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;

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Modern drugs have changed epilepsy, which affects people of all ages. But for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people <18y antiseizure medications (ASMs) need separate proof of efficacy and safety (E&S), overall called “pediatric drug development.” This has been corrected to some extent. Authorities accept that ASMs are effective in <18y as well, but they still require "extrapolation of efficacy," as if minors were another species. In our view, the real problem is less that relevant parts of pediatric clinical epilepsy research over the past decades were useless, but that this has hampered research on meaningful challenges. We do not need to show that ASMs work also before the 18th birthday. But we need to learn how to best use ASMs to prevent brain damage in young patients and optimize ASMs use considering a broader range of aspects

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.

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.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

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

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.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

Moose (Alces alces) are generalist herbivores but are important aquatic-terrestrial ecotone specialists. Aquatic macrophytes are a high-quality food source for moose during the summer, however their relative importance to moose diet is difficult to study. We used stable isotope analysis of carbon and nitrogen from moose hooves and forage (terrestrial plants, aquatic macrophytes, and arboreal lichen) to estimate the diet of moose at Isle Royale National Park, Michigan, USA, and to evaluate the isotopic variability along chronologies of serially sampled hooves. We hypothesized that aquatic macrophyte consumption and winter body condition (as measured by bone marrow fat content) would be greater at the eastern end of the island where aquatic habitats were most abundant. We were unable to evaluate spatial differences in aquatic macrophyte consumption, but overall, our mixing model results suggest that between 13% and 27% of summer moose diet was from aquatic sources. Among moose that died during winter, body condition was impaired and hoof δ¹⁵N (measured at the hairline) was higher at the western end of the island, where aquatic habitats are sparse. Although isotope chronologies preserved in hooves could significantly enhance our understanding of ungulate foraging ecology, interpretation of such chronologies is presently limited by our lack of knowledge pertaining to hoof growth rate and seasonal dynamics in relation to age and health. Significant isotope distinction among terrestrial plants, aquatic macrophytes, and arboreal lichens indicate that continued methodological advances in stable isotope ecology will lead to more precise estimates of the contribution of aquatic feeding to moose population dynamics.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

In radiotherapy, accurate deposition of energy to the targeted volume is vital to ensure effective treatment. Gel dosimeters are attractive detection systems, as tissue substitutes with potential to yield three-dimensional dose distributions. Radio-fluorogenesis is creation fluorescent chemical products in response to energy deposition from high-energy radiation. This report shares studies of a radio-fluorogenic gel dosimetry system, gelatin with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission, following UV to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated for this system. The response of the system was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship with a dose-rate dependency and no energy or type dependencies. This report supports the utility of gelatin-C3CA for phantom studies of radio-fluorogenic processes.

Brain magnetic resonance imaging (MRI) offers a unique lens to study neuroanatomic support of human neurocognition and intelligence. A core mystery is the MRI explanation of individual differences in neurocognition and intelligence. The past four decades have seen great advancement in studying this century-long mystery, but the sample size and population-level studies limit the explanation at the individual level. The recent rise of big data and artificial intelligence offers novel opportunities. Yet, data sources, harmonization, study design, and interpretation need to be carefully considered. This review aims to summarize past work, discuss rising opportunities and challenges, and facilitate further investigations on machine intelligence inferring human intelligence.

Tropical forest and savanna biomes are pivotal in the functioning of the Earth system. Tropical forests are one of the largest terrestrial biosphere carbon pools, whereas savannas exchange carbon between the biosphere and atmosphere via frequent and extensive landscape fires. Both are biodiverse and under increasing threat due to land clearing and anthropogenic climate change. Reliable mapping of tropical forest and savanna is essential to provide understanding of how anthropogenic impacts are affecting the extent of these biomes. Using Google Maps satellite imagery, we manually classified 24,239 random points as forest, savanna, or anthropogenic landscapes within the tropics. Because fire and climate are correlated, we developed separate geospatial models to rank the importance of climate, topography, and human influence on vegetation present. This modelling confirmed that those areas with more fires had lower probabilities of tropical forest, that forest was most likely in areas with high mean annual rainfall with little seasonal variation in precipitation, and that anthropogenic factors disrupt this environmental predictability. We found there were environments where tropical forest and savanna were equally probable are geographically restricted. These relationships suggest that future drier climates projected under anthropogenic climate change, combined with clearing and burning that have reduced tropical forest extent to a subset of its theoretical distribution, will lead to irreversible loss of tropical forests. Our modelling provides global mapping that can be used track further changes to distribution of rainforests.

