Background: There is an upsurge in the consumption of chicken meat leading to a high influx of imported frozen chicken parts into the Ghanaian markets with little information on their microbial qualities. This study examined the microbial quality of imported frozen chicken parts from three major import countries (USA, the Netherlands and Brazil) into the Kumasi Metropolis. Methods: A total of 45 chicken meat parts of 15 thighs, wings and backs from wholesale cold stores market in the Kumasi Metropolis were randomly sampled for laboratory examinations. A ten-fold serial dilution was performed on each homogenized chicken parts to determine microbiological quality using Plate Count Agar [1], MacConkey Agar (MCA), Mannitol Salt Agar (MSA) and Desoxycholate Citrate Agar (DCA) for the total viable count (TVC), total coliform count (TCC), Staphylococcus and Salmonella spp counts respectively incubated at 37oC for 48 hours. Sabouraud Dextrose Agar (SDA) was used for fungal counts. We identified bacterial and fungal isolates using appropriate laboratory and biochemical tests. Descriptive data analysis was carried using SPSS-IBM version 16. Results: Mean TVCs of 5.93, 5.98 and 6.14 log10cfu/g were recorded for frozen chicken meats from the USA, the Netherlands and Brazil respectively. Means TCCs of 6.14, 5.93 and 5.98 log10cfu/g were obtained for chicken meats from Brazil, USA and the Netherlands respectively. Staphylococcus spp. (35.4%), E. coli (26.2%), Salmonella spp. (24.6%), and Klebsiella spp. (13.8%) were isolated with Aspergillus spp (33.3%), Rhizopus spp (27.3%), Penicillin spp (24.2%), and Cladosporium spp (15.2%). Chicken thighs, backs and wings recorded 46.2%, 29.2% and 24.6% bacterial contaminants in this order. Bacterial isolates of 49.2%, 28.8% and 22.0% were recorded in frozen chicken meat products from Brazil, the Netherlands USA respectively. Conclusion: The results suggest that imported frozen chicken meats into the Ghanaian market have moderate quality with potential pathogens such as E. coli and Salmonella spp.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

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.

In the particular configuration of the scalar field K-essence in the Wheeler-DeWitt quantum equation, for some age in the Bianchi type I anisotropic cosmological model, a fractional differential equation for the scalar field arises naturally. The order of the fractional differential equation is $\beta=\frac{2\alpha}{2\alpha - 1}$. This fractional equation belongs to different intervals, depending on the value of the barotropic parameter; when $\omega_{X} \in [0,1]$, the order belongs to the interval $1\leq \beta \leq 2$, and when $\omega_{X}\in[-1,0)$, the order belongs to the interval $0<\beta \leq 1$. In the quantum scheme, we introduce the factor ordering problem in the variables $(\Omega,\phi)$ and its corresponding momenta $(\Pi_\Omega, \Pi_\phi)$, obtaining a linear fractional differential equation with variable coefficients in the scalar field equation, then the solution is found using a fractional power series expansion. The corresponding quantum solutions are also given. We found the classical solution in the usual gauge N obtained in the Hamiltonian formalism and without a gauge. In the last case, the general solution is presented in a transformed time $T(\tau)$, however in the dust era we found a closed solution in the gauge time $\tau$.

The impact of snow darkening by deposition of light absorbing aerosols (LAAs) on snow cover over the Himalaya-Tibetan-Plateau (HTP) and influence on the Asian monsoon are investigated using the NASA Goddard Earth Observing System Model Version 5 (GEOS-5). We find that during April-May-June, deposition of LAAs on snow leads to a reduction in surface albedo, initiating a sequence of feedback processes, starting with increased surface solar radiation, rapid snowmelt in HTP and warming of the surface and upper troposphere, followed by enhanced low-level southwesterlies and increased dust loading over the Himalayas-Indo-Gangetic Plain. The warming is amplified by increased dust aerosol heating, and subsequently amplified by latent heating from enhanced precipitation over the Himalaya foothills and northern India, via the Elevated Heat Pump (EHP) effect during June-July-August. The reduced snow cover in the HTP anchors the enhanced heating over the Tibetan Plateau and its southern slopes, in conjunction with an enhancement of the Tibetan Anticyclone, and the development of an anomalous Rossby wavetrain over East Asia, leading to weakening of the subtropical westerly jet, and northward displacement and intensification of the Mei-Yu rainbelt. Our results suggest that atmosphere-land heating by LAAs, particularly desert dust play a fundamental role in physical processes underpinning the snow-monsoon relationship proposed by Blandford more than a century ago.

Objectives Independent validation of risk scores after hip fracture is uncommon, particularly for evaluation of outcomes other than death. We aimed to assess the Nottingham Hip Fracture Score (NHFS) for prediction of mortality, physical function, length of stay and postoperative complications. Design Analysis of routinely collected prospective data partly collected by follow-up interviews. Setting and Participants Consecutive hip fracture patients were identified from the Northumbria hip fracture database between 2014-2018. Patients were excluded if they were not surgically managed or if scores for predictive variables were missing. Methods C-statistics were calculated to test the discriminant ability of the NHFS, Abbreviated Mental Test Score (AMTS), and ASA grade for in-hospital, 30- and 120-day mortality, functional independence at discharge, 30-days and 120-days, length of stay, and postoperative complications. Results We analysed data from 3208 individuals, mean age 82.6 (SD 8.6). 2192 (70.9%) were female. 194 (6.3%) died during the first 30-days, 1686 (54.5%) were discharged to their own home, 211 (6.8%) had no mobility at 120-days, 141 (4.6%) experienced a postoperative complication. The median length of stay was 18 days (IQR 8-28). For mortality, c-statistics for the NHFS ranged from 0.68-0.69, similar to ASA and AMTS. For postoperative mobility, the c-statistics for the NHFS ranged from 0.74-0.83, similar to AMTS (0.61-0.82) and better than the ASA grade (0.68-0.71). Length of stay was significantly correlated with each score (p<0.001 by Jonckheere-Terpstra test); NHFS and AMTS showed inverted U-shaped relationships with length of stay. For postoperative complications, c-statistics for NHFS (0.54-0.59) were similar to ASA grade (0.53-0.61) and AMTS (0.50-0.58). Conclusions and Implications The NHFS performed consistently well in predicting functional outcomes, moderately in predicting mortality, but less well in predicting length of stay and complications. There remains room for improvement by adding further predictors such as measures of physical performance in future analyses.

