<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

(SoNS) School of Natural Sciences

Autoimmunity and cancer have a multifarious epidemiology. Often, it is because of an impaired genome, culminating in functional aberrations in the human system. Systemic lupus erythematosus (SLE) is a heterogeneous complex disease which ensues due to the failure of the immune system to distinguish between self and non-self antigens, thus producing autoantibodies against DNA, RNA and proteins. Cancer, the other side of the same coin, results from an excessive proliferation of cells that evade immune regulation as a result of incompetent defense by T-cells, B-cells and macrophages. Recent findings have indicated that lupus autoantibodies could be used as an effective weapon to kill cancerous cells. This is an attempt to take an account of malicious 'lupus autoantibodies' and their role in neutralizing cancerous cells which may help in enhancing the survival rate of cancer patients, hence, killers can be saviors. © 2016 SAGE Publications.

World University root node

Life Sciences

Fulltext

Lupus

Can killers be saviors?

Sorafenib is a small molecule, multi-kinase inhibitor used as an anti-cancer drug for treatment of Liver and Kidney cancers. It is reported to be in phase 2 clinical trials for colorectal cancer (CRC). This drug was reported to inhibit both surface associated and intracellular kinases such as Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), Fibroblast Growth Factor Receptor (FGFR), RAF, BRAF etc. This was shown to be effective against both mutant and wild type BRAF. There are some preliminary clinical reports of patients showing resistance to this drug on long-term usage. Our study aims at developing a resistant cell line model for the above drug and to understand the pathways and mechanisms involved in resistance development. Resistant model of HCT-116 cell line was developed by continuously culturing parental cell line in the presence of the drug. The IC50 values were compared between the parental cells and the cells exposed to drug continuously. BCL2 an anti-apoptotic protein was seen overexpressed in resistant cells in contrast to decreased expression in parental cells supporting the development of resistance.Further the multidrug resistance proteins MDR1 and ABCG-2 are highly up regulated in resistance model reconfirming the resistance development. This study aims at understanding how the JAK-STAT signaling pathway is modulated during drug resistance by expression profiling of molecules from this pathway by real time PCR. In this study, we found that JAK-STAT pathway is suppressed in the parental cells when treated with the sorafenib, but found actively expressed in resistant model. JAK-STAT signaling pathway is known to be activated in cancers and helps in regular proliferation of cancer cells. But as noticed from the above results upon drug treatment in parental cells this pathway get suppressed thereby leading to cell death. The active involvement of JAK-STAT pathway, which supports proliferation, was seen over expressed in drug resistance model.

Biochemical and Cellular Archives

Role of Jak-Stat signaling in sorafenib resistant HCT-116 cells

In this research paper, in total 212 individual leakage-free Polymethylmethacrylate (PMMA) microfluidic devices are fabricated by maskless lithography, hot embossing lithography and direct bonding technique. The effect of channel aspect ratio on dyed water flow is investigated using these microfluidic devices. Experimental studies show that the dyed water flow is faster on the surface of higher wettability. The effect of capillary pressure on dyed water flow is studied in the fabricated PMMA microfluidic devices. According to the experimental observations, the centrifugal force has prominent effect on the dyed water flow. Also, the effect of bend angle is investigated on the surface-driven capillary flow of water. The polystyrene microparticles have been separated in the microfluidic lab-on-a-chip systems using the investigated flow features. A 100\% separation efficiency is achieved in these lab-on-a-chip systems. These microfluidic lab-on-a-chip systems can be used to separate blood cells from human whole blood for further clinical tests. These experimental studies are important in bioengineering applications. The effect of bend angle as channel geometry to control the surface-driven capillary flow is investigated as a novel approach to control the separation time in microfluidic lab-on-a-chip systems. Also, the effect of surface wettability as surface property to control the surface-driven capillary flow is investigated as a novel approach to control the separation time in microfluidic lab-on-a-chip systems. © 2017 World Scientific Publishing Company.

Physics

Surface Review and Letters

Effects of surface properties on fluid engineering generated by the surface-driven capillary flow of water in Microfluidic Lab-On-A-Chip systems for bioengineering applications

One-dimensional diamond nanorods (DNRs) were fabricated from nanocrystalline diamond films using a facile combination of microwave plasma enhanced chemical vapor deposition and reactive ion etching (RIE) techniques. Structural and electrochemical properties of undoped and nitrogen doped DNRs were thoroughly investigated. A cyclic voltammetry study revealed the increase in density of charge carriers when doped with nitrogen. Mott Schottky analysis was implemented for the quantitative determination of the flat band potential, effective density of charge carriers and energy band diagram, which revealed that the undoped sample exhibit p-type behavior, whereas the nitrogen doped sample showed n-type behavior. Defect related damage due to graphitization and hydrogen termination in the undoped DNRs (during RIE) was correlated with the p-type conductivity. Nitrogen doping induces n-type conductivity and enhances effective density of charge carriers. © 2017 Elsevier Ltd

Electrochimica Acta

Probing the flat band potential and effective electronic carrier density in vertically aligned nitrogen doped diamond nanorods via electrochemical method

We obtain necessary and sufficient conditions for a matrix A to be Birkhoff-James orthogonal to another matrix B in the Ky Fan k-norms. A characterization for A to be Birkhoff-James orthogonal to any subspace W of M(n) is also obtained. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Mathematics

