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Free Calcium ions in the cytosol are essential for many physiological and physical functions. The free calcium ions are commonly regarded as a second messenger, are an essential part of brain communication. Numerous physiological activities, such as calcium buffering and calcium ion channel flow, etc. influence the cytosolic calcium concentration. In light of the above, the primary goal of this study is to develop a model of calcium distribution in neuron cells when a Voltage-Gated Calcium Channel and Sodium Calcium Exchanger are present. As we know, decreased buffer levels and increased calcium activity in the Voltage-Gated Calcium Channel and Sodium Calcium Exchanger lead to Alzheimer's disease. Due to these changes, the calcium diffusion in that location becomes disrupted and impacted by Alzheimer's disease. The model has been constructed by considering key factors like buffers and ER fluxes when Voltage-Gated Calcium Channels and Sodium Calcium Exchangers are present. Based on the physiological conditions of the parameters, appropriate boundary conditions have been constructed in the fuzzy environment. This model is considered a fuzzy boundary value problem with the source term and initial boundary conditions are modeled by triangular fuzzy functions. In this, paper we observed the approximate solution of the mathematical model which was investigated by the fuzzy undetermined coefficient method. The solution has been performed through MATLAB and numerical results have been computed using simulation. The observation made that the proper operation of the Voltage-Gated Calcium Channel and Sodium Calcium Exchanger is critical for maintaining the delicate equilibrium of calcium ions, which regulates vital cellular activities. Dysregulation of Voltage-Gated Calcium Channel and Sodium Calcium Exchanger activity has been linked to neurodegenerative illnesses like Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Tight control of acid–base balance is fundamental to many core physiological processes. p H affects the transmembrane movement of charged ions and the conformation of proteins and consequently, acidosis and alkalosis can cause multi-system adverse effects in the human body. The most clinically relevant concepts to understanding human acid–base physiology are the Bronsted–Lowry theory, p H , p K a (which has a significant influence on local anaesthetic pharmacokinetics) and the Henderson–Hasselbalch equation. The human body has evolved multiple endogenous buffer systems to maintain exquisite control of intra-cellular and extracellular p H , including proteins, haemoglobin, phosphate and the bicarbonate system. Bicarbonate is one of the most important buffer systems and is involved in both respiratory and renal control of acid–base balance through a series of reactions mediated by carbonic anhydrase. The renal system is an important medium to long term regulator of acid base balance through its ability to excrete hydrogen ions and retain bicarbonate. Systemic metabolic derangements and exogenous drugs can disrupt the renal acid–base system and will be discussed in this article. [ABSTRACT FROM AUTHOR]

Interest is growing in potable reuse in response to water scarcity and the desire for sustainable supplies. While potable reuse systems must control a variety of physical, chemical, and microbiological contaminants, human enteric viruses are particularly concerning and drive process performance objectives due to their often‐high occurrence in source waters, small size, potential resistance to treatment, and laborious methods to determine infectivity. This paper reviews the alignment of online monitoring practices with the mechanisms and time scales of the various barriers for enteric viruses. While there are numerous studies and reviews of individual barriers, no other review has been identified that covers operational monitoring of the entire potable reuse system. This paper also provides a critical assessment of the efficacy of current practices for operational and verification monitoring of the integrity of barriers to enteric viruses in potable reuse systems. The prevalence of human enteric viruses in wastewater and associated challenges of quantifying them through treatment are discussed within the risk management frameworks currently in use or under development for potable reuse systems. Monitoring approaches are then reviewed throughout the potable reuse water cycle. Current monitoring practices are compared with treatment process mechanisms and time scales, for the treatment barriers of biological wastewater treatment, membrane bioreactors, microfiltration/ultrafiltration, reverse osmosis, ultraviolet irradiation/advanced oxidation, ozonation, granular media/biologically active filtration, and chlorination. Monitoring and pathogen removal mechanisms are also reviewed for both environmental and engineered buffers. Implications are then discussed for future areas of research in potable reuse. [ABSTRACT FROM AUTHOR]

Cytosolic-free calcium ions play an important role in various physical and physiological processes. A vital component of neural signaling is the free calcium ion concentration often known as the second messenger. There are many parameters that effect the cytosolic free calcium concentration like buffer, voltage-gated ion channels, Endoplasmic reticulum, Mitochondria, etc. Mitochondria are small organelles located within the nervous system that are involved in processes within cells such as calcium homeostasis management, energy generation, response to stress, and cell demise pathways. In this work, a mathematical model with fuzzy boundary values has been developed to study the effect of Mitochondria and ER fluxes on free Calcium ions. The intended findings are displayed utilizing the physiological understanding that amyloid beta plaques and tangles of neurofibrillary fibers have been identified as the two main causes of AD. The key conclusion of the work is the investigation of Ca 2 + for healthy cells and cells affected by Alzheimer's disease, which may aid in the study of such processes for computational scientists and medical practitioners. Also, it has been shown that when a unique solution is found for a specific precise problem, it also successfully deals with any underlying ambiguity within the problem by utilizing a technique based on the principles of linear transformation. Furthermore, the comparison between the analytical approach and the generalized hukuhara derivative approach is shown here, which illustrates the benefits of the analytical approach. The simulation is carried out in MATLAB. [ABSTRACT FROM AUTHOR]

