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.

The manipulation of participant allocation in randomized controlled trials to achieve equal groups sizes may introduce allocation bias potentially leading to larger treatment effect estimates. This study aimed to estimate the proportion of nursing trials that have precisely equal group sizes and examine if there was an association with trial outcome. Data were extracted from a sample of 148 randomized controlled trials published in nursing science journals in 2017. One hundred trials (68%) had precisely equal group sizes. Respectively, a positive outcome was reported in 70% and 58% of trials with equal/unequal groups. Trials from Asia were more likely to have equal group sizes than those from the rest of the world. Most trials reported a sample size calculation (n=105, 71%). In a third of trials (n=36, 34%), the number of participants recruited precisely matched the requirement of the sample size calculation; this was significantly more common in studies with equal group sizes. The high number of nursing trials with equal groups may suggest nurses con-ducting clinical trials are manipulating participant allocation to ensure equal group size increasing the risk of bias.

This article explores the implementation of high accuracy GPS denied Ad-Hoc localization. There is little research on Ad-Hock UWB-enabled localization systems with mobile and stationary nodes. This work aims to demonstrate the localization of bicycle-modeled robots in a non-static environment through a mesh network of mobile, stationary robots and ultra-wideband sensors. The non-static environment adds a layer of complexity when actors can enter and exit the node’s field of view. The method starts with an initial localization step where each unmanned ground vehicle (UGV) uses the surrounding, available anchors to derive an initial local or, if possible, global position estimate. The initial localization uses a simplified implementation of the iterative multi-iteration Ad-Hoc Localization System (AHLos). This estimate was refined using an unscented Kalman filter (UKF) following a constant turn rate and velocity magnitude model (CTRV). The UKF fuses the robot’s odometry and the range measurements from the Decawave ultra-wideband receivers stationed on the network nodes. Through this position estimation stage, the robot broadcasts to its neighbors its estimated position to help the others further improve their localization estimates and localize themselves. This wave-like cycle of nodes helping to localize each other allows the network to act as a mobile Ad-Hoc localization network.

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

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.

Stream chemistry effectively integrates watershed ecosystem processes on both spatial and temporal scales. Streams of coastal areas integrate a more homogeneous, flat topography wherein there can be interactions between the stream and the body of water into which it drains, especially where tidal fluxes occur. The present study assessed water quality of Thompson Bayou, which comes to the campus of the University of West Florida in a wetland after flowing through 4 km of commercial and private property with associated impacts on water quality. Sampling was carried out for one year at eight discrete sites along Thompson Bayou from the UWF campus to the Escambia River. We used a portable field meter to measure temperature, pH, dissolved O2 (DO), and specific conductivity (SC). Except for temperature, all variables exhibited a spatial pattern of significant variation with distance, with consistent increases in DO and SC as the stream approached the river. These variables also exhibited a temporal pattern of significant seasonal variation, including—and especially—temperature. Data suggest that spatial and temporal patterns of water quality of Thompson Bayou are determined by (1) processing of water by the wetland, (2) interactions of the stream channel with upland forest stands, and (3) the tidal hydrology of the Escambia River.

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.

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target actin-binding protein gelsolin that is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2-binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood. Here, we model LPA binding to the PIP2-binding domain of gelsolin in the gelsolin-actin complex through extensive ten microsecond atomistic molecular dynamics (MD) simulations. We predict that LPA binding causes a local conformational rearrangement due to LPA interactions with both gelsolin and actin residues. These conformational changes are a result of the amphipathic nature of LPA, where the anionic phosphate, polar glycerol and ester groups, and lipophilic aliphatic tail mediate LPA binding via charged electrostatic, hydrogen bonding, and van der Waals interactions. The negatively-charged LPA headgroup binds to the PIP2-binding domain of gelsolin-actin while its hydrophobic tail is inserted into actin, creating a strong LPA-insertion pocket that weakens the gelsolin–actin interface. The computed structure, dynamics, and energetics of the ternary gelsolin–LPA–actin complex confirms that a quantitative OC assay is possible based on LPA-triggered actin release from the gelsolin-actin complex.

Is it possible to develop a meaningful measure for the complexity of a simulation model? Algorithmic information theory provides concepts that have been applied in other areas of research for the practical measurement of object complexity. This article offers an overview of complexity from a variety of perspectives and provides a body of knowledge with respect to the complexity of simulation models. Key terms of model detail, resolution, and scope are defined. An important concept from algorithmic information theory, Kolmogorov complexity, and an application of this concept, normalized compression distance, are used to indicate the possibility of measuring changes in model detail. Additional research in this area can advance the modeling and simulation body of knowledge toward the practical application of measuring simulation model complexity. Examples show that KC and NCD measurements of simulation models can detect changes in scope and detail.

