Influence of partition layouts on speech privacy in open-plan offices.

Different partition layouts were compared to determine how to increase speech privacy while maintaining communication efficiency between workers in an open-plan office. A preliminary survey was used to determine current usage and conditions of partitions in open-plan offices. The survey results were used to select four partition layouts for testing: face-to-face, parallel, crossed-rod, and orthogonal. A computer modeling was used to test the partition layouts at three different partition heights: 1.2, 1.5, and 1.8 m. The modeling results showed that the parallel- and crossed-rod-type layouts offered the best speech privacy at the lowest partition height, but the differences among layouts disappeared as the partition height was increased. Furthermore, an acoustic field experiment was performed using partitions with a 1.5 m height following the ISO 3382-3 standard. The experimental results showed that the face-to-face layout resulted in the least speech privacy. Based on these results, an open-plan office needs to ensure that workers are spaced a sufficient distance apart and that they do not face each other to ensure speech privacy. Additionally, speech privacy should be considered in the design stage of the office space.

Epicardial pulsed-field ablation-impact of electric field and heat distribution induced by coronary metallic stents.

Background: Pulsed-field ablation (PFA) technique is a nonthermal ablation technique. No study has yet evaluated the effect of the positional relationship between the ablation electrode (AE) and the coronary metal stent (CMS) on the electric field distribution and temperature distribution in epicardial ablation. Our study aimed to evaluate the effect of the CMS on the electric field as well as the temperature distribution in different models. Methods: Multi-angle modeling of the CMS and AE was performed. The PFA ablation region was evaluated with a field strength contour of 1,000 V/cm, which was used to assess the validity of the two-dimensional (2D) model simulation data as well as the distribution of the multi-angle electric field and temperature in the three-dimensional (3D) model. Results: The presence of the CMS had little effect on the width of the ablation area (0.2 mm). In the 3D model, the temperature of the ablation area was highest when the angle between the AE and the CMS was in the 90° position (43.4°C, 41.3°C); a change in the distance between the AE and the CMS affected the temperature of the ablation area (maximum 2.1°C) and the width of the ablation (maximum 0.32 mm). Conclusion: The presence of the CMS distorts the distribution of the electric field, but does not produce a change in the extent of the ablation damage, nor does it bring thermal damage to the ablation region. Different simulation models give similar results in PFA calculations, and this study effectively reduces the complexity of modeling simulation.

Lectins CGL and MTL, representatives of mytilectin family, exhibit different antiproliferative activity in Burkitt's lymphoma cells.

Lectins are carbohydrate-binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels Crenomytilus graynus (CGL) and Mytilus trossulus (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells. Both lectins suppressed the formation of colonies as well as cell cycle progression. The mechanism of action of these lectins was not mediated by reactive oxygen species but included damaging of mitochondria, inhibition of key cell cycle points, and activation of MAPK signaling pathway in tumor cells. Computer modeling suggested that various effects of CGL and MTL on lymphoma cells may be due to the difference in the energy of binding of these lectins to carbohydrate ligands on the cell surface. Thus, molecular recognition of residues of terminal carbohydrates on the surface of tumor cells is a key factor in the manifestation of the biological action of lectins.

Activation of the influenza B M2 proton channel (BM2).

Influenza B viruses have co-circulated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we perform the membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant to explore its pH-dependent conformational switch. Simulations capture the activation as the first histidine (His19) protonates and reveal the transition at lower pH values compared to AM2 is a result of electrostatic repulsions between His19 and pre-protonated His27. Crucially, we provide an atomic-level understanding of the symmetric proton conduction by identifying pre-activating channel hydration in the C-terminal portion. This research advances our understanding of the function of BM2 function and lays the groundwork for further chemically reactive modeling of the explicit proton transport process as well as possible anti-flu drug design efforts.

Polar Glycerolipids and Membrane Lipid Rafts.