Flow cytometry has been widely used to estimate relative and absolute genome sizes (DNA contents) of plants for more than 50 years. However, the accuracy of these estimates can vary widely because of many factors, including errors in the genome size estimates of reference standards and various experimental methods. The objectives of this study were to reassess genome sizes of commonly used reference standards and quantify sources of variation and error in estimating plant genome sizes that arise from buffers, confounding plant tissues, tissue types, and plant reference standards using both 4′,6-diamidino-2-phenylindole (DAPI) and propidium iodide (PI) fluorochromes. Five separate studies were performed to elucidate these objectives. Revised estimates of genome sizes of commonly used plant reference standards were determined using human male leukocytes as a primary standard with an updated genome size (6.15 pg; 12.14% lower than that of earlier studies) using both DAPI and PI fluorochromes. Comparison of six different buffers (Galbraith’s, LB01, MB01, MgSO4, Otto’s, and Sysmex) resulted in variations in genome size estimates by as much as 18.1% for a given taxon, depending on the buffer–fluorochrome combination. The addition of different confounding plant tissues (representing 10 diverse taxa and associated secondary metabolites) resulted in variations in genome size estimates by as much as 10.3%, depending on the tissue–fluorochrome combination. Different plant tissue types (leaf color/exposure and roots) resulted in a variation in genome size estimates of 10.7%, independent of the fluorochrome. The selection of different internal reference standards introduced an additional variation in genome size estimates of 5.9%, depending on the standard–fluorochrome combination. The choice of fluorochrome (DAPI vs. PI) had one of the largest impacts on genome size estimates and differed by as much as 32.9% for Glycine max ‘Polanka’ when using human male leukocytes as an internal standard. A portion of this variation (∼10.0%) can be attributed to the base pair (bp) bias of DAPI and variations in Guanine-Cytosine (GC):Adenine-Thymine (AT) ratios between the sample and standard. However, as much as 22.9% of the variation in genome size estimates may result from how effectively these fluorochromes stain and report the genome. The combined variation/error from all these factors (excluding variation from bp bias for different fluorochromes, and assuming variations from confounding tissues and tissue types to both result from secondary metabolites) totaled 57.6%. Additional details of how selected factors impact accuracy, precision, and the interaction of these factors are presented. Overall, flow cytometry can be precise, repeatable, and extremely valuable for determining the relative genome size and ploidy of closely related plants when using consistent methods, regardless of fluorochrome. However, accurate determination of the absolute genome size by flow cytometry remains elusive, and estimates of genome size using flow cytometry should be considered gross approximations that may vary by ±29% or more as a function of experimental methods and plant environments. Additional recommendations of best practices are provided.

Calcium (Ca 2 + ) signals have a crucial role in regulating various processes of almost every cell to maintain its structure and function. Calcium dynamics has been studied in various cells including hepatocytes by many researchers, but the mechanisms of calcium signals involved in regulation and dysregulation of various processes like ATP degradation rate, IP 3 and NADH production rate respectively in normal and obese cells are still poorly understood. In this paper, a reaction diffusion equation of calcium is employed to propose a model of calcium dynamics by coupling ATP degradation rate, IP 3 and NADH production rate in hepatocyte cells under normal and obese conditions. The processes like source influx, buffer, endoplasmic reticulum (ER), mitochondrial calcium uniporters (MCU) and Na + /Ca 2 + exchanger (NCX) have been incorporated in the model. Linear finite element method is used along spatial dimension, and Crank-Nicolson method is used along temporal dimension for numerical simulation. The results have been obtained for the normal hepatocyte cells and for cells due to obesity. The comparative study of these results reveal significant difference caused due to obesity in Ca 2 + dynamics as well as in ATP degradation rate, IP 3 and NADH production rate. [ABSTRACT FROM AUTHOR]

Background: Liming agricultural land is essential to optimise crop yield and soil nutrients. Despite the importance of pH management in agricultural soils, liming applications have been decreasing in the United Kingdom for decades. There is no comparison of contemporary and historical liming requirement (LR) methods for Northern European, temperate climate mineral soils high in organic matter (OM). Aims: The aims of this research were to thoroughly comparatively analyse current methodologies and to ascertain which soil characteristics contribute to LR reactions. Methods: Analysis compared methods for determining liming values common in the United Kingdom (Scottish Agricultural College [SAC] look‐up chart, RothLime model), Europe and the United States (Shoemaker–McLean–Pratt, Sikora, Modified Mehlich buffers), and the 30‐min calcium hydroxide titration developed by the University of Georgia. Results: RothLime and SAC highly underestimated the LR value in acidic soils. The buffers highly over or underestimated LRs. The UGA titration method is a cheap, easy and accurate method which could be utilised for high OM soils but requires further calculation development. The characteristics most associated with soil–lime reactions in this experiment were measures of exchangeability (cation exchange capacity and loss on ignition, and by proxy, lime buffering capacity). Conclusions: There is an opportunity to create buffer calculators and titration equations adapted to high OM soils. These are suggested for further development, through a larger diversity of UK soil types grouped by buffering capacity ranges. Including soil exchangeability factors in lime management calculations may contribute to more accurate values and therefore better resource management. Increasing LR accuracy for site‐specific soil pH management, used in precision agriculture technologies, is a necessary tool for the conservation of natural resources like limestone, managing resource use efficiency, and for optimising yields. [ABSTRACT FROM AUTHOR]

