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"Shekhar, Shashank"
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Apache Superset Quick Start Guide
by
Shekhar, Shashank
in
Apache (Computer file : Apache Group)-Handbooks, manuals, etc
,
COMPUTERS / Data Science / General
2018,2024
Apache Superset is a modern, open source, enterprise-ready Business Intelligence web application. This book will teach you how Superset integrates with popular databases like Postgres, Google BigQuery, Snowflake, and MySQL. You will learn to create real time data visualizations and dashboards on modern web browsers for your organization.
New perspectives on twinning events during strain-induced grain boundary migration (SIBM) in iteratively processed 316L stainless steel
by
Shekhar, Shashank
,
Sharma, Nitin Kumar
in
Analysis
,
Austenitic stainless steels
,
Characterization and Evaluation of Materials
2021
Characterization of microstructure and grain boundary character distribution (GBCD) during iterative thermo-mechanical processing (TMP) of 316L stainless steel were done using electron backscatter diffraction (EBSD). Results from EBSD scans were analyzed in terms of the fraction of special boundaries, their deviation from ideal misorientation, connectivity of random high-angle grain boundaries, and grain size. In order to understand the efficacy of the iterative processing route leading to a well-connected twin boundary network, additional analysis was done in terms of twin-related domain statistics and triple junction distribution. Results from these analyses show that initial iteration results in a microstructure with insufficient twin boundary density, and a poor twin boundary network. Although the next iteration leads to a small increase in twin statistics, it also does not significantly improve the statistics of favorable grain boundaries and their network. However, the fourth iteration of the processing results in a large improvement in both the population and distribution of favorable grain boundaries. All the subsequent iterations were found to result in microstructural deterioration in terms of both population and network of these grain boundaries. Based on the analysis, role of underlying mechanisms such as strain-induced grain boundary migration and static recrystallization in the effective optimization of GBCD was analyzed. The present research gives important insights into these mechanisms and their control during TMP in order to achieve an engineered microstructure.
Graphic abstract
Journal Article
Global treadmilling coordinates actin turnover and controls the size of actin networks
2017
In animal cells, actin is dynamically distributed between multiple coexisting arrays. Carlier and Shekhar propose that a global treadmilling process — whereby the various actin networks grow and shrink depending on the local activity of actin regulators — establishes a steady-state concentration of actin monomers that supports this homeostatic actin turnover.
Various cellular processes (including cell motility) are driven by the regulated, polarized assembly of actin filaments into distinct force-producing arrays of defined size and architecture. Branched, linear, contractile and cytosolic arrays coexist
in vivo
, and cells intricately control the number, length and assembly rate of filaments in these arrays. Recent
in vitro
and
in vivo
studies have revealed novel molecular mechanisms that regulate the number of filament barbed and pointed ends and their respective assembly and disassembly rates, thus defining classes of dynamically different filaments, which coexist in the same cell. We propose that a global treadmilling process, in which a steady-state amount of polymerizable actin monomers is established by the dynamics of each network, is responsible for defining the size and turnover of coexisting actin networks. Furthermore, signal-induced changes in the partitioning of actin to distinct arrays (mediated by RHO GTPases) result in the establishment of various steady-state concentrations of polymerizable monomers, thereby globally influencing the growth rate of actin filaments.
Journal Article
Worldwide contamination of water by fluoride
by
Ali, Shakir
,
Shekhar, Shashank
,
Sarkar, Aditya
in
Alkalinity
,
Analytical Chemistry
,
anthropogenic activities
2016
Fluoride contamination in water is a major problem across the globe, with health hazards such as dental and skeletal fluorosis. Most earlier studies are confined to local or regional scales. As the problem has serious socioeconomic implications, there is a need for a global perspective. Thus, here we review worldwide research for nearly a century on fluoride contamination in water. We investigated the distribution of fluoride contamination in water, its sources, mobilization and association. The major findings are: (1) Anomalous fluoride concentration in groundwater is mainly confined to arid and semiarid regions of Asia and North Africa. (2) The geogenic sources of fluoride in water are mainly fluorine-bearing minerals in rocks and sediments, whereas anthropogenic sources of fluoride in water are mainly pesticides and industrial waste. (3) Fluoride mobilization from geogenic sources is mainly controlled by alkalinity and temperature. (4) Fluoride occurrence in water is associated with ions such as sodium, arsenic chloride and bicarbonate. There are few associations of fluoride in water with calcium and magnesium.
Journal Article
Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein
2023
Cells control actin assembly by regulating reactions at actin filament barbed ends. Formins accelerate elongation, capping protein (CP) arrests growth and twinfilin promotes depolymerization at barbed ends. How these distinct activities get integrated within a shared cytoplasm is unclear. Using microfluidics-assisted TIRF microscopy, we find that formin, CP and twinfilin can simultaneously bind filament barbed ends. Three‑color, single-molecule experiments reveal that twinfilin cannot bind barbed ends occupied by formin unless CP is present. This trimeric complex is short-lived (~1 s), and results in dissociation of CP by twinfilin, promoting formin-based elongation. Thus, the depolymerase twinfilin acts as a pro-formin pro-polymerization factor when both CP and formin are present. While one twinfilin binding event is sufficient to displace CP from the barbed-end trimeric complex, ~31 twinfilin binding events are required to remove CP from a CP-capped barbed end. Our findings establish a paradigm where polymerases, depolymerases and cappers together tune actin assembly.
Actin networks in eukaryotic cells mediate essential processes such as cell migration, endocytosis, and morphogenesis. Here, using microfluidics assisted TIRF microscopy, the authors investigate how actin barbed-end polymerases, cappers, and depolymerases cooperate to regulate assembly of these networks.