Relativistic atomic and molecular structure calculations start from very different premises to quantum electrodynamics (QED). QED predicts radiative corrections that can nly be approximated crudely in today's atomic structure programs. This paper describes rigorous simple algorithms for including accurate vacuum polarization and self-energy corrections in the GRASP programs.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Fire risk can be defined as the probability that a fire will spread. Reliable monitoring of fire risk is essential for effective landscape management. Compilation of fire risk records enable identification of seasonal and inter-annual patterns and provide a baseline to evaluate the trajectories in response to climate change. Typically, fire risk is estimated from meteorological data. In regions with sparse meteorological station coverage environmental proxies provide important additional data stream for estimating past and current fire risk. Here we use a 60-year record of daily flows from two rivers (Franklin and Davey) in the remote Tasmanian Wilderness World Heritage Area (TWWHA) to characterize seasonal patterns in fire risk in temperate Eucalyptus and rainforests. We show that river flows are strongly related to landscape soil moisture estimates derived from down-scaled re-analysis of meteorological data available since 1990. To identify river flow thresholds where forests are likely to burn, we relate river flows to known forest fires that have occurred in the previously defined ecohydrological domains that surround the Franklin and Davey catchments. Our analysis shows that the fire season in the TWWHA is centered on February (70% of all years below the median threshold), with shoulders on December-January and March. Since 1954 forest fire can occur in at least one month for all but four summers in the ecohydrological domain that includes the Franklin catchment, and since 1964 fire fires could occur in at least one month in every summer in the ecohydrological domain that includes the Davey catchment. Our analysis shows that mangers can use river flows as a simple index that provide a landscape-scale forest fire risk in the TWWHA.

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

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

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.

In many countries, governments have implemented non-pharmaceutical techniques to limit COVID-19 transmission. Restricting human mobility is one of the most common interventions, including lockdown, travel restrictions, working from home, etc. However, due to the strong transmission ability of the virus variants, further rounds of interventions, including a strict lockdown, are not considered as effective as expected. The paper aims to understand how the lockdown policy and pandemics changed human mobility in the real scenario. Here we focus on understanding the mobility changes caused by compliance with restrictions and risk perceptions, using the mobility index from the Google report during three strict lockdown periods in Leeds, the largest city in the county of West Yorkshire, England from March 2020 to March 2021. The research proposed the time-varying z-scores and Principal Component Analysis (PCA) to simulate how local people dynamically process and perceive health risk based on multi-dimensional daily COVID-19 reports first. Further modelling highlights exponentially increasing policy non-compliance through the duration of lockdown, probably attributable to factors such as mental anxiety and economic pressures. Finally, the proposed nonlinear regression model examines the mobility changes caused by the population's dynamic risk perceptions and lockdown duration. The case study at Leeds fits data well and shows that the third lockdown policy took effect much slower than the first. At the same time, the negative impact of the epidemic on population mobility decayed 40% in the third lockdown period in contrast with the first lockdown. The risk perception estimation methods could reflect that the local population became increasingly accustomed to the COVID-19 situation, and local people rationally evaluated the risks of COVID in the third lockdown period. The results prove that simulated risk perceptions and policy decay could explain urban mobility behaviour during the mobility well during lockdown periods, which could be a reference for future decision-making processes.

