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.

Shiv Nadar University

(SoNS) School of Natural Sciences

The currently available anthrax vaccines are limited by being incompletely characterized, potentially reactogenic and have an expanded dosage schedule. Plant based vaccines offer safe alternative for vaccine production. In the present study, we expressed domain IV of Bacillus anthracis protective antigen gene [PA(dIV)] in planta (by nuclear agrobacterium and chloroplast transformation) and E. coli [rPA(dIV)]. The presence of transgene and the expression of PA(dIV) in planta was confirmed by molecular analysis. Expression levels up to 5.3% of total soluble protein (TSP) were obtained with AT rich (71.8% AT content) PA(dIV) gene in transplastomic plants while 0.8% of TSP was obtained in nuclear transformants. Further, we investigated the protective response of plant and E. coli derived PA(dIV) in mice by intraperitoneal (i.p.) and oral immunizations with or without adjuvant. Antibody titers of &gt;104 were induced upon i.p. and oral immunizations with plant derived PA(dIV) and oral immunization with E. coli derived PA(dIV). Intraperitoneal injections with adjuvanted E. coli derived PA(dIV), generated highest antibody titers of &gt;105. All the immunized groups demonstrated predominant IgG1 titers over IgG2a indicating a polarized Th2 type response. We also evaluated the mucosal antibody response in orally immunized groups. When fecal extracts were analyzed, low sIgA titer was demonstrated in adjuvanted plant and E. coli derived PA(dIV) groups. Further, PA(dIV) antisera enhanced B. anthracis spore uptake by macrophages in vitro and also demonstrated an anti-germinating effect suggesting a potent role at mucosal surfaces. The antibodies from various groups were efficient in neutralizing the lethal toxin in vitro. When mice were challenged with B. anthracis, mice immunized with adjuvanted plant PA(dIV) imparted 60% and 40% protection while E. coli derived PA(dIV) conferred 100% and 80% protection upon i.p. and oral immunizations. Thus, our study is the first attempt in highlighting the efficacy of plant expressed PA(dIV) by oral immunization in murine model. © 2011 Elsevier Ltd.

World University root node

Life Sciences

Vaccine

A plant based protective antigen [PA(dIV)] vaccine expressed in chloroplasts demonstrates protective immunity in mice against anthrax

Fulltext

Blood

AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties (Blood (2011) 117, 2 (708-718))

Sustained and complete inhibition of HER3 and its output to PI3K/Akt are required for the optimal antitumor effect of therapeutic inhibitors of the HER2 oncogene. Here, we show that, after inhibition of the HER2 tyrosine kinase with lapatinib, there is PI3K/Akt and FoxO3a-dependent up-regulation of HER3 mRNA and protein. Up-regulated HER3 was then phosphorylated by residual HER2 activity, thus partially maintaining P-Akt and limiting the antitumor action of lapatinib. Inhibition of HER3 with siRNA or a neutralizing HER3 antibody sensitized HER2+ breast cancer cells and xenografts to lapatinib both in vitro and in vivo. Combined blockade of HER2 and HER3 inhibited pharmacodynamic biomarkers of PI3K/Akt activity more effectively than each inhibitor alone. These results suggest that because of HER3-mediated compensation, current clinical inhibitors of HER2 and PI3K/Akt will not block the PI3K pathway completely. They also suggest that therapeutic inhibitors of HER3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with HER2- and PI3K-dependent cancers.