Early diagnosis of paroxysmal atrial fibrillation (PAF) could suggest patients to receive timely interventions in clinical practice. Various PAF onset prediction algorithms might benefit from accurate heart rate variability (HRV) analysis and machine learning classification but to be challenged in real-time monitoring scenarios. The aim of this study is to present an end-to-end deep learning based PAFNet model that integrates a sliding window technique on raw R-R interval of electrocardiogram (ECG) segments to achieve a real-time prediction of PAF onsets. This integration enable the deep convolutional neural network (CNN) to be customized as a light-weight architecture that accommodates the size of sliding windows simply by altering the input layer, specifically its effectiveness in making a new prediction with each new heartbeat. Catering to potential influence of input sizes, three CNN models were trained using 50, 100, and 200 R-R intervals, respectively. For each model, the performance of automated algorithms was evaluated for PAF prediction using a ten-fold cross-validation. As a results, a total of 56,381 PAFN-type and 56,900 N-type R-R interval segments was collected from publicly accessible ECG databases, and a promising prediction performance of the automated algorithm with a 100 R-R intervals was achieved in terms of the sensitivity of 97.12%, the specificity of 97.77%, and the accuracy of 97.45%, respectively. Importantly, the automated algorithm with a sliding windows step of 1 could process one sample in only 23.1 milliseconds and identify the onset of PAF at least 45 minutes in advance. The present results suggest that the sliding window technique on raw R-R interval sequences along by deep learning based algorithms may offers the possibility of providing an accurate, real-time, and end-to-end clinical tool for mass monitoring of PAF.

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as sub-Saharan Africa (SSA). The advent of coronavirus has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis (PRISMA). We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full-text via EBSCOhost databases from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to the gold reference standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458-0.541); 0.535 (95% CI: 0.401-0.663); 0.952 (95% CI: 0.60-1.324); 1.381 (95% CI: 0.391-4.879); and 0.944 (95% CI: 0.579-1.538), respectively. Evidence shows that mobile-linked POC diagnostics' diagnostic accuracy is presently moderate in detecting infections in sub-Saharan Africa. Future research is recommended to evaluate mHealth devices' diagnostics with excellent sensitivities and specificities in diagnosing diseases in this setting.

Surgical knots are sequences of half-knots (H) or half-hitches (S), defined by their number of throws, by an opposite or similar rotation compared with the previous one and for half-hitches, whether sliding (s) or blocking (b). Opposite rotation results in (more secure) symmetric (s) knots, similar rotation in asymmetric (a) knots, and changing active and passive ends has the same effect as changing rotation. Loop security is the force to keep tissue together after a first half-knot or sliding half-hitches. With polyfilament sutures H2, H3, SSs and SSsSsSs have a loop security of 10, 18, 28 and 48 Newton (N), respectively. With monofilament sutures, they are only 7, 16, 18 and 25N. Since many knots can reorganise, the definition of knot security as the force at which the knot opens or the suture breaks should be replaced by the clinically more relevant percentage of clinically dangerous and insecure knots. Secure knots with polyfilament sutures require a minimum of 4 or 5 throws, but the risk of destabilisation is high. With monofilament sutures, only 2 symmetric+4 asymmetric blocking half-hitches are secure. In conclusion, half-hitch sequences are recommended since mandatory for monofilament sutures, adding flexibility for loop security with less risk of destabilisation.

The present study aims to show on the one hand how easily one can get confused when doing research on the internet. Different platforms, fora and homepages supply the visitor with different - and sometimes contradictory - information. On the other hand, we show how to overcome these contradictions and produce valuable research based on almost all sources. For our study, we use the example of the Feit-Thompson conjecture, which is - in opposite to the well-known Feit-Thompson theorem - not widely known. We try to clarify the scientific literature on this topic and we embed our own result into the present state of art. We prove that pq−1p−1 does not divide qp−1q−1 if p and q are twin primes, i.e. p=q+2. Thus we prove that the Feit-Thompson conjecture is true for twin prime numbers.

A simple protocol for preparation of O-acylated enol form - (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by 1H-, 13C-and DEPT135 NMR spectra, including {1H,1H} COSY, {1H,13C} HSQC, {1H,13C} HMBC and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in 4-th position in the chroman ring and accounting the steric hindrance of the ester group in 3-th place was confirmed.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

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;

This paper sets out to reconsider the Hohfeldian framework of rights in celebration of the centenary anniversary of Hohfeld's death. It begins by conceptualising each of the Hohfeldian incidents or rights before outlining the molecular or complex structure of rights to ‘things’. I adopt a broad use of the term of ‘right’ and apply it to Legal, Moral, Equitable and Human conceptions and constructions. It sets out an argument in favour of a further definitional model - in addition to Hohfeld’s scheme of opposites and correlatives – which focuses on the function of these conceptual rights. Finally, it will consider the broader implications of how rights are held and the relationships which these rights govern. Ultimately, this paper seeks to demonstrate the benefit, and indeed necessity, of the Hohfeldian model in any discussion of rights. Without it ‘rights talk’ is debased and impoverished.

Background: Mental health difficulties during teenage years e are common and are a risk factor for later mental and physical health problems. Rural young people are at greater risk for mental health difficulties and have less access to services than their urban counterparts. The purpose of this study was to explore young people and their carers’ experiences of mental health support provided by a rural mobile service, and to identify access enablers from the service users’ perspective. Methods: A qualitative descriptive approach was used to analyse twelve interviews with current service users and eight interviews with family members of young people who had accessed the service.Results: Three main themes were identified: (a) Access and flexibility, (b) Clinicians’ qualities and strategies, and (c) Experiences of change. The mobile service was perceived to be effective in producing positive change in mental health, relationships and attainment of life goals. Key enablers to access included the flexibility of the mobile service, the variety of service delivery modes and therapeutic methods offered, the ease of access facilitated by location in schools, and young people’s autonomy in how they chose to utilise the service. Conclusion: This study provides information about what is important to rural young people and their families in mental health service provision. The findings have implications for changing the way services are organized and operated. Healthcare policy and services could support user-led model design that incorporates the access and use enablers and removes the barriers to rural mental health support.