Current understanding of the structure and functioning of biomembranes is impossible without determining the mechanism of formation of membrane lipid rafts. The formation of liquid-ordered and disordered phases (Lo and Ld) and lipid rafts in membranes and their simplified models is discussed. A new consideration of the processes of formation of lipid phases Lo and Ld and lipid rafts is proposed, taking into account the division of each of the glycerophospholipids into several groups. Generally accepted three-component schemes for modeling the membrane structure are critically considered. A four-component scheme is proposed, which is designed to more accurately assume the composition of lipids in the resulting Lo and Ld phases. The role of the polar head groups of phospholipids and, in particular, phosphatidylethanolamine is considered. The structure of membrane rafts and the possible absence of a clear boundary between the Lo and Ld phases are discussed.

Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends.

Significance: Despite the widespread use of photodynamic therapy in clinical practice, there is a lack of personalized methods for assessing the sufficiency of photodynamic exposure on tumors, depending on tissue parameters that change during light irradiation. This can lead to different treatment results. Aim: The objective of this article was to conduct a comprehensive review of devices and methods employed for the implicit dosimetric monitoring of personalized photodynamic therapy for tumors. Methods: The review included 88 peer-reviewed research articles published between January 2010 and April 2024 that employed implicit monitoring methods, such as fluorescence imaging and diffuse reflectance spectroscopy. Additionally, it encompassed computer modeling methods that are most often and successfully used in preclinical and clinical practice to predict treatment outcomes. The Internet search engine Google Scholar and the Scopus database were used to search the literature for relevant articles. Results: The review analyzed and compared the results of 88 peer-reviewed research articles presenting various methods of implicit dosimetry during photodynamic therapy. The most prominent wavelengths for PDT are in the visible and near-infrared spectral range such as 405, 630, 660, and 690 nm. Conclusions: The problem of developing an accurate, reliable, and easily implemented dosimetry method for photodynamic therapy remains a current problem, since determining the effective light dose for a specific tumor is a decisive factor in achieving a positive treatment outcome.

Simulating left atrial arrhythmias with an interactive N-body model.

BACKGROUND: Heart disease and strokes are leading global killers. While atrial arrhythmias are not deadly by themselves, they can disrupt blood flow in the heart, causing blood clots. These clots can travel to the brain, causing strokes, or to the coronary arteries, causing heart attacks. Additionally, prolonged periods of elevated heart rates can lead to structural and functional changes in the heart, ultimately leading to heart failure if untreated. The left atrium, with its more complex topology, is the primary site for complex arrhythmias. Much remains unknown about the causes of these arrhythmias, and computer modeling is employed to study them. METHODS: We use N-body modeling techniques and parallel computing to build an interactive model of the left atrium. Through user input, individual muscle attributes can be adjusted, and ectopic events can be placed to induce arrhythmias in the model. Users can test ablation scenarios to determine the most effective way to eliminate these arrhythmias. RESULTS: We set up muscle conditions that either spontaneously generate common arrhythmias or, with a properly timed and located ectopic event, induce an arrhythmia. These arrhythmias were successfully eliminated with simulated ablation. CONCLUSIONS: We believe the model could be useful to doctors, researchers, and medical students studying left atrial arrhythmias.

Effect of dispersive electrode position (anterior vs. posterior) in epicardial radiofrequency ablation of ventricular wall: A computer simulation study.

