The quality of veterinary medicinal products (VMP) is essential for efficient disease management. Therefore, VMPs that do not meet the required standards of quality can lead to increased sickness, death, and the development of antimicrobial resistance, posing a danger to both animals and humans. This study aimed to identify substandard and falsified VMPs on the Rwandan market using the Global Pharma Health Fund (GPHF)-Minilab™. VMP samples were purchased and collected in a cross-sectional study from veterinary retail pharmacies from five districts in four provinces of Rwanda, during May and June 2023. These samples were transported to the Veterinary Laboratory of the School of Animal Sciences and Veterinary Medicine, Nyagatare campus, University of Rwanda, and stored until analysis. The samples were subjected to physical and chemical analysis following the GPHF-Minilab™’s guidelines. A total of 130 samples from two categories of VMP were purchased from 10 veterinary retail pharmacies in urban and rural areas. The results of this study revealed that none of the assessed VMP samples failed physical tests (visual inspection, weight verification, and disintegration test). 10 samples (Sulfamethoxazole/Trimethoprim) out of 130 (7.7%) passed the visual inspections but later failed to comply with Thin-Layer Chromatography result specifications. This is an indication of the presence of substandard and falsified VMP circulating in Rwanda that warrants regular inspection and chemical quality control of VMPs along the supply chain.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

Adequate serum vitamin D and iron levels are thought to positively influence physical training adaptations and mood. The purpose of this prospective, observational, study was to investigate relationships between serum 25-OH vitamin D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (49 female) from 7 indoor and outdoor sports were tested pre-season and post-season for: nutrient biomarkers (serum 25-OH vitamin D and serum ferritin) via venipuncture; body composition (total lean mass, bone mineral densi-ty/BMD, and % body fat) via dual energy x-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female co-horts were combined, significant relationships were noted between pre-season serum 25-OH vit-amin D versus the change (∆: post-season minus pre-season) in both BMD (r=-0.34;p=0.0003) and % body fat (r=-0.28;p=0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r=-0.34;p=0.003). For burnout symptoms, serum 25-OH vitamin D ∆ significantly explained 20.6% of the variance for devaluation of sport in the male cohort only. Across time, serum 25-OH vitamin D levels increased while serum ferritin levels decreased, non-significantly, in both males and fe-males. Relationships between nutrient biomarkers and body composition were opposite of physio-logical expectations.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

This paper aims to study and analyze the effect of the flow rate and amplitude of walling waves on the peristaltic flow of Jeffrey’s fluid through an irregular channel. In addition, it analyses streamlined patterns and their local and global bifurcation flow. The theory of dynamical systems is used to explore the position of critical points and their bifurcation. Numerical and analytical methods are presented to display effective changes in amplitude and rate of the flow on the transport of fluid. Three types of streamline patterns occur backward, trapping and augmented flow in the channel through movement due to changes in the value rate parameters.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

During speciation-with-gene-flow, a transition from single-locus to multi-locus processes can occur, as strong coupling of multiple loci creates a barrier to gene flow. Testing predictions about such transitions with empirical data requires building upon past theoretical work and the continued development of quantitative approaches. We simulated genomes under different evolutionary scenarios of gene flow and divergent selection, extending previous work with the additions of neutral sites and coupling statistics, allowing us to investigate if and how selected and neutral sites differ in the conditions they require for transitions during speciation. As the per-locus strength of selection grew and/or migration decreased, it became easier for selected sites to show divergence – and thus to rise in linkage disequilibrium (LD) with each other as a statistical consequence – farther in advance of the conditions under which neutral sites could diverge. Indeed, even very low rates of gene flow were sufficient to prevent differentiation at neutral sites. However, once strong enough, coupling among selected sites eventually reduced gene flow at neutral sites as well. To explore whether similar transitions might be detectable in empirical data, we used published genome resequencing data from three taxa of Heliconius butterflies. We found that allele-frequency outliers and F ST outliers exhibited stronger patterns of LD than the genomic background, as expected. The statistical characteristics of LD – likely indicative of the strength of coupling of barrier loci – varied between chromosomes and taxonomic comparisons. Broad qualitative agreement between the patterns we observed in the empirical data and our simulations suggests that selection drives rapid genome-wide transitions to multi-locus coupling, illustrating how divergence and gene flow interact along the speciation continuum.

Many corporations aspire to become Net Zero Carbon Dioxide by 2030-2050. This paper examines what it will take. It requires understanding where energy is produced and consumed, the magnitude of CO2 generation, and the Carbon Cycle. Reviews are provided for prior technologies for reducing CO2 emissions from fossil to focus on their limitations and to show that none offer a complete solution. Both biofuels and CO2 sequestration reduce future CO2 emissions from fossil fuels. They will not remove CO2 already in the atmosphere. Planting trees has been proposed as one solution. Trees are a temporary solution. When they die, they decompose and release their carbon as CO2 to the atmosphere. The only way to permanently remove CO2 already in the atmosphere is to break the Carbon Cycle by growing biomass from atmospheric CO2 and sequestering biomass carbon. Permanent sequestration of leaves is proposed as a solution. Leaves have a short Carbon Cycle time constant. They renew and decompose every year. Theoretically, sequestrating a fraction of the world’s tree leaves can get the world to Net Zero without disturbing the underlying forests. This would be CO2 capture in its simplest and most natural form. Permanent sequestration may be achieved by redesigning landfills to discourage decomposition. In traditional landfills, waste undergoes several stages of decomposition, including rapid initial aerobic decomposition to CO2, followed by slow anaerobic decomposition to methane and CO2. The latter can take hundreds to thousands of years. Understanding landfill chemistry provides clues to disrupting decomposition at each phase.

It is standard to identify and compare predicted protein sequence of the Drosha and Pasha genes subsidiary to detection and identification of novel microRNAs in newly sequenced taxa or review of previous deep sequencing data. Drosha and Pasha proteins are the key, conserved members of the ‘microprocessor’ protein complex which facilitates nuclear nuclear localized, pri to pre miRNA processing miRNAs of the canonical eumetazoan complement. Because of the necessity of the microprocessor for production of c anonical eumetazoan miRNA, the detection of both (1) bona fide microRNAs and (2) presence of Drosha/Pasha orthologs (or homologs) is often presented as sufficient to represent a functional canonical eumetazoan microRNA biogenesis pathway. However, the fun ctional role of the Drosha and Pasha homologs sometimes, though not always experimentally validated in non model taxa. Differentiation of ‘bona fide miRNAs’, opposed to ‘non bona fide’ small RNAs of similar size, are also necessary for miRNA identificatio n projects. Recent rubrics are based on structural and sequence elements of the miRNAs themselves, however these inclusion criteria include paraphyletic groupings of miRNAs, for example eumetazoan miRNAs and S treptophyte (green plant) miRNAs which are not produced by the Drosha/Pasha microprocessor mechanism. Therefore, a dichotomy exists between the structural definitions for miRNAs and understanding of the evolutionarily conserved function of the microprocessor and its components. In this article, I re view literature in the context of this topic and discuss philosophical significance for understanding the importance of the microprocessor in understanding the evolutionary and molecular origins of miRNA.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

A new model of gravity is presented here similar to the earlier work of Verlinde on Emergent Gravity but without the use of Verlinde's main assumption on the nature of gravity as an entropic force using the First Law of Thermodynamics. Instead, the model will be shown to be consistent with the Second Law of Thermodynamics as used in Black Hole Physics. Moreover, it does not use the Equipartition Theorem such that there is no need to define a thermal bath enclosed within a holographic screen. The theory uses $E=NE_{p}$, for the total energy of a massive object where $E_{p}$ is the Planck Energy while $N$ is the number of Planck Energy to represent the maximum possible density of information that can reside in matter. The theory uses also the Holographic Principle as the basis for an information-theoretic approach to the nature of gravity. It is shown here that gravity emerges whenever there is an updating of the information within a given volume of space by the presence of matter.

Many corporations and governments aspire to become Net Zero Carbon Dioxide by 2030-2050. Achieving this goal requires understanding where energy is produced and consumed, the magnitude of CO₂ generation, and the Carbon Cycle. Many prior proposed solutions focus on reducing future CO₂ emissions from continued use of fossil fuels. Examination of these technologies exposes their limitations and shows that none offer a complete solution. For example, bioethanol is shown to be both carbon and energy inefficient. Direct Air Capture technologies are needed to reduce CO₂ already in the air. The most natural form of Direct Air Capture involves letting nature do the work of creating biomass via photosynthesis. However, it is necessary to break the Carbon Cycle by permanently sequestering that biomass carbon in “landfills” modified to discourage decomposition to CO₂ and methane. Tree leaves and biomass grown on-purpose, such as high yield switchgrass, are proposed as good biomass sources for this purpose. Left unsequestered, leaves decompose with a short Carbon Cycle time constant releasing CO₂ back to the atmosphere. While in any given year, leaves represent a small fraction of a tree’s above ground biomass, leaves can represent a substantial fraction of the total biomass generated by a tree when integrated over a tree’s lifetime. Understanding the chemistry of the distinct phases landfills undergo is the key to minimizing or eliminating decomposition. First, the compact cross-linked structure of cellulose and keeping water out will make it difficult for initial depolymerization to release sugars. Air ingress should be minimized to minimize Phase I aerobic decomposition. pH manipulation can discourage acid formation during Phase II. Lignocellulose is low in nutrients needed for anaerobic decomposition. Inhibitors can be added if needed. The goal is to move quickly to the dormant phase where decomposition stops. The cost for Carbon Capture and Storage (CCS) for growing and sequestering high yield switchgrass is estimated to be lower than CCS for steam reforming of methane hydrogen plants (SRM) and supercritical or combined cycle coal power plants. Thus, sequestration of biomass is a natural, carbon efficient, and low-cost method of Direct Capture. Biomass sequestration can provide CO₂ removal on giga tonnes per year scale and can be implemented in the needed timeframe (2030-2050).

