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

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

Zephyranthes citrina Baker is a bulbous herb, commonly known as yellow rain lily belongs to the family Amaryllidaceae. It is a native of tropical and subtropical America but nowadays it is cultivated as a popular ornamental herb in several parts of the world including India. This herb represents one of the richest sources of phytochemicals, especially alkaloids and possesses great potential for pharmaceutical applications. It shows remarkable antiprotozoal, antimicrobial, anti-Alzheimer, cytotoxic, antioxidant, anti-inflammatory, analgesic, and dye removal activities. This review is an effort to give a detailed study of the literature on the biological activities of Zephyranthes citrina. This review concludes that Zephyranthes citrina has a great potential to treat various diseases and could be used as a source for novel healthcare products in the near future, which requires further experimentation.

An oxidation resistant coating on cemented tungsten carbides is characterised in this work. Cemented tungsten carbides (cWCs) are routinely used in mining and manufacturing but are also candidate materials for compact radiation shielding in fusion power generation. In both environments, cWCs will suffer significant degradation due to oxidation at relatively low temperatures. In a recent study, a Si-deposition coating method was demonstrated to improve the oxidation resistance of cWCs by up to a factor of 1,000. This work focusses on the growth kinetics, phase composition, and mechanical properties of these coatings. By combining quantitative X-ray diffraction, electron microscopy and nanoindentation, we show that the coating layer has a 20 % higher hardness than the substrate, which was explained on the basis of a previously-unknown presence of a fine distribution of very hard SiC laths. To interpret the coating stability, a coating growth map is developed. The map shows the structure is stable under a broad range of processing temperatures and composite compositions, demonstrating the potential application of these coatings in a variety of nuclear shielding cWCs.

Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago. Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids (aldosterone, cortisol), and sex steroids (estrogen, progesterone, testosterone) also are young, with an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. Through gene duplication and divergence of the 3-ketosteroid receptor, receptors that respond to androgens, glucocorticoids, mineralocorticoids and progestins evolved in vertebrates. Thus, an ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, evolved in jawless vertebrates (cyclostomes: lampreys, hagfish). This was followed by evolution of an androgen receptor, distinct glucocorticoid and mineralocorticoid receptors and estrogen receptor-α and -β in cartilaginous fishes (gnathostomes: sharks). Further evolution of mineralocorticoid signaling occurred with the evolution of aldosterone synthase in lungfish, a forerunner of terrestrial vertebrates. Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The evolution of steroid receptors at key nodes in the evolution of vertebrates, in which steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for an important role for steroid receptors in the evolutionary success of vertebrates, considering that the human genome contains about 22,000 genes, which is not much larger than genomes of invertebrates, such as Caenorhabditis elegans (~18,000 genes) and Drosophila (~14,000 genes).

There is much concern about disruption of endocrine physiology regulated by steroid hormones in humans, other terrestrial vertebrates and fish by industrial chemicals, such as bisphenol A, and pesticides, such as DDT. These endocrine-disrupting chemicals influence steroid-mediated physiology in humans and other vertebrates by competing with steroids for receptor binding sites, disrupting diverse responses involved in reproduction, development and differentiation. Here I discuss that due to evolution of the progesterone receptor (PR) and mineralocorticoid receptor (MR) after ray-finned fish and terrestrial vertebrates diverged from a common ancestor, each receptor evolved to respond to different steroids in ray-finned fish and terrestrial vertebrates. In elephant shark, a cartilaginous fish, ancestral to ray-finned fish and terrestrial vertebrates, both progesterone and 17,20-beta-dihydroxy-progesterone activate the PR. During the evolution of ray-finned fish and terrestrial vertebrates, the PR in terrestrial vertebrates continued responding to progesterone and evolved to weakly respond to 17,20-beta-dihydroxy-progesterone. In contrast, the physiological progestin for the PR in zebrafish and other ray-finned fish is 17,20-beta-dihydroxy-progesterone, and ray-finned fish PR responds weakly to progesterone. The MR in fish and terrestrial vertebrates also diverged to have different responses to progesterone. Progesterone is a potent agonist for elephant shark MR, zebrafish MR and other fish MRs, in contrast to progesterone’s opposite activity as an antagonist for aldosterone, the physiological mineralocorticoid for human MR. These different physiological ligands for fish and terrestrial vertebrate PR and MR need to be considered in applying data for their disruption by chemicals in fish and terrestrial vertebrates to each other.

Fluxgate magnetometers require calibration methods appropriate to their application levels and particularities; however the development of fully controlled calibration procedures presents a particular challenge regarding the inevitable influence of the local geomagnetic field and other external interferences when a laboratory with magnetically shielded walls is not available. In that context, we discussed the development of an automated calibration method for fluxgate magnetometers, considering those limitations in time and space, and avoiding some of the problems commonly found in other proposed solutions for the same challenge. For this task, we designed and built a new set of high level procedures, electronic systems and software, which perform active testing and automated calibration of fluxgate magnetometers, considering some resource constraints and employing instruments commonly found in electronic calibration laboratories.

Proteins in biological systems function at the interface of single molecule and bulk chemistry and thus provide novel insights into the basic physical chemistry of scaling and emergent phenomena. For example, a binary mechanical model based on the chemistry of muscle contraction unifies molecular mechanics and thermodynamics and provides an explicit solution to the Gibbs paradox. Using the same model system, here I show that chemical activities of molecular states have no effect on chemical kinetics or energetics. Specifically, while the concentration or number of molecules in a molecular state is widely thought to contribute to reaction free energies, here I show that it is not the physical presence of molecules that pushes a reaction forward but the number of microstates, , accessible in a chemical state that pulls a reaction toward equilibrium with an entropic force down an entropic funnel. With the derivation of an entropic contribution to chemical kinetics, I develop a novel chemical kinetic formulation that fully describes the chemical thermodynamics of both equilibrium and non-equilibrium reactions in terms of an a priori system reaction energy landscape.

Contact tracing is one of the oldest social network health interventions used to reduce the diffusion of various infectious diseases. However, some infectious diseases like COVID-19 amass at such a great scope that traditional methods of conducting contact tracing (e.g., face-to-face interviews) remain difficult to implement, pointing the need to develop reliable and valid survey approaches. The purpose of this research is to test the effectiveness of three different egocentric survey methods for extracting contact tracing data: (1) a baseline approach, (2) a retrieval cue approach, and (3) a context-based approach. A sample of 397 college students were randomized into one of each condition and were prompted to anonymously provide contacts and populated places visited from the past four days. After controlling for various demographic, social identity, psychological, and physiological variables, participants in the context-based condition were significantly more likely recall more contacts (medium effect size) and places (large effect size) than the other two conditions. Theoretically, the research supports suggestions by field theory that assume network recall can be significantly improved by activating relevant activity foci. Practically, the research contributes to developing innovative social network data collection methods for contract tracing survey instruments.

Botulinum neurotoxin (BoNT) intoxication can lead to the disease botulism, characterized by flaccid muscle paralysis that can cause respiratory failure and death. Due to the significant morbidity and mortality costs associated with BoNTs high toxicity, developing highly sensitive, rapid, and field-deployable assays are critically important to protect the nation’s food supply against either accidental or intentional contamination. We report here that the B-cell based biosensor assay (CANARY^® Zephyr) detects BoNT/A in buffer and various food matrices rapidly in ≤ 40 min, in small volumes ≈ 50 μL, with minimal processing of samples, and is extremely portable (suitcase-sized equipment). BoNT/A was detected at limits of detection (LOD) < 0.075 ng ± 0.02 in assay buffer while milk matrices (non-fat, 2 %, whole milk) increased the LOD to < 0.175 – 0.314 ng. Limits of detection for the assay in complex foods were < 1 ng ± 0.0 (neutralized acidic juices-carrot, orange and apple); < 16.7 ng ± 7.7 (liquid egg); and varied from < 0. 39 – 3.125 ng for solid complex foods (ground beef, green bean baby puree, smoked salmon). These results show that the CANARY^® Zephyr assay can be a highly useful tool in clinical, environmental, and food safety surveillance programs.

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response and tissue-specific response to myocardial infarction. To investigate the contribution of the LINC00961/SPAAR locus to determination of longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961-/- mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest a role for the LINC00961/SPAAR locus in cardiac endothelial cell and fibroblast cell function and hypoxic-response, and in growth and development, and basal cardiovascular function in adulthood.

