Manish Singh - Academia.edu (original) (raw)

Papers by Manish Singh

Organic & Biomolecular Chemistry, 2022

This review summarizes applications of 3-, 4-, 5-, and 6-membered azaheterocycles as tools to int... more This review summarizes applications of 3-, 4-, 5-, and 6-membered azaheterocycles as tools to introduce conformational restrictions in the design of peptidomimetics.

Diabetes care, Aug 12, 2018

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent ... more Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks. Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) levels. When included in the standard treatment for type 2 diabetes, empagliflozin was significantly better at reducing liver fat (mean MRI-PDFF difference betw...

ChemCatChem, 2015

1-(Aryl)methoxy-1H-benzotriazoles (ArCH 2 OBt) are bench-stable reagents that are prepared readil... more 1-(Aryl)methoxy-1H-benzotriazoles (ArCH 2 OBt) are bench-stable reagents that are prepared readily from 1H-benzotriazol-1-yl-4-methylbenzenesulfonate (BtOTs) and benzylic alcohols. These compounds, which contain a NO -C bond, undergo cross-coupling with arylboronic acids by CO bond scission with catalysts that comprise Pd(OAc) 2 and biarylphosphine ligands. Such reactivity of ArCH 2 OBt derivatives, leading to diarylmethanes, has not been described previously and constitutes a new activation of benzylic alcohols. With regard to the various ligands-metal complexes that support catalytic activity, it appears that those with smaller "percent buried volumes" (%V bur) provide better outcomes. This factor has been evaluated in the initial optimization studies and in further reactions with difficult coupling partners. Ligand electronics of the biaryl moiety seem to play a lesser role in this type of reaction. The bis-coordinating bis[(2diphenylphosphino)phenyl]ether appears to be suitable to improve the yields of low-yielding reactions.

Oxford Handbooks Online, 2014

Perceptual grouping is the process by which the visual system organizes the image into distinct o... more Perceptual grouping is the process by which the visual system organizes the image into distinct objects or clusters. Here we briefly describe a Bayesian approach to grouping, formulating it as an inverse probability problem in which the goal is to estimate the organization that best explains the observed set of visual elements. We pose the problem as an instance of mixture modeling, in which the image configuration is assumed to have been generated by a set of distinct data-generating components or sources ("objects"), whose locations and structure we seek to estimate. We illustrate the approach with three classes of source models: dot clusters, contours, and axial shapes. We show how this approach to the problem unifies and gives natural accounts of a number of perceptual grouping problems, including contour integration, shape representation, and figure/ground estimation. Highlight: A novel framework for perceptual grouping uses Bayesian mixture estimation to provide a unifying account of grouping problems, including contour integration, shape representation, and figure-ground estimation.

International Journal of Antimicrobial Agents, 2010

New antimicrobials are needed to combat drug resistance and have often been equated with the iden... more New antimicrobials are needed to combat drug resistance and have often been equated with the identification and exploitation of novel targets. This study focused on the synthesis of new benzimidazole analogues with improved DNA minor groove-binding affinity and having lower cytotoxicity to mammalian cells as well as selective targeting of bacterial DNA over host DNA. 5-(4-Methylpiperazin-1yl)-2-[2-(3,4-dimethoxyphenyl)-5-benzimidazolyl]benzimidazole (DMA) cleared bacterial infections from mammalian cell culture without apparent cytotoxicity to mammalian cells. Moreover, DMA inhibited microbial topoisomerase over mammalian topoisomerase, with a 50% inhibitory concentration (IC 50) value for human topoisomerase I of >54 M compared with an IC 50 of <10 M for Escherichia coli topoisomerase I in vitro.

Clinical and Experimental Immunology, 2006

Summary Human visceral leishmaniasis (VL), also known as kala azar (KA) in India, is a systemic p... more Summary Human visceral leishmaniasis (VL), also known as kala azar (KA) in India, is a systemic progressive disease caused by Leishmania donovani. In VL, Th1 responses correlate with recovery from and resistance to disease and resolution of infection results in lifelong immunity against the disease. However, recent data suggest an important role for interleukin (IL)-10 in maintaining the resistant state. We evaluated whole cell extract (WE) and 11 antigenic fractions [F1–F11, molecular weight (MW) range of 139–24·2 kDa] from L. donovani (2001 strain, a fresh field isolate from Bihar), for their ability to induce in vitro T cell proliferation and production of interferon (IFN)-γ, interleukin (IL)-12, IL-10 and IL-4 by peripheral blood mononuclear cells (PBMCs) of exposed immune individuals (14 patients with history of VL, 10 household endemic contacts) and 20 non-endemic healthy controls. Twenty-one of 24 exposed individuals and no healthy controls showed proliferative response to WE...