Melanoma, a deadly form of skin cancer, has seen improved survival rates due to advances in diagnosis and treatment, yet the need for further improvement remains critical. Tumor-associated antigens, such as PRAME (Preferentially Expressed Antigen in Melanoma), offer promising avenues for enhanced diagnostic precision, prognostic assessment, and targeted immunotherapy. PRAME, a cancer-testis antigen, is selectively expressed in various cancers, including melanoma, and plays a key role in promoting tumorigenesis through inhibition of retinoic acid signaling, epithelial-to-mesenchymal transition, and immune evasion. This review explores the diagnostic utility of PRAME in distinguishing melanoma from benign nevi, its prognostic value in aggressive melanoma subtypes, and its potential as a therapeutic target in cancer vaccines and adoptive T-cell therapies. While PRAME-targeted therapies face challenges such as tumor heterogeneity and immune suppression, ongoing research aims to overcome these barriers, offering hope for more effective melanoma treatments.

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

We reviewed various physical and biological manifestations of an unprecedented large-scale water temperature anomaly that emerged in the Northeast Pacific in late 2013. The anomaly dubbed “The Blob” persisted through 2014-2016, with some signs of its persistence through 2017-2018 and a possible reemergence in 2019. The tentative timeline of The Blob’s successive appearances around the Northeast Pacific is suggestive of its advection by currents around the Gulf of Alaska, along the Aleutians, into the Bering Sea, and eventually to the Bering Strait. During the initial phase of The Blob’s development in 2013-2014, advection along the Polar Front might have played a certain role. The extreme persistence and magnitude of The Blob resulted in numerous and sometimes dramatic ecosystem responses in the eastern Bering Sea. The multi-year duration of The Blob might have preconditioned the Bering Sea for the record low seasonal sea ice extent during the winter of 2017-2018 and disappearance of the cold pool in 2016 and 2018 that profoundly affected zooplankton, invertebrates, fishes, sea birds, and marine mammals. Comparison of time-series of population responses across trophic levels suggests that The Blob lowered primary production during spring, increasing small copepod production and jellyfish, and reducing energy transfer efficiently to higher trophic levels. While the Bering Sea’s water temperature, seasonal sea ice, and cold pool seem to return to the long-term mean state in 2022, it remains to be seen if the Bering Sea ecosystem will completely recover. The two most likely alternative scenarios envision either irreversible changes or hysteresis recovery.

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

Due to their independent structure, piping, and access, townhouses offer great flexibility in floor plan changes and high spatial autonomy, making them the mainstream housing type in Taiwan. This study focuses on row houses and examines 2022 completion cases in Kaohsiung City. It collects floor plans from 14 newly constructed buildings, totaling 227 units, and analyzes spatial dimensions including facade width, depth, habitable room, staircases, bathrooms, and total floor area for each case. The objective of this study is to examine the spatial layout of row houses in Kaohsiung City, with the aim of providing reference for future planning and design of such structures. The study resulted showed that 81.8% of the row houses analyzed have a total floor area per unit ranging from 136 to 192 m², a facade width between 4.1 and 6.38 meters, and a building depth from 7.67 to 12.68 meters. In addition, low negative correlation between facade width and total floor area, a high positive correlation between building depth and total floor area, and a moderate negative correlation between facade width and building depth. The spatial distribution within these houses includes 78% allocated to habitable room, 13.1% to staircases, and 8.7% to bathrooms. The total area of habitable room and bathrooms increases with the total floor area of the building. However, the total area of staircases remains almost constant as the area of habitable room increases. Furthermore, the most common location for staircase planning is the rear-right (RB) position, while the least common is the rear-left (LB) position. Among various staircase types, the C-shaped staircase has the largest average area per floor and the highest average proportion. Conversely, the I-shaped staircase has the smallest average area and the lowest average proportion. The U-shaped staircase is the most frequently planned, whereas the C-shaped staircase is the least frequently used.

: Belize is located within the Mesoamerican biodiversity hotspot and is an important link between critical biodiverse habitats in Central America. Despite considerable research on biodiversity in marine environments of Belize, research in freshwater environments is limited, with the most recent checklists having been published in obscure, mostly unavailable references more than 20 years ago.Belize is currently experiencing serious degradation of some of its major freshwater resources such as the New River in the northern part of the country. These unique habitats are increasingly threatened by agro-urban development, invasive species and erratic climatic events. The economically important barrier coral reef is also experiencing impacts from the degraded freshwater watersheds that empty into the sea near the reefs. This work addresses the paucity of documentation of the freshwater fishes of Belize, particularly for the Shipstern Peninsula area. The Shipstern Peninsula is a unique region in northern Belize, adjacent to the southern border of Mexico and the northeastern end of the Corozal Bay Wildlife Sanctuary. This paper reports on fish collected in 2015, with comparisons to historical data in surveys published in 1990, 1993, and 1997. We report on 12 genera/species collected in 2015 and provide molecular barcode data on several, which was not available in previous publications. Floridichthys polyommus, a new observation for the Shipstern Lagoon, and Dajaus monticola, a revised name and new observation for the Inland Blue Hole, were confirmed by barcodes. This update is vital to the continued management of freshwater environments in Belize, and especially for the Shipstern Peninsula and its important habitats held in trust for perpetuity for the Belizean people.

A consistent theory of quantum entanglement requires that constituent single-particle states belong to the same Hilbert space, the coherent eigenstates of a complete set of operators in a given representation, defined with respect to a shared continuous parameterization. Formulating such eigenstates for a single relativistic particle with spin, and applying them to the description of many-body states, presents well-known challenges. In this paper, we review the covariant theory of relativistic spin and entanglement in a framework first proposed by Stueckelberg and developed by Horwitz, Piron, et.\ al. This approach modifies Wigner's method by introducing an arbitrary timelike unit vector $n^\mu$ on which one induces a representation of $SL(2,C)$, rather than induce on the spacetime momentum $p^\mu$. Generalizing this approach, we construct relativistic spin states on an extended phase space $\{(x^\mu,p^\mu),(\zeta^\mu,\pi^\mu)\}$, inducing a representation on the momentum $\pi^\mu$, thus providing a novel dynamical interpretation of the timelike unit vector $n^\mu = \pi^\mu / M$. Studying the unitary representations of the Poincar\'e group on the extended phase space allows us to define basis quantities for quantum states and develop the gauge invariant electromagnetic Hamiltonian in classical and quantum mechanics. We write plane wave solutions for free particles and construct stable singlet states, and relate these to experiments involving temporal interference, analogous to the spatial interference known from double slit experiments.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

Within this paper, a machine learning algorithm is used to investigate the importance of certain setpoints and parameters in the filtration processes of a large-scale water treatment facility. Previously, a model for the filtration process based on Run-to-Run Control was proposed and tested against sample data from the treatment plant, but it was quickly found that such a model was incompatible for successfully computing setpoints of operation which minimize the energy cost of running the filtration systems. The machine learning model described herein is an attempt to elucidate the importance of the available data on the filtration systems and to identify the most important variables that influence the filtration run time.

This article addresses the generic dynamic decision problem of how to achieve sustained market growth by increasing two interdependent organizational resources needed (1) to increase and (2) to sustain demand. The speed and costs of increasing each resource are different. Failure to account for this difference has been reported to lead to policies that drive a quick increase of demand followed by decline. Three generic policies derived from the literature have been implemented in a system dynamics model. Simulation shows that all three policies can generate sustained exponential growth but differ in performance. These results suggest that even policies which risk generating overshoot and collapse can avoid it. This poses two questions for further research: (1) what is the reasoning of human decision-makers when choosing between these policies and (2) how can the important but easily overlooked features of such decision situations be made sufficiently salient to be accounted for?

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

There are two generic approaches to curing any medical condition. The first treats every patient for all of the known possible causes that contribute to pathogenesis; the second individualizes potentially curative therapy by identifying in each separate patient only those components of pathogenesis that are actually operative, and treating those. This article adopts the second approach for formulating a cure of Alzheimer’s dementia (AD). Components of AD’s pathogenesis are, in alphabetical order: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree by which its prevalence is more in the patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did, because the former group is the pool of patients from among which future AD may develop. Addressing only those components that are present in a particular individual, is potentially a curative strategy. Published data indicate that curative therapy requires that the number of such components to address should be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit those tract

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

COVID-19 affects many organs in our body, including the heart and lungs. COVID-19 cases that require hospitalization often exhibit pulmonary hypertension (PH) due to changes in the lung microvasculature in which the blood vessels become stiff, damaged, or narrow, causing increased pulmonary arterial pressure. This review examines the hypothesis that PH can lead to right ventricular hypertrophy (RVH) as a long-lasting aftereffect of COVID-19. Recent studies have shown that significant percentages of hospitalized patients develop right ventricular hypertension and right ventricular dilatation (RVD), which may lead to right ventricular failure and death. Despite recommendations for echocardiogram reports to include right ventricular wall thickness to assess RVH, few published reports have reported this parameter. Relevant studies on animal models of PH in which the timing of PH can be precisely controlled suggest that one to three weeks of PH can cause RVH. Thus, according to the hypothesis proposed here COVID-19 patients who have long-lasting severe disease (e.g., needed to be on a ventilator for one or more weeks) accompanied by PH and RVD may develop RVH as a long-lasting sequela outlasting the infection itself. Echocardiogram studies of recovered COVID-19 patients may determine whether oft-reported cardiovascular sequelae include RVH.

The rapid spread of African swine fever virus (ASFV), causing severe and often lethal disease in domestic pigs and Eurasian wild boar, continues to be a threat for pig populations and dependent industries. Despite scientific achievements that deepen our understanding of ASFV pathogenesis, alternative transmission routes for ASFV remain to be elucidated. We previously demonstrated the efficient transmission of ASFV from infected boars to naïve recipient gilts via artificial insemination, thereby highlighting the importance of surveillance in boar semen prior to shipment. Since accurate and reliable detection of even low amounts of ASFV in boar semen is key for disease prevention and control, we established a suitable diagnostic pipeline to efficiently detect ASFV genome in boar semen. Here, we assessed sensitivity, specificity and overall performance of various routine nucleic acid extraction kits as well as qPCR protocols in detecting ASFV genome in blood and semen of boars. Feasibility of respective kits and methods for future use in boar studs was also considered. Variability in sensitivity mostly concerned samples with low to very low amounts of ASFV genome. Ultimately, we defined a well-suited pipeline to precisely detect ASFV genome in boar semen, as early as 2 days post ASFV infection.