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

Development of K-Ras independence may explain failure of targeted therapy for pancreatic cancer (PC). In this paper active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. Knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism but only K-Ras depletion caused a decrease in G2 cyclins, proteasome inhibition reversed this and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from G2 phase to slow relative to completion of S-phase, suggesting mutant K-Ras may inhibit APC/c prior to anaphase but stabilizes G2 cyclins independently of this. We propose that during tumorigenesis, cancer cells expressing wild type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of cell cycle independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division even in cells where K-Ras is inhibited. Keywords: Pancreatic Ductal Adenocarcinoma, K-Ras, N-Ras, G2 cyclins.

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.

Volatile compounds, abundant in breath, can be used to accurately diagnose and monitor a range of medical conditions. This offers a non-invasive, low-cost approach with screening applications; however, uptake of this diagnostic approach has been limited by conflicting published outcomes. Most published reports rely on large scale screening of the public, at single time points and without reference to ambient air. Here, we present a novel approach to volatile sampling from cellular headspace and mouse breath that incorporates multi-time point analysis and ambient air subtraction revealing compound flux as an effective proxy of active metabolism. This approach to investigating breath volatiles offers a new avenue for disease biomarker discovery and diagnosis. Using gas chromatography mass spectrometry (GC/MS), we focus on low molecular weight, metabolic substrate/by-product compounds and demonstrate that this non-invasive technique is sensitive (reproducible at ~1 µg cellular protein, or ~500,000 cells) and capable of precisely determining cell type, status and treatment. Isolated cellular models represent components of larger mammalian systems and we show that stress- and pathology-indicative compounds are detectable in mice, supporting further investigation using this methodology as a tool to identify volatile targets in human patients.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

Helmholtz energy of ice VII-X is determined in a pressure regime extending to 450 GPa at 300 K using local basis functions in the form of b splines. The new representation for the equation of state is embedded in a physics-based inverse theory framework of parameter estimation. Selected pressures as a function of volume from 14 prior experimental studies and two theoretical studies constrain the behavior of Helmholtz energy. Separately measured bulk moduli, not used to construct the representation, are accurately replicated below about 20 GPa and above 60 GPa. In the intermediate range of pressure, the experimentally determined moduli are larger and have greater scatter than values predicted using the Helmholtz representation. Although systematic experimental error in the experimental elastic moduli is possible and likely, the alternative hypothesis is a slow relaxation time associated with changes in proton mobility or the ice VII to X transition. A correlation is observed between anomalies in the pressure derivative of the predicted bulk modulus and previously suggested higher-order phase transitions. Improved determinations of elastic properties at high pressure would allow refinement of the current equation of state. More generally, the current method of data assimilation is broadly applicable to other materials in high-pressure studies.

In this paper, we present sums and partial sums of Horadam sequences via generating functions which extends a recent result of Prodinger.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

There are potential overlapping distributions of the protozoan parasite Leishmania and the parasitic helminth Schistosoma mansoni in eastern Africa most notably in endemic regions in the Sudan and Kenya. In murine model studies, the Th₁-Th₂ model of CD4+ T helper cell differentiation is a well-established paradigm for understanding the basis of protective versus pathogenic immune responses in the concomitance state that result in enhanced pathological changes and impaired parasite resolution. In complementation to the experimental studies, the concern for presages of human leishmaniases and schistosomiasis co-infections occurring is increased by their chronicity, displacement of people between endemic areas owing to conflict, climatic changes due to human activities, the spread through irrigation, pisciculture, water conservation schemes and human mobility in pursuit of economic dynamics and resources. Based on diseases prevalence, epidemiology and analyzing the associated risk factors undercurrents, several portents of comorbidity in Kenya are pinpointed. Taking into consideration the limited local resources and diminished surveillance of the areas affected by the two neglected tropical diseases, the discourse concludes that elimination of the diseases is still a challenge. There is need for pilot studies and/or elaborate field surveillance of concomitance and development strategies to mitigate the impending defy in Kenya and beyond.

Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States, and is carried by the Lone Star tick (Amblyomma americanum). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5-10\% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum. In addition, the recent 2017 introduction of the Asian longhorned tick (Haemaphysalis longicornis) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen

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;

Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.

In this paper, closed forms of the sum formulas $\sum_{k=0}^{n}x^{k}W_{k}^{3}$ and $\sum_{k=1}^{n}x^{k}W_{-k}^{3}$ for the cubes of generalized Fibonacci numbers are presented. As special cases, we give sum formulas of Fibonacci, Lucas, Pell, Pell-Lucas, Jacobsthal, Jacobsthal-Lucas numbers.

Recent advancements in vascular organoid (VO) and vessel-on-chip (VoC) technologies have revolutionized our approach to studying cardiovascular diseases (CVDs), offering unprecedented insights through more physiologically relevant models. VOs generated from human pluripotent stem cells exhibit remarkable self-organization capabilities, forming complex three-dimensional structures that closely mimic human blood vessel architecture and function, while VoCs engineered with groundbreaking microfluidic systems that meticulously recreate the physical and functional attributes of blood vessels. These innovative constructs serve as powerful tools for investigating vascular development, disease progression, and therapeutic efficacy. By enabling the creation of patient-specific VOs and VoCs, they pave the way for personalized medicine approaches, allowing researchers to delve into genetic variations, intricate cellular interactions, and dynamic processes with exceptional resolution. The synergy between VOs and VoCs with cutting-edge technologies such as single-cell sequencing and high-resolution imaging has further amplified their potential, unveiling novel mechanisms underlying CVDs and identifying promising therapeutic targets. Herein, we summarize different types of VOs and VoCs and present an extensive overview on the generation and applications of VOs and VoCs in CVDs. We will also highlight clinical and translational challenges and future perspectives around VOs and VoCs.

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

The excessive intake of sodium (Na) and insufficient intake of potassium (K) are major concerns to prevent hypertension. Using low-Na/K seasonings (reducing 25% of the NaCl and adding K salt) may improve the dietary Na/K ratio and help prevent hypertension. To devise an intervention study using low-Na/K seasonings at a company cafeteria, we calculated the Na and K contents of the meals served at the cafeteria and estimated changes in the intakes when suitable low-Na/K seasonings were used. We also considered using milk as a good source of K. We used an ingredient list of a company cafeteria and calculated Na and K contents in each dish. The average amounts of NaCl and K per use were 5.04 g and 718 mg, respectively. Seasonings contributed 70.9% of the NaCl. With the use of low-Na/K seasonings, an estimated reduction in NaCl of 0.8 g/day and an estimated increase in K of 308 mg/day was achieved. An additional serving (200 mL) of milk, NaCl was reduced by 0.57 g/day and K was increased by 610 mg/day, with an overall decrease in the dietary Na/K ratio from 3.20 to 2.40. The use of low-Na/K seasonings and dairy may improve the dietary Na/K ratio among cafeteria users and help prevent hypertension.

