40 research outputs found

    Surface defects incorporated diamond machining of silicon

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    Abstract This paper reports the performance enhancement benefits in diamond turning of the silicon wafer by incorporation of the surface defect machining (SDM) method. The hybrid micromachining methods usually require additional hardware to leverage the added advantage of hybrid technologies such as laser heating, cryogenic cooling, electric pulse or ultrasonic elliptical vibration. The SDM method tested in this paper does not require any such additional baggage and is easy to implement in a sequential micro-machining mode. This paper made use of Raman spectroscopy data, average surface roughness data and imaging data of the cutting chips of silicon for drawing a comparison between conventional single-point diamond turning (SPDT) and SDM while incorporating surface defects in the (i) circumferential and (ii) radial directions. Complementary 3D finite element analysis (FEA) was performed to analyse the cutting forces and the evolution of residual stress on the machined wafer. It was found that the surface defects generated in the circumferential direction with an interspacing of 1 mm revealed the lowest average surface roughness (Ra) of 3.2 nm as opposed to 8 nm Ra obtained through conventional SPDT using the same cutting parameters. The observation of the Raman spectroscopy performed on the cutting chips showed remnants of phase transformation during the micromachining process in all cases. FEA was used to extract quantifiable information about the residual stress as well as the sub-surface integrity and it was discovered that the grooves made in the circumferential direction gave the best machining performance. The information being reported here is expected to provide an avalanche of opportunities in the SPDT area for low-cost machining solution for a range of other nominal hard, brittle materials such as SiC, ZnSe and GaAs as well as hard steels.</jats:p

    The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86

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    Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response

    Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection

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    The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called ‘FLip’ mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86

    A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity.

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    BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility

    A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75

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    Variants of SARS CoV-2 have caused successive global waves of infection. These variants, with multiple mutations in the spike protein are thought to facilitate escape from natural and vaccine-induced immunity and often increase in the affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor binding domain (RBD). Here we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared to BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection which may explain the rapid spread in India, where BA.2.75 is now the dominant variant. ACE2 affinity appears to be prioritised over greater escape

    Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

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    The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections

    Method to protect Human hearing ability from Impact sound & Dynamic gain correction using ML technique to preserve the Hearing sensitivity

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    In this document Hearing protection issue is analyzed and taken the critical problem statement to provide the product solution. The product solution finalized with one audio CODEC and FPGA board to demonstrate POC(Proof of concept) This POC targeted to do with the actual acoustical transducer Microphone and the speaker that will be used in real product. The motivation of working on this product idea is to apply the industrial domain understanding and taking the most critical functional need for the Hearing protection as problem statement. This Problem statement carefully analyzed and the product solution is concluded with working POC. The same content briefed above is taken for the detail update in following chapters with the required supporting text, POC setup details, the method of audio signal handling, Algorithm, Few techniques based on the real world application, Audio processor configuration and Probed data

    Assessment of Environmentally Sensitive Area and Desertification Severity using GIS for an Indian Region - Virudhunagar District, Tamil Nadu

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    1734-1741Desertification is one of the fundamental hazards threatening the arid and semi-arid regions on ecological as well as economic perspective. Mapping and quantifying the land degradation have become urgent tasks in order to avoid the depletion or deterioration of the resources we need to know the causes for the depletion. In this study, the desertification status and the severity of desertification were studied using remote sensing and field data at Virudhunagar district, Tamil Nadu region, in south India. Modified Medalus method was used to identify the ecological sensitive areas (ESA) with landuse, climatic controls, soil quality, ground water quality and demographic factors. A number of indexes were prepared from the above parameters and the severity was identified by Environmental Sensitivity Area Index (ESAI). The desertification severity was classified into three classes such as low, moderate and high. The desertification severity from 2003 to 2012 was increased from moderate (1.34) to severe (1.42) at Sivakasi and Srivilliputhur taluk, which is located in the western side of the study area. Results showed that climate and demographic pressure were the most important indicators for describing desertification process in the study area

    Molecular dynamics simulation approach to explore atomistic molecular mechanism of peroxidase activity of apoptotic cytochrome c mutants

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    Mutations in cytochrome c (Cyt c) have been reported in tuning peroxidase activity, which in-turn cause Cyt c release from mitochondria and early apoptosis. However, the molecular tuning mechanism underlying this activity remains elusive. Herein, multiple 20 ns molecular dynamics (MD) simulations of wild type (WT), Y67F and K72W mutated Cyt c in aqueous solutions have been carried out to study how the changes in structural features alters the peroxidase activity of the protein. MD simulation results indicate that Y67F mutation caused, (i) increased distances between critical electron-transfer residues, (ii) higher fluctuations in omega loops, and (iii) weakening of intraprotein hydrogen bonds result in open conformation at heme crevice loop in Cyt c leading to an enhanced peroxidase activity. Interestingly, the aforementioned structural features are strengthened in K72W compared to WT and Y67F, which triggers K72W mutated Cyt c into a poor peroxidase. Essential dynamics results unveil that first two eigenvectors are responsible for overall motions of WT, Y67F and K72W mutated Cyt c. This study thus provides atomic level insight into molecular mechanism of peroxidase activity of Cyt c, which will help in designing novel Cyt c structures that is more desirable than natural Cyt c for biomedical and industrial processe
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