Is the trust that participants have in their pension fund affected by its funding ratio (i.e., asset/liabilities ratio)? Based on survey, carried out in October 2021, among Dutch pension fund participants we link our survey data to the funding ratio of their pension fund as registered by the pension regulator. First, we show that the level of the funding ratio of their pension fund is positively associated with the trust level of participants. Pension funds with large buffers are associated with a high level of trust. Second, sub-group analyses show that the trust of younger participants is weakly related to the level of the funding ratio and this association is strong and positive for older (55+)/retired participants. It suggests that an interest in or awareness about the financial health of one's pension fund is associated with a higher responsiveness of participants in terms of trust. And third, firm-based pension funds enjoy a higher level of trust compared to sector-based pension funds. [ABSTRACT FROM AUTHOR]

Objetivo. Este estudio busca relevar la composición, abundancia, gremios, variaciones estacionales y diversidad de arañas en cultivos de lechuga con cilantro como planta acompañante. Materiales y métodos. Realizado en invernaderos con cobertura plástica y riego por goteo, el cultivo de lechuga, con cilantro como acompañante, fue muestreado en las cuatro estaciones del año, cuando alcanzaba tamaño comercial y el cilantro estaba en floración. Se aplicaron análisis de diversidad basados en el índice de Shannon-Wiener (H) con pruebas estadísticas de t de Hutcheson, determinando la estructura de gremios presentes. Resultados. Se identificaron ocho familias de arañas, las Linyphiidae (41%) y Thomisidae (27%) fueron las más abundantes, con Araneidae (10%) y Anyphaenidae (10%) también presentes. Durante todo el año se recolectaron arañas en las parcelas tratamiento, con mayor riqueza de especies en invierno (H=0.36). En las parcelas control sólo se recolectaron ejemplares en otoño y verano, siendo Thomisidae las únicas recolectadas en primavera. Las arañas cazadoras predominaron (87%), con diversidad consistente en otoño y verano, independientemente de las plantas acompañantes. En estaciones frías, las arañas estuvieron sólo en parcelas con acompañantes, lo que destaca su potencial función en el control biológico. Conclusión. Los resultados obtenidos refuerzan la relevancia de adoptar estrategias de manejo integrado de plagas (MIP), impulsando la presencia de enemigos naturales como las arañas, lo que contribuye a prácticas agrícolas más sostenibles y respetuosas con el medioambiente.

The preparation of buffer solutions used in the biopharmaceutical industry is typically performed manually by the addition of one or multiple buffering reagents to water. Recently, the adaptation of powder feeders for continuous solid feeding was demonstrated for continuous buffer preparation. However, the intrinsic characteristics of powders can change the stability of the process, due to the hygroscopic nature of some substances and humidity-induced caking and compaction behavior, but there is no simple and easy methodology available for predicting this behavior for buffer species. To predict which buffering reagents are suitable without special precautions and investigate their behavior, force displacement measurements were conducted with a customized rheometer over 18 h. While most of the eight investigated buffering reagents indicated uniform compaction, especially sodium acetate and dipotassium hydrogen phosphate (K 2 HPO 4) showed a significant increase in yield stress after 2 h. Experiments conducted with a 3D printed miniaturized screw conveyor confirmed the increased yield stress measurements by visible compaction and failure of the feeding. By taking additional precautions and adjusting the design of the hopper, we demonstrated a highly linear profile of all buffering reagents over a duration of 12 and 24 h. We showed that force displacement measurements accurately predict the behavior of buffer components in continuous feeding devices for continuous buffer preparation and are a valuable tool to identify buffer components that need special precautions. Stable, precise feeding of all tested buffer components was demonstrated, highlighting the importance of identifying buffers that need a specialized setup with a rapid methodology. [Display omitted] • Displacement measurements predict caking behavior of buffers in mini-screw feeders. • Displacement measurements identify buffers that need airing for continuous feeding. • 3D printing enables fast prototyping of pharmaceutical equipment at small scale. • Geometric freedom by 3D printing allows easy air flushing usage for buffer salts. [ABSTRACT FROM AUTHOR]

The presence of flying-fox camps in settled areas is often a contentious issue for residents and businesses. The Flying-fox Camp Management Policy 2015 sets the framework for land managers in New South Wales (NSW) to work with communities to manage flying-fox camps. To facilitate this, the NSW Government delivered the Flying-fox Grants Program, which provided funds for land managers to prepare and implement flying-fox management plans and undertake community engagement. There were three funding rounds, the first spanning 2016-18, followed by rounds in 2019 and 2020. Each funding round was fully subscribed, totalling 76 grants for 39 recipient organisations. Compared to the first funding round, there was a progressive decline in grants for works involving vegetation removal to create and maintain cleared buffers in the second and third funding rounds. Furthermore, only one grant was awarded for camp dispersal during the first funding round and none in subsequent funding rounds. Rather, the latter two funding rounds contained a greater representation of grants awarded for works aligned with biodiversity conservation objectives, such as replanting of native vegetation and community education, as well as the emergence of grants sought for heat stress mitigations in the subsequent funding rounds. Grants awarded for preparing flying-fox management plans progressed over the course of the program from predominantly camp-specific plans to regionwide management plans. The latter provide land managers with a streamlined approach that allows new flying-fox camps to be incorporated into management planning as they appear. [ABSTRACT FROM AUTHOR]