A neglected dimension of the fire regime concept is fire patchiness. Habitat mosaics that emerge from the grain of burned and unburned patches (pyrodiversity) are critical for the persistence of a diverse range of plant and animal species. This issue is of particular importance in frequently burned tropical Eucalyptus savannas, where coarse fire mosaics have been hypothesized to have caused the recent drastic population declines of small mammals. Satellites routinely used for fire mapping in these systems are unable to accurately map fine-grained fire mosaics, frustrating our ability to determine whether declines in biodiversity are associated with local pyrodiversity. To advance this problem, we have developed a novel method (we call ‘double-differenced dNBR’) that combines the infrequent (c. bi-monthly) detailed spatial resolution Landsat with daily coarse scale coverage of MODIS and VIIRS to map pyrodiversity in the savannas of Kakadu National Park. We used seasonal Landsat mosaics and differenced Normalized Burn Ratio (dNBR) to define burned areas, with a modification to dNBR that subtracts long-term average dNBR to increase contrast. Our results show this approach is effective in mapping fine-scale fire mosaics in the homogenous lowland savannas, although inappropriate for nearby heterogenous landscapes. Comparison of this methods to other fire metrics (e.g., area burned, seasonality) based on Landsat and MODIS imagery suggest this method is likely accurate and better at quantifying fine-scale patchiness of fire, albeit it demands detailed field validation.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

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.

Food security (FS) during infancy is associated with lifelong outcomes. New Zealand is a developed economy that reports poor childhood nutrition-related health statistics, particularly among minority children, yet has no measure of FS applicable to infancy. The objective was to develop a FS index for New Zealand infants and examine its association with demographic covariates and health outcomes. Within a large (n=6853) nationally representative cohort, variables describing infant food consumption, breastfeeding, and maternal food-related coping methods were collected from mothers during late infancy. A FS index was derived using confirmatory factor analysis. Associations were assessed by logistic regressions and described using odds ratios (OR) and ≥95% confidence intervals (CI). 15% of the cohort was highly FS, 43% tenuously food insecure (FIS), and 16% highly food insecure (FIS). Infants from minority ethnic groups had lower odds of being food secure, as did those born to the youngest mothers, mothers who smoked, or lived in low-income households. FIS infants had higher odds of morbidity. Interventions to improve infant FS should focus on improving dietary quality, and give particular consideration to minority infants. We identified that FIS shows wide ethnic and socioeconomic inequity, and is associated with poorer health. The most important driving factors of FIS included poor quality weaning diets, and poverty and its proxies. Any interventions to improve infant FS should focus on increasing fruit and vegetable consumption to recommended intake levels, and give particular consideration to minority infants.

Studies into the cognitive effects of alcohol have been mixed. They also present methodological challenges, often relying on self-report of alcohol consumption leading to hangover. The current study used BAC (obtained via breathalyser) and self-reported drinking behavior during a night out and related these to hangover severity and cognitive function measured over the internet in the same subjects the following morning. Volunteers were breathalysed and interviewed as they left a central entertainment district of an Australian state capital. They were provided with a unique identifier and, the following morning, logged on to a website. This included an online version of the Alcohol Hangover Severity Scale (AHSS), and number and type of drinks consumed the previous night and the eTMT-B - a validated, online analogue of the Trail Making Test B of executive function and working memory. Hangover severity was significantly correlated with one measure only, namely the previous night’s BAC (r = .228, p = .019). Completion time on the eTMT-B was significantly correlated with hangover severity ( r = .245, p = .012), previous night’s BAC (r = .197, p = .041) and time spent dinking (r = .376, p < .001). These findings confirm that alcohol hangover negatively affects cognitive functioning and that poorer working memory and executive performance correlates with hangover severity. The results also support the utility of using online measures in hangover research.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+)ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.

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.

Electrical microgrids are deemed to be the future of modern power systems. Microgrids are sophisticated, decentralized, and self-sufficient small-scale power systems consisting of various resources ranging from wind turbines, solar photovoltaics, electric vehicles, smart energy storage, and complex communication infrastructure. However, renewable energy sources such as solar photovoltaics and wind-based generators are highly intermittent, and if not appropriately planned, they can compromise the stability of the grid. Formal methods can define and analyze the functionality and behavior of any system and show if the system design is correct before the actual system is implemented. Although formal methods have been around for many years, it is surprising that little to none are utilized in the design of safety-critical electrical power systems. Currently, in modeling microgrids, few to no attempts of formalization are being used to improve the design reliability and reduce system operating costs and time. This work demonstrates how complex systems such as microgrids can be modeled elegantly using a formal specification method. In this work, the Z state-based formal specification language (Z-Method) is used to model and verify microgrid designs. In this work, 3-interconnected microgrid systems with a high penetration level of solar and wind-based renewable energy sources with plugin hybrid electric vehicles (PHEV) as battery energy storage systems (BESS) are modeled using the Z-method. To the best of authors, the knowledge presented formal method is one of the first reported attempts in modeling microgrid communities using Software Engineering formalism.