The aim of the present study was to provide initial validity evidence of a Greek translation of the 24-item Brunel Mood Scale, referred to as the BRUMS-Greek, a measure of anger, confusion, depression, fatigue, tension, and vigour. Data were collected from 1,417 Greek adult exercise participants and 369 physically inactive adults, totaling 1,786 adults (male = 578, female = 1,208) aged 18–64 years (M = 34.73 ± 11.81 years). Given the large univariate and multivariate non-normality, confirmatory factor analyses treating responses as ordered categorical variables was conducted, which supported the hypothesised six correlated-factor measurement model. Internal consistency reliability of BRUMS-Greek subscales was supported via Cronbach alpha coefficients. Construct validity of scales was supported (a) via correlations in the hypothesised direction with trait positive and negative affect, (b) with more positive and less negative moods reported immediately after participation in a single exercise class compared to pre-exercise mood, and (c) with exercise participants reporting more positive and less negative mood states compared to physically inactive adults. Women reported higher tension and lower vigour scores than men. Tension scores were higher and confusion scores lower among younger participants (≤ 35 years) than older participants (≥ 36 years). Participants with obesity reported higher negative mood scores than those who were underweight or normal weight. In sum, the BRUMS-Greek demonstrated acceptable psychometric characteristics, and is proposed to be a suitable measure for use with exercise participants, physically inactive adults, and other Greek populations to explore research questions related to mood.

INTRODUCTION There have been several advances in the treatment of hepatitis C virus (HCV) infection which have resulted in major reductions in the morbidity and mortality from liver-associated disease. These are not widely available in the Caribbean, due in part, to lack of knowledge of the epidemiology of infections with HCV. As efforts are made to eliminate HCV from the region, these and other existing barriers such as lack of an established database on HCV must be addressed. This review seeks to identify gaps in the knowledge of HCV in the Caribbean with respect to seroprevalence, genotype distribution and general epidemiologic characteristics. MATERIALS AND METHODS The literature for the period January 1, 2005, to October 2022, was reviewed to gather country specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases. The usage pattern of HCV drugs was determined from data obtained from Pharmacists and Infectious Diseases Specialists across the region. RESULTS The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate prevalence. Notably, data from specific countries were limited. The prevalence of HCV among intravenous drug users (21.9-58.8%); persons living with HIV/AIDS (0.8 to 58.5%); prisoners (32.8-64%) and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83% was most prevalent followed by genotypes 2 (7.2%) and 3(2.1%), respectively. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (Sofosbuvir/velpatasvir), and Harvoni (Ledipasvir/sofosbuvir). Some of these drugs, are only available in the private sector and are sourced externally whenever needed. CONCLUSION There is a paucity of current data on the seroprevalence of HCV in the Caribbean and well-designed prospective studies are indicated to drive the implementation of treatment and control programs for HCV in the region. Barriers which need to be first overcome include unavailability and high cost of drugs used to treat HCV infections, injecting drug use and limited access to medical care and laboratory testing.

The topic of technology development and its disruptive effects has been the subject of much debate over the last 20 years with numerous theories at both macro and micro scale offering potential models of technology progression and disruption. This paper focuses on how the potential theories of technology progression can be integrated and considers whether suitable indicators of this progression and any subsequent disruptive effects (particularly considering these geographically) might be derived, based on the use of big data analytic techniques. Given the magnitude of the economic, social and political implications of many disruptive technologies, the ability to quantify disruptive change at the earliest possible stage could deliver major returns by reducing uncertainty, assisting public policy intervention and managing the technology transition through disruption into deployment. However, determining when this stage has been reached is problematic because small random effects in the timing, direction of development, the availability of essential supportive technologies or “platform” technologies, market response or government policy can all result in failure of a technology, its form of adoption or optimality of implementation. This paper reviews some of the key models of technology evolution and their disruptive effect including, in particular, the geographical spread of disruption. It suggests a methodology for utilising the recent explosion of open and web-discoverable data to determine a methodology to achieve this earlier determination and considers the potential exploitation of big data modelling and predictive analytical techniques to achieve this goal.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Objective: In low- and middle-income countries (LMICs), household survey data are a main source of information for planning, evaluation, and decision-making. Standard surveys are based on censuses, however, for many LMICs it has been more than ten years since their last census and they face high urban growth rates. Over the last decade, survey designers have begun to use modelled gridded population estimates as sample frames. We summarize the state of the emerging field of gridded population survey sampling, focussing on LMICs. Methods: We performed a systematic review and identified 43 national and sub-national gridded population-based household surveys implemented across 29 LMICs. Findings: Gridded population surveys used automated and manual approaches to derive clusters from WorldPop and LandScan gridded population estimates. After sampling, many surveys interviewed all households in each cluster or segment, though some sampled households from larger clusters. Tools to select gridded population survey clusters include the GridSample R package, Geo-sampling tool, and GridSample.org. In the field, gridded population surveys generally relied on geographically accurate maps based on satellite imagery or OpenStreetMap, and a tablet or GPS technology for navigation. Conclusions: For gridded population survey sampling to be adopted more widely, several strategic questions need answering regarding cell-level accuracy and uncertainty of gridded population estimates, the methods used to group/split cells into sample frame units, design effects of new sample designs, and feasibility of tools and methods to implement surveys across diverse settings.

Asymmetry plays a major role in biology at all scales. This can be seen examining the helix of DNA, the fact that the human heart is on the left side, or that most people use their right hand. A single protein such as Myosin 1D can induce helical motion in another molecule. This causes cells, organs, and even entire bodies to twist in a domino effect, causing left-right behaviour. More in general, athlete movements are often asymmetric and, during the physical rehabilita-tion after injury the asymmetry is visually discernible. Herein we review the molecular basis of movement asymmetries and report on the available knowledge on the few therapeutics inves-tigated so far such as meloxicam. From a more rehabilitative perspective, it is very important to use effective methods to control the process of resolving the injury-related movement asym-metry through the complex use of specialized exercises, measurements and gait analysis which all can provide useful information on the effectiveness of rehabilitation plans. If for each athlete the normal range of asymmetry is known, the asymmetry can be treated individually and the evolution can be monitored over time. Appropriate measures should be taken if the movement asymmetry is outside this range. In addition, genetic, physiological, and psychological factors relevant to athlete health should be considered in the process of assessing and improving exer-cise asymmetry as we also discuss in this review. The main proposal of this work is that move-ment asymmetries in athletes should be treated individually, taking into account the athlete’s genetics, physical condition, and previous injuries.

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

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

Anthracnose and root rot are major foliar and root diseases of strawberry, respectively that cause most yield and quality losses. Anthracnose is caused by multiple species belonging to Colletotrichum spp complex. This disease alone can causeup to 70% yield loss in North America. Colletotrichum spp. cause several disease symptoms on strawberries, including root, fruit, and crown rot, lesions on petioles and runners, and irregular black spots on the leaf. In many cases, a lower level of infection on foliage remains non-symptomatic (quiescent), posing a challenge to growers as these plants can be a significant source of inoculum for the fruiting field. Reliable detection methods for quiescent infection should play an important role in preventing infected plants' entry into the production system or guiding growers to take appropriate preventative measures to control the disease. The selection of highly effective fungicides and including them in a schedule to prevent the development of fungicide resistance in fungal populations will remain an area of continued research. Disease management methods should entail sensitive molecular testing of suspected fungal isolates for resistance, rotation of products, and monitoring of quiescent infections in transplant materials. Testing and the inclusion of non-chemical methods such as biologicals and biorational treatments especially for soilborne pathogens will also be necessary to make disease management economically feasible and sustainable.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds would advance rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize the unstable organocopper compounds. The bidentate ligands can chelate to the same copper atom via ?2-mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via ?1-mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via ?2-mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.

The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. Indeed, little is known of physiological activities of progesterone via any vertebrate MR.

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

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

This study investigates the hybridization scenario of a single flash geothermal power plant with a biomass driven sCO2-steam Rankine combined cycle where a solid local biomass source, olive residue, is used as a fuel. The hybrid power plant is modeled using the simulation software EB-SILON®Professional. A topping sCO2 cycle is specifically chosen for its potential for flexible elec-tricity generation. A synergy between the topping sCO2 and bottoming steam Rankine cycles is achieved by a good temperature match between the coupling heat exchanger where the waste heat from the topping cycle is utilized in the bottoming cycle. The high temperature heat addition problem common sCO2 cycles is also eliminated by utilizing the heat in the flue gas in the bottoming cycle. Combined cycle thermal efficiency and biomass to electricity conversion efficiency of 24.9% and 22.4% are achieved, respectively. The corresponding fuel consumption of the hybridized plant is found as 2.2 kg/s.

