John lch Technology Center

Bangalore, India

John lch Technology Center

Bangalore, India
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Joglekar M.M.,Shivaji University | Bavkar L.N.,Shivaji University | Sistla S.,John lch Technology Center | Arvindekar A.U.,Shivaji University
International Journal of Biological Macromolecules | Year: 2017

Protein glycation is a major mechanism for establishing secondary complication in diabetes mellitus. Effective inhibition of this process can prevent progression of the disorder into secondary complications. Aminoguanidine (AMG) and limonene (LM) are known protein glycation inhibitors. The aim of the present study was to demonstrate their differential mechanisms of action and to study whether combinatorial therapy can act synergistically and lower dosage, and thereby lower toxicity in treatment of secondary complications in diabetes. Glycation in the presence of 2 M urea was inhibited by 23% with AMG and by 66% with LM. AMG is more effective than LM in reducing protein carbonyl formation. SPR studies revealed binding of LM reduces affinity of BSA for glucose. LM demonstrated an increase by 2 °C in thermal transition in DSC studies as against reduction by 0.4 °C by AMG proving that LM can effectively stabilize the protein structure. Combinatorial treatment of AMG and LM prevented α-helix to β-sheet transitions in BSA at 100 μM and inhibited AGE related fluorescence and pentosidine formation by 80 and 90% respectively. The combination can reduce dosage of AMG by almost twenty times, paving the way for effective protein glycation inhibition without toxicity. © 2017

Gerdes M.J.,General Electric | Sevinsky C.J.,General Electric | Sood A.,General Electric | Adak S.,John lch Technology Center | And 27 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

Limitations on the number of unique protein and DNA molecules that can be characterized microscopically in a single tissue specimen impede advances in understanding the biological basis of health and disease. Here we present a multiplexed fluorescence microscopy method (MxIF) for quantitative, single-cell, and subcellular characterization of multiple analytes in formalin-fixed paraffinembedded tissue. Chemical inactivation of fluorescent dyes after each image acquisition round allows reuse of common dyes in iterative staining and imaging cycles. The mild inactivation chemistry is compatible with total and phosphoprotein detection, as well as DNA FISH. Accurate computational registration of sequential images is achieved by aligning nuclear counterstain-derived fiducial points. Individual cells, plasma membrane, cytoplasm, nucleus, tumor, and stromal regions are segmented to achieve cellular and subcellular quantification of multiplexed targets. In a comparison of pathologist scoring of diaminobenzidine staining of serial sections and automated MxIF scoring of a single section, human epidermal growth factor receptor 2, estrogen receptor, p53, and androgen receptor staining by diaminobenzidine and MxIF methods yielded similar results. Single-cell staining patterns of 61 protein antigens by MxIF in 747 colorectal cancer subjects reveals extensive tumor heterogeneity, and cluster analysis of divergent signaling through ERK1/2, S6 kinase 1, and 4E binding protein 1 provides insights into the spatial organization of mechanistic target of rapamycin and MAPK signal transduction. Our results suggest MxIF should be broadly applicable to problems in the fields of basic biological research, drug discovery and development, and clinical diagnostics.

Upadhyay S.,John lch Technology Center | Adda R.,Indian Institute of Technology Kanpur | Mishra S.,Indian Institute of Technology Kanpur | Joshi A.,Indian Institute of Technology Kanpur
2010 9th International Power and Energy Conference, IPEC 2010 | Year: 2010

This paper proposes a novel switched-boost converter suitable for microgrid application. The proposed converter can provide a DC output, which is greater than the input voltage. Apart from a DC, it can be, simultaneously, used to supply an AC load. In order to supply an AC load it has to be cascaded with a Voltage source inverter (VSI). While operating with a VSI, it avails all the advantages of a Z-source inverter, with half the number of passive components. During AC operation, it prevents the shoot-though current due to mis-gating and provides superior noise immunity. The circuit operation, analysis, PWM control strategy, and experimental results are provided to verify the proposed topology. ©2010 IEEE.

