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

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.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay demonstrated that variant c.449+5G>A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

To date, the patent foramen ovale (PFO) does not get the deserved medical attention. The PFO poses a serious threat to health and even life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to do harm. Yet at the same time by the sheer number, it discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting at the same time mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for prevention of paradoxical embolism not infrequently betters or cures migraine or exercise dyspnea, thereby improving quality of life as a collateral benefit.

Dry periods and drought are inherent natural occurrences. However, due to the increasing pressures of global warming and climate change, these events become more frequent and severe on a global scale. These phenomena can be traced with various indicators and related indices proposed by various scholars. In general, drought risk assessment is done by modelling these indicators and determining the drought occurrence probabilities. The proposed adaptation introduces the "Kaplan-Meier Estimator," a non-parametric statistic traditionally used in medical contexts to estimate survival functions from lifetime data. The study aims to repurpose this methodology to assess drought risk by treating past droughts as "events" and evaluating the Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) and map these results for a better understanding of the drought risks within larger spatial scales such as a river basin. The adapted method provides the probability of non-occurrence, with inverted results indicating the likelihood of drought occurrence. As a case study, the method is applied to SPI and SPEI values at different time steps (3, 6, and 12 months) across 27 meteorological stations in the Gediz River Basin, located in Western Turkey—a region anticipated to be profoundly affected by global climate change. The results are represented as the generated drought risk maps and curves, which indicate that (i) drought risks increase as the considered period extends, (ii) drought risks decrease as the utilized indicator timescales increase, (iii) locally plotted drought curves indicate higher drought risks as their initial slope get steeper. The method used enables the generation of historical evidence based spatially distributed drought risk maps which expose more vulnerable areas within the river basin.

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

There is a long standing ‘two times problem’ in that a satisfactory reconciliation between the time of physics and that of psychology has not been realized. A partial solution to the past/present/future phenomenon has been successfully given by the Hartle information gathering and processing system (IGUS) view. That model IGUS robot is enhanced here for the entire ‘two times problem’ to deal with not only the temporal experiences of the flow of time but also those of manifest time. A dualistic robot is proposed which has a veridical system of temporal experiences that are compatible with various spacetime cosmologies. It also has an illusory system of corresponding temporal experiences. This dualistic IGUS robot was made possible by discovering temporal experience within the brain that correspond to those of physics. The dualistic theory suggests that the veridical system, as a result of evolution, begets the illusory system to enhance behavioral adaptation. Thus, there is just one fundamental physical time which the brain does, indeed, possess and then enhances with illusory counterparts. Therefore, there should no longer be a need to reify illusory temporal experiences as modern spacetime cosmologies tend to do. Physical time already resides within human time.

International trade has been one of the most significant economic activities among countries, and its contributions towards a country’s economic growth and sustainable development have been acknowledged. In recent times, international trade and global trade networks have received preeminent attention due to the sharp growth in trade volumes and its contributions to poverty reduction and general welfare. Despite the growth in global trade volumes, there are worrying concerns about the unprecedented changes in international trade patterns and growing imbalances in trade in recent times. Whereas China’s trade volumes have more than tripled over the last decades and have maintained the largest trade surplus spot ahead of Germany, other major trade surplus countries such as Japan, the USA, etc. have become trade deficit countries with their trade volumes increasing at a much slower pace. In view of the growing imbalances in global trade volumes, we use an augmented gravity model of trade that incorporates social network measurement, the real effective exchange rate which is a measurement of international competitiveness, as well as the Linder theory of trade, to investigate the factors that determine the export performance of countries. Using data from 51 countries for 41 years, our results indicate that the GDP of both the home country and the partner country affects the home country’s exports positively. Similarly, the real effective exchange rate REER, trade openness OPEN and dummy variables BORDER, ENGLISH, and EU have produced positive and statistically significant coefficient estimates, and these are in line with our theoretical expectations.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

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.

In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for small-scale active pharmaceutical ingredient production. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling a fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and for the further growth processes. The nucleator was evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using the continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of in-situ generation of nuclei free-flowing product particles were successfully obtained. This is particularly useful during drug development when no material is available for seed addition and quickly obtain product for further characterization.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

Measurement-Device-Independent Quantum Key Distribution (MDI-QKD) is a two-photon protocol devised to eliminate eavesdropping attacks that interrogate or control the detector in realized quantum key distribution systems. In MDI-QKD, the measurements are carried out by an untrusted third party, and the measurement results are announced openly. Knowledge or control of the measurement results gives the third party no information about the secret key. Error-free implementation of the MDI-QKD protocol requires the crypto-communicating parties, Alice and Bob, to independently prepare and transmit single photons that are physically indistinguishable, with the possible exception of their polarization states. In this paper, we apply the formalism of quantum optics and Monte Carlo simulations to quantify the impact of small errors in wavelength, bandwidth, polarization and timing between Alice's photons and Bob's photons on the MDI-QKD quantum bit error rate (QBER). Using published single-photon source characteristics from two-photon interference experiments as a test case, our simulations predict that the finite tolerances of these sources contribute (4.04+/-20/N_sifted) to the QBER in an MDI-QKD implementation generating an N_sifted-bit sifted key.