β-alanine does not have an ergogenic effect by itself, but it does as a precursor for the synthesis of carnosine in human skeletal muscle. β-alanine and carnosine together help improve the muscles' functionality, especially in high-intensity exercises such as combat sports. Therefore, β-alanine could be considered a nutritional ergogenic aid to improve sports performance in combat athletes. We aimed to critically review clinical trial evidence on the impact of β-alanine supplementation on sports performance, perception, and anthropometric parameters, as well as circulating biochemical markers in combat athletes. This systematic review was conducted following the specific methodological guidelines of the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), the PICOS question model, the Critical Review Form of McMaster, and the PEDro scale. Furthermore, the Cochrane risk-of-bias assessment tool was used. The search was carried out in the SCOPUS, Web of Science (WOS), and Medline (PubMed) databases for studies published from the beginning of the database until July 31, 2023. Of the 41 registers identified, only 7 met the established criteria and were included in this systematic review. Overall, performance parameters related to strength, power, total exercise work capacity, and combat-specific parameters were significantly improved (p < 0.05). Perception parameters increased non-significantly (p > 0.05). Regarding biochemical parameters, carnosine increased significantly (p < 0.05), pH decreased non-significantly (p > 0.05), and the results for blood bicarbonate and blood lactate were heterogeneous. Finally, there was a non-significant (p > 0.05) improvement in the anthropometric parameters of lean mass and fat mass. β-alanine supplementation appears to be safe and could be a suitable nutritional ergogenic aid for combat athletes. [ABSTRACT FROM AUTHOR]

Histones belong to a family of highly conserved proteins in eukaryotes. They pack DNA into nucleosomes as functional units of chromatin. Post-translational modifications (PTMs) of histones, which are highly dynamic and can be added or removed by enzymes, play critical roles in regulating gene expression. In plants, epigenetic factors, including histone PTMs, are related to their adaptive responses to the environment. Understanding the molecular mechanisms of epigenetic control can bring unprecedented opportunities for innovative bioengineering solutions. Herein, we describe a protocol to isolate the nuclei and purify histones from sorghum leaf tissue. The extracted histones can be analyzed in their intact forms by top-down mass spectrometry (MS) coupled with online reversed-phase (RP) liquid chromatography (LC). Combinations and stoichiometry of multiple PTMs on the same histone proteoform can be readily identified. In addition, histone tail clipping can be detected using the top-down LC-MS workflow, thus, yielding the global PTM profile of core histones (H4, H2A, H2B, H3). We have applied this protocol previously to profile histone PTMs from sorghum leaf tissue collected from a large-scale field study, aimed at identifying epigenetic markers of drought resistance. The protocol could potentially be adapted and optimized for chromatin immunoprecipitation-sequencing (ChIP-seq), or for studying histone PTMs in similar plants.

Ergogenic strategies have been studied to alleviate muscle fatigue and improve sports performance. Sodium bicarbonate (NaHCO3) has improved repeated sprint performance in adult team-sports players, but the effect for adolescents is unknown. The aim of the present study was to evaluate the effect of NaHCO3 supplementation on repeated sprint performance in semiprofessional adolescent soccer players. In a double-blind, placebo-controlled, crossover trial, 15 male semiprofessional adolescent soccer players (15 ± 1 years; body fat 10.7 ± 1.3%) ingested NaHCO3 or a placebo (sodium chloride) 90 min before performing the running anaerobic sprint test (RAST). A countermovement jump was performed before and after the RAST, and ratings of perceived exertion, blood parameters (potential hydrogen and bicarbonate concentration), and fatigue index were also evaluated. Supplementation with NaHCO3 promoted alkalosis, as demonstrated by the increase from the baseline to preexercise, compared with the placebo (potential hydrogen: +0.07 ± 0.01 vs. −0.00 ± 0.01, p < .001 and bicarbonate: +3.44 ± 0.38 vs. −1.45 ± 0.31 mmol/L, p < .001); however, this change did not translate into an improvement in RAST total time (32.12 ± 0.30 vs. 33.31 ± 0.41 s, p = .553); fatigue index (5.44 ± 0.64 vs. 6.28 ± 0.64 W/s, p = .263); ratings of perceived exertion (7.60 ± 0.33 vs. 7.80 ± 0.10 units, p = .525); countermovement jump pre-RAST (32.21 ± 3.35 vs. 32.05 ± 3.51 cm, p = .383); or countermovement jump post-RAST (31.70 ± 0.78 vs. 32.74 ± 1.11 cm, p = .696). Acute NaHCO3 supplementation did not reduce muscle fatigue or improve RAST performance in semiprofessional adolescent soccer players. More work assessing supplementation in this age group is required to increase understanding in the area. [ABSTRACT FROM AUTHOR]

