In a continuation and extension of an earlier publication, the calculation of the refractivity and polarizability of organic molecules at standard conditions is presented, applying a commonly applicable computer algorithm based on an atom-group additivity method, where the molecules are broken down into their constituting atoms, these again being further characterized by their immediate neighbor atoms. The calculation of their group contributions, carried out by means of a fast Gauss–Seidel fitting calculus, used the experimental data of 5988 molecules from literature. An immediate subsequent ten-fold cross-validation test confirmed the extraordinary accuracy of the prediction of the molar refractivity, indicated by a correlation coefficient R^2 and a cross-validated analog Q^2 of 0.9997, a standard deviation σ of 0.38, a cross-validated analog S of 0.41, and a mean absolute deviation of 0.76%. The high reliability of the predictions has been exemplified with three classes of molecules: ionic liquids, silicon- and boron-containing compounds. The corresponding molecular polarizabilities have been calculated indirectly from the refractivity using the inverse Lorentz-Lorenz relation. In addition, it could be shown that there is a close relationship between the "true" volume and the refractivity of a molecule, revealing an excellent correlation coefficient R^2 of 0.9645 and a mean absolute deviation of 7.53%.

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol (N=3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol (N=1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol (N=373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K (N=2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K (N=2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules, for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R² of 0.6066.

The calculation of the vapour pressure of organic molecules at 298.15K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q2 of 0.9938 and a standard deviation  of 0.26. Based on these data, the molecules' standard Gibbs free energy G°vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization S°vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R2 of 0.9598, a standard error  of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

Assessment of the environmental impact of organic chemicals has become an important subject in chemical science. Efficient quantitative descriptors of their impact are their partition coefficients logPow, logKoa and logKaw. We present a group-additivity method that has proven its versatility for the reliable prediction of many other molecular descriptors for the calculation of the first two partition coefficients and indirectly of the third with high dependability. Based on the experimental logPow data of 3332 molecules and the experimental logKoa data of 1900 molecules at 298.15K the respective partition coefficients have been calculated with cross-validated standard deviations of only 0.42 and 0.48 log units and a goodness of fit Q^2 of 0.9599 and 0.9717, respectively, in a range of ca. 17 log units for both descriptors. The third partition coefficient logKaw has been derived from the calculated values of the former two descriptors and compared with the experimentally determined logKaw values of 1937 molecules, yielding a standard deviation of 0.67 log units and a correlation coefficient R^2 of 0.9467. This approach enabled the quick calculation of 29462 logPow, 27069 logKoa and 26220 logKaw values for the more than 37100 molecules of ChemBrain's database available to the public.

The calculation of the surface tension of ordinary organic and ionic liquids, based on a computer algorithm applying a refined group-additivity method, is presented. The refinement consists of a complete breakdown of the molecules into their constituting atoms, further distinguishing them by their immediate neighbour atoms and bond constitution. The evaluation of the atom-groups’ contributions was carried out by means of a fast Gauss-Seidel fitting method founded upon the experimental data of 1895 compounds from literature. The result has been tested for plausibility using a 10-fold cross-validation (cv) procedure. The direct calculation and the cv test proved the applicability of the present method by the close similarity and excellent goodness of fit R2 and Q2 of 0.9023 and 0.8821, respectively. The respective standard deviations are ±2.01 and ±2.16 dyn/cm. Some correlation peculiarities have been observed in a series of ordinary and ionic liquids with homologous alkyl chains which are illustrated and discussed in detail, exhibiting the limit of the present method.

The application of a commonly used computer algorithm based on the group-additivity method for the calculation of the liquid viscosity coefficient at 292.15K and the activity coefficient at infinite dilution in water at 298.15K of organic molecules is presented. The method is based on the complete breakdown of the molecules into their constituting atoms, further subdividing them by their immediate neighbourhood. A fast Gauss-Seidel fitting method using experimental data from literature is applied for the calculation of the atom groups’ contributions. Plausibility tests have been carried out on each of the calculations using a 10-fold cross-validation procedure which confirms the excellent predictive quality of the method. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the viscosity coefficient, expressed as log(η), was 0.9728 and 0.11, respectively, for 413 test molecules, and for the activity coefficient log(γ)^∞ the corresponding values were 0.9736 and 0.31, respectively, for 621 test compounds. The present approach has proven its versatility in that it enabled at once the evaluation of the liquid viscosity of normal organic compounds as well as of ionic liquids.

Background: The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System was developed as an intuitive and research-based scoring system that could be validated through beta testing and easily introduced to healthcare providers of several subspecialties who treat nasal obstruction and breathing disorders (MDs, PAs, PTs, APRNs, DDSs, and DCs). This scoring system was shown to increase the knowledge of airway function, nasal measurement parameters, and identification of proper treatment options for sleep and breathing disorders. The basis for the DAFNE score was developed from a systematic review of nasal measurement data. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were used to identify studies validating nasal function measurement parameters to create the algorithm for the DAFNE Score™. The systematic review was accomplished using the 2020 ‘Preferred Reporting Items for Systematic Reviews’ (PRISMA) guidelines. Results: Twenty studies met the inclusion criteria for systematic review. Primary outcomes measurements demonstrated reliability, repeatability and validity of the DAFNE measurement technologies, data and output. Conclusions: The data analysis and systematic review uncovered a need and framework to develop and validate a web-based software algorithm for global access to improve the understanding of data interpretation of nasal measurements from three nasal measurement technologies. DAFNE Scoring should be used as an adjunct tool in routine clinical practice and research to further understand the technology data output and how to collaborate with other healthcare providers to improve patient outcomes.

Abstract: Background: The diagnosis of nasal airway disorders relies on questionnaires, subjective data, and objective data. Interpretation of objective data obtained from measurement technology is not well understood by providers and researchers who use the equipment to test nasal airway function, justifying the need to cre-ate a new clinical tool. The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System is a web-based scoring system that allows healthcare providers (MDs, PAs, PTs, APRNs, DMDs, DDSs, SLPs, and DCs) and researchers who treat nasal obstruction and breathing disorders to make more accurate diagnostic decisions, select the appropriate treatment for individualized patient care, monitor treatment progression and outcomes, and show how to approach a collaborative care model with other healthcare professionals. The current technologies, such as 4-phase rhinomanometry, use a simple approach that relies on a measurement tracing intersecting a color-coded y-axis on a four-quadrant graph with diagnostic numeric data output de-scribing nasal airflow and resistance. This is a good source of biofeedback demonstrating abnormal nasal breathing patterns but lacks interpretation guidelines to describe the severity of disease. The more sophisti-cated proprietary DAFNE approach uses multiple parameters which include airflow restriction, speed, vol-ume, and patient characteristics to identify patients’ disease progression much more accurately. Additionally, it explains how to segregate patients into appropriate treatment options which minimizes risks and compli-cations associated with sleep and breathing disorders while improving patient outcomes. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were necessary to identify studies which determined the ranges of nasal function measurement parameters among three airway measurement technologies used in writing the DAFNE Score algorithm. The performance of DAFNE was evaluated compared to the research data and patient demographics used in previous studies. Results: By using primary outcome measurements from the literature, we were able to create a reliable, re-peatable, and validated tool to facilitate patient identification, treatment stratification, and collaboration for sleep and nasal breathing dysfunction. Subsequently, we found DAFNE could be used to identify the appro-priateness of a sleep study. Conclusions: DAFNE Scoring System has demonstrated the ability to detect high risk patients in the pediatric and adult populations susceptible of sleep apnea and breathing dysfunction needing a sleep study and treatment to improve nasal airway function and sleep. DAFNE Scoring System should be used as an adjunct tool in routine clinical practice and research to further understand the technol-ogy data output, identify patients at risk, stratify treatment options, progress, and stabilization after treatment, and how to collaborate with other healthcare providers to improve patient outcomes.

This work presents significant results obtained by the application of global optimization techniques to the design of finite, normal form games with mixed strategies. To that end, the Fuzzy ASA global optimization method is applied to several design examples of strategic games, demonstrating its effectiveness in obtaining payoff functions whose corresponding games present a previously established Nash equilibrium. In other words, the game designer becomes able to choose a convenient Nash equilibrium for a generic finite state strategic game and the proposed method computes payoff functions that will realize the desired equilibrium, making it possible for the players to reach the favorable conditions represented by the chosen equilibrium. Considering that game theory is a very significant approach for modeling interactions between competing agents, and Nash equilibrium represents a powerful solution concept, portraying situations in which joint strategies are optimal in the sense that players cannot benefit from individually modifying their current strategies provided that other players do not change their strategies as well, it is natural to infer that the proposed method may be very useful for strategists in general. In summary, it is a genuine instance of artificial inference of payoff functions after a process of global machine learning, applied to their numerical components.

Transporting water from one side of a valley or gorge to the other requires construction of an aqueduct bridge or elevated aqueduct. These features are striking elements on cultural landscapes. Unlike previous research that emphasized architecture or design and relied on documentary sources and published works, this study focuses on details of construction and first-hand observation. Roman and Medieval elevated aqueducts in Spain were subjected to rigorous field examination. Marked variations were found to exist between structures of each age. No two aqueduct bridges are alike indicating the absence of standard designs. Locally available materials were used. Construction seems to have been overseen and carried out by individuals who possessed inconsistent degrees of skill. Roman treatises discussed aqueduct bridges, but not how to build them. Many palaces were clearly designed and built by highly skilled personnel during Medieval times, but more mundane public works projects such as aqueducts appear to have been carried out by less-skilled individuals. These findings have implications regarding the construction of elevated aqueducts by Spaniards in the Americas during the 16th century.