Early reporting of the introduction and establishment of exotic species is of paramount importance for successful management. Here we report the introduction and rapid spread of the Bare-eyed Pigeon, Patagioenas corensis, on the binational island of Saint-Martin, West Indies. This range-restricted species naturally occurs in the arid coastal areas of Columbia and Venezuela and nearby islands. Its introduction on Saint-Martin represents an expansion of about 1000 km beyond its established native range. Using observations recorded in e-bird and results from a recent field survey, we show that since its introduction, most probably between late 2012 and early 2013, the species is expanding fast in Saint-Martin and has recently broadened its habitat to include anthropized, built areas. The expansion of Bare-eyed Pigeon on Saint-Martin and the neighbouring Leeward Islands, possibly facilitated by climate change in the future, could be a threat to both native columbid species and other bird species, through competition for resources. We therefore recommend to local authorities and stakeholders to rapidly eradicate the species or at least prevent its further spread on Saint-Martin, possibly though listing it as a game species, while it is still possible to do so.

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

People wore clothes for warmth, survival and necessity in modern life as well but in modern era, eco-friendliness, shorten production time, design, and intelligence also matters. The seamless bonding technology strengthen the bond between fabrics in textiles, while Grey relational analysis (GRA) can be applied to fabrics to measure the relationship between data series and determine the closeness of each data series. In this study, polyurethane prepolymer, 2-Hydroxyethyl acrylate (2-HEA) as an end-capping agent, and n-octyl acrylate (ODA) as a photo-initiator were used to synthesize dual-curing polyurethane hot-melt adhesive. The Taguchi quality engineering and grey relational analysis used to discuss the influence of different mole ratio of NCO:OH, and the effect of the molar ratio of addition of octyl decyl acrylate on the mechanical strength. The Fourier transform infrared spectroscopy (FTIR) results showed the termination of prepolymer's polymerization reaction and the C=O peak intensity at 1730 cm-1 indicating the efficient bonding to main chain. The high molecular weight polymer (20,000-30,000) described by advanced polymer chromatography (APC) confirmed the polyurethane polymer bonded with octyl decyl acrylate to achieve the photo-thermosetting effect. The thermogravimetric analysis (TGA) results showed the thermal decomposition temperature of polyurethane hot melt adhesive also increased and highest pyrolysis temperature (349.89℃) for the polyhydric alcohols. The high value of shear strength (34.94 kg/cm2) as well as peel strength (1.68 kg/cm) were also observed in dual-cure photo-thermosetting polyurethane hot melt adhesive. The signal-to-noise ratio also used to generate the grey relational degree. It was observed that the best parameter ration of NCO: OH was 4:1 with 5 moles of monomer. The Taguchi quality engineering method was used to find the parameters of single quality optimization, and then the grey relation calculation was used to obtain the parameter combination of multi-quality optimization for thermosetting polyurethane hot melt adhesive. The study aims to meet the requirements of seamless bonding in textile factories and optimized experimental parameter design by setting target values can effectively increase production speed, reduce processing time and costs as well.

Sediment cores were collected from a mudflow lobe (80 m water depth) offshore of the Mississippi River’s Southwest Pass in 2017 to better understand the sedimentology near the lobe entraining the SS Virginia shipwreck (sunk by a German U-Boat in 1942) and surrounding Mississippi River Delta Front. Core analyses included 210Pb/137Cs geochronology, granulometry, and X-radiography. Sediment accumulation rates (SAR) calculated from excess 210Pb activity in multicores are 0.22–0.29 cm/yr at seabed depths less than 20 cm and 0.29–0.51 cm/year at depths greater than 20 cm. 137Cs accumulation rates are ~0.15 to ~ 0.37 cm/year since 1954 and 1963 respectively. Sediment accumulation rates from 210Pb and 137Cs geochronology and indicators of relative sedimentation and bioturbation from X-radiographs suggest that rates of sediment accumulation near Virginia have declined since ca. the mid-20th century. This may be explained by the multi-decade downslope mass transport of the mudflow lobe in which the shipwreck is embedded, and decreases in sediment supply delivered offshore from the Mississippi River. Mass-transport calculations of the Virginia lobe derived from core properties and published lobe advection rates suggest downslope mass transport is far higher than sediment resupply from the Mississippi River, consistent with recent studies of delta retreat.

This study describes the AMD impacted environments and critically discusses the effects of AMD, current prediction and prevention methods and treatment technologies. The study further, crit-ically analyses the case studies, gaps in AMD research and the challenges and opportunities of-fered by AMD. The study outlined future technological intervention aiming at a paradigm shift towards reducing the volume of sludge generated as well as the operating cost and improving AMD treatment efficiency. The integrated AMD treatment technologies that result in a holistic approach toward sustainable AMD treatment are a current need. As a result, a sustainable AMD treatment strategy has been made possible due to water reuse and rich resource recoveries such sulphuric acid, rare earth elements, and metals. The cost of AMD treatment can be decreased with the use of recovered water and resources, which is essential for developing a sustainable AMD treatment process.

A well known technique to enhance the signal to noise ratio (SNR) of repetitive signals is to average them. The coherent parts of the signal add up constructively while the incoherent parts are averaged out. The prerequisite is that the signals are acquired under conditions of high repeatability, i.e.\ the signals must be sufficiently similar. In the present technical note we describe an efficient method for maintaining signal similarity by ensuring spatial and temporal proximity of laser waveform signals obtained by a sensor operated from an airborne platform. The method makes use of a few auxiliary parameters such as laser pulse repetition rate, mirror rotation rate, platform altitude, and flight speed. The method can be extended to be operated in real time.

Context: The compartmental description, well-known from the description of infection diseases and epidemics, is applied to describe the temporal evolution of the baryonic matter in interstellar gas and stars. The introduction of gaseous and stellar fractions of the total baryonic matter as the basic dynamical variables is advantageous because it allows to apply the description to a variety of astrophysical systems. Aims: The competition of spontaneous star formation, stellar feedback and stellar evolution is theoretically investigated to understand the baryonic matter cycle including luminous baryonic matter in main-sequence stars and weakly luminous matter in white dwarfs, neutron stars and black holes (referred to as locked-in matter). Of particular interest is the understanding of the cosmic star formation history and the present-day gas fraction with compartmental models. Methods: For stationary rates of spontaneous star formation, continuous stellar feedback and stellar evolution exact analytical solutions of the time evolution of the fractions of gaseous, luminous stellar and locked-in stellar matter are derived. The accuracy of the analytical solutions is proven by the favorite comparison with the exact numerical solutions of the dynamical equations. Results: The observed cosmological star formation rate and the integrated stellar density as a function of redshift are reasonably well explained by the compartmental model without triggered star formation by the competition of spontaneous star formation and stellar evolution whereas the influence of stellar feedback is less important. The action of stellar evolution provides a significant redshift dependent reduction factor when calculating the integrated stellar density from the star formation rate. Without stellar evolution the observations cannot be reproduced very well. Then the fits to the observation allow us conclusions on the relative importance of spontaneous star formation, stellar evolution and feedback in the early universe after the recombination era until today. The gas, luminous star and locked-in stellar matter fractions indicate that the vast majority of the baryons in the present-day universe resides in the form of locked-in stellar matter in white dwarfs, neutron stars and black holes.

The aim of the present study was to evaluate the association between television viewing/physical activity (TVV/PA) interactions and cardiometabolic risk in an adult European population. A total of 2,155 subjects (25-64 years) (45.2% males), a random population-based sample were evaluated in Brno, Czechia. TVV was classified as low (&lt;2hours/day), moderate (2-4), and high (≥4). PA was classified as insufficient, moderate, and high. To assess the independent association of TVV/PA categories with cardiometabolic variables, multiple linear regression was used. After adjustments, significant associations were: high TVV/insufficient PA with body mass index (BMI) (β=2.61,SE=0.63), waist circumference (WC) (β=7.52,SE=1.58), body fat percent (%BF) (β=6.24,SE=1.02), glucose (β=0.25,SE=0.12), triglycerides (β=0.18,SE=0.05), and HDL-C (β=-0.10,SE=0.04); high TVV/moderate PA with BMI (β=1.98,SE=0.45), WC (β=5.43,SE=1.12), %BF (β =5.15,SE=0.72), triglycerides (β =0.08,SE=0.04), total cholesterol (β=0.21,SE=0.10), LDL-c (β=0.19,SE=0.08), and HDL-c (β=-0.07,SE=0.03); and moderate TVV/insufficient PA with WC (β=2.68,SE=1.25), %BF (β=3.80,SE=0.81), LDL-c (β=0.18,SE=0.09), and HDL-c (β=-0.07,SE=0.03). Independent of PA levels, higher TVV was associated with higher amounts of adipose tissue. Higher blood glucose and triglycerides were present in subjects with high TVV and insufficient PA, but not in those with high PA alone. These results affirm the independent cardiometabolic risk of sedentary routines even in subjects with high-levels of PA.

Recognition, decoding and tracking of vortex patterns is of increasing importance in many fields reaching from astronomical observation of distant galaxies to turbulence phenomena in liquids or gases. Currently, coherent light beams with orbital angular momentum (OAM) are of particular interest for optical communication, metrology, micro-machining or particle manipulation. One common task is to identify characteristic spiral patterns in pixelated intensity maps at real-world signal-to-noise ratios. Recently, Fast Fourier Transform (FFT) was applied to the quantitative analysis of spiral interference patterns of OAM beams. Our study considers this approach in more detail. It is demonstrated that specific information can be extracted by combining conformal mapping by polar transform with determining one- or two-dimensional angular frequency spectra either in spatially fixed or scanning mode. Results of proof-of-principle experiments are presented.

In a series of recent papers we developed a formulation of general relativity in which spacetime and the dynamics of matter evolve with a Poincaré invariant parameter τ. In this paper we apply the formalism to derive the metric induced by a `static’ event evolving uniformly along its t-axis at the spatial origin x=0. The metric is shown to vary with t and τ, as well as spatial distance r, taking its maximum value for a test particle at the retarded time τ=t−r/c. In the resulting picture, an event localized is space and time produces a metric field similarly localized, where both evolve in τ. We first derive this metric as a solution to the wave equation in linearized field theory, and discuss its limitations by studying the geodesic motion it produces for an evolving event. By then examining this solution in the 4+1 formalism, which poses an initial value problem for the metric under τ-evolution, we clarify these limitations and indicate how they may be overcome in a solution to the full nonlinear field equations.

