The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Methods are currently lacking to prove artificial general intelligence (AGI) safety. An AGI ‘hard takeoff’ is possible, in which first generation AGI1 rapidly triggers a succession of more powerful AGIn that differ dramatically in their computational capabilities (AGIn≪AGIn+1). No proof exists that AGI will benefit humans or of a sound value-alignment method. Numerous paths toward human extinction or subjugation have been identified. We suggest that probabilistic proof methods are the fundamental paradigm for proving safety and value-alignment between disparately powerful autonomous agents. Interactive proof systems (IPS) describe mathematical communication protocols wherein a Verifier queries a computationally more powerful Prover and reduces the probability of the Prover deceiving the Verifier to any specified low probability (e.g., 2-100). IPS procedures can test AGI behavior control systems that incorporate hard-coded ethics or value-learning methods. Mapping the axioms and transformation rules of a behavior control system to a finite set of prime numbers allows validation of ‘safe’ behavior via IPS number-theoretic methods. Many other representations are needed for proving various AGI properties. Multi-prover IPS, program-checking IPS, and probabilistically checkable proofs further extend the paradigm. In toto, IPS provides a way to reduce AGIn↔AGIn+1 interaction hazards to an acceptably low level.

Artificial general intelligence (AGI) progression metrics indicate AGI will occur within decades. No proof exists that AGI will benefit humans and not harm or eliminate humans. I propose a set of logically distinct conceptual components that are necessary and sufficient to 1) ensure various AGI scenarios will not harm humanity and 2) robustly align AGI and human values and goals. By systematically addressing pathways to malevolent AI we can induce the methods/axioms required to redress them. Distributed ledger technology (DLT, ‘blockchain’) is integral to this proposal, e.g. ‘smart contracts’ are necessary to address evolution of AI that will be too fast for human monitoring and intervention. The proposed axioms: 1) Access to technology by market license. 2) Transparent ethics embodied in DLT. 3) Morality encrypted via DLT. 4) Behavior control structure with values at roots. 5) Individual bar-code identification of critical components. 6) Configuration Item (from business continuity/disaster recovery planning). 7) Identity verification secured via DLT. 8) ‘Smart’ automated contracts based on DLT. 9) Decentralized applications - AI software modules encrypted via DLT. 10) Audit trail of component usage stored via DLT. 11) Social ostracism (denial of resources) augmented by DLT petitions. 12) Game theory and mechanism design.

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

During the development of new medicines mutually exclusive specificity appears to be required but hitherto is most often included at the late clinical trial stage. Here, I describe the use of Hedgehog signalling in Drosophila as a model to represent a mutually exclusive relationship within the context and report the identification of CG43658, a putative Rho guanine nucleotide exchange factor and orthologue of the Charcot-Marie-Tooth disease associated gene ARHGEF10. Furthermore, a Computer that is able to consider the whole and describe the sum of everything in it absolutely in unambiguous terms is a useful tool. Here I describe such a computer with a suggestion for an application to examine any component in the context where a medicine is sought. Taken, together I would like to propose this method as a fundamental necessity and improvement upon current existing methods related not only to Hedgehog signalling but plausibly to life science research and the search for medicines in general.

This study aimed to determine the persistence of Salmonella Javiana, Listeria monocytogenes, and Listeria innocua in hydroponic nutrient solution (NS) at 15, 25, 30, and 37°C over a 21-day period to mimic time from seedling to mature lettuce. Bacteria were inoculated in modified Hoagland's NS at 106 CFU/ml and maintained at 15, 25, 30, and 37°C. Samples were collected at various time points and quantified. Data were analyzed using a mixed effect model to compare mean log CFU/ml obtained from each sampling point for all three bacteria at four different temperatures. Least mean squares were calculated to compare mean log CFU/ml. Tukey-Kramer honest significant difference test was used to compare mean values. At all temperatures, S. Javiana persisted in NS throughout the 21-day study period, compared to L. innocua and L. monocytogenes where persistence was limited to d 5 to d 14 and d 1 to d 14, respectively. Similarly, decimal reduction values (D-values) of S. Javiana indicated longer persistence in nutrient solution than L. innocua and L. monocytogenes at most temperatures. For instance, at 15°C and 25°C D-values for S. Javiana were estimated at 82 and 26 d, respectively, compared to D-values of 3.6 and ~3 d for L. monocytogenes. Data indicate that temperature has minimal effect on S. Javiana and thus may pose a greater risk during hydroponic production of leafy greens due to longer survival in NS when compared to Listeria spp. This study furthers the understanding of potential food safety risks associated with hydroponic systems and may aid in developing management strategies to reduce foodborne outbreaks, fresh produce recalls, and economic losses.

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.

Introduction: Desmoid tumor (DT) is a rare benign neoplasm rising from muscle aponeurosis, having been associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When they occur in pregnancy, are all pregnancies and deliveries taken as individual case for optimal management by the physicians and midwifes, who need to be cautious in finding the optimal delivery mode for patients, which depends on tumor size, location, behavior and past history. Study Objectives: We present a case report of a large desmoid tumor of the anterior abdominal wall in a 29-year-old woman in pregnancy, presenting a delivery problem, which resolved in surgical management. Moreover, we are bringing a systematic review of the literature to provide an overview on pathomechanism, symptoms, diagnostics and treatment management of the pregnant women affected by DT. Results: The authors report a case of pregnant women who underwent systemic oncological treatment for abdominal wall desmoid tumor and have been pregnant afterwards. The observational conservative management was chosen with an elective cesarean section at the 38+4 pregnancy week with uncomplicated postpartum follow-up. Conclusion: Pregnancy-associated desmoid tumors are very rare and optimal management of this tumor is not well established, despite some guidelines for non-pregnant patients. The authors reviewed the literature focusing on the actual modern management of desmoid tumors at all, including patients during the pregnancy, as well.

This paper explores the tuning and results of two-part models on rich datasets provided through the Casualty Actuarial Society (CAS). These data sets include BI (bodily injury), PD (property damage) and COLL (collision) coverage, each documenting policy characteristics and claims across a four year period. The datasets are explored, including summaries of all variables, then the methods for modeling are set forth. Models are tuned and the tuning results are displayed, after which we train the final models and seek to explain select predictions. All of the code will be made available on GitHub. Data was provided by a private insurance carrier to the CAS after anonymizing the data set. This data is available to actuarial researchers for well-defined research projects that have universal benefit to the insurance industry and the public. Our hope is that the methods demonstrated here can be a good foundation for future ratemaking models to be developed and tested more efficiently.

Complex modeling has received significant attention in recent years and is increasingly used to explain the statistical phenomenon with increasing and decreasing fluctuations such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which ends up a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID database, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains of Wuhan, Beijing, New York, German, and UK variant B.1.1.7) were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2 for which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolvement of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS>SARS-CoV-1>SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

Objective: Our goal is to develop an online questionnaire to survey the prevalence of suicidal behavior. Methods: We developed a questionnaire with 51 variables and proceeded with validations. Validations were performed using face validity, content validity, and construct validity. Reliability was performed by test-rest. Results: The face validity was 1.0 and the content validity was 0.91. The exploratory factor analysis got KMO = 0.86 and extracted one principal factor. The confirmatory factor analysis demonstrates RMSEA= 0.000 and CFI=1.000. The test-retest had an intraclass correlated coefficient of 0.98. Conclusion: The adequate development questionnaire was validated, and we have an instrument to survey suicide behaviors in the pandemic time.