Metallo-β-lactamases (MBLs) are a group of Zn(II)-dependent enzymes that pose a major threat to global health. They are linked to an increasing number of multi-drug resistant bacterial pathogens, but no clinically useful inhibitor is yet available. Since β-lactam antibiotics, which are inactivated by MBLs, constitute ~65% of all antibiotics used to treat infections, the search for clinically relevant MBL inhibitors is urgent. Here, derivatives of a 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile (1a) were synthesised and their inhibitory effects assessed against representatives of each of the three subgroups of MBLs (B1, B2, B3). Several compounds are potent inhibitors of each MBL tested, making them excellent candidates for the development of broad-spectrum drug leads. In particular, compound 5f is highly potent across the MBL subfamilies, with Ki values in the low µM range. Furthermore, this compound also dis-plays synergy in combination with antibiotics such as penicillin G, cefuroxime or meropenem. This molecule thus represents one of the most promising compounds developed yet to combat MBLs.

This article introduces existential wellbeing (EWB) as one of the most ignored but also the most important kind of wellbeing, especially for people who experience life-limiting diseases and need palliative care (Wong & Yu, 2021). This article will not only review the literature regarding the nature and practice of existential wellbeing in palliative care, but also propose a preliminary Existential Wellbeing Scale. EWB is defined as the quality-of-life characterized by living well and dying well in spite of pain, obstacles, and the shadow of death; wellbeing within the context of human suffering can only be fully understood from the perspective of existential positive psychology (EPP), dedicated to the study of sustainable wellbeing based on the foundation of transcending suffering. The basic tenets of EPP are (1) redefining positivity or wellbeing in terms of seeing and being the light in the darkness; (2) focusing on the dialectical process of navigating an adaptive balance; and (3) re-orienting one’s life attitude from egotism to self-transcendence (Wong, 2023a). More specifically, EWB depends on some combination of the following experiences: (1) Prior experience of overcoming adversity; (2) Existential intelligence (Gardner, 2020) in addressing existential concerns; (3) Existential wisdom of the soul (Wong 2022a; Wong, Ho, et al, 2023a) to achieve existential wellbeing and sustainable flourishing; (4) Spiritual wellbeing based on spiritual values such as faith, hope, and love (Wong, 2023); (5) Knowledge of meaning-focused coping (Eisenbeck et al., 2021); and (6) The new paradigm of self-transcendence (Reed & Haugan, 2021; Wong, Arslan et al., 2021; Wong, Ho et al., 2023b) to transcend and transform suffering into wellbeing and triumph.

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.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Because of the need to replace the current clinical artemisinins in artemisinin combination therapies, we are evaluating fitness of amino-artemisinins for this purpose. These include the thiomorpholine derivative artemiside obtained in one scalable synthetic step from dihydroartemisinin (DHA) and the derived sulfone artemisone. We have recently shown that artemiside undergoes facile metabolism via the sulfoxide artemisox into artemisone and thence into the unsaturated metabolite M1; DHA is not a metabolite. Artemisox and M1 are now found to be approximately equipotent with artemiside and artemisone in vitro against asexual P. falciparum (Pf) blood stage parasites (IC50 1.5 – 2.6 nM). Against Pf NF54 blood stage gametocytes, artemisox is potently active (IC50 18.9 nM early-stage, 2.7 nM late-stage). Comparative drug metabolism and pharmacokinetic (DMPK) properties were assessed via po and iv administration of artemiside, artemisox and artemisone in a murine model. Following oral administration, the composite Cmax value of artemiside plus its metabolites artemisox and artemisone formed in vivo is some 2.6-fold higher than that attained following administration of artemisone alone. Given that efficacy of short half-life rapidly-acting antimalarial drugs such as the artemisinins is associated with Cmax, it is apparent that artemiside will be more active than artemisone in vivo, due to additive effects of the metabolites. As is evident from earlier data, artemiside indeed possesses appreciably greater efficacy in vivo against murine malaria. Overall, the higher exposure levels of active drug following administration of artemiside coupled with its synthetic accessibility indicate it is much the preferred drug for incorporation into rational new artemisinin combination therapies.

We introduce the notion of p-adic magic contraction on p-adic Hilbert space. We derive p-adic Halmos dilation, p-adic Egervary N-dilation, p-adic von Neumann inequality and p-adic Sz.-Nagy dilation for p-adic magic contraction.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

In this paper, we define and investigate modified p-Leonardo, p-Leonardo-Lucas and p-Leonardo sequences as special cases of the generalized Leonardo sequence. We present Binet's formulas, generating functions, Simson formulas, and the summation formulas for these sequences. Moreover, we give some identities and matrices related with these sequences. Furthermore, we show that there are close relations between modified p-Leonardo, p-Leonardo-Lucas, p-Leonardo numbers and Fibonacci, Lucas numbers.

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.

