Open Configuration Research Articles

Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.

Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. We approached Ca spark activation as an emergent phenomenon of an interactive system of release channels. We constructed a weakly lumped Markov chain that applies an Ising model formalism to such release channel clusters and probable open channel configurations and demonstrated that spark activation is described as a system transition from a metastable to an absorbing state, analogous to the pressure required to overcome surface tension in bubble formation. This yielded quantitative estimates of the spark generation probability as a function of various system parameters. We performed numerical simulations to find spark probabilities as a function of sarcoplasmic reticulum Ca concentration, obtaining similar values for spark activation threshold as our analytic model, as well as those reported in experimental studies. Our parametric sensitivity analyses also showed that the spark activation threshold decreased as Ca sensitivity of RyR activation and RyR cluster size increased.

A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia

Glial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning the neurogenic potential of adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition along a linear differentiation trajectory that allows them to retain neurogenic potential while acquiring mature glial functions. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a cell culture model of enteric neurogenesis and a gut injury model demonstrate that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits.

Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A

Long-chain acyl-coenzyme A (LC-CoA) is a crucial metabolic intermediate that plays important cellular regulatory roles, including activation and inhibition of ion channels. The structural basis of ion channel regulation by LC-CoA is not known. Transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6) are epithelial calcium-selective ion channels. Here, we demonstrate that LC-CoA activates TRPV5 and TRPV6 in inside-out patches, and both exogenously supplied and endogenously produced LC-CoA can substitute for the natural ligand phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in maintaining channel activity in intact cells. Utilizing cryo-electron microscopy, we determined the structure of LC-CoA-bound TRPV5, revealing an open configuration with LC-CoA occupying the same binding site as PI(4,5)P2 in previous studies. This is consistent with our finding that PI(4,5)P2 could not further activate the channels in the presence of LC-CoA. Our data provide molecular insights into ion channel regulation by a metabolic signaling molecule.

Numerical and experimental study of a very low head (VLH) turbine in an open channel at no-load conditions

Very low head (VLH) turbines are axial turbines with the capability of extracting power at a high efficiency of over 80% from very low heads (less than 4.5 m) and high flow rates of up to 30 m3/s per unit, with a significant reduction in construction costs, compared to conventional hydropower turbines. At no-load conditions, the turbine reaches its runaway speed, which is its theoretical maximum speed, causing damage to the equipment and the turbine structure, thereby imposing a considerable financial burden. As a result, understanding the performance of the turbine at the runaway speed is of utmost importance. The present paper centers its experimental and simulation efforts on predicting the runaway speed of the turbine rotor. An experimental study is conducted to determine the relationship between the runaway speed of the turbine and the flow rate, as well as compare its value with the rotational speed at the design point. Through the conducted experiments, it has been observed that at the mass flow rate corresponding to the design point, the runaway speed is 2.12 times higher than the rated value. Transient simulations using Computational Fluid Dynamics (CFD) are employed to investigate the performance under no-load conditions by estimating the generated torque as a key parameter. Simulations are carried out in an open channel configuration using the Ansys CFX software, and the results are compared to the experiments. In this study, a portion of the work focuses on simulating the free surface flow over the turbine, which allows for more realistic simulations of the turbine's operational behavior. The results of these simulations indicate that the homogeneous model is able to correctly predict free surface flow downstream and upstream. The numerical approach can also predict the runaway state of the VLH turbine with high accuracy, exceeding 95%; however, this variation is due to mechanical and hydraulic losses that have not been factored into the simulation. In this CFD modeling, setting up the boundary conditions accurately is vital, especially for the water levels at the inlet and outlet.

The Human Cytomegalovirus Latency-Associated Gene Product Latency Unique Natural Antigen Regulates Latent Gene Expression.

