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Heritable forms of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) represent starkly diverging clinical phenotypes, yet may be caused by mutations to the same sarcomeric protein. The precise mechanisms by which point mutations within the same gene bring about phenotypic diversity remain unclear. Our objective was to develop a mechanistic explanation of diverging phenotypes in two TPM1 mutations, E62Q (HCM) and E54K (DCM). Drawing on data from the literature and experiments with stem cell-derived cardiomyocytes expressing the TPM1 mutations of interest, we constructed computational simulations that provide plausible explanations of the distinct muscle contractility caused by each variant. In E62Q, increased calcium sensitivity and hypercontractility was explained most accurately by a reduction in effective molecular stiffness of tropomyosin and alterations in its interactions with the actin thin filament that favor the \"closed\" regulatory state. By contrast, the E54K mutation appeared to act via long-range allosteric interactions to increase the association rate of the C-terminal troponin I mobile domain to tropomyosin/actin. These mutation-linked molecular events produced diverging alterations in gene expression that can be observed in human engineered heart tissues. Modulators of myosin activity confirmed our proposed mechanisms by rescuing normal contractile behavior in accordance with predictions.

A quinoline-derived Schiff base ligand, namely 2,5-Dimethyl-N1,N4-bis((quinoline-4-yl)-methylene) benzene-1,4-diamine 1 was characterized by single crystal X-ray structural studies that included a thorough examination of visualizing and investigating intermolecular interactions in molecular crystals via the Hirshfeld surface. The crystal packing of 1 displays intermolecular π∙∙∙π stacking interactions, resulting in a one-dimensional array. The major role of π∙∙∙π stacking interactions in stabilizing the crystal is also supported by the pre-eminence of dispersion energy over the other components in interaction energy calculation and energy framework analysis. The electronic structure of the ligand computed at B3LYP/6-311++G( d , p ) level shows a good correlation with the experimentally obtained structure. Additionally, the Fukui function is calculated to identify the electrophilic and nucleophilic active sites in the molecule.

Highlights The goal is to optimize the microsponge drug delivery system’s preparation. Scaling up ensures product repeatability. FTIR, DSC, and SEM confirmed the drug-loaded microsponge particles’ compatibility and porous shape. The final gel dosage had shear-thinning rheology, suggesting dermal use. Ultimately, it supports and advances the UN’s sustainable development goals and G20. In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5–300 μm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative. Graphical Abstract

Brain–computer interfaces (BCIs) enable people with paralysis to communicate with their environment. Motor imagery can be used to generate distinct patterns of cortical activation in the electroencephalogram (EEG) and thus control a BCI. To elucidate the cortical correlates of BCI control, users of a sensory motor rhythm (SMR)-BCI were classified according to their BCI control performance. In a second session these participants performed a motor imagery, motor observation and motor execution task in a functional magnetic resonance imaging (fMRI) scanner. Group difference analysis between high and low aptitude BCI users revealed significantly higher activation of the supplementary motor areas (SMA) for the motor imagery and the motor observation tasks in high aptitude users. Low aptitude users showed no activation when observing movement. The number of activated voxels during motor observation was significantly correlated with accuracy in the EEG-BCI task (r=0.53). Furthermore, the number of activated voxels in the right middle frontal gyrus, an area responsible for processing of movement observation, correlated (r=0.72) with BCI-performance. This strong correlation highlights the importance of these areas for task monitoring and working memory as task goals have to be activated throughout the BCI session. The ability to regulate behavior and the brain through learning mechanisms involving imagery such as required to control a BCI constitutes the consequence of ideo-motor co-activation of motor brain systems during observation of movements. The results demonstrate that acquisition of a sensorimotor program reflected in SMR-BCI-control is tightly related to the recall of such sensorimotor programs during observation of movements and unrelated to the actual execution of these movement sequences. ► Brain processes during observation of movement predict SMR-BCI aptitude. ► BCI aptitude is unrelated to brain processes during execution of movement. ► Higher activation in SMA of high aptitude users during imagery and observation tasks. ► Higher activation in middle frontal gyrus of high aptitude users during observation.

Despite recent successes, patients suffering from locked-in syndrome (LIS) still struggle to communicate using vision-independent brain–computer interfaces (BCIs). In this study, we compared auditory and tactile BCIs, regarding training effects and cross-stimulus-modality transfer effects, when switching between stimulus modalities. We utilized a streaming-based P300 BCI, which was developed as a low workload approach to prevent potential BCI-inefficiency. We randomly assigned 20 healthy participants to two groups. The participants received three sessions of training either using an auditory BCI or using a tactile BCI. In an additional fourth session, BCI versions were switched to explore possible cross-stimulus-modality transfer effects. Both BCI versions could be operated successfully in the first session by the majority of the participants, with the tactile BCI being experienced as more intuitive. Significant training effects were found mostly in the auditory BCI group and strong evidence for a cross-stimulus-modality transfer occurred for the auditory training group that switched to the tactile version but not vice versa. All participants were able to control at least one BCI version, suggesting that the investigated paradigms are generally feasible and merit further research into their applicability with LIS end-users. Individual preferences regarding stimulus modality should be considered.