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.

Marginalised families faced significant challenges during the COVID-19 pandemic. This study explores inequalities in Japanese mothers’ and children’s health and wellbeing and family economic stability before and during the pandemic. Data sources were: nationwide surveys in 2019 and 2021 of families with children using medical institutions across Japan; infant mortality and adolescent suicide rates between 2018 and 2021 from publicly available sources. Outcomes by poor and non-poor families were compared for 2019 and 2021 using simple descriptive statistics. Poor mothers' part-time working increased from 41% to 61% and regular employment was reduced by two-thirds. Well-being of poor mothers worsened from 39% to 55%. Employment opportunities and wellbeing did not change for non-poor mothers. School subsidies among poor families increased from 23% to 55%. The infant mortality rate (IMR) among unemployed families increased significantly from 12.9/1,000 to 18.2/1,000 between 2018 and 2021 compared with a decreasing overall IMR from 1.9/1000 to 1.7/1000. Suicide rates in 10-19 year olds increased over the same period although no socio-economic indicators were available. Inequalities in mothers’ and children’s health and well-being indicators and family economics increased between 2019 to 2021 in Japan. This study cannot attribute cause but suggests a possible role of the pandemic.

Repeated cocaine produces an enhanced locomotor response (sensitization) paralleled by biological adaptations in the brain. Previous studies demonstrated region-specific responsiv-ity of adenosine monophosphate-activated protein kinase (AMPK) to repeated cocaine. AMPK maintains cellular energy homeostasis at the organismal and cellular level. Here we first quanti-fied changes in phosphorylated (active) and total AMPK in the cytosol and synaptosome of the medial prefrontal cortex, nucleus accumbens, and dorsal striatum following acute or sensitizing cocaine injections. Rats were given cocaine (15 mg/kg, IP) or saline for six days with a challenge injection on day seven resulting in four groups: saline-saline, saline-cocaine, cocaine-saline, and cocaine-cocaine. Brain region and cellular compartment selective changes in AMPK and pAMPK were found with some differences associated with acute withdrawal versus ongoing cocaine treatment. Other rats were pretreated with the indirect AMPK activator metformin. Metformin potentiated the locomotor activating effects of acute cocaine but blocked the development of sensi-tization. Sex differences largely obscured protein level treatment group effects, although pAMPK in the NAc shell cytosol was surprisingly reduced by metformin in rats receiving repeated co-caine. These data inform our understanding of AMPK activation dynamics in subcellular com-partments and provide additional support for repurposing metformin for cocaine use disorder.

A foundational model has been developed based on trends built from empirical data of space exploration and computing power through the first six plus decades of the Space Age which projects earliest possible launch dates for human-crewed missions from cis-lunar space to selected Solar System and interstellar destinations. The model uses computational power, expressed as transistors per microprocessor, as a key broadly limiting factor for deep space missions’ reach and complexity. The goal of this analysis is to provide a projected timeframe for humanity to become a multi-world species through off-world colonization, and in so doing all but guarantees the long-term survival of the human race from natural and human-caused calamities that could befall life on Earth. Be-ginning with the development and deployment of the first nuclear weapons near the end of World War II, humanity entered a ‘Window of Peril’ which will not be safely closed until robust off-world colonies become a reality. Our findings suggest the first human-crewed missions to land on Mars, selected Asteroid Belt objects, and selected moons of Jupiter and Saturn can occur before the end of the 21^st century. Launches of human-crewed interstellar missions to exoplanet destinations within roughly 40 lightyears of the Solar System are seen as possible during the 23^rd century and launch of intragalactic missions by the end of the 24^th century. An aggressive and sustained space exploration program, which includes colonization, is thus seen as critical to the long-term survival of the human race.

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.

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

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

In modern data analysis, working with diverse dataset formats is essential for ensuring compatibility across different software tools and platforms. However, manual conversion between formats can be time-consuming and error-prone. To address this challenge, we developed an interactive Shiny application that facilitates the seamless conversion of datasets between popular software formats such as CSV, Excel, SAS, SPSS, Stata, and RData. This user-friendly app enables users to upload datasets, select an output format, and download the converted file with a single click. The application also incorporates a real-time progress indicator, enhancing the user experience by showing conversion progress. Built with simplicity and efficiency in mind, the app is designed for researchers, data analysts, and practitioners who regularly handle multiple file formats in their workflows. Additionally, the app features a clean, intuitive interface with clear guidance, making it accessible even to users with minimal technical background. The development process, key features, and potential applications of this tool are discussed in this article.

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.

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining disease pre-antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we will discuss evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model is providing insights into the pathogenesis of JCPyV CNS disease.

Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects deriving from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding of how MAPK/ERK activity contributes to the regulation of ureteric bud branching morphogenesis, which dictates the final size, shape, and nephron number of the kidney. Recent studies also demonstrate that MAPK/ERK pathway is directly involved in nephrogenesis, regulating both the maintenance and differentiation of the nephrogenic mesenchyme. Interestingly, aberrant MAPK/ERK signaling is linked to many cancers, and recent studies suggest it also plays a role in the most common pediatric renal cancer, Wilms’ tumor.

Additive manufacturing (AM) has revolutionized the field of biopolymers by providing a range of opportunities to create complex and intricate structures. Here we provide an overview of developments in biopolymer AM, first in the context of how natural systems have impacted the synthetic processes of AM, and secondly in the context of how synthetically derived structures can be used for biomedical applications. In particular, we explore the range of biopolymers developed for AM, AM techniques for biopolymers, and potential biocompatible medical applications with a focus on four categories of tissue in the human body: skin, bone, heart, and nerve. Despite the current challenges of the technology, exciting results in tissue regeneration, synthetic replacements for natural grafts, and complex dynamic organoids have already come to pass - with many more possible in the future.

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.

Manual visual inspections typically conducted after an earthquake are high-risk, subjective, and time-consuming. Delays from inspections often exacerbate the social and economic impact of the disaster on affected communities. Rapid and autonomous inspection using images acquired from unmanned aerial vehicles offer the potential to reduce such delays. Indeed, a vast amount of re-search has been conducted toward developing automated vision-based methods to assess the health of infrastructure at the component and structure level. Most proposed methods typically rely on images of the damaged structure, but seldom consider how the images were acquired. To achieve autonomous inspections, methods must be evaluated in a comprehensive end-to-end manner, incorporating both data acquisition and data processing. In this paper, we leverage recent advances in computer generated imagery (CGI) to construct a 3D synthetic environment for simulation of post-earthquake inspections that allows for comprehensive evaluation and valida-tion of autonomous inspection strategies. A critical issue is how to simulate and subsequently render the damage in the structure after an earthquake. To this end, a high-fidelity nonlinear finite element model is incorporated in the synthetic environment to provide a representation of earthquake-induced damage; this finite element model, combined with photo-realistic rendering of the damage, is termed herein a physics-based graphics models (PBGM). The 3D synthetic en-vironment with PBGMs provide a comprehensive end-to-end approach for development and validation of autonomous post-earthquake strategies using UAVs, including: (i) simulation of path planning of virtual UAVs and image capture under different environmental conditions; (ii) au-tomatic labeling of captured images, potentially providing an infinite amount of data for training deep neural networks; (iii) availability of the ground truth damage state from the results of the finite-element simulation; and (iv) direct comparison of different approaches to autonomous as-sessments. Moreover, the synthetic data generated has the potential to be used to augment field datasets. To demonstrate the efficacy of PBGMs, models of reinforced concrete moment-frame buildings with masonry infill walls are examined. The 3D synthetic environment employing PBGMs is shown to provide an effective testbed for development and validation of autonomous vision-based post-earthquake inspections that can serve as an important building block for ad-vancing autonomous data to decision frameworks.