Lichens are unique extremophilic organisms due to their phenomenal resistance to adverse environmental factors, including ultraviolet (UV) irradiation. Melanization plays a special role in the protection of lichens from UV-B stress. In present study, we analyzed the binding of melanins with the components of cell walls of mycobiont of upper cortex in the melanized lichen thalli Lobaria pulmonaria. Using scanning electron and atomic force microscopy, the morphological and nanomechanical characteristics of melanized layer of mycobiont cells were visualized. Melanization of lichen thalli led to the smoothing the surface relief and thickening mycobiont cell walls and resulted in the increase of deformation values and reduction of adhesion properties of lichen thallus. Treatment of thalli with hydrolytic enzymes, especially chitinase and lichenase, enhanced the yield of melanin from melanized thalli and release of carbohydrates, while treatment with pectinase increased the release of carbohydrates and phenols. Our results suggest that melanin by firmly binding with hyphal cell wall carbohydrates, particularly chitin and 1,4-β-glucans, can form associations, strengthen the melanized upper cortex of lichen thalli, and thereby can contribute to lichen survival under UV stress.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

Crop production in Afghanistan suffers from limited phosphorus (P) availability, which severely hinders national agriculture sustainability. This present study hypothesized that deep fertilizer placement could significantly enhance uptake of immobile P and thus tissue P accumulation and crop yield. A two-year pot experiment growing two maize (Zea mays) hybrid cultivars (Xida-789 and Xida-211) was therefore conducted to test these hypotheses under three contrasting fertilizer placement methods (broadcast, side band, and deep band). In doing so, P concentrations in both maize tissues and soils were compared at 45, 60, and 115 days after sowing (DAS) under nine combinations of nitrogen (N) and P fertilizer rates (kg ha-1: N112P45, N112P60, N112P75, N150P45, N150P60, N150P75, N187P45, N187P60, N187P75). Results have shown that deep band placement significantly increased P uptake efficiency, leading to greater P concentration and accumulation in maize tissues compared to other two fertilization methods. This improved P uptake was attributed to several factors associated with deep placement, including reduced P fixation, enhanced root access to P, and moisture availability for P uptake. Additionally, deep band placement combined with higher N application rates (N187 and N150) further enhanced plant P uptake by promoting P availability and utilization mechanisms. Deep band placement also resulted in significantly higher total soil P, Olsen-P, and P use efficiency than broadcast and side band methods, indicating a more efficient P fertilization strategy for maize that can improve growth and yield. This present study also found positive correlations between P concentration in plant organs and soil Olsen-P, highlighting the importance of adequate soil P levels for optimal plant growth. Overall, our results have showed that deep band fertilizer placement emerged as a superior strategy for enhancing P uptake efficiency, utilization, and maize productivity compared to broadcast and side band placement. This approach can potentially optimize P fertilizer utilization, improve maize growth and yield, while minimizing environmental P losses associated with broadcast applications.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

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.

We introduce the notion of p-adic equiangular lines and derive the first fundamental relation between common angle, dimension of the space and the number of lines. More precisely, we show that if {τj} n j=1 is p-adic γ-equiangular lines in Qd p , then (1) |n| 2 ≤ |d| max{|n|, γ2 }. We call Inequality (1) as the p-adic van Lint-Seidel relative bound. We believe that this complements fundamental van Lint-Seidel [Indag. Math., 1966] relative bound for equiangular lines in the p-adic case. Keywords: Equiangular lines, p-adic Hilbert space.

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.

(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about 2 million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e. distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to their numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy of using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5'-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5 bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding.

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 describe a forecast system based on the Weather Research and Forecasting (WRF) model for the prediction of high-impact weather events affecting power utilities, particularly conditions conducive to wildfires. The system was developed for Pacific Gas and Electric Corporation (PG&E) to operationally forecast conditions in Northern and Central California. It was established in 2014 and has been periodically improved. In the current configuration, WRF forecasts are routinely performed multiple times each day on a 2-km grid, and the results are used as input to wildfire fuel moisture, fire probability, and wildfire spread models. Components of the system include a stochastically perturbed ensemble; an annually updated reanalysis covering more than 30 years; and validation against PG&E’s extensive mesonet and other observing networks. We describe the development and validation of the next operational edition. Configurations tested include irrigation triggered by crop growing season and an ensemble-based approach with intelligently sub-selected Global Ensemble Forecast System (GEFS) members. The latter approach allows for enhanced uncertainty sampling in WRF forecasts and can greatly improve WRF forecasts when calibrated by observations.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

Information on the nutritive value and in vitro fermentation characteristics of native shrubs in New Zealand is scant. This is despite their potential as alternatives to exotic trees and shrubs for sup-plementary fodder, and mitigation of greenhouse gas and soil erosion on hill country sheep and beef farms. The objectives of this study were to measure the in vitro fermentation gas production, predict parameters of in vitro fermentation kinetics and to estimate in vitro fermentation of volatile fatty acids (VFA), microbial biomass (MBM) and greenhouse gases of four native shrubs (Coprosma robusta, Griselinia littoralis, Hoheria populnea and Pittosporum crassifolium) and an exotic fodder tree species, Salix schwerinii. Total in vitro gas production was higher (p<0.05) for natives than S. schwerinii. Prediction using the single pool model resulted in biologically incorrect negative in vitro total gas production from the immediately soluble fraction of the native shrubs. However, the dual pool model better predicted in vitro total gas production and was in alignment with measured in vitro fermentation end products. In vitro VFA and greenhouse gas production from fermentation of leaf and stem material were higher (p<0.05), and MBM lower (p<0.05), for native shrubs com-pared to S. schwerinii. The lower in vitro total gas production, VFA and greenhouse gases produc-tion, and higher MBM of S. schwerinii may be explained by the presence of condensed tannins (CT), although this was not measured and requires further study. In conclusion, results from this study suggests that when consumed by ruminant livestock, the browsable native shrubs can provide adequate energy and microbial protein, and that greenhouse gas production from these species is within ranges reported for typical New Zealand pastures.