This study examined the effect of buffer salts on the physical stability of spray-dried and lyophilized formulations of a model protein, bovine serum albumin (BSA). BSA formulations with various buffers were dried by either lyophilization or spray drying. The protein powders were then characterized using solid-state Fourier transform infrared spectroscopy (ssFTIR), powder X-ray diffraction (PXRD), size exclusion chromatography (SEC), solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS), and solid-state nuclear magnetic resonance spectroscopy (ssNMR). Particle characterizations such as Brunauer-Emmett-Teller (BET) surface area, particle size distribution, and particle morphology were also performed. Results from conventional techniques such as ssFTIR did not exhibit correlations with the physical stability of studied formulations. Deconvoluted peak areas of deuterated samples from the ssHDX-MS study showed a satisfactory correlation with the loss of the monomeric peak area measured by SEC (R2 of 0.8722 for spray-dried formulations and 0.8428 for lyophilized formulations) in the 90-day accelerated stability study conducted at 40°C. mDSC and PXRD was unable to measure phase separation in the samples right after drying. In contrast, ssNMR successfully detected the occurrence of phase separation between the succinic buffer component and protein in the lyophilized formulation, which results in a distribution of microenvironmental acidity and the subsequent loss of long-term stability. Moreover, our results suggested that buffer salts have less impact on physical stability for the spray-dried formulations than the lyophilized solids. [ABSTRACT FROM AUTHOR]

Measuring the density of alcohol outlets around schools is a critical step towards understanding the drivers of drinking among adolescents. Different methodologies have been used in the literature for this purpose, but the implications of using one methodology or another have not been clearly assessed. Our aim was to compare different methods to measure alcohol outlet density and highlight under which characteristics of the environment might be best using each approach. We used Geographic Information Systems to geolocate schools (n = 576) and alcohol outlets (n = 21,732) in Madrid. We defined the density of alcohol outlets as the number of establishments within an area of 400 m around schools measured using two buffering methods: crow flies' and street network distances. We evaluated the agreement between both methods visually and through regression models, including street connectivity, population density, and density of recreational venues as predictors of disagreement. The density of alcohol outlets around schools was higher using crow flies' distances compared to street network distances. The differences between methodologies were wider in areas of higher density of outlets, especially in the downtown areas, where there are higher population density and street connectivity. Our results suggest that the spatial characteristics and morphology of the study area (e.g., street connectivity and population density) should be considered when deciding the methodology to be used to measure alcohol outlet density. Future studies should explore the implications of different exposure measures in their association with drinking prevalence and consumption patterns among different geographical contexts. [ABSTRACT FROM AUTHOR]

It has been acknowledged for years that compounds containing sulfur (S) are an important source of endogenous acid production. In the metabolism, S is oxidized to sulfate, and therefore the mEq sulfate excreted in the urine is counted as acid retained in the body. In this study we show that pH in fluids with constant [Na] and [HEPES] declines as sulfate ions are added, and we show that titratable acidity increases exactly with the equivalents of sulfate. Therefore, sulfate excretion in urine is also acid excretion per se. This is in accordance with the down-regulation of proximal sulfate reabsorption under acidosis and the observation that children with distal renal tubular acidosis may be sulfate depleted. These results are well explained using charge-balance modeling, which is based only on the three fundamental principles of electroneutrality, conservation of mass, and rules of dissociation as devised from physical chemistry. In contrast, the findings are in contrast to expectations from conventional narratives. These are unable to understand the decreasing pH as sulfate is added since no conventional acid is present. The results may undermine the traditional notion of endogenous acid production since in the case of sulfur balance, S oxidation and its excretion as sulfate exactly balance each other. Possible clinical correlates with these findings are discussed. [ABSTRACT FROM AUTHOR]

It has been shown that the ability to predict the pH in any chemically characterized fluid, together with its buffer-capacity and acid content can be based on the requirement of electroneutrality, conservation of mass, and rules of dissociation as provided by physical chemistry. More is not required, and less is not enough. The charge in most biological fluids is dominated by the constant charge on the completely dissociated strong ions but, nonetheless, a persistent narrative in physiology has problematized the notion that these have any role at all in acid-base homeostasis. While skepticism is always to be welcomed, some common arguments against the importance of strong ions are examined and refuted here. We find that the rejection of the importance of strong ions comes with the prize that even very simple systems such as fluids containing nothing else, or solutions of sodium bicarbonate in equilibrium with known tensions of CO2 become incomprehensible. Importantly, there is nothing fundamentally wrong with the Henderson–Hasselbalch equation but the idea that it is sufficient to understand even simple systems is unfounded. What it lacks for a complete description is a statement of charge-balance including strong ions, total buffer concentrations, and water dissociation. [ABSTRACT FROM AUTHOR]

The lumenal pH of an organelle is one of its defining characteristics and central to its biological function. Experiments have elucidated many of the key pH regulatory elements and how they vary from compartment-to-compartment, and continuum mathematical models have played an important role in understanding how these elements (proton pumps, counter-ion fluxes, membrane potential, buffering capacity, etc.) work together to achieve specific pH setpoints. While continuum models have proven successful in describing ion regulation at the cellular length scale, it is unknown if they are valid at the subcellular level where volumes are small, ion numbers may fluctuate wildly, and biochemical heterogeneity is large. Here, we create a discrete, stochastic (DS) model of vesicular acidification to answer this question. We used this simplified model to analyze pH measurements of isolated vesicles containing single proton pumps and compared these results to solutions from a continuum, ordinary differential equations (ODE)-based model. Both models predict similar parameter estimates for the mean proton pumping rate, membrane permeability, etc., but, as expected, the ODE model fails to report on the fluctuations in the system. The stochastic model predicts that pH fluctuations decrease during acidification, but noise analysis of single-vesicle data confirms our finding that the experimental noise is dominated by the fluorescent dye, and it reveals no insight into the true noise in the proton fluctuations. Finally, we again use the reduced DS model explore the acidification of large, lysosome-like vesicles to determine how stochastic elements, such as variations in proton-pump copy number and cycling between on and off states, impact the pH setpoint and fluctuations around this setpoint.