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

Atomic state preparation can benefit from a compact and uniform magnetic field source. Simulations and experimental measurements have been used to design, build, and test such a source as shown by optical pumping of atomic Helium. This source is a 9.5 mm (3/8") OD x 6.7 mm (1/4") ID x 9.5 mm (3/8") long, NdFeB-N42 assembly of 1.6 mm (1/16") thick customized annular magnets. It has octopole decay with a residual dipole far field from imperfect dipole cancelations. It has greater than 50% clear aperture with uniform and collimated magnetic field consistent with the prediction of several models. Octopole roll-off localizes the field minimizing the need for shielding in applications. The device is applied to a high precision 3,4He laser spectroscopy experiment using σ+ or σ- optical pumping currently resulting in a measured 99.3% preparation efficiency and in accordance with a rate-equation model.

Heat stress (HS) is a strong stress factor that significantly affects the metabolism of dairy cows. The aim of the present study was to investigate how HS affects some biochemical indicators in the blood of dairy cows reared in Bulgaria. The study was conducted on a cattle farm with a capacity of 500 Holstein cows, loose housed in a free stall barn shed type. The research was carried out in three seasons - summer, autumn and winter, and a total of 77 samples were taken from the cows of the farm - 30 blood samples for each season. The cows included in the study were from 30 to 60 days in milk (DIM). Temperature and humidity data were taken from the closest to the farm weather station. Based on the conducted research, it was found that the HS reported during the summer season had a significant impact on the following blood parameters: glucose, urea, total protein and cortisol. In summer, blood glucose values were low and ranged from 1.32 to 1.63 mmol/l in cows on different lactations. Probably because of these low glucose levels, high levels of total protein, ranging from 76.92 to 86.10 g/l, were reported in cows from the first to third lactation. This protein was used by cows to provide energy from non-carbohydrate sources and as a residual product, higher blood urea levels were reported in summer, ranging from 4.79 to 5.23 mmol/l. As proof of the stressful influence of heat on the metabolism of the examined cows, the cortisol values in the summer were in the upper reference norms - 38.44 nmol/l or higher and reached 59.09 nmol/l.

Abstract: The baculovirus expression vector (BEV) system is an efficient, cost effective and scalable method to produce recombinant adeno-associated virus (rAAV) gene therapy vectors. Most BEV designs emulate the wild type AAV transcriptome and translate the AAV capsid proteins, VP1, VP2 and VP3 from a single mRNA transcript with three overlapping open reading frames (ORFs). Non-canonical translation initiation codons for VP1 and VP2 reduce their abundances relative to VP3. Changing capsid ratios to improve rAAV vector efficacy requires theoretical modification of translational context. We have made a Lac repressor inducible system to empirically regulate expression of VP1 and VP2 proteins relative to VP3 in the context of the BEV. We demonstrate the use of this system to tune the abundance, titer and potency of a neurospecific rAAV9 serotype derivative. VP1:VP2:VP3 ratios of 1:1:8 gave optimal potency for this rAAV. It was discovered that ratios of capsid proteins expressed were different than ratios that ultimately were in purified capsids. Over expressed VP1 did not become incorporated into capsids while over expressed VP2 did. Overabundance of VP2 correlated with reduced rAAV titers. This work demonstrates a novel technology for controlling production of rAAV in the BEV system and shows a new perspective on the biology of rAAV capsid assembly.

In this study, we examine the relationship of bank level lending and borrowing decisions and the risk preferences on the dynamics of the interbank lending We develop an agent-based model that incorporates individual bank decisions using the temporal difference reinforcement learning algorithm with empirical data of 6600 S. banks. The model can successfully replicate the key characteristics of interbank lending and borrowing relationships documented in the recent literatur A key finding of this study is that risk preferences at individual bank level can lead to unique interbank market structures which are suggestive of the capacity that the market responds to surprising

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorders in children and is frequently associated with Epstein-Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or NK-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with vesiculopapules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory therapy is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated, overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

Under suitable continuity and uniqueness conditions, solutions of an α order Caputo fractional boundary value problem are differentiated with respect to boundary values and boundary points. This extends well-known results for nth order boundary value problems. The approach used is a standard technique and makes heavy use of recent results for differentiation of solutions of Caputo fractional intial value problems with respect to initial conditions and continuous dependence for Caputo fractional boundary value problems.

In the transition towards sustainable energy sources, hydrogen has emerged as the predominant alternative after fossil fuels. This comprehensive literature review delves into the evolving landscape of hydrogen launching strategies within the energy market. Numerous countries have strategically initiated efforts to introduce products based on hydrogen, underscoring the global acknowledgment of the potential inherent in hydrogen. Despite witnessing significant growth in the adoption of hydrogen energy worldwide, impediments to its widespread commercialization persist. This review identifies key barriers, including cost structures, technical complexities, and marketing challenges, hindering the establishment of a robust hydrogen energy market. The article critically examines the actions already undertaken to harness hydrogen energy for commercial purposes, leveraging scientific insights and statistical data. By carefully examining the current state of hydrogen energy initiatives, the review highlights gaps in existing strategies that require thoughtful consideration. Insights derived from scientific and statistical analyses inform the identification of barriers and contribute to a nuanced understanding of the challenges faced in the journey towards hydrogen energy commercialization. Ultimately, the article presents a strategic proposal outlining marketing actions geared towards expediting the commercialization and widespread adoption of hydrogen energy. Grounded in a thorough review of existing literature and supported by scientific and statistical evidence, this comprehensive analysis offers valuable insights for stakeholders seeking to navigate the intricate landscape of hydrogen energy in the global energy market.

Rapid spread of African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries world-wide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemi-nation. Twelve out of 13 gilts aborted at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to im-planted embryos. These results underline the critical role that boar semen could play in ASFV transmission.

The genus Rhodotorula includes basidiomycetous oleaginous yeast species. R. babjevae can produce compounds of biotechnological interest such as lipids, carotenoids and biosurfactants from low value substrates such as lignocellulose hydrolysate. High-quality genome assemblies are needed to develop genetic tools and to understand fungal evolution and genetics. Here, we combined short- and long-read sequencing to resolve the genomes of two R. babjevae strains, CBS 7808 (type strain) and DBVPG 8058 at chromosomal level. Both genomes have a size of 21 Mbp and a GC content of 68.2%. Allele frequency analysis indicated tetraploidy in both strains. They harbor 21 putative chromosomes with sizes ranging from 0.4 to 2.4 Mb. In both assemblies, the mitochondrial genome was recovered in a single contig, which shared 97% pairwise identity. The pairwise identity between the majority of chromosomes ranges from 82% to 87%. We found indications for strain-specific extrachromosomal endogenous DNA. 7,591 protein-coding genes and 7,607 associated transcripts were annotated in CBS 7808 and 7,481 protein-coding genes and 7,516 associated transcripts in DBVPG 8058. CBS 7808 has accumulated a higher number of tandem duplications than DBVPG 8058. We identified large translocation events between putative chromosomes and a high genetic divergence between the two strains.

Polyhydroxyalkanotes (PHA) are bio-based microbial biopolyesters with stiffness, elasticity, crystallinity and degradability tunable by the monomeric composition, bio-production strategy and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. The article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. Particular attention is devoted to the adaptation of traditional polymer processing techniques for production of medicine-related devices based on PHA, such as melt-spinning, melt extrusion, or solvent evaporation, and to emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, or electrospinning.

Astrocytes are considered to possess a noticeable role in brain metabolism and as a partners in neuron-glia cooperation contribute to synthesis, bioconversions and regulation of the flux of substrates for neuronal metabolism. With the aim to investigate to which extend are human astrocytes metabolizing amino acids and by which compounds are they enriching their surrounding we employed the metabolomics analysis of their culture media by 1H-NMR. In addition, we compered the composition of media with either 5 mM or 25 mM glucose. The quantitative analysis of culture media by 1H-NMR revealed that astrocytes readely dispose from their milieu glutamine, branched-chain amino acids, and pyruvate with significantly high rate, while they enrich the culture media with lactate, branched-chain keto acids, citrate, acetate, ketone bodies, and alanine. The hyperglycemia suppressed the capacity of astrocytes to release branched-chain amino acids while stimulating the generation of ketone bodies. Our results highlight the active involvement of astrocytes in metabolism of several amino acids, and the regulation of key metabolic intermediates. The observed metabolic activities of astrocytes provide valuable insights into their roles in supporting neuronal function, brain metabolism, and intercellular metabolic interactions within the brain. Understanding the complex metabolic interactions between astrocytes and neurons is essential for elucidating brain homeostasis and the pathophysiology of neurological disorders.

Predicting the growth response of seedlings from the environmental responses of photosynthesis and metabolism may be improved by considering the dynamics of non-structural carbohydrate, NSC, over a diurnal cycle. Attenuation of growth metabolism when NSC content is low could explain why some NSC is conserved through the night. A dynamic model, incorporating diurnal variation in NSC, was developed to simulate growth of seedlings hour-by-hour. I compared predictions of this model to published growth and NSC data for seedlings that varied according to temperature, light, day length, or CO₂. Prolonged-darkness experiments showed a temperature dependent upper limit on the respiration capacity. Respiration was attenuated as NSC was depleted. Furthermore, when NSC was high at dawn, inhibition of photosynthesis could attenuate the accumulation of NSC under low temperature, or high light, or high CO₂. These concepts were used to simulate plant metabolism and growth rates and diurnal variation of NSC in tomato seedlings under two light levels and various temperatures. Comparison of other results using the same model parameters showed the dynamic model could predict results for starch and starch-less plants, and when growth was affected by CO₂ enrichment and day length.