An epicardial approach is often used in radiofrequency (RF) catheter ablation to ablate ventricular tachycardia when an endocardial approach fails. Our objective was to analyze the effect of the position of the dispersive patch (DP) on lesion size using computer modeling during epicardial approach. We compared the posterior position (patient's back), commonly used in clinical practice, to the anterior position (patient's chest). The model considered ventricular wall thicknesses between 4 and 8 mm, and electrode insertion depths between .3 and .7 mm. RF pulses were simulated with 20 W of power for 30 s duration. Statistically significant differences (P < .001) were found between both DP positions in terms of baseline impedance, RF current (at 15 s) and thermal lesion size. The anterior position involved lower impedance (130.8 ± 4.7 vs. 146.2 ± 4.9 Ω) and a higher current (401.5 ± 5.6 vs. 377.5 ± 5.1 mA). The anterior position created lesion sizes larger than the posterior position: 8.9 ± 0.4 vs. 8.4 ± 0.4 mm in maximum width, 8.6 ± 0.4 vs. 8.1 ± 0.4 mm in surface width, and 4.5 ± 0.4 vs. 4.3 ± 0.4 mm in depth. Our results suggest that: (1) the redirection of the RF currents due to repositioning the PD has little impact on lesion size and only affects baseline impedance, and (2) the differences in lesion size are only 0.5 mm wider and 0.2 mm deeper for the anterior position, which does not seem to have a clinical impact in the context of VT ablation.

Formation of Amyloid-Like Conformational States of ß-Structured Membrane Proteins on the Example of OMPF Porin from the Yersinia pseudotuberculosis Outer Membrane.

The work presents results of the in vitro and in silico study of formation of amyloid-like structures under harsh denaturing conditions by non-specific OmpF porin of Yersinia pseudotuberculosis (YpOmpF), a membrane protein with ß-barrel conformation. It has been shown that in order to obtain amyloid-like porin aggregates, preliminary destabilization of its structure in a buffer solution with acidic pH at elevated temperature followed by long-term incubation at room temperature is necessary. After heating at 95°C in a solution with pH 4.5, significant conformational rearrangements are observed in the porin molecule at the level of tertiary and secondary structure of the protein, which are accompanied by the increase in the content of total ß-structure and sharp decrease in the value of characteristic viscosity of the protein solution. Subsequent long-term exposure of the resulting unstable intermediate YpOmpF at room temperature leads to formation of porin aggregates of various shapes and sizes that bind thioflavin T, a specific fluorescent dye for the detection of amyloid-like protein structures. Compared to the initial protein, early intermediates of the amyloidogenic porin pathway, oligomers, have been shown to have increased toxicity to the Neuro-2aCCL-131™ mouse neuroblastoma cells. The results of computer modeling and analysis of the changes in intrinsic fluorescence during protein aggregation suggest that during formation of amyloid-like aggregates, changes in the structure of YpOmpF affect not only the areas with an internally disordered structure corresponding to the external loops of the porin, but also main framework of the molecule, which has a rigid spatial structure inherent to ß-barrel.

Ablation catheter-induced mechanical deformation in myocardium: computer modeling and ex vivo experiments.

Cardiac catheter ablation requires an adequate contact between myocardium and catheter tip. Our aim was to quantify the relationship between the contact force (CF) and the resulting mechanical deformation induced by the catheter tip using an ex vivo model and computational modeling. The catheter tip was inserted perpendicularly into porcine heart samples. CF values ranged from 10 to 80 g. The computer model was built to simulate the same experimental conditions, and it considered a 3-parameter Mooney-Rivlin model based on hyper-elastic material. We found a strong correlation between the CF and insertion depth (ID) (R2 = 0.96, P < 0.001), from 0.7 ± 0.3 mm at 10 g to 6.9 ± 0.1 mm at 80 g. Since the surface deformation was asymmetrical, two transversal diameters (minor and major) were identified. Both diameters were strongly correlated with CF (R2 ≥ 0.95), from 4.0 ± 0.4 mm at 20 g to 10.3 ± 0.0 mm at 80 g (minor), and from 6.4 ± 0.7 mm at 20 g to 16.7 ± 0.1 mm at 80 g (major). An optimal fit between computer and experimental results was achieved, with a prediction error of 0.74 and 0.86 mm for insertion depth and mean surface diameter, respectively.

Impact of surrounding tissue-type and peri-electrode gap in stereoelectroencephalography guided (SEEG) radiofrequency thermocoagulation (RF-TC): a computational study.