Introduction: Given increasing adult use of amphetamine and methylphenidate and their high misuse potential, we examined suspected suicide attempts and other intentional misuse and medical outcomes and their associations with co-used other substances among amphetamine and methylphenidate exposure cases age 50+.Methods: Using the 2015-2021 U.S. National Poison Data System (N=7,701 amphetamine and/or methylphenidate cases), we fit two generalized linear models for a Poisson distribution with log link function, with suspected suicide attempt versus intentional misuse and major medical effect/death versus other outcomes as the dependent variables. Results: Of all amphetamine/methylphenidate exposure cases, suspected suicide attempts and intentional misuse were 28.4% and 13.2%, respectively. Benzodiazepine use was associated with a higher likelihood but any illicit drug use was associated with a lower likelihood of suspected suicide attempts compared to intentional misuse. Type of stimulant involved (amphetamine or methylphenidate) was not significant. Co-use of antidepressants (IRR=1.43, 95% CI=1.16-1.76), prescription opioids (IRR=1.48, 95% CI=1.21-1.81), drugs for cardiovascular disease (IRR=1.51 95% CI=1.20-1.90), antipsychotics (IRR=1.26, 95% CI=1.02-1.55), or illicit drugs (IRR=2.40, 95% CI=1.82-3.15) was associated with a higher likelihood of major effect/death.Conclusions: Suspected suicide attempts or intentional misuse accounted for more than 40% of amphetamine or methylphenidate exposure cases age 50+. The higher likelihood of major effect/death in cases involving antidepressants, antipsychotics, and cardiovascular disease drugs also suggests confounding effects of comorbid mental and physical health problems. Careful monitoring of those who were prescribed amphetamine or methylphenidate and use other substances are needed.

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-minute eccentric exercise bout in non-athletic, non-obese males (n=92, ages 18-55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-second Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the 4th and 5th days of recovery (Cohen's d &gt;0.80); pea protein versus water supplementation had an intermediate, non-significant effect (Cohen's d &lt;0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated efflux of muscle damage biomarkers, with intake of pea protein having an intermediate effect in part due to the 24% lower leucine amino acid content.

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

The usage of Quantum Similarity through the equation Z = {∀θ ∈ Z → ∃s ∈ S ∧ ∃t ∈ T : θ = (s, t)}, represents a way to analyze the way communication works in our DNA. Being able to create the object set reference for z being (s, t) in our DNA strands, we are able to set logical tags and representations of our DNA in a completely computational form. This will allow us to have a better understanding of the sequences that happen in our DNA. With this approach, we can also utilize mathematical formulas such as the Euler–Mascheroni constant, regression analysis, and computational proofs to answer important questions on Quantum biology, Quantum similarity, and Theoretical Physics.

With widespread resistance to a limited number of insecticides available for medical and veterinary pests, new insecticides and insecticide synergists are desperately needed in this market space. We assessed the topical toxicity of carvone, menthone, and fenchone compared to permethrin and methomyl against the yellow fever mosquito, Aedes aegypti, and the house fly, Musca domestica. We also evaluated the synergistic potential of the monoterpenoids with permethrin and methomyl. Additionally, we assessed the acetylcholinesterase inhibitory potential of each monoterpenoid compared to methomyl. While all three monoterpenoids performed relatively poorly as topical insecticides (LD50 > 4000 ng/mg on M. domestica; > 6000 ng/mg on Ae. aegypti), they synergized both permethrin and methomyl as well as or better than piperonyl butoxide (PBO). Carvone and menthone yielded synergistic co-toxicity factors (23 and 29, respectively), which were each higher than PBO at 24 h. Acetylcholinesterase inhibition did not appear to explain the toxic or synergistic effects of the three monoterpenoids with IC50 values greater than 1 mM for all, compared to the 2.5 and 1.7 µM for methomyl on Aedes aegypti and Musca domestica, respectively. This study provides valuable monoterpenoid toxicity and synergism data on two pestiferous insects and highlights potential for these chemistries in future pest control formulations.

Apple (Malus x domestica) fruit size is dependent on cell division and cell expansion, processes which are subsequently regulated by plant hormones such as auxins, gibberellins, and cytokinins. In this study, we investigated the role of cell division and cell expansion in apple growth and identified which of the two was more deterministic to final fruit size. Three cultivars of different sizes were selected, namely, ‘Twenty Ounce’ (large-sized), ‘Royal Gala’ (medium-sized), and ‘Crabapple’ (small-sized). Gene expression and cell size analyses were conducted over the course of two consecutive seasons. The expression patterns of three classes of genes were markedly similar across all cultivars. Two cell division markers, namely, MdCDKB2;2 and MdANT2, were discovered to be correlatively expressed as both displayed initially high expression levels, which gradually declined from the early to late stages of growth time course. For cell expansion markers, MdEXP3 was upregulated as the cells expanded, while MdARF106 was expressed in both the cell division and expansion stages. Meanwhile, the ripening related gene MdACO1 was expectedly expressed only during the ending stages associated with ripening. Interestingly, the cell measurements taken regularly from each cultivar throughout the same eperimental timespan showed that cell sizes were unaltered and remained constant from initial pollination at the zeroth Days After Pollination (DAP), to ripening at 120 Days After Full Bloom (DAFB).

Conventional data visualization software have greatly improved the efficiency of the mining and visualization of biomedical data. However, when one applies a grid computing approach the efficiency and complexity of such visualization allows for a hypothetical increase in research opportunities. This paper will present data visualization examples presented in conventional networks, then go into higher details about more complex techniques related to leveraging parallel processing architecture. Part of these complex techniques include the attempt to build a basic general adversarial network (GAN) in order to increase the statistical pool of biomedical data for analysis as well as an introduction to the project utilizing the decentralized-internet SDK. This paper is meant to show you said conventional examples then go into details about the deeper experimentation and self contained results.

Direct assessments of executive function (EF) are increasingly used in research and clinical settings, with a central assumption that they assess “universal” underlying skills. Their use is spreading globally, raising questions about the cultural appropriateness of assessments devised in Western, industrialized countries. We reviewed multidisciplinary evidence and theory to identify sets of cultural preferences that may be at odds with the implicit assumptions of EF assessments. These preferences relate to motivation and compliance; cultural expectations for interpersonal engagement; contextualized vs. academic thinking; cultural notions of speed and time; the willingness to be silly, be incorrect, or do the opposite; and subject-matter familiarity. In each case, we discuss how the cultural preference may be incompatible with the assumptions of assessments, and how future research and practice can address the issue. Many of the cultural preferences discussed differ between interdependent and independent cultures and between schooled and unschooled populations. Adapting testing protocols to these cultural preferences in different contexts will be important for expanding our scientific understanding of EF from the narrow slice of the human population that has participated in the research to date.

3D printing facilitates the straightforward construction of microchannels with complex three-dimensional architectures. Here, we demonstrate 3D-printed modular mixing components that operate on the basis of splitting and recombining fluid streams to decrease interstream diffusion length. These are compared to helical mixers that operate on the principle of chaotic advection.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Background: As long-lived organisms, urban trees often encounter development and redevelopment activities in close proximity during their lifespans. These activities can damage tree roots, often through methods like root severing during trenching or excavation. Methods: In 2017, we simulated trenching damage on mature Quercus virginiana Mill. trees at three different distances from the base (3x, 6x, and 12x the stem diameter). After five years, we revisited these trees to assess root regrowth based on the cut root's cross-sectional area (CSA) and distance from the base. Results: We observed regrowth in all but 38 (6.7%) of the 557 cut roots revisited. The lack of regrowth in some roots was not associated with our original treatments, the CSA of the roots at the time of trenching, or distance between the cut root end and the trunk (minimum P-value = 0.841). On average, the observed CSA of the regrowth was 22.2% of the original root's CSA. Only our original trenching treatments significantly predicted the level of regrowth observed five years after pruning (P-value = 0.024). Discoloration due to root pruning was minimal. Conclusion: In summary, our findings indicate that root systems require many years to recover from trenching damage. Increasing the distance between trenching activities and trees may have a minor effect on root regrowth but primarily helps reduce initial stress on the tree.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections