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.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

Despite the abundance of tree diversity in the natural world, and generally high tree species richness in urban areas, urban forests continue to be dominated by a limited number of species. As socio-ecological systems, urban forests are shaped by historical and current management efforts and decision-making of a wide range of human actors. Drawing on past research, we offer a conceptual framework for describing the complex interactions among tree producers and consumers as trees are selected, grown, specified, and planted in private and public urban areas. We illustrate how multiple layers of selection criteria filter down the entirety of potential local tree diversity to a handful of commonly used and accepted tree species. We detail the actors and decision makers who impact tree composition and diversity across several land types. Finally, we identify research, education and outreach needs as they relate to creating more diverse and resilient urban forest ecosystems.

PdRe/Al2O3 catalysts are highly selective for hydrogenation of furfural to furfuryl alcohol (FAL). Moreover, synergy between the metals can result in greater specific activity (higher turnover frequency, TOF) than exhibited by either metal alone. Bimetallic catalyst structure depends strongly on the metal precursors employed and their addition sequence to the support. In this work, PdRe/Al2O3 catalysts were prepared by: (i) co impregnation (CI) and sequential impregnation (SI) of  Al2O3 using HReO4 and Pd(NO3)2, (ii) SI using NH4ReO4 and [Pd(NH3)4(NO3)2], (iii) HReO4 addition to a reduced and passivated Pd/Al2O3 catalyst, and (iv) impregnation with the double complex salt (DCS), [Pd(NH3)4(ReO4)2]. Raman spectroscopy and temperature-programmed reduction (TPR) evidence larger supported PdO crystallites in catalysts prepared using Pd(NO3)2 than [Pd(NH3)4(NO3)2]. Surface [ReO4]- species detected by Raman exhibit TPR peak temperatures from ranging 85 to 260°C (versus 375°C for Re/Al2O3). After H2 reduction at 400°C, the catalysts were characterized by chemisorption, temperature-programmed hydride decomposition (TPHD), CO diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and scanning transmission electron microscopy (STEM) with energy-dispersive x-ray (EDX) spectroscopy. The CI catalyst containing supported Pd-Re alloy crystallites had a TOF similar to Pd/Al2O3 but higher (61%) FAL selectivity. In contrast, catalysts prepared by methods (ii-iv) containing supported Pd-Re nanoparticles exhibit higher TOFs and up to 78% FAL selectivity.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

Background: HIV self-testing (HIVST) is one of the recommended approaches for HIV testing services, particularly for helping reach populations who would not normally access facility-based HIV testing. HIVST must be tailored to different populations to ensure uptake. Objective: The main objective of this study was to develop an acceptable HIVST delivery strategy to help improve urban men’s engagement with HIV services. Methods: We invited key stakeholders for urban men’s HIV services to participate in a co-creation workshop aimed at developing HIVST delivery approaches for urban men, using eThekwini municipality as a study setting. We conducted purposive sampling to include health care users and health care providers, representing a range of views across the public sector and voluntary sector. We employed the Nominal Group Technique (NGT) method for data collection. The NGT workshop was conducted in two consecutive phases: phase one was focused on determining barriers for men’s engagement with the current/facility-based HIV testing services; phase two was aimed at determining HIVST delivery strategies. We used the results of the NGT to design a tailored HIVST strategy for urban men in eThekwini District. Results: Participants identified the following psychological factors as the most important barriers to uptake of HIV testing services by urban men: stigma, ignorance about the importance of testing and testing process as well as fear of positive test results. Key stakeholders suggested internal motivation strategies as a potentially effective approach to support HIVST delivery strategy. Guided by the NGT results, we designed a HIVST delivery strategy that is supported by a risk communication approach Conclusion: We designed an evidence-based risk communication mobile health (mHealth) strategy coupled with SARS COV-2 self-testing tailored to improve men’s uptake of HIVST. A follow-up study to evaluate the feasibility of implementing these approaches is recommended.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

This research undertakes a quantitative exploration of the impact of procurement mo-dalities on economic efficiency and inclusive procurement within the Dominican Repub-lic's public sector. Applying data science methodologies and machine learning techniques, this study analyzes a rich dataset of public procurement contracts spanning from 2018 to 2023. A focus is placed on understanding how different procurement modalities affect contract amounts and processing times—two key indicators of economic efficiency. Machine learning models, including Random Forest and Gradient Boosting, are em-ployed to predict these essential metrics across different procurement modalities. The findings indicate a significant positive correlation between certain procurement modali-ties and economic efficiency. The machine learning models reveal that procurement strategies focused on local sourcing and transparent bidding processes tend to yield high-er economic returns and more equitable outcomes. This research underscores the poten-tial of quantitative analysis to inform procurement policies, fostering a more economi-cally efficient and inclusive procurement ecosystem in the Dominican Republic's public sector. The insights garnered from this study could have significant implications for the design of more inclusive procurement strategies, contributing to socio-economic growth and corruption reduction in the Dominican Republic.