Adak S.,John lch Technology Center | Bhalla R.,Grove Center | Vijaya Raj K.K.,John lch Technology Center | Mandal S.,John lch Technology Center | And 2 more authors.
Radiochimica Acta | Year: 2012

Single photon emission computed tomography (SPECT) has been the cornerstone of nuclear medicine and today it is widely used to detect molecular changes in cardiovascular, neurological and oncological diseases. While SPECT has been available since the 1980s, advances in instrumentation hardware, software and the availability of new radiotracers that are creating a revival in SPECT imaging are reviewed in this paper. The biggest change in the last decade has been the fusion of CT with SPECT, which has improved attenuation correction and image quality. Advances in collimator design, replacement of sodium iodide crystals in the detectors with cadmium zinc telluride (CZT) detectors as well as advances in software and reconstruction algorithms have all helped to retain SPECT as a much needed and used technology. Today, a wide spectrum of radiotracers is available for use in cardiovascular, neurology and oncology applications. The development of several radiotracers for neurological disorders is briefly described in this review, including [ 123I]FP-CIT (DaTSCAN ™) available for Parkinson's disease. In cardiology, while technetium-99m labeled tetrofosmin and technetium-99m labeled sestamibi have been well known for myocardial perfusion imaging, we describe a recently completed multicenter clinical study on the use of [ 123I]mIBG (AdreView ™) for imaging in chronic heart failure patients. For oncology, while bone scanning has been prevalent, newer radiotracers that target cancer mechanisms are being developed. Technetium-99m labeled RGD peptides have been reported in the literature that can be used for imaging angiogenesis, while technetium-99m labeled duramycin has been used to image apoptosis. While PET/CT is considered to be the more advanced technology particularly for oncology applications, SPECT continues to be the modality of choice and the workhorse in many hospitals and nuclear medicine centers. The cost of SPECT instruments also makes them more attractive in developing countries where the cost of a scan is still prohibitive for many patients. © by Oldenbourg Wissenschaftsverlag, München.

Liu C.H.,Massachusetts General Hospital | Liu C.H.,U.S. National Institutes of Health | Ren J.Q.,Massachusetts General Hospital | You Z.,Massachusetts General Hospital | And 5 more authors.
FASEB Journal | Year: 2012

The presence of pericytes in brain regions undergoing repair is evident of the recruitment of bone marrow-derived multipotent regenerative cells to the neurovascular unit during angiogenesis. At present, post mortem sampling is the only way to identify them. Therefore, such cell typing is inadequate for preserving neural progenitor cells for any meaningful stem cell therapy. We aimed to target cerebral pericytes in vivo using dual gene transcript-targeted MRI (GTtMRI) in male C57black6 mice after a 60-min bilateral carotid artery occlusion (BCAO). We attached superparamagnetic iron oxide nanoparticles (SPIONs) to phosphorothioate-modified micro-DNA that targets actin or nestin mRNA. Because BCAO compromises the blood-brain barrier (BBB) and induces expression of α-smooth muscle (αSM)-actin and nestin antigens by pericytes in new vessels, we delivered pericyte-specific magnetic resonance contrast agents (SPION-actin or SPION-nestin at 4 mg Fe/kg) by i.p. injection to C57black6 mice that had experienced BCAO. We demonstrated that the surge in cerebral iron content by inductively coupled plasma-mass spectrometry matched the increase in the frequency of relaxivity. We also found that SPION-nestin was colocalized in αSM-actin- and nestin-expressing pericytes in BCAO-treated C57black6 or transgenic mice [B6.Cg-Tg(CAG-mRFP1) 1F1Hadj/J, expressing red fluorescent protein by actin promoter]. We identified pericytes in the repair patch in living brains after BCAO with a voxel size of 0.03 mm3. The presence of electron-dense nanoparticles in vascular pericytes in the region of BBB injury led us to draw the conclusion that GT-tMRI can noninvasively reveal neural progenitor cells during vascularization. © FASEB.

Allen T.T.,Ohio State University | Rajagopalan R.,John lch Technology Center
Journal of Quality Technology | Year: 2011

This paper proposes a plot-based method for fractional factorial data analysis. The proposed plot is called a "response-probability model analysis plot" (RPMAP) because it displays the predicted responses associated with alternative models and decisions versus the model posterior probabilities. Benefits of the proposed method include unique information about whether the current state of model uncertainty and achievement of objectives warrants additional experimentation. Also, in some cases, the RPMAP leads to settings with arguably superior robustness to model uncertainty compared with normal probability plots or Posterior probability plots. The methods are illustrated using the well-studied injection molding data and another real-world case study. In both cases, new insights are gained with potential value to practitioners.