PURPOSE: To use computational modeling to provide a complete and logical description of the electrical and thermal behavior during stereoelectroencephalography-guided (SEEG) radiofrequency thermo-coagulation (RF-TC). METHODS: A coupled electrical-thermal model was used to obtain the temperature distributions in the tissue during RF-TC. The computer model was first validated by an ex vivo model based on liver fragments and later used to study the impact of three different factors on the coagulation zone size: 1) the difference in the tissue surrounding the electrode (gray/white matter), 2) the presence of a peri-electrode gap occupied by cerebrospinal fluid (CSF), and 3) the energy setting used (power-duration). RESULTS: The model built for the experimental validation was able to predict both the evolution of impedance and the short diameter of the coagulation zone (error < 0.01 mm) reasonably well but overestimated the long diameter by 2 - 3 mm. After adapting the model to clinical conditions, the simulation showed that: 1) Impedance roll-off limited the coagulation size but involved overheating (around 100 °C); 2) The type of tissue around the contacts (gray vs. white matter) had a moderate impact on the coagulation size (maximum difference 0.84 mm), and 3) the peri-electrode gap considerably altered the temperature distributions, avoided overheating, although the diameter of the coagulation zone was not very different from the no-gap case (<0.2 mm). CONCLUSIONS: This study showed that computer modeling, especially subject- and scenario-specific modeling, can be used to estimate in advance the electrical and thermal performance of the RF-TC in brain tissue.

Optimizing inferior vena cava filter design: A computational fluid dynamics study on strut configuration for enhanced hemodynamic performance and thrombosis reduction.

Background and objective: Inferior vena cava filters have been shown to be effective in preventing deep vein thrombosis and its secondary complication, pulmonary embolism, thereby reducing the high mortality rate. Although inferior vena cava filters have evolved, specific complications like inferior vena cava thrombosis-induced deep vein thrombosis worsening and recurrent pulmonary embolism continue to pose challenges. This study analyzes the effects of geometric parameter variations of inferior vena cava filters, which have a significant impact on the thrombus formation inside the filter, the capture, dissolution, and hemodynamic flow of thrombus, as well as the shear stress on the filter and vascular wall. Methods: This study used computational fluid dynamic simulations with the carreau model to investigate the impact of varying inferior vena cava filter design parameters (number of struts, strut arm length, and tilt angle) on hemodynamics. Results: Recirculation and stagnation areas due to flow velocity and pressure, along with wall shear stress values, were identified as key factors. It is important to find a balance between wall shear stress high enough to aid thrombolysis and low enough to prevent platelet activation. The results of this paper show that the risk of platelet activation and thrombus filtration may be lowest when the wall shear stress of the filter ranges from 0 to 4 [Pa], minimizing stress concentration within the filter. Conclusion: 16 arm struts with a length of 20 mm and a tilt angle of 0° provide the best balance between thrombus capture and minimization of hemodynamic disturbance. This configuration minimizes the size of the stagnation and recirculation zones while maintaining sufficient wall shear stress for thrombus dissolution.

A His bundle pacing protocol for suppressing ventricular arrhythmia maintenance and improving defibrillation efficacy.