Osteoarthritis (OA) is a debilitating degenerative joint disease that results in chronic pain and inflammation due to progressive mechanical and proteolytic cartilage degradation. Articular chondrocytes, the main cell type present in cartilage, are responsible for the deposition and maintenance of the cartilage extracellular matrix (ECM). However, following damage and inflammation, chondrocytes undergo hypertrophy, apoptosis, and contribute to inflammation and ECM degradation. NF-κB signaling is known to be dysregulated in OA. TRAPPC9, a vesicle trafficking protein, is known to directly activate NF-κB signaling in neuronal and bone cells, however, the biological significance of this protein in chondrocytes has yet to be elucidated. Here, we demonstrate that TRAPPC9 enhances pro-inflammatory gene and protein expression in murine primary articular chondrocytes. Furthermore, we show that TRAPPC9 elicits these responses via phosphorylation of P-100 that activates non-canonical NF-κB signaling. Taken together, these findings suggest TRAPPC9 may be a potential therapeutic target to decrease inflammation and matrix degradation during OA pathology.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Resistance training increases myofiber hypertrophy, but the morphological adaptations that occur within myofibers remain largely unresolved. Fifteen males with minimal training experience (24±4 years, 17.9±1.4 kg/m2 lean body mass index) performed 10 weeks of conventional, full-body resistance training (2x weekly). Body composition, the radiological density of the vastus lateralis muscle using peripheral quantitative computed tomography (pQCT), and vastus lateralis muscle biopsies were obtained one week prior to and 72 hours following the last training bout. Fiber typing and the quantification of myofibril and mitochondrial areas per fiber were performed using histology/immunohistochemistry (IHC) techniques. Relative myosin heavy chain and actin protein abundances per wet muscle weight as well as citrate synthase (CS) activity assays were also obtained on tissue lysates. Training increased whole-body lean mass, mid-thigh muscle cross-sectional area, various strength metrics, and mean and type II fiber cross sectional areas (fCSA) (p<0.05). Myofibril areas in type I or II fibers were not altered with training, suggesting a proportional expansion with fCSA increases. Relative myosin heavy chain and actin protein abundances also did not change with training. IHC indicated training increased mitochondrial areas in both fiber types (p=0.018). However, CS activity levels remained unaltered with training. Interestingly, although pQCT-derived muscle density increased with training (p=0.036), suggestive of myofibril packing, a positive association existed between training-induced changes in this metric and changes in type I+II myofibril areas (r=0.600, p=0.018). Shorter-term resistance training seemingly involves a proportional expansion of myofibrils and an accelerated expansion of mitochondria in type I and II fibers. Additionally, histological and biochemical techniques should be viewed independently from one another given the lack of agreement between the variables assessed herein. Finally, the pQCT may be a viable tool to non-invasively track morphological changes in muscle tissue.

Inconsistent results published in previous studies make it difficult to determine the precise effect of consumer knowledge on their acceptance of functional foods, which were developed to improve consumers’ health status by providing adequate nutrition. We conducted a systematic review and meta-analysis by identifying and collecting relevant literature from three databases. Of the 1050 studies we reviewed, we included 40 in the systematic review and 18 in meta-analysis. Based on the focus of each included study, we operationally defined knowledge as knowledge of the functional food concept, nutritional-related knowledge, and knowledge of specific functional products. Results from the systematic review indicate that most participants from the included studies had a low level of knowledge, especially nutrition-related knowledge associated with consuming functional foods, and they were generally not familiar with the concept of functional foods. It is possible that participants’ level of knowledge was influenced by their demographic characteristics (e.g., age, gender, educational level, marital status, nationality). Results from the meta-analysis generated a summary effect size (r = 0.14, 95% CI [0.05; 0.23]), measured by the correlation coefficient r, which indicates that a small positive relationship exists between consumers’ level of functional foods knowledge and their acceptance of functional foods.

This article explores the Role and Contributions of Small and Medium Enterprises (SMEs) in a globalized and innovative economy, looking specifically at the challenges and opportunities. The establishment and expansion of new firms provides a sizable amount of net new jobs. While high-expectation entrepreneurial enterprises and gazelles are usually found among innovative and technology-based new organizations, it is also essential that there be a sizable supply for them to play a significant part in economic growth. In other words, encouraging all forms of en-trepreneurship is likely to increase the number of innovative, fast-growing enterprises as well as entrepreneurship. In many European countries, entrepreneurship needs to be encouraged. Findings show the crucial role the SME sector plays in the South African economy in tackling sustainable development. About 90% of all official firms in South Africa are thought to be small, medium, or micro-enterprises. The study concluded that one of the major contributions to the South African economy is the SME sector. The SME is not just viewed as a source of new jobs, but also as a sector that absorbs laid-off workers from both the private and public sectors.

Telerehabilitation is an appealing service delivery option for optimising recovering. Internationally, the equity of telerehabilitation services for people from culturally and linguistically diverse (CALD) backgrounds has been questioned. Using a 31-item survey, our study explored the access, readiness, and willingness of 260 patients to use allied health telerehabilitation services for adults receiving interventions from a large tertiary health service located in Sydney, Australia. Overall, 72% patients reported having access to technology, 38% met our readiness criteria, and 53% reported willingness to engage in telerehabilitation. There were no difference in access, readiness and willingness to engage in telerehabilitation between patients from CALD and non-CALD backgrounds. Age was the only factor that influenced access, readiness and willingness to engage in telerehabilitation. Past experience of telerehabilitation was related to willingness, but not access or readiness. Findings highlight the importance of ensuring positive patient experiences to promote ongoing willingness to use telerehabilitation. Efforts are needed to improve patients’ digital health literacy, especially patients from older age groups, to ensure equitable access to telerehabilitation services.

A mild, efficient, and photocatalytic synthesis of 6-phosphorylated phenanthridines via tandem radical addition/cyclization/aromatization of 2-isocyanobiphenyls with diarylphosphine oxides is reported. The method features operational simplicity, metal-free conditions, using low-cost rose Bengal as catalyst and sustainable air as terminal oxidant at room temperature, and providing the desired products in moderate to good yields.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

The impact of riparian wetlands on the cycling, retention and export of nutrients from land to water varies according to local environmental conditions and is poorly resolved in catchment management approaches. To determine the role a specific wetland might play in a catchment mitigation strategy, an alternative approach is needed to the high frequency and spatially detailed monitoring programme that would otherwise be needed. Here, we present a new approach using a combination of novel and well-established geochemical, geophysical and isotope ratio approaches. This was developed and tested against a 2-year high-resolution sampling programme in a lowland permeable wetland in the Lambourn catchment, UK. The monitoring programme identified multiple pathways and water sources feeding into the wetland, generating large spatial and temporal variations in nutrient cycling, retention and export behaviours within the wetland. This complexity of contributing source areas and biogeochemical functions within the wetland were effectively identified using the new toolkit approach. We propose that this technique could be used to determine the likely net source/sink function of riparian wetlands prior to their incorporation into any catchment management plan, with relatively low resource implications when compared to a full high frequency nutrient speciation and isotope geochemistry-based monitoring approach.

This paper considers the solution of the equations for ruin probabilities in infinite continuous time. Using the Fourier Transform and certain results from the theory of complex functions, these solutions are obtained as com- plex integrals in a form which may be evaluated numerically by means of the inverse Fourier Transform. In addition the relationship between the re- sults obtained for the continuous time cases, and those in the literature, are compared. Closed form ruin probabilities for the heavy tailed distributions: mixed exponential; Gamma (including Erlang); Lognormal; Weillbull; and Pareto, are derived as a result (or computed to any degree of accuracy, and without the use of simulations).

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4 butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. The PU made with polycarbonate diol polyol (YCD) was the only showing intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis and dynamic mechanical thermal analysis was carried out. It was concluded that the self-healing at 20 °C of YCD was due to non-covalent dynamic exchange interactions among the carbonate groups of the soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

During analysis of kiwifruit derived from hybrids between the high AsA species Actinidia eriantha and A. chinensis var chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis we performed whole-genome sequencing on pools of high and low AsA fruit from tetraploid A. chinensis var. deliciosa x A. eriantha backcross families. Pool-GWAS revealed a single QTL spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis x A. eriantha) x A. chinensis backcross families, showing that the eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNASEQ. This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harboring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on 1) the therapeutic potential of exosomes in stroke treatment, 2) the optimization process of upstream and downstream production, and 3) preclinical application in stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

The number of engineers who are transitioning into environmental sustainability careers is growing, though a gap still exists between supply and demand. This presents an opportunity for undergraduate engineering students to fulfill the demand as environmental sustainability professionals. This qualitative exploratory study investigated environmental sustainability learning experiences and future career interests in environmental sustainability. The social cognitive theory (SCCT) was utilized as a theoretical lens, exploring undergraduate students’ environmental sustainability interests, related learning experiences and their interest in pursuing a future career in environmental sustainability. Twenty-five undergraduate engineering students in various engineering disciplines were interviewed for this study. Data were analyzed to (1) identify students’ interest in pursuing a career in environmental sustainability, (2) determine if students’ interests have changed since they began their undergraduate studies, and (3) explore how learning experiences have impacted students’ future career choice. The findings posit that exposure to environmental sustainability learning experiences is impactful and plays an important role, impacting students' interests in pursuing careers in sustainability. Results reveal that elements such as personal beliefs and salary considerations inspire career choices. This research contributes to addressing the demand for additional working professionals who are prepared to tackle environmental sustainability issues, highlighting the role of learning experiences in shaping students' career interests.