Solvent accessible surface area (SASA) of amino acid residues plays a significant role in inter-residue, protein-ligand, and protein-protein interactions. Affecting the exposure and interactions of hydrophobic and hydrophilic regions, driving protein folding. While previous SASA calculations are accurate with respect to the chosen parameters of simulation, they do not account for the dynamic behavior of peptides in solution under physiological conditions and cannot be used to compare populations within phi,psi dihedral angle space (phi,psi space). Molecular dynamics trajectories obtained at 310 K, 1 atm, and 150 mM NaCl for the Ac-Ala-Xaa-Ala-NH2 model peptides simulated using the CHARMM36m force field and TIP3Pm water as implemented in GROMACS 2022 were used to study SASA. The more balanced parametrization of CHARMM36m, resulted in increased sampling of beta region compared to alpha, alphaL, and epsilon regions were observed. There are statistically significant differences in SASA for the backbone and side chain comparing the beta, alpha, alphaL, epsilon and contiguous regions of phi,psi space. Differences occur in sampled phi,psi space particularly in the alphaL and epsilon regions of phi,psi space as a function of side chain size and chemical properties. The epsilon region of phi,psi space is not significantly sampled for multiple amino acids while the alphaL region is.

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).

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

X-ray absorption fine structure (XAFS) spectroscopy, temperature-programmed reduction (TPR) and temperature-programmed hydride decomposition (TPHD) were employed to elucidate the structures of a series of PdRe/Al2O3 bimetallic catalysts for selective hydrogenation of furfural. TPR evidenced low-temperature Re reduction in the bimetallic catalysts consistent with migration of [ReO4]- (perrhenate) species to hydrogen-covered Pd nanoparticles on highly hydroxylated  Al2O3. TPHD revealed strong suppression of β-PdHx formation in the reduced catalysts prepared by (i) co-impregnation and (ii) [HReO4] impregnation of reduced Pd/Al2O3 indicating formation of Pd-rich alloy nanoparticles; however, reduced catalysts prepared by (iii) [Pd(NH3)4]2+ impregnation of calcined Re/Al2O3 and subsequent re-calcination did not. Re LIII X-ray absorption edge shifts were used to determine average Re oxidation states after reduction at 400°C. XAFS spectroscopy and high-angle annular dark field (HAADF)-scanning transmission electron microscopy (STEM) revealed that a reduced 5 wt.% Re/Al2O3 catalyst contained small Re clusters and nanoparticles comprising Re atoms in low positive oxidation states (~1.5+) and incompletely reduced Re species (primarily Re4+). XAFS spectroscopy of the bimetallic catalysts evidenced Pd-Re bonding consistent with Pd-rich alloy formation. Pd and Re total first-shell coordination numbers suggest that either Re is segregated to the surface (and Pd to the core) of alloy nanoparticles and/or segregated Pd nanoparticles are larger than Re nanoparticles (or clusters). The Cowley short-range order parameters are strongly positive indicating a high degree of heterogeneity (clustering or segregation of metal atoms) in these bimetallic catalysts. Catalysts prepared using the Pd(NH3)4[ReO4]2 double complex salt (DCS) exhibit greater Pd-Re intermixing but remain heterogeneous on the atomic scale.

Coral reefs are critical ecosystems globally for marine fauna, biodiversity and through the services they provide to humanity. However, they are significantly threatened by anthropogenic stressors, such as climate change. By combining 9 environmental variables and ecological and health-based thresholds obtained from the available literature, we develop, using fuzzy logic (discontinuous functions), a Coral Reef Stress Exposure Index (CRSEI) for remotely monitoring coral reef exposure to environmental stressors. Our approach capitalises on the abundance of readily available satellite Earth Observation (EO) data available in the Google Earth Engine (GEE) cloud-based geospatial processing platform. CRSEI values from 3157 distinct reefs were generated and mapped across 12 important coral reef ecosystem regions. Quantitative analyses indicated that the index detected significant temporal differences in stress and was, therefore, able to capture historic change at a global scale. We also applied the CRSEI to three case-study reef ecosystems, previously well-monitored for stress and disturbance using other methods. PCA analysis indicated that depth, current, sea surface temperature (SST) and SST anomaly accounted for the greatest contribution to the variance in stress in these three regions. The CRSEI corroborated temporal and spatial differences in stress exposure from known disturbances within these reference regions, in addition to identifying the potential drivers of inter- and intra-region differences in stress, namely depth, degree heating weeks and SST anomaly. We discuss how the index can be further improved in future with site-specific thresholds for each stress variable, and the incorporation of additional variables not currently available in GEE. This index provides an open access tool, built around a free and powerful processing platform, that has broad potential to assist in the regular monitoring of our increasingly imperilled coral reef ecosystems, and, in particular, those that are remote or inaccessible.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

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.

Significant Wave Height(SWH) is a crucial parameter in oceanographic research, essential for understanding various marine and atmospheric processes. Traditional methods for obtaining SWH, such as ship-based and buoy measurements, face limitations like limited spatial coverage and high operational costs. With the advancement of Global Navigation Satellite Systems reflectometry(GNSS-R) technology, a new method for retrieving SWH has emerged, demonstrating promising results. This study utilizes Radio occultation sounder(GNOS) data from the FY-3E satellite and incorporates the latest Vision Transformer(ViT) technology to investigate GNSS-R-based SWH retrieval. We designed and evaluated various deep learning models, including ANN-Wave, CNN-Wave, Hybrid-Wave, Trans-Wave, and ViT-Wave. Through comparative training using ERA5 data, the ViT-Wave model was identified as the optimal retrieval model. The ViT-Wave model achieved an Root Mean Square Error(RMSE) accuracy of 0.4052 meters and Mean Absolute Error(MAE) accuracy of 0.2700 meters, significantly outperforming both traditional methods and newer deep learning approaches utilizing Cyclone Global Navigation Satellite Systems(CYGNSS) data. These results underscore the potential of integrating GNSS-R technology with advanced deep learning models to enhance SWH retrieval accuracy and reliability in oceanographic research.