Kothakapu D.,John lch Technology Center | Avishetti S.,John lch Technology Center
ASME 2014 Gas Turbine India Conference, GTINDIA 2014 | Year: 2014

The configuration of the compartment ventilation system is an important requirement in the gas turbine industry. The purpose of heating and ventilation system is to keep the turbine compartment within a fixed temperature envelope for at least personnel safety, equipment protection and reduction of turbine distortion by maintaining circumferentially uniform temperature distribution. The ventilation system also provides capability to detect and dilute the leaks by continually purging potential gas build up areas. Displacement ventilation is commonly used for the above considerations. The current GE approach is to perform CFD analysis to quantify the ventilation fan flow rate and arrive at fan static pressure head through simplified 1-D calculations. A detailed CFD geometric model is developed by including the entire turbine, piping, major support structure, all components with stringent temperature limits, ventilation inlets and outlets, enclosure roof and walls to verify the flow field. The fan static pressure head for various ambient conditions is obtained through 1-D calculations using the American Society of Heating, Refrigeration and Air Conditioning Engineers (ASHRAE) duct-fitting database. The goal of this work is: (1) accurate modeling of the components within the enclosure for better prediction of component temperatures; (2) consideration of solar radiation; and (3) integration of the 1-Dimensional Flowmaster models and 3-Dimensional CFD results to improve the predictions from One-Dimensional model. Copyright © 2014 by ASME.

Patil S.,Shivaji University | Srinivas S.,John lch Technology Center | Jadhav J.,Shivaji University
International Journal of Biological Macromolecules | Year: 2014

Tyrosinase inhibitors have potential applications in the cosmetics and food industries for preventing browning reactions and also as therapeutic drugs for neurodegenerative diseases such as Parkinson's. In this article, crocin and curcumin were evaluated as mushroom tyrosinase inhibitors. Results showed that, both compounds strongly inhibited the diphenolase activity than monophenolase. The IC50 values for diphenolase activity were estimated to be 0.11mM and 0.18mM for crocin and curcumin respectively. The binding kinetics of crocin and curcumin was studied with mushroom tyrosinase using surface plasmon resonance (SPR). Tyrosinase was immobilized on the gold surface of a Biacore sensor chip through amine coupling. Binding of inhibitors was analyzed by SPR without the need to further modify the surface or the use of other reagents. The binding constant KD (M) for mushroom tyrosinase obtained was 1.21×10-4M for crocin and 1.64×10-4M for curcumin, while showing a higher affinity for L-DOPA 1.95×10-8M, a substrate for tyrosinase (positive control). The study reveals the SPR sensor's ability to detect binding of the inhibitors. © 2014 Elsevier B.V.

Patil S.,Shivaji University | Sistla S.,John lch Technology Center | Jadhav J.,Shivaji University
International Journal of Biological Macromolecules | Year: 2016

Studies on tyrosinase have recently gained the attention of researchers due to the enzyme's biological functions and potential applications in food and cosmetic applications. In this present study, screening and kinetic evaluation of small molecules (>300 Da) on human tyrosinase was carried out using surface plasmon resonance and molecular docking studies. Four molecules showed significant binding were further characterized. The binding constant KD (M) values obtained for crocin, curcumin, tannic acid, pyrogallol and hydroquinone are 5.60 × 10−5, 1.52 × 10−3, 6.45 × 10−5, 1.34 × 10−5 and 2.433 × 10−7 M respectively. In silico docking studies using autodock indicated significant binding and revealed the binding pocket residues for all molecules. The study shows the Biacore/SPR sensor's ability for screening and detection of inhibitors for human tyrosinase. This study can be used to rapidly screen and optimize various lead compounds as binders/inhibitors/modulators of human tyrosinase enzyme activity. © 2016

Chanda C.,Birla Institute of Technology and Science | Sarkar A.,Birla Institute of Technology and Science | Sistla S.,John lch Technology Center | Chakrabarty D.,Birla Institute of Technology and Science
Biochemical and Biophysical Research Communications | Year: 2013

A low molecular weight anti-platelet peptide (6.9. kDa) has been purified from Naja kaouthia venom and was named KT-6.9. MALDI-TOF/TOF mass spectrometry analysis revealed the homology of KT-6.9 peptide sequence with many three finger toxin family members. KT-6.9 inhibited human platelet aggregation process in a dose dependent manner. It has inhibited ADP, thrombin and arachidonic acid induced platelet aggregation process in dose dependent manner, but did not inhibit collagen and ristocetin induced platelet aggregation. Strong inhibition (70%) of the ADP induced platelet aggregation by KT-6.9 suggests competition with ADP for its receptors on platelet surface. Anti-platelet activity of KT-6.9 was found to be 25 times stronger than that of anti-platelet drug clopidogrel. Binding of KT-6.9 to platelet surface was confirmed by surface plasma resonance analysis using BIAcore X100. Binding was also observed by a modified sandwich ELISA method using anti-KT-6.9 antibodies. KT-6.9 is probably the first 3FTx from Indian monocled cobra venom reported as a platelet aggregation inhibitor. © 2013 Elsevier Inc.

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