated over upright bounding boxes. While the YOLOv3-rotated model was superior in terms of total panicle count, the R2CNN-upright model was more accurate for panicle stage classification. To demonstrate practical application, panicle counts were made weekly for an orchard of 994 trees, with a peak detection routine applied to document multiple flowering events.

Optical tweezers offer a non-contact method for selecting single cells and translocating them from one microenvironment to another. We have characterized the optical tweezing of yeast S. cerevisiae and can manipulate single cells at velocities up to 0.77 mm/s using laser powers of 40 mW from a 785 nm diode laser. We have fabricated and tested three cell isolation devices; a micropipette, a PDMS chip and laser machined fused silica chip and we have isolated single bacteria, yeast and cyanobacteria cells. The most effective isolation was achieved in PDMS chip, where single yeast cells were grown and observed for 18 hours without contamination. The duration of budding in S. cerevisiae was not affected by the laser parameters used, but the time from tweezing until the first budding event began increased with increase laser energy (laser power x time). Cells tweezed using 25 mW for 1 minute were viable after isolation. We have constructed a micro-consortium of yeast cells, and a co-culture of yeast and bacteria, using optical tweezers in combination with the PDMS network of channels and isolation chambers, which may impact on both industrial biotechnology and understanding pathogen dynamics.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

We present a general theory of estimation of analysis error covariances based on cross-validation as well as a geometric interpretation of the method. In particular we use the variance of passive observation–minus-analysis residuals and show that the true analysis error variance can be estimated, without relying on the optimality assumption. This approach is used to obtain near optimal analyses that are then used to evaluate the air quality analysis error using several different methods at active and passive observation sites. We compare the estimates according to the method of Hollingsworth-Lönnberg, Desroziers et al., a new diagnostic we developed, and the perceived analysis error computed from the analysis scheme, to conclude that, as long as the analysis is near optimal, all estimates agree within a certain error margin.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

High concentrations of Na⁺ or [Co(NH₃)₆]³⁺ can induce the B to Z conformational transition in alternating (dC-dG) oligo and polynucleotides. The use of short DNA oligomers (dC-dG)₄ and (dm⁵C-dG)₄ as models can allow a thermodynamic characterization of the transition. Both form right handed double helical structures (B-DNA) in standard phosphate buffer with 115 mM Na⁺ at 25 ^oC. However, at 2.0 M Na⁺ or 200 mM [Co(NH₃)₆]³⁺, (dm⁵C-dG)₄ assumes a left handed double helical structure (Z-DNA) while the unmethylated (dC-dG)₄ analogue remains right handed under those conditions. We have previously demonstrated that the enthalpy of the transition at 25 ^oC for either inducer can be determined using isothermal titration calorimetry (ITC) [Ferreira, J. M. & Sheardy, R. D., Biophys. J. 2006, 91, 1–7]. Here, ITC is used to investigate the linkages between temperature, water activity and DNA conformation. We found that the determined enthalpy for each titration varied linearly with temperature allowing determination of the heat capacity change (DC_p) between the initial and final states. As expected, the DC_p values were dependent upon the cation (i.e. Na⁺ vs [Co(NH₃)₆]³⁺) as well as the sequence of the DNA oligomer (i. e., methylated vs unmethylated). Osmotic stress experiments were carried out to determine the gain or loss of water by the oligomer induced by the titration. The results are discussed in terms of solvent accessible surface areas, electrostatic interactions and the role of water.

Formulating a novel concept about the origin of human aging has been constrained by the dominance of a “classic theory” that was proposed nearly 70 years ago. Despite concern over the validity of some of its assumptions, the theory remained basic to our understanding of aging’s relationship with natural selection (NS). However, the logic upon which it rests was tested and subsequently challenged. The present theory describes the single cause of human aging consistent with Darwin’s evolutionary requirement for selection of adaptive traits. It describes an emergent property of the developmental program (DP), that is expressed upon completion of ontogenesis. It involves redundant expression of regulatory processes from the last stage of the DP. That mechanism subsequently preserves a non-aging, stable interval of unchanging NS during which reproductive fitness is achieved. Thereafter, loss of DP regulatory redundancy due to reliability limits, stochastic mutation accumulation, reproductive and a specific type of DNA damage, initiates aging which causes an inexorable decline in strength of NS to begin. It starts approximately a decade later than proposed in the classic theory. Since reproduction and aging are inextricably linked by the same emergent property, selection of that regulatory mechanism makes both traits products of NS.