Human cytomegalovirus (HCMV) infection can lead to either lytic or latent infection, which is dependent on the regulation of the viral major immediate early promoter (MIEP). Suppression of the MIEP is a pre-requisite for latency and is driven by repressive epigenetic modifications at the MIEP during latent infection. However, other viral genes are expressed during latency and this is correlated with activatory epigenetic modifications at latent gene promoters. Yet the molecular basis of the differential regulation of latent and lytic gene expression by epigenetics is unclear. LUNA, a latent viral transcript, has been suggested to be important for HCMV latency and has also been shown to be important for efficient reactivation likely through its known deSUMOylase activity. Intriguingly, we and others have also observed that LUNA enhances latency-associated expression of the viral UL138 gene. Here, we show that in the absence of LUNA, the expression of multiple latency-associated transcripts is reduced during latent infection, which is correlated with a lack of activatory marks at their promoters. Interestingly, we also show that LUNA interacts with the hematopoietic transcription factor GATA-2, which has previously been shown to bind to a number of latency-associated gene promoters, and that this interaction is dependent on the deSUMOylase domain of LUNA. Finally, we show that the deSUMOylase activity of LUNA is required for the establishment and/or maintenance of an open chromatin configuration around latency-associated gene promoters. As such, LUNA plays a key role in efficient latency-associated viral gene expression and carriage of viral genome during latent carriage.

Lighting Performance: Simulation Methodology Assessment for A Single Story House at Desa Pinggiran Putra, Sepang, Selangor Darul Ehsan

This paper depicts the lighting simulation and analysis for a single-story house at Desa Pinggiran Putra, Sepang, Selangor. The study aims to enhance and maximize daylighting strategies based on the proposed design, suggest design modifications and other related adjustments. Appropriate lighting strategies free from glare and shadows may lessen eye strain and headaches to building occupant. Lighting, either natural or artificial is essential to provide comfortable environment. However, disproportionate lighting could cause discomfort to building occupants such as the case of excessive sunlight may make the visual environment uncomfortable and interfere with inhabitants' vision due to glare. The scope of this study is to ascertain and establish design with optimum lighting conditions at home using building performance modelling, as well as outlining the significance of daylight variables and examining the effects of different opening configurations including door and window sizes, heights, and placement. The study was carried out using Autodesk REVIT 2023 software (educational version). The findings of this study show possible improvements to the proposed design solutions to optimise daylighting strategies. It shall elucidate potential design improvement to residential units, reducing the need for artificial lighting and unnecessary energy use. This technical knowledge shall enable future homes to be designed properly for optimising daylight use.

Effect of void space arrangement on wind power potential and pressure coefficient distributions for high-rise void buildings

High-rise void building complexes can augment the permeation of airflows over buildings, and thereby strengthen urban wind energy harvesting for realization of the sustainable development goals (SDGs). This paper considers the wind over a typical 2×2 compact high-rise building array with the openings to analyze the wind power potential at varying void sizes, locations of voids, and direction of incoming wind. The predicted mean wind speeds and turbulence intensities are compared against the measured data with 4 generic high-rise building models having voids in an atmospheric boundary layer wind tunnel for validation of the computational model. Based on the comparative results from four common Reynolds-averaged Navier-Stokes (RANS) turbulence models including the standard, realizable, renormalization group (RNG) k-ε, and shear-stress transport (SST) k-ω models as well as the Reynolds stress model (RSM), the RSM approach can provide the most accurate predictions of streamwise mean velocity and turbulence intensity. The present study then conducts CFD simulations to explore the effects of opening configuration and wind direction on the wind field around high-rise void buildings. Considering the variations of void sizes of 10 × 10 m2, 12.5 × 12.5 m2, 15 × 15 m2, void heights of z/H = 0.25, 0.5, 0.75 and wind directions of 0°, 45°, respectively, the simulated results indicate elevated wind power densities with acceptable turbulence intensities over the upstream gap passage and void channels to achieve prospective urban wind power harvest and mitigate wind load on structures of high-rise void buildings.