Proceedings of the National Academy of Sciences of the United States of America

Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase

In breast cancer cells with HER2 gene amplification, HER2 receptors exist on the cell surface as monomers, homodimers, and heterodimers with EGFR/HER3. The therapeutic antibody trastuzumab, an approved therapy for HER2+ breast cancer, cannot block ligand-induced HER2 heterodimers, suggesting it cannot effectively inhibit HER2 signaling. Hence, HER2 oligomeric states may predict the odds of a clinical response to trastuzumab in HER2-driven tumors. To test this hypothesis, we generated nontransformed human MCF10A mammary epithelial cells stably expressing a chimeric HER2-FKBP molecule that could be conditionally induced to homodimerize by adding the FKBP ligand AP1510, or instead induced to heterodimerize with EGFR or HER3 by adding the heterodimer ligands EGF/TGFα or heregulin. AP1510, EGF, and heregulin each induced growth of MCF10A cells expressing HER2-FKBP. Trastuzumab inhibited homodimer-mediated but not heterodimer-mediated cell growth. In contrast, the HER2 antibody pertuzumab, which blocks HER2 heterodimerization, inhibited growth induced by heregulin but not AP1510. Lastly, the HER2/EGFR tyrosine kinase inhibitor lapatinib blocked both homodimer- and heterodimer-induced growth. AP1510 triggered phosphorylation of Erk1/2 but not AKT, whereas trastuzumab inhibited AP1510-induced Erk1/2 phosphorylation and Shc-HER2 homodimer binding, but not TGFα-induced AKT phosphorylation. Consistent with these observations, high levels of HER2 homodimers correlated with longer time to progression following trastuzumab therapy in a cohort of patients with HER2-overexpressing breast cancer. Together, our findings confirm the notion that HER2 oligomeric states regulate HER2 signaling, also arguing that trastuzumab sensitivity of homodimers may reflect their inability to activate the PI3K (phosphoinositide 3-kinase)/AKT pathway. A clinical implication of our results is that high levels of HER2 homodimers may predict a positive response to trastuzumab. ©2011 AACR.

Cancer Research

Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers

High altitude (HA) generates a deleterious effect known as hypobaric hypoxia (HBH). This causes severe physiological and psychological changes such as acute mountain sickness (AMS) and cognitive functions in terms of learning and memory. The present study has evaluated the effect of cholinesterase inhibitors on memory consolidation following HBH. Adult male Sprague Dawley rats (80-90 days old) with an average body weight of 250 ± 25 g were used. Rats were assessed memory consolidation by using Morris water maze (MWM) for 8 days. After assessment of memory consolidation, rats were then exposed to HBH in stimulated chamber for 7 days at 6,100 m. After exposure to HBH, the memory consolidation of rats has been assessed in MWM. The results showed that there was memory consolidation impairment in HBH-exposed rats as compared to normoxic rats in terms of time spent in quaradents, rings, and counters. The rats which have been treated with physostigmine (PHY) and galantamine (GAL) showed better time spent in quaradents, rings, and counters as compared with hypoxic rats. In conclusion, the cholinesterase inhibitors could ameliorate the impairment of memory consolidation following HBH. © 2011 Informa Healthcare USA, Inc.

International Journal of Neuroscience

Possible role of cholinesterase inhibitors on memory consolidation following hypobaric hypoxia of rats

This book is broadly about the mathematical aspects of finance. It introduces the reader to the basic concepts and products of modern finance and explores various mathematical models dealing with quantification of risk, which form the backbone of modern financial analysis. The emphasis is not so much on the details of the financial world as the basic principles by which one seeks an understanding of it. No prior knowledge of economics or finance is called for—an exposure to basic calculus and probability is all that is required of the reader. The appendix covers this ground in fair detail and would itself serve as a comprehensive primer of mathematics for finance for a beginner. The book is peppered with examples that use real-life data to ground the theory covered in the book. The exercises to be worked out are also interspersed in the text—their purpose varies from simple practice in applying formulas to extending the ideas learnt to new situations. Solutions to all the exercise problems are included as Appendix C, a feature that will be welcomed by both students and faculty. The book will serve well as an introductory book on applied mathematics in finance, of interest to students of mathematics, finance and financial management. For those starting out as practitioners of mathematical finance, this is an ideal introduction.