The recent Russian invasion of Ukraine has led many commentators to remark that 'geopolitics is back'. And with geopolitics, the interest in buffer zones is back as well. Yet, International Relations scholarship on buffer zones is confusing and outdated. Scholars disagree on the definition of buffer zones and whether such zones are a vestige of the great power politics of the past or a continuous phenomenon. In this article, we take three steps to reconceptualize buffer zones and their role in international relations. First, we clarify the conceptual confusion by advancing a new definition differentiating between nominal and active buffer zones. Second, we make the case that buffer states and internal buffer zones (i.e., geographic borderlands located within states in rivalry, adjacent to the international borders between the two rivals) share much in common and therefore should be analysed in tandem. Third, we offer a typology of buffer zones with short case-studies based on the dyadic relations of rival states vis-à-vis buffer zones between them. Our goal is to provide a new analytical framework that can serve as a base for a robust research agenda on the role of buffer zones in regional and international stability and security. [ABSTRACT FROM AUTHOR]

Although buffers of inventories, time, and capacity are commonly recommended to mitigate variability in construction, they abstract away the role played by human agency. This study argues for slack as a socio-technical complement to buffers for dealing with variability. The investigation is based on two case studies conducted in construction projects that adopted the Last Planner® System. Data collection focussed on understanding how slack practices and resources (SPR) were used in production planning and control, and was based on observations, analysis of documents, and interviews. Findings revealed 57 instantiations of slack practices and 8 types of slack resources. Several of these SPR diverge from what are traditionally called buffers, highlighting how the concept of SPR gives visibility to a wider range of variability coping mechanisms. Thus, it is important to make SPR explicit so that managers can reflect on why SPR are necessary, understand how they relate to each other, and assess their unintended consequences. Five propositions are presented, encompassing: how to identify SPR; the variety and general- or context-specific nature of SPR; and the value of maintaining SPR. These propositions contribute to risk management in production planning and control. [ABSTRACT FROM AUTHOR]

The ability to manipulate droplets on a substrate using electric signals1-known as digital microfluidics-is used in optical2,3, biomedical4,5, thermal6 and electronic7 applications and has led to commercially available liquid lenses8 and diagnostics kits9,10. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)11-13; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown14, electric charging15 and biofouling16. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.

BackgroundHeart failure (HF) is characterized by electrophysiological remodeling resulting in increased risk of cardiac arrhythmias. Previous reports suggest that elevated inward ionic currents in HF promote action potential (AP) prolongation, increased short-term variability of AP repolarization, and delayed afterdepolarizations. However, the underlying changes in late Na+ current (INaL), L-type Ca2+ current, and NCX (Na+/Ca2+ exchanger) current are often measured in nonphysiological conditions (square-pulse voltage clamp, slow pacing rates, exogenous Ca2+ buffers).MethodsWe measured the major inward currents and their Ca2+- and β-adrenergic dependence under physiological AP clamp in rabbit ventricular myocytes in chronic pressure/volume overload-induced HF (versus age-matched control).ResultsAP duration and short-term variability of AP repolarization were increased in HF, and importantly, inhibition of INaL decreased both parameters to the control level. INaL was slightly increased in HF versus control even when intracellular Ca2+ was strongly buffered. But under physiological AP clamp with normal Ca2+ cycling, INaL was markedly upregulated in HF versus control (dependent largely on CaMKII [Ca2+/calmodulin-dependent protein kinase II] activity). β-Adrenergic stimulation (often elevated in HF) further enhanced INaL. L-type Ca2+ current was decreased in HF when Ca2+ was buffered, but CaMKII-mediated Ca2+-dependent facilitation upregulated physiological L-type Ca2+ current to the control level. Furthermore, L-type Ca2+ current response to β-adrenergic stimulation was significantly attenuated in HF. Inward NCX current was upregulated at phase 3 of AP in HF when assessed by combining experimental data and computational modeling.ConclusionsOur results suggest that CaMKII-dependent upregulation of INaL in HF significantly contributes to AP prolongation and increased short-term variability of AP repolarization, which may lead to increased arrhythmia propensity, and is further exacerbated by adrenergic stress.

Objectives: This study examines the potential relationship between the incidence of dental caries in adults and the level of mucin-7 glycoprotein, a specific parameter in saliva. Methods: In a case-control study, samples of whole unstimulated saliva from 40 volunteers in two different groups were classified according to the decayed, missing, filled teeth (DMFT) index. One group was caries-free (n = 17), and the other had severe carries (n = 23). We measured the level of mucin-7, salivary buffer system, and pH and examined for relationships to the DMFT index. Results: There was a statistically significant difference among the groups (p < 0.001) in the level of mucin-7, salivary buffer system, and pH. The DMFT index for case and control groups was calculated as 0 and 14.09 ± 3.78. There was a strong, negative relationship between the level of mucin-7 and the DMFT index. Conclusion: The development of dental caries is linked to a reduced concentration of mucin-7 in saliva. The level of mucin-7 may be clinically useful for evaluating dental caries risk.