Negative temperature coefficient (NTC) materials are usually based on ceramic semiconductors and electrons are involved in their transport mechanism. A new type of NTC material, adequate for alternating current (AC) applications, is represented by zeolites. Indeed, zeolites are single-charge carrier ionic conductors with a temperature-dependent electrical conductivity. In particular, electrical transport in zeolites is due to the monovalent charge-balancing cations, like K⁺, capable of hopping between negatively charged sites in the aluminosilicate framework. Owing to the highly non-linear electrical behavior of the traditional electronic NTC materials, the possibility to have alternative types of materials, showing linearity in the electrical behavior, is very desirable. Among different zeolites, the natural clinoptilolite has been selected for investigating the NTC behavior since it is characterized by high zeolite content, convenient Si/Al atomic ratio, good mechanical strength, due to its compact microstructure, and low toxicity. Clinoptilolite has shown a rapid and quite reversible impedance change under heating, characterized by a linear dependence on temperature. X-ray diffraction (XRD) has been used to identify the natural zeolite, to establish all types of crystalline phases present in the mineral, and to investigate the thermal stability of these phases up to 150°C. X-ray photoelectron spectroscopy (XPS) analysis has been used for the chemical characterization of the natural clinoptilolite sample, providing important information on the cationic content and framework composition. In addition, since electrical transport takes place in the zeolite free-volume, a Brunauer–Emmett–Teller (BET) analysis of the mineral has been also performed.

Concrete contributes 8% of all global carbon emissions making the need to find substitute critical for environmental sustainability. Research has indicated the potential for recycled plastics to be used as concrete substitutes. This study extends existing research by investigating the use of polycarbonate (PC) in plastic sand bricks as a mechanical equivalent to concrete. PC has high compressive strength, durability, impact strength, thermal resistivity, clarity, fatigue resistance, and UV resistance. This work provides a method and mold to produce a matrix of sand-plastic sample compositions with dimensions adhering to ASTM D695 standard for compressive properties of rigid-plastic. Compositions of 0% (control), 20%, 30%, 40%, and 50% sand by weight were tested. Samples were tested for compressive strength until yield and stress-strain behaviors plotted. The results for 100% PC demonstrated an average and maximum compressive strength of 71 MPa and 72 MPa, respectively. The 50% PC and 50% sand composition yielded an average and maximum compressive strength of 71 MPa and 73 MPa respectively with an increase in compressive stiffness, and transition to shear failure resembling cement. With a composite density of 1.86 g/cm3 against concrete’s average 2.4 g/cm3, and a compressive strength exceeding commercial concrete demands of 23.3 MPa to 30.2 MPa, this lightweight alternative meets the strength demands of concrete, reduces the need for new construction materials, and provides an additional recycling opportunity for nonbiodegradable waste plastic.

Chronic diseases (e.g., heart disease, cancer, diabetes) are of major public concern. Such chronic diseases are often caused by a dietary pattern characterized as relatively high in fat, refined sugar, salt, and cholesterol. Societal interest in consuming healthy foods and the demand for healthy food products has increased significantly. As a result, functional foods have gained significant research attention in the food health and technology innovations field. To date, many studies have investigated the factors that may predict consumer acceptance of functional foods, and a wide range of influential factors have been reported. However, studies conducted in different contexts pose challenges to gaining a clear understanding of the factors influencing consumer acceptance. This scoping review identified 75 articles published with varying populations around the globe that empirically investigated consumers’ acceptance of functional foods. We identified and categorized a wide range of determinants related to consumer acceptance of different types of functional foods. The five categories of determinants were product characteristics, socio-demographic characteristics, psychological characteristics, behavioral characteristics, and physical characteristics. Each of the determinants were more fully described by sub-determinants in our scoping review. These determinants should be considered and used by leaders and scientists in product development to aid decision making and, ultimately, the successful launch of novel functional foods.

Offsite construction is increasingly being presented as a way to increase housing delivery and reduce the housing crisis. Housing Associations play a pivotal role in the delivery of affordable homes and therefore offsite construction could be beneficial in alleviating the crisis. For offsite construction uptake to increase, the conceptual and pragmatic advantages and challenges surrounding offsite housing in relation to evolving social domestic needs to be explored and understood. The purpose of this paper is to discuss the viability of offsite construction as not only a full-service solution to social housing provision, but an integral strategic partner for meeting the range of specialised fabrication needs for these new properties. A literature review is carried out to explore the conceptual and pragmatic advantages and challenges encountered by HAs adopting offsite construction methods. The paper also investigates which the housing tenures are most suited to offsite construction technology. The paper highlighted that whilst individual case studies and example homes offer one mode of justification for Housing Associations to move forward, it is the cumulative effect of cost savings, sustainability, specialised skill sets, labour reduction, structural innovation, and rate of construction that should be weighed and incorporated into this consideration-making process.

Many metrics exist for the evaluation of binary classifiers, all with their particular advantages and shortcomings. Recently an “Efficiency Index” for the evaluation of classifiers has been proposed, based on the consistency, or matching, and contradiction, or mismatching, of outcomes. This metric and its confidence intervals are easy to calculate from base data in a 2x2 contingency table, and values can be qualitatively and semi-quantitatively categorised. For medical tests, in which context the Efficiency Index was originally proposed, it facilitates communication of risk (of correct diagnosis versus misdiagnosis) to both clinicians and patients. Variants of the efficiency index (balanced, unbiased) which take into account disease prevalence and test cut-offs have also been described. The objectives of the current paper were firstly to extend the EI construct to other formulations (balanced level, quality) and secondly to explore the utility of EI and all four of its variants when applied to the dataset of a large prospective test accuracy study of a cognitive screening instrument. This showed that the balanced level, quality, and unbiased formulations of EI are more stringent measures.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently emerged as global infections with consequential disability adjusted life years (DALYs) and economic burden. This study aimed to explore the spatiotemporal heterogeneity in the occurrence of CHIKV and ZIKV outbreaks throughout Barranquilla, Colombia during 2014 and 2016 and explored the potential for clustering. Incidence data were fitted using multiple Bayesian Poisson models based on a suite of explanatory variables as potential risk factors and multiple options for random effects. A best fit model was used to analyse the case incidence risk for both epidemics to identify any risk factors during their epidemics. Neighbourhoods in the northern region of Barranquilla were hotspots for the outbreaks of both CHIKV and ZIKV. Additional hotspots occurred in the south-western and central regions of the CHIKV and ZIKV outbreaks, respectively. Multivariate conditional autoregressive models strongly identified higher socioeconomic strata (SES) and residing in detached houses as risk factors for ZIKV case incidences. These novel findings challenge the belief that these infections are driven by social vulnerability and merits further study both in Barranquilla and throughout the tropical and subtropical regions of the world.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently emerged as global infections with consequential disability adjusted life years (DALYs) and economic burden. This study aimed to explore the spatiotemporal heterogeneity in the occurrence of CHIKV and ZIKV outbreaks throughout Barranquilla, Colombia during 2014 and 2016 and explored the potential for clustering. Incidence data were fitted using multiple Bayesian Poisson models based on a suite of explanatory variables as potential risk factors and multiple options for random effects. A best fit model was used to analyse the case incidence risk for both epidemics to identify any risk factors during their epidemics. Neighbourhoods in the northern region of Barranquilla were hotspots for the outbreaks of both CHIKV and ZIKV. Additional hotspots occurred in the south-western and central regions of the CHIKV and ZIKV outbreaks, respectively. Multivariate conditional autoregressive models strongly identified higher socioeconomic strata (SES) and residing in detached houses as risk factors for ZIKV case incidences. These novel findings challenge the belief that these infections are driven by social vulnerability and merits further study both in Barranquilla and throughout the tropical and subtropical regions of the world.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wavefunction just prior to the entrance of ‘gravitons’ to a small region of space-time prior to a nonsingular start to the universe. We compare this to a solution worked out using Klauder Enhanced quantization, for the same given problem. The solution of the first Cosmological Constant problem relies upon the geometry of the multiverse generalization of CCC cosmology which is explained in this paper. The second solution, used involves Klauder enhanced quantization. We look at energy given by our methods and compare and contrast it with the negative energy of the Rosen model for a mini sub universe and estimate GW frequencies