The present work presents and discusses experimental performance and gaseous emission results of the use of ternary mixtures of diesel oil, biodiesel and ethanol in an ASTM-CFR engine. Eight different mixtures with biodiesel content equal to 8%, 20% and 60%, and ethanol content equal to 0%, 5% and 8% were analyzed. After the selection and preparation of the mixtures, the determination of the cetane number for each one was performed following the ASTM D613 standard. After cetane number evaluation, two off-standard operating conditions were selected, and performance and emissions were obtained. A thermodynamic analysis and a Bayesian inverse approach were applied and physical quantities of interest, such as indicated work, maximum pressure, rate of heat released by the fuel, ignition delay, and combustion duration, were obtained. In-cylinder pressure data were obtained through an AVL Indicating system installed in the ASTM-CFR engine. The heating values of each mixture were determined using a bomb calorimeter and thermal and indicated efficiencies were evaluated based on the total heat released by the fuel and the indicated work. Finally, a gaseous emissions analysis was conducted to evaluate the influence of the blend compositions, as well as of their cetane numbers, on the formation of NOx, CO and CO₂.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

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).

Tomato (Solanum lycopersicum L.) has almost 190 million tonnes produced in 2023. Tomato fruit suffer losses of up to 50% during harvest and transport, which causes financial hardship, reduces the amount of food available and causes environmental harm. Calcium plays an important role in cell wall strength. This work assessed the use of a calcium transport stimulants (MCAS) to increase the firmness of tomato fruit in the laboratory and the foliar application to tomato plants. Then handling damage was simulated. In the laboratory, the calcium with MCAS significantly increased the fruit firmness compared to the untreated and calcium without MCAS, which were not significantly different. When calcium with MCAS was applied to tomato plants foliarly before harvest, the calcium with MCAS treated fruit were significantly firmer than the untreated or calcium without MCAS treated fruit for up to 10 weeks after harvest, and this was achieved by applying only 0.91 kg ha-1 calcium. Finally, when fruit were exposed to a simulated drop, the calcium with MCAS treated fruit remained firmer than the undamaged fruit or dropped fruit with calcium without MCAS. Calcium with MCAS could significantly increase the fruit firmness and increase the shelf-life of tomatoes while applying less calcium.

Recently a measure termed F* was described, as an interpretable transformation of the F measure, also known as the Dice coefficient. Using elementary mathematical methods, it is shown that F* is in fact identical to a previously described measure, monotonically related to the F measure, and variously termed in previous publications, dating from the late 19^th to the late 20^th century, as the ratio of verification, the Jaccard similarity measure or index, the threat score, the Tanimoto index, and the critical success index. The origins of these different terms in different disciplines (weather forecasting, ecology, machine learning) may explain the repeated independent redescription of this measure.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

In this review paper, we present a pellucid proof of how x tanh(x/µ) approximates |x|and is better than √x² +µ  when we are concernedwith accuracy.

In recent decades, perovskite-type compounds (ABB′O3) have been exhaustively studied due to their unique ferroelectric properties. In this work, a systematic study aiming to prepare fine particles in the binary system SrZrO₃–SrTiO₃ was conducted under hydrothermal conditions in a KOH (5 M) solution at 200 °C for 4 h under a constant stirring speed of 130 rpm. The precursors employed were SrSO₄ powder (&lt; 38 μm size) and coprecipitated hydrous gels of Zr(OH)₄•9.64 H₂O (Zr-gel) and Ti(OH)₄•4.5H₂O (Ti-gel), which were mixed according to the stoichiometry of the SrZr_1-xTixO₃ in the compositional range of 0.0&gt;x&gt;100.0 mol% Ti⁴⁺. The XRD results revealed the formation of two crystalline phases rich in Zr⁴⁺, an orthorhombic structured SrZr0.93Ti0.07O3 and a cubic structured SrZr0.75Ti0.25O3 within the compositional range of 0.1–0.5 mol of Ti4+. A cubic perovskite-structured solid solution, SrTi1-xZrxO3, was preferentially formed within the compositional range of 0.5&gt;x&gt;0.1 mol% Ti⁴⁺. The SrZrO₃ and SrZr_0.93Ti_0.07O₃-rich phases had particle sizes averaging 3 m with a cubic morphology. However, a remarkable reduction in the particle size occurred on solid solutions prepared with hydrous Ti-gel over contents of 15 mol% Ti⁴⁺ in the reaction media, resulting in the formation of nanosized particles agglomerates with cuboidal shape self-assembled via a 3D hierarchical architecture, the sizes of these particles varied in the range between 141.0–175.5 nm. The limited coarsening of the particles is discussed based on the Zr-gel and Ti-gel dehydration capability differences that occurred under hydrothermal processing.

Bacteria play a key role in both human health and disease. One of the most prevalent harmful bacteria is E. coli which is responsible for several illnesses ranging from diarrhea, stomach cramp and fever. In this work we explore the application of moderate electric or magnetic fields for treating deionized water that is contaminated with E. coli. We found that moderate alternating electric (AC) fields (10 V/cm to 1kV/cm) and moderate static magnetic fields (10 to 65 mT) can significantly inactivate E. coli by up to 90% or more. This provides the possibilities of developing a low cost and a practical bacteria inactivation technique using electric or magnetic fields.

Oxygen and hydrogen isotopes (18O and 2H) in polar ice offer strong evidence of both long-term and abrupt climate changes. However, reliably estimating surface air temperatures from past climates has proven difficult because the relationship between 18O and temperature cannot be calibrated. In this study, we investigated the 17O and 18O of modern rain and ice cores using published data. We found that precipitation 17O is influenced by two factors: mass-dependent fractionation (MDF) that occurs during ocean evaporation, and mass-independent fractionation (MIF) that happens in the stratosphere. The MDF contribution remains constant and can be understood from studying tropical rain, as the overall movement of mass in the tropics is upward towards the stratosphere. On the other hand, the MIF effect comes from the mixing of stratospheric air in the troposphere, which is a result of the Brewer-Dobson circulation. This MIF effect on precipitation 17O increases from the tropics towards the poles. Therefore, the relative 17O and 18O composition, denoted as '17O, in modern precipitation can be calibrated with surface air temperature, creating a new, independent tool for estimating past temperatures. We used this calibration along with '17O of Antarctic and Greenland ice cores and our results for past temperatures are in excellent agreement with those from borehole thermometry or gas phase analysis of air trapped in the ice. The 17O method overcomes the problems associated with using 18O for paleothermometry. Our findings align with climate models that suggest a weakening of the Brewer-Dobson circulation during the Last Glacial Maximum. Furthermore, our method could be used to monitor future changes in response to a warming climate caused by increasing greenhouse gases.