Immediate-early response genes (IEGs) are rapidly and transiently induced following an extracellular signal. Elucidating the IEG response patterns in single cells (SCs) requires assaying large numbers of timed samples at high accuracy while minimizing handling effects. To achieve this, we developed and validated RNA stabilization Buffer for Examination of Single-cell Transcriptomes (RNA-Best), a versatile single-step cell and tissue preservation protocol that stabilizes RNA in intact SCs without perturbing transcription patterns. We characterize for the first time SC heterogeneity in IEG responses to pulsatile gonadotropin-releasing hormone (GnRH) stimuli in pituitary gonadotrope cells. Our study identifies a gene-specific hierarchical pattern of all-or-none transcript induction elicited by increasing concentrations of GnRH. This quantal pattern of gene activation raises the possibility that IEG activation, when accurately resolved at the SC level, may be mediated by gene bits that behave as pure binary switches.

Networks-on-Chip (NoCs) have become the de-facto on-chip interconnect for multi/manycore systems. A typical NoC router is made up of buffers used to store packets that are unable to advance to their desired destination. However, buffers consume significant power/area and are often underutilized, especially in cases of applications with non-uniform traffic patterns thus leading to performance degradation for such applications. To improve network performance, the Roundabout NoC (R-NoC) concept is considered. R-NoC is inspired by real-life multi-lane traffic roundabouts and consists of lanes that are shared by multiple input/output ports to maximize buffering resource utilization. R-NoC relies on router-internal adaptive routing that decides the lane path based on back pressure. Back pressure makes it possible to assess lane utilization and route packets accordingly. This is made possible thanks to the use of elastic buffers for control flow, a clever type of handshaking in a way similar to asynchronous circuits. Another prominent feature of R-NoC is that internal routing and arbitration are completely distributed which allows for significant freedom in deciding internal router topology and parameters. This work leverages this property and proposes novel yet unexplored configurations for which an in-depth evaluation of corresponding implementations on 45 nm CMOS technology is given. Each configuration is evaluated performance and power-wise on both synthetic and real application traffic. Several R-NoC configurations are identified and demonstrated to provide very significant performance improvements over standard mesh configurations and a typical input-buffered router, without compromising area and power consumption. Exploiting the distributed nature of R-NoC routers, a diagonally-linked configuration is then proposed which incurs moderate area overhead and features yet better performance and energy efficiency. [ABSTRACT FROM AUTHOR]

Non-carbonic buffer power (ßNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, ßNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess ßNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cellmembrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The ßNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of ßNC and pCO2 on the Base excess of blood was examined. In the control samples, ßNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that ßNC rose by 0.36mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p < 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium wasmore pronounced in lactic acidosis. Lastly, we found that the rise of ßNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare anion gap estimated through measured and calculated bicarbonate modalities to be used interchangeably in critically ill metabolic acidosis patients. METHODS: This cross-sectional study was conducted at Rehman Medical Institute, Peshawar, Pakistan from September 2019 to March 2020. Out of 390 critically ill patients, 200 cases of metabolic acidosis were selected by non-probability consecutive sampling technique. Measured and calculated bicarbonate values were obtained through Cobas-c 501© (Roche) using enzymatic method and Cobas-b 221© (Roche) blood gas analyzer respectively. Statistical analysis was done by using SPSS-23. RESULTS: Normal anion gap metabolic acidosis (NAG-MA) and high anion gap metabolic acidosis (HAG-MA) based on calculated bicarbonate levels was observed in 57 (28.5%) and 143 (71.5%) cases as compared to 55 (27.5%) and 145 (72.5%) cases based on measured bicarbonate levels respectively (p>0.45). A significant correlation (r=0.888 and 0.656, r2=0.788 and 0.431) (p

Linearly polarized modes were generated from the fundamental LP01 using Lee holograms displayed on a digital micromirror device. The phase in the holograms was optimized using simulated annealing algorithm and complex amplitude correlation to improve the quality of the converted modes. The correlation measurements, and comparisons between numerical and experimental results, show the fidelity of the obtained modes and the effectiveness of the optimization. Furthermore, the optimized holograms can be combined to generate multiple modes spatially addressed with individual control. The results, and the use of a digital micromirror device instead of the most common liquid crystal modulators, make this method suitable for Modal Division Multiplexing systems and compatible with other optical telecommunication techniques like Wavelength and Polarization Division multiplexing, and reconfigurable optical networks.

β-alanine does not have an ergogenic effect by itself, but it does as a precursor for the synthesis of carnosine in human skeletal muscle. β-alanine and carnosine together help improve the muscles’ functionality, especially in high-intensity exercises such as combat sports. Therefore, β-alanine could be considered a nutritional ergogenic aid to improve sports performance in combat athletes. We aimed to critically review clinical trial evidence on the impact of β-alanine supplementation on sports performance, perception, and anthropometric parameters, as well as circulating biochemical markers in combat athletes. This systematic review was conducted following the specific methodological guidelines of the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), the PICOS question model, the Critical Review Form of McMaster, and the PEDro scale. Furthermore, the Cochrane risk-of-bias assessment tool was used. The search was carried out in the SCOPUS, Web of Science (WOS), and Medline (PubMed) databases for studies published from the beginning of the database until July 31, 2023. Of the 41 registers identified, only 7 met the established criteria and were included in this systematic review. Overall, performance parameters related to strength, power, total exercise work capacity, and combat-specific parameters were significantly improved (p < 0.05). Perception parameters increased non-significantly (p > 0.05). Regarding biochemical parameters, carnosine increased significantly (p < 0.05), pH decreased non-significantly (p > 0.05), and the results for blood bicarbonate and blood lactate were heterogeneous. Finally, there was a non-significant (p > 0.05) improvement in the anthropometric parameters of lean mass and fat mass. β-alanine supplementation appears to be safe and could be a suitable nutritional ergogenic aid for combat athletes.