This study aimed to determine whether camelina oil is safe for use in canine diets, using canola oil and flax oil as controls as they are similar and generally regarded as safe (GRAS) for canine diets. Thirty privately-owned adult dogs of various breeds (17 females; 13 males), with an average age of 7.2 ± 3.1 years (mean ± SD) and body weight (BW) of 27.4 ± 14.0 were used. After a 4-week wash-in period using sunflower oil and kibble, dogs were blocked by breed, age, and size, and randomly allocated to one of three treatment oils (camelina (CAM), flax (FLX), or canola (OLA)) at a level of 8.2 g oil/100g total dietary intake. Body condition score (BCS), BW, food intake (FI), and hematological and select biochemical parameters were measured at various timepoints over a 16-week feeding period. All data were analyzed with ANOVA using PROC GLIMMIX of SAS. No biologically significant differences were seen between treatment groups for BW, BCS, FI, hematological and biochemical results. Statistically significant differences noted among some serum biochemical results were considered small and due to normal biological variation. These results support a conclusion that camelina oil is safe for use in canine nutrition.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

Continuous-variable quantum key distribution (CV-QKD) shows potential for the rapid development of an information-theoretic secure global communications network; however, the complexities of CV-QKD implementation remain a restrictive factor. Machine learning (ML) has recently shown promise in alleviating these complexities. ML has been applied to almost every stage of CV-QKD protocols, including ML-assisted phase error estimation, excess noise estimation, state discrimination, parameter estimation and optimization, key sifting, information reconciliation, and key rate estimation. This survey provides a comprehensive analysis of the current literature on ML-assisted CV-QKD. In addition, the survey compares the ML algorithms assisting CV-QKD with the traditional algorithms they aim to augment, as well as providing recommendations for future directions for ML-assisted CV-QKD research.

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.

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.

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.

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.

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.

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.

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).

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.

The minimum energy structures of the Si3C5 and Si4C8 clusters are planar and contain planar tetracoordinate carbons (ptCs). These species have been classified, qualitatively, as global () and local () aromatics according to the adaptive natural density partitioning (AdNDP) method, which is an orbital localization method. This work evaluates these species' aromaticity, focusing on confirming and quantifying their global and local aromatic character. For this purpose, we use an orbital localization method based on the partitioning of the molecular space according to the topology of the electronic localization function (LOC-ELF). In addition, the magnetically induced current density is analyzed. The LOC-ELF-based analysis coincides with the AdNDP study (double aromaticity, global and local). Besides, the current density analysis detects global and local ring currents. The strength of the global and local current circuit is significant, involving 4n+2 - and -electrons, respectively. The latter implicates the Si-ptC-Si fragment, which would be related to the 3c-2e -bond detected by the orbital localization methods in this fragment.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

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.

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.

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. Similar to higher organisms, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence and pathogen extrinsic incubation period all influence pathogen transmission. Interestingly, the mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps in the biology of the mosquito – microbe symbiosis that need to be addressed in order to understand these interactions more thoroughly and exploit them efficiently. Here, we review current evidence of the impacts of the microbiome on aspects of vectorial capacity highlighting opportunities for novel vector control strategies and areas where further studies are required.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

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.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

Milk fat production is important in the New Zealand (NZ) dairy industry. Elsewhere, an amino acid substitution (K232A) in the enzyme diacylglycerol acyl-CoA acyltransferase (DGAT1) has been reported to explain variation in some milk traits, including variation in milk fatty acid (FA) profile. In this study, associations between K232A, and milk traits including milk FA composition, were studied in wholly pasture-fed NZ Holstein-Friesian × Jersey (HF×J) cross-bred dairy cows. With a high frequency of K variant (61.9%), the KK cows produced more milk fat than the AA cows (5.41 ± 0.04 % vs 4.42 ± 0.05 %). The milk volume, fat concentration and protein concentration of AK cows were between the genotypes, AA and KK. More C16:0, CLA and C18:3 cis-9, 12, 15 FA were found in the milk of Kiwi-cross cows feed in outdoor pasture grazing system., and the influence of DGAT1 K232A, on these FAs from mid- and late lactation stages were significant. The AA cows produced (P < 0.001) more CLA and C18:3 cis-9, 12, 15, but less C16:0 (1.137 ± 0.047, 0.855 ± 0.015 and 35.170 ± 0.355) than the KK cows (0.934 ± 0.025, 0.778 ± 0.009 and 38.010 ± 0.250).