The Australian and New Zealand Journal of Obstetrics and Gynaecology, 2002

It is also possible that your web browser is not configured or not able to display style sheets. ... more It is also possible that your web browser is not configured or not able to display style sheets. In this case, although the visual presentation will be degraded, the site should continue to be functional. We recommend using the latest version of Microsoft or Mozilla web browser to ...

Perception & Psychophysics, 1999

Visual completion is a ubiquitous phenomenon: Human vision often constructs contours and surfaces... more Visual completion is a ubiquitous phenomenon: Human vision often constructs contours and surfaces in regions that have no sharp gradients in any image property. When does human vision interpolate a contour between a given pair of luminance-defined edges? Two different answers have been proposed: relatability and minimizinginflections. Westate and prove a proposition that links these two proposals by showing that, under appropriate conditions, relatability is mathematically equivalent to the existence of a smooth curve with no inflection points that interpolates between the two edges. The proposition thus provides a set of necessary and sufficient conditions for two edges to be relatable. On the basis ofthese conditions, we suggest a way to extend the definition of relatability (1) to include the role of genericity, and (2) to extend the current all-or-none character of relatability to a graded measure that can track the gradedness in psychophysical data.

Microscopy and Microanalysis, 2021

Investigating the earliest stages of crystallization requires the transmission electron microscop... more Investigating the earliest stages of crystallization requires the transmission electron microscope (TEM) and is particularly challenging for materials which can be affected by the electron beam. Typically, when imaging at magnifications high enough to observe local crystallinity, the electron beam's current density must be high to produce adequate image contrast. Yet, minimizing the electron dose is necessary to reduce the changes caused by the beam. With the advent of a sensitive, high-speed, direct-detection camera for a TEM that is corrected for spherical aberration, it is possible to probe the early stages of crystallization at the atomic scale. High-quality images with low contrast can now be analyzed using new computing methods. In the present paper, this approach is illustrated for crystallization in a Ge2Sb2Te5 (GST-225) phase-change material which can undergo particularly rapid phase transformations and is sensitive to the electron beam. A thin (20 nm) film of GST-225 h...

We investigate robust data aggregation in a multi-agent online learning setting. In reality, mult... more We investigate robust data aggregation in a multi-agent online learning setting. In reality, multiple online learning agents are often deployed to perform similar tasks and receive similar feedback. We study how agents can improve their collective performance by sharing information among each other. In this paper, we formulate the -multi-player multi-armed bandit problem, in which a set of M players that have similar reward distributions for each arm play concurrently. We develop an upper confidence bound-based algorithm that adaptively aggregates rewards collected by different players. To our best knowledge, we are the first to develop such a scheme in a multi-player bandit learning setting. We show that under the assumption that pairwise distances between the means of the player-dependent distributions for each arm are small, we improve the (collective) regret bound by nearly a factor of M , in comparison with a baseline algorithm in which the players learn individually using the ...

Scientific Reports, 2021

Li-ion batteries function by Li intercalating into and through the layered electrode materials. I... more Li-ion batteries function by Li intercalating into and through the layered electrode materials. Intercalation is a solid-state interaction resulting in the formation of new phases. The new observations presented here reveal that at the nanoscale the intercalation mechanism is fundamentally different from the existing models and is actually driven by nonuniform phase distributions rather than the localized Li concentration: the lithiation process is a ‘distribution-dependent’ phenomena. Direct structure imaging of 2H and 1T dual-phase microstructures in lithiated MoS2 and WS2 along with the localized chemical segregation has been demonstrated in the current study. Li, a perennial challenge for the TEM, is detected and imaged using a low-dose, direct-electron detection camera on an aberration-corrected TEM and confirmed by image simulation. This study shows the presence of fully lithiated nanoscale domains of 2D host matrix in the vicinity of Li-lean regions. This confirms the nanosca...

Applications of Microscopy in Materials and Life Sciences, 2021

Frontiers in Intelligent Computing: Theory and Applications, 2019

In the modern era, the vehicles are made for the comfort of the humans and the automation of the ... more In the modern era, the vehicles are made for the comfort of the humans and the automation of the vehicle focusses on the safety and comfort of the humans by giving them relaxing time. In the field of automobile industries, technological progress are taking place to a greater extent and to make a vehicle automated various aspects have to be taken into consideration. In this paper, we have focussed on the application in which the vehicle system knows the shortest route between the two destinations and follow this route based on its intuition from the surrounding to take further direction or not. The idea described in this paper has somewhat been taken from Google Car, i.e. Dynamic routing. This can be done using the neural network in which a method of intuition is applied and an artificial brain is to be integrated into the system that decides the shortest path through which one can reach its destination and follow that path based on its data that it collected from the surroundings. Since taking any intelligent decisions in the traffic is also an issue for the automated vehicle system. This aspect has been taken into consideration in this paper.

