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Gaurav Sharma

Other affiliations: Northeastern University, D. E. Shaw & Co., Hewlett-Packard  ...read more
Bio: Gaurav Sharma is an academic researcher from Shenzhen University. The author has contributed to research in topics: Medicine & Photocatalysis. The author has an hindex of 82, co-authored 1244 publications receiving 31482 citations. Previous affiliations of Gaurav Sharma include Northeastern University & D. E. Shaw & Co..


Papers
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Journal ArticleDOI
TL;DR: The results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation.
Abstract: Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known antitumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action. Early passage DT-derived cells were treated with increasing doses of sorafenib (0-10 µM) and demonstrated up to 90% decrease in proliferation and invasion relative to controls. Signaling arrays identified multiple potential targets of sorafenib in the Ras/MEK/ERK and PI3K/Akt/mTOR signaling cascades. Immunoblot analysis revealed that sorafenib inhibited Akt, MEK and ERK phosphorylation, and this effect correlated with inhibition of total Akt and total MEK, while total ERK levels remained unchanged. Sorafenib also inhibited 4E-BP1 phosphorylation, and this effect correlated with decrease of p-eIF4E and total eIF4E. Finally, in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus, sorafenib decreased phosphorylation of the ribosomal protein and mTOR effector S6K in an additive manner. Taken together, our results suggest that sorafenib suppresses DT proliferation and invasion via inhibition of Ras/MEK/ERK and PI3K/Akt/mTOR signaling pathways with additional effects on translation. Sorafenib may be a promising therapeutic option in the treatment of DTs. Additional studies in DT patients are warranted to examine the efficacy of combination therapy using sorafenib.

38 citations

Journal ArticleDOI
TL;DR: In this paper, the anatase form of TiO2 has been applied to fluorine-doped tin oxide (FTO)-coated glass; 304L stainless steel; and titanium substrates using isopropanol and acetylacetone-based solutions at 20, 40, 60 and 80 V.
Abstract: This paper describes the application of electrophoretic deposition for air pollution removal using anatase as a photoactive coating. In this study, the anatase form of TiO2 has been applied to (1) fluorine-doped tin oxide (FTO)-coated glass; (2) 304L stainless steel; and (3) titanium substrates using isopropanol and acetylacetone-based solutions at 20, 40, 60 and 80 V. In order to increase the strength of the substrate–anatase interface without transforming the phase into rutile, samples were calcined at 450 °C for 2 h. The resulting coatings were characterised by Raman spectroscopy, X-ray diffraction, non-contact optical profilometry and scanning electron microscopy. The photocatalytic activity of the deposited coatings were evaluated in the gas phase for nitrogen dioxide (NO2) removal by electron ionisation mass spectrometry, whilst irradiated by light of wavelength 376–387 nm for 100 min. Anatase phase titania supported on a FTO-coated glass substrate showed the highest photoactivity for NO2 remediation. This was attributed to the formation of a three-dimensional nanostructure with properties determined by the deposition conditions. This work provides routes for the development of low-cost and large area photoactive coatings for pollution control.

38 citations

Book ChapterDOI
TL;DR: Several studies in literature survey revealed anticancer properties of curcumin against prostate cancer, cervical cancer, colorectal carcinoma, leukemia, and human breast cancer cells, which are summarized in this chapter.
Abstract: Cancers have been found to be the leading causes of death worldwide, with 8.2 million people dying in 2012 and approximately 14 million new cases reported. These cases are estimated to rise by about 70% over the next 2 decades. More than 60% of the world's new annual cancer cases occur in Africa, Asia, and Central and South America. The analysis, literature survey, and observed reports have indicated cancer is responsible for 70% of all deaths. In men, the 5 most common sites of cancer diagnosed in 2012 were lung, prostate, colorectal, stomach, and liver cancer while in women breast, colorectal, lung, cervix, and stomach cancer were more prevalent. Modern science is devoting resources to and acquiring knowledge of different types of cancer through high throughput advanced technology and by revisiting the hidden treasure of traditional medicine. In Asia, Zingiberaceous plants have been used since ancient times as spices and medicines in traditional Chinese and Indian medicine. Among the Zingiberaceae family, the genus Curcuma, with more than 30 species, has raised hopes for use in cancer therapy. The genus is predominantly found in Asia, and several species, particularly C. longa, C. aromatica, and C. xanthorrhiza, have been extensively used to treat ailments including indigestion, hepatitis, jaundice, diabetes, atherosclerosis, and bacterial infections. Curcuminoids, the principal bioactive component of Curcuma species, share a common unsaturated alkyl-linked two phenyl structural feature. Curcumin [diferuloylmethane, 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3, 5-dione], a broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of C. longa L., is a nontoxic compound and has been classified as “generally recognized as safe” (GRAS) by the National Cancer Institute. Several studies in literature survey revealed anticancer properties of curcumin against prostate cancer, cervical cancer, colorectal carcinoma, leukemia, and human breast cancer cells. However, the clinical use of curcumin has been hampered by its poor solubility, absorption, bioavailability, and rapid metabolism. To overcome these limitations, various synthetic bioactive curcumin analogs were developed based on the structure-activity relationship (SAR) studies. This chapter highlights the research-based importance of curcumin and its analogues. Based on the available data, the chapter summarizes the potential and future of curcumin in anticancer therapy.

38 citations

Journal ArticleDOI
TL;DR: The 10.33 Mb whole genome of a starch-degrading myxobacterium Sandaracinus amylolyticus DSM 53668T is reported that encodes 8,962 proteins, 56 tRNA, and two rRNA operons and identifies several novel amylases acquired via horizontal transfer from members of phylum Deinococcus-Thermus, Acidobacteria, and Cyanobacteria.
Abstract: Myxobacteria are members of δ-proteobacteria and are typified by large genomes, well-coordinated social behavior, gliding motility, and starvation-induced fruiting body formation. Here, we report the 10.33 Mb whole genome of a starch-degrading myxobacterium Sandaracinus amylolyticus DSM 53668(T) that encodes 8,962 proteins, 56 tRNA, and two rRNA operons. Phylogenetic analysis, in silico DNA-DNA hybridization and average nucleotide identity reveal its divergence from other myxobacterial species and support its taxonomic characterization into a separate family Sandaracinaceae, within the suborder Sorangiineae. Sequence similarity searches using the Carbohydrate-active enzymes (CAZyme) database help identify the enzyme repertoire of S. amylolyticus involved in starch, agar, chitin, and cellulose degradation. We identified 16 α-amylases and two γ-amylases in the S. amylolyticus genome that likely play a role in starch degradation. While many of the amylases are seen conserved in other δ-proteobacteria, we notice several novel amylases acquired via horizontal transfer from members belonging to phylum Deinococcus-Thermus, Acidobacteria, and Cyanobacteria. No agar degrading enzyme(s) were identified in the S. amylolyticus genome. Interestingly, several putative β-glucosidases and endoglucanases proteins involved in cellulose degradation were identified. However, the absence of cellobiohydrolases/exoglucanases corroborates with the lack of cellulose degradation by this bacteria.

38 citations

Journal ArticleDOI
TL;DR: It is demonstrated that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs), indicating a DDR defect even though the virus is latent.
Abstract: Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells. These results indicate a DDR defect even though the virus is latent. DDR-inducing agents, specifically high doses of nucleoside RT inhibitors (NRTIs), caused greater increases in gamma-H2AX levels in latently infected cells. Additionally, latently infected cells are...

37 citations


Cited by
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08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

10,124 citations

Journal ArticleDOI

7,335 citations

Journal ArticleDOI

6,278 citations