Herbicide-resistant weed populations in numerous cropping systems pose a significant threat to global food security by reducing crop yields and increasing production costs. Multiple herbicide-resistant (MHR) Avena fatua L. (wild oat) plants with non-target site resistance (NTSR) mechanisms can express resistance to herbicides without previous exposure and are thus particularly troubling. Although precise molecular mechanisms for resistance to five different mechanisms of action are not clear, numerous transcription factors and stress-related proteins are preferentially subjected to constitutive post-translational modifications (PTMs) in MHR plants. Transient assays to quickly assess if changes to specific genes can change the MHR response will facilitate the development of new strategies to manage MHR weeds. Our study showed that the Barley Stripe Mosaic Virus (BSMV) mediated system can be an option for A sa-tiva (cultivated oat) and A. fatua (wild oat) functional analysis. The inoculation efficiency of this system ranged from 48% to 100%. Its efficacy was demonstrated by successfully knocking down phy-toene desaturase (PDS) expression and overexpressing green fluo-rescent protein (GFP), suggesting its potential for oat functional genomics.

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.

This work presents the first evidence that dissolved globular proteins change the arrangement of hydrogen bonds in water, with different proteins showing quantitatively different effects. Using ATR-FTIR (Attenuated Total Reflection – Fourier Transform Infrared) spectroscopic analysis of OH-stretch bands, we obtain quantitative estimates of the relative amounts of the previously reported four subpopulations of water structures coexisting in a variety of aqueous solutions. Where solvatochromic dyes can measure the properties of solutions of non-ionic polymers, the results correlate well with ATR-FTIR measurements. In protein solutions to which solvatochromic dye probes cannot be applied, NMR (Nuclear Magnetic Resonance) spectroscopy was used for the first time to estimate the hydrogen bond donor acidity of water. We found strong correlations between the solvent acidity and arrangement of hydrogen bonds in aqueous solutions for several globular proteins. Even quite similar proteins are found to change water properties in dramatically different ways.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

Silver particles are prepared by dewetting Ag films coated on glass using a fiber laser. The size of the particles is controlled in the range of 92 nm ~ 1.2 μm by adjusting the thickness of the Ag film. The structural properties and surface roughness of the particles are evaluated by means of scanning electron microscopy. In addition, the antifungal activity of the Ag particles is examined using spore suspensions of Colletotrichum gloeosporioides. It is shown that the particles with a size of 1.2 μm achieve 100% inhibition of the conidia growth of the Colletotrichum gloeosporioides after a contact time of just 5 min. Furthermore, the smaller particles also achieve a good antibacterial activity given a longer contact time. Similar results are observed in spore germination and pathogenicity tests performed on mango fruit and leaves. Overall, the results confirm that the Ag particles have an excellent antifungal effect on Colletotrichum gloeosporioides.

Periodontal disease is one of the most common conditions affecting dogs worldwide and is reported to be particularly prevalent in racing greyhounds. A range of potential risk factors have been hypothesised. Previous research has suggested, regular tooth brushing can reduce both calculus and gingivitis, but the frequency required is unclear. Here, we report a controlled blinded in-situ in which kennel staff brushed 160 racing greyhounds’ teeth (living at six kennel establishments), either weekly, daily or never over two-month period. All visible teeth were scored for calculus and gingivitis, using previously validated scales. We calculated average scores for each of three teeth groups and overall averaging the teeth groups. Changes were compared to baseline. After two months, the total calculus scores (controlling for baseline) were significantly different in the three treatemnet groups, (F(2,129) = 10.76, p&lt;0.001) with both weekly and daily brushing resulting in significant reductions. Gingivitis was also significantly different (F(2,128) = 4.57, p=0.012), but in this case, only daily brushing resulted in a significant reduction. Although dogs in different kennels varied significantly in their levels of both calculus (F(5,129) =8.64, p&lt;0.001), and gingivitis (F(5,128)=3.51 p=0.005), the intervention was generally similarly effective in all establishments. Teeth groups varied and incisors were not significantly affected by treatment. Since trainers implementing the routine, reported minimal time commitment and positive experiences, we suggest that daily brushing is recommended for racing greyhounds, and that demonstrations should include attention to all teeth groups including incisors. Similar trials need to be conducted with retired greyhounds since these have been shown to present particularly high levels of periodontal disease.

Primary materials supply is the heart for engineering and sciences; depletion of natural resources and an increase in the human population by a billion in 13 to 15 years pose a critical concern on the sustainability of the materials. Therefore, functionalizing renewable materials, such as nanocellulose, possibly exploiting its properties for various practical applications, has been undertaken worldwide. Nanocellulose has emerged as a dominant green natural material with attractive and tailorable physicochemical properties, renewable, sustainable, biocompatibility, and tunable surface properties. Nanocellulose is derived from cellulose, the most abundant polymer in nature with remarkable properties of nanomaterials. This article provides a comprehensive overview of the methods used for nanocellulose preparation, structure-property and processing-property correlations, and the application of nanocellulose and its nanocomposite materials. This article differentiates the classification of nanocellulose, provides a brief account of the production methods that have been developed for isolating nanocellulose, highlights a range of unique properties of nanocellulose that have been extracted from different kinds of experiments and studies; and elaborates on nanocellulose potential applications in various areas. The present review is anticipated to provide the readers regarding the progress and knowledge related to nanocellulose. Pushing the boundaries of nanocellulose further into cutting edge applications will be of particular interest for the future, especially as cost-effective commercial sources of nanocellulose continue to emerge.

Florida geologic units and soils contain a wide range in concentrations of naturally-occurring arsenic. The average range of bulk rock concentrations is 1 to 13.1 mg/kg with concentrations in accessary minerals being over 1,000 mg/kg. Soils contain natural arsenic concentrations of between 0.18 and 2.06 mg/kg with organic-rich soils having the highest concentrations. Anthropogenic sources of arsenic have added about 610,000 metric tons of arsenic into the Florida environment since 1970, thereby increasing background concentrations in soils. The anthropogenic sources of arsenic in soils include: pesticides (used in Florida beginning in the 1890’s), fertilizers, chromated copper arsenate (CCA)-treated wood, soil amendments, cattle-dipping vats, chicken litter, sludges from water treatment plants, and others. The default Soil Cleanup Target Level (SCTL) in Florida for arsenic in residential soils is 2.1 mg/kg which is below some naturally-occurring background concentrations in soils and anthropogenic concentrations in agricultural soils. A review of risk considerations shows that adverse health impacts associated with exposure to arsenic is dependent on many factors and that the Florida cleanup levels are very conservative. Exposure to arsenic in soils at concentrations that exceed the Florida residential cleanup level in residential environments does not necessarily pose a meaningful public health risk.