Journal Article
Synergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude
2019
Cellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize slowly over minutes. The cellular mechanisms enabling actin to depolymerize this fast have so far remained obscure. Using microfluidics-assisted TIRF, we show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends at a rate 330-fold faster than spontaneous depolymerization. Single molecule imaging further reveals that hexameric CAP molecules interact with the pointed ends of Cofilin-decorated filaments for several seconds at a time, removing approximately 100 actin subunits per binding event. These findings establish a paradigm, in which a filament end-binding protein and a side-binding protein work in concert to control actin dynamics, and help explain how rapid actin network depolymerization is achieved in cells.
Cellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize over minutes. Here the authors show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends 330-fold faster than spontaneous depolymerization.
Journal Article
A generalized theoretical framework to investigate multicomponent actin dynamics
by
Shekhar, Shashank
,
Choubey, Sandeep
,
Nandi, Mintu
in
Actin
,
Actin Cytoskeleton - chemistry
,
Actin Cytoskeleton - metabolism
2025
The length of actin filaments is regulated by the combined action of hundreds of actin-binding proteins. While the roles of individual proteins are well understood, how they combine to regulate actin dynamics in vivo remains unclear. Recent advances in microscopy have enabled precise, high-throughput measurements of filament lengths over time. However, the absence of a unified theoretical framework has hindered a mechanistic understanding of the multicomponent regulation of actin dynamics. To address this, we propose a general kinetic model that incorporates the combined effects of an arbitrary number of regulatory proteins on actin dynamics. We derive exact closed-form expressions for the moments of (1) the distribution of filament lengths over time and (2) the long-time distribution of changes in filament lengths within a fixed time window. We show that these moments allow us to distinguish between different regulatory mechanisms of multicomponent regulation of actin dynamics. Our theoretical framework provides a powerful tool for interpreting existing data and guiding future experiments.
Journal Article
Sanjeevini: a freely accessible web-server for target directed lead molecule discovery
2012
Background
Computational methods utilizing the structural and functional information help to understand specific molecular recognition events between the target biomolecule and candidate hits and make it possible to design improved lead molecules for the target.
Results
Sanjeevini
represents a massive on-going scientific endeavor to provide to the user, a freely accessible state of the art software suite for protein and DNA targeted lead molecule discovery. It builds in several features, including automated detection of active sites, scanning against a million compound library for identifying hit molecules, all atom based docking and scoring and various other utilities to design molecules with desired affinity and specificity against biomolecular targets. Each of the modules is thoroughly validated on a large dataset of protein/DNA drug targets.
Conclusions
The article presents
Sanjeevini
, a freely accessible user friendly web-server, to aid in drug discovery. It is implemented on a tera flop cluster and made accessible via a web-interface at
http://www.scfbio-iitd.res.in/sanjeevini/sanjeevini.jsp
. A brief description of various modules, their scientific basis, validation, and how to use the server to develop
in silico
suggestions of lead molecules is provided.
Journal Article
Bed sill effectiveness in reducing flow separation at open channel confluences: an openfoam-VOF 3D CFD study
by
Das, Bhabani Shankar
,
Sandilya, Shashank Shekhar
,
Pandey, Abhishek Kumar
in
639/166
,
639/4077
,
639/705
2026
The Flow Separation Zone (FSZ) is a key hydrodynamic feature of open channel confluences, and its reduction contributes to improved channel efficiency. This study employs the open-source computational fluid dynamics (CFD) software OpenFOAM to examine the influence of a bed sill on reducing the FSZ at a right-angled open channel confluence. The flow is simulated by solving the three-dimensional (3D) Reynolds-averaged Navier–Stokes (RANS) equations with the SST
k–ω
turbulence model, while the interFoam multiphase solver is used to capture the water–air interface via the Volume of Fluid (VOF) method. The numerical model is validated against experimental data from the literature by comparing velocity fields and water surface elevations. Different sill sizes, locations, and configurations are tested to evaluate their effectiveness in reducing the FSZ. The results indicate that strategically placed sills can shorten the FSZ length by up to 55%, while modifying velocity profiles and reducing flow recirculation. Using multiple sills, particularly a three-sill configuration, further enhances this effect, reducing the FSZ length by as much as 74%. Analysis of secondary currents shows that sills intensify these currents, thereby enhancing momentum exchange and reducing the flow separation. Furthermore, energy loss analyses conducted for various sill configurations demonstrate that strategically positioned sills can reduce the energy loss significantly.
Journal Article
Synthesis and characterization of hexanary Ti–Zr–V–Cr–Ni–Fe high-entropy Laves phase
by
Mukhopadhyay, Semanti
,
Yadav, Thakur Prasad
,
Srivastava, Onkar Nath
in
Alloy systems
,
Alloying elements
,
Alloys
2019
Three different high entropy-alloys consisting of six elements (Ti, Zr, V, Cr, Ni, and Fe) with varying Fe content were synthesized by using the RF induction melting technique. All the as-cast, slow-cooled, and rapidly quenched alloys exhibit C14 Laves phase, and it is found to be stable at high temperature. A lattice contraction has been observed with the addition of Fe. To the best of our knowledge, this is the first report on the synthesis of a single-phase high-entropy complex intermetallic compound in the hexanary alloy system. It has been shown that the thermodynamic calculations following Miedema’s approach and the parametric approach utilizing several descriptors comprising configurational entropy, mixing enthalpy, atomic size mismatch, electronegativity, and valence electron concentration favor the stability of the high-entropy multicomponent Laves phase.
Journal Article