88 research outputs found
Abstract 5270: Disease subtype independent biomarkers of breast cancer prevention by withaferin a
No full textAbstract
Breast cancer is a rather complex and heterogeneous disease broadly grouped into four major subtypes, including luminal-type, basal-like, HER2 amplified, and normal-like, and each with a distinct molecular signature. A non-toxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study not only demonstrates chemoprevention of breast cancer in rats by the Ayurvedic medicine phytochemical withaferin A (WA) but also identifies its mechanistic biomarkers common to different subtypes of this disease. Chemopreventive efficacy of WA (4 and 8 mg per kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU). The mechanisms underlying breast cancer chemoprevention by WA were elucidated by western blotting, biochemical assays, immunohistochemistry, and cytokine profiling using plasma and tumors from the MNU-rat and/or mouse mammary tumor virus-neu (MMTV-neu) models. Inhibitory effect of WA on exit from mitosis and leptin-induced oncogenic signaling was determined using MCF-7 and MDA-MB-231 cells. Incidence, multiplicity, and burden of MNU-induced breast cancer in rats were decreased by WA administration. For example, the tumor weight in the 8 mg per kg group was lower by 67% compared with controls (P = 0.004). Mitotic arrest and apoptosis induction were common determinants of breast cancer chemoprevention by WA in the MNU-rat and MMTV-neu models. Cytokine profiling showed suppression of plasma leptin levels by WA in rats. WA inhibited leptin-induced oncogenic signaling in cultured MCF-7 and MDA-MB-231 cell lines. WA is a promising phytochemical with the ability to inhibit at least two different subtypes of breast cancer, including neu-driven estrogen receptor negative (ER-) breast cancer in MMTV-neu model and MNU-induced ER+ breast cancer in rats. This study was supported by the grant RO1 CA142604-07 awarded by the National Cancer Institute.
Citation Format: Eun-Ryeong Hahm, Suman K. Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Subrata K. Pore, Krishna B. Singh, Susan M. Christner, Yongli Shuai, Jan H. Beumer, Ruchi Roy, Nancy E. Davidson, Shivendra V. Singh. Disease subtype independent biomarkers of breast cancer prevention by withaferin a [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2017-5270</jats:p
Dynamic response of an Offshore wind turbine using linear (LIM) and non-linear (NLIM) environmental interaction models: A Parametric study
No full textThe present state-of-the-art modelling tools (such as FAST, BLADED) used for modelling an offshore wind turbine (OWT) are too detailed and computationally expensive. These tools are required only at detailed design stages of a project. For the preliminary phase, however, a much simpler (yet reliable) 3D model can improve and speedup the design process. Therefore, the aim of this thesis was to develop two different finite element models of an offshore wind turbine and compare their dynamic responses. In order to assess the extent of non-linearities in the environmental interactions arising due to structural motions, one model included the non-linear models of soil, hydrodynamic and aerodynamic loads (called NLIM henceforth) while the other used linearized expressions for modelling them (called LIM henceforth). The soil was modelled as a series of non-linear (and linear) elastic springs using p-y curves. The conventionally used Morison's equation was compared with MacCamy and Fuchs' equation for modelling the hydrodynamic loads on a large diameter pile. It was found that the MacCamy and Fuchs' equation is a better way of modelling the hydrodynamic loads on submerged cylinders than Morison's equation as it takes the wave diffraction effects into account. Several load cases were defined and the models were subjected to these load cases to check whether they are able to capture the physical behaviour of the OWT. The modal decomposition technique was used for reducing simulation time. It was found that the model(s) adequately captured the physical behaviour of the OWT till a wind speed of 20 m/s. Its side-side plane physical behaviour needs further investigation for a constant wind speed of 24 m/s. The LIM and the NLIM compared well for most load cases. For the side-side plane responses, however, the LIM developed a phase lag. A strong coupling was found between the motions (rotations) in fore-aft plane and the motions about the yaw axis. The structural velocities were found to be very small to influence hydrodynamic drag terms. Also, the defections of the pile in the soil were found to be too small suggesting that p-y curves do not capture the non-linear behaviour of soil accurately. Finally, a damping matrix resulting from the linearised aerodynamic forces was used for calculating the modal damping ratios related to different modes. The results were compared to the literature, with addition of side-side and yaw damping.Mechanical, Maritime and Materials EngineeringHydraulic EngineeringOffshore Engineerin
Effect of activation function symmetry on training of SFFANNs with the backpropagation algorithm
No full text
Biopesticides: Use of Rhizosphere Bacteria for Biological Control of Plant Pathogens
No full textThe pesticides used to control pests and diseases are also implicated in ecological, environmental and human health hazards. To reduce the deleterious effects of these agrochemicals, certain antagonistic microorganisms have been characterised from rhizosphere of different crop plants that suppress various plant diseases and thus, minimize the use of pesticides. The application of these specific antagonistic microorganisms in biological control of soilborne pathogens has been studied intensively in the last two decades. These beneficial rhizosphere microorganisms inhibit the pathogenic bacteria and fungi by producing antibiotics, bacteriocins, siderophores, hydrolytic enzymes and other secondary metabolites. The efficiency of these biocontrol products can be improved by manipulation of the environment, using mixtures of beneficial organisms, physiological and genetic enhancement of the biocontrol mechanisms, manipulation of formulations and integration of biocontrol with other alternative methods that provide additive effects. These biocontrol agents could be effectively utilised in sustainable agriculture for improving growth of crop plants
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