Human rhabdomyosarcomas are rarely cured by surgical resection alone. This is also true for high grade soft tissue sarcomas in dogs. Dogs with spontaneous sarcoma are good models for clinical responses to new cancer therapies. Strategic combinations of immunotherapy and oncolytic virotherapy (OV) could improve treatment responses in canine and human cancer patients. To develop an appropriate combination of immunotherapy and OV for dogs with soft tissue sarcoma (STS), canine cancer cells were inoculated with myxoma viruses (MYXVs) and gene transcripts were quantified. Next, cytokine concentrations in canine cancer cells were altered to evaluate their effect on MYXV replication. These studies indicated that, as in murine and human cells, type I interferons (IFN) play an important role in limiting MYXV replication in canine cancer cells. To reduce type I IFN production during OV, oclacitinib (a JAK1 inhibitor) was administered twice daily to dogs for 14 days starting ~7 days prior to surgery. STS tumors were excised and MYXV deleted for serp2 (MYXV∆SERP2) was administered at the surgical site at two time points post-operatively to treat any remaining microscopic tumor cells. Tumor regrowth in dogs treated with OV was decreased relative to historical controls. However, regrowth was not further inhibited in patients given combination therapy.

Antimicrobial use in agriculture has been identified as an area of focus for reducing overall antimicrobial use and improving stewardship. In this paper, we outline the design of a complex antimicrobial stewardship (AMS) intervention aimed at developing a national Veterinary Prescribing Champion programme for Welsh farm animal veterinary practices. We describe the process by which participants were encouraged to design and deliver bespoke individualised AMS activities at practice level by forging participant ‘champion’ identities and Communities of Practice through participatory and educational online activities. We describe the key phases identified as important when designing this complex intervention, namely (i) involving key collaborators in government and industry to stimulate project engagement; (ii) grounding the design in the literature, the results of stakeholder engagement, expert panel input and veterinary clinician feedback to promote contextual relevance and appropriateness; and (iii) taking a theoretical approach to implementing intervention design to foster critical psychological needs for participant motivation and scheme involvement. With recruitment of over 80% of all farm animal practices in Wales to the programme, we also describe demographic data of the participating Welsh Veterinary Prescribing Champions in order to inform recruitment and design of future AMS programmes.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

Abstract: Aedes aegypti were exposed to water treated with mosquitocidal chips containing the insecticide pyriproxyfen in a polymer formulation. Chips were tested under different conditions; different water volumes, in containers made of different material, and in water with different levels of organic matter. Treated chips caused 100% mortality of Ae. aegypti during their pupal stage independent of conditions chips were exposed to in water. When tested for longevity, the chips containing 840 µg of pyriproxyfen killed 100% of Ae. aegypti for 4 sequential months of the chips being reused in water. Chips containing 8.4 µg of pyriproxyfen ceased to work after the first week of treatment. When mosquitocidal chips were used in > 25% of the oviposition containers within their cages, there was a significant control of the mosquito populations. Mosquitocidal chips worked in different environments, lasted for extended periods of time, caused significant mosquito population decreases, and were effective in controlling Ae. Aegypti.

Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluate the pathology and molecular characteristics of DIPG, the current and future approaches to DIPG treatment; and, lastly, we will discuss clinical trials that have been completed to develop successful treatment options.

Exposure to adverse childhood experiences (ACE) has been found to have a profound negative impact on multiple child outcomes, including academic achievement, social cognition patterns, and behavioral adjustment. However, these links have yet to be examined in preschool children that are already experiencing behavior or social-emotional problems. Thus, the present study examined the links between the caregiver's and the child's exposure to ACE and multiple child and caregiver's outcomes in a sample of 30 preschool children enrolled in a Therapeutic Nursery Program (TNP). Children are typically referred to this TNP due to significant delays in their social emotional development that often result in difficulty functioning in typical childcare, home, and community settings. Analyses revealed some contradictory patterns that may be specific to this clinical sample. Children with higher exposure to ACE showed more biased social information processing patterns and their caregivers reported lower child social skills than caregivers of children with less exposure, however their inhibitory control levels were higher (better control) and staff reported that these children exhibited better social skills as well as better approaches to learning than children with less exposure. No such contradictions were found in relation to the caregiver's exposure to ACE, as it was positively associated with a number of negative child and caregiver outcomes.

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.

Objective: To determine if higher weight-to-length z-scores after 32 weeks of gestation are associated with higher Pulmonary Scores (PS) in preterm infants requiring respiratory support using a prospective observational study. Methods: Infants born <30 weeks, with a post-menstrual age (PMA) of 30-33 weeks were enrolled. Weight, infant’s length, and head circumference were measured weekly. Data on calories/kg/d, protein g/kg/d, weight for length percentiles, z-scores, and BMI at 33 through 40 weeks PMA were collected. PS was calculated. Results: We analyzed 91 infants. The mean gestational age was 26.9 ± 1.7 weeks. There was a significant association between PS and W/L z scores(p<0.0001). For every one-unit increase in W/L z-scores, PS increased by 0.063. There was a significant association between PS and W/L percentiles (p = 0.0017) as well as BMI (p = <0.0001). For every unit increase in W/L percentiles, PS increased by 0.002, and for a unit increase in BMI, PS increased by 0.04. The association remained significant after postnatal steroids, sex, corrected, and birth gestational ages were included in the regression analysis. Nutrition did not affect anthropometric measurements. Conclusion: Our study is the first to demonstrate that higher BMI and W/L may adversely affect respiratory severity in infants.

An optimal withdrawal strategy beginning at age 65 provides a lifetime income from a portfolio, adjusted annually for inflation, while reducing the probability of living in financial ruin to an ac-ceptable level. This paper analyzes the probability of living in financial ruin, potentially for multiple years, rather than just the event of ruin. A stochastic Excel model was developed to simulate the effect of varying investment returns on a portfolio with two asset classes; large company stocks and long-term government bonds. A stochastic model is also applied to retiree mortality. The following variables were analyzed to determine their relative impact on withdrawal strategies: • Withdrawing a constant percentage of the portfolio, • Gender, • Initial asset allocation, • Asset allocation rebalancing methods, and • Low investment return environments. For both genders and most withdrawal rates, an approximately equal initial asset allocation of stocks and bonds, combined with a level rebalancing function, provided the lowest probability of living in financial ruin. Because each investment return followed its own probability distribution function, some retirees experienced financial ruin even in the most conservative simulations.