Access to urban green and blue spaces (UGBS) has been associated with positive effects on health and wellbeing; however, the past decades have seen a decline in quality and user satisfaction with UGBS. This reflects the mounting challenges that many UK cities face in providing appropriate public facilities alongside issues such as health inequalities, an ageing population, climate change, and loss of biodiversity. At present, little is known about the preferences of different population subgroups and, specifically, the UGBS they visit and the spaces they avoid. Using a public participatory geographic information system (PPGIS), the overall aim of the research presented here was to investigate the preferences of different population subgroups in urban areas, and the UGBS they visit, using Edinburgh, Scotland as a case study. We created a baseline visitor demographic profile for UGBS use, and highlighted how visitors perceive, physically access, use, and engage with UGBS. The results revealed considerable variation in UGBS preference: one person’s favourite UGBS may be one that someone else dislikes and avoids. It is clear that adapting UGBS to suit local communities should not be a ‘one-size-fits-all’ approach. The conflicting views and preferences of different groups of respondents point to the importance of developing policies and park management plans that can accommodate a variety of uses and experiential qualities within individual parks. PPGIS offers an ideal tool for achieving this

.Abstract: Indonesia, one of the Asia Pacific LMICs, has suffered from a chronic medical workforce shortage. However, there are limited published studies describing the approaches implemented by the Indonesian government regarding the recruitment and retention of the medical workforce. This case study aimed to understand the current practices for recruitment and retention of the medical workforce in Indonesian rural and remote provinces. We conducted a case study of the Maluku Province of Indonesia with document analysis and key informant interviews with officials responsible for medical workforce recruitment and retention. We used the WHO’s guidelines as an analytical matrix to examine the recruitment and retention practices under four domains, i) educational, ii) regulatory, iii) financial, and iv) professional and personal development, and classified them into University/Medical School level and Government/Non-government level. Our findings suggest that Indonesia has implemented most of the WHO-recommended medical workforce recruitment and retention strategies. However, implementation is still problematic; hence, the aim of establishing an adequate, sustainable medical workforce has not been reached. Nationwide government intervention in educational aspects is important to magnify the impact of the regional medical school initiatives. Relevant programs must be re-evaluated and re-enforced concerning significance, comprehensiveness and effectiveness for sustainable rural and remote medical workforce.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

Sexual issues and treatment side effects are not routinely discussed with men receiving treatment for prostate cancer and support to address these concerns is not consistent across settings. This study evaluates a brief e-learning resource designed to improve sexual wellbeing support and examine its effects on healthcare professionals’ sexual attitudes and beliefs. Healthcare professionals (n=44) completed an online questionnaire at baseline which included a modified 12-item sexual attitudes and beliefs survey (SABS). Follow-up questionnaires were completed immediately after the e-learning and at 4 weeks. Data were analysed using one-way, repeat measures ANOVAs to assess change in attitudes and beliefs over time. Significant improvements were observed at follow-up for a number of survey statements including ‘knowledge and understanding’, ‘confidence in discussing sexual wellbeing’ and the extent to which participants felt ‘equipped with the language to initiate conversations’. The resource was seen as concise, relevant to practice, and as providing useful information on potential side effects of treatment. Brief, e-learning has potential to address barriers to sexual wellbeing communication and promote delivery of support for prostate cancer survivors. Practical methods and resources should be included with these interventions to support implementation of learning and long-term changes in clinical behaviour.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

This study evaluated the use of filtration and UV-A photocatalysis for the reduction of particulate matter (PM) and airborne bacterial pathogens in swine barns. Two MERV filters (8 and 15) were used to mitigate PM concentrations measured at the PM 1, PM 2.5, respirable PM, and PM 10 ranges. Filtration was also used to generate different levels of airborne pathogens to be treated by UV-A. Results show that MERV 8 and 15 filters effectively reduced PM concentrations (96-98%) in air exhausted from a swine barn (p ranged from < 0.01 to 0.04). UV-A photocatalysis did not mitigate PM concentrations. UV-A photocatalysis treatment reduced measured colony-forming units (CFUs) by 15-95%. The CFU percent reduction was higher when airborne PM concentration was low. The numeric results suggested a real mitigation effect despite p-values that did not meet the usual statistical cut-off of <0.05 for significance due to the large variability of the CFU control samples. Normalization of measured airborne pathogen concentrations by smaller PM size range concentrations led to emerging significant treatment differences for CFUs. A significant decrease (~60% reduction; p < 0.03) in the concentration of viable airborne bacteria was shown for all PM below the 10-micron range.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

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

Crop plants should be resilient to climatic factors in order to feed ever-increasing populations. Plants have developed stress-responsive mechanisms by changing their metabolic pathways and switching the stress-responsive genes. The discovery of plant transcriptional factors (TFs) as key regulators of different biotic and abiotic stresses have opened up new horizons for plant scientists. TFs perceive the signal and switch certain stress-responsive genes on and off by binding to different cis-regulatory elements. The above 50 species of plant TFs have been reported in nature. DREB, bZIP, MYB, NAC, Zinc-finger, HSF, Dof, WRKY, and NF-Y are important with respect to biotic and abiotic stresses whereas the role of many TFs is yet to explore. In this review, we summarize the role of different stress-responsive TFs with respect to biotic and abiotic stresses. Further, challenges and future opportunities linked with TFs for developing climate-resilient crops are also elaborated.