Urban Tree Canopy (UTC) greatly enhances the livability of cities by reducing urban heat buildup, mitigating stormwater runoff, and filtering airborne particulates, among other ecological services. These benefits, combined with the relative ease of measuring tree cover from aerial imagery, have led many cities to adopt management strategies based on UTC goals. In this study, we conducted canopy analyses for the 300 largest cities in Florida to assess the impacts of development practices, urban forest ordinances, and hurricanes on tree cover. Within the cities sampled, UTC canopy ranged from 5.9% to 68.7% with a median canopy coverage of 32.3% Our results indicate that the peak gust speeds recorded during past hurricanes events were a significant predictor of canopy coverage (P-value = <0.001) across the sampled cities. As peak gust speeds increased from 152 km/h (i.e., a lower-intensity Category 1 storm) to 225 km/h (lower-intensity Category 4 and the maximum gusts captured in our data), predicted canopy in developed urban areas decreased by 7.7%. Beyond the impacts of hurricanes and tropical storms, we found that historic landcover and two out of eight urban forest ordinances were significant predictors of existing canopy coverage (P-landcover <0.001; P-tree preservation ordinance = 0.02, P-heritage tree ordinance = 0.03). Results indicate that local policies and tree protections can protect or enhance urban tree canopy, even in the face of rapid development and periodic natural disturbances.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, using the Rosen and Israelit model of a nonsingular universe. In doing so we are in addition to obtaining a wavelength 10^30 times greater than Planck’s length so we can calculate DE, may be able to with the help of the Rosen and Israelit model have a first approximation as to the arrow of time, and a universe with massive gravity. We have left the particulars of the nonsingular starting point undefined but state that the Rosen and Israelit model postulates initial temperatures of 10^-180 Kelvin and also a value of about Planck temperature, at 10^-3 centimeters radii value which may satisfy initial conditions asked by t’Hooft for describing an arrow of time. A key assumption is that the DE is formed at 10^-3 cm, after an expansion of 10^30 times in radii, from the Planck length radius nonsingular starting point. The given starting point for DE in this set of assumptions is where there is a change in the cosmic acceleration, to a zero value, according to Rosen and Israel, with time t = 1.31 times 10^-42 seconds. Which may be where we may specify a potential magnitude, V, which has ties into inflaton physics. The particulars of the model from Rosen and Israelit allow a solution to be found, without discussion of where that nonsingular starting point came from, a point the author found in need of drastic remedies and fixes.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.

This work introduces a new architecture for a time-domain feedback-based beamformer designed to meet real-time processing demands. The primary goal of this design is to locate reflective sources by estimating their direction of arrival (DOA) and signal range. Incorporating a feedback mechanism in this architecture is a unique aspect that refines localization precision. We conduct an in-depth analysis highlighting their respective benefits and limitations to compare the effectiveness of time-domain feedback beamforming against conventional time-domain methods. Our evaluation of the proposed architecture, based on critical performance indicators such as peak-to-sidelobe ratio, mainlobe width, and directivity factor, demonstrates its ability to improve beamformer effectiveness significantly.

Ageing is the strongest known risk factor for many of the neurodegenerative diseases causing cognitive decline and dementia. Identification of cognitive impairment may be a prelude to appropriate treatment, hopefully disease-modifying. Use of cognitive screening instruments may be an equitable way to identify cognitive impairment. This study examined the use of two such instruments, Free-Cog and Mini-Addenbrooke’s Cognitive Examination (MACE), in patient cohorts referred to a dedicated cognitive disorders clinic based at a tertiary neurosciences centre. Results showed that: (1) specificity and positive predictive value increased with patient age for both tests with some loss of sensitivity and negative predictive value. (2) In the oldest age groups (≥75 and ≥70 years respectively) where specificity was at maximum, a positive test result (i.e. below the specified test cut-off) rules in the diagnosis of cognitive impairment. (3) Values of an “Efficiency Index” for each test indicated qualitatively a moderate change in the probability of correct diagnosis and quantitatively an approximately 15-25% increase in the probability of correct diagnosis. These findings show that both Free-Cog and MACE may be used with confidence for the identification of cognitive impairment and dementia in older patient cohorts. These findings may have implications for public health policies directed to case-finding in clinical practice as opposed to population-based screening.

Alzheimer’s disease (AD) is the leading cause of dementia, characterised by beta-amyloid plaques, neurofibrillary tangles, and oxidative stress. Iron is suspected to enhance disease progression, and chelation may be a potential treatment. We propose that Aloysia citrodora Paláu (AC), a plant in the Verbenaceae family, can act as a moderate chelator of iron. It may reduce the effect of iron on beta-amyloid 1-42 (Aβ1-42) aggregation. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to demonstrate that AC can interact with iron (II) and iron (III), the two most abundant forms of iron within the body. DPV was also used to characterise Aβ1-42 aggregation, and two main features were obtained. The first is the tyrosine peak (~0.6 V) decreased in magnitude over time, which is a sign of aggregation and folding. The other is a conglomerate of peaks at ~0 V, whose identity is unknown. Furthermore, iron (II) increased the rate of tyrosine peak depreciation, and the addition of AC negated this induced effect. This implied that iron (II) increases Aβ1-42 aggregation into higher order, and AC may be an effective countermeasure.

The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

There are a large number of wildlife and insect species that are in trouble on this planet, and most believe that monarch butterflies in eastern North America are too, because of the well-publicized declines of their winter colonies in central Mexico in the last 25 years. A small number of studies over the last decade have cast doubt on this claim by showing declines are not evident at other stages of the annual cycle. To determine how extensive this pattern is, I conducted an exhaustive review of peer-reviewed and grey literature on (eastern) monarch population censuses and studies, conducted across all seasons, and extracted data from these sources to evaluate how monarch abundance has or has not changed over time. I identified 20 collections of data that included butterfly club reports, compilations of citizen-science observations, migration roost censuses, long-term studies of isotopic signatures, and even museum records. These datasets range in duration from 15 years to over 100 years, and I endeavored to also update each with information from the most current years. I also re-examined the winter colony data after incorporating historical records of colony measurements dating back to 1976. This represents the most complete and up-to-date synthesis of information regarding this population. When I examined the long-term trajectory within each dataset a distinct pattern emerged. Modest declines are evident within the winter colonies (over the full 45 year dataset), and, within three censuses conducted during the spring recolonization. Meanwhile, 16 completely separate monitoring studies conducted during the summer and fall (and from varying locations) revealed either no trend at all or in fact an increase in abundance. While each of these long-term studies has inherent limitations, the fact that all 16 sources of data show the same pattern is undeniable. Moreover, this evidence is consistent with recently-conducted genetic work that shows a lack of decline. Collectively, these results indicate that despite diminishing winter colonies and spring migrations, monarchs in eastern North America are capable of rebounding fully each year, implying that milkweed is not limiting within their collective range. Moreover, there is no indication from these data that the summer population was ever truly diminished by changing agricultural practices in the Midwest that reduced milkweed in crop fields within that region. It is possible that the larger population is not as dependent on Midwestern agricultural milkweed as once thought, and/or that monarchs are adapting to increasingly human-altered landscapes. These results are timely and should bear on the upcoming USFWS decision on whether the monarch requires federal protection in the United States. Importantly, they argue that despite losses of many insects globally, the eastern North American monarch population is not in the same situation.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, while using Karen Freeze’s criteria as to the breakup of primordial black holes to give radiation era contributions to GW generation. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes of the order of Planck mass (10^15 grams) which isabout when the mass of relic black holes is created, 10^-27 or so seconds after expansion starts. Need to state a key result will be in the initial potential V calculated, in terms of other input variables

The α(1,2)fucosyltransferase (Se enzyme) encoded by FUT2 is involved in the secretor status of ABH(O) blood group antigens. The sedel2 allele is one of the non-functional FUT2 (se) alleles in which 9.3 kb containing the entire coding region of FUT2 is deleted by Alu-mediated nonhomologous recombination. In addition to this allele, three SNPs of FUT2, c.375A>G, c.385A>T, and c.571C>T, appear to be prevalent in certain Oceanian populations such as Polynesians. Recently, we developed an endpoint genotyping assay to determine the sedel2 zygosity, using a FAM-labeled probe for detection of the sedel2 allele and a VIC-labeled probe for detection of FUT2. In this study, instead of the VIC probe, a HEX-labeled probe covering both c.375A>G and c.385A>T and a Cy5-labeled probe covering c.571C>T were added to the sedel2 allele assay mixture to allow simultaneous detection of these four variations by endpoint genotyping for the sedel2 zygosity and fluorescence melting curve analysis for c.375A>G, c.385A>T, and c.571C>T genotyping. The results obtained from 24 Samoan subjects with this method were identical to those obtained with previous methods. Therefore, it appears that present method can accurately determine these four variations simultaneously.