As the search for exoplanets continues, more are being discovered orbiting Red Giant stars. We use current data from the NASA Exoplanet Archive to investigate planet distribution around Red Giant stars and their presence in the host’s habitable zone. As well, we explore the distribution of planet mass and orbital semi major axis for evolved stars with increasing stellar radii. We found 9 Red Giant-hosted exoplanets, and 21 Subgiant-hosted exoplanets to be in the optimistically calculated habitable zone, 5 and 17 of which are in a more conservatively calculated habitable zone. All the planets detected within their habitable zone orbit stars that are in early stages of evolution. We believe that with more powerful instrumentation, more habitable planets may be found around stars that are in later stages of evolution.

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.

(1) Background: a study was undertaken to determine the prevalence of chronic diseases and health conditions that affect oral health and oral health self-care among independent living older adults in rural areas of Victoria, Australia; (2) Methods: The study analysed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants self-completed questionnaires about health conditions, service use, and demographics. 572 attended a 2-hour health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD=9.2) years. Participants had a high prevalence of medical conditions, the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, with potential impact on oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.

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.

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.

Knowledge regarding egg morphology can aid the selection of postharvest fumigants for insect control. Accordingly, scanning electron microscopy (SEM) was used to examine eggs of spotted lanternfly (SLF), Lycorma delicatula (White) (Hemiptera: Pentatomidae), a pest recently invasive to the mid-Atlantic region of the United States. As the overwintering life stage of SLF, eggs are deposited on a variety of refugia, including many forestry products that can be distributed geographically via travel, commerce, and/or trade. For fumigation to control SLF, and potentially translate into a viable strategy for limiting the spread of SLF by subject pathways, the fumigant must permeate the chorion to react with biomolecules and/or disrupt cellular processes. SLF chorion was characterized by a porous network of aeropyles localized around the operculum, in cranial and caudal relation to the developing nymph, as well as an interstice between the operculum edge and the opercular rim. The confirmation of chorionic ultrastructure that allows for ready gas exchange warrants further investigation of fumigation efficacy, even for those “non-reactive” fumigants, such as phosphine and hydrogen cyanide, which must overcome the suppression of cellular processes coincident with overwintering.

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

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.

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.

As renewed interest in human space-exploration intensifies, a coherent and modernized strategy for mission-design and planning has become increasingly crucial. Biotechnology has emerged as a promising approach to increase mission resilience, flexibility, and efficiency by virtue of its ability to efficiently utilize in situ resources and reclaim resources from waste streams. Since its infancy during the Apollo years, biotechnology, and specifically biomanufacturing, have witnessed significant expansions of scope and scale. Here we outline four primary mission classes, on Luna and Mars, that drive a staged and accretive biomanufacturing strategy. Each class requires a unique approach to integrate biomanufacturing into the existing mission architecture and so faces unique challenges in technology development.These challenges stem directly from the resources available in a given mission class – the degree to which feedstocks are derived from cargo and in situ resources – and the degree to which loop-closure is necessary. We see that as mission duration and distance from Earth increase, the benefits of specialized sustainable biomanufacturing processes increases. Here we present a strategic approach, guided by technoeconomics, to development, testing, and deployment of these technologies serves to nucleate the larger effort of supporting a sustained human presence in space. The processes needed for each scenario spans the technical breadth of synthetic biology to design engineering, from sophisticated genetic tailoring of chassis-organisms to building scalable, automated, easily operable bioreactors and processing systems. As space-related technology development often does, these advancements are likely to have profound implications for the creation of a stable, resilient bioeconomy on Earth.

Developing a biomolecular detection method that minimizes photodamage while maintaining an environment suitable for biological constituents to maintain their physiological state is expected to drive new diagnostic and mechanistic breakthroughs. In addition, ultra-sensitive diagnostic platforms are needed for rapid and point-of-care technologies for various diseases. Considering this, surface-enhanced Raman scattering (SERS) is proposed as a non-destructive and sensitive approach to address the limitations of fluorescence, electrochemical, and other optical detection techniques. However, to advance the applications of SERS, novel approaches to enhance the signal of substrate materials are needed to improve reproducibility and costs associated with manu-facture and scale-up. Due to their physical properties and synthesis, semiconductor-based nanostructures have gained increasing recognition as SERS substrates; however, low signal en-hancements have offset their widespread adoption. To address this limitation and assess the po-tential for use in biological applications, zinc oxide (ZnO) was coated with different concentra-tions (0.01-0.1 M) of gold (Au) precursor. When crystal violet (CV) was used as a model target with the synthesized substrates, the highest enhancement was obtained with ZnO coated with 0.05 M Au precursor. This substrate was subsequently applied to differentiate exosomes derived from three cell types to provide insight into their molecular diversity. We anticipate this work will serve as a platform for colloidal hybrid SERS substrates in future bio-sensing applications.

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.

Chronic wasting disease is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and is closely related to sheep scrapie. Variations in a host’s prion gene, PRNP, and its primary protein structure, dramatically affect susceptibility to specific prion disorders, and breeding for PRNP variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. In the present study, we developed a selective breeding program for farmed white-tailed deer in a CWD-endemic area, focused on reducing frequencies of highly susceptible PRNP variants and introducing animals with less-susceptible variants into historically high prevalence areas. We found that breeding followed predictable Mendelian inheritance, and early data support our project’s utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.

Oil spills from offshore drilling and coastal refineries often cause degradation of coastal wetlands that can take a long time to recover. Early oil detection may prevent losses and speed up recovery if monitoring of the initial oil extent, oil impact, and recovery are in place. Satellite imagery data can provide a cost-effective alternative to expensive airborne imagery or labor intensive field campaigns for monitoring effects of oil spills on wetlands. However, these satellite data may be restricted in their ability to detect and map ecosystem recovery post-spill given their spectral measurement properties and temporal frequency. In this study, we assessed whether spatial and spectral resolution, and other sensor characteristics influence the ability to detect and map vegetation stress and die-off due to oil. We compared how well three satellite multispectral sensors: WorldView2, RapidEye and Landsat EMT+, match the ability of the airborne hyperspectral AVIRIS sensor to map oil-induced vegetation stress, recovery, and die-off after the DeepWater Horizon oil spill in the Gulf of Mexico in 2010. We found that finer spatial resolution (3.5m) provided better delineation of the oil-impacted wetlands and better detection of vegetation stress along oiled shorelines in saltmarsh wetland ecosystems. As spatial resolution become coarser (3.5m to 30m) the ability to accurately detect and map stressed vegetation decreased. Spectral resolution did improve the detection and mapping of oil-impacted wetlands but less strongly than spatial resolution, suggesting that broad-band data may be sufficient to detect and map oil-impacted wetlands. AVIRIS narrow-band data performs better detecting vegetation stress, followed by WorldView2, RapidEye and then Landsat 15m (pan sharpened) data. Higher quality sensor optics and higher signal-to-noise ratio (SNR) may also improve detection and mapping of oil-impacted wetlands; we found that resampled coarser resolution AVIRIS data with higher SNR performed better than either of the three satellite sensors. The ability to acquire imagery during certain times (midday, low tide, etc.) or a certain date is also important in these tidal wetlands; WorldView2 imagery captured at high-tide detected a narrower band of shoreline affected by oil likely because some of the impacted wetland was below the tideline. These results suggest that while multispectral data may be sufficient for detecting the extent of oil-impacted wetlands, high spectral and spatial resolution, high-quality sensor characteristics, and the ability to control time of image acquisition may improve assessment and monitoring of vegetation stress and recovery post oil spills.