BACKGROUND: The excitable gap (EG), defined as the excitable tissue between two subsequent wavefronts of depolarization, is critical for maintaining reentry that underlies deadly ventricular arrhythmias. EG in the His-Purkinje Network (HPN) plays an important role in the maintenance of electrical wave reentry that underlies these arrhythmias. OBJECTIVE: To determine if rapid His bundle pacing (HBP) during reentry reduces the amount of EG in the HPN and ventricular myocardium to suppress reentry maintenance and/or improve defibrillation efficacy. METHODS: In a virtual human biventricular model, reentry was initiated with rapid line pacing followed by HBP delivered for 3, 6, or 9 s at pacing cycle lengths (PCLs) ranging from 10 to 300 ms (n=30). EG was calculated independently for the HPN and myocardium over each PCL. Defibrillation efficacy was assessed for each PCL by stimulating myocardial surface EG with delays ranging from 0.25 to 9 s (increments of 0.25 s, n=36) after the start of HBP. Defibrillation was successful if reentry terminated within 1 s after EG stimulation. This defibrillation protocol was repeated without HBP. To test the approach under different pathological conditions, all protocols were repeated in the model with right (RBBB) or left (LBBB) bundle branch block. RESULTS: Compared to without pacing, HBP for >3 seconds reduced average EG in the HPN and myocardium across a broad range of PCLs for the default, RBBB, and LBBB models. HBP >6 seconds terminated reentrant arrhythmia by converting HPN activation to a sinus rhythm behavior in the default (6/30 PCLs) and RBBB (7/30 PCLs) models. Myocardial EG stimulation during HBP increased the number of successful defibrillation attempts by 3%-19% for 30/30 PCLs in the default model, 3%-6% for 14/30 PCLs in the RBBB model, and 3%-11% for 27/30 PCLs in the LBBB model. CONCLUSION: HBP can reduce the amount of excitable gap and suppress reentry maintenance in the HPN and myocardium. HBP can also improve the efficacy of low-energy defibrillation approaches targeting excitable myocardium. HBP during reentrant arrhythmias is a promising anti-arrhythmic and defibrillation strategy.

Electrophysiological patterns and structural substrates of Brugada syndrome: Critical appraisal and computational analyses.

Brugada syndrome (BrS) is a cardiac electrophysiological disease with unknown etiology, associated with sudden cardiac death. Symptomatic patients are treated with implanted cardiac defibrillator, but no risk stratification strategy is effective in patients that are at low to medium arrhythmic risk. Cardiac computational modeling is an emerging tool that can be used to verify the hypotheses of pathogenesis and inspire new risk stratification strategies. However, to obtain reliable results computational models must be validated with consistent experimental data. We reviewed the main electrophysiological and structural variables from BrS clinical studies to assess which data could be used to validate a computational approach. Activation delay in the epicardial right ventricular outflow tract is a consistent finding, as well as increased fibrosis and subclinical alterations of right ventricular functional and morphological parameters. The comparison between other electrophysiological variables is hindered by methodological differences between studies, which we commented. We conclude by presenting a recent theory unifying electrophysiological and structural substrate in BrS and illustrate how computational modeling could help translation to risk stratification.

Cell-to-cell heterogeneity in ion channel conductance impacts substrate vulnerability to arrhythmia.

Determining whether an ectopic depolarization will lead to a self-perpetuating arrhythmia is of critical importance in determining arrhythmia risk, so it is necessary to understand what factors impact substrate vulnerability. This study sought to explore the impact of cell-to-cell heterogeneity in ion channel conductance on substrate vulnerability to arrhythmia by measuring the duration of the vulnerable window in computational models of one-dimensional cables of ventricular cardiomyocytes. We began by using a population of uniform cable models to determine the mechanisms underlying the vulnerable window phenomenon. We found that in addition to the known importance of GNa, the conductances GCa,L and GKr also play a minor role in determining the vulnerable window duration. We also found that a steeper slope of the repolarizing action potential during the vulnerable window correlated with a shorter vulnerable window duration in uniform cables. We applied our understanding from these initial simulations to an investigation of the vulnerable window in heterogeneous cable models. The heterogeneous cables displayed a great deal of intra-cable variation in vulnerable window duration, highly sensitive to the cardiomyocytes in the local environment of the ectopic stimulus. Coupling strength modulated not only the magnitude of the vulnerable window duration but also the extent of intra-tissue variability in vulnerable window duration.NEW & NOTEWORTHY We investigate the impact of cell-to-cell heterogeneity in ion channel conductance on substrate vulnerability to arrhythmia by measuring the vulnerable window duration in computational cardiomyocyte cable models. We demonstrate a wide range of intra-cable variability in vulnerable window duration (VWD) and show how this is changed by ion channel block and coupling strength perturbations.

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies.