Proof of concept of a self-tightening needle-less suture using a NiTi shape memory alloy

Among surgical procedures, suturing is considered simple. However, in some situations, suturing is not easy or feasible. Here, we present proof of concept of a new self-tightening needle-less suture made of a NiTi alloy. The new device is designed to overcome two demanding steps of traditional suturing: needle introduction and manual knotting. Our novel suture is composed only of a short NiTi wire that is able to change shape by exploiting a thermoelastic phase transition. This shape change is achieved by increasing the temperature from that of the operating room (e.g., 20–22 °C) to 32 °C using warm water. Suturing consists of two steps: suture introduction, in which the suture is in an open configuration, and shape recovery (i.e., closed configuration). The closed configuration is maintained at human body temperature thanks to peculiar pseudoelastic properties of the NiTi material. Finally, thermal and functional characterization verified the simplicity and effectiveness of the proposed device.Graphic abstract

Bach1 inhibitor HPP-D mediates γ-globin gene activation in sickle erythroid progenitors

Sickle cell disease (SCD) is the most common β-hemoglobinopathy caused by various mutations in the adult β-globin gene resulting in sickle hemoglobin production, chronic hemolytic anemia, pain, and progressive organ damage. The best therapeutic strategies to manage the clinical symptoms of SCD is the induction of fetal hemoglobin (HbF) using chemical agents. At present, among the Food and Drug Administration-approved drugs to treat SCD, hydroxyurea is the only one proven to induce HbF protein synthesis, however, it is not effective in all people. Therefore, we evaluated the ability of the novel Bach1 inhibitor, HPP-D to induce HbF in KU812 cells and primary sickle erythroid progenitors. HPP-D increased HbF and decreased Bach1 protein levels in both cell types. Furthermore, chromatin immunoprecipitation assay showed reduced Bach1 and increased NRF2 binding to the γ-globin promoter antioxidant response elements. We also observed increased levels of the active histone marks H3K4Me1 and H3K4Me3 supporting an open chromatin configuration. In primary sickle erythroid progenitors, HPP-D increased γ-globin transcription and HbF positive cells and reduced sickled erythroid progenitors under hypoxia conditions. Collectively, our data demonstrate that HPP-D induces γ-globin gene transcription through Bach1 inhibition and enhanced NRF2 binding in the γ-globin promoter antioxidant response elements.

The dynamic characteristics in the wake systems of a propeller operating under different loading conditions

Improved delayed detached-eddy simulations (IDDES) on the computational domain composed of 48 million cells were employed to numerically simulate the propeller wake with various advance coefficients, shedding light on the dynamic characteristics and the evolution mechanisms for the entire wake system subject to different loading conditions. Validation against available experimental data under open water configuration was conducted to verify the numerical modelling in the present work. Dynamic mode decomposition, or to be more specific, its sparisity promoting varient, was further adopted to capture the fundamental spatio-temporal scales of the propeller wakes. The results of the simulation revealed that the low streamwise convection velocity with the high advance coefficient suppresses the wake vortex transportation, resulting in a helicoidal tip vortex system with strong interference effects and low pitch that leads to the earlier occurrence of propeller wake instability. The wake systems with high advance coefficient better maintain the memory of propeller rotation, resulting in more coherent downstream wakes. Moreover, the different interaction modes leading to wake instability were discussed.