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.

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.

A recent study demonstrated that noninvasive measurements of cortical hemodynamics and metabolism in the resting human prefrontal cortex can facilitate quantitative metrics of unilateral mitochondrial-hemodynamic coupling and bilateral connectivity in infraslow oscillation (ISO) frequencies in young adults (YA). The ISO includes three distinct vasomotions with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. The goal of this study was to prove the hypothesis that there are significant differences between young and older adults (OA) in the unilateral coupling (uCOP) and bilateral connectivity (bCON) in the prefrontal cortex. Accordingly, we performed measurements from 24 OA (67.2 ± 5.9 years of age) using the same 2-channel broadband near-infrared spectroscopy (bbNIRS) setup and resting-state experimental protocol as those in the recent study (Shahdadian et al, Cerebral Cortex Communications, 2022). After quantification of uCOP and bCON in three E/N/M frequencies and statistical analysis, we demonstrated that OA had significantly weaker bilateral hemodynamic connectivity but significantly stronger bilateral metabolic connectivity than YA in the M band. Furthermore, OA exhibited significantly stronger unilateral coupling on both prefrontal sides in all E/N/M bands, particularly with a very large effect size in the M band (&gt; 1.9). These age-related results clearly support our hypothesis and were well interpreted following neurophysiological principles. The key finding of this paper is that the neurophysiological metrics of uCOP and bCON are highly associated with age and may have the potential to become meaningful features for human brain health and be translatable for future clinical applications, such as early detection of Alzheimer’s disease.

Climate change is the long-term shift in global weather patterns, largely caused by anthropogenic activity of greenhouse gas emissions. Global climate temperatures have unmistakably risen and naturally-occurring climate variability alone cannot account for this trend. Human activities are estimated to have caused about 1.0 °C of global warming above the pre-industrial baseline and if left unchecked, will continue to drastically damage the Earth and its inhabitants. Globally, natural disasters and subsequent economic losses have become increasingly impactful as a result of climate change. Both wildlife ecosystems and human habitats have been negatively impacted, from rising sea levels to alarming frequency of severe weather events around the world. Attempts towards alleviating the effects of global warming have often been at odds and remain divided among a multitude of strategies, reducing the overall effectiveness of these efforts. It is evident that collaborative action is required for avoiding the most severe consequences of climate change. This paper evaluates the main strategies (industrial/energy, political, economic, agricultural, atmospheric, geological, coastal, and social) towards both mitigating and adapting to climate change. As well, it provides an optimal combination of seven solutions which can be implemented simultaneously, working in tandem to limit and otherwise accommodate the harmful effects of climate change. Previous legislation and deployment techniques are also discussed as guides for future endeavors.

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.

(R)-2-Amino-1-hydroxyethylphosphonic acid 2 was prepared by hydrolytic kinetic resolution of rac-diethyl oxiran-2-ylphosphonate followed by reaction with benzylamine, acid hydrolysis, catalytic hydrogenolysis and anion exchange chromatography. Recrystallization from water-ethanol gave 2, which was characterized by IR, 1H NMR, 13C NMR, 31P NMR, polarimetry, elemental microanalysis, high-resolution mass spectrometry and single-crystal X-ray diffraction. The acid 2 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.303(2) Å, b = 7.104(2) Å, c = 11.627(3) Å. The X-ray crystal structure confirmed the (R)-configuration of 2 and revealed that 2 is zwitterionic in the solid state, with extensive intermolecular hydrogen bonding between the hydroxyl, ammonium cation and phosphonate anion groups.

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.

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.

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.

Of the 100,000 railroad bridges in the United States, 50% are over 100 years old. Many of these bridges do not meet the minimum vertical clearance standards, making them susceptible to impacts from over-height vehicles. Impacts can cause structural damage and unwanted disruption to railroad bridge services; rapid notification of the railroad authorities is crucial to ensure that the bridges are safe for continued use and to affect timely repairs. Therefore, researchers have developed approaches to identify these impacts to railroad bridges. Some recent approaches use machine learning to more effectively identify impacts from the sensor data. Typically, the collected sensor data is transmitted to a central location for processing. However, the challenge with this centralized approach is that the transfer of data to a central location can take considerable time, which is undesirable for time-sensitive events like impact detection that require rapid assessment and response to potential damage. To address the challenges posed by the centralized approach, this study develops a framework for edge implementation of machine learning predictions on wireless smart sensors. Wireless sensors are used because of their ease of installation and lower costs compared to their wired counterparts. The framework is implemented on the Xnode wireless smart sensor platform, thus bringing artificial intelligence models directly to the sensor nodes and eliminating the need to transfer data to a central location for processing. This framework is demonstrated using data obtained from events on a railroad bridge near Chicago; results illustrate the efficacy of the proposed edge computing framework for such time-sensitive structural health monitoring applications.

Prolonged sedentary behaviour (SB) has shown to be detrimental to health. Nevertheless, population levels of SB are high and interventions to decrease SB are needed. This study aimed to explore the effect of an individualized consultation intervention aimed at reducing SB and increasing breaks in SB among college employees. A pre-experimental study design was used. Participants (n=36) were recruited at a college in Massachusetts, USA. SB was measured over 7 consecutive days using an activPAL3 accelerometer. Following baseline measures, all participants received an individualized SB consultation which focused on limiting bouts of SB >30 minutes, participants also received weekly follow-up e-mails. Post-intervention measures were taken after 16 weeks. Primary outcome variables were sedentary minutes/day and SB bouts >30 minutes. Differences between baseline and follow-up were analyzed using paired t-tests. The intervention did not change daily sedentary time (-0.48%; p>0.05). The number of sedentary bouts >30 minutes decreased significantly by 0.52 bouts/day (p=0.015). In this study a consultation based SB intervention was successful in reducing number of bouts >30 minutes of SB. However, daily sedentary time did not reduce significantly. These results indicate that consultation-based interventions may be effective if focused on a specific component of SB.

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.

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.

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.

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.

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.

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

Feral cats are both difficult to manage and harder to monitor. We analysed the cost-efficacy of monitoring the pre- and post-bait abundance of feral cats via camera-traps or track counts using four years of data from the Matuwa Indigenous protected Area. Additionally, we report on the recovery of the feral cat population and the efficacy of subsequent Eradicat® aerial baiting programs following 12 months of intensive feral cat control in 2019 that consisted of aerial baiting and leg-hold trapping. Significantly fewer cats were captured in 2020 (n = 8) compared to 2019 (n = 126). Pre-baiting surveys for 2020 and 2021 suggested that the population of feral cats on Matuwa was very low, at 5.5 and 4.4 cats/100 km respectively, which is well below our target threshold of 10 cats/100 km. Post-baiting surveys then recorded 3.6 and 3.0 cats/100 km respectively, which still equates to a 35% and 32% reduction in cat activity. Track counts recorded significantly more feral cats than camera traps and were cheaper to implement. We recommend that at least two methods of monitoring cats be implemented to prevent erroneous conclusions.