Here, we report the draft genome sequence of the type strain of Ideonella azotifigens DSMZ21438^T (formally 1a22^T = JCM15503^T). Ideonella azotifigens DSMZ21438T a novel betaproteobacterial non-symbiotic nitrogen-fixing grass rhizosphere dwelling microbe. The 891,561 paired-end shotgun reads were quality filtered and decontaminated with the ATLAS pipeline, then assembled with Unicycler. The genome size is 6,257,981 bp, an N50 size of 7,849 bp, with a G+C content of 66.71%, and with 5,882 predicted protein-coding genes. I. azotifigens DSMZ21438^T represents the first member of the genus isolated from rhizosphere soil, providing a framework for further study into non-alphaproteobacterial nitrogen fixation and synthetic biology applications.

In this paper, we prove the existence of three solutions for a $p$-Kirchhoff problem with $\psi$-Hilfer fractional derivative. To be more precise, we use the variational method and we prove that the associated functional energy admits a critical point in each of the three constructed sets, these critical points are weak solutions for a studied problem. Moreover, by definition of these sets, one of these solutions is positive, the second is negative, and the third one change sign. At the end of this work, we present an example to validate our main results.

Dielectric elastomers, such as thermoplastic polyurethanes (TPU), are widely used as dielectric layer, emulation layer and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become an urgent need to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This article reports a device for in-situ measuring the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.47 to 2.94. In addition, combined Fourier-transform infrared spectroscopy, X-ray scattering technique, and atomic force microscopy have been utilized to characterize the evolution of microstructure under strain. The investigation under tensile strain reveals that a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction of the dielectric constant parallel to the electric field in TPU. Our work provides valuable experimental reference for improving the stability of flexible sensors and actuators based on dielectric elastomers.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Materials based on platinum metals with very good catalytic activity were tested in the reduction of p–nitrophenol (pNP) to p–aminophenol (pAP). The majority of presented catalytic materials are based on the adsorption of p–nitrophenol on the surface of the catalyst simultaneously with molecular hydrogen, coming from sodium borohydride in an aqueous medium, which reduces it. In the present paper, a catalytic material based on osmium dispersed in n–decanol or n–dodecanol is presented, which also works as an emulsion membrane, for the absorption of p–nitrophenol and molecular hydrogen at the n–alcohol aqueous solution interface. The hydrogenation of p–nitrophenol is carried out in a reaction and separation column in which the acid receiving phase emulsion is dispersed in the osmium nanodispersion, in n–alcohols. This emulsion circulates from the base of the column to its upper part in co-current or counter-current with the source phase consisting of p–nitrophenol and sodium borohydride. Experiments show that the circulation of counter-current phases is superior to that in co-current, and the emulsion based on n–decanol is more efficient than the one based on n–dodecanol. The increase in the pH difference between the source and receiving phases leads to the increase in the conversion of p–nitrophenol to p–aminophenol. The efficiency of separation of the reaction product in the receiving phase is lower than the conversion at the same operating time. The apparent catalytic rate constant (kapp) of the new catalytic material based on the emulsion membrane with nanodispersion of osmium nanoparticles (0.1×10−3 for n–dodecanol and 0.9×10−3 for n-decanol) is lower by an order of magnitude compared to those based on adsorption on catalysts from platinum metal group. The advantage of the tested membrane catalytic material is that it extracts p–aminophenol in the acid receiving phase. The paper proposes a mechanism of the studied reduction system.

The environment is seldom optimal for plant growth and changes in abiotic and biotic signals, including temperature, water availability, radiation and pests, induce plant responses to optimise survival. The New Zealand native plant species and close relative to Arabidopsis thaliana, Pachycladon cheesemanii grows under environmental conditions that are unsustainable for many plant species. Here we compare the responses of both plant species to different stressors (low temperature, salt and UV-B radiation) to help understand how P. cheesemanii can grow in such harsh environments. The stress transcriptomes were then determined and comparative transcriptome and network analyses discovered similar and unique responses within species between different stresses, and between the two plant species. A number of widely studied plant stress processes were highly conserved in A. thaliana and P. cheesemanii. However, in response to cold stress, Gene Ontology terms related to glycosinolate metabolism were only enriched in P. cheesemanii. Salt stress was associated with alteration of the cuticle and proline biosynthesis in A. thaliana and P. cheesemanii, respectively. Anthocyanin production may be a strategy to cope with UV-B radiation stress in P. cheesemanii only. These results allowed us to construct broad stress response pathways in A. thaliana and P. cheesemanii and identify possible novel plant strategies that help mitigate environmental stress.