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Mountain fire can become more complex than fires at lower elevation due to the complex interaction of fire, topography, and weather. The Gell River Fire in Tasmania, Australia occurred in rugged terrain where there are abundant fire sensitive vegetation communities, as well as the presence of infrastructure including high-voltage transmission lines. The fire began at the end of December 2018 and lasted a few months, with a final burnt area of approximately 350km² despite significant fire suppression effort. The fire was investigated by employing wind vector maps, numerical weather model vertical sounding charts (NWMVS) and Prototype 2, which is an integrated fire simulator and can detect lateral fire channeling (LFC). Our analysis of the fire found its spread was likely to be introduced into a valley by forced channeling (FC), which is modified synoptic wind, and showed rapid spread in the valley. The simulated fire also showed wider spread than the observed data in the valley, with the simulated fire impacting highly sensitive vegetation communities on the fringes of the valley. This alludes to some potential conclusions: (1) The loss of fire sensitive vegetation would have increased if fire suppression activity had not been conducted. (2) Spotting fires could be produced by LFC because these spotting fire would allow spreading fire in a shorter period. (3) Heterogeneity of vegetation, such as combination of buttongrass and forest, could help carry fire rapidly in the valley with LFC. Fire can propagate faster in buttongrass than in forests while the forests allow the spotting fire.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

In 1990 the Malaysian Government launched Vision 2020 with the goal of Malaysia becoming a ‘fully developed country’ by the year 2020. In this drive for development the country has been examining many of its key natural assets, exploring how to both preserve them whilst ensuring that they make the maximum possible contribution to national development goals. Endau Rompin is one of these assets, being the second largest National Park in Peninsula Malaysia. The rich tropical rainforest flora and fauna of the Park and its hinterland, however, are threatened by various anthropogenic forces, most notably deforestation and poaching; both of which have taken the Park’s flagship species - the Tiger Panthera tigris jacksoni – towards the brink of local extinction. Malaysia’s statutory East Coast Economic Region Development Council commissioned a study to consider ways of increasing tourism revenues from the Park while at the same time reversing these threats. The key conclusion drawn is that a more holistic, landscape-scale approach should be adopted, with Endau Rompin forming part of a wider strategic economic zone based around sustainable tourism and land management. The proposed expanded zone extends eastwards beyond the confines of the Park, across the coastal plain to the South China Sea, and onwards to the neighbouring Mersing Islands. This expanded zone is referred to as Malaysia’s new ‘Rainforest to Reef Region’.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

Wastewater (WW) analysis is a critical step in various operations such as control of a WW treatment facility, and speeding-up the analysis of WW quality can significantly improve such operations. This work demonstrates the capability of neural network (NN) regression models to estimate WW characteristic properties such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), ammonia (NH3-N), total dissolved substances (TDS), total alkalinity (TA), and total hardness (TH) by training on WW spectral reflectance in the visible to near-infrared spectrum (400nm-2000nm). The dataset contains samples of spectral reflectance intensity, which were the inputs, and the WW parameter levels (BOD, COD, NH3-N, TDS, TA, and TH), which were the outputs. Various NN model configurations were evaluated in terms of regression model fitness. The mean-absolute-error (MAE) was used as the metric for training and testing the NN models, and the coefficient of determination (R2) between the model predictions and true values was also computed to measure how well the NN models predict the true values. With online spectral measurements, the trained neural network model can provide non-contact and real-time estimation of WW quality at minimum estimation error.

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

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.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

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 main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

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.

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.

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.

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

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.

Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

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%.