In the past decade, a growing demand for sustainable cosmetic ingredients has yielded numerous biodegradation protocols. While OECD (Organization for Economic Co-operation and Development) aquatic assays are suitable for water-borne chemicals, it is crucial for the personal care industry to consider the persistence of plastics in soil, compost, and municipal sludge. Adopting this cradle-to-grave holistic approach would strengthen product appeal, while increasing the accuracy and ethical integrity of green-product labeling. Our study employs quantitative CO2 detection and thermophilic composting protocols specified in ASTM D5338, along with pass level criteria outlined in ASTM D6400, to assess the mineralization of plastics commonly formulated into personal care products. The results indicate that many cellulose ethers, cationic guars, starches, and labile polyesters demonstrate satisfactory disintegration, biodegradation, and seed germination rates to secure an ASTM D6400 compostability claim. In contrast, macromolecules designed with carbon-carbon backbones resisted acceptable mineralization in composting experiments, suggesting that unadulterated municipal compost lacks the microbial diversity to enzymatically digest many synthetically derived resins. Additionally, polymers that demonstrated acceptable biodegradability in internal and published OECD aquatic studies—including chitosan and polyvinyl alcohol—exhibited limited fragmentation in local municipal compost; hence, untested correlations between aquatic, soil, and compost testing outcomes should never be assumed.

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

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

Responses to water stress were measured for sugar maple (Acer saccharum subsp. saccharum Marshall) sources from Oklahoma (Caddo sugar maple), Missouri, Tennessee, Ontario and a black maple (Acer saccharum subsp. nigrum F. Michx.) source from Iowa. Seedling sources were selected for differences in temperature and precipitation of their geographic origins. Seedlings were preconditioned through moist (watered daily) or dry (watered every 4-7 days) cycles and then exposed to prolonged water stress. Dry preconditioned sugar maple seedlings from Oklahoma, Missouri, and Tennessee, sources from warmer and/or drier climates with greater relative evapotranspiration potentials, declined less rapidly in net photosynthesis, stomatal conductance, and water use efficiency (WUE) as water stress increased than dry preconditioned seedlings from Ontario and Iowa having origins in cooler, moister climates. Under imposed water stress the Ontario and Iowa sourced seedlings increased their root to shoot ratios and decreased their specific leaf area, mechanisms for drought avoidance. However, no corresponding changes in these values occurred for Oklahoma, Missouri, and Tennessee sources. Results from this study suggest greater tolerance of water stress in the Oklahoma, Missouri and Tennessee ecotypes from the western and southern range of sugar maple resulted primarily with WUE rather than other water stress coping mechanisms.

The narrow process window during intercritical annealing and discontinuous yielding have limited the commercialisation of medium Mn steels. In this study, a double annealing process based on the commercial continuous annealing line is proposed. The cold-rolled medium Mn steels were first fully austenitized and quenched during the first annealing, followed by the intercritical annealing for reverted austenite transformation. The microstructure of duplex lath-shaped austenite and ferrite is produced and the steel exhibit a desirable continuous yielding during tensile deformation. Al is added into the medium Mn steel to enlarge the process window and to improve partitioning efficiency of Mn. The produced steel is more robust with temperature fluctuation during the industrial process due to the enlarged intercritical region. Mn partitioning is more efficient owing to elevated annealing temperature, which results in the improvement of ductility in the Al-added steel with increased austenite stability.

In this paper, we study the third order semilocal convergence of the Newton-like method for finding the approximate solution of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis under ω-continuity condition, which is weaker than the Lipschitz and Hölder continuity conditions. Second, we apply our approach to solve Fredholm integral equations, where the first derivative of involved operator not necessarily satisfy the Hölder and Lipschitz continuity conditions. Finally, we also prove that the R-order of the method is 2p + 1 for any p $\in$ (0,1].

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.

Globally, an approximate of 380,000 patients succumbed to death due to the pandemic COVID-19 which also infected more than six million people since December 2019. Not sparing anyone, COVID-19 infections are widely reported among healthcare professionals, sanitation workers and researchers too while global leaders and various governments are providing their best in defending their citizens against this airborne and contact spread virus. In order to contain the virus and protect millions of lives from this deadly coronavirus, there is a need to have a combination of advanced engineering technology and medical facilities. Application of applied science, engineering and technology diffuse almost every aspect of contemporary living. Grasping the fundamentals to determine humanity's most imperative and forthcoming challenges is essential. Artificial Intelligence, the technology that learns, adapts and reciprocates the actions according to the situations, finds optimum position in the fight against corona virus and acts as a powerful tool against this pandemic. In this research article, the authors discusses how Artificial Intelligence (AI) can be leveraged to fight the deadly virus. The research paper further discusses the efficient utilization of AI across the globe to help in testing, treating and serving the population in these hard times. This manuscript focuses on the potential impact of the process in which AI can be implemented to prevent, test and treat.

In the paper, the authors generalize the notion "k-Mittag-Leffler function'', establish some integral transforms of the generalized k-Mittag-Leffler function, and derive several special and known conclusions in terms of the generalized Wright function and the generalized k-Wright function.

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.

Marine macroalgae have garnered significant attention in the field of cosmeceutical research due to their rich abundance of bioactive compounds. These compounds offer remarkable skin benefits without inducing any adverse effects on human health, such as cytotoxicity, reproductive toxicity, genotoxicity, mutagenicity, or carcinogenicity. Among the various bioactive compounds found in brown algae, phenolic compounds exhibit diverse chemical structures and are present in high concentrations. In addition to phenolic compounds, brown algae also contain terpenoids, bro-mophenols, mycosporine amino acids (MAAs), and flavonoids, with the well-studied poly-phenol compound, phlorotannin, being particularly prominent. Marine macroalgae further possess an array of pigments derived from their natural pigmentation, including chlorophylls, carotenoids (such as fucoxanthin and β-carotene), phycobiliproteins (such as phycoerythrin and phycocyanin), and melanin. These pigments have been extensively investigated for their potential cos-meceutical applications. The phenolic compounds and pigments derived from marine macroalgae have been thoroughly studied for their beneficial effects on the skin, including skin whitening, moisturizing, photoprotection, anti-aging, anti-wrinkle, anti-melanogenic, and anti-oxidant properties. This comprehensive review aims to explore the extraction, characterization, and skin cosmetic effects of phenolic compounds and pigments derived from marine macroalgae, as documented in the existing literature, thereby enhancing our understanding of their therapeutic potential.