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.

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

Symmetry concepts in parametrized dynamical systems may reduce the number of external parameters by a suitable normalization prescription. If, under the action of a symmetry group G, parameter space A becomes a (locally) trivial principal bundle, A ~ A/G x G, then the normalized dynamics only depends on the quotient A/G. In this way, the dynamics of fractional variables in homogeneous epidemic SI(R)S models, with standard incidence, absence of R-susceptibility and compartment independent birth and death rates, turns out to be isomorphic to (a marginally extended version of) Hethcote's classic endemic model, first presented in 1973. The paper studies a 10-parameter master model with constant and I -linear vaccination rates, vertical transmission and a vaccination rate for susceptible newborns. As recently shown by the author, all demographic parameters are redundant. After adjusting time scale, the remaining 5-parameter model admits a 3-dimensional abelian scaling symmetry. By normalization we end up with Hethcote's extended 2-parameter model. Thus, in view of symmetry concepts, reproving theorems on endemic bifurcation and stability in such models becomes needless.

Previous studies demonstrate the critical importance of non-coding RNAs interfacing with chromatin-modifying machinery resulting in promoter-enhancer-based gene regulation and raise the possibility that many other enhancer-like RNAs may operate via similar mechanisms. Critically, more than 80% of the disease-linked variations identified in genome-wide studies are located in the non-coding regions of genomes, especially non-coding RNA, suggesting non-coding RNAs are relevant to disease. Thus, a critical path forward for understanding non-coding RNAs' role, especially long non-coding RNAs, is to understand the genomic regions' transcriptional regulation, especially non-coding regions. Here, we developed a user-friendly R package called SomaGene for studying and identifying enhancer-like non-coding RNAs with enriched somatic mutations in the cancer genome. SomaGene accepts different genomic variants (whole genome/exome somatic point mutations, structural variations, copy number variations) to identify those RNAs that significantly mutated in diseases (e.g., cancer). It then uses multiple publicly available genomics and epigenetics datasets including ENCODE epigenomics annotations, FANTOM5 tissue-specific expression profiles, disease-associated genome-wide association SNPs, and tissue-specific eQTL pairs to identify those RNAs with potentially enhancer function. SomaGene, as a powerful R package, can provide the opportunity to cancer scientists to study the roles of non-coding RNAs in different cancer genomes.

The authors previously found a model of universal quantum computation by making use of the coset structure of subgroups of a free group $G$ with relations. A valid subgroup $H$ of index $d$ in $G$ leads to a \lq magic' state $\left|\psi\right\rangle$ in $d$-dimensional Hilbert space that encodes a minimal informationally complete quantum measurement (or MIC), possibly carrying a finite \lq contextual' geometry. In the present work, we choose $G$ as the fundamental group $\pi_1(V)$ of an exotic $4$-manifold $V$, more precisely a \lq small exotic' (space-time) $R^4$ (that is homeomorphic and isometric, but not diffeomorphic to the Euclidean $\mathbb{R}^4$). Our selected example, due to to S. Akbulut and R.~E. Gompf, has two remarkable properties: (a) it shows the occurence of standard contextual geometries such as the Fano plane (at index $7$), Mermin's pentagram (at index $10$), the two-qubit commutation picture $GQ(2,2)$ (at index $15$) as well as the combinatorial Grassmannian Gr$(2,8)$ (at index $28$) , (b) it allows the interpretation of MICs measurements as arising from such exotic (space-time) $R^4$'s. Our new picture relating a topological quantum computing and exotic space-time is also intended to become an approach of \lq quantum gravity'.

It has been a long time since the world has experienced a pandemic with such a rapid devastating impact as the current COVID-19 pandemic. The causative agent, the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is further unusual in that it appears capable of infecting many different mammal species. As a significant proportion of people worldwide are infected with SARS-CoV-2 and may spread the infection unknowingly before symptoms occur or without any symptoms ever occurring, there is a non-negligible risk of humans spreading SARS-CoV-2 to wildlife, in particular mammals. Because of SARS-CoV-2’s evolutionary origins in bats and reports of humans transmitting the virus to pets and zoo animals, regulations for prevention of human-to-animal transmission have so far focused mostly on these animal groups. Here, we summarize recent studies and reports that show that a wide range of distantly related mammals are likely susceptible to SARS-CoV-2 and that susceptibility or resistance to the virus is in general not predictable, or only to some extent, by phylogenetic proximity to known susceptible or resistant hosts. In the absence of solid evidence on the SARS-CoV-2 susceptibility/resistance for each of the >5,500 mammal species, we argue that sanitary precautions should be taken when interacting with any mammal species in the wild. Preventing human-to-wildlife SARS-CoV-2 transmission is important for protecting these (sometimes endangered) animals from disease, but also to avoid establishment of novel SARS-CoV-2 reservoirs in wild animals. The risk of repeated re-infection of humans from such a wildlife reservoir could severely hamper SARS-CoV-2 control efforts. For wildlife fieldworkers interacting directly or indirectly with mammals, we recommend sanitary precautions such as physical distancing, wearing face masks and gloves, and frequent decontamination, which are very similar to regulations currently imposed to prevent transmission among humans.

Anxiety in older adults is a prevalent yet under-recognized condition associated with significant societal and individual burdens. This study used a machine learning approach to compare the relative importance of 57 risk and protective factors for anxiety symptoms in a population-representative sample of middle-aged and older European adults (N = 65,684; ages 45–103 years; 55.7% women; 15 countries represented). Results revealed loneliness and self-rated poor health as primary risk factors (Nagelkerke R2 = .272), with additional predictive contributions from country of residence, functional limitations, financial distress, and family care burden. Notably, follow-up analysis showed that none of 16 social network variables were associated with loneliness; rather, cohabitating with a partner/spouse was most strongly associated with reduced loneliness. Further research is needed to elucidate directional associations between loneliness and anxiety (both general and sub-types). These findings underscore the imperative of addressing loneliness for mitigating anxiety and related mental health conditions among aging populations.

In this article, we give a brief review of the origin of the neutrino mass in some interesting non-linear supersymmetric models with R-symmetry. These models are able to address and solve the most important problems of the particle physics and provide mechanisms for neutrino mass generation and their mixing parameters in agreement with the current experimental data. Their prediction could be experimentally tested in the near future by collider experiments.

This paper presents a script that classify spatial patterns of residential urban growth using a morpho-structural approach. The script performs a combination of variography analysis and morphological closings over buildings possessing a residential function in 2002 and 2017 within a region located in southern France named Centre-Var. The different bounding regions then allow classifying new residential buildings into different categories according to their degrees of clustering/scattering and to their locations regarding existing urban areas. Preliminary results show that this protocol is able to provide useful insights regarding the degree of contribution of each new residential building to different patterns of urban growth (clustered infill, scattered infill, clustered edge-expansion, scattered edge-expansion, clustered leapfrog and scattered leapfrog). Open-access to the script and to the test region data is provided.

