Mechanosensitive response of voltage-gated ion channels

Neurons communicate via a traveling wave of electrical excitation that propagates down an axon at speeds in the range of 10–100 m/s. This electrical wave is triggered and regulated by opening and closing of voltage-gated ion channels. These channels have been traditionally believed to be sensitive to the local electrochemical environment. A growing number of experiments now conclusively show that lipid-associated mechanical stimuli can control the channel response. We develop a quantitative model to elucidate the mechanosensitivity exhibited by these channels. With the help of a single model, we are able able to consolidate the findings of the various experimental studies that have investigated the effect of different mechanical stimuli

Elucidating the mechanics of clathrin-mediated endocytosis

Clathrin-mediated endocytosis (CME) is a key metabolic pathway that plays a central role in the delivery of nutrients and drug carriers into cells. In this study, we model the interactions of lipid membranes with different types of protein scaffolds and active forces to provide mechanistic insights into CME. To this end, we develop and employ an extended theoretical framework of lipid membranes that entertains spatial heterogeneity and local anisotropy that could arise from membrane–protein interactions. We show that a departure from homogeneity and isotropy can lead to a variable surface tension field, conventionally assumed to be a constant parameter. We model the impact of resting tension in a cell and discuss its consequences on the minimal protein machinery needed to complete vesicle formation. Based on our quantitative model and findings, we highlight the physical principles that unify CME in apparently distinct yeast and mammalian cells

ISLTranslate: Dataset for Translating Indian Sign Language

Sign languages are the primary means of communication for many hard-of-hearing people worldwide. Recently, to bridge the communication gap between the hard-of-hearing community and the rest of the population, several sign language translation datasets have been proposed to enable the development of statistical sign language translation systems. However, there is a dearth of sign language resources for the Indian sign language. This resource paper introduces ISLTranslate, a translation dataset for continuous Indian Sign Language (ISL) consisting of 31k ISL-English sentence/phrase pairs. To the best of our knowledge, it is the largest translation dataset for continuous Indian Sign Language. We provide a detailed analysis of the dataset. To validate the performance of existing end-to-end Sign language to spoken language translation systems, we benchmark the created dataset with a transformer-based model for ISL translation.Comment: Accepted at ACL 2023 Findings, 8 Page

A Study of Fuzzy Continuous Mappings

The paperndeals with the conceptnof semi-compactness in thengeneralized setting of a fuzzyntopological space.We achievena number of characterizationsnof a fuzzynsemi-compact space.The notionnof semi-compactness is furthernextended to arbitrary fuzzyntopological sets.Such fuzzynsets are formulated inndifferent ways and a fewnpertinent properties are discussed.Finallynwe compare semi-compact fuzzynsets with some ofnthe existing types ofncompact-like fuzzynsets.We ultimately shownthat so far as thenmutual relationships among differentnexisting allied classes of fuzzynsets are concerned,thenclass of semi-compact fuzzynsets occupies a naturalnposition in the hierarchy.Thenpurpose of this papernis to introduce thenconcepts of semi*-connectednspaces, semi*compactnspaces.We investigate theirnbasic properties. We alsondiscuss their relationship withnalready existing concepts

Pectoralis major myocutaneous flap in head and neck reconstruction: an interesting experience from central India regional cancer center

Background: Head and neck cancer are sixth most common cancers worldwide with cancer of oral cavity most common. The primary treatment modality for oral cavity cancer has been surgery and defects resulting from the ablation of the tumors require reconstruction. the PMMC flap offer an easy, less time consuming with minimal postoperative complication as a reconstructive option in the hands of reconstructive surgeon. The objective of our study was to give a precise description of our experience with the PMMC flap as a reconstructive option in post-ablative head and cancer surgery.Methods: The current prospective study was conducted in the Department of Surgical Oncology, Regional cancer center, Pt. JNMC, Raipur (C.G.), India from the January 2014 to June 2015. Detailed clinical history and examination of the patients were recorded. All Investigations relevant to the study were done before the surgical procedure. Procedure was performed as per standard protocol and reconstruction was made with PMMC flap. Data was compiled in MS Excel and checked for its completeness and correctness. Then it was analyzed.Results: In the present study male to female ratio was 2:1. Most of the patients belongs to the age group of 41-60 (55.55%) followed by 21-40 (30.15%). In the present study majority of patient of oral malignancy presented with lower alveolus malignancy (36.5%) followed by buccal mucosa malignancy (19.06%).Conclusions: Pectoralis major myocutaneous flap was found to be a versatile flap for reconstruction of large defects in Head and Neck region with minimal complication rate.

Endothelium and subendothelial matrix mechanics modulate cancer cell transendothelial migration

Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin-rich protrusions generate complex push–pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.Peer ReviewedPostprint (published version