Current research on smart cities is primarily focused on the area of applicability of information and communication technologies. However, in the context of a multidisciplinary approach, it is also necessary to pay attention to the resilience and converged security of individual infrastructures. Converged security represents a particular security type based on a selected spectrum of certain convergent security types of, assuming the creation of a complementary whole. Considering the outputs of the analysis of security breaches manifestations, this kind of security makes it possible to detect emerging security breaches earlier (still in the symptom stage), thus providing a more efficient and targeted solution suitable for building smart city infrastructure. In its essence, the article refers the practical application of the theoretical principles of converged security presented in the publication to a functional sample, deployed and tested in practical conditions of selected smart city infrastructure protection and resilience. Considering the nature of the practical application, the convergence of a wider spectrum of smart security alarm systems in the context of resilience assessment is defined. In the beginning, the general principles of security/ safety and the need for their convergence are presented. In this context, the mathematical model called Converged Resilience Assessment method is presented for better understanding. Subsequently, PSIM and SIEM systems are described as a technological concept that can be used for resilience assessment. The most beneficial part is the structural, process and functional description of the Converged Security and Information Management System (CSIM) using the concept of smart security alarm systems converged security.

This article considers the basic psychological needs theory and tries to determine how much autonomy support from a coach is required for basic psychological needs and how autonomy, competence, relatedness, and the psychological motivational climate can explain task and ego involvement in a group of young elite ice hockey players. Our three hypotheses were as follows: autonomy support from the coach will have an impact on motivational involvement, all three basic needs will have an impact on motivational involvement, and motivational involvement will be explained by the motivational climate. A total of 175 male elite ice hockey players from Norway, ranging in age from 15 to 18 years old, answered questionnaires about autonomy support, perceived motivational climate, achievement goal orientation, and basic psychological needs. A multiple regression analysis was run to predict ego–task involvement using autonomy support from the coach, the need for autonomy, the need for competence, the need for relatedness, the task climate, and the ego climate. The only two variables that statistically significantly predicted ego–task involvement were autonomy support from the coach and the ego climate. The analysis revealed that the athletes had a higher score on task than ego involvement, but when this was transformed into two variables (high and low) for task and ego involvement, we found that most players scored high for both task and ego involvement. We found that autonomy from the coach had a positive relationship with a high score for players on both task and ego involvement. We also found that the three basic psychological needs had no impact on the motivational involvement of the athletes. Lastly, we found that the ego climate had an impact on the motivational involvement. There was a positive relationship between a high score for the ego climate and a high score for both ego and task involvement.

This article addresses a challenge modeling novices face in model conceptualization: the recognition of behavior modes. Despite behavior modes being at the heart of system dynamics modeling, there is no unifying taxonomy for them, making them harder to learn for beginners. The article proposes criteria a taxonomy should satisfy, critically reviews previous taxonomies in the literature, and then introduces a new consistent taxonomy based on slope and curvature with mode names that refer only to visual cues and free of references to prior mathematical or domain-specific knowledge. Evidence from an exploratory experiment suggests that novices actually have difficulties classifying curves when using previous taxonomies. Links from these elementary modes to analogous terms in other taxonomies in diverse disciplines allow this taxonomy to be related to other ones. The article concludes by mentioning relevant limitations and future steps.

Attempts to use computers to aid in the detection of breast malignancies date back more than 20 years. Despite significant interest and investment, this has historically led to minimal or no significant improvement in performance and outcomes with traditional computer aided detection. However, recent advances in artificial intelligence and machine learning are now starting to deliver on the promise of improved performance. There are at present more than 20 FDA approved AI applications for breast imaging, but adoption and utilization are widely variable and overall low. Breast imaging is unique and has aspects that create both opportunities and challenges for AI development and implementation. Breast cancer screening programs worldwide rely on screening mammography to reduce the morbidity and mortality of breast cancer and many of the most exciting research and available AI applications focus on cancer detection for mammography. There are however multiple additional potential applications for AI in breast imaging including decision support, risk assessment, breast density quantitation, workflow and triage, quality evaluation, response to neoadjuvant chemotherapy assessment, and image enhancement. In this review the current status, availability, and future directions of investigation of these applications are discussed, as well as the opportunities and barriers to more widespread utilization.

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

Due to the impacts from climate change, the allocation of water resources must urgently be optimized worldwide to ensure that the needs of both water managers and farmers are balanced. In this study, manager-oriented and farmer-oriented assessment models were developed for irrigation water optimization and allocation. The distance from water sources and hydraulic head were the main factors in the manager-oriented assessment model; crop value, water demand of crops, and soil type were additional factors in the farmer-oriented assessment model. The developed assessment models were used to assess irrigation water allocation in five villages in Neimen District. Cadasters at high elevation were discovered to not be suitable for cultivation of crops because of the difficulties in constructing irrigation facilities and the loss of irrigation water during transportation. The result obtained from the manager-oriented assessment system was related to the costs involved in the construction and maintenance of irrigation facilities, which indicated that cadasters located at long distances from water sources and at high elevation are unsuitable for cultivation. By contrast, the result obtained from the farmer-oriented assessment system was related to the profits of farmers and revealed that more cadasters would be suitable for cultivation if suitable crops were chosen.

For older adults, approaching end-of-life (EOL) brings unique transitions related to family relationships. Unfortunately, most families greatly underestimate the need to discuss these difficult issues. For example, parents approaching EOL issues often struggle with receiving assistance from others, avoiding family conflict, and maintaining their sense of personhood. In addition, discussions of EOL issues force family members to face their parents’ mortality, which can be particularly difficult for the adult children to process emotionally. This study explored aging issues identified by aging parents and their families as they traverse these impending EOL changes. Ten focus groups of seniors (n = 65) were conducted. Focus groups were organized according to race (African American/Caucasian), gender, and whether the older adult was living independently or in an assisted care facility. When asked open-ended questions about discussing aging and EOL issues with family members, participants revealed tensions that led us to consider Relational Dialectics Theory as a framework for analysis. The predominant tension highlighted in this report was certainty versus uncertainty, with the two sub-themes of sustained life versus sustained personhood and confronting versus avoiding EOL issues. For these data, there were more similarities than differences as a result of gender, race, or living situation than one might expect, although culture and financial status were found to be influential in the avoidance of EOL discussions. The results of this study help to provide additional insight into relational dialectics related to aging, EOL, and the importance of communication in facilitating family coping.

Based on surveys of winter roost sites, the eastern migratory population of the monarch butterfly (Danaus plexippus) in North America appears to have declined in the last 20 years and this has prompted the implementation of numerous conservation strategies. However, there is little information on the survivorship of first-generation monarchs in the core area of occupancy in Texas, Oklahoma, and Louisiana where overwinter population recovery begins. The purpose of this study was to determine the survivorship of first-generation eggs to third instars at a site in north Texas and to evaluate host plant arthropods for their effect on survivorship. Survivorship to third instar averaged 13.4% and varied from 11.7% to 15.6% over three years. The host plants harbored 77 arthropod taxa, including 27 predatory taxa. Despite their abundance, neither predator abundance nor predator richness predicted monarch survival. However, host plants upon which monarchs survived often harbored higher numbers of non-predatory arthropod taxa and more individuals of non-predatory taxa. These results suggest that ecological processes may have buffered the effects of predators and improved monarch survival in our study. The creation of diverse functional arthropod communities should be considered for effective monarch conservation, particularly in southern latitudes.

Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

Ferrite body is the origin of crack and corrosion initiation of steels. Distribution and density of ferrite in seven steel ingots were examined by light optical microscopy and computational modeling in the study to explore the correlation of ferrite formation to chemical composition and mushy zone temperature in ingot forming. The central segregation phenomenon in ferrite distribution was observed in all the examined steel specimens except 0Cr17Ni4Cu4Nb stainless steel. No significant difference was found in distribution and density of ferrite amongst zones of the surface, ½ radius and core in neither risers nor tails of 0Cr17Ni4Cu4Nb ingots. Additionally, fewer ferrite was found in 0Cr17Ni4Cu4Nb compared to other examined steels. The difference of ferrite formation in 0Cr17Ni4Cu4Nb elicited a debate on the traditional models explicating ferrite formation. Considering the compelling advantages in mechanical strength, plasticity and corrosion resistance, further investigation on the unusual ferrite formation in 0Cr17Ni4Cu4Nb would help understand the mechanism to improve steel quality. In summary, we observed that ferrite formation in steel was correlated with mushy zone temperature. The advantages of 0Crl7Ni4Cu4Nb in corrosion resistance and mechanical stability could be resulted from that fewer ferrites formed and distributed in a scattered manner in microstructure of the steel.

Tungsten oxides play a pivotal role in a variety of modern technologies e.g., switchable glasses, wastewater treatment, and modern gas sensors. Metallic tungsten is used as armor material, for e.g., gas turbines as well as future fusion power devices. In the first case, oxides are desired as functional materials, while in the second case, oxides can lead to catastrophic failures, so avoiding the oxidation of tungsten is desired. In both cases, it is crucial to understand the reactivity of tungsten oxides with other chemicals. In this study, the different reactivities of tungsten oxides with the highly-oxophilic beryllium are studied and compared. Tungsten-(IV)-oxide and tungsten-(VI)-oxide layers are prepared on a tungsten substrate. In the next step, a thin film of beryllium is evaporated on the samples. In consecutive steps, the sample is heated in steps of 100 K from r. t. to 1273 K. The chemical composition is investigated after each experimental step by high-resolution X-ray photoelectron spectroscopy (XPS) of all involved core levels as well as the valence band. A model is developed to analyze the chemical reactions after each step. In this study, we find that tungsten trioxide was already reduced by beryllium at r. t. and started to react to form the ternary compounds BeWO₃ and BeWO₄ at temperatures starting from 673 K. However, tungsten dioxide is resistant to reduction at temperatures of up to 1173 K. In conclusion, we find WO₂ to be much more chemically resistant to the reduction agent Be than WO₃.

Polyhydroxyalkanoates (PHA) are microbial biopolyesters utilized as “green plastics”. Their production under controlled conditions resorts to bioreactors operated in different modes. Because PHA biosynthesis constitutes a multiphase process, both feeding strategy and bioreactor operation mode need smart adaptation. Traditional PHA production setups based on batch, repeated batch, fed-batch or cyclic fed-batch processes are often limited in productivity, or display insufficient controllability of polyester composition. For highly diluted substrate streams like it is the case for (agro)industrial waste streams, fed-batch enhanced by cell recycling were recently reported as a viable tool to increase volumetric productivity. As emerging trend, continuous fermentation processes in single-, two-, and multi-stage setups are reported, which bring the kinetics of both microbial growth and PHA accumulation into agreement with process engineering, and allow tailoring PHA´s molecular structure. Moreover, we currently witness an increasing number of CO2-based PHA production processes using cyanobacteria; these light-driven processes resort to photobioreactors similar to those used for microalgae cultivation, and can be operated both discontinuously and continuously. This development goes in parallel to the emerging use of methane and syngas as an abundantly available gaseous substrates, which also calls for bioreactor systems with optimized gas transfer. The review sheds light on the challenges of diverse PHA production processes in different bioreactor types and operational regimes using miscellaneous microbial production strains such as extremophilic Archaea, chemoheterotrophic eubacteria and phototrophic cyanobacteria. Particular emphasize is dedicated to the limitations and promises of different bioreactor-strain combinations, and to efforts devoted to upscaling these processes to industrially relevant scales.