Air change rates and infection risk in school environments: Monitoring naturally ventilated classrooms in a northern Italian urban context

The importance of building ventilation in avoiding long-distance airborne transmission has been highlighted with the advent of the COVID-19 pandemics. Among others, school environments, in particular classrooms, present criticalities in the implementation of ventilation strategies and their impact on indoor air quality and risk of contagion. In this work, three naturally ventilated school buildings located in northern Italy have undergone monitoring at the end of the heating season. Environmental parameters, such as CO2 concentration and indoor/outdoor air temperature, have been recorded together with the window opening configurations to develop a two-fold analysis: i) the estimation of real air change rates through the transient mass balance equation method, and ii) the individual infection risk via the Wells-Riley equation. A strong statistical correlation has been found between the air change rates and the windows opening configuration by means of a window-to-volume ratio between the total opening area and the volume of the classroom, which has been used to estimate the individual infection risk. Results show that the European Standard recommendation for air renewal could be achieved by a window opening area of at least 1.5 m2, in the most prevailing Italian classrooms. Furthermore, scenarios in which the infector agent is a teacher show higher individual infection risk than those in which the infector is a student. In addition, the outcomes serve school staff as a reference to ensure adequate ventilation in classrooms and keep the risk of infection under control based on the number of the students and the volume of the classroom.

Efficient Scale-Resolving Simulations of Open Cavity Flows for Straight and Sideslip Conditions

This study aims to facilitate a physical understanding of resonating cavity flows with efficient numerical treatments of turbulence. It reinforces the efficiency and affordability of scale-adaptive numerical techniques for simulating open cavity flows with a separated shear layer consisting of a wide range of flow scales. Visualization of the resonant modes occurring due to the acoustic feedback loop aids in a better understanding of large-scale flow oscillations. Under this scope, scale-adaptive simulation (SAS) based on the k-ω SST RANS model with different turbulence treatments has been studied for an open cavity configuration with a length-to-depth (L/D) ratio of 5.7 featuring Mach number (Ma) 0.8 and Reynolds number (Re) 12×106. It is shown that the essential cavity flow physics has been captured using the SAS approach with more than 90% improved computational efficiency compared to commonly used hybrid RANS-LES approaches. In addition, wall-modeled SAS when supplemented with an artificial forcing concept to trigger the model provides very good spectral estimates comparable with hybrid RANS-LES results. Following the validation of numerical approaches, the directional dependence of the cavity resonance is investigated under asymmetric flow conditions, and spanwise interference of waves due to the lateral walls of the cavity has been observed.

Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.

The Influence of Geometry on Continuous and Split Bipolar Electrochemistry Applied to Corrosion Studies

Bipolar electrochemistry provides a wireless approach for driving redox reactions and has been applied in corrosion, electrodeposition, sensing, and electrocoagulation. Despite the extensive study of the method, the significance of geometric aspects of the experimental setup still remain ill-explored, and a justification for geometries used in previous works is missing. The aim of this study is to provide information about how current/potential distributions of a split bipolar electrode in an open configuration are affected by geometric components. Through PDE-constrained optimizations, the most influential parameters are identified to be the bipolar electrode size, electrolyte height, and applied current. It is shown that a general Wagner number may be used to inform the form of the current distribution for bipolar electrochemistry but with limitations. The results also show that the current through the bipolar electrode is directly associated with cell components and higher bipolar current efficiencies will promote the primary current distribution.

Full Scale Bend Test of a Multi Stage Aerospace Vehicle

Evaluation of structural integrity of a missile involves sectional and full scale tests. Tests are carried out for transportation, articulation and aerodynamic loads. Uniqueness of carrying full scale bend test of a multi stage aerospace vehicle lies in the qualification of not only structural integrity of different sections but also the joints. Empty missile structure forms the testing frame. A bending moment envelope is simulated using a combination of upward and downward loads. Design and realization of open configuration test rig frames in order to simulate the necessary boundary conditions was executed. The output measurements for the test are strains, deflections and joint rotation constants. Linear Variable Displacement Transducers (LVDTs) measures the deflections normal to the missile axis and help in mapping of the deflection pattern along the length of the missile. CODs (Crack Opening Devices), developed in-house, are used to measure the joint openings during the bend test. The measured Joint Rotation Constants (JRCs) are in-turn used as input to refine the Finite Element (FE) model, thereby improvising the accuracy of the predicted results from the FE model.