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.

In this paper, we introduce the (ρ,q)-analogue of the p-adic factorial function. By utilizing some properties of (ρ,q)-numbers, we obtain several new and interesting identities and formulas. We then construct the p-adic (ρ,q)-gamma function by means of the mentioned factorial function. We investigate several properties and relationships belonging to the foregoing gamma function, some of which are given for the case p = 2. We also derive more representations of the p-adic (ρ,q)-gamma function in general case. Moreover, we consider the p-adic (ρ,q)-Euler constant derived from the derivation of p-adic (ρ,q)-gamma function at x = 1. Furthermore, we provide a limit representation of aforementioned Euler constant based on (ρ,q)-numbers. Finally, we consider (ρ,q)-extension of the p-adic beta function via the p-adic (ρ,q)-gamma function and we then investigate various formulas and identities.

Accelerating, exact, explicit and simple solutions of relativistic hydrodynamics allow for a simple and natural description of highly relativistic p+p collisions. These solutions yield a finite rapidity distribution, thus they lead to an advanced estimate of the initial energy density of high energy collisions. We show that such an advanced estimate yields an initial energy density in $\sqrt{s}=7$ and 8 TeV p+p collisions at LHC around or above the critical energy density from lattice QCD, and a corresponding initial temperature above the critical temperature from QCD and the Hagedorn temperature. This suggests that the collision energy of the LHC corresponds to a large enough initial energy density to create a non-hadronic perfect fluid even in pp collisions. %We also show, that several times the %critical energy density may have been reached in high multiplicity events, hinting at a non-hadronic medium created in %high multiplicity $\sqrt{s}=7$ and 8 TeV p+p collisions.

It is increasingly common for experiments in biology and medicine to involve large numbers of hypothesis tests. A natural graphical method for visualizing these tests is to construct a histogram from the p-values of these tests. In this article, we examine the shapes, both normal and abnormal, that these histograms can take on, as well as present simple inferential procedures that help to interpret the shapes in terms of diagnosing potential problems with the experiment. We examine potential causes of these problems in detail, and discuss potential remedies. Throughout, examples of abnormal-looking p-value histograms are provided and based on case studies involving real biological experiments.

P versus NP is considered as one of the most fundamental open problems in computer science. This consists in knowing the answer of the following question: Is P equal to NP? It was essentially mentioned in 1955 from a letter written by John Nash to the United States National Security Agency. However, a precise statement of the P versus NP problem was introduced independently by Stephen Cook and Leonid Levin. Since that date, all efforts to find a proof for this problem have failed. Another major complexity class is NP-complete. It is well-known that P is equal to NP under the assumption of the existence of a polynomial time algorithm for some NP-complete. We show that the Monotone Weighted Xor 2-satisfiability problem (MWX2SAT) is NP-complete and P at the same time. Certainly, we make a polynomial time reduction from every directed graph and positive integer k in the K-CLOSURE problem to an instance of MWX2SAT. In this way, we show that MWX2SAT is also an NP-complete problem. Moreover, we create and implement a polynomial time algorithm which decides the instances of MWX2SAT. Consequently, we prove that P = NP.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to in-healable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. Initially, a descriptive statistical treatment of PM10 concentrations took place. Furthermore, the AirQ2.2.3 software developed by the WHO was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, during the examined period PM10 concentrations present a significant decreasing trend. Also, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70% of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.

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.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

The increase in the frequency of droughts in Africa has increased the interest in crops with drought escape mechanisms like grain Amaranth (Amaranthus hypochondriacus). However, the white-seeded grain Amaranth is easily cross-pollinated by its black seeded wild relatives such as smooth pigweed (Amaranthus hybridus). A study to investigate a minimum isolation distance enough to prevent seed contamination study was carried out at three sites namely Gweru and Bindura (2020/2021 rainy season) and Shamva (2021/2022 rainy season). Smooth pigweed was planted at distances of 3 to 150 m from pure grain Amaranth. Close monitoring of phenology and measurement of meteorological conditions such as temperature, wind speed and direction were done during the anthesis period. Cross-pollination in grain Amaranth was influenced by distance from the pollen source. A maximum of 12.9 % contamination rate was measured within the 10 m radius from the pollen donor plot and a minimum outcrossing rate of 0.45 % was recorded at the widest distance of 150 m. It can be concluded that complete removal of wild relatives of grain Amaranth is important within the field at as far as 150 m from the crop.

The application of graph theory in chemical and molecular structure research far exceeds people's expectations, and it has recently grown exponentially. In the molecular graph, atoms are represented by vertices and bonded by edges. In this report, we study the silicon-carbon Si₂C₃-I[p,q] and Si₂C₃-II[p,q]. We compute several Zagreb polynomials and Redefined Zagreb indices of these silicon-carbons.

