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Manual welding and hemming processes don’t deliver higher speeds and efficiency resulting in reduced production rate. Hence, robotic hemming and welding processes are to be implemented to overcome the risk involved in manual welding and achieving greater efficiency. Based on the present system layout in a local automotive industry, a virtual work cell was created with various robot models, fixtures and work tools like clamps, welding guns, rollers, etc. The robot operations were simulated and checked for collision, zoning and the cycle time which was estimated for both the virtual and real work environment. The simulated work cell was replicated in the real environment and checked for any discrepancies with the virtual work cell. The estimated total process time of various processes carried out in the closure panel assembly line by both the automated method and conventional method was compared and the percentage reduction in the total process time was determined.

We present here a new insight into the chemical reactivity and bioactivity of dopamine (DA) and gallic acid (GA) and their hyaluronic acid (HA) conjugates. Our data suggest that HA-GA scaffolds are superior to HA-DA, with higher oxidation kinetics, improved tissue adhesive properties, and radical scavenging ability with a lower pro-inflammatory response. This journal is, QC 20220309

Tauopathies are a subclass of neurodegenerative diseases characterized by an accumulation of microtubule binding tau fibrils in brain regions. Diseases such as Alzheimer's (AD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and corticobasal degeneration (CBD) belong to this subclass. Development of tracers which can visualize and discriminate between different tauopathies is of clinical importance in the diagnosis of various tauopathies. Currently, several tau tracers are available for in vivo imaging using a positron emission tomography (PET) technique. Among these tracers, PBB3 is reported to bind to various types of tau fibrils with comparable binding affinities. In contrast, tau tracer AV-1451 is reported to bind to specific types of tau fibrils (in particular to AD-associated and CTE) with higher binding affinity and only show nonspecific or weaker binding toward tau fibrils dominant with 3R isoforms (associated with PiD). The tau fibrils associated with different tauopathies can adopt different microstructures with different binding site microenvironments. By using detailed studies of the binding profiles of tau tracers for different types of tau fibrils, it may be possible to design tracers with high selectivity toward a specific tauopathy. The microstructures for the tau fibrils from patients with AD, PiD, and CTE have recently been demonstrated by cryogenic electron microscopy (cryo-EM) measurements allowing structure-based in silico simulations. In the present study, we have performed a multiscale computational study involving molecular docking, molecular dynamics, free energy calculations, and QM fragmentation calculations to understand the binding profiles of tau tracer AV-1451 and its potential use for diagnosis of AD, CTE, and PiD tauopathies. Our computational study reveals that different affinity binding sites exist for AV-1451 in the tau fibrils associated with different tauopathies. The binding affinity of this tracer toward differe

Abnormal deposition of hyperphosphorylated tau as neurofibrillary tangles (NFTs) is an important pathological hallmark of Alzheimer's disease (AD) and of other neurodegenerative disorders. A noninvasive positron emission tomography (PET) tracer that quantifies neurofibrillary tangles in vivo can enhance the clinical diagnosis of AD and can also be used to evaluate the efficacy of therapeutics aimed at reducing the abnormal aggregation of the tau fibril in the brain. In this paper, we study the binding profile of fibrillar tau aggregates with a PET tracer PI2620, which is a new second generation tau PET tracer that is presently experimentally and clinically studied. The target structure for the tau fibril is based on cryo-electron microscopy (cryo-EM) structure. A multiscale simulation workflow including molecular docking, molecular dynamics simulation, metadynamics simulation, and free energy calculations was implemented. We find that PI2620 can bind to eight surface binding sites, three core binding sites, and one entry site. The binding at the core sites and entry site is found to be much more favorable than that on the surface sites due to stronger hydrophobic interactions and less solvent exposure. Furthermore, the entry site which is formed by the terminal beta-sheets of the fibril is found to have the highest binding affinity to PI2620. Importantly, the binding capacity at the entry site can be much higher than that at other core sites, due to its easy accessibility. Therefore, the entry site is believed to be the major binding site for PI2620. A previous computational study on tracers with tau fibrils reports a maximum of four binding sites. Through use of methods that allow us to locate "cryptic binding sites", we report here additional core sites available for binding and we address the limitation of using the cryo-EM structure alone for structure-based tracer design. Our results could be helpful for elucidating the binding mechanism of imaging tracers with, QC 20200525