Linear and Multilinear Algebra

Orthogonality of matrices in the Ky Fan k-norms

<p>A new analytical approximate expression for K distribution is proposed by expanding it in terms of orthogonal associated Laguerre polynomial. The expansion is truncated after first three terms, which yields a fairly close approximation to K distribution. The advantage of the proposed approximation is that the analytical closed form expression for bit error rate can be easily derived. KL measure is used to show the accuracy of the proposed approximation. The proposed approximate probability density function and bit error rate work well within the desired range of the channel parameter α, which is 1 &lt; α &lt; 2 and corresponds to the scintillation index value ranging from 2 to 3. We have also demonstrated the utility of our approximation for other quality of service metric such as fade probability. © 2009-2012 IEEE.</p>

Computer Science and Engineering

(SoE) School of Engineering

IEEE Photonics Journal

A novel approximation for K distribution: Closed-form BER using DPSK modulation in free-space optical communication

The modifications of Poly(3-Hexylthiophene) (P3HT) thin films have been investigated by irradiating with 90 MeV Ni7+ ions at different fluences (1 × 109 to 1 × 1011 ions/cm2). Thin films have been characterized by micro-Raman Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), UV-visible absorption Spectroscopy, Photoluminescence spectroscopy (PL), Atomic Force Microscopy (AFM) and small angle X-ray scattering (SAXS) analysis. The narrow FWHM of C=C mode and the larger intensity ratio of C-C and C=C modes are identified at low fluences. The IR active modes with increased intensity indicates the increased conjugation length, while the XRD analysis revels the improved crystallinity with enhanced molecular ordering. The XPS analysis shows that chemical bonding nature near the film surface is not affected by irradiation. The room temperature electrical conductivity is found to be increased from 2.48 × 10−6 to 1.35 × 10−5 Ω−1cm−1 at the fluence of 1 × 1010 ions/cm2. The temperature dependence of dc conductivity has been explained using Mott's variable range hopping model. SAXS detector images confirm the presence of ion tracks and density variation between the track core and halo regions. It is found that less intense heating effect in the halo region of ion path could induce the molecular ordering of P3HT. © 2016 Elsevier Ltd

Vacuum

Ion irradiation induced modifications of P3HT: A donor material for organic photovoltaic devices

In the present work, the suitability of Aloe vera (AV) as a 'green reducing agent' has been investigated for the reduction of graphene oxide (GO). The extent of reduction was studied by varying the amount of AV. The physical and chemical properties of the GO and reduced graphene oxide (rGO) were investigated using UV-Vis spectrophotometry, FT-IR spectroscopy, High Resolution Transmission Electron Microscopy (HRTEM) and Selected Area Electron Diffraction (SAED). Partially reduced graphene oxide sheets obtained with 7.5 g of AV (rGO-7.5) demonstrated a maximum reduction efficiency of about 73\% as evident from FT-IR data. Cyclic voltammetry and electrochemical impedance spectroscopy studies revealed a significant enhancement in current density and a decrease in charge transfer resistance for the rGO-7.5 sample. Moreover, the as prepared rGO-7.5 sample showed a remarkable dye removal ability with a maximum efficiency of ∼98\%. The enhanced surface area, π-π interaction and strong electrostatic attraction were correlated with the dye removal capability. The adsorption kinetics were also studied and pseudo second order adsorption phenomena were confirmed. The recyclability of the rGO-7.5 sample was further investigated and an excellent desorption capability was established. © 2017 The Royal Society of Chemistry.

RSC Advances

Aloe vera assisted facile green synthesis of reduced graphene oxide for electrochemical and dye removal applications

Context: Thrombospondin1 (TSP1) participates in numerous signaling pathways critical for vascular physiology and disease. The conserved signature domain of thrombospondin 1 (TSP1-Sig1) comprises three epidermal growth factor (EGF), 13 calcium-binding type 3 thrombospondin (T3) repeats, and one lectin-like module arranged in a stalk-wire-globe topology. TSP1 is known to be present in both calcium-replete (Holo-) and calcium-depleted (Apo-) state, each with distinct downstream signaling effects. Objective: To prepare a homology model of TSP1-Sig1 and investigate the effect of calcium on its dynamic structure and interactions. Methods: A homology model of Holo-TSP1-Sig1 was prepared with TSP2 as template in Swissmodel workspace. The Apo-form of the model was obtained by omitting the bound calcium ions from the homology model. Molecular dynamics (MD) simulation studies (100 ns) were performed on the Holo- and Apo- forms of TSP1 using Gromacs4.6.5. Results and discussion: After simulation, Holo-TSP1-Sig1 showed significant reorientation at the interface of the EGF1-2 and EGF2-3 modules. The T3 wire is predicted to show the maximum mobility and deviation from the initial model. In Apo-TSP1-Sig1 model, the T3 repeats unfolded and formed coils with predicted increase in flexibility. Apo-TSP1-Sig1model also predicted the exposure of the binding sites for neutrophil elastase, integrin and fibroblast growth factor 2. We present a structural model and hypothesis for the role of TSP1-Sig1 interactions in the development of vascular disorders. Conclusion: The simulated model of the fully calcium-loaded and calcium-depleted TSP1-Sig1 may enable the development of its interactions as a novel therapeutic target for the treatment of vascular diseases. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Journal of Receptors and Signal Transduction

Calcium-induced conformational changes of Thrombospondin-1 signature domain: implications for vascular disease

Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP–EPAC1–AKAP9 direction to the development of additional biotherapeutics for breast cancer. © 2017, Springer Science+Business Media New York.