The work proposes a new approach for evolutionary global optimization which, in simple terms, may be described as a fusion of quantum and simulated annealing. This becomes possible by using basic concepts from Homotopy Theory, conjugated to the already existing Fuzzy Adaptive Simulated Annealing paradigm and other components. In this fashion, it occurs a temporal and nonlinear superposition of the two types of annealing, provoking interesting effects in runtime, including the so-called quantum tunneling, when there is a sudden transition between attraction basins of different minima without "climbing" potential barriers. In addition, the proposal includes a generalization of the "deformation" of Hamiltonians used in quantum annealing by suggesting the use of general homotopies between the surface corresponding to the cost function under processing and another specific landscape, being this possible because of the ability of Fuzzy ASA of handling time-varying objective functions. The proposed paradigm shows that it is possible and beneficial to superpose the two types of annealing, displaying amazing numerical results and suggesting a kind of interlacing or synergic behavior - perhaps we could call it an "annealing entanglement". Finally, given the fast advances in commercial quantum annealing processors, it seems sensible to expect that an implementation of the proposed approach using such devices may occur very soon. In order to demonstrate the efficacy of the proposed algorithm, some significant and detailed examples are included in the text, so as to illustrate and clarify the presented ideas.

In this paper the problem of sampling from uniform probability distributions is approached by means of space-filling curves (SFCs), a topological concept that has found a number of important applications in recent years. Departing from the theoretical fact that they are surjective but not necessarilly injective, the investigation focused upon the structure of the distributions obtained when their domain is swept in a uniform and discrete manner, and the corresponding values used to build histograms, that are approximations of their true PDFs. This work concentrates on the real interval [0,1], and the Sierpinski space-filling curve was chosen because of its favorable computational properties. In order to validate the results, the Kullback-Leibler distance is used when comparing the obtained distributions in several levels of granularity with other already established sampling methods. In truth, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. In this fashion, sequences resulting from this sort of process are not truly random.

The Motile Aeromonad Septicemia (MAS) caused by Aeromonas species has been a serious problem in fish health management particularly in Nile tilapia (Orechromis niloticus). This study characterized an Aeromonas species isolated from farmed tilapia fingerlings in Binangonan, Rizal, Philippines, and tested for its pathogenicity in tank trials. We designated this isolate as Aeromonas veronii DFR01 (Diseased Fish Rizal) based on 16S rRNA phylogenetic analysis, 16S rRNA homology and MALDI-TOF MS identification with its biochemical profile generated from API and BiOLOG Gen III systems. A median lethal dose of A. veronii DFR01 was determined at 107 CFU/ml in tank trials and was utilized as whole cell inactivated antigen for oral vaccine development. The immunized tilapia fingerlings produced elevated levels of IgM in the blood as determined by enzyme-linked immunosorbent assay (ELISA). The increase in IgM levels is significantly higher 14 days post vaccination. The relative IgM gene expression as determined by quantitative polymerase chain reaction (qPCR) showed increasing levels after vaccination until 38 days of culture. The vaccinated fish showed 25-35% cumulative mortalities compared to the non-vaccinated-challenged group. Results showing improved relative percent survival (RPS) rate in tilapia fingerlings and induced immune response after vaccination indicate the potential use of the oral vaccine in cultured tilapia.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.

We assume that poetic devices have an implicit goal: producing an overall sound scheme that will induce the reader to associate intended and expressed meaning to the sound of the poem. Sounds may be organized into categories and assigned presumed meaning as suggested by traditional literary studies. In my work, I have extracted automatically the sound grids of all the sonnets by William Shakespeare and have combined them with the themes expressed by their contents. In a first experiment I have computed lexically and semantically based sentiment analysis obtaining an 80% of agreement. In a second experiment sentiment analysis has been substituted by Appraisal Theory thus obtaining a more fine-grained interpretation which in some cases contradicts the first one. The computation for the second poet - regarded by many critics the best of last century - includes both vowels and consonants. In addition, it combines automatic semantically and lexically based sentiment analysis with sound grids. The results produce visual maps that clearly separate poems into three clusters: negative harmony, positive harmony and disharmony where the latter instantiates the need by the poet to encompass the opposites in a desperate attempt to reconcile them.

Ensembles of Species Distribution Models (SDMs) represent the geographic ranges of pathogen vectors by combining alternative analytical approaches and merging information on vector occurrences with more extensive environmental data. Biased collection data impact SDMs, regardless of the target species but no studies have compared the differences in the distributions predicted by the ensemble models when different sampling frameworks are used for the same species. We compared Ensemble SDMs for two important Ixodid tick vectors, Amblyomma americanum and Ixodes scapularis in mainland Florida, USA, when inputs were either convenience samples of ticks, or collections obtained using the standard protocols promulgated by the U.S. Centers for Disease Control and Prevention. The Ensemble SDMs for the convenience samples and standard surveys showed only a slight agreement (Kappa = 0.060, A. americanum; 0.053, I. scapularis). Convenience sample SDMs indicated A. americanum and I. scapularis should be absent from 34.5% and 30.9% of the state where standard surveys predicted the highest likelihood of occurrence of the respective vectors. Ensemble models from standard surveys predicted 81.4% and 72.5% (A. americanum and I. scapularis) of convenience sample sites. Omission errors by standard survey SDMs, of the convenience collections, frequently were associated with adjacency to at least one SDM or errors in geocoding algorithms that failed to correctly locate convenience samples. These geocoding errors emphasize commonly overlooked needs to explicitly evaluate and improve data quality for vector survey data used in spatial models.

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.

Ammonia-nitrogen (NH3 -N) loss from agriculture decreases crop yield potential and environ-mental quality. Incorporating animal manures by chisel plowing (CP) can reduce NH3 loss but may increase erosion and compaction potential compared to lower disturbance methods. Vertical tillage (VT) is designed to reduce disturbance and conserve more crop residue than CP, however its effect on NH3 loss from manure application is largely unknown. Six trials in corn production systems were conducted to evaluate the impacts of manure incorporation method (CP, VT, or broadcast) and weather conditions on NH3-N concentrations during 2013 to 2016 at a research farm in central Wisconsin, USA. Passive samplers were used to measure NH3-N concentrations at 30-cm above the ground during the first 0 to 24 and 24 to 48 hr post-application/incorporation. Average NH3 -N concentrations for CP and VT were 44 to 86% of surface broadcast and similar for most trials, while crop residue coverage was greater for VT than CP (39 and 22% of control plots, respectively). Concentrations of NH3 -N were correlated with the amount of plot area covered by manure for the first (r = 0.56, P<0.0001) and second measurement periods (r = 0.85, P<0.0001). Results show that VT had comparable NH3-N concentration reductions to CP while conserving more crop residue.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

Purpose: The purpose of this study is to further explore how e-loyalty and E-marketing influences E-trust and satisfy the demand by offering fresh perspectives based on research as well as emphasis on the factors influencing the E-trust such as culture as a mediator. This study not only contributed theoretically but also presented practical implementations. Design/methodology/approach: Online survey was used to obtain data by focusing the Hospitality sector (Hotel Industry) and verifying the conceptual framework. Data was collected in multiple time lags. Findings: Findings showed that the E-trust influenced by E-loyalty and E-Marketing. E-trust comes from the previous experiences, e-loyalty and e-marketing. Further, some trends such as culture influenced the e-trust. Research limitation/implications: The present study is quite suitable for those Researchers interested in learning more about the effects of E-loyalty and E-marketing on user E-trust and how to mitigate cultural influences can benefit from the current study. This research also has implications for those who wish to improve market allure and survival in digital world. This study focused on the hospitality sector (Hotel Industry) in China; however, the sector and geography could be altered to suit the needs of the study's participants. Practical implications: The present study delivers the practical guidelines which are quiet suitable for understanding the formation of E-loyalty, E-marketing, and E-trust through which specific E-marketing strategy can be designed to deal with the consumer’s E-loyalty and their expectations as per their Cultural perspective. At some particular regions/countries, cultural trends are more important than practical market. This research study practically showed that how culture changed the consumer set of mind. Originality/value: The relationship between E-loyalty, E-marketing, E-trust, specifically with the cultural influence in digital market has been the subject of few research.

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Mehtods: In Trypanosoma cruzi, the causal agent of the Chagas disease, an NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that are clearly detached from the other Trypanosomatidae such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that an NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.

Low-frequency electron paramagnetic resonance (EPR) is used to extract the EPR parameter A-mid and support the approximate X-band value of g-mid for Ba(Co_yZn_1/3-yTa_2/3)O₃. Although cobalt hyperfine structure for the [+/−1/2> state is often unresolved at X-band or S-band, it is resolved in measurements on this compound. This allows for detailed analysis of the molecular orbital for the [+/−1/2> state, which is often the ground state. Moreover, this work shows that the EPR parameters for Co substituted into Zn compounds gives important insight into the properties of zinc binding sites.

The mining industry is known for the intense environmental impacts it triggers, especially when it is developed in an open environment. Pit lakes are formed in depleted deposits and may be promising opportunities for use by society as well as troubling environmental liabilities. While these artificial basins are increasing numerically in many parts of the world, they are still little known researchers in the Environmental Sciences, which makes their environmental management challenging. The main objective of this study was to evaluate the environmental quality of sediments from three deactivated open-pit gold mines, located in the Mara Rosa, Brazil, through chemical, ecotoxicological and genotoxicology analyses. For this purpose, we collected samples in the dry season boom, and subsequently, we analysed metals. In sequence, acute ecotoxicological and a genotoxicology test (comet assay) were developed with Danio rerio fishes, in concentrations of 3.12%; 6.25%; 12.5%; 25%; 50% and 100%, in addition to the control group. The results indicated that the three lakes are environmentally compromised, especially Lago Azul, whose waters and sediments are undergoing an intense process of geological conditioning. Our results did not verify the ecotoxicity of the sediments of any of the lakes, only behavioural alterations in the test organisms exposed to the concentrations of 25%, 50% and 100% of the samples obtained in the Lago Azul. About the sediments, DNA damage at Danio rerio was detected in the three investigated environments, although fishes kept in the water sampled at Lago Azul presented the most extension of DNA damages.

