The regioselective epoxide ring opening at less substituted carbon atom of epoxide were reported by
nucleophiles like heterocyclic amines which gives well known 1,2-difunctionalized amino alcohols.
...These are present in many synthetic as well as natural products. The ring opening of epoxide is achieved
by cleavage with amines in presence of copper(0) as a catalyst. It is observed that the lithium
napthalenide reduction of copper(I) produces a highly reactive form of copper(0) that acts as a catalyst
for ring opening of epoxides with an amine.
An efficient strategy toward 4-arylquinolines and 4-arylpyrimidines from readily available precursors is described. Oxidative annulation promoted by K2S2O8 involving anilines, aryl ketones, and DMSO ...as a methine (CH−) equivalent leads to 4-arylquinolines via a cascade that entails generation of a sulfenium ion, subsequent C–N and C–C bond formations, and cyclization. The application of this strategy to the activation of acetophenone–formamide conjugates toward the synthesis of 4-arylpyrimidines is also described.
Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 ...as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020.
Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken.
Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population.
Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.
Meningeal immunity along with its associated lymphatic vasculatures is widely discussed recently. Lymphatic vessels in meninges drain interstitial fluid into the deep‐cervical lymph nodes. The ...vessels are composed of cells that express the cardinal marker for lymphatic endothelium—the lymphatic vessel hyaluronan receptor‐1 (Lyve‐1). However, studies also show the presence of nonendothelial Lyve‐1 expressing cells in certain tissues. Therefore, we were curious if nonendothelial Lyve‐1+ cells are also present in dura mater of meninges. We show that Lyve‐1+ endothelial cells are distributed adjacent to the blood vessels in the brain dura mater of rats. We did not observe any lymphatic vessels in spinal dura mater. Interestingly, we also observed isolated population of nonlymphatic Lyve‐1+ cells in both brain and spinal dura mater. Morphologically, the Lyve‐1+ cells were extensively pleomorphic, sometimes elongated or round. Surprisingly, the thoracolumbal meningeal Lyve‐1+ cells were predominantly round in morphology. Using endothelial specific marker VEGFR3 and macrophage markers CD68 and CD169, we observed that the isolated Lyve‐1+ cells lacked endothelial cell signature, but were either CD68+ or CD169+ macrophages. Moreover, we observed that the Lyve‐1+ cells colocalized with collagen fibers in the meninges, and some of Lyve‐1+ cells had intracellular collagen. The study for the first time demonstrates the presence of Lyve‐1 positive macrophages in the lymphatic and nonlymphatic regions in the meninges of rats.
In the study, we identified two subsets of Lyve‐1 positive cells in the cervical dura of rats. The first subset was lymphatic VEGFR3 positive endothelial cells, while the second subset were nonlymphatic VEGFR3 negative, but CD68 or CD169 positive macrophage. Interestingly, there were no dual VEGFR3‐Lyve‐1 positive cells in the spinal dura, but were CD169 positive macrophages. The endothelial Lyve‐1 positive cells were aligned with collagen fibers in the meningeal connective tissue. Moreover, some of the Lyve‐1 positive macrophages contained intracellular collagen. The role of these Lyve‐1 positive macrophages in meninges is yet unknown.
As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and ...evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.
Exploring barriers in lean implementation Jadhav, Jagdish R; Mantha, Shankar S; Rane, Santosh B
International journal of lean six sigma,
05/2014, Volume:
5, Issue:
2
Journal Article
Peer reviewed
Purpose
– The purpose of this paper is to present an analysis of research on lean focusing on barriers in its implementation through a systematic literature survey.
Design/methodology/approach
– A ...literature survey of peer-reviewed journal articles, survey reports, master theses, doctoral theses and paradigmatic books with managerial impact is used as the research methodology.
Findings
– The findings derived from the evaluation of the publications analyzed have led to the identification of 24 lean barriers. The success of lean implementation will not be entirely based on application of appropriate tools and techniques alone but also on the top managements' involvement and leadership, workers' attitude, resources and the organizational culture.
Research limitations/implications
– This literature survey is primarily focused on lean implementation in the manufacturing sector.
Practical implications
– This paper explores barriers for successful lean implementation and provides a concise description of the barriers that will be helpful for further studies in the domain of lean manufacturing.
Social implications
– Government of many countries around the world is encouraging and helping small- and medium-scale industries to understand and implement lean systems by preparing accessible database of lean consultants, providing financial assistance for training by professionals and establishing professional associations. However, many industries experienced failure in lean implementation. This research work provides a launching pad to develop a strategy to tackle barriers for successful lean implementation.
Originality/value
– This paper puts forward the key barriers that should be tackled for successful lean implementation. It might represent new opportunities for rigorous and relevant research that would contribute to more translucent knowledge of lean being gained.
The activation of ethyl bromofluoroacetate employing a visible light mediated, Eosin Y catalyzed photoredox transformation is reported. Using indoles and anilines as nucleophiles, the reaction leads ...to the formation of two Csp2 –Csp3 bonds resulting in an efficient synthesis of bisindolyl and bisanilinoyl acetate derivatives. Application of this method to the direct synthesis of unsymmetrical diarylacetates featuring indoles and N-substituted anilines was also demonstrated.
The Influenza A pandemic H1N1 2009 (H1N1pdm) virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. ...Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus.
H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA) gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers.
The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases.
The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity.
A-kinase anchoring proteins (AKAPs) belong to a family of scaffolding proteins that bind to protein kinase A (PKA) by definition and a variety of crucial proteins, including kinases, phosphatases, ...and phosphodiesterases. By scaffolding these proteins together, AKAPs build a "signalosome" at specific subcellular locations and compartmentalize PKA signaling. Thus, AKAPs are important for signal transduction after upstream activation of receptors ensuring accuracy and precision of intracellular PKA-dependent signaling pathways. Since their discovery in the 1980s, AKAPs have been studied extensively in the heart and have been proven essential in mediating cyclic adenosine monophosphate (cAMP)-PKA signaling. Although expression of AKAPs in the heart is very low, cardiac-specific knock-outs of several AKAPs have a noteworthy cardiac phenotype. Moreover, single nucleotide polymorphisms and genetic mutations in crucial cardiac proteins play a substantial role in the pathophysiology of cardiovascular diseases (CVDs). Despite the significant role of AKAPs in the cardiovascular system, a limited amount of research has focused on the role of genetic polymorphisms and/or mutations in AKAPs in increasing the risk of CVDs. This review attempts to overview the available literature on the polymorphisms/mutations in AKAPs and their effects on human health with a special focus on CVDs.
Ethyl bromofluoroacetate has been developed as a precursor for the convenient synthesis of unsymmetrical α,α-diarylacetates featuring indoles, anilines, and other electron-rich aromatics. In ...conjunction with a mild Lewis acid catalyzed C–N → C–C exchange, intermediate arylglycines can be synthesized and transformed into α,α-diarylacetates in a one-pot protocol, resulting in a net diarylation reaction exhibiting a wide scope. In the context of diarylacetates, the synthetic equivalence of the fluorinated reagent with α-nitro-α-diazo carbonyls was established.
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