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.

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

Population based studies have associated poor living conditions with the persistent disparity in the health of Aboriginal and non-Aboriginal Australians. This project assesses the applicability of the Health Community Assessment Tool and its role in improving the environment of a small community in the Midwest of WA. The action research cycles started with the initial reflection on the suitability of the HCAT version 2 for the local community context and whether it was fit-for-purpose. The researcher provided ‘critical companionship’, while the participants of the study were invited to be co-researchers (the Assessors) who critically examined the HCAT and assess the community. The relevant domains to the serviced town (an outer regional community) were pest control and animal management; healthy housing; food supply; community vibrancy, pride and safety; reducing environmental tobacco smoke; and promoting physical activity. The Assessors found the HCAT descriptors mostly aligned with their community context but found some of the items difficult to apply. Based on participant’s suggestions, some of the original scoring scales were reformatted. School attendance and illicit drug use were identified as a key outcome indicator for youth but were missing from the HCAT. The HCAT domains applied helped streamlining core business of agencies in the local community. The face validity of HCAT items were confirmed in this research with minor adjustments to reflect local context. Youth engagement to education is of high community concern and the development of an item would create similar interagency collaborative dialogues.

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.

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

The incidence of Severe Combined Immunodeficiency (SCID) in Manitoba, (1/15,000), is at least three to four times higher than the national average and that reported from other jurisdictions. It is overrepresented in two population groups: Mennonites (ZAP70 founder mutation) and First Nations of Northern Cree ancestry (IKBKB founder mutation). We have previously demonstrated that in these two populations the most widely utilized T-cell receptor excision circle (TREC) assay is an ineffective newborn screening test to detect SCID as these patients have normal numbers of mature T-cells. We have developed a semi-automated, closed tube, high resolution DNA melting procedure to simultaneously genotype both of these mutations from the same newborn blood spot DNA extract used for the TREC assay. Parallel analysis of all newborn screening specimens utilizing both TREC analysis and the high resolution DNA procedure should provide as complete ascertainment as possible of SCID in the Manitoba population.

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.

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

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.

Background: Neurosarcoidosis is a great mimic, and its distinction from multiple sclerosis and other disorders can be particularly troublesome. We investigated whether cerebrospinal fluid (CSF) examination could help distinguish these two conditions and propose new diagnostic criteria. Methods: Stringent hierarchical diagnostic criteria were formulated. These were then applied prospectively to 531 neurological patients in whom neurosarcoidosis entered the differential diagnosis. The CSF total protein (TP), white cell count (WCC) and angiotensin-converting enzyme (ACE) levels were measured. The CSF and serum IgG patterns after isoelectric focusing were compared. Not all CSF parameters were measured in every patient. Results: 85/531 (16%) cases examined were diagnosed with neurosarcoidosis. Only 22 of these 85 (26%) met stringent diagnostic criteria. Intrathecal synthesis of oligoclonal IgG was evident in only 1/19 (5%) who fulfilled these criteria compared to 19/59 (32%) cases who did not (p = 0.03). CSF TP levels > 1g/L were more common in patients meeting the stringent criteria compared to the remainder of the patients, i.e. 11/22 (50%) vs 14/58 (24%) (p<0.05). Eleven out of 20 cases (55%) fulfilling stringent criteria had elevated CSF WCCs, and 6/12 cases (50%) had raised CSF ACE, neither significantly different from the remaining cases. Mean CSF TP, WCC, and ACE levels did not differ significantly between any groups of patients. Interpretation: Large elevations in CSF total protein, white cell count, and ACE occur in neurosarcoidosis but are rare in multiple sclerosis. However, the diagnostic use of these tests is limited since minimal changes may occur in both conditions. In contrast, intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is very uncommon in neurosarcoidosis whilst occurring in 95-98% of cases of multiple sclerosis. This observation implies that the immunopathogenesis of the two disorders is quite different. We suggest caution in diagnosing neurosarcoidosis when intrathecal oligoclonal IgG synthesis is detected. We propose new diagnostic criteria for neurosarcoidosis for future research.

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

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

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

Achieving global goals on sustainable nutrition, health, and wellbeing will depend on delivering enhanced diets to humankind. This will require, among others, instantaneous access to information on food quality at key points within agri-food systems. Although stationary methods are usually used to quantify grain quality (wet-lab chemistry, benchtop NIR spectrometer); these do not suit many required user-cases, such as stakeholders in decentralized agri-food-chains that are typical for emerging economies. Therefore, we explored new technologies and models that might aid these particular user-cases. For this purpose, we generated the NIR spectra of 328 grain samples from multiple cereals (finger millet, foxtail millet, maize, pearl millet, sorghum) with a standard benchtop NIR Spectrometer (DS2500, FOSS) and a novel mobile NIR-based sensor (HL-EVT5, Hone). We explored a range of classical deterministic and novel machine learning (ML)-driven models to build calibrations out of the NIR spectra. We were able to build relevant calibrations out of both types of spectra. At the same time, ML-based methods enhanced the prediction capacity of calibration models compared to classical deterministic methods. We also documented that the prediction of grain protein content based on NIR spectra generated by a mobile sensor (HL-EVT5, Hone) was highly relevant for quantitative protein predictions (R2 = 0.91, RMSE = 0.97, RPD = 3.48). Thus, the findings of this study lay the foundations on which to expand the utilization of NIR spectroscopy applications for agricultural research and development.