Households and businesses are generating unprecedented levels of electrical and electronic wastes (e-waste), fueled by modernisation and rapid obsolescence. While the challenges imposed by e-waste are similar everywhere in the world, disparities in progress to deal with it exists; with developing nations such as South Africa lagging. The increase in e-waste generation increases the need to formulate strategies to manage it. This paper presents an overview of e-waste management on a global and South African scenarios with a specific case for Cathode Ray Tube (CRT) waste management practices in South Africa. CRTs present the biggest problem for recyclers and policy makers because they contain hazardous elements such as lead and antimony. Common disposal practices have been either landfilling or incineration. The research into the South African practices with regards to CRT waste management showed that there is still more to be done to effectively manage this waste stream. This is despite clear waste regulatory frameworks in the country. However, recent developments have placed e-waste as a priority waste stream, which should lead to intensified efforts in dealing with it. Overall, these efforts should aim to maximise diversion from landfilling and to create value-addition opportunities, leading to social and environmental benefits.

This study investigated the accuracy and precision of a commercially available PNT solution that uses DGNSS-SBAS technology. Time and position data were sampled at a frequency of 20Hz during both short and long trajectory of a simulated controlled dry-land slalom, as well as during a real-world on-water slalom exercise. The primary objective was to assess the positional accuracy, availability, integrity, and service continuity of the PNT solution while evaluating its ability to differentiate between trajectories. Additionally, the simulated results were compared with an on-water real-world slalom test to validate the findings. The results of the controlled dry-land slalom test indicate that the PNT solution provided accurate measurements with an overall mean±SD Hrms of 0.20±0.02m. The integrity measures, HDOD and PDOP were found to be ideal to excellent, with values of 0.68±0.03, and 1.36±0.07, respectively. The PNT solution utilised an average of 20±1 satellites from the constellation, resulting in an accuracy of

Nollywood, based on the idea of Bollywood from India, is a series of outstanding movies that originate from Nigeria. Unfortunately, while the movies are in English, they are hard to understand for many native speakers due to the dialect of English that is spoken. In this article, we accomplish two goals: (1) create a phonetic sub-title model that is able to translate Nigerian English speech to American English and (2) use the most advanced toxicity detectors to discover how toxic the speech is. Our aim is to highlight the text in these videos which is often times ignored for lack of dialectal understanding due the fact that many people in Nigeria speak a native language like Hausa at home.

The development of biofuels and biodiesel industry specifically, has resulted in the generation of large amounts of glycerol as a surplus. The conversion of glycerol, into chemicals with indus-trial interest, through anaerobic fermentation using E. coli as a biocatalyst is an attractive alter-native to improve economic performance in the biodiesel industry, for example through the bi-otransformation of residual glycerol into ethanol. For 2019, the size of the global ethanol market was valued at $ 89.1 billion US dollar. Biodiesel can be produced from several materials like rapeseed, palm, soya, corn, palm kernel, frying oil or olive-pomace oil (OPO). The last, can be extracted from alperujo, byproduct of olive oil process. However, olive-pomace oil converting into biodiesel is not enough established to achieve a global olive-oil/biodiesel derived process with minimized waste generation. Traditionally biodiesel production process produces an equivalent of 10% by mass of glycerol as a waste or by-product. This work explores the conver-sion of residual glycerol into chemicals like ethanol and hydrogen with a focus on projecting raw material potential availability from OPO, contributing to the promotion of the use of biofu-els and biodegradable compounds.

Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction of antiviral effective concentration of drugs already approved by the FDA, such as ivermectin  (IVM), ribavirin (RIBA) and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV) and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecule with broad-spectrum antiviral activity, the ferruginol analogue 18-(phthalimid-2-yl)ferruginol (phthFGL). In general, the combination of IVM, phthFGL and Oregano EO showed the greatest synergism potential against CHIKV, ZIKV and HHV-2, obtaining a reduction in the EC99 value of up to ~8, and ~27, and ~12-fold for CHIKV, in example, respectively. The ternary combination RIBA, phthFGL, Oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, Oregano EO which indicates that IVM could contribute more to the differentiations of cell targets (for example by inhibition of host heterodimeric importin IMP α/β1 complex) than ribavirin. PhthFGL showed a good pharmacokinetic profile.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

This note applies the Logistic model approximation to determine the suitable start and end dates for the observed epidemic curves in the total number of cases for different countries. The Logistic model is presented and explicit relations for the beginning and end dates are obtained together with the total epidemic duration. Using data from Brazil, Germany, Italy, and South Korea, the extreme dates are calculated. Since the epidemic onset time is found, a fair comparison of the epidemic curve for these countries is obtained. The result does not depend on the poor statistics available in the early phase of the epidemic when the initial number of infectives is unknown. In fact, the total duration depends only on the characteristic time parameter of the LM model.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Emerging information on the interactions between the COVID-19 pandemic and global food systems has highlighted how the pandemic is accentuating food crises across Africa. Less clear, however, are how the impacts differ between farming systems. Drawing on 50 key informant interviews with farmers, village leaders and extension officers, in South Africa and Tanzania, we identify the effects of COVID-19 and associated measures to curb the spread of the disease on farming production systems, the coping mechanisms adopted by farmers, and explore their longer-term plans for adaptation. We focus on a diverse range of production systems, from small-scale mixed farming systems in Tanzania, to large-scale corporate farms in South Africa. Our findings highlight how COVID-19 restrictions have interrupted the supply chains of agricultural inputs and commodities, increasing the storage time for produce, decreasing income and purchasing power, and reducing labour availability. Farmers’ responses were heterogeneous, with highly diverse small-scale farming systems and those less engaged with international markets least affected by the associated COVID-19 measures. Large-scale farmers were most able to access capital to buffer short-term impacts, whereas smaller-scale farms shared labour, diversified to subsistence produce and sold assets. However, compounded shocks, such as recent extreme climate events, limited the available coping options, particularly for smaller-scale and emerging farmers. The study highlights the need to understand the characteristics of farm systems to better equip and support farmers, particularly in contexts of uncertainty. We propose that policy actions should focus on (i) providing temporary relief and social support and protection to financially vulnerable stakeholders, (ii) job assurance for farmworkers, and engaging an alternative workforce in farming, (iii) investing in farming infrastructure, such as storage facilities, digital communication tools, and extension services, and iv) supporting diversified agroecological farming systems.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Keywords: Lightning; Land Cover and Land Use; Topographic Effects, Itacaiúnas River Hydrographic Basin

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. The biomechanics of the cornea plays a significant role in managing patients with glaucoma. While evidence suggests a higher risk of glaucoma in patients with thin and stiffer corneas, it also affects the measurement of intraocular pressure (IOP). We reviewed the pertinent literature to help the understanding of corneal biomechanics and how it can help optimize clinical and surgical treatments and a better approach to diagnosing and managing patients with glaucoma.

We develop new theory from a broad case-study approach to explore a better understanding of what constitutes knowledge and its value as identifiable to human-machine teams. From past research, this trail of exploration will lead to these initial questions: What is the value of debate in the furtherance of knowledge? Will machines with AI be able to contribute to a debate if we humans cannot define it or determine its value sufficiently for a machine’s understanding, contribution, exploration and identification? Like humans, as teammates, machines must be able to determine with AI what constitutes the usable knowledge that contributes to a team’s success in the field (e.g., testing "knowledge" in the field, identifying new knowledge, using knowledge to develop innovation) or its failure (viz., trouble shooting; identifying weaknesses; discovering vulnerabilities, hiding by deception). It matters not whether a debate is public, private or unexpressed by an individual human or machine agent alone; we speculate in this exploration that the process advances the science of autonomous human-machine teams and assists in interpretable machine learning. We conclude with questions and a speculation: How does a human become aware or express its awareness of knowledge? Can a machine be as expressive as its human teammates? And how does a human-machine teammate become aware that its teammates possess sufficient knowledge to perform a task? We speculate that the structure of “knowledge," once found, is resistant to alternatives (i.e., it is ordered); that its functional utility is generalizable; and that its applications are multifaceted (akin to maximum entropy production). The complexity of the team is taken into consideration in our search for knowledge, which can also be used as an information metric.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

The companion paper (Rice 2020) found that the centromeric repeats of the Western European house mouse (Mus musculus domesticus) have unusual structure: i) despite moderate pairwise sequence divergence (average = 5.9%), no monomer sequence was common and many hundreds of monomer sequences were observed, ii) local sequence divergence among neighboring monomers was nearly as high as genome-wide divergence, and iii) matching sequences were rare between side-by-side monomers. Here I integrate information from many published studies to formulate a hypothesis for the evolution of this structure. Non-matching sequences of neighboring centromeric monomers is hypothesized to be selectively favored in the context of molecular drive because it reduces the rate of monomer deletion during repair of double strand breaks (DSBs) via the Single Strand Annealing (SSA) pathway. The foundation for the hypothesis is the observation that centromeres of most populations of M. m. domestics reside close to the telomere, i.e., all their chromosomes are telocentrics. This proximity influences repair of centromeric DSBs because it places at least part of the centromere within the Telomere-Affected Repair Region (TARR; a location with increased concentrations of the shelterin-complex proteins that bind telomeres, especially TRF2). Shelterin proteins increase the level of 5’→3’ end resection at DSBs and thereby: i) decrease the frequency of repair via the c- NHEJ pathway, and ii) increase the frequency of homology-directed repair (HD-repair) –including the SSA repair pathway. It is hypothesized that certain ‘trigger’ events (e.g., sub-telomeric deletions) occur in local populations that increase the influence of TARR on the centromere. This increase elevates the occurrence of SSA repair of centromeric DSBs to a level that causes centromeres to begin to gradually shrink. Chronic shrinkage leads to coevolution between centromere size and karyotype number. Once centromeres shrink to a size below a critical minimum (that causes substantially reduced kinetochore size), fusions between non- homologous telocentrics with undersized centromeres produces metacentrics with an expanded centromere size (and a corresponding ‘quantum-jump’ in kinetochore size). These metacentrics: i) accumulate to fixation because they are favored by centromere drive, and ii) are released from the influence of TARR and thereby gradually recover larger centromere size. Fission of metacentrics with enlarged centromeres can next plausibly regenerate pairs of telocentrics with sufficiently large centromeres (which recruit normal-sized kinetochores) to be favored by centromere drive and accumulate to fixation. This fixation completes a cycle of coevolution within genomes that oscillate between two extremes: i) high karyotype number (2N = 40; all telocentrics) with larger centromeres, and ii) low karyotype number (2N << 40; mainly metacentrics) with initially small centromeres that gradually increase in size.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