Background: The Davidson Airway Function &amp; 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.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

Imagination is more important than knowledge, but if intellect does not provide the needed logical structures, capacities for envisioning new possibilities are overly constrained. The sustainability problems we face today cannot be solved with the same kind of thinking that created them, but clarity on what counts as a new kind of thinking is sorely lacking. This article proposes methodical, model-based ways of heeding Bateson's warning about the negative consequences for the ecology of mind that follow from ignoring the contexts of relationships. Informed by S. L. Star's sense of boundary objects, a sequence of increasingly complex logical types distinguishes and interconnects qualitatively different kinds of thinking in ways that liberate imaginative new possibilities for life. The economy of thought instantiated at each level of complexity is only as meaningful, useful, beautiful, ethical, and efficient as the standards informing local adaptive improvisations. Standards mediating the general and specific, global and local, universally transcendent and embodied particulars enable meaningful negotiations, agreements, and communications. Attending to the differences between levels of discourse sets up new possibilities for creative and imaginative entrepreneurial approaches to viable, feasible, and desirable goals for measuring and managing sustainable development.

The life and work of Ignacio Ellacuría, S.J. is of radical vision, and revolutionary change. His dynamic life and works accompanied El Salvador and the Universidad Centroamericana through perhaps the most tumultuous years of the country’s history, yet there has been limited work done to examine his contributions. This paper shows how Ellacuría viewed the role of a Christian intellectual, and a Christian university within his philosophical and theological framework. I argue that Ignacio Ellacuría held, similarly to his soteriological views, that the intellectual must also be willing to sacrifice all for the sake of his/her work in a pattern of discipleship/martyrdom prefigured by his exemplars Christ and Socrates. It was this dedication to praxis and theory that western theology and philosophy had respectfully lost since their foundations which he sought to restore to a central role. In conclusion, the Christian intellectual and institution, according to Ellacuría, must use its voice and life in service of the people even to the point of martyrdom; he would argue, the implicit reason for Christian martyrdom and the crucifixion of Christ himself.

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.

Objective: To compare the incidence of skin abrasions caused by traditional straight edge flip flop straps versus rolled inner seam (RIS) designs in a controlled laboratory setting using preserved fetal pig skin as a proxy for human skin.Methods: This study utilized a custom-built apparatus to apply friction from two flip flop strap designs to preserved fetal pig skin samples. Three trials were conducted for each strap design to determine the time to initial abrasion onset. A paired t-test was employed for statistical analysis.Results: The RIS design demonstrated a statistically significant delay in abrasion onset compared to the standard design across all trials (p < 0.05), indicating a gentler interaction with the skin.Conclusion: The RIS strap design may offer a beneficial alternative to traditional straps by reducing the friction that can lead to skin abrasions, suggesting a potential to decrease the risk of dorsal foot ulcers. Further studies involving human subjects are warranted to validate these findings in a real-world context.Keywords: Flip flop strap design, skin abrasions, dorsal foot ulcers, footwear design, developing countries, diabetic foot care.

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%.

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.

The increasing concern regarding climate change continues to motivate research in the Arctic. Within the delicate cycle of the cryosphere, leads are an important kinematic feature that regulates heat balances and gaseous exchanges in the Arctic. Therefore, it is necessary to quantify the genesis of leads over time to identify when and where changes are occurring. The use of learning techniques is one such tool that is used to identify the characteristics of seasonal ice variability. This paper utilizes the Sentinel-1 RADAR imagery with a support vector machine learning scheme through Google Earth Engine to classify lead types in the Beaufort Sea.

A systematic study has been conducted on barbiturate complexes of all five alkali metals Li–Cs prepared from the metal carbonates or hydroxide in aqueous solution without other potential ligands present, varying the stoichiometric ratio of metal ion to barbituric acid (BAH). Eight polymeric compounds (two each for Na, K, and Rb and one each for Li and Cs) have been characterised by single-crystal X-ray diffraction. All contain some combination of barbiturate anion BA− (necessarily in a 1:1 ratio with the metal cation M+), barbituric acid, and water. All organic species and water molecules are coordinated to the metal centres via oxygen atoms as either terminal or bridging ligands. Coordination numbers range from 4 (for the Li complex) to 8 (for the Cs complex). Extensive hydrogen bonding plays a significant role in all the crystal structures, almost all of which include pairs of N–H…O hydrogen bonds linking BA− and/or BAH components into ribbons extending in one dimension. Factors influencing the structure adopted by each compound include cation size and reaction stoichiometry as well as hydrogen bonding.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