A theoretical framework for agricultural landscape pattern transitions in rural areas is proposed to fill the gap of current research with an empirical study in the Alabata farm settlement in Ogun State, Southwest Nigeria. Adopting the use of ArcGIS 10.8 and Surfer 27.3 to calculate the surface area and volume of the ground surface degraded and exposed to harsh weather conditions due to both natural and man-made anthropogenic activities causing runoffs and continuous soil erosion, which has affected agricultural production and sent some of the farmers packing and abandoning their farmlands. The farm settlement within the total sampled frame area of 1.50 km² covers a total distance of 5.11 km. The sample frame was divided into 36 frames with similar ecological terrain and soil types, which fell into either identified soil types 1 and 2. The study completed a questionnaire onsite using three major criteria. Only 23 farmers responded positively to the few questions with farmers either living on the farm or working as hired laborers on-site at the visit. The transition characteristics of agricultural landscape patterns as represented in abandoned land, and orchards are analyzed from a local perspective.

This study presents a novel Fe-CNs-P/S carbon composite material, synthesized by doping elements P and S into NH2-MIL-101 (Fe) using carbonization method. The material's application in sustainable water treatment was evaluated, focusing on its effectiveness in activating persulfate for pollutant degradation. The research thoroughly investigates the synthesis process, structural characteristics, and performance in degrading pollutants. Results indicate that Fe-CNs-P/S-5 with 50% P and S co-doping is higher than that of other samples, where the degradation rate of TC in 30min is as high as 98.11% under the optimum conditions, that is temperature at 25 ℃, 0.05 g/L of catalyst concentration, and 0.2 g/L of PMS concentration. The composite material demonstrates robust versatility and stability, maintaining high degradation efficiency across multiple organic pollutants, with no significant reduction in catalytic performance after four cycles. Furthermore, the free radical quenching experiments displays that the singlet oxygen 1O2 is the main active species. It is demonstrated that the doping of P and S play a role in the enhancement of PMS activation over the Fe-CNs-P/S catalyst. This material demonstrates remarkable efficacy in treating a range of organic contaminants and exhibits excellent reusability, presenting a promising approach for enhancing sustainability in water treatment applications.

K-band radar waves have high penetration and low attenuation coefficients. However, the wavelength of this radar wave is relatively short; thus, designing and preparing both broadband and wide-angle radar wave absorbers in this band presents considerable challenges. In this study, a resin-based K-band radar wave absorber with a biomimetic lotus leaf structure was designed and formed by UV curing. Here, microscale lotus leaf papillae and antireflection structures were prepared using a DLP 3D printer, and the contact angle between the material and water droplets was increased from 56° to 130°. In addition, the influence of the geometric parameters of the lotus leaf antireflection structure on the electromagnetic absorption performance and mechanical strength was investigated. After simulation optimization, the maximum electromagnetic loss of the lotus leaf structure 3D printed sample was −32.3 dB, and the electromagnetic loss was below −10 dB in the 20.8–26.5 GHz frequency range. When the radar incidence angle was 60°, the maximum electromagnetic loss was still less than −10 dB. The designed lotus leaf structure has a higher mechanical energy absorption per unit volume (337.22 KJ/m3) and per unit mass (0.55 KJ/Kg) than commonly used honeycomb lightweight structures during the elastic deformation stage, and we expect that the designed structure can be used as an effective lightweight material for K-band radar stealth.

The structure characterization of two new polysaccharides from Agrocybe aegerita (AA-P) and Hygrophorus olivaceoalbus (HO-P) by HPGPC, GC-MS, NMR and FT-IR indicated that AA-P was composed of Galactose, Glucose and Arabinose, in the ratio of 3:2:1. Its skeleton structure was consisted of (1→4)-Arap, (1→4,6)-Glup and (1→6)-Galp with one branched chain. The HO-P was consisted of mannose, galactose and glucose in a ratio of 1:1:2. Its skeleton structure was consisted of (1→6)-Galactose residues, (→1)-glucose residues, (1→4)-glucose residues and (1→4,6)-D-mannose residues. There were two branched chains connected to the main chain. AA-P and HO-P had the best stimulation effect on B cells and RAW264.7 cells, respectively, and could both mainly by impacting and reducing G0/G1 phase which lead to a significant proliferation of B cells, T cells and RAW264.7 cells. In addition, AA-P and HO-P could significantly promote the secretion of TNF-α from T cells, the secretion of IgA, IgD, IgE, IgG and IgM from B cells, and the secretion of TNF-α from RAW264.7 cells, but neither of them could impact the secretion of IL-1β from RAW264.7 cells.

The laser melting process (DED-LB-p) is used for the production of large components due to the high deposition rates. The large number of process parameters and printing strategies makes it difficult to optimize this process to achieve the optimal properties. Intensive post-processing is still the main obstacle to the widespread use of this process. In this work, the relationship between different printing strategies, printing strategies and process parameters on the microstructural, and tensile mechanical performance at room temperature is investigated. The porosity was measured in both printing directions. Grain orientation and size were analyzed by EBSD. A very low porosity of less than 0.4% was found in all printed samples. The samples printed with the optimized offset printing strategy show a significant improvement in tensile strength of 1000 MPa without heat treatment compared to other processing routes.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

The question does P = NP has confounded mathematicians and computer scientists alike for over 50 years and although there is an almost unanimous agreement that it in fact does not, there still is no absolute proof. In this paper, I attempt to prove to that P does not equal NP.