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.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017/2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four parameter logistic) curves. The NHANES cohort (n=2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs 44 [25, 61] µmol/L, p&lt;0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs 53 [24, 104] mg/d, p=0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst the those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had lower a BMI than the NHANES cohort (26 [24, 28] kg/m2 vs 29 [25, 34] kg/m2, respectively). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes have 1.4- to 1.6-fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

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.

This paper will explore analogs of groups formed by the transformations of two ropes as presented by Minh-Tam Quang Trinh.1 The two operations acting on these ropes are T and S, defined as twists and clockwise turns, respectively. These actions intertwine the ropes, creating tangles. T and S also have the ability to untangle the rope when used in certain combinations. In the two-rope case, these actions expressed as a group presentation were shown to be isomorphic to SL₂(Z). We explored the analog of these opera- tions, T and S, and conjectured the corresponding group to which they are isomorphic. Partial proofs for this conjecture are included and future work would include proving our conjecture as well as generalizing results to k ropes.

Evidence that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible children has mounted for more than a decade. Evidence is diverse, including extensive work with laboratory animals, otherwise unexplained associations, factors associated with the metabolism of acetaminophen, and some limited studies in humans. Although evidence has reached an overwhelming level and has been reviewed in detail recently, some controversy remains. In this narrative review, some of those controversies are evaluated. First, the associations through time between acetaminophen use and the prevalence of neurodevelopmental disorders are considered. A systematic review reveals that the use of acetaminophen in the pediatric population was never tracked carefully, but historical events that affected use of the drug were documented and are sufficient to establish apparent correlations with changes in the prevalence of neurodevelopmental disorders. Second, problems with exclusive reliance on results from meta-analyses of large datasets and from studies involving small time frames of drug exposure are reviewed. Third, the potential bias in a study designed to separate the role of vaccines and acetaminophen in the induction of autism spectrum disorder (Autism 2008;12:293-307) is carefully evaluated. Finally, evidence demonstrating why some children are susceptible to acetaminophen-induced neurodevelopmental injury is examined. It is concluded that, at least among the factors considered, there is no valid rationale for controversy regarding the conclusion that early life exposure to acetaminophen causes neurodevelopmental injury in susceptible babies and small children.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

:Peat substrate is made from peat from drained peatlands, which is a limited resource. A realistic estimate is that 50% of the world’s wetlands have been lost. Peat is used in horticulture, especially for the cultivation of vegetables in greenhouses. The consequences of peatland exploitation are an in-crease in the greenhouse effect and a decrease in carbon stocks. Wood fiber can be used as an al-ternative to peat. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the growing container. This study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) variety “Dirigent H” developed in the Netherlands, were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) con-ventional fertilization (CF); (2) N13; (3) N23; (4) N30. The experiment was carried out in three repli-cations. As the amount of wood fiber increased, the humidity and pH of the growing medium in-creased. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in 50/50 and 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat sub-strate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K⁺ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K⁺ ions are at least 10,000 times more permeant than Na⁺ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na⁺ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

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.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognised disease limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (<65 years) patients undergoing arthroplasty, the demand for revision arthroplasty after implant failure is also set to increase. Statins are cholesterol modulating drugs widely used for cardiovascular risk reduction which have been noted to have pleiotropic effects including potentially influencing arthroplasty survival. In vitro studies have demonstrated pleiotropic effects in human bone cells, including enhancement of osteoblastogenesis following simvastatin exposure, and in vivo studies have demonstrated that intraperitoneal simvastatin can increase peri-implant bone growth in rats following titanium tibial implant insertion. There is evidence also that statins may also influence osseointegration, enhancing bone growth at the bone-implant interface, subsequently improving the functional survival of implants. Data from the Danish Hip Arthroplasty Registry and Clinical Practice Research Datalink in the UK suggest a reduction in the risk of lower limb revision arthroplasty in statin ever-users vs never users, and a time dependent effect of statin administration on reduction in risk of revision. In this article we review the clinical and scientific evidence linking statins and risk of revision arthroplasty.

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.

Abstract The aim of the present review is to discuss the roles of vitamin K and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. Adequate vitamin K status is required for carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanism, such as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through dietary adequacy of vitamin K (phylloquinone or menaquinone). Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3 we find that an adequate supply of vitamin K on top of an optimal vitamin D status seems to add to the benefit for maintaining bone health. More research related to synergism and possible mechanisms of vitamins D3 and K interaction in bone health is needed.

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.

A remote sensing-based evapotranspiration (ET) study was conducted over the Central Arizona Irrigation and Drainage District (CAIDD), an Arizona agricultural region. ET was assessed means for 137 wheat plots, 183 cotton plots, and 225 alfalfa plots. The remote sensing ET models were the Satellite-Based Energy Balance for Mapping Evapotranspiration with Internalized Calibration (METRIC), the Two Source Energy Balance (TSEB), and Vegetation Index ET for the US Southwest (VISW). Remote sensing data were principally Landsat 5, supplemented by Landsat 7, MODIS Terra, MODIS Aqua, and ASTER. The models produced similar daily ET for wheat, with 6–8 mm/d mid-season. For cotton and alfalfa daily ET showed greater differences, where TSEB produced largest daily ET, METRIC the least, and VISW in the midrange. Modeled cotton ET at mid-season ranged from 9.5 mm/d (TSEB), to 8 mm/d (VISW), and 6 mm/d (METRIC). For alfalfa ET, values at peak cover ranged from 8 mm/d (TSEB), 6 mm/d (VISW), and 5 mm/d (METRIC). Model bias ranged −10% to +18%. Relative to potential ET, FAO-56 ET, and USDA-SW gravimetric-ET, model variability ranged from negligible to 35% of annual crop water use. Model averaging was found a useful way to consider and reconcile all ET estimates.

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.