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

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

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

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

Pelagic stingray (Pteroplatytrygon violacea) is the only species of stingray (Dasyatidae) that utilizes both pelagic and demersal habitats. It is the main bycatch species in pelagic longline fisheries targeting bluefin tuna in the Gulf of Lions. In the Mediterranean Sea, their stock structure, behavioural ecology and movements are unknown. For the first time in the Mediterranean, 17 individuals (39 to 60 cm disc width) were tagged with pop-up satellite archival transmitting tags using a novel method of tag attachment, to investigate horizontal and vertical movements. The tags were attached for between two and 60 days. Between the months of July and October, pelagic stingray occupied a temperature range of 12.5 to 26.6°C, and a depth range extending from the surface to 480 m. Monthly trends in catch-per-unit-effort (CPUE) of pelagic stingray peaked in August and decreased by late autumn. Pelagic stingray may aggregate on the continental shelf during summer, and move southwards in early autumn, and this movement pattern is considered in relation to the reproductive cycle and overwintering. Future work and options for bycatch mitigation are discussed.

In this paper, spatial pulse position modulation (SPPM) is used as a case study to investigate the performance of the optical spatial modulation (SM) technique in outdoor atmospheric turbulence (AT). A closed-form expression for the upper bound on the asymptotic symbol error rate (SER) of SPPM in AT is derived and validated by closely-matching simulation results. The error performance is evaluated in weak to strong AT conditions. As the AT strength increases from the weak to strong, the channel fading coefficients become more dispersed and differentiable. Thus, a better error performance is observed under moderate-to-strong AT compared to weak AT. The performance in weak AT can be improved by applying unequal power allocation to make FSO links more distinguishable at the receiver. Receive diversity is considered to mitigate irradiance fluctuation and improve the robustness of the system to turbulence-induced channel fading. The diversity order is computed as half of the number of detectors. Performance comparisons, in terms of energy and spectral efficiencies, are drawn between the SPPM scheme and conventional MIMO schemes such as repetition coding and spatial multiplexing.

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.

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

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 oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

The loop and knot securities of 2 braided and 2 monofilament sutures of four diameters (3.0, 2.0, 0, 1) were evaluated with a tensiometer for four 4-throw knots known to be secure with a 2.0 polyfilament suture. Loop security of monocryl 1 is low, being 14.7 + 3.0 Newton (N) for a 3-throw half-knot (H3) and 15.4 + 2.4 N and 28.3+ 10 N for 2 (SSs) and 4-throw (SSsSsSs) symmetrical sliding half-hitches. This is lower than 18, 24, and 46 N for similar knots with vicryl. Polyfilament sutures have excellent knot security for all diameters. Occasionally, some slide to open with slightly lower knot security, especially for larger diameters, although not clinically problematic. Knot se-curity of monofilament sutures was unpredictable for all 4 knots, especially for larger diameters, resulting in many clinically insecure knots. A secure monofilament knot requires a 6-throw knot with 2 symmetrical sliding half-hitches or 2 symmetrical half-knots secured with 4 asymmetric blocking half-hitches. In conclusion, with polyfilament sutures, 4 or 5-throw half-knot or half-hitch sequences result in secure knots. For monofilament sutures, loop and knot security is much less, half-knot combinations should be avoided, and secure knots require 6-throw knots with 4 asym-metric half hitches. This conclusion is valid for gynecologic laparoscopic and open surgery, and for surgery in general.

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.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

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.

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

The use of strobilurin fungicides in agriculture has increased steadily during the past 25 years, and although strobilurins have minimal water solubility, they regularly appear in surface waters, at times in concentrations approaching toxic levels for aquatic life. The present study examined concentrations of strobilurin fungicides in designated trout streams draining an agricultural watershed in southeastern Minnesota, USA, where fungicides may have contributed to a recent fish kill. Water samples (n = 131) were analyzed for the presence of five different strobilurin fungicides (azoxystrobin, fluoxastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin). Samples were collected via grab and automated sampling during baseflow and stormflow events throughout an entire crop growing season from sites on each of three forks of the Whitewater River. Detection frequencies for the five strobilurins ranged from 44 to 82%. Fluoxastrobin and pyraclostrobin concentrations were above known toxic levels in 3% and 15% of total samples analyzed, respectively. The highest concentrations were detected in mid-summer (mid-June to mid-August) samples, coincident with likely strobilurin applications. Lower concentrations were present in water samples collected during the non-application periods in spring and fall, suggesting groundwater-stream interactions or steady leaching of fungicides from watershed soils or stream sediments. Further study is required to determine strobilurin concentrations in sediments, soils, and groundwater. Better tracking and guidance regarding strobilurin use is necessary to adequately protect aquatic life as fungicide use continues to increase.

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

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumor recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumor dissemination and regrowth. One current aim of GBM research focusses on assessing anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and focal adhesion dynamics. By determining the migrastatic activity of Turmeric, Indigo and Magnolia on GBM cell migration, we demonstrate a potential role for Turmeric as a novel GBM anti-migratory therapeutic, in combination with the current standard of care, to prevent tumor recurrence and promote patient survival.

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

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.