Incobotulinumtoxin A and Yoga-like Isometric Exercise in Adolescent Idiopathic Lumbar Scoliosis – a randomized pilot study Abstract: Background: Approximately 90% of scoliosis is adolescent idiopathic (AIS). From its first appearance at 10-14 until age 18 it is most vulnerable to deterioration; young people are most susceptible to the condition worsening. An effective non-surgical means of remediation would be welcome. Design: Randomized control two-arm study, assessing the safety and efficacy of combining incobotulinum injections with yoga to reverse lumbar and thoracolumbar AIS. Methods: In a private clinic setting, non-pregnant healthy 12 – 18 year-olds were either taught a symmetrical “placebo” yoga pose (control sub-group 1), given the side plank (Vasisthasana) done thrice daily with placebo injection (control sub-group 2) or given the thrice-daily side-plank with botulinum injection (Intervention group 3). Injection: 33 IU of incobotulinum toxin type A (Xeomin) injected into concave-side lumbar paraspinals and quadratus lumborum at L2-3 and the psoas muscle at L3-4, or injected similarly with placebo. Randomization by Random.com. Objective: Assess whether muscular asymmetry treated with botulinum toxin injection and the side-plank are safe and effective in AIS. Results: Outcome: Twelve intervention and 12 placebo patients (Groups 1 + 2), 12 -18 years old completed the three-month study period. Mean daily side-plank time = 165 seconds. Mean initial lumbar curvature was 36.9 degrees (SD 14.36), (p<0.0001); mean curvature at 3 weeks was 29.5 degrees. (SD 14.23) (p<0.0001); mean curvature at 3 months was 26.0 degrees (SD 12.81) Onset vs 3-month value: p<0.0001. Two patients in Group 3 complained of shoulder pain, and 2 of wrist pain that resolved when the side-plank was done on the elbow. Conclusion: Muscle asymmetry appears relevant to AIS treatment. Incobotulinum injections combined with the side-plank done with the convex side downward may be safe and helpful in adolescent idiopathic lumbar scoliosis.

Aims: To review canine rabies, mass parental vaccination, human post-exposure prophylaxis, gene therapy and costs for fighting rabies. Place and Duration of Study: Department of Animal Science – Other, Nelwan Institution for Human Resource Development, Indonesia, between December 2017 and March 2018. Methodology: The author searched the Pubmed Database at NCBI for articles on rabies disease published between 2007 and 2018. All articles were open access and in English. For rabies virus examination, Seller’s test was used. In this article, references written by the author and other relevant publications were included. The author reviewed a rabies dog case kept at Nelwan Institution for Human Resource Development. Results: The dog showed clinical signs such as inappetance, urinary frequency and soaking in a small, juicy drain. Currently, to treat rabies, no drugs are available. For rabies prevention, vaccination is the best way. To eradicate rabies, mass vaccination in dogs, post-exposure prophylaxis, and gene therapy should be used. Fort rabies disease eradication, minimum of 70% of the dog population should receive the vaccination. In addition, humans with category II exposure should receive a rabies vaccine and rabies immunoglobulin. Conclusion: To eradicate rabies, vaccinations are required. In addition, gene therapy can eliminate rabies from the infected neurons by using rAAV-N796. CRISPR/Cas9 system in combination with the MMEJ-based method. Furthermore, mass parental vaccination, post-exposure prophylaxis, and gene therapy can reduce costs in controlling rabies disease.

Salmon farming has been blamed for the collapse of the sea trout (Salmo trutta) fishery in Loch Maree on Scotland’s west coast despite the absence of any direct evidence. Stocks of west coast demersal marine fish, especially around the Clyde Estuary have also declined over a similar time span. The decline of these marine fish stocks can be attributed to the removal of the “three-mile fishing limit” in 1984 by UK Government legislation. Sea trout inhabit the same inshore waters as targeted demersal fish and can be caught as by-catch. Comparisons of the decline of demersal species and the sea trout from Loch Maree and the west coast show a high degree of correlation. Stocks of whiting (Merlangius merlangus) from inshore waters have found to consist of small fish which mirrors the stock makeup of the Loch Maree sea trout stock.

This paper describes the dielectric relaxation spectroscopy (DRS) method for obtaining glass transition temperature and the onset of crystallinity of skim milk powder (SMP). The methodology consists of exposing SMP samples to numerous constant temperatures, T, and water activities, a_w, and measuring the relaxation time. Measurements are based on changes in the loss-tangent height at its peak frequency. Glass transition times are identified at peaks in the loss-tangent height versus time curve and the onset of crystallinity times are identified when the loss-tangent height collapses. The analysis leads to two boundary curves: glass transition T_g, a_w curve and the onset of crystallinity T_c, a_w curve. They separate the SMP stable (long shelf life) and unstable (short shelf life) regions. Two curve fitting algorithms were developed for (a) a_w², t_g curve where t_g is the time to glass transition and a_w², t_c curve where time t_c is the time to onset of crystallinity and (b) T_g, a_w and T_c, a_w boundary curves. Finally, the DRS data are compared to differential scanning calorimetry (DSC) results.

This is a methodological contribution to reference mode development in system dynamics model conceptualization. Existing behavior mode taxonomies-developed for various modeling phases-provide no comprehensive method for mode classification based on an exhaustive set of mutually exclusive modes, and derivation of questions the simulation model should answer. Novice modelers need such guidance. The article proposes a conceptual framework for systemic behavior with a hierarchical taxonomy of elementary, composite, and overlaid modes. A structured method identifies the intervals of each respective mode, orders them into episodes and then condenses the variables’ episodes to systemic episodes. Each transition then gives rise to a fundamental question for the model under development. Three classical cases illustrate the application and contrast the proposed taxonomy to others in the extant literature. The article then discusses some validation criteria referring to reference modes and their link to the dynamic hypothesis, current limitations, and questions for further research.

The importance of Muscovy ducks in industrial poultry production is growing; however, little is known about the physiology of their reproductive cycles. This study investigated the influence of male biostimulation on female ducks before the commencement of the laying phase. A total of 15 female Muscovites were kept in contact with a male duck until the point of laying, while 15 other females were kept without any contact with a male conspecific. Before reaching egg-laying maturity, the cloacae of 29 adult ducks were subjected to daily clinical assessments. The evaluations yielded four unique categories of outcomes, determined by assessing factors such as the degree of redness and protrusion of the mucous membrane, moisture level, and swelling of the cloacal sphincter muscle. In terms of biostimulation, the findings demonstrated that, on average, ducks in contact with males laid the first egg 16 days earlier than isolated ducks. Furthermore, there was no significant difference observed in the mean initial egg weight between both groups (p = 0.841). The changes in the cloacal morphology indicated significant morphological changes 25–26 days before laying. Efforts to improve Muscovy production and develop biotechnological techniques to modify the reproductive cycle will benefit from these advancements.

The advent of the era of big data will bring more convenience to people and greater development to society. But at the same time, it will also bring people the problem of 'information overload', i.e., when people are faced with huge information data, there are many redundant and worthless data. The redundant and worthless data information seriously interferes with the accurate selection of information data. Even though people can use Internet search engines to access information data, they cannot meet the individual needs of specific users in specific contexts. The personalized needs of a particular user in a particular context. Therefore, how to find useful and valuable information quickly has become one of the key issues in the development of big data. With the advent of the era of big data, recommendation systems, as an important technology to alleviate information overload, have been widely used in the field of e-commerce. Recommender systems suffer from a key problem: data sparsity. The sparsity of user history rating data causes insufficient training of collaborative filtering recommendation models, which leads to a significant decrease in the accuracy of recommendations. In fact, traditional recommendation systems tend to focus on scoring information and ignore the contextual context in which users interact. There are various contextual modal information in people's real life, which also plays an important role in the recommendation process. In this paper we achieve data degradation and feature extraction, solving the problem of sparse data in the recommendation process. An interaction context-aware sub-model is constructed based on a tensor decomposition model with interaction context information to model the specific influence of interaction context in the recommendation process. Then an attribute context-aware sub-model is constructed based on the matrix decomposition model and using attribute context information to model the influence of user attribute contexts and item attribute contexts on recommendations. In the process of building the model, the method not only utilizes the explicit feedback rating information of users in the original dataset, but also utilizes the interaction context and attribute context information of the implicit feedback and the unlabeled rating data. We evaluate our model by extensive experiments. The results illustrate the effectiveness of our recommender model.

Arctic sea ice characteristics have been changing rapidly and significantly in the last few decades. Using a long-term time series of sea ice products from satellite observations - the extended AVHRR Polar Pathfinder (APP-x), trends in sea ice concentration, ice extent, ice thickness, and ice volume in the Arctic from 1982 to 2020 are investigated. Results show that the Arctic has become less ice-covered in all seasons, especially in summer and autumn. Arctic sea ice thickness has been decreasing at the rate of -3.24 cm per year, resulting in about a 52% reduction in thickness from 2.35 m in 1982 to 1.13 m in 2020. Arctic sea ice volume has been decreasing at the rate of -467.7 km³ per year, resulting in about a 63% reduction in volume, from 27590.4 km³ in 1982 to 10305.5 km³ in 2020. These trends are further examined from a new perspective, where the Arctic Ocean is classified into open water, perennial, and seasonal sea ice-covered areas based on the sea ice persistence. The loss of the perennial sea ice-covered area is the major factor in the total sea ice loss in all seasons. If the current rates of sea ice changes in extent, concentration, and thickness continue, the Arctic is expected to have ice-free summer by the early 2060s.