In healthy ageing, capacity declines in the neural, muscular, and skeletal systems, and each system decline has its effect on the execution of complex motor tasks. This decline in capacity can result in the inability to stand up (sit-to-stand, sit-to-walk), which is a key movement for independence. The mechanisms leading to mobility limitations or inabilities are complex, overlapping, and interdependent and the complementary fields of biomechanics, motor control, and physiology need to be combined to understand these mechanisms. The aim of this review is to provide an overview of the current knowledge of age-related compensation in standing up and to consider the limitations of these results when analysing standing up in daily life using the Capacity, Reserve, Movement Objectives, and Compensation (CaReMoOC) framework that combines biomechanics, motor control, and physiology. A literature search was performed in the search engine Scopus, using the keywords and their synonyms: strateg*(approach, technique, way) AND, sit-to-walk OR sit-to-stand OR rise (raise, arise, stand, stand-up) AND chair (seat). Inclusion criteria were: biomechanics or motor control on sit-to-stand or sit-to-walk in healthy and/or frail adults (<60y) and elderly (>60y), and/or osteoarthritis patients as a specific case of ageing related decline. The review shows that movement compensations in standing up manifest as changes in planned trajectory (Compensation by Selection) and in muscle recruitment (Compensation by Reorganisation). However, as most studies in the literature typically use standardized experimental protocols where movement compensation is restricted, these studies cannot be directly translated to functional tasks, such as the mobility of the elderly in their homes, communities, and clinic. Compensation must be included in future studies in order to facilitate clinical translation. Specifically, future studies in the standing up task should 1) determine the effect of varying arm use strategies (e.g., armrests, knees, chair, cane) on trunk and both lower limb and upper limb joint loading, 2) analyse control strategies in elderly people, 3) determine the biomechanical implications of asymmetry, and 4) incorporate assessments of age-related physical and neural decline as well as changes in psychological priorities.

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.

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

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

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.

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.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

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.

Sudden cardiac arrest (SAC) is a leading cause of mortality. In recent years, though, many lives have been saved through the use of defibrillators by random bystanders. As a result, defibrillators have been popping up in various locations. In this work we propose a state mandate demanding the presence of a defibrillator at every pharmacy store and argue that it could greatly enhance and augment the impact of the defibrillator network. We support our claim via detailed calculations of the immediate (a defibrillator readily available) and partial (a defibrillator available at a reasonable distance) population coverage achievable by the implementation of our proposal, taking the Argolis area in Peloponnese Greece as a case study. Our findings indicate that, in addition to other benefits, the use of pharmacies to establish a defibrillator network could bring an eight-fold increase in the immediate population coverage of defibrillators and would provide immediate / partial access to a defibrillator to 18 / 24 incidents of SCA per year that would otherwise lead to death, potentially leading to the saving of numerous lives. Alternative scenaria are also discussed.

Mortality rates in sub-Saharan Africa remains unacceptably high, and disproportionately affecting economically disadvantaged communities. And healthcare delivery which is considered a major contributor to this is challenged by the limited resources and high service costs, prompting many patients to opt for outpatient department services. This study addresses the need for a data-driven approach to healthcare policy formulation by proposing a model for the implementation of a data warehousing system that integrates outpatients into the national healthcare framework. By leveraging data warehousing, healthcare delivery can be made more efficient through a robust repository that supports decision-making and policy formulation. The research focuses on the outpatient department in resource-scarce settings, proposing a novel multidimensional data model and practical framework implementation. The benefits include improved patient experiences, cost-effective service delivery, and enhanced patient management through electronic health records. Additionally, mobile apps are explored for patient navigation and reminders to enhance treatment adherence. The study’s results indicate that data warehousing can significantly improve healthcare delivery by consolidating critical data and facilitating better planning, resource allocation, and policy formulation. Ultimately, this approach offers valuable insights for optimizing healthcare systems in resource-constrained environments, enabling data-driven policies, and improving health outcomes across sub-Saharan Africa.

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

This article investigated the Automatic Generation Control(AGC) of multi-area multi-source interconnected systems with hydropower plants, thermal power plants, and wind energy. Adaptive Neuro-fuzzy controller integrated with the cascaded proportional-integral-derivative with filter (PIDF-PIDF) is a new cascaded controller (ANF-PIDF-PIDF) that has been presented as a secondary controller for applied hybrid power systems. The recent Skill Optimization Algorithm (SOA) is employed to optimize PIDF- PIDF controller parameter gains and the Adaptive Neuro-Fuzzy controller's inputs and output scaling factors. SOA is used to update the controller parameters with integral square error (ISE) employed as the objective function. A 1% step load disturbance was considered simultaneously in all three areas. The controller's performance is evaluated and compared with and without considering the effects of wind energy sources and non-linearity for ANF-PIDF-PIDF, PIDF-PIDF, and PIDF and it was determined that the ANF-PIDF-PIDF was the most efficient. The dynamic system performance is also compared with parallel high voltage direct current (HVDC) tie-lines. The investigation clearly shows that incorporating HVDC tie-line with multi-area, multi-source provides better dynamic performance in maximum amplitude, oscillation, and settling time. Additionally, sensitivity analysis is done and the optimum controller gains does not need to be reset to uncertain values in system loading conditions. All simulation results were evaluated using MATLAB 2016b.

This study used 10 replicate pens per treatment in a randomized complete block design and each pen contained 8 steers (initial BW = 305 ± 30.4 kg; n=80 steers/treatment) to determine if a phytogenic feed additive (PFA) with essential oils and plant extracts (PHYTOsolvan 200; DOSTOFARM, Westerstede, Germany) influences measures of growth or growth efficiency during the feedlot receiving phase in auction-derived beef steers. No steers were removed from the study; one steer from the control treatment was treated for respiratory disease. No mortality was noted in the present experiment. No appreciable differences were noted for BW, ADG, DMI, or feed conversion efficiency from d 1 to 29, 29 to 53, or during the cumulative receiving period (P ≥ 0.12). Performance based NEm and NEg were not influenced by dietary treatment (P ≥ 0.79). The ratio of observed-to-expected dietary net energy was not impacted by dietary treatment (P ≥ 0.71). These were healthy, high-growth potential Northern Plains steers. There was minimal morbidity (0.63%) and no mortality noted during the 53 d receiving study. Steers performed well and met growth performance expectations (the ratio of observed-to-expected NEm = 1.00), hence, it was not anticipated that the phytogenic compound would appreciably influence growth or health outcomes under the conditions of this experiment.