Cells, 2021

Autophagy is a physiological degradation process that removes unnecessary or dysfunctional compon... more Autophagy is a physiological degradation process that removes unnecessary or dysfunctional components of cells. It is important for normal cellular homeostasis and as a response to a variety of stresses, such as nutrient deprivation. Defects in autophagy have been linked to numerous human diseases, including cancers. Cancer cells require autophagy to migrate and to invade. Here, we study the intracellular topology of this interplay between autophagy and cell migration by an interdisciplinary live imaging approach which combines micro-patterning techniques and an autophagy reporter (RFP-GFP-LC3) to monitor over time, during directed migration, the back–front spatial distribution of LC3-positive compartments (autophagosomes and autolysosomes). Moreover, by exploiting a genetically controlled cell model, we assessed the impact of transformation by the Ras oncogene, one of the most frequently mutated genes in human cancers, which is known to increase both cell motility and basal autopha...

Journal of Public Affairs, 2020

The global outbreak of COVID-19 and subsequent lockdowns raises serious economic concern and havo... more The global outbreak of COVID-19 and subsequent lockdowns raises serious economic concern and havoc worldwide. This article tries to provide an economic perspective of COVID-19 in India using some statistical figure of economic indicators. Analysis is based on the data collected for macro-economy, travel & tourism, transportation, stock market, human capital and trade. Finding revel that India could experience a health debacle at present and excruciating economic contraction in the near future if the government is unable to execute a proper policy framework. Based on the discussion, a few policy suggestions have been presented to counter both health and economic crisis.

eLife, 2018

The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cance... more The two Ral GTPases, RalA and RalB, have crucial roles downstream Ras oncoproteins in human cancers; in particular, RalB is involved in invasion and metastasis. However, therapies targeting Ral signalling are not available yet. By a novel optogenetic approach, we found that light-controlled activation of Ral at plasma-membrane promotes the recruitment of the Wave Regulatory Complex (WRC) via its effector exocyst, with consequent induction of protrusions and invasion. We show that active Ras signals to RalB via two RalGEFs (Guanine nucleotide Exchange Factors), RGL1 and RGL2, to foster invasiveness; RalB contribution appears to be more important than that of MAPK and PI3K pathways. Moreover, on the clinical side, we uncovered a potential role of RalB in human breast cancers by determining that RalB expression at protein level increases in a manner consistent with progression toward metastasis. This work highlights the Ras-RGL1/2-RalB-exocyst-WRC axis as appealing target for novel ant...

Pediatric blood & cancer, Jan 31, 2018

Karyotyping along with a 3-probe fluorescence in situ hybridization (FISH) strategy was used to r... more Karyotyping along with a 3-probe fluorescence in situ hybridization (FISH) strategy was used to risk stratify therapy in 303 children with B-cell precursor acute lymphoblastic leukaemia. Of the 166 patients risk stratified, karyotype identified 91 (55%). FISH identified all karyotypes accurately, with the exception of hypodiploidy, and risk stratified an additional 75 patients. The frequency of ETV6-RUNX1 is lower and high hyperdiploidy, higher than reported in the west. An adapted 3-probe FISH strategy identified two patients with ETV6-ABL1 fusion who received imatinib. In limited-resource settings, a 3-probe FISH approach provides a practical approach for risk-stratified therapy in childhood ALL.

Methods in molecular biology (Clifton, N.J.), 2018

During mesenchymal cell motility, various actin regulators are recruited to the leading edge with... more During mesenchymal cell motility, various actin regulators are recruited to the leading edge with exquisite precision in time and space to generate protrusion and retraction cycles. We present here an automated method, named CorRecD (from Correlation Recruitment Dynamics), which quantifies cell edge dynamics, protein recruitment and analyze their cross-correlation. The Wave Regulatory Complex (WRC), a master driver of protrusions, is used as a case-of-study. This biologist-friendly method relies on free software tools and can be applied to any fluorescently tagged protein of interest.

Journal of Thermal Biology, 2017

Heat shock proteins are important for maintaining protein homeostasis and cell survival. Among di... more Heat shock proteins are important for maintaining protein homeostasis and cell survival. Among different classes of highly conserved Hsps, low molecular weight Hsps (sHsps) have significant place, particularly Hsp27, whose role has been demonstrated in wide range of biological processes, including development, immunity, diseases and therapy. In this review, the structure and functions of Hsp27 and related genes, their role in different cellular processes as well as in stress tolerance, is highlighted.

Hematology/Oncology and Stem Cell Therapy, 2017

Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases... more Acute promyelocytic leukemia (APML) with variant RARa translocations comprises 1-2% of APML cases. However, the diagnosis of these cases is challenging as the routine practice includes fluorescence in situ hybridization (FISH) reverse transcription polymerase chain reaction targeting the PML and RARA genes to detect PML/RARA fusions. Here, we report a case highlighting the importance of atypical FISH signal patterns in standard dual-color dualfusion PML/RARa FISH analysis complimented by karyotyping to detect these variant RARA translocations.