When animals evolve sufficient intelligence and dexterity to be able to learn to fabricate utility products (UPs) like tools, the UP's they produce become part of an induced-reproduction system that intrinsically shares many life-like traits with biological organisms, including genome-like fabrication and operation information that is physically-encoded in the animal fabricator’s neural networks. When this set of life- like traits includes a sufficient capacity for system-improving cultural evolution (UP-evolvability), the UPs become ‘para-alive’, i.e., nearly alive, or a form of non-biological UP-paralife that is equivalent to the life- status of biological viruses, plasmids, and transposons. In the companion paper I focus on the evolution of UP-paralife in the context of modern, language-capable humans and its predicted evolution going forward in time (Rice 2022). Here I look backward in time and focus on the origin of UP-paralife and its subsequent coevolution with human intelligence. I begin by determining the pathways leading to the evolution of large brains in the rare lineages of biological life that have sufficient intelligence to learn to fabricate tools –a critical first step in the evolution of UP-paralife. The simplest forms of these learning- based UPs, made by species like chimpanzees and New Caledonian crows, represent only proto-UP- paralife because they lack sufficient UP-evolvability. Expanded UP-evolvability required a combination of three attributes that enabled continuous niche-expansion of the animal fabricator via a new and advanced form of UP-mediated teamwork (TW): i) self-domestication that facilitated TW among low-related individuals, ii) learned volitional words (protolanguage) that represent ephemeral UPs that coordinate TW, and iii) learned fabrication of simple flaked-stone tools with cutting and chopping capabilities (a UP to make other structural UPs) that expanded teammate phenotypes and TW capabilities. This specific triad of attributes is synergistic because each one acts as a TW-enhancer that can gradually erode different components of the three major constraints on TW operation and expansion: too much selfishness, insufficient coordination signals, and insufficient physical traits of teammates. The increase in UP- evolvability was transformative and marked the origin of UP-paralife and the initiation of coevolution between UP-paralife (cultural evolution) and the intelligence of its hominin/human symbiont (genetic evolution) that fostered 2.5 million years of: i) continuous brain size increase and niche-expansion within the genus Homo, and ii) parallel advances in the diversity, complexity and uses of UP-paralife. This coevolution also fostered evolutionary expansion of word-based communication, and eventually language, that acted in a catalyst-like manner to facilitate the evolution of increasingly complex forms of imagination, reasoning, mentalizing, and UP-generating technology. I next focus on the evolution of creativity in the human lineage –in the form of divergent thinking and creative imagination. I conclude that the evolution of this advanced cognitive feature required a preadaptation of sufficient intelligence and is the component of human cognition that was the major causal factor generating the greatly expanded diversity and complexity of UP-paralife currently associated with modern humans. Lastly, I apply my findings to the issue of the prevalence of extraterrestrial intelligent life. I conclude that any exoplanets with detected chemical life will very rarely (e.g., probability ~10-5 for a planet closely matching Earth’s characteristics) have evolved intelligence equalling or exceeding that of humans.

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.

Centromeres are among the fastest evolving genomic regions in a diverse array of organisms. The evolutionary process driving this rapid evolution has not been unambiguously established. Here I integrate diverse information to motivate a model in which centromeres evolve rapidly because of their intrinsic molecular phenotype: they tightly bind centromeric proteins throughout the cell cycle. DNA-bound proteins have been shown to cause stalling and collapse of DNA replication forks in many genomic regions, including centromeres. Collapsed replication forks generate one-sided double strand breaks (DSBs) that are repaired by the Break-Induced Repair (BIR) pathway. Here I show why this repair is expected to generate tandem repeat structure and three key features at centromeres: i) increased nucleotide substitution mutation rates, ii) out-of- register re-initiation of replication that leads to indels spanning one or more repeat units, and iii) elevated rates of large and small transpositions within centromeres and between genomic regions. These phenotypes lead to: i) a rapid rate of nucleotide substitutions within a clade of centromeric sequences, ii) continual turnover of monomers within centromeres that fosters molecular-drift and molecular-drive, and iii) recurrent quantum leaps in centromere sequence due to the formation of mosaic monomers and new sequences transposed into non-homologous centromeres. These features are plausibly the major reason centromeres evolve so rapidly. I also speculate on how the DNA sequence of centromeres might perpetually coevolve with the protein sequence of histone CENH3 –the major epigenetic mark of centromeres.

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future coronaviruses.

Mycobacterium tuberculosis variant bovis (MBO) has one of the widest known mammalian host ranges, including humans. Despite characterization of this pathogen in the 1800s, and whole genome sequencing of a UK strain (AF2122) nearly two decades ago, the basis of its host specificity and pathogenicity remains poorly understood. Recent experimental calf infection studies show that MBO strain Ravenel (MBO Ravenel) is attenuated in the cattle host. In the present study, experimental infections were performed to define attenuation and whole genome sequencing completed to identify regions of differences (RD) and single nucleotide polymorphisms (SNPs) to explain the observed attenuation. Comparative genomic analysis of MBO Ravenel against three pathogenic strains of MBO (strains AF2122-97, 10-7428 and 95-1315) was performed. Experimental infection studies on 5 calves each, with either MBO Ravenel or 95-1315, revealed no visible lesions in all 5 animals in the Ravenel group despite robust IFN-γ responses. Out of 486 polymorphisms in the present analysis, 173 were unique to MBO Ravenel among the strains compared. A high-confidence subset of 9 unique SNPs were missense mutations in genes with annotated functions impacting 2 major MBO survival and virulence pathways: 1) Cell wall synthesis & transport [espH (A103T), mmpL8 (V888I), aftB (H484Y), eccC5 (T507M), rpfB (E263G)], and 2) Lipid metabolism & respiration [mycP1(T125I), pks5 (G455S), fadD29 (N231S), fadE29 (V360G)]. These substitutions likely contribute to the observed attenuation. Results from experimental calf infections and the functional attributions of polymorphic loci on the genome of MBO Ravenel provide new insights into the strain’s genotype-disease phenotype associations.

Here I describe an overlooked form of non-biological paralife (i.e., near-life) that has been evolving on Earth for millions of years, and is currently in the final stages of transitioning into a new form of life. Any consideration of non-biological life or paralife is complicated by the fact that there is no consensus among biologists for the definition of life. This ambiguity has caused disagreement about whether subcellular reproduction systems like viruses are a form of life, despite having genomes, mutations, heritable phenotypes and system-improving evolution. To resolve this problem, I develop a definition of life that is entirely functional and independent of any of the structural idiosyncrasies of biological life on Earth: an order-generating system controlled by internally-encoded information that perpetuates itself by functioning to counteract its entropic decay. Using this definition, subcellular transposons, plasmids, and viruses are paralife because they match the definition of life in all ways except that they induce their order-generating functioning by a living host rather through their own self-sustaining production system. Using this functional definition of life, I show that utility- products (UPs) like fabricated hand tools are part of induced-reproduction systems that have features equivalent to biological genomes, mutations, heritable phenotypes, and a process of system-improving evolution. The perceived benefit of utility-products causes them to induce their reproduction by a biological life-form (humans). For these reasons, human utility products are functionally just as close to being a form of life as subcellular transposons, plasmids, and viruses, i.e., they are Utility-Product paralife (UP-parlife). I also show that some forms of UP-paralife are currently evolving into mechanical life that is capable of both self- sustaining reproduction and system-improving evolution without outside assistance. This transition requires the development of a high level of factory and/or UP automation and artificial intelligence (AI) that is capable of complex reasoning, imagination and creativity. Finally, I consider the influence of UP-life and UP-paralife on the development of the level of structural complexity in the universe, and I briefly speculate about how these non-biological forms of life and paralife will influence the expansion of scientific knowledge about the universe.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Sexual Issues played a significant role in Judaism’s engagement with its Greco-Roman world. This paper will examine that engagement in the Hellenistic Greco-Roman era to the end of the first century CE. In part sexual issues were a key element of demarcation between Jews and the wider community, alongside such matters as circumcision, food laws, sabbath keeping and idolatry. Jewish writers, such as Philo of Alexandria, make much of the alleged sexual profligacy of their Gentile contemporaries, not least in association with wild drunken parties, same-sex relations and pederasty. Jews, including the emerging Christian movement, claimed the moral high ground. In part, however, matters of sexuality were also areas where intercultural influence is evident, such as in the shift in Jewish tradition from polygyny to monogyny, but also in the way Jewish and Christian writers adapted the suspicion and sometimes rejection of passions characteristic of some popular philosophies of their day, seeing them as allies in their moral crusade.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