In this work, an innovative numerical approach for polylinear approximation (polylinearization) of non-self-intersecting compact sensor characteristics (transfer functions) specified either pointwise or analytically is introduced. The goal is to optimally partition the sensor characteristic, i.e. to select the vertices of the approximating polyline (approximant) along with their positions on, the sensor characteristics so that the distance (i.e. the separation) between the approximant and the characteristic is rendered below a certain problem-specific tolerance. To achieve this goal, two alternative non-linear optimization problems are solved, whose essential difference is in the adopted quantitative measure of the separation between the transfer function and the approximant. In the first problem, which relates to absolutely integrable sensor characteristics (their energy is not necessarily finite, but they can be represented in terms of convergent Fourier series), the polylinearization is constructed by numerical minimization of the L^1--metric (a distance-based separation measure), concerning the number of polyline vertices and their locations. In the second problem which covers the quadratically integrable sensor characteristics (whose energy is finite, but they do not necessarily admit a representation in terms of convergent Fourier series), the polylinearization is constructed by minimizing numerically the L^2-metric (area-, or energy-based separation measure) for the same set of optimization variables –the locations, and the number of polyline vertices.

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

The current global business landscape demands an acute commitment of international businesses’ sustainable practices to attain a global sustainability agenda. This paper examines the intricate nexus of Multinational Enterprises' (MNEs) Corporate Social Responsibility (CSR) practices, particularly environmental innovation, business ethics, CSR reporting and their environmental performance, social performance, as well as the influence of their alignment with the United Nations Sustainable Development Goals (SDGs). Using data from Refinitiv Eikon workspace for 91 MNEs from the Middle East and North Africa (MENA) region as a point of the study, the Partial Least Squares Structural Equation Modeling (PLS-SEM) results underline the potential and significant involvement of MNEs in sustainable development shaping, especially in developing and emerging countries. The harmonization and convergence of MNEs’ CSR practices and their adoption of the SDGs emerges as a pivotal approach to enhance MNEs’ contribution to a global development and sustainability agenda.

A survey of the trends in metal-ligand coordination and hydrogen bonding has been carried out on complexes of singly deprotonated cyanuric acid CY− and alkaline earth metals, synthesised from aqueous solution and characterised by X-ray crystallography. Involvement of cyanurate in the metal coordination increases from Mg through Ca and Sr to Ba relative to coordination by water, in parallel with the increasing ionic radius and coordination number. The incidence of bridging of metal centres by both water and cyanurate also increases in this series. The Mg complex contains hexaaqua-coordinated cations, uncoordinated CY− anions, and additional water molecules. Ca and Sr complexes feature polymeric chains of coordinated metal ions, the Ca complex with uncoordinated anions and the Sr complex with all potential ligands coordinated. The Ba complex has a two-dimensional coordination network. Extensive hydrogen bonding plays a key role in generating a three-dimensional network in all four structures. The competition between cyanurate and water for coordination to the alkaline earth metal cations, and that between coordination and hydrogen bonding propensities of the cyanurate anion, appear to be finely balanced, with the structural outcomes depending on the relative sizes and degrees of hardness of the four cations of the group.

Estimating parameters for multiple datasets can be time consuming, especially when the number of datasets is large. One solution is to sample from multiple datasets simultaneously using Bayesian methods such as adaptive multiple importance sampling (AMIS). Here we use the AMIS approach to fit a von Misses distribution to multiple datasets for wind trajectories derived from a Lagrangian Particle Dispersion Model driven from a 3D meteorological data. The primary objective is to characterise the uncertainties in wind trajectories in a form that can be used as inputs for predictive models of wind-dispersed insect pests and pathogens of agricultural crops for use in evaluating risk and in planning mitigation actions. Our results show that AMIS can significantly improve the efficiency of parameter inference for multiple datasets.

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.