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

Construction Design Management (DM) involves the coordination of design process and activity to ensure quality project design, yet it involves many challenges. This work reports on a collaborative Knowledge Transfer Project (KTP) that tackled several challenges faced by construction design management practitioners. Employing a design science research methodology (DSRM), qualitative analysis of semi-structured interviews with purposively identified design managers first uncovered real world concerns around design coordination, and designer performance monitoring. Then to address these concerns, a web-based design management prototype dashboard was developed which uses typical project data to aid the management of design coordination activity and facilitate design management task prioritization and reporting functionalities. By digitalizing selected design management processes to improve efficiency, and productivity, the visual reporting capability of the dashboard enables design production to be monitored at project and portfolio levels; trends in designer performance to be assessed and focus to be retained on technical queries (TQs) and requests for information (RFIs). By reporting on the development of this web-based Design Management prototype dashboard and illustrating how it can enhance design management productivity in construction firms, this work also provides further evidence of how employing a design science research methodology in construction can produce practical solutions that address real world construction concerns.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.

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

Snow crab replaced groundfish fisheries as the primary focus of the Newfoundland and Labrador (NL) fishing industry in the mid-1990s. Over the past three decades, management philosophies in this male-only fishery have shifted from promoting industry expansion to promoting industry rationalization to implementing Precautionary Approach (PA) management. Until the mid-2010s, there were regionalized management strategies characterized by higher exploitation rates in northern than southern sub-stock units along the NL marine shelves. However, in the late 2010s, exploitation rates were permitted to elevate to high levels across the entire stock range in association with a large resource decline and evidence of biological harm through fishing emerged in chronically depleted areas. In 2019, when stock and fishery productivity were near historic lows, a multi-indicator PA system was informally introduced into management of the resource. This event coincided with anticipated improvements in stock and fishery performance. This paper examines the extent to which the multi-indicator PA management system, focused on promotion of both biological protection and maximization of fishing efficiency, may have contributed to recent improvements in stock and fishery status. A suite of indicators from areas implementing PA guidance into management in 2019 prior to formal adoption of the PA system in 2023 suggest the system has been highly beneficial in promoting rapid recovery, improving stock and fishery performance metrics to levels matching or exceeding historic levels under similar conditions. We discuss capacity of the system to better safeguard biological aspects of resource and fisheries productivity moving forward under a scenario of an expectant resource decline.

Identification and segmentation of rock particles is very important in geology, mining, engineering construction, and environmental monitoring. Traditional methods for recognizing the rock particle characteristics are time-consuming, labor-intensive, and limited by the geographical scope of the sampling sites, which makes it more difficult to represent the spatial distribution of the rock particles accurately. Recent advancements in deep learning techniques offer promising solutions to automate this process. This study aims at utilizing state-of-the-art (SOTA) Mask R-CNN deep learning algorithm from the Detectron2 framework, to capture global features of rocks that will enable the recognition of rock particles more efficiently, just from having the rock images. These images are subject to image processing techniques such as a Gaussian filter, to denoise and smoothen the image, and an Illumination Adaptive Transformer (IAT) framework, to adjust the lighting exposure; all of which add to improve the quality of the image dataset. Afterward, the Mask R-CNN and Detectron2 models are utilized in training the images using transfer learning. Experimental results from evaluating the performance of the proposed algorithms showcase the effectiveness of the approach, thereby highlighting its potential to revolutionize rock particle segmentation across various domains.

(R)-(+)-3,5-Dinitro-N-(1-phenylethyl)benzothioamide 1 is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers by 1H NMR spectroscopy. The single enantiomer of 1 was synthesized from commercially (R)-(+)-a-methylbenzylamine 2 in two-steps with 85% yield.

We study certain function algebras and their operator algebra completions on r-discrete abelian groupoids, the corresponding conditional expectations, maximal abelian subalgebras (masa) and eigen-functionals.

CAMx-LPiG (Comprehensive Air Quality Model with Extensions – Linear Plume in Grid) is an online hybrid model, based on the Chemistry and Transport Model (CTM) CAMx, that includes a sub-grid scale module to simulate the dispersion of linear road traffic emissions, called LPiG. LPiG is a plume in grid module specifically developed by extending the capabilities of the Lagrangian puff sub-grid model available in CAMx. The online integration of the local scale model within the Eulerian CTM allows for a multiscale simulation of air quality from the regional scale to the urban scale, preserving a coherent description of the chemical state of the atmosphere at all spatial scales and avoiding any double counting of the emissions simulated by the sub-grid module. In this work the model is presented and evaluated against measured NO2 concentrations for the city of Milan for the month of January 2017. The model is able to introduce road traffic induced gradient in NO2 concentration at sub-grid resolution. Moreover, CAMx-LPiG is shown to reduce the bias compared to CAMx stand-alone simulations.

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

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

This article aims to determine the different factors that are associated with anxiety symptoms among Filipino farmers in Central Luzon. Eligible participants were screened for anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), while the Data Collection Tool for Factors Associated with Anxiety Symptoms (DCFAAS) was constructed and validated to determine the exposure of these factors. Among the 113 eligible farmers, only 19 (16.8%) experienced anxiety symptoms, with excessive worrying (39.8%) being the most frequent anxiety symptom. The mental health of Filipino farmers was significantly affected by the presence of physical illness (OR = 10.70 [1.367, 83.773]) and having relatives affecting work completion (OR = 6.45 [1.346, 30.896]). Therefore, policies must be focused on tackling these issues to address the mental health issues faced by farmers. The low prevalence of anxiety symptoms may stem from existing perceptions and barriers encountered in confiding psychological issues, and the Filipino’s religiosity and resiliency. Keywords: Farmers, Agriculture, Central Luzon, Generalized Anxiety Disorder, GAD-7

Coccidioides spp are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with a symptomatic pneumonic disease as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

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

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

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