Simple Summary: 200 words Will biology, including humans, benefit or harm from new developments in information such as artificial intelligence (AI). First, are biology and information different? Life is an ordered form that can reproduce, maybe with variation; and any ordered arrangement, biological or not, potentially contains information. There have been ordered forms since earth was just a ball of chemicals, and some such chemicals can reproduce. So biological and non-biological information might be components of a unified process, ‘PanEvolution’ or ‘Pan-Evo’, based on the same four operations for living or non-living entities - Innovation; Transmission and replication; Adaptation; and Movement. This can produce separate groups called ‘species’. In a current Panspeciation event, information held in biology - especially our brains - is moving into its own environment. Harm to biology might be minimal if humans and AI both behave intelligently, because vastly different environments are optimal for humans and machines containing AI. This would be the first speciation-like event involving humans for millennia, but will not be particularly hostile to humans, if humans learn how to evaluate information and cooperate, to minimize the effect of both human stupidity and artificial simulated stupidity (ASS – a failure of AI). Abstract: 200 words Many people wonder whether biology, including humans, will benefit or harm from new developments in information such as artificial intelligence (AI). Biological and non-biological information might be components of a unified process, ‘Pan-Evolution’ or ‘Pan-Evo’, based on four basic operations – Innovation, Transmission, Adaptation, and Movement. Pan-Evo contains many types of variable objects, from molecules to ecosystems. Biological innovation includes mutations and behavioural changes; non-biological innovation includes naturally-occuring physical innovations, and innovation in software. Replication is commonplace in and outside biology, including autocatalytic chemicals, and autonomous software replication. Adaptation includes biological selection, autocatalytic chemicals and ‘evolutionary programming’ used in AI. Extension of biological speciation to non-biological information, creates a concept called ‘Panspeciation’. Panevolution might benefit or harm biology, but harm might be minimal if AI and the humans behave intelligently, because humans, and the machines in which AI resides, might split to the vastly different environments that suit them. That is a possible example of panspeciation, and would be the first speciation event involving humans for thousands of years. This event will not be particularly hostile to humans, if humans learn to evaluate information and cooperate better, to minimize both human stupidity and artificial simulated stupidity (ASS – a failure of AI).

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

The North American Monsoon (NAM) in southern Arizona continues to be a topic of interest to ecologists, climatologists, and citizens as well as the triggers and characteristics of plant growth and reproduction in relation to the onset of the monsoon. In researching the onset of the North American Monsoon (NAM) in south-central Arizona relative to the phenology of Saguaro cactus (Carnegiea gigantea) and other Sonoran Desert species we identified interesting and previously unreported features in the NAM rainfall data. We present preliminary descriptive analyses of (1) monsoon onset as measured by the first day after June 1 with precipitation ≥10 mm (1990-2022), (2) first day of year warming of Sea Surface temperatures (SST) in the Gulf of California to ≥29º C measured across five open-sea blocks (mean 9452 km2), and (3) El Niño Southern Oscillation (ENSO) anomaly with a threshold of +/- 0.5º C for the Oceanic Niño Index (ONI) in the Niño 3.4 region (5ºN-5ºS, 120º-170ºW). Three patterns emerge from our analyses: (1) The day of the year of monsoon onset occurs approximately 12 days earlier in the year from 1990-2022 in south-central Arizona. (2) There appears to be a signal in the rainfall onset data very roughly approximating cycles of ENSO Oceanic Niño Index (ONI) anomalies in Niño region 3.4. (3) Gulf of California sea surface temperature (SST) and monsoon onset data support an expected link between the timing of SST warming and monsoon rainfall onset.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

Topoisomerases, common targets for anti-tumor therapeutics, are crucial enzymes for DNA replication, transcription, and many other aspects of DNA metabolism. The potential anti-cancer effect of thiosemicarbazones (TSC) and metal-TSC complexes has been demonstrated by targeting several biological processes, including DNA metabolism. Human topoisomerases were discovered among the molecular targets for TSCs, and metal-chelated TSCs specifically displayed significant inhibition. The processes by which metal-TSCs or TSCs inhibit topoisomerases are still being studied. In this brief review, we summarize the TSCs and metal-TSCs that inhibit various types of human topoisomerases.

Quasistatic nanoindentation is a proven tool that provides information on the micromechanical behavior of wood cell walls. However, quasistatic tests cannot probe the time-dependent mechanical behavior shown by wood. Nanoindentation dynamic mechanical analysis (nanoDMA) can mesaure the viscoelastic properties of wood cell walls. This research aimed to study the quasistatic and viscoelastic properties of individual radiata pine wood (Pinus radiata D. Don) cell wall layers. To minimize variability and retrieve both properties at the same locations, a load function composed of a multiload-quasistatic function followed by dynamic reference frequency segments was developed. Nanoindentations were then performed on the S2 layer and compound corner middle lamella (CCML) of unembedded latewood cells. Because the S2 layer is anisotropic, both transverse and longitudinal-tangential wood planes were studied. In the transverse plane, the average results of the quasistatic elastic moduli (Es) for the S2 layer and CCML were 15.7 GPa and 4.6 GPa, respectively. In the longitudinal-tangential plane, the E_s was 3.9 GPa. In the transverse section, the hardness (H) of the S2 layer and CCML were 331 MPa and 277 MPa, respectively, and in the longitudinal-tangential section H was 244 MPa. To acquire the viscoelastic properties, measurements were made over more than three decades of frequency. An increase of the storage modulus (E'), and a reduction of the loss modulus (E'') and loss factor (tan⁡ δ ) as frequency increased were found in both wood orientations. The quasi-static and dynamic indentations equivalent at 0.1 Hz showed similar values for Es and E’. This study contributes to our knowledge of wood cell wall micromechanical properties.

We review our theory of interdependence applied to autonomous human-machine teams, with which we have made several generalizations based on theory that have led to new discoveries, compared to social science which is struggling to break free of its validation crisis, but also has no generalizations to new discoveries with human teams, let alone to human-machine teams. In this invited article, based around the stability of a team, of our discoveries, we review the uncertainty between a team's structure and its performance, our first finding. We generalize that finding to deception, vulnerability, innovation and fittedness. From there, our next generalization is to the quantum likeness of interdependence and quantum mechanics; we move on to Shannon holes, knowledge, and conclude with the value of debate and the need for boundaries to contain debate, to reduce interference, and to protect states of interdependence. After the introduction, we extend our model in Section 2 to energy and time, and we close with a brief review of innovation and future plans.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

Equine-assisted services (EAS) are being increasingly used as complementary interventions for military veterans who have experienced trauma. However, there is limited evidence of benefit for this population and almost no literature describing desired potential outcomes and possible mechanisms of action. The aim of this article is to address these gaps by reviewing the extant literature of animal-assisted interventions in general, and equine-assisted services in particular, with the goal of providing guidance for future investigations in the field. Currently, the field is in the early stage of scientific development, but published results are promising. Interventions that enhance treatment compliance and/or outcomes could benefit this population. Preliminary results, reviewed herein, indicate that EAS interventions might benefit the military veteran population by enhancing treatment engagement and therapeutic alliance, as well as contributing to symptom reduction and resulting in various transdiagnostic benefits. It is recommended that future studies include exploration of potential beneficial outcomes discussed herein as well as investigate suggested mechanisms of action.

We report the application of a recently proposed approach for modeling biological systems using a maximum entropy production rate principle in lieu of having in vivo rate constants. The method is applied in four steps: (1) a new ODE-based optimization approach based on Marcelin’s 1910 mass action equation is used to obtain the maximum entropy distribution, (2) the predicted metabolite concentrations are compared to those generally expected from experiment using a loss function from which post-translational regulation of enzymes is inferred, (3) the system is re-optimized with the inferred regulation from which rate constants are determined from the metabolite concentrations and reaction fluxes, and finally (4) a full ODE-based, mass action simulation with rate parameters and allosteric regulation is obtained. From the last step, the power characteristics and resistance of each reaction can be determined. The method is applied to the central metabolism of Neurospora crassa and the flow of material through the three competing pathways of upper glycolysis, the non-oxidative pentose phosphate pathway, and the oxidative pentose phosphate pathway are evaluated as a function of the NADP/NADPH ratio. It is predicted that regulation of phosphofructokinase (PFK) and flow through the pentose phosphate pathway are essential for preventing an extreme level of fructose 1, 6-bisphophate accumulation. Such an extreme level of fructose 1,6-bisphophate would otherwise result in a glassy cytoplasm with limited diffusion, dramatically decreasing the entropy and energy production rate and, consequently, biological competitiveness.

The concept of ecosystem services (ESs) provides a valuable approach to communicate societies' dependence on natural ecosystems, assisting in the evaluation of measures to protect vegetation in watersheds that promote water-related ESs. Vegetation cover and land use are important factors related to the capacity of ecosystems to provide soil loss regulation and sediment retention services, which are highly relevant for sediment management in watersheds draining into reservoirs with multiple water uses. This study aims to assess the relationship between potential changes in land use and land cover and the sediment retention service provided by riparian vegetation in a watershed draining into a hydroelectric reservoir in the Brazilian Cerrado. Sediment load was selected as a physical variable that affects different water uses in reservoirs, with these uses being dependent on the quality or quantity of stored water. Scenarios were analyzed to represent landscape reconfigurations from a baseline condition in order to account for the recovery of riparian vegetation by the agricultural sector, as foreseen in the Brazilian Forest Code. To map and quantify variations in annual sediment retention, the InVEST model was used, which allows estimating an integrated response of the drainage basin to large-scale land use changes over time and space. The results show that for the drainage basin of the Corumbá IV Hydroelectric Power Plant (HPP), the recovery of riparian areas occupied by annual crops has the potential to generate greater benefits to water use in the reservoir. In the studied catchment area, 14% of the total vegetation deficit in riparian areas is occupied by crops, while 86% is occupied by pastures. This highlights the buffering role of riparian vegetation as an effective practice for managing sediment flows originating from sheet erosion in agricultural landscapes. The methodology employed in this study allows for the quantification and mapping of the effects of soil and water conservation measures in river basins. This enables the prioritization of sectoral efforts for the restoration of native vegetation, considering the highest returns in benefits perceived by water users affected by sediment input in reservoirs. The study's results reinforce the importance of conserving vegetation in riparian areas and their surroundings for sediment retention, highlighting the role of these areas as assets in providing water-related ecosystem services.