Cardiac myosin-binding protein C (MyBPC) is a thick-filament associated regulatory protein in the sarcomere. It regulates the sensitive contractile system of the myocardium by acting as a mechanical tether, sensitizing the thin filament or modulating myosin motor activity. Mutations in the MYBPC3 gene are a frequent cause for the development of hypertrophic cardiomyopathy, the most frequent cardiac disorder. Recently, the monoallelic double mutation MYBPC3Δ25bp/D389V has been discovered as a subset of the common MYBPC3Δ25bp variant in South Asia. MYBPC3Δ25bp/D389V carriers exhibit hyperdynamic features, which are considered an early finding for the development of hypertrophic cardiomyopathy. Using correlation-guided molecular dynamics simulations sampling, we show that the D389V mutation shifts the conformational distribution of the C2 domain of MyBPC. We further applied biochemical approaches to probe the effects of the D389V mutation on structure, thermostability and protein-protein interactions of MyBPC C2. The melting temperature (Tm) of MyBPC C2 D389V is decreased by 4 to 7 °C compared to wild type while the interaction of the C0-C2 domains with myosin and actin remains unchanged. Additionally, we utilized steered molecular dynamics (SMD) simulations to investigate the altered unfolding pathway of MyBPC C2 D389V. Based on our data, we propose a pathomechanism for the development of HCM in MYBPC3Δ25bp and MYBPC3Δ25bp/D389V carriers.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

The differentiation of ESCs into cardiomyocytes in vitro is an excellent and reliable model system for studying normal cardiomyocyte development in mammals, modeling cardiac diseases, and for use in drug screening. Mouse ESC differentiation still provides relevant biological information about cardiac development. However, the current methods for efficiently differentiating ESCs into cardiomyocytes are limiting. Here, we describe a “WNT Switch” method to efficiently commit mouse ESCs into cardiomyocytes using the small molecule WNT signaling modulators CHIR99021 and XAV939 in vitro. This method significantly improves the yield of beating cardiomyocytes, reduces number of treatments, and is less laborious.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC &gt;32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

Accurate forecasting of wind power generation plays a key role in improving the operation and management of a power system network and thereby its reliability and security. However, predicting wind power is complex due to the existence of high non-linearity in wind speed that eventually relies on prevailing weather conditions. In this paper, a novel hybrid deep learning model is proposed to improve the prediction accuracy of very short-term wind power generation for the Bodangora Wind Farm located in New South Wales, Australia. The hybrid model consists of convolutional layers, gated recurrent unit (GRU) layers and a fully connected neural network. The convolutional layers have the ability to automatically learn complex features from raw data while the GRU layers are capable of directly learning multiple parallel sequences of input data. The data sets of five-minute intervals from the wind farm are used in case studies to demonstrate the effectiveness of the proposed model against other advanced existing models, including long short-term memory (LSTM), GRU, autoregressive integrated moving average (ARIMA) and support vector machine (SVM), which are tuned to optimise outcome. It is observed that the hybrid deep learning model exhibits superior performance over other forecasting models to improve the accuracy of wind power forecasting, numerically, up to 1.59 per cent in mean absolute error, 3.73 per cent in root mean square error and 8.13 per cent in mean absolute percentage error.

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

We 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.

In this paper, a multi-operator differential evolution algorithm (MODE) is proposed to solve the Optimal Power Flow (OPF) problem and is called MODE-OPF. The MODE-OPF utilizes the strengths of more than one differential evolution (DE) operator in a single algorithmic framework. Additionally, an adaptive method (AM) is proposed to update the number of solutions evolved by each DE operator based on both the diversity of population and quality of solutions. This adaptive method has the ability to maintain diversity at the early stages of the optimization process and boost convergence at the later ones. The performance of the proposed MODE-OPF is tested by solving OPF problems for both small and large IEEE bus systems (i.e., IEEE-30 and IEEE-118) while considering the intermittent solar and wind power generation. To prove the suitability of this proposed algorithm, its performance has been compared against several state-of-the-art optimization algorithms, where MODE-OPF outperforms other algorithms in all experimental results and thereby improving a network's performance with lower cost. MODE-OPF decreases the total generation cost up to 24.08%, the real power loss up to 6.80% and the total generation cost with emission up to 8.56%.

Recent data suggest that K-Ras4B (hereafter K-Ras) can drive cancer cell stemness via calmodulin (CaM)-dependent, non-canonical Wnt-signalling. Here we examined whether another Ca2+-binding protein, the CaM-related centrin1, binds to K-Ras and could mediate some K-Ras functions that were previously ascribed to CaM. While CaM and centrin1 appear to distinguish between peptides that were derived from their classical targets, they both bind to K-Ras in cells. Cellular BRET-data suggest that CaM engages more with K-Ras than centrin1 and that the interaction with the C-terminal membrane anchor of K-Ras is sufficient for this. Surprisingly, binding of neither K-Ras nor its membrane anchor alone to CaM or centrin1 is sensitive to inhibition of prenylation. In support of an involvement of the G-domain of K-Ras in cellular complexes with these Ca2+-binding proteins, we find that oncogenic K-RasG12V displays increased engagement with both CaM and centrin1. This is abrogated by addition of the D38A effector-site mutation, suggesting that K-RasG12V is held together with CaM or centrin1 in complexes with effectors. When treated with CaM-inhibitors the BRET-interaction of K-RasG12V with centrin1 was also disrupted in the low micromolar range, comparable to that with CaM. While CaM predominates in regulating functional membrane anchorage of K-Ras, it has a very similar co-distribution with centrin1 on mitotic organelles. Given these results, a significant overlap of the CaM- and centrin1-dependent functions of K-Ras is suggested.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

CGT is composed of fiber residues, leaves, dust particles, soil and others derived during the ginning and yarn spinning process at processing industries,. In the cotton spinning industrial clusters, farmers are using CGT) as one of the alternative roughage feed for their sheep, mainly during forage shortages in the summer months. To have baseline information on farmers using gin and factors driving them to choose CGT as a roughage source, which need to be identified for future planning on the usage of CGT in sheep feeding. Considering the above facts, the present study was undertaken to assess socio-personal characteristics, managemental practices associated with farmers using cotton gin in the feeding of sheep and also identify the factors driving the choice of the CGT as the primary source of roughage in the cotton spinning industry cluster of Tamil Nadu. For this, a survey among 80 sheep farmers was carried out using a pre-tested in-terview schedule. The collected data was analysed using descriptive statistics and logit regres-sion. The results indicated that the majority of male, aged, and large-land farmers were involved in practicing CGT feeding during the summer and also indicated the non-availability of green fodder during the summer season. The coarse type of CGT preferred more than the fine type of CGT trash in that area due to quality perception and price. The replacement level of CGT as roughage ranged from 33 to 75% of the total roughage requirement per day. About 88 percent-age of farmers were highly satisfied with the results of using CGT and they also expressed that the presence of foreign particles and dust were the major problems with using CGT. The choice of CGT as primary roughage among sheep farmers was primarily influenced by selective farming contexts, namely landholding, access to labour, and feeding practices of other livestock with cotton gin. Further, research has to be focused on to improve the quality of CGT in the future, as it is being utilised largely by sheep farmers.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.