MicroRNAs (miRNAs) are small RNAs that bind to mRNA targets and regulate their translation. A functional study of miRNAs and exploration of their utility as disease markers require miRNA extraction from biological samples, which contain large amounts of interfering compounds for downstream RNA identification and quantification. The most common extraction methods employ silica columns or the TRIzol reagent but give out low recovery for small RNAs probably due to their short strand lengths. Herein, we fabricated the titanium dioxide nanofibers using electrospinning to facilitate miRNA extraction and developed the optimal buffer conditions to improve miRNA recovery from biological matrices of cell lysate and serum. We found that our TiO2 fibers could obtain a recovery of 18.0 ± 3.6% for miRNA fibers while carrying out the extraction in the more complex medium of cell lysate, much higher than the 0.02 ± 0.0001% recovery from the commercial kit. The much improved extraction of miRNAs from our fibers could be originated from the strong coordination between TiO2 and RNA's phosphate backbone. In addition, the binding, washing, and elution buffers judiciously developed in the present study can achieve selective extraction of small RNA shorter than 500 nucleotides in length. Our results demonstrate that TiO2 nanofibers can work as a valuable tool for extraction of miRNAs from biological samples with high recovery. Graphical abstract Schematic for extraction of small RNAs using TiO2 nanofibers.

The ability of the heterochromatin protein-1 (HP1) to phase separate into droplets suggests new mechanisms of gene organization in the cell nucleus. An accumulating body of work suggests that other nuclear proteins also display phase separation behaviors in vitro. To understand the mechanistic and biological significance of such droplet formation a rigorous biophysical characterization of this behavior is necessary. Herein we describe procedures for imaging HP1 droplets by brightfield microscopy, and two methods to quantify phase separation.

Non-carbonic buffer power (βNC) of blood is a pivotal concept in acid-base physiology as it is employed in several acid-base evaluation techniques, including the Davenport nomogram and the Van Slyke equation used for Base excess estimation in blood. So far, βNC has been assumed to be independent of metabolic acid-base status of blood, despite theoretical rationale for the contrary. In the current study, we used CO2 tonometry to assess βNC in blood samples from 10 healthy volunteers, simultaneously analyzing the electrolyte shifts across the red blood cell membrane as these shifts translate the action of intracellular non-carbonic buffers to plasma. The βNC of the blood was re-evaluated after experimental induction of metabolic acidosis obtained by adding a moderate or high amount of either hydrochloric or lactic acid to the samples. Moreover, the impact of βNC and pCO2 on the Base excess of blood was examined. In the control samples, βNC was 28.0 ± 2.5 mmol/L. In contrast to the traditional assumptions, our data showed that βNC rose by 0.36 mmol/L for each 1 mEq/l reduction in plasma strong ion difference (p < 0.0001) and was independent of the acid used. This could serve as a protective mechanism that increases the resilience of blood to the combination of metabolic and respiratory acidosis. Sodium and chloride were the only electrolytes whose plasma concentration changed relevantly during CO2 titration. Although no significant difference was found between the electrolyte shifts in the two types of acidosis, we observed a slightly higher rate of chloride change in hyperchloremic acidosis, while the variation of sodium was more pronounced in lactic acidosis. Lastly, we found that the rise of βNC in metabolic acidosis did not induce a clinically relevant bias in the calculation of Base excess of blood and confirmed that the Base excess of blood was little affected by a wide range of pCO2.

Objectives: The relative effect of pH and titratable acidity on tooth erosion remains unclear. We determined the effect of both properties on in vivo salivary pH recovery and on enamel and dentine early erosion in situ. Methods: Solutions simulating acidic beverages with different pHs (2.5 or 3.5) and titratable acidities (0, 25, or 100 mM citric acid) were tested. In an in vivo study (n = 20 participants), the salivary pH was determined before, during, and up to 2 min after exposure to the tested solutions. In situ, 12 participants exposed enamel and root dentine slabs to the tested solutions simulating a beverage consumption; early erosion was assessed by percentage of surface hardness loss (%SHL). Groups were compared by ANOVA (p < 0.05). Results: Saliva pH was lower after exposure to solutions at pH 2.5, irrespective of titratable acidity; pH recovery took longer for solutions with higher titratable acidities, irrespective of their pHs. In situ, the highest %SHL was observed for the solution with lower pH and higher titratable acidities. The addition of citric acid increased the %SHL by 2.5–3 times in enamel, and at least 5 times in dentine. Conclusions: Both pH and titratable acidity may play a role on the erosive potential of acidic beverages. Clinical relevance: Acidic beverages with lower pHs promote erosion by an initial acid etching of the surface; those with a higher titratable acidity slow down the salivary pH recovery. Both properties contribute to the overall erosive potential. [ABSTRACT FROM AUTHOR]