In 2020, students of Pakistan had to adapt to the online environment for the very first time. This study aims to analyze the perceptions of medical, dental, and allied health students about online education in Pakistan. A descriptive, cross-sectional study was done to assess the level of acceptance of undergraduate students. A pre-validated questionnaire regarding demographics, past-experience of e-learning, advantages disadvantages of e-learning, and general perception of students towards e-learning was distributed. Descriptive statistics were computed for demographics, Mann-Witney-U test was used to compare the differences of perceptions between pre-clinical year and clinical years students. Kruskal-Wallis test was applied to compare the results of three specialties of students. Chi-square was used to compare overall category-wise positive and negative responses of students. 1200 students participated in the study. The major advantage identified by all students was the ‘comfortable environment’ in which they studied online. The major disadvantage selected by preclinical year students was ‘anxiety due to social isolation’ and that chosen by clinical year students was ‘lack of patient interaction’. Overall, 72% of students had a negative perception of e-learning. Student-teacher training, student counselling sessions, and innovative techniques need to be introduced to enhance student engagement and reduce pandemic stress.

The rapid growth of the global wearable technologies market is projected to reach $61.30 billion by 2030 which reflects a shift towards personalised health monitoring embedded in everyday activities. This paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. Experimental results demonstrate the sensor’s capability to detect water droplets and glucose concentrations, showcasing promising applications for health monitoring. The embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

This work analyzes the severity and risk associated with Automatic Dependent Surveillance-Broadcast (ADS-B) message drop out in Detect and Avoid (DAA) function of Unmanned Aircraft System (UAS). Performance assessment of the Universal Access Transceiver (UAT) ADS-B message implies that in some cases ADS-B fails to update within a specified update interval, which is referred to as drop out in this work. ADS-B is a fundamental surveillance sensor for both class 1 and class 2 DAA systems. Message loss or drop out has been found as one of the common limitations of the ADS-B system. The key feature of this study is incorporating the update rate of real ADS-B data transmitted from the manned aircraft. The data were received from the Grand Forks International Airport, North Dakota. Monte Carlo method has been adopted to resolve encounter scenarios in the presence of drop out. The change in the alert triggered by the UAS DAA in the presence of ADS-B drop out has been investigated. Furthermore, the risk matrices are created to quantify the associated risk with drop out affected alerts. Simulation results depict that both the duration of drop out and DAA look-ahead time affect the alert-triggering function of UAS. With a small look- ahead window and longer duration of drop out, the number of warning alerts increases. Also, alerts are affected more during an overtaking encounter than that of a head-to-head encounter. A system-level analysis is also carried out to recognize the potential reasons behind the ADS-B drop out.

In this work, Gd-filled skutterudite GdxCo4Sb12 has been prepared in one-step method under high-pressure conditions in a piston-cylinder press at 3.5 GPa and moderate temperature of 800 °C. A detailed structural characterization was performed using synchrotron X-ray diffraction (SXRD), revealing a filling fraction of x = 0.066(4) and an average &lt;Gd–Sb&gt; bond length of 3.3499(3) Å. The lattice thermal expansion accessed via temperature-dependent SXRD led to a precise determination of a Debye temperature of 322(3) K, from the fitting of the unit-cell volume expansion using the second order Grüneisen approximation. Such parameter, when evaluated from the mean square displacements of Co and Sb, displayed a value of 265(2) K, meaning that the application of the harmonic Debye theory underestimates the Debye temperature in skutterudites. Regarding the Gd atom, its intrinsic disorder value is ~5× and ~25× higher than those of Co and Sb, respectively, denoting that Gd has a strong rattling behavior with an Einstein temperature of θE = 67(2) K. As a result, an ultra-low thermal conductivity of ~0.89 W/m·K at 773 K was obtained, leading to a thermoelectric efficiency zT of ~0.5 at 673 K.

Satellite communication (Satcom) is an artificial geostationary satellite that facilitates a wide range of telecommunications. Considering its quality of service (QoS) and security is crucial in government/military applications. The most challenging situation for efficient Satcom is radio frequency interference (RFI) environment. Thus, it is necessary to ensure that transmissions are incorruptible or at least sense the quality of its spectrum. This paper presents a new method to recognize received signal characteristics using a hierarchical classification in a multi-layer perceptron neural network. We consider signal modulation and the type of RFI as the characteristics of a real-time video stream transmitted in the direct broadcast satellite. Four different modulation types are investigated in this study. Moreover, the combination of the communication signal with various kinds of interference and their effects on the classification method widely have been analyzed. Besides, two robust feature selection techniques have been developed to reduce the data-set dimensional, which leads to optimizing the classification process. The results show that the Genetic Algorithm (GA) slightly outperforms Principal Component Analysis (PCA) for feature selection. Furthermore, the robustness of the proposed techniques is assessed to detect unknown signals at different signal to noise ratios.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Abstract: Chikungunya virus (CHIKV) is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates following the introduction of its major vector, Ae. albopictus. Recent cases have been documented in Europe, the Caribbean, and the Americas. CHIKV causes a disease frequently misdiagnosed as Dengue fever, with potentially life-threatening symptoms that can result in long term debilitating arthritis. There have been ongoing investigations of possible therapeutic interventions for both acute and chronic symptoms, but to date none have proven effective in reducing the severity or lasting effects of CHIKV disease. Recently, a promising vaccine candidate has received accelerated FDA approval, indicating the importance of remedies to this emerging worldwide health threat. Nonetheless, therapeutic interventions for CHIKV and other mosquito borne virus diseases are urgently needed yet remain elusive. The increasing risk of spread from endemic regions via human travel and commerce, coupled with the absence of a vaccine or FDA approved therapeutic, puts a significant proportion of the world population at risk for this disease. In this report we explore the possibility of using SOFA (Specific On/oFf Adapter) Hepatitis Delta Virus Ribozymes (HDV-Rzs) as antivirals in cells infected with CHIKV. The results we obtained suggest there could be some role in using these SOFA HDV molecules as antiviral therapies for not only CHIKV, but potentially other viruses as well.

The basis for computation in the brain is the quantum threshold of the ‘soliton’ accompanying the ion changes of the action potential and the refractory membrane at convergences. We provide a logical explanation from the action potential to a neuronal model of the coding and computation of the retina and have explained how the visual cortex operates by quantum phase processing. In the small world network parallel frequencies collide into definable patterns of distinct objects. Elsewhere we have shown how many sensory cells are mean sampled to a single neuron and that convergences of neurons are common. We have also demonstrated, using the threshold and refractory period of a quantum phase pulse, that action potentials diffract across a neural network due to the annulment of parallel collisions in phase ternary computation (PTC). Thus, PTC applied to neuron convergences results in collective mean sampled frequency and is the only mathematical solution within the constraints of brain neural networks (BNN). In the retina and other sensory areas, we discuss how this information is coded and then understood in terms of network abstracts within the lateral geniculate nucleus (LGN) and visual cortex. First by defined neural patterning within a neural network, and then in terms of contextual networks, we demonstrate that the output of frequencies from the visual cortex contain information amounting to abstract representations of objects in increasing detail. We show that nerve tracts from the LGN provide time synchronisation to the neocortex (defined as the location of the combination of connections of the visual cortex, motor cortex, auditory cortex, etc). The full image is therefore combined in the neocortex with other sensory modalities so that it receives information about the object from the eye, and all abstracts that make up the object. Spatial patterns in the visual cortex are formed from individual patterns illuminating the retina and memory is encoded by reverberatory loops of computational actions potentials (CAPs). We demonstrate that a similar process of PTC may take place in the cochlea and associated ganglia, as well as ascending information from the spinal cord, and that this function should be considered universal where convergences of neurons occur.

This article discusses an international scientific expedition to Greenland that researched geography, geodesy, botany, and glaciology of the area. The results here focus on the geodetic and glaciological results obtained with the eBee drone in the eastern part of Greenland at the front of the Knud Rasmussen glacier. From two overflights nearby the glacier front, it was possible to obtain the speed of the glacier flow and the distribution of velocities in the glacier stream. The results correlate with other measurement methods and this technology has been shown as feasible. Of course, there are more accurate and long-term options or devices for monitoring the flow of glaciers. In this case of short-term visits to the site, the possibility of using a drone is interesting and the results show not only the flow speed of the glacier, but also the shape and structure from a height of up to 200m. The second part of the paper focuses on the analysis of modern satellite images of the Knud Rasmussen glacier from Google Earth (Landsat series 1984-2016) and a comparison with historical aerial images from 1932-1933. Experimentally, historical images were processed photogrammetrically into a 3D model.