In this work, the mechanical and fracture performance of epoxy nanocomposites consisting of epoxide and imidazole functionalized silica nanoparticles has been studied. The post-synthesis grafting method was utilized to functionalized SiO2 nanoparticles with GPTMS (GGS) and used them as reinforcement (0-2 wt%) in epoxy resin. The cure behavior of nanocomposites demonstrated that the composite has excellent cure capability at 0.5 wt% of GGS. The composite containing 0.5 wt% of GGS exhibited significant improvement in tensile strength (~65 %) and modulus of toughness (~272 %), respectively. Additionally, the flexural strength, flexural modulus, and work of flexural were enhanced by ~48, ~50, and ~48%, respectively. Interestingly, the GGS showed its tremendous potential to improve the fracture toughness (K1C) and the fracture energy (G1C) of the nanocomposite by ~97 and ~292 %, which is also evident by the study of cure behavior. The fractography analysis endorsed the enhancement of material properties due to the use of GGS in the epoxy matrix. Failure investigation examined under FESEM elucidated forced the crack to move around the poles of the nanoparticles due to better interfacial adhesion. Hence, GGS nanoparticle has the potential to use as an excellent cost-effective reinforcement for the epoxy matrix to mitigate the brittle failure in epoxy composites.

Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. This confirms that structural brain traits contribute to individual performance in BCI use.

A new coordination compound of Co(II) [Co(pydc) 2 ](pydcH 2 )(Hapy)(H 2 O) 5 ( 1 ) (where, pydcH 2  = pyridine-2,6-dicarboxylic acid; Hapy = protonated 2- aminopyridine) was synthesized and characterized by single crystal X-ray diffraction (SC-XRD) analyses. Crystallographic analysis (CIF file CCDC no. 2236169) revealed that complex 1 has distorted octahedral geometry with pydc coordinated as a tridentate ligand to a metal ion. The electronic structure of the complex was determined using DFT calculations with pseudo potential of LANL2DZ basis function for Cobalt atom while B3LYP/GEN level using 6-31+G* basis set for other atoms. The optimized structure can reproduce the crystal structure with good accuracy at this computational level. Frontier molecular orbital analysis and molecular electrostatic potential (MEP) have been evaluated to understand the reactivity characteristics of the complex. Natural bond orbital analysis illustrates the charge transfer between the donor and acceptor sites of the investigated complex. Further, the intermolecular contacts of the complex areanalyzed through Hirshfeld surface analysis and finger print plots.

Self-healing polymers are the materials which can heal the internal cracks or damages automatically without any external intervention. The concept of self-healing has been derived from the biological systems such as human bone or skin which can heal automatically. This paper reviews the self-healing polymers based on Diels-Alder reaction where diene and dienophile groups form reversible covalent bond between them in the polymer matrix. A comprehensive review on Diels-Alder based self-healing composites reinforced with nano-fillers from the last decade have been reported here. The present status followed by future scope in this area has also been discussed briefly at the end of this review.

The spatio-temporal variability of Indian Summer Monsoon is well studied based on different types of rainfall data. However, very few attempts have been made to study the underlying role of clouds and its hydrometeors on Monsoon Intraseasonal Oscillations. The northward propagating Monsoon Intraseasonal Oscillations and its characteristics remain a challenge for the numerical modelers even today. In view of this, we have set out to analyze the role of cloud hydrometeors and their linkage with northward propagating Monsoon Intraseasonal Oscillations. The science question that we intend to address here is whether the different phases of the cloud hydrometeors show similar propagation characteristics as that of rainfall, and what are the relations of their phases with the convection centre using Tropical Rainfall Measuring Mission data. In answering the question, we have analyzed ten years of Tropical Rainfall Measuring Mission 2A12 hydrometeor data over Indian region. Our analyses show that the cloud water and cloud ice do show a large scale organization during the Indian Summer Monsoon regime of June–September, and systematically progress northward getting initiated over equatorial Indian Ocean. On further analyses, we found that cloud water actually leads the rainfall and cloud ice lags the rainfall. We have further demonstrated the process by analyzing dynamical parameters from Modern Era-Retrospective Analysis for Research and Applications. The presence of cloud water in the lower troposphere in the leading edge of rainfall indicates the lower level moistening and preconditioning of the convective instability due to enhanced moisture convergence. Subsequently, deep convection is triggered, which generates hydrometeor above freezing level and cloud ice in the upper troposphere. To quantify objectively the relation among cloud liquid water, cloud ice and rainfall, the lag correlation is computed with respect to convection center, where the above hypothesis is established that cloud liquid water leads the rainfall and cloud ice lag. This relation among hydrometeors may help the numerical modelers to incorporate such processes for capturing the characteristics of Monsoon Intraseasonal Oscillations.