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.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

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.

The Mediterranean region offers good weather conditions for outdoor pig production (OPP), which is considered more environmentally friendly than intensive indoor production. However, the continuous input of food and pigs' excreta increases the soil organic matter (SOM) and phosphorus (P), increasing the risk of waterbodies eutrophication. This work aimed at evaluating in OPP areas soil P dynamics and the role of SOM on P sorption and P release. The experiment was done for two years, at an area of 2.8 ha with an animal charge of 9 adults ha-1. Georeferenced soil samples were taken at 0.20 m depth, and a soil P sorption experiment was carried out. At the end of the experiment, for the background value, the levels of SOM increased between 85–376%, and Olsen P values ranged between -82–884%. SOM levels above 2% caused a decrease in the binding energy of P sorption according to the linear model b=-15.541SOM+115.20 (p <0.01) as well as a decrease of the soil P sorption capacity Qmax=-41.272SOM+298.37 (p <0.01). To avoid the accumulation of SOM and P preventing hotspots for waterbodies eutrophication, an adequate animal charge together with soil cultivation for pig grazing can be a cost-effective practice.

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.

For Sir Ronald Fisher, it is important to consistently obtain significant p-values to support an experimental hypothesis. So, replicating experiments to obtain independent p-values is a legitimate and desirable research practice. Several simple statistics have been proposed to meta-analyze p-values, all assuming that they are genuine, i.e. observations from independent standard Uniform random variables. But, as publication bias favors the studies that report "significant" p-values, when a p&gt;0.05 is obtained for the outcome of an experiment, some researchers will "fall into temptation" and decide to replicate the experiment in the hope of getting a smaller second p-value, ideally a significant one. Consequently, if the smallest of two p-values is reported, this is a Beta(1,2) distributed "fake" p-value, not a uniformly distributed genuine p-value. This is an unacceptable scientific research practice, and moreover the detection of fake p-values is unpractical. Even when it is possible, the analytic results to accommodate their existence in combined tests are cumbersome. For an informed decision, inclusive when the presence of fake p-values in a sample of p-values to be meta-analyzed is probable, tables with simulated critical values for the usual combined testing are supplied. This will also allow comparisons to be made between several combined tests.

We prove the continuous non-Archimedean (resp. p-adic) Banach space and Hilbert space versions of non-Archimedean (resp. p-adic) Welch bounds proved by M. Krishna. We formulate continuous non-Archimedean and p-adic functional Zauner conjectures.

We prove the non-Archimedean (resp. p-adic) Banach space version of non-Archimedean (resp. p-adic) Welch bounds recently obtained by M. Krishna. More precisely, we prove following results. \begin{enumerate}[\upshape(i)] \item Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying $\left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2$ for all $ \lambda_j \in \mathbb{K}, 1\leq j \leq n$, for all $n \in \mathbb{N}.$ Let $\mathcal{X}$ be a $d$-dimensional non-Archimedean Banach space over $\mathbb{K}$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and the operator $S_{f, \tau} : \text{Sym}^m(\mathcal{X})\ni x \mapsto \sum_{j=1}^nf_j^{\otimes m}(x)\tau_j^{\otimes m} \in \text{Sym}^m(\mathcal{X})$, is diagonalizable, then \begin{align}\label{NONFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{NONFUNCTIONALWELCH}) as non-Archimedean functional Welch bounds. \item For a prime $p$, let $\mathbb{Q}_p$ be the p-adic number field. Let $\mathcal{X}$ be a $d$-dimensional p-adic Banach space over $\mathbb{Q}_p$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and there exists $b \in \mathbb{Q}_p$ such that $ \sum_{j=1}^{n}f_j^{\otimes m}(x) \tau_j^{\otimes m} =bx$ for all $ x \in \text{Sym}^m(\mathcal{X}),$ then \begin{align}\label{PADICFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{PADICFUNCTIONALWELCH}) as p-adic functional Welch bounds. \end{enumerate} We formulate non-Archimedean functional and p-adic functional Zauner conjectures.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

Oleuropein, glycosylated secoiridoid present in olive leaves is known to be an important antioxidant phenolic compound. We studied the antioxidant effect of low doses of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by the H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions, H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggests that the growth arrest and cell death of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects the myogenesis of C2C12 cells; because MyoD mRNA levels and the differentiation process are restored with 3,4-DHPEA-EA(P) after treatment. Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process in a genomic and epigenomic manner by functioning as an efficient antioxidant.