The horizontal storm structure surrounding lightning ignited wildfires is examined using Vaisala’s National Lightning Detection Network (NLDN), NCEP’s Stage IV gauge corrected radar precipitation mosaic, and the US Forest Service’s Fire Occurrence Database. Though lightning flash density peaks strongly around fire ignitions on the instantaneous 1 km scale, on the hourly 10 km scale both the lightning and precipitation peaks are typically offset from fire ignitions. Lightning density is higher and precipitation lower around ignition points compared to non-ignition points. Both regression and horizontal distributions are consistent with the claim that positive flashes have a stronger association with ignition than negative flashes, but the statistical significance remains ambiguous

The term Conjugated Linoleic Acid (CLA) refers generically to a class of positional and geometric conjugated dienoic isomers of linoleic acid. Among the isomers of linoleic acid cis9, trans11-CLA (c9, t11-CLA) and trans10, cis12-CLA (t10, c12-CLA) are found to be bio-logically active isomers, and they occur naturally in milk, dairy products and meat from ruminants. In addition, some vegetables and some sea-foods have also been reported to contain CLA. Although the CLA levels in these natural sources are insufficient to confer the essential health benefits, anti-carcinogenic or anti-cancer effects are of current interest. In the rumen, CLA is an intermediate of isomerization and the biohydrogenation process of linoleic acid to stearic acid conducted by ruminal microorganisms. In addition to rumen bacteria, some other bacteria, such as Propionibacterium, Bifidobacterium and some lactic acid bacteria (LAB) are also capable of producing CLA. In this regard, Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) has demon-strated the ability to produce CLA isomers from linoleic acid by multiple enzymatic activi-ties, including hydration, dehydration, and isomerization. L. plantarum is one of the most versatile species of LAB and the bacterium is widely used in the food industry as a micro-bial food culture. The studies reviewed in this article reveal how, in the production of some fermented foods, the use of appropriate strains of L. plantarum, as a starter or additional culture, can be considered a critical factor in the design of new CLA-enriched functional foods.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

An analysis of the performance of Automatic Dependent Surveillance-Broadcast (ADS-B) data received from the Grand Forks, North Dakota International Airport was carried out in this study. The purpose was to understand the vulnerabilities of Universal Access Transceiver (UAT) ADS-B system and recognize the effects on present and future Air Traffic Control (ATC) operation. The Federal Aviation Administration (FAA) mandated all the General Aviation aircraft to be equipped with ADS-B. The aircraft flying within United States and below the transition altitude (18,000 feet) are more likely to install an UAT ADS-B. At present unmanned aircraft systems (UAS) and autonomous air traffic control (ATC) towers are being integrated into the aviation industry and UAT ADS-B is a basic sensor for both class 1 and class 2 Detect and Avoid (DAA) systems. As a fundamental component of future surveillance system, the anomalies and vulnerabilities of ADS-B system need to be identified to enable a fully utilized airspace with enhanced situational awareness. The data received was archived in GDL-90 format, which was parsed into readable data. The anomaly detection of ADS-B messages was based on the FAA ADS-B performance assessment report. The data investigation revealed ADS-B message suffered from different anomalies including drop out; missing payload; data jump; low confident data and altitude discrepancy. Among those studied, the most severe was drop out and 32.49% of messages suffered from this anomaly. Dropout is an incident where ADS-B failed to update within a specified rate. Considering the potential danger being imposed, an in-depth analysis was carried out to characterize message dropout. Three flight parameters were selected to investigate their effect on drop out. Statistical analysis was carried out and Friedman Statistical Test identified that altitude affected drop out more than any other flight parameters.

Globally, humans are struggling with the double threat of communicable and non-communicable diseases, which are presenting new challenges to public health. Public health problems are generally studied and addressed at primary, secondary and tertiary levels. Most effective results are seen with primary interventions. Public health is becoming more aware of the importance of environment-gene interactions in the ontology of health and disease using epigenetics. Epigenetics is the study of altered gene expression without change in base pairs. Be it physical, social, behavioral, or economic factors; they all influence quality of life and health of individuals and populations. That environments are changing the human health phenotype and these changed phenotypes are heritable is of concern for the future of the human race. Knowing the causes of non-communicable human diseases using epigenetics will contribute to the development of new policies to encourage prevention using primary public health initiatives. Research and application of epigenetics shows great promise for improving population health. Continued advances in epigenetics will enhance how we understand and address the way environments are affecting the human health phenotype. For some time, health systems have been and continue to be tertiary in nature. Epigenetic changes can provide information necessary to better understand how social determinants of health can be used to build societies focused on equitable health for all people, rather than continuing to focus on treatment of diseases in the tertiary phase that leads to health disparities. Understanding mechanisms of social determinants of disease, will allow society to evolve in a health-oriented rather than a disease-oriented world. For this reason, we must enhance and apply epigenetics (physical, social, behavioral, economic) research to policy development. We will discuss how bringing social determinants together with biology can be used as new tools for public health policy.

This paper reports on the optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation systems for cattle farming in rural areas of Bangladesh. Bangladesh is a lower middle-income country with declining rates of poverty among its 160 million people due to persistent economic growth in conjunction with balanced agricultural improvements. Most of the rural households adopt a mixed farming system by cultivating crops and simultaneously rearing livestock. Among the animals raised, cattle are considered as the most valuable asset for the small/medium-scale farmers in terms of their meat and milk production. Currently, along with the major health issue, the COVID-19 pandemic is hindering the world’s economic growth and has thrust millions into unemployment; Bangladesh is also in this loop. However, natural disasters such as COVID-19 pandemic and floods, largely constrain rural smallholder cattle farmers from climbing out of their poverty. In particular, small and medium-scale cattle farmers face many issues that obstruct them from taking advantage of market opportunities and imposing a greater burden on their families and incomes. An appropriate measure can give a way to make those cattle farmers’ businesses both profitable and sustainable. Optimization of thin-film coating assisted self-sustainable off-grid hybrid power generation system for cattle farming is a new and forward-looking approach for sustainable development of the livestock sector. In this study, we design and optimize a thin-film coating assisted hybrid (photovoltaic-battery-generator) power system by using the Hybrid Optimization of Multiple Energy Resources (HOMER, Version 3.14.0) simulation tool. An analysis of the results has suggested that the off-grid hybrid system is more feasible for small and medium-scale cattle farming systems with long-term sustainability to overcome the significant challenges faced by smallholder cattle farmers in Bangladesh.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades with current research unable to fully account for this dramatic increase in prevalence. One explanation proposes that both intrinsic (e.g., genetic) and extrinsic (e.g., environmental) risk factors may be involved in the etiology of ASD. The goal of this review paper is to explore modifiable pathways for intervention in children at risk for ASD, specifically examining how early social experience may be correlated with epigenetic change in genes associated with autism. We present an innovative model which proposes that polygenic risk and social experience (via epigenetic mechanisms) may both contribute to the observed ASD phenotype. Previous research on genetic, environmental, and epigenetic mechanisms implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which is epigenetically altered by early social experience, plays a crucial role in mammalian social and cognitive development, and is associated with both genetic and epigenetic risk for ASD. Identifying intrinsic (e.g., genetic) and extrinsic (e.g., social experience) risk markers for ASD, a combination of which has not previously been examined, would transform our understanding of this condition, facilitate earlier identification of ASD risk, and guide early intervention efforts. This may have a far-reaching impact on individuals with ASD, their families, and society.

While low serotonergic activity is often associated with psychological disorders like depression, anxiety, mood and personality disorders, variations in serotonin also contribute to normal personality differences. Here we investigate the role of blood DNA methylation levels at individual CpG sites of two key serotonergic genes (serotonin receptor gene 1A, HTR1A; serotonin transporter gene, SLC6A4) in predicting personality of captive chimpanzees. We find associations between methylation at 9/48 CpG sites with four personality dimensions: Dominance, Reactivity/Dependability, Agreeableness and Openness. Directionality of effects were CpG location-dependent and confirmed a role of serotonergic methylation in reducing anxiety (Dominance) and aggression related personality (Reactivity/Undependability) while simultaneously promoting prosocial (Agreeableness) and exploratory personality (Openness). While early-life adversity has been shown to impact serotonergic methylation patterns in other species, here, atypical early social rearing experiences only had a modest impact on CpG methylation levels in this chimpanzee sample. While the precise environmental factors impacting serotonergic methylation in chimpanzees thus remain to be identified, our study suggests a role in shaping natural variation in animal personality. The results of this study offer a basis for future hypothesis driven testing in additional populations and species to better understand the impact of ecology and evolution on complex behavioral traits.

The assessment of caprock integrity for underground storage of CO2 and/or enhanced oil recovery (EOR) systems is a multiscale endeavor. Caprock sealing behavior depends on coupled processes that operate over a broad range of length and time scales including nanoscale heterogeneity in capillary and wettability properties to depositional heterogeneity that is basin wide. Larger-scale sedimentary architecture, fractures, and faults can govern properties of potential “seal-bypass” systems that may be difficult to assess. We present a multiscale investigation of geologic sealing integrity of the caprock system that overlies the Morrow B sandstone reservoir, Farnsworth Unit, Texas, USA. The Morrow B sandstone is the target geologic unit for an on-going combined CO2 storage–EOR project by the Southwest Regional Partnership on Carbon Sequestration (SWP). Methods and/or data encompass small-to-large scales, including: petrography using electron and optical microscopy; mercury porosimetry; core examinations of sedimentary architecture and fractures; well logs; a suite of geomechanical testing; and a noble gas profile through sealing lithologies into the reservoir, as preserved from fresh core. The combined data set allows a comprehensive examination of sealing quality by scale, by primary features that control sealing behavior, and an assessment of sealing behavior over geologic time.