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimental data can become a significant computational burden. To mitigate the computational burden, the present study introduces a neural network (NN) that emulates the AP for given maximum conductances of selected ion channels, pumps, and exchangers. Its applicability in pharmacological studies was tested on synthetic and experimental data. The NN emulator potentially enables massive speed-ups compared to regular simulations and the forward problem (find drugged AP for pharmacological parameters defined as scaling factors of control maximum conductances) on synthetic data could be solved with average root-mean-square errors (RMSE) of 0.47 mV in normal APs and of 14.5 mV in abnormal APs exhibiting early afterdepolarizations (72.5% of the emulated APs were alining with the abnormality, and the substantial majority of the remaining APs demonstrated pronounced proximity). This demonstrates not only very fast and mostly very accurate AP emulations but also the capability of accounting for discontinuities, a major advantage over existing emulation strategies. Furthermore, the inverse problem (find pharmacological parameters for control and drugged APs through optimization) on synthetic data could be solved with high accuracy shown by a maximum RMSE of 0.22 in the estimated pharmacological parameters. However, notable mismatches were observed between pharmacological parameters estimated from experimental data and distributions obtained from the Comprehensive in vitro Proarrhythmia Assay initiative. This reveals larger inaccuracies which can be attributed particularly to the fact that small tissue preparations were studied while the emulator was trained on single cardiomyocyte data. Overall, our study highlights the potential of NN emulators as powerful tool for an increased efficiency in future quantitative systems pharmacology studies.

Translating myosin-binding protein C and titin abnormalities to whole-heart function using a novel calcium-contraction coupling model.

Mutations in cardiac myosin-binding protein C (cMyBP-C) or titin may respectively lead to hypertrophic (HCM) or dilated (DCM) cardiomyopathies. The mechanisms leading to these phenotypes remain unclear because of the challenge of translating cellular abnormalities to whole-heart and system function. We developed and validated a novel computer model of calcium-contraction coupling incorporating the role of cMyBP-C and titin based on the key assumptions: 1) tension in the thick filament promotes cross-bridge attachment mechanochemically, 2) with increasing titin tension, more myosin heads are unlocked for attachment, and 3) cMyBP-C suppresses cross-bridge attachment. Simulated stationary calcium-tension curves, isotonic and isometric contractions, and quick release agreed with experimental data. The model predicted that a loss of cMyBP-C function decreases the steepness of the calcium-tension curve, and that more compliant titin decreases the level of passive and active tension and its dependency on sarcomere length. Integrating this cellular model in the CircAdapt model of the human heart and circulation showed that a loss of cMyBP-C function resulted in HCM-like hemodynamics with higher left ventricular end-diastolic pressures and smaller volumes. More compliant titin led to higher diastolic pressures and ventricular dilation, suggesting DCM-like hemodynamics. The novel model of calcium-contraction coupling incorporates the role of cMyBP-C and titin. Its coupling to whole-heart mechanics translates changes in cellular calcium-contraction coupling to changes in cardiac pump and circulatory function and identifies potential mechanisms by which cMyBP-C and titin abnormalities may develop into HCM and DCM phenotypes. This modeling platform may help identify distinct mechanisms underlying clinical phenotypes in cardiac diseases.

The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions.