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Ultraviolet imaging has been applied in volcanology over the last ten years or so. This provides considerably higher temporal and spatial resolution volcanic gas emission rate data than available previously, enabling the volcanology community to investigate a range of far faster plume degassing processes, than achievable hitherto. To date this has covered rapid oscillations in passive degassing through conduits and lava lakes, as well as puffing and explosions, facilitating exciting connections to be made for the first time between previously rather separate sub disciplines of volcanology. Firstly, there has been corroboration between geophysical and degassing datasets at ≈ 1 Hz expediting more holistic investigations of volcanic source-process behaviour. Secondly, there has been the combination of surface observations of gas release, with fluid dynamic models (numerical, mathematical and laboratory) for gas flow in conduits, in attempts to link subterranean driving flow processes to surface activity types. There has also been considerable research and development concerning the technique itself, covering error analysis and most recently adaptation of smartphone sensors for this application, to deliver gas fluxes at a significantly lower instrumental price point than possible previously. At this decadal juncture in the application of UV imaging in volcanology, this article provides an overview of what has been achieved to date as well as a forward look to potential future research directions, in particular covering the first use of UV cameras to generate volcanic gas composition ratio imagery.

Pure-compression shells have been the central topic in the form-finding of shells. This paper studies tension-compression mixed type shells by utilizing a NURBS-based isogeometric form-finding approach that analyzes Airy stress functions to expand the possible plan geometry. A complete set of smooth version graphic statics tools is provided to support the analyses. The method is validated using examples with known solutions, and a further example demonstrates the possible forms of shells that the proposed method permits. Additionally, a guideline to configure a proper set of boundary conditions is presented through the lens of asymptotic lines of the stress functions.

A series of dinuclear copper(I) N,C,N- and P,C,P-carbodiphosphorane (CDP) complexes using multidentate ligands CDP(Py)2 (1) and (CDP(CH2PPh2)2 (13) have been isolated and characterized. Detailed structural information was gained by single crystal XRD analyses of nine representative examples. The common structural motive is the central double ylidic carbon atom with its characteristic two lone-pairs involved into binding of two geminal L-Cu(I) fragments at Cu-Cu distances in the range 2.55 – 2.67 Å. In order to enhance conformational rigidity within the characteristic Cu-C-Cu triangle, two types of chelating side arms were symmetrically attached to each phosphorus atom: two 2-pyridyl functions in ligand CDP(Py)2 (1) and its dinuclear copper complexes 2-9 and 11, as well as two diphenylphosphinomethylene functions in ligand CDP(CH2PPh2)2 (13) and its di- and mononuclear complexes 14-18. Neutral complexes were typically obtained via reaction of 1 with Cu(I) species CuCl, CuI, and CuSPh or via salt elimination reaction of [(CuCl)2(CDP(Py)2] (2) with sodium carbazolate. Cationic Cu(I) complexes were prepared upon treating 1 with two equivalents of [Cu(NCMe)4]PF6, followed by the addition of either two equivalent of an aryl phosphine (PPh3, P(C6H4OMe)3) or one equivalent of a bisphosphine ligands DPEPhos, XantPhos or dppf. For the first time carbodiphosphorane CDP(CH2PPh2)2 (13) could be isolated upon treating its precursor [CH(dppm)2]Cl (12) with NaNH2 in liquid NH3. A protonated and a deprotonated derivative of ligand 13 were prepared and their coordination was compared to neutral CDP ligand 13. NMR analysis and DFT calculations reveal, that the most stable tautomer of 13 does not show a CDP (or carbone) structure in its uncoordinated base form. For most of the prepared complexes, photoluminescence upon irradiation with UV light at room temperature was observed. Quantum yields (PL) were determined to 36% for dicationic [(CuPPh3)2(CDP(Py)2)](PF6)2 (4) and to 60% for neutral [(CuSPh)2(CDP(CH2PPh2)2] (16).

In this paper, several two-dimensional clustering scenarios are given. In those scenarios, soft partitioning clustering algorithms (Fuzzy C-means (FCM) and Possibilistic c-means (PCM)) are applied. Afterward, VAT is used to investigate the clustering tendency visually, and then in order of checking cluster validation, three types of indices (e.g., PC, DI, and DBI) were used. After observing the clustering algorithms, it was evident that each of them has its limitations; however, PCM is more robust to noise than FCM as in case of FCM a noise point has to be considered as a member of any of the cluster.

We first of all define the arrow of time. Definition of the arrow of time will allow choosing different initial starting points. One of the issues we will also discuss is the interconnection be-tween the arrow of time, entropy and quantum information. Seth Lloyd in his 2001 work made a linkage between entropy, bits, and information via an axiomatic approach involving time in-tervals. Our take is a bit more general. We will discuss as well the t’Hooft’s statement as to in-itial conditions and times arrow, and how different cosmological models may influence initial conditions. Spoilers alert, if a nonsingular start to expansion existed, this would provide the most straightforward way to avoid a datum from classical relativity. That is, that in the actual equations of classical GR, there is no reason to have time asymmetry. Time asymmetry is built into initial conditions and we will detail several candidates. The first half of the paper brings up cosmology models and forming the arrow of time. The second is related to entropy itself and the problem of information. .

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

The Kanchenjunga Conservation Area (KCA) is a high mountain protected area in eastern Nepal undergoing socio-economic and environmental changes that are unprecedented in the region’s history. In the following paper, we discuss recent changes involving new road construction, climate change, adventure tourism, and the wildlife/forest cover/medicinal plant sectors. Our assessments are based on the collective results of past and recent field research, remote sensing analysis, oral histories, and literature reviews. While similar changes are occurring in mountain protected areas (MPA) throughout Nepal, it is suggested that the KCA differs from other regions in that it still retains the option of conducting detailed feasibility, environmental, and impact assessments prior to the implementation of major change-associated projects, particularly the construction of roads. In turn, the KCA might avoid many of the environmental, social, and economic problems experienced elsewhere in Nepal, while enhancing its status, income-generating capacities, and sustainability as a global destination for adventure, nature, and cultural tourism.

Introduction Despite efforts to use scaffolds to treat meniscus tears, minimal progress has been made in facilitating meniscus regeneration and return of function. Our research objective was to develop a meniscus repair and regeneration implant by applying a resorbable scaffold in combination with cells and growth factors. We report here the results of using platelet-rich plasma (PRP) as a source of growth factors to induce fibrochondrogenic differentiation of human adipose-derived mesenchymal stem cells (hADSC) in a three-dimensional (3D) Type I collagen-based scaffold in vitro. Methods Scaffold Preparation. Type I collagen scaffolds were prepared following a protocol previously published. Two different densities of scaffolds, high density (HD) and low density (LD), were produced for in vitro study. hADSC and PRP Preparation. hADSCs were cultured to the fifth passage to reach the desired number for experimentation. PRP was collected from human blood and activated. Cell Culture Procedure. Effects of PRP on hADSC proliferation and differentiation into fibrochondrogenic cells were examined in four scaffold groups: LD, HD, LD+PRP and HD+PRP. hADSCs were seeded onto scaffolds (n=5) at a concentration of 2 × 106 cells/scaffold. 1% of PRP was added to the experimental media. Cellular proliferation was assessed at 1, 7, 14, and 21 days. Differentiation was measured using qRT-PCR on Days 14 and 21. qRT-PCR analysis of gene expression was completed with primers for COLLAGEN 1 and AGGRECAN. Data Analysis. ANOVAs were conducted (two-tailed tests) at the .05 significance level. Results Cellular proliferation of hADSCs seeded on each scaffold increased over time. Similar trend was observed for cells seeded on HD scaffolds with and without PRP. hADSC showed significant increase in cellular proliferation on the LD scaffolds at Days 1 and 7. At Day 21, PRP treatment and LD scaffold had a synergistic positive effect on Type I collagen gene expression. PRP did not elevate type I collagen gene in the HD group, the HD scaffold alone had the same level of type I collagen gene expression as LD+PRP. Aggrecan expression was elevated in the presence of PRP in both the HD and LD scaffold groups, indicating enhanced fibrochondrogenic differentiation of hADSCs. Effective cell infiltration was observed across both HD and LD scaffolds with and without PRP treatment. HD scaffolds displayed larger cell clusters and more extensive cell migration over time compared to LD scaffolds. However, LD scaffolds resulted a more uniform cellular distribution than HD scaffolds. Conclusion Our study demonstrates that PRP can play an important role in directing hADSCs towards fibrochondrogenic differentiation in Type I collagen-based scaffolds in vitro. Additionally, our study shows that collagen scaffold density can influence the spatial distribution and cellular behavior of infiltrated cells.