The holistic approach of One Health, which sees human, animal, plant, and environmental health as a unit, rather than discrete parts, requires not only interdisciplinary cooperation, but standardized methods for communicating and archiving data, enabling participants to easily share what they have learned and allow others to build upon their findings.Ongoing work by NCBI and the GenomeTrakr project illustrates how open data platforms can help meet the needs of federal and state regulators, public health laboratories, departments of agriculture, and universities. Here we describe how microbial pathogen surveillance can be transformed by having an open access database along with Best Practices for contributors to follow. First, we describe the open pathogen surveillance framework, hosted on the NCBI platform. We cover the current community standards for WGS quality, provide an SOP for assessing your own sequence quality and recommend QC thresholds for all submitters to follow. We then provide an overview of NCBI data submission along with step by step details. And finally, we provide curation guidance and an SOP for keeping your public data current within the database. These Best Practices can be models for other open data projects, thereby advancing the One Health goals of Findable, Accessible, Interoperable and Re-usable (FAIR) data.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

Arguments have been made that violation of the CHSH and similar inequalities shows that reality at the quantum level must be non-local. The derivation of Bell inequality is re-examined and it is shown that violations of these inequalities merely demonstrates the existence of contextuality - they say nothing about the causal influences underlying such contextuality. It is argued that contextual systems do not possess enduring (propositional) properties, merely contingent properties. An example is presented of a classical situation, a two player co-operative game, whose random variables are consistently connected in the sense of Dzhafarov, and which is contextual, violating the CHSH inequality. In fact it also violates the Tsierl'son bound. The key is that this system is generated and its properties are disposed, not determined.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Arterial wall remodeling underlies increased pulmonary vascular resistance and right heart failure in pulmonary arterial hypertension (PAH). None of the established vasodilator drug therapies for PAH prevents or reverses established arterial wall thickening, stiffening and hypercontractility. Therefore, new approaches are needed to achieve long-acting prevention and reversal of occlusive pulmonary vascular remodeling. Several promising new drug classes are emerging from better understanding of pulmonary vascular gene expression programs. In this review potential epigenetic targets for small molecules and oligonucleotides will be described. Most are in preclinical studies aimed at modifying growth of vascular wall cells in vitro or normalizing vascular remodeling in PAH animal models. Initial success with lung-directed delivery of oligonucleotides targeting microRNAs suggests other epigenetic mechanisms might also be suitable drug targets. Those targets include DNA methylation, proteins of the chromatin remodeling machinery and long noncoding RNAs, all of which act as epigenetic regulators of vascular wall structure and function. Progress in testing small molecules and oligonucleotide-based drugs in PAH models is summarized.

The Process Algebra model has been shown to provide an alternative mathematical framework for non-relativistic quantum mechanics (NRQM). It reproduces the wave functions of non-relativistic quantum mechanics to a high degree of accuracy. It posits a fundamental level of finite, discrete events upon which the usual entities of NRQM supervene. It has been suggested that the Process Algebra model provides a true completion of NRQM, free of divergences and paradoxes, with causally local information propagation, contextuality and realism. Arguments in support of these claims have been mathematical. Missing has been an ontology of this fundamental level from which the formalism naturally emerges. In this paper it is argued that information and information flow provides this ontology. Higher level constructs such as energy, momentum, mass, spacetime, are all emergent from this fundamental level.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3–4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008-2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3–4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children’s reciprocal social and repetitive behaviors and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no association between plasma PCB concentrations and autistic behavior, However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest quartile of plasma PCB concentrations compared with the lowest quartile; for instance, an average increase of 1.1 [95%PCI: −0.5, 2.6] in the mean SRS (exposure contrast 4^th versus 1^st quartile) for PCB138 translated to an odds ratio of 1.6 [95%PCI: 1.0, 2.5]. Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Two pilot scale desalination system employing carbon modified nano-sized, zero valent metals (n-ZVM) were maufactured and tested to determine (1) the degree to which high salt water (20 to 130 mS) could be desalinated and (2) if this degree of desalination could be maintained throughout an extended treatment period. Two pilot systems were tested (referred to as Generation 1 and Generation 2) consisting of parallel lines of 4 individual reactors in series, a settling tank and an activated carbon cell at the end of each reactor line. The system capacity was 300 gal in Generation 1 and 600 gal in Generation 2 total with a total hydraulic residence time of 6 hours per reactor line (one hour per cell/tank). A slurry of n-ZVM was introduced in the first reactor on each line to yield approximately 5 to 45 grams of nano-metal per 100 L of influent salt water. The n-ZVM slurry was made from mixing tea extract with metal salts (eg ferrous sulfate, ferric chloride) to produce the carbon modified metal slurry. Initial runs focused on dosing required to achieve maximum salt removal at each of three influent salt contents, 28 mS, 44 mS and 123 mS. Once dosing was set, continuous runs (14 days, 23 days and 9 days) were carried out to (1) examine the ability of the pilot to maintain the removal efficiency over an extended period, (2) to determine the weaknesses inherent in the pilot systems, and (3) to begin to develop CAPEX and OPEX estimates for the pilot and pre-design full scale mobile desalination unit (MDU) system. Results demonstrated that maximum removal occurred with 10 g/100L of salt for the 30 mS salt solution,16 g/100 L of salt for the 40 mS influent water and 40 g/100 L for the 130 mS influent. Salt removal (expressed as Na and Cl removed) approached 78% for the 30 mS influent and 41 mS influent respectively while removal for the highest salt influent (130 mS) approached 81 %. Addition of greater amounts of carbon modified slurry than those described resulted in a pH less than 6 which inhibits continued salt removal and would require addition of calcium or magnesium oxides/hydroxides or bicarbonate solutions at the influent side to achieve greater salt removal and of course greater cost per gallon. Continuous operation over the extended time-period showed no significant decrease in salt removal with typical day to day variation of no more than 10% suggesting that this approach to desalination could rapidly provide usable water from saline aquifers, seawater or even produced water. Treatment of saline waters at 30 mS or less yields effluent water in the range necessary for irrigation use of many crops while treatment of seawater or produced water levels of salt (40 mS or higher) yields effluent in the range of 8 to 10 mS a range ideal for RO influent that would prevent the production of large volumes of brine. Pilot testing continues with seawater extracted from Puget Sound, Seattle WA and higher levels of salt to better represent produced water.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

Money launderers prefer to use financial services as the ideal medium to launder. The study aimed to provide an overview of the global AML/CFT regulations, application and how they should evolve in this dynamic environment. To gather more insight, a qualitative study was undertaken with relevant documents analysed. The main findings were: country implementation of the global AML/CFT regulations differed due to political and economic factors amongst others. While the various AML/CFT enforcements done by sampled countries were mainly cease and desist orders and monetary penalties which were publicized; and drawbacks of global AML/CFT regulations centered on application of these regulations and emerging trends. These include among other definitions of money laundering, reference to the three stage of money laundering, link between penalty and violations, technological innovations and regulations paradigm shift, cyber-attacks and data privacy. The study contributes to application and growing body of knowledge in that the advent of technology has resulted in better consumer experiences, new payment platforms, products, and services. However, these innovations have broadened emerging money laundering risks and risks in general to the financial system. Hence the need to conduct research based FATF Recommendations as risk is dynamic and not static.

The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.

The purpose of this study is to investigate the perceived benefits of community gardening. A garden colony is a collection of adjacent plots of land primarily for the purpose of gardening. The methodology of this research consists of observations, interviews, questionnaires, and focus group. As a result of this research we found that gardening is a natural and safe way to meet the lifelong demands for a healthy life. We found specific mental and physical benefits as a result of this community gardening. We encourage communities to allow people to buy plots of land away from their homes to promote this healthy activity. The garden colony provides a place for individual renewal and restoration; this urban oasis offers a way to maintain and promote lifelong healthy living, and they are an important contribution to one’s life by adding a sense of meaning and purpose.

The novel coronavirus has presented specimen-access challenges to geoscientific researchers, including paleobiologists interested in fossil ammonoids. Ammonoid sutures are geometric patterns formed by the intersection of the septa and the shell wall, and have long been a diagnostic tool for ammonite researchers for such applications as species identification, taxonomic relationships, ontogenetic change, functional and evolutionary morphology, and other aspects of ammonoid paleobiology. Without access to specimens in museum and institutional collections, researchers must rely on previously published illustrations and photographs of ammonoid sutures. However, many of these illustrations were published decades ago without an index of scale. Suture tracings lacking a scale bar are not usable by researchers interested in applying the quantitativeness of fractal geometry to the interpretation of septal complexity. Additonally, distortion of the marginal elements of suture geometry occurs due to shell curvature near the venter and umbilicus. The revised approach described here eliminates the problem of missing scale information in fractal analysis of ammonite sutures, making use of just the lateral lobe and adjacent saddle. Our revised method’s non-requirement of a full hemisuture also facilitates comparisons among sutures within an ontogenetic sequence, or sutures from multiple ammonite taxa.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

We estimate the effect of household social expenditure on vulnerability to poverty using the four latest cross-sectional waves of Ghana Living Standard Survey (GLSS) from 1999 to 2017. Using a 3-Stage Least Square and Quantile Regression, our results show a widening consumption ex-post welfare gap between the poorest households and the non-poor households in a per-cedi social expenditure. Also, we estimate the probability of an ex-ante poverty using vulnerability to expected poverty. The results, however, indicate that regardless of poverty status, household vulnerability to poverty increased consistently between 1999 and 2017, and the very poor households showing the severest vulnerability. Hence, it is concluded that social expenditure increases the chances of a poor household falling into chronic poverty a non-poor household into transient poverty in the future.

Abstract: Seismic performance and loss assessments can have widely varying degrees of uncertainty. An essential issue is whether a particular assessed seismic loss or performance result has sufficient reliability to serve as the basis for risk management decisions and actions, including whether or not a code prescribed performance level is met, or if an assessed loss level is acceptable. A method is developed measuring the reliability of performance and loss assessments for individual buildings and for portfolios. Consideration is given to how well the building investigation and corresponding evaluation process have been performed, the qualifications of the person(s) doing the assessment, the thoroughness of the evaluation, and the technical validity of the assessment procedure or model. The approach characterizes the uncertainty of each component of the assessment procedure for each building in qualitative terms. The resulting reliability measure is likely to be most useful for the cases where an entity is determining whether/or not a building has acceptable life safety performance, or if a portfolio has an acceptably low risk of seismic damage loss over a given period of time. In both cases, the reliability must either be sufficient to warrant action, or serve to indicate need for improved assessment.