Mathematics

The Calculus of Finance

Four new neutral copper azido polymers, [Cu 4(N 3) 8(L 1)2] n (1), [Cu 4(N 3) 8(L 2)2] n (2), [Cu 4(N 3) 8(L 3)2] n (3) and [Cu9(N3)18(L 4)4]n (4) [L 1-4 are formed in situ by reacting pyridine-2-carboxaldehyde with 2-[2-(methylamino)ethyl]pyridine (mapy, L 1), N,N-dimethylethylenediamine (N,N-dmen, L 2), N,Ndiethylethylenediamine (N,N-deen, L 3) and N,N,2,2- tetramethylpropanediamine (N,N,2,2-tmpn, L 4)], have been synthesized by using 0.5 mol equiv of the chelating tridentate ligands with Cu- (NO 3) 2 33H 2O and an excess of NaN 3. Single-crystal X-ray structures show that the basic unit of these complexes, especially 1-3, contains very similar Cu II4 building blocks. The overall structure of 3 is two-dimensional, while the other three complexes are one-dimensional in nature.Complex 1 represents a unique example containing hemiaminal ether arrested by copper(II). Complexes 1 and 2 have a rare bridging azido pathway: both end-on and end-to-end bridging azides between a pair of Cu II centers. Cryomagnetic susceptibility measurements over a wide range of temperature exhibit dominant ferromagnetic behavior in all four complexes. Density functional theory calculations (B3LYP functional) have been performed on complexes 1-3 to provide a qualitative theoretical interpretation of their overall ferromagnetic behavior. {\textcopyright} 2011 American Chemical Society.

Chemistry

Inorganic Chemistry

Synthesis, structures and magnetic behavior of a series of copper(II) azide polymers of Cu 4 building clusters and isolation of a new hemiaminal ether as the metal complex

We consider the possibility that the vacuum energy density of the MSSM (Minimal Supersymmetric Standard Model) flat direction condensate involving the Higgses H1 and H2 is responsible for inflation. We also discuss how the finely tuned Higgs potential at high vacuum expectation values can realize cosmologically flat direction along which it can generate the observed density perturbations and after the end of inflation - the coherent oscillations of the Higgses reheat the universe with all the observed degrees of freedom, without causing any problem for the electroweak phase transition. {\textcopyright} 2011 IOP Publishing Ltd and SISSA.

Physics

Journal of Cosmology and Astroparticle Physics

Tuned MSSM Higgses as an inflaton

We show that a five-dimensional Universal Extra Dimension model, compactified on a line segment, is consistently formulated even when the gauge symmetry is broken solely by non-zero Dirichlet boundary conditions on a bulk Higgs field, without any quartic interaction. We find that the longitudinal W+W- elastic scattering amplitude, under the absence of the Higgs zero mode, is unitarized by exchange of infinite towers of KK Higgs bosons. Resultant amplitude scales linearly with the scattering energy ∝ √S, exhibiting five-dimensional nature. A tree-level partial-wave unitarity condition is satisfied up to 6.7 (5.7) TeV for the KK scale mKK = 430 (500) GeV, favored by the electroweak data within 90% CL. © Springer-Verlag / Società Italiana di Fisica 2011.

European Physical Journal C

Unitarity in Dirichlet Higgs model

In order to realize Si as a negative electrode material in commercial Li-ion batteries, it is important to understand the mixing mechanism of Li and Si, and stress evolution during lithiation in Si negative electrode of Li-ion batteries. Available experiments mainly provide the diffusivity of Li in Si as an averaged property, neglecting information regarding diffusivity of Si. However, if Si can diffuse as fast as Li, the stress generated during Li diffusion can be reduced. We, therefore, studied the diffusivity of Li as well as Si atoms in the Si-anode of Li-ion battery using an ab initio molecular dynamics-based methodology. The electrochemical insertion of Li into crystalline Si prompts a crystalline-to-amorphous phase transition. We considered this situation and thus examined the diffusion kinetics of Li and Si atoms in both crystalline and amorphous Si. We find that Li diffuses faster in amorphous Si as compared to crystalline Si, while Si remains relatively immobile in both cases and generates stresses during lithiation. To further understand the mixing mechanism and to relate the structure with electrochemical mixing, we analyzed the evolution of the structure during lithiation and studied the mechanism of breaking of Si-Si network by Li. We find that Li atoms break the Si rings and chains and create ephemeral structures such as stars and boomerangs, which eventually transform to Si-Si dumbbells and isolated Si atoms in the LiSi phase. Our results are found to be in agreement with the available experimental data and provide insights into the mixing mechanism of Li and Si in Si negative electrode of Li-ion batteries. © 2011 American Chemical Society.