Numerical Analysis of Natural Ventilation on One Side of a Room with Two Different Opening Configurations

Single-side natural ventilation is a commonly used means of ventilation to effectively regulate the thermal environment in building interiors without any fossil energy consumption. To achieve most of the potential for the efficiency of single-side natural ventilation, research needs to be undertaken into the forces that drive single-side natural ventilation. This paper examines the single-side natural ventilation of a single vertical single opening (SSO) and a vertical double opening (SDO) in a freestanding building under wind and thermal pressure. The change in the trajectory of vortex shedding when the building is leeward as well as the frequency of vortex shedding in square buildings was investigated by large eddy simulation (LES), and computational fluid dynamics was used to analyze the difference in the air exchange rate of single-side natural ventilation of SSO and SDO in the windward and leeward conditions of the building. Both of these methods were used in conjunction with one another. According to the findings, the creation of vortices at SSO and SDO in the presence of low wind speeds reduces the ventilation effect of thermal pressure under windward circumstances. Consequently, the influence of thermal stress and wind stress ultimately cancel each other out, and this phenomenon finally disappears as the wind blowing from the outside of the structure increases. The shedding of vortices in the leeward state accomplishes a form of air supply pumping with a particular periodicity of airflow fluctuations in the lateral direction. The Strouhal number computed using the LES simulation acts in a manner consistent with the experimental findings.

Synthesis, spectroscopic, and lead(II) binding behavior of three novel dibenzo-18-crown-6 hydrazones

Three novel hydrazonic derivatives of dibenzo-18-crown-6 were synthesized and their vibrational and electronic absorption spectroscopic properties thoroughly investigated. Their lead binding behaviors were also characterized and the observations rationalized by density functional theoretical modeling. All three cis-dihydrazonic compounds are of low overall molecular symmetry with their ether cavity adopting an open configuration at the global energy minima where the hydrazonic side-arms are electronically and vibrationally nonequivalent. Their optical absorption features are dominated by π → π * transitions where one side of the molecule exhibits Lewis acid behavior whereas the other behaves like a Lewis base. In addition to their sensitivity to pH, all three derivatives form stable 2:1 metal-ligand complexes with lead, due to coordination at the ether cavity, in addition to the hydrazone “backbone” and possibly the heterocyclic ring. The most stable lead complex is formed with the thiophene carboxylic acid hydrazide derivative due to favorable soft-soft interactions between lead and the ring-based sulfur atom.

Performance of a Tank Filled with Desublimated Uranium Hexafluoride as a Function of the Configuration of Central Openings in its Ribs

Performance of a Tank Filled with Desublimated Uranium Hexafluoride as a Function of the Configuration of Central Openings in its Ribs

Effect of fence opening configurations on dune development

Effect of fence opening configurations on dune development

Comparative Study of Soft Tissue and Hard Tissue Variables Correlation between Two Different Racial groups: A Canonical study

Aims: The purpose of this study was to investigate the correlation between dental, skeletal, and soft tissue variables and compare the results with Saudi study and other previous studies. Material and Method: The sample size consisted of 29 adult Sudanese patients (ages 18 to 25) seeking orthodontic treatment, and 19 variables were examined. The error of the method was assessed using Student's t-test, and canonical correlation analysis was used to analyze the correlation between soft and hard tissues. Results: The study found that the Sudanese population had higher mean values in dental and soft tissue variables compared to the Saudi population, while similar mean values were found in the skeletal sagittal relationship, except for the vertical relationship, where the Saudi population had a higher tendency for an open basal configuration. The canonical analysis revealed that the upper and lower incisors' inclinations had a strong negative loading, while the nasolabial angle and lower lip thickness and position had moderate loading. Conclusion: These findings show the impact of these variables which can help the clinician in diagnosis, prediction and assessment of post treatment changes. Additionally, the multivariate statistical analysis extracted a clinically significant association between soft tissue and hard tissue.