The steep decline in the price of wind and solar photovoltaics provides a possibility to decarbonize electricity deeply and affordably. This study uses HOMER Pro energy modeling tool to model an optimized grid-connected renewable energy system for a community in southern Alberta, Canada. The study's goal is to identify the best renewable energy technology combinations that can provide electricity at the lowest levelized cost of energy (LCOE) and has lesser greenhouse gas emission as compared to the electricity produced by traditional fossil fuel. Gleichen, is a small town in southern Alberta and is near to numerous commercial wind and solar projects given the region’s high quality renewable resources. “Tri-brid” systems consisting of wind turbines, solar photovoltaics, and battery energy storage systems (BESS) are considered and compared based on electricity prices, net present cost, and greenhouse gas emissions savings. This tri-brid system is connected to the grid to sell excess electricity generated or buying electricity when there is less or no availability of solar and wind. The tri-brid energy system has an estimated LCOE of 0.0705 CAD/kWh which is competitive with the price of electricity generated by natural gas and coal which is 0.127 CAD/kWh.

Multiple Sclerosis (MS) is a progressive neurodegenerative disease that affects more than 2 million people worldwide. Increasing knowledge about MS in different populations has advanced our understanding of disease epidemiology and variation in the natural history of MS among White and minority populations. In addition to differences in incidence, African American (AA) and Hispanic patients have greater disease burden and disability in earlier stages of disease compared to White patients. To further characterize MS in AA and Hispanic populations, we conducted a retrospective chart analysis of 112 patients treated at an MS center in Houston, Texas. Here, we describe differences in clinical presentation, MRI findings, treatment regimens, disability progression, and relapse rate. We found that patients who were evaluated by a neurologist at symptom onset had significantly decreased odds of greater disability [defined as Expanded Disability Status Scale (EDSS) &gt; 4.5] at last presentation compared to patients who were not evaluated by a neurologist (OR: 0.04, 95% CI: 0.16-0.9). We also found that active smokers had significantly increased odds of greater disability both at diagnosis and at last clinical encounter compared to nonsmokers (OR: 2.44, 95% CI: 1.10-7.10, OR= 2.44, 95% CI: 1.35-6.12, p= 0.01, respectively). Assessment of the degree of brain atrophy and progression over time along with enumeration of T1, T2, and gadolinium-enhancing brain lesions did not reveal differences across groups.

Rice has become the second major food among rural people. It is one of the most nutrient and low-cost food available in Asia. Rice is composed of two major subspecies as Japonica and Indica and it belongs to the Poaceae family. The World Bank predicts that rice demand will grow 51% faster than population growth in 2025. It is high time to develop a model which predicts the type of infected paddy leaf and avoids the loss of grains. In this paper, the proposed hybrid CNN model, three CNN networks with different layer properties are trained parallel. The extracted feature from these CNN networks is combined to provide the classification of the type of infected leaf. Fieldwork was carried and about 340 samples are collected from five different types of classes. The proposed hybrid model was tested with both the fieldwork dataset and also with an available dataset on the internet. The experimental results show that the proposed model outperforms the other CNN network and yields an accuracy value of 98%, a precision value of 95%, and a misclassification rate of 4% respectively.

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

Background: Positive person-centered attributes of inpatient rehabilitation need to be identified from the patient perspective to be further developed and sustained. Purpose: To identify which attributes patients openly evoke as being great care experiences, using an open appreciative inquiry during the inpatient rehabilitation stay. Methods: Qualitative secondary analysis of appreciative patient comments during a bedside patient experience rounding, facilitated by a neutral party. Two independent analysts employed an inductive, summative form of content analysis. Results: Among 150 patients rounded, 122 provided categorizable appreciative accounts. Over two thirds of the patients (67.2%) focused on “staff attributes” in their great-experience accounts. Those attributes were mostly interpersonal such as being “attentive & caring - beyond clinical duty” and being “encouraging (but not too hard) & reassuring”. These interpersonal staff attributes were reported with words showing deep levels of personal significance or patient appreciation. Beyond staff attributes, the perceived quality of the “patient care” (31.1%) and opportunities for “leisure and social activities” (9.0%) were also frequently evoked. Amenities like food or costumer service were the least evoked, rarely so as an exclusive attribute (0.8% for each). Conclusions: The human(e) factor, especially the interpersonal qualities of staff, emerged as greatly appreciated from the patient experience perspective during inpatient rehabilitation. These experiences help identify which person-centered attributes of care might be further developed and sustained.

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

Telemedicine is the use of Information and Communication Technology (ICT) for clinical health care from a distance. The exchange of radiographic images and electronic patient health information/records (ePHI/R) for diagnostic purposes has the risk of confidentiality, ownership identity, and authenticity. In this paper, a data hiding technique for ePHI/R is proposed. The color information in the cover image is used for key generation, and stego-images are produced with ideal case. As a result, the whole stego-system is perfectly secure. This method includes the features of watermarking and steganography techniques. The method is applied to radiographic images. For the radiographic images, this method resembles watermarking, which is an ePHI/R data system. Experiments show promising results for the application of this method to radiographic images in ePHI/R for both transmission and storage purpose.

Recent algorithmic-based research in the stock market has predominantly focused on ultra-high-frequency trading and index estimation. We developed an improved algorithm to address the need for a low-frequency, real-world trading model to build on the existing high hit-ratio and low maximum drawdown. We utilized established price indicators, Stochastic and Williams %R, and introduced a volume factor to increase the model's safety to enhance the model's performance. This improved algorithm demonstrated superior returns while maintaining high hit-ratio and low maximum drawdown. Specifically, we leveraged the existing algorithm to trade using 2X and 3X signals, incorporating volume data, the 52-week average, standard deviation, and other factors. The data set comprised SPY ETF price and volume from 2010 to 2023, covering over 13 years. Our enhanced algorithmic trading model outperformed both the benchmark and previous results, achieving a hit rate of over 90%, a maximum drawdown of less than 1%, an average of 1.5 trades per year, a total return of +519.3%, and an annualized return (AnnR) of +15.1%. The analysis demonstrates that the model's simplicity, ease of application, and comprehensibility can assist investors in making informed investment decisions albeit the past performance does not guarantee future returns.

Study aimed to evaluate the impact of integrating family planning with maternal, newborn, and child health (FP-MNCH) on uptake of modern contraceptive methods and related health outcomes in two districts of the province of Sindh, Pakistan. Impact of intervention was evaluated using a quasi-experimental control before-after study design. Intervention included capacity building of healthcare providers and outreach workers, ensuring sustained supplies of family planning commodities, data-driven decision-making, and community engagement activities. Data was collected through household surveys at baseline (December2020) and endline (December 2022). The sample size was estimated as 880 married women of reproductive age (MWRA) in each district. The Difference and Difference(DiD) analytical method was used to estimate the impact of intervention adjusted for potential confounding factors. There was statistically significant increase of 11.3% in the current use of MCM in the intervention group compared to the control group (p value <0.001), with increases observed in the uptake of injection , implants, and condoms. Additionally, there was an increase in the proportion of women who had ANC visits (DiD 10.5% p value 0.003), FP counselling during ANC (DiD 15.6% p value < 0.001), LHW visits during pregnancy (DiD 15.1% p value 0.021), PNC check-ups for mother (DiD 25.2% p value <0.001), LHW visits after delivery (DiD 20.4% p value <0.001), and LHW advised for family planning at PNC visit n (DiD 14.5% p value 0.030). This study provides strong evidence for the scaling-up of integrated interventions through existing health care platforms utilizing human resources deployed by the government. This FP-MNCH model has the potential to be adopted in other provinces and at federally administered areas for both health and population planning. This model should be considered for replication in other districts of Sindh to accelerate current level of integration already existing.