Purpose: Prostate cancer remains the 2nd leading cancer killer of men, yet it is also a disease with a high rate of overtreatment. Diffusion weighted imaging (DWI) has shown promise as a reliable, grade-sensitive imaging method, but it is limited by low image quality. Currently, DWI image quality is directly related to low gradient ampli-tudes, since weak gradients must be compensated with long echo times. Methods: We propose a new type of MRl accessory, an "inside-out" and nonlinear gradient, whose sole purpose is to deliver diffusion encoding to a region of interest. Performance was simulated in OPERA and the resulting fields were used to simulate DWI with two compartment and kurtosis models. Experiments with a nonlinear head gradient prove the accuracy of DWI and ADC maps diffusion encoded with nonlinear gradients. Results: Simulations validated thermal and mechanical safety while showing a 5 to 10-fold increase in gradient strength over prostate. With these strengths, lesion CNR in ADC maps approximately doubled for a range of anatomical positions. Proof-of-principle experiments show that spatially varying b-values can be corrected for accurate DWI and ADC. Conclusions: Dedicated nonlinear diffusion encoding hardware could improve prostate DWI.

Previous evidence in support of a slowly acting (scale of 100s of seconds) and volume-transmitted component of cholinergic signaling was based largely on studies using measures of extracellular brain acetylcholine (ACh) levels which required several minutes to generate a single data point and typically employed AChEsterase inhibitors (AChEIs) to foster the measurement of ACh. Moreover, collecting such data points in correlation with relatively stable behavioral states has supported the view that extracellular ACh levels vary at a relatively slow rate. Here we argue that forebrain cholinergic signaling is exclusively phasic (milliseconds to perhaps seconds), unlikely to be volume-transmitted, and that previous neurochemical evidence and associated behavioral correlates may be re-interpreted in terms of integrated phasic cholinergic activity and specific behavioral and cognitive operations. The highly potent catalytic enzyme for ACh, AChE, limits the presence of an ambient extracellular ACh level and thus renders it unlikely that ACh influences target regions via relatively slow changes in extracellular ACh concentrations. Real-time amperometric recordings of cholinergic signaling have suggested a specific function of rapid, phasic or transient cholinergic signaling in attentional contexts. Optogenetic studies support a causal relationship between these transients on behavior. Combined electrochemical and neurophysiological recordings revealed that the powerful behavioral control by cholinergic transients involves the generation of high-frequency oscillations. Such oscillations are thought to recruit efferent circuitry to (re)activate dormant task sets. Evidence showing the impact of genetic variations of the capacity of cholinergic synapses likewise can be interpreted in terms of their impact on the ability to sustain generation of repeated phasic cholinergic signals, as opposed to effects on ambient ACh levels. Further, while notions of slowly-changing, sleep stage-associated variations in extracellular ACh levels and their functions are widely accepted, the evidence is in fact limited. An alternative hypothesis offers a role for high-frequency cholinergic transient signaling during REM sleep. By employing a theoretical framework that focuses on the phasic and causative characteristics and functions of cholinergic signaling, results from human cognitive neuroscience studies of cholinergic function may be substantially clarified and simplified. Compared to the current treatment of cholinergic deficits using AChEIs, the conceptualization of forebrain cholinergic signaling as wired, phasic, and causative predicts that drugs that either rescue transient presynaptic signaling or amplify or rescue the postsynaptic impact of phasic signals will be more efficacious in treating age- and dementia-related cognitive and cognitive-motor disorders.

Glioblastoma is a highly malignant brain tumor consisting of heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in single run, those may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even the both types of glioblastoma cells share several common metabolic aspects, they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites - polaromics.

The field of applied behavior analysis has been directly involved in both research and applications of behavioral principles to improve the lives of captive zoo animals. Thirty years ago, Forthman and Ogden (1992) wrote one of the first papers documenting some of these efforts. Since that time, considerable work has been done using behavioral principles and procedures to guide zoo welfare efforts. The current paper re-examines and updates Forthman and Ogden’s original points, with attention to the five categories they detailed: (1) promotion of species-typical behavior, (2) reintroduction and repatriation of endangered species, (3) animal handling, (4) pest control, and (5) animal performances. In addition, we outline three current and future directions for behavior analytic endeavors: (i) experimental analyses of behavior and the zoo, (ii) applied behavior analysis and the zoo, and (iii) within-subject methodology and the zoo. The goal is to provide a framework that can guide future behavioral research in zoos, as well as create applications based on these empirical evaluations.

We confirm that energy dissipation weighting provides the most accurate approach to determining the effective hydraulic conductivity (Keff) of a binary K grid. A deep learning algorithm (UNET) can infer Keff with extremely high accuracy (R2 > 0.99). The UNET architecture could be trained to infer the energy dissipation weighting pattern from an image of the K distribution with high fidelity, although it was less accurate for cases with highly localized structures that controlled flow. Furthermore, the UNET architecture learned to infer the energy dissipation weighting even if it was not trained on this information directly. However, the weights were represented within the UNET in a way that was not immediately interpretable by a human user. This reiterates the idea that even if ML/DL algorithms are trained to make some hydrologic predictions accurately, they must be designed and trained to provide each user-required output if their results are to be used to improve our understanding of hydrologic systems most effectively.

Sustainable agricultural production is endangered by several ecological factors such as drought, extreme temperatures, excessive salts, parasitic ailments, and insect pest infestation. These challenging environmental factors may have adverse effects on future agriculture production in many countries. In modern agriculture, conventional crop breeding techniques alone are inadequate for achieving the increasing population’s food demand on a sustainable basis. The advancement of molecular genetics and related technologies are promising tools for the selection of new crop species. Gene pyramiding through marker assisted selection (MAS) and other techniques have accelerated the development of durable resistant/tolerant lines with high accuracy in the shortest possible period of time for agricultural sustainability. Gene stacking has not been fully utilized for biotic stress resistance development and quality improvement in most of the major cultivated crops. This review emphasizes on gene pyramiding techniques that are being successfully deployed in modern agriculture for improving crop tolerance to abiotic and biotic stresses for sustainable crop improvement.

The success of deep learning (DL) in offline brain-computer interfaces (BCIs) has not yet translated into efficient online applications. This is due to three primary challenges. First, most DL solutions are designed for offline decoding, making the transition to online decoding complex and unclear. Second, the use of sliding windows in online decoding increases the computational complexity of DL training. Third, DL models typically require large amounts of training data, which are often scarce in BCI applications. To address these issues and enable real-time decoding, even across different subjects without calibration data, we first introduce a novel approach called real-time adaptive pooling (RAP). RAP modifies the pooling layers of existing offline DL models towards the online decoding requirements. Additionally, it significantly reduces the computational demand during training by jointly decoding consecutive windows. To reduce the amount of training data required, our approach leverages different levels of domain adaptation. We show how different settings enable different adaptation solutions. The results demonstrate that our approach is both powerful and can be calibration-free, providing a robust and practical solution for real-time BCI applications. These findings pave the way for the development of co-adaptive and highly efficient DL-based online BCI systems.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

The recent past has witnessed a growing interest in technologies for creating chatbots. Advances in Large Language Models for natural language processing are underpinning rapid progress in chatbot development, and experts predict revolutionary changes in the labour market as many manual tasks are replaced by virtual assistants in a range of business functions. As the new technology becomes more accessible and advanced, more companies are exploring the possibilities of implementing virtual assistants to automate routine tasks and improve service. This article reports on qualitative inductive research undertaken within a chatbot development team operating in a major international enterprise. The findings identify critical success factors for chatbot projects, and, based on the in-depth case study, a model is put forward to aid the manageability of chatbot implementation. The presented model can serve as an exemplar guide for researchers and practitioners working on the design, development and implementation of virtual assistants. It is flexible and applicable in a wide range of business contexts, linking strategic business goals with execution steps. It is particularly applicable for teams with no experience of chatbot implementation, reducing uncertainty and managing decisions and risks throughout the project lifecycle, thereby increasing the likelihood of project success.

The textile and clothing (T&C) industry is not usually viewed as an exemplar of sustainable de-velopment and the circular economy, as the industry has hitherto made its products in linear fashion, with relatively little recycling of the finished goods. This article examines the industry’s approach to the core sustainability concept and the circular economy in particular, through a re-view of the available academic literature, evidence from corporate sustainability reports and websites, and feedback from an online survey of industry professionals. The role of digital technology deployment in engendering sustainability and the circular economy in the industry is also explored. The study finds that whilst sustainability is now firmly embedded at the strategic level in the vast majority of companies studied, attitudes towards the circular economy remain fickle. The use of digital technologies in support of sustainability objectives is also limited at present, but the article concludes that the need to meet compliance requirements and new cus-tomer perceptions of sustainability will speed the transition to circular economy activities, facili-tated by greater exploitation of digital technologies. Building upon the research findings, existing models and an initial conceptual framework, a simple operational model for initiating such a transition for small-to-medium sized enterprises in the T&C industry is put forward.

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.

This article explores how digitalisation is impacting the hospitality industry and assesses the evolving role of Information Technology (IT) strategy in the digitalisation process. The research approach is qualitative and inductive, based on six in-depth interviews with senior IT professionals in the hospitality industry. Findings indicate significant differences in the role of IT strategy in guiding digitalisation in the companies studied. The depth of information provided by the interviewees supports the development and application of a model that profiles the companies regarding their degree of digitalisation and technology integration. Analysis of interview material allows the identification of key properties for successful digitalization: process agility, workforce adaptability, and technology manageability, along with a clear data culture and ensured cybersecurity. However, disparate systems and technologies, and a lack of data integrity, are key issues that leave hospitality companies with difficult choices in progressing digitalisation initiatives. The applied model and identification of key properties for successful digitalisation contribute to the development of related theory and can also be used as a reference point for senior IT professionals working in the industry.

Increasing traffic loads and changes in code provisions lead to deficits in shear and flexural capacity of many existing highway bridges. Therefore, a lot of structures in Europe and North America are expected to require refurbishment and strengthening in the future. This projection is based on the current condition of many older road bridges. Different strengthening methods for bridges exist to extent their service life, all having specific advantages and disadvantages. By applying a thin layer of carbon textile reinforced mortar (CTRM) to bridge deck slabs and the webs of prestressed concrete bridges, the fatigue and ultimate strength of these members can be increased significantly. The CTRM-layer is a combination of a corrosion resistant carbon fibre reinforced polymer (CFRP) fabric and an efficient mortar. In this paper, the strengthening method and the experimental results obtained at RWTH Aachen University are presented.