The study of dog point following has been increasingly popular, at least partially due to the initial claims that dogs outperform apes and the suggestion that our domestication process caused dogs to have a biological capacity to communicate with humans. We take the view that dog pointing is more complicated than was initially reported, and in this study, we explore several potential variables that may make a difference. Our variables include point type (ipsilateral (same-side) vs contralateral (cross-body) points), position (standing vs seated), and distance (proximal vs distal). We find that most dogs follow ipsilateral points while less than half of the dogs in our sample follow contralateral points, and that position and distance also affect dogs’ success. We suggest that dogs acquire ipsilateral points via associative mechanisms, but that contralateral points require the dogs to understand the humans’ communicative intent.

Using a safe subset of C++ is a promising direction for increasing the safety of the programming language while maintaining its performance and productivity. In this paper, we examine how close existing C/C++ code is to conforming to a safe subset of C++. We examine the rules presented in existing safe C++ standards and safe C++ subsets. We analyze the code characteristics of 5.8 million code samples from the Exebench benchmark suite and 5 modern C++ applications using a static analysis tool. We find that raw pointers, unsafe casts, and unsafe library functions are used in both C++ code at large and modern C++ applications. In general, C++ code at large does not differ much from modern C++ code, and continued work will be required to transition from existing C/C++ code to a safe subset of C++.

Human and animal waste, including waste products originating from human or animal digestive systems such as urine, feces, and animal manure, have constituted a nuisance to the environment. Inappropriate disposal and poor sanitation of human and animal waste often cause negative impacts on human health through contamination of the terrestrial environment, soil, and water bodies. Therefore, it is necessary to convert these wastes into useful resources to mitigate their adverse environmental effect. The present study provides an overview and research progress of different thermochemical and biological conversion pathways for the transformation of human- and animal-derived waste into valuable resources. The physicochemical properties of human and animal waste are meticulously discussed as well as nutrient recovery strategies. In addition, a bibliometric analysis is provided to identify the trends in research and knowledge gaps. The results reveal that the U.S.A, China and England are the dominant countries in the research areas related to resource recovery from human or animal waste. In addition, researchers from the University of Illinois, the University of California Davis, the Chinese Academy of Science and Zhejiang University are front runners in research related to these areas. Future research should be centred on developing technologies for the on-site recovery of resources, exploring integrated resource recovery pathways, and exploring different safe waste processing methods.

This study offers a concise summary of the research that has been done on alternative methods of HRM. A survey of 47 articles on the topic of creative human resource management uncovered three primary schools of thinking. At its core, innovation in HRM entails nothing more than that. One such topic worthy of investigation is the way human resource management approaches new situations. Third, research on inventiveness in the business world has given rise to the concept of "innovative HRM." Each of these three approaches, as well as the theoretical underpinnings of each, will be covered in this article. The note wraps up with a discussion of the significance of the findings for next research as well as clinical practice.

Anion exchange of the halides, Br and I, is demonstrated through the direct mixing of two pure perovskite quantum dot solutions, CsPbBr3 and CsPbI3, and is shown to be both facile and result in a completely alloyed single phase mixed halide perovskite. Anion exchange is also observed in an interlayer printing method utilizing the pure, unalloyed perovskite solutions and a commercial inkjet printer. The halide exchange was confirmed by optical absorption spectroscopy, photoluminescent spectroscopy, X-ray diffraction, and X-ray photoemission spectroscopy characterization, and indicates that alloying is thermodynamically favorable, while the formation of a clustered alloy is not favored. Additionally, a surface-to-bulk photoemission core level transition is observed for the Cs 4d photoemission feature which indicates the electronic structure of the surface is different from the bulk. Time resolved photoluminescence spectroscopy indicates the presence of multiple excitonic decay features which is argued to originate from states residing at surface and bulk environments.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

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

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

As urban development increases in density, the space to grow urban trees becomes more constrained. In heavily developed areas, small stature trees can be planted to reduce both above- and below-ground conflicts with infrastructure elements. However, even these species have their limits when placed in extremely confining conditions. In this study, we build on past work to determine the minimum planting widths of small stature urban trees. We found that species, stem diameter, and the height at which stem diameter measurements occurred were all strong predictors of trunk flare diameter (adjusted R² of 0.843). Additionally, we modelled the relationship between planting space and the presence or absence of hardscape conflicts – using the predictions derived from this effort to project the potential cost savings in two United States cities. Study results provide a guideline to create sufficient space for urban trees and minimize infrastructure damage and associated cost savings.

There is a need for developmental screening that is easily administered in resource-poor settings. 1) We hypothesized that known risk factors would predict failed developmental screening on an adapted screening tool in East African children living in poverty. 2) The sample included 100 healthy Ugandan children aged 6-59 months. We adapted a parent-reported developmental screener based on the Child Development Review chart. The primary outcome was failure to meet age-appropriate milestones for any developmental domain. Venous blood was analyzed for lead, and caregivers completed a demographics questionnaire. We used multivariate logistic regression models to determine if elevated blood lead and stunting predicted failure on the screener, controlling for maternal education level, age in months past the lower bound of the child’s developmental age group, and absence of home electricity. 3) In the sample, 14% (n=14) of children failed one or more milestones on the screener. Lead levels or stunting did not predict failing the screener after controlling for covariates. 4) Though this tool was feasibly administered, it did not demonstrate preliminary construct validity and is not yet recommended for screening in high-risk populations. Future research should include a larger sample size and cognitive interviews to ensure it is contextually relevant.

Testicular heat stress is a well described phenomenon that occurs in mammals that possess a scrotum. Different models to induce testicular hyperthermia, such as surgical cryptorchidism, hot water bath, scrotal insulation or increased environmental temperature have all shown that spermatocytes and spermatids are unambiguously affected by high temperature, resulting in poor sperm production weeks later. Furthermore, a body of evidence suggest the involvement of oxidative stress is either a major or contributory pathway, which gives rise to the potential to overcome this condition. Whilst experimental models conclusively show the deleterious effect of testicular heat on sperm quality, the physiological relevance of the work is still debated. Herein we summarise a cohort of studies that report the effect of “season” on sperm quality. The data show season can affect sperm production, motility and morphology depending on where the work was performed. In countries where temperatures drop below zero, there is evidence showing summer conditions tend to improve semen quality. However, in sub-tropical countries, some studies show a decrease in summer, whilst others show no change. Herein we offer a reasonable explanation for this apparent controversy and present a range of antioxidant supplements that may offer some protection against testicular hyperthermia.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

Modules composed of a resistance gene flanked by Xer site-specific recombination sites, the vast majority of which were found in Acinetobacter baumannii, are thought to behave as elements that facilitate horizontal dissemination. The A. baumannii xerC and xerD genes were cloned, and the recombinant clones used to complement the cognate Escherichia coli mutants. The complemented strains supported resolution of plasmid dimers, and, as is the case with E. coli and Klebsiella pneumoniae plasmids, the activity was enhanced when cells were growing in low osmolarity growth medium. Binding experiments showed that partially purified A. baumannii XerC and XerD proteins (XerC_Ab and XerD_Ab) bound synthetic Xer site-specific recombination sites, some of them with a nucleotide sequence deduced from existing A. baumannii plasmids. Incubation with suicide substrates resulted in covalent attachment of DNA to a recombinase, probably XerC_Ab, indicating that the first step in the recombination reaction took place. The results described show that XerC_Ab and XerD_Ab are functional proteins and support the hypothesis that they participate in horizontal dissemination of resistant genes among bacteria.

Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, leaving a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequent frequent variants and associated mechanisms. Variants of unknown significance (VUS) in these genes are discovered at a rate that outpaces current ability to classify them using databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns, and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.