This study develops a hybrid machine learning (ML) algorithm integrated with IoT technology to improve the accuracy and efficiency of soil monitoring and tomato crop disease prediction in Anakapalle, a south Indian station. An IoT device collected one-minute and critical soil parameters—humidity, temperature, pH values, nitrogen (N), phosphorus (P), and potassium (K)—essential for assessing soil health and optimizing crop growth. Kendall's correlations were computed to rank these parameters for utilization in hybrid ML techniques. Various ML algorithms including K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Decision Tree (DT), Random Forest (RF), and Logistic Regression (LR) were evaluated. A novel hybrid algorithm, 'Bayesian Optimization with KNN', was introduced to combine multiple ML techniques and enhance predictive performance. The hybrid algorithm demonstrated superior results with 95% accuracy, precision, and recall, and an F1 score of 94%, while individual ML algorithms achieved varying results: KNN (80% accuracy), SVM (82%), DT (77%), RF (80%), and LR (81%) with differing precision, recall, and F1 scores. This hybrid ML approach proved highly effective in predicting tomato crop diseases in natural environments, underscoring the synergistic benefits of IoT and advanced ML techniques in optimizing agricultural practices.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Single image deraining (SID) has shown its importance in many advanced computer vision tasks. Though many CNN based image deraining methods have been proposed, how to effectively remove raindrops while maintaining background structure remains a challenge that needs to be overcome. Most of the deraining work focuses on removing rain streaks, but in heavy rain images, the dense accumulation of rainwater or the rain curtain effect significantly interferes with the effective removal of rain streaks, and often introduces some artifacts that make the scene more blurry. In this paper, we propose a new network structure R-PReNet for single image deraining with good background structure maintaining. This framework fully utilizes the cyclic recursive structure of PReNet. Moreover, we introduce residual channel prior (RCP) and feature fusion modules for better deraining performance by focusing on background feature information. Compared with the previous methods, our method has significantly improvement effect on the rainstorm image with the artifacts removing and good visual detail restoring.

We analyze the behavior of relativistic spherical objects within the context of modified $f(R,T)$ gravity considering Tolman VI spacetime, where gravitational lagrangian is a function of Ricci scalar(R) and trace of energy momentum tensor(T) i.e,$ f(R,T)= R+ 2\beta T$, for some arbitrary constant $\beta$. For developing our model, we have chosen $\pounds_{m} = -p$, where $ \pounds_{m}$ represents matter lagrangian. For this investigation, we have chosen three compact stars namely PSR J1614-2230 [Mass=(1.97$\pm$ 0.4)M$_\odot$; Radius= 9.69$_{-0.02} ^{+0.02}$ Km] ,Vela X-1 [Mass=(1.77$\pm$ 0.08)M$_\odot$; Radius= 9.560$_{-0.08} ^{+0.08}$ Km] and 4U 1538-52 [Mass=(9.69)M$_\odot$; Radius= 1.97 Km]. In this theory the equation of pressure isotropy is identical to standard Einstein's theory. So all known metric potential solving Einstein's equations are also valid here. In this paper, we have investigated the effort of coupling parameter ($\beta$) on the local matter distribution. Sound of speed and adiabatic index are higher with grater values of $\beta$ while on contrary mass function and gravitational redshift are lower with higher values of $\beta$ . For supporting the theoretical results, graphical representation are also employed to analyze the physical viability of the compact stars.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p &lt; 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.

In recent years, there is a growing concern about the alarming spread of antimicrobial resistance (AMR) in different environments. Increasingly, many species of bacteria, fungi and viruses are becoming immune to the most commonly used pharmaceuticals. One of the causes of the development of the resistance is the persistence of these drugs, excreted by humans, in municipal and hospital wastewater (WW). Consequently, wastewater treatment plants (WWTPs) are a primary source of antimicrobial resistance genes as novel pollutants. This systematic review sought to examine the relevant literature on pharmaceutical residues (PRs) responsible for AMR in municipal and hospital WW in order to propose a classification of the PRs of greatest concern and provide an updated source for AMR management in WWTPs. Among 546 studies collected from four databases, 18 were included in the present review. The internal and external validity of each study was assessed, and the risk of bias was evaluated on a 20-parameter basis. Results were combined in a narrative synthesis discussing influents and effluents PR concentrations at 88 WWTPs, seasonal variations, differences between hospital and municipal WW, environmental risk assessment values of antimicrobial substances and treatment facilities removal efficiencies. Among the 45 PRs responsible for AMR evaluated in this study, the antibiotics ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole and trimethoprim constitute a considerable risk in terms of ubiquitous distribution, worrying concentrations, risk quotients values, and resistance to removal treatments. Gaps in knowledge, data and information reported in this review provide a valuable source for managing AMR in WWTPs.

For the set of probability measures ${\sf I}(X)$, where $X$ is a compact Hausdorff space, we propose a new way to introduce the topology by using open subsets of the space $X$. Then, among other things, we give a new proof that for a compact Hausdorff space $X$ the space ${\sf I}(X)$ is also a compact Hausdorff space. For a Tychonoff space $X$, we consider the topological space ${\sf I_{\tau}}(X)$ of $\tau$-smooth idempotent probability measures on $X$,and show that the space ${\sf I_{\tau}}(X)$ is \v{C}ech-complete if and only if the given space $X$ is \v{C}ech-complete.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

Early detection of wildfires has been limited using the sun-synchronous orbit satellites due to their low temporal resolution and wildfires’ fast spread in the early stage. NOAA’s geostationary weather satellites GOES-R can acquire images every 15 minutes at 2km spatial resolution, and have been used for early fire detection. However, advanced processing algorithms are needed to provide timely and reliable detection of wildfires. In this research, a deep learning framework, based on Gated Recurrent Units (GRU), is proposed to detect wildfires at early stage using GOES-R dense time series data. GRU model maintains good performance on temporal modelling while keep a simple architecture, makes it suitable to efficiently process time-series data. 36 different wildfires in North and South America under the coverage of GOES-R satellites are selected to assess the effectiveness of the GRU method. The detection times based on GOES-R are compared with VIIRS active fire products at 375m resolution in NASA’s Fire Information for Resource Management System (FIRMS). The results show that GRU-based GOES-R detections of the wildfires are earlier than that of the VIIRS active fire products in most of the study areas. Also, results from proposed method offer more precise location on the active fire at early stage than GOES-R Active Fire Product in mid-latitude and low-latitude regions.