Nitrogen (N) is an essential nutrient and plays an important role in plant growth and physiology. In addition, N is also the limiting nutrient in most terrestrial ecosystems. The increasing use of N fertilizers increases agricultural production, but also has negative impacts on biodiversity, water quality and increases emissions of greenhouse gases such as nitrogen oxides (NOx) and nitrous oxide (N2O) into the atmosphere. N2O is a strong greenhouse gas and the product of microbial transformation processes of N introduced into soil and groundwater (nitrification and denitrification). The production of N2O in soils is highly dependent on oxygen and water content, soil temperature and texture and the available amount of reactive nitrogen (NO3- or NH4+). In agricultural soils, N2O emissions are also influenced by the type of fertilizer used, crops grown, soil pH and NO3- concentration. Refined forms of land management, such as the cultivation of legumes, can reduce the use of fertilizers and thus also the emission of N2O. Legumes can use symbiotic nodule bacteria (rhizobia) to bind atmospheric N2 and make it available to the plant. Non-symbiotic soil microorganisms such as cyanobacteria or other heterotrophic and autotrophic prokaryotes are also able to fix N2. Furthermore, the N2-fixing enzyme nitrogenase, which is specific for most organisms, is not specific for other N2 compounds, especially N2O. To study the N2 and N2O fixation potential of soils and legumes, experiments with isotope-enriched N-gases (100 mol% 15N2 and 15N2O) were performed. Three different soil types (forest, meadow and wetland) as well as legume plants inoculated with rhizobia bacteria (Rhizobium leucaneae) (Leucaena leucocephala) were incubated in microcosms with different mixing ratios of N2 and N2O over a period of one week. The measured 15N enrichment was then used to determine the biological uptake rates. Both in plants and in soils admixtures of up to 40% N2O had no influence on the N2 fixation rate. N2 uptake rates were 1.2 ± 0.4 ug N gdw-1 d- 1in forest and grassland soils and 3.9 ± 1.2 ug N gdw-1 d- 1 in wetland soils. In contrast, the N2 fixation rates of leguminous plants were significantly higher (130 ± 40 ug N gdw-1 d- 1), with the highest accumulation not in root nodules but in the roots. In both plants and soil, the N2O fixation of 0.2 ± 0.1 ug N gdw-1 d- 1 could only be measured from a concentration of 4 vol%. The results indicate that both soils and legumes have a high potential to bind atmospheric nitrogen in the form of both N2 but not N2O. The fate of nitrogen in soil needs to be further investigated. N2 fixation seems to play an important role in wetland soils. Legumes in particular have the potential for NH4+ input and N2O reduction, as most of the solid nitrogen has been transferred to the roots, which can contribute significantly to soil nutrient input.

Based on hospital capacities, facts from past experience with the coronavirus disease 2019 (COVID-19) virus and the number of dark infections during the second wave (DII = 2D2), a reasonable limiting value of 140/D2 for the 7-day incidence per 100,000 persons (MSDIHT) and a second wave herd immunization threshold fraction value of 0.26 in Germany were calculated. If the MSDIHT is held below this limiting value, the German hospital system can cope with the number of new seriously infected persons without any triage decisions. On the basis of the SIRV epidemics model, the classical threshold values for herd immunization were calculated for 18 countries. For these countries, the dates regarding when herd immunization against the second COVID-19 wave will be reached were estimated

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.

The primary purpose of this prospective cohort study was to determine if treating endometriosis with optimal excision surgery leads to lower rates of repeat surgery as compared to historical rates of repeat surgery by ablation. A secondary outcome was to examine whether the use of hormonal suppression differed before surgery, depending on the stage of endometriosis found at surgery. Optimal excision was defined as completely excising all areas of abnormal peritoneum, wherever found in the pelvis, having looked systematically with near contact laparoscopy. All surgeries were performed by a single surgeon specializing in optimal excision at a tertiary referral center. The rate of repeat surgery after optimal excision surgery for endometriosis was remarkably low (2.5%, 15/620) as compared to historical rates of repeat surgery by ablation. Additionally, the lack of significant evidence between hormonal suppression use and progression of stage of endometriosis provides implicit evidence that hormonal suppression does not prevent progression of the disease. Further controlled studies are needed to verify these findings.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.

"Metaverse" as a term came to the fore in 2021 when Facebook rebranded its corporate identity to Meta, and signaled its intention to invest at least $10 billion in developing the concepts and related products that year. However, there is still little consensus in defining what constitutes the metaverse, although there is a widespread, though not universal, agreement that it will bring a wide range of benefits across society. More specifically, the advent, and continuing evolution, of the metaverse has strategic and operational implications for, and impacts on, industry and business at large. Adopting an inductive, interpretivist approach, this exploratory research article presents case examples of the guidance on the responsible development of the metaverse provided by two IT business services companies. The article identifies the major risks and responsibilities associated with the metaverse and assesses how companies might address these responsibilities. Very little research has been published in this area and this article attempts to make a small contribution to filling this gap in the literature. The article finds that responsibilities are largely in line with those currently associated with corporate digital responsibility, and concludes that the strategic impact and extent of regulatory change will depend on the nature of the metaverse that materialises in the forthcoming decade.

Pharmacy personnel often answer telephones to respond to pharmacy customers (subjects) who received messages from automated systems. This research examines the communication process in terms of how users interact and engage with pharmacies after receiving automated messages. No study has directly addressed automated telephone calls and subjects’ interactions. The purpose of this study is to test the interpersonal communication (IC) process of uncertainty in subjects in receipt of automated telephone calls from pharmacies. Subjects completed a survey of validated scales for Satisfaction (S); Relevance (R); Quality (Q); Need for Cognitive Closure (NFC). Relationships between S, R, Q, NFC, and subject preference to an automated telephone call (ATC) were analyzed to determine whether subjects contacting pharmacies display information seeking behavior. This research demonstrates that seeking information occurs if subjects: are dissatisfied with the content of the ATC; perceive that the Q of the ATC is high; perceive that the Q of ATC is high, and like receiving the ATC or with high NFC, and do not like receiving ATCs. Other interactions presented complexities amongst uncertainty and tolerance of NFC within the IC process.

Despite the increasing popularity of liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, there is a lack of accepted and validated method for lipid extract quality and quantity assessment prior to LC-MS. Fourier-Transform Infrared Spectroscopy (FTIR) has been reported for quantification of pure lipids, however, the sample complexity and purity complex lipid extract quantification in lipidomics experiments could be impact quantification accuracy. Here, we report comprehensive assessment of the sample matrix on the accuracy of lipid quantification using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Pure lipids are characterized by CH-and C=O-stretching vibrations on FTIR, with quantitative range of 40–3000 ng and a limit of detection of 12 ng. Sample extraction method and local baseline subtraction during FTIR spectral processing significantly impact lipid quantification by CH-stretching. To facilitate sample quality screening, we developed the Lipid Quality (LiQ) score from a spectral library of common contaminants, using a ratio of peak heights between CH-stretching vibrations maxima and the collective vibrations from amide/amine, CH-stretching minima and sugar moieties. We evaluated LiQ score as a rapid sample quality control method by comparing to total LC-MS intensity of targeted lipidomics of 107 human plasma lipid extracts. Exclusion of poor-quality samples based on LiQ score improved the correlation between FTIR and LC-MS quantification. Finally, the uncertainty of absolute quantification by FTIR was estimated using a 795 ng SPLASH LipidoMix standard to be &lt;10%. In summary, this study identified key parameters for accurate FTIR-based quantification of complex lipid mixture, and developed a rapid workflow requiring only 1 µL of MS-ready sample and &lt; 5 minutes for routine lipidomics sample quality and quantity assessment.

The urban heat island (UHI) and its intensity is one of the phenomena that are of determining importance for the comfort of living in cities and their sustainable development in the face of deepening climate change. The study is objectively difficult due to the large dynamics like land cover and the considerable diversity of land use patterns in urban areas. Various approaches and methods are used in research practice, based both on ground measurements and in the use of remote methods and satellite information. However, most of these approaches provide information with problematic spatial and temporal resolution, making them difficult to apply for sustainable urban planning purposes, which require adequate information provision. This paper presents the results of the application of thermal photogrammetry based on the use of unmanned aerial systems (UAS), combined with geographic information systems (GIS), in the study of surface urban heat island intensity (SUHI), at the local level for the largest housing complex in Bulgaria - Lyulin district of the capital of Sofia city. The studies were carried out during a heat wave in July 2023. A difference of 16.5oC was found between locations with SUHI occurrence and suburban areas. The information benefits of locally addressed data and their direct applicability are discussed to support decision-making processes in the planning and management of urban areas, including their climate adaptation and sustainable development.

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

As a result of extensive research in the field of mobile robots (rovers) and swarms, a number of algorithms exist to assist them for executing a mission in the three levels of software architecture: strategic (interaction loop level), tactic (planning) and operational (sensing, control and actuation). They allow them to achieve their goals while adapting to their environment through a multitude of methods designed for each situation. For this reason, a literature review of the latest research conducted in previous years is required to identify new research trends in human-swarm interaction applied to help humans in hazardous environment such as militarized zone. In this paper, we will present some interesting algorithms for interactive and autonomous mobile robots acting in swarms in an open and crowded environment. A discussion will focus on comparing different algorithms and their advantages and disadvantages.

The main foundations of the standard $\Lambda $CDM model of cosmology are that: 1) The redshifts of the galaxies are due to the expansion of the Universe plus peculiar motions; 2) The cosmic microwave background radiation and its anisotropies derive from the high energy primordial Universe when matter and radiation became decoupled; 3) The abundance pattern of the light elements is explained in terms of primordial nucleosynthesis; and 4) The formation and evolution of galaxies can be explained only in terms of gravitation within a inflation+dark matter+dark energy scenario. Numerous tests have been carried out on these ideas and, although the standard model works pretty well in fitting many observations, there are also many data that present apparent caveats to be understood with it. In this paper, I offer a review of these tests and problems, as well as some examples of alternative models.