Abstract: (1) Background: Post-COVID syndrome is defined as symptoms that occur simultane-ously with or after COVID-19 infection, last for 12 weeks, and are not due to another diagnosis. Limited data are available on people’s long-term quality of life (QoL) following COVID-19 infection. The aim of this cross-sectional study was to investigate long-term QoL after COVID-19 among employees of the St. Josef Hospital in Paderborn, Germany, and to identify risk factors. (2) Methods: A monocentric, cross-sectional study was conducted using the validated and digitized WHOQOL-BREF questionnaire via Netigate® between 10/2022 and 02/2023. Data on QoL and global health status were collected in the following four domains: physical health, mental health, social relationships, and environment. (3) Results: The response rate was 73.84% (923/1250). Furthermore, 63.45% of hospital staff respondents reported at least one persistent symptom after COVID-19 infection, leading to significant differences in QoL. Pre-existing conditions, persistent symptoms, and disability after COVID-19 infection, as well as high BMI, no partnership, and low educational level were found to significantly contribute to long-term low QoL. (4) Conclusions: Obesity, lack of partnership, and a low level of education were independent risk factors for lower QoL post-COVID-19 infection in this cohort of hospital staff. Further multicenter studies are re-quired to validate the incidence and their suitability as independent risk factors for post-COVID syndrome.

Adenine nucleotide (AN) 2^nd messengers such as 3’,5’-cyclic adenosine monophosphate (cAMP) are central elements of intracellular signaling, but many details of underlying processes remain still elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca²⁺ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Consequently, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

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.

The application of graph theory in chemical and molecular structure research far exceeds people's expectations, and it has recently grown exponentially. In the molecular graph, atoms are represented by vertices and bonded by edges. Closed forms of multiplicative degree-based topological indices which are numerical parameters of the structure and determine physico-chemical properties of the concerned molecular compound. In this article, we compute and analyze many multiplicative degree-based topological indices of silicon-carbon Si₂C₃-I[p,q] and Si₂C₃-II[p,q].

This paper assessed rice farmers' perceptions of agricultural and irrigation practices through their choices. A survey was carried out among 278 rice farmers on five irrigation schemes in three agro-ecological zones of Togo, viz. the savannah region, the forest region and the coastal region. The sample of random respondents was selected from a list of rice farmers provided by the managers of these irrigated schemes. Data collected through face-to-face interviews using kobocollect software were analyzed with R 4.2 software, and the Pearson test was validated at the 5% level. The results showed that the socio-economic characteristics of the rice growers, such as access to agricultural credit, experience, non-agricultural activities, membership of a rice growers' cooperative, gender, level of education and training in growing irrigated rice, and farm labor, significantly influenced the choice of agronomic practices and irrigation management. Characteristics such as experience, training and hired farm labor enhanced paddy yields, while access to agricultural credit was unproductive. Chemical clearing combined with stump removal, tiller ploughing, transplanting and high plant density are the agricultural practices that increased paddy yields, while tiller mudding and basal mineral fertilization were inefficient. In the same way, water distribution by demand, water depth above the soil of less than 5 cm, use of water-saving technologies and farmer's knowledge of how to improve water and fertilizer use-efficiency also helped to boost paddy yields. For sustainable rice production in the context of labor shortages and the financial resources required, future studies will focus on the effectiveness of motorized mudding and agricultural credits for rice farmers. Furthermore, considering the crucial role of training in the adopting of good agricultural and irrigation practices, future research will study strategies for wide diffusion of knowledge to rice producers.

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.

Organic electrophoretic coatings have gained significant attention due to their ability to provide a uniform and controlled coating thickness, high coating adhesion, and excellent corrosion protection properties. In this work, to investigate the aging behaviors of an organic electrophoretic coating for magnesium alloys, water absorption kinetics curves of the coatings after immersion in 3.5 wt.% NaCl at 20℃ and 40℃ were measured, and parameters such as the saturated water absorption and saturation time of the free film coatings were fitted to determine the densification evolution of the organic coatings. A tensile test was used to test the tensile strength of the organic coating during service to determine the evolution of the strength and toughness of the organic coating. The evolution of wet adhesion of organic coatings with service time was tested by ASTM D4541-02. The impedance spectra of the organic coatings under the above conditions were detected by EIS, and finally, the failure behavior of the organic coatings under immersion was analyzed.

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.

Oleuropein, glycosylated secoiridoid present in the olive leaves, is known as an important antioxidant phenolic compound. We studied the antioxidant effect of low dose of oleuropein aglycone (3,4-DHPEA-EA) and oleuropein aglycone peracetylated (3,4-DHPEA-EA(P)) in murine C2C12 myocytes treated with hydrogen peroxide (H2O2). Both compounds were used at a concentration of 10 μM and were able to inhibit cell death induced by H2O2 treatment, with 3,4-DHPEA-EA(P) being more. Under our experimental conditions H2O2 efficiently induced the phosphorylated-active form of JNK and of its downstream target c-Jun. We demonstrated, by Western blot analysis, that 3,4-DHPEA-EA(P) was efficient in inhibiting the phospho-active form of JNK. This data suggest that growth arrest and cell dead of C2C12 proceeds via the JNK/c-Jun pathway. Moreover, we demonstrated that 3,4-DHPEA-EA(P) affects myogenesis of C2C12 cells; because the MyoD mRNA levels and the differentiation process are restored after treatment with 3,4-DHPEA-EA(P). Overall, the results indicate that 3,4-DHPEA-EA(P) prevents ROS-mediated degenerative process by functioning as an efficient antioxidant.

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.