Mammalian cytosolic thioredoxin reductase (TrxR1) serves as an antioxidant protein by transferring electrons from NADPH to various substrates. The action of TrxR1 is achieved via reversible changes between NADPH-reduced and non-reduced forms, which involves C-terminal selenolthiol/selenenylsulfide exchanges. TrxR1 may be released into extracellular environment, where TrxR1 is present mainly in the non-reduced form with active-site disulfide and selenenylsulfide bonds. The relationships between extracellular TrxR1 and tumor metastasis or cellular signaling have been discovered, but there are few reports on small-molecule compounds in targeted the non-reduced form of TrxR1. Using eight types of small-molecule thiol-reactive reagents as electrophilic models, we report that the selenenylsulfide bond in the non-reduced form of TrxR1 functions as a selector for the thiol-reactive reagents at pH 7.5. The non-reduced form of TrxR1 is resistant to hydrogen peroxide/oxidized glutathione, but is sensitive to certain electrophilic reagents in different ways. With 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) and S-nitrosoglutathione (GSNO), the polarized selenenylsulfide bond breaks, and selenolate anion donates electron to the dynamic covalent bond in DTNB or GSNO, forming TNB-S-Se-TrxR1 complex or ON-Se-TrxR1 complex. The both complexes lose the ability to transfer electrons from NADPH to substrate. For diamide, the non-reduced TrxR1 actually prevents irreversible damage by this oxidant. This is consistent with the regained activity of TrxR1 through removal of diamide via dialysis. Diamide shows effective in the presence of human cytosolic thioredoxin (hTrx1), Cys residue(s) of which is/are preferentially affected by diamide to yield disulfide, hTrx1 dimer and the mixed disulfide between TrxR1-Cys497/Sec498 and hTrx1-Cys73. In human serum samples, the non-reduced form of TrxR1 exists as dithiothreitol-reducible polymer/complexes, which might protect the non-reduced TrxR1 from inactivation by certain electrophilic reagents under oxidative conditions, because cleavage of these disulfides can lead to regain the activity of TrxR1. The details of the selective response of the selenenylsulfide bond to electrophilic reagents may provide new information for designing novel small-molecule inhibitors (drugs) in targeted extracellular/non-reduced TrxR1.

Dendritic effects of tDCS insights from a morphologically realistic model neuron.

Transcranial direct current stimulation (tDCS) induces subcellular compartmental-dependent polarization, maximal in the distal portions of axons and dendrites. Using a morphologically realistic neuron model, we simulated tDCS-induced membrane polarization of the apical dendrite. Thus, we investigated the differential dendritic effects of anodal and cathodal tDCS on membrane potential polarization along the dendritic structure and its subsequent effects on dendritic membrane resistance, excitatory postsynaptic potential amplitude, backpropagating action potential amplitude, input/output relations, and long-term synaptic plasticity. We further showed that the effects of anodal and cathodal tDCS on the backpropagating action potential were asymmetric, and explained this asymmetry. Additionally, we showed that the effects on input/output relations were rather weak and limited to the low-mid range of stimulation frequencies, and that synaptic plasticity effects were mostly limited to the distal portion of the dendrite. Thus, we demonstrated how tDCS modifies dendritic physiology due to the dendrite's unique morphology and composition of voltage-gated ion channels.

Fully angularly resolved 3D microrheology with optical tweezers.

Microrheology with optical tweezers (MOT) is an all-optical technique that allows the user to investigate a materials' viscoelastic properties at microscopic scales, and is particularly useful for those materials that feature complex microstructures, such as biological samples. MOT is increasingly being employed alongside 3D imaging systems and particle tracking methods to generate maps showing not only how properties may vary between different points in a sample but also how at a single point the viscoelastic properties may vary with direction. However, due to the diffraction limited shape of focussed beams, optical traps are inherently anisotropic in 3D. This can result in a significant overestimation of the fluids' viscosity in certain directions. As such, the rheological properties can only be accurately probed along directions parallel or perpendicular to the axis of trap beam propagation. In this work, a new analytical method is demonstrated to overcome this potential artefact. This is achieved by performing principal component analysis on 3D MOT data to characterise the trap, and then identify the frequency range over which trap anisotropy influences the data. This approach is initially applied to simulated data for a Newtonian fluid where the trap anisotropy induced maximum error in viscosity is reduced from ~ 150% to less than 6%. The effectiveness of the method is corroborated by experimental MOT measurements performed with water and gelatine solutions, thus confirming that the microrheology of a fluid can be extracted reliably across a wide frequency range and in any arbitrary direction. This work opens the door to fully spatially and angularly resolved 3D mapping of the rheological properties of soft materials over a broad frequency range.