Understanding tissue morphology: model repurposing using the CoSMoS process

We present CoSMoS as a way of structuring thinking on how to reuse parts of an existing model and simulation in a new model and its implementation. CoSMoS provides a lens through which to consider, post-implementation, the assumptions made during the design and implementation of a software simulation of physical interactions in the formation of vascular structures from endothelial cells. We show how the abstract physical model and its software implementation can be adapted for a different problem: the growth of cancer cells under varying environmental perturbations. We identify the changes that must be made to adapt the model to its new context, along with the gaps in our knowledge of the domain that must be filled by wet-lab experimentation when recalibrating the model. Through parameter exploration, we identify the parameters that are critical to the dynamic physical structure of the modelled tissue, and we calibrate these parameters using a series of in vitro experiments. Drawing inspiration from the CoSMoS project structure, we maintain confidence in the repurposed model, and achieve a satisfactory degree of model reuse within our in silico experimental system

Kepentingan Indonesia Melarang Ekspor Benih Lobster ke Vietnam Tahun 2015

This research will explain why Indonesia banned the export of breeding lobster out of state that described is in the study case of a ban on the export of breeding lobster to Vietnam. The purpose of this research is to find out how the mining lobster in Indonesia, and how the necessity of Vietnam about breeding lobster in Indonesia and to discover why Indonesia banned the export of breeding lobster to Vietnam that is listed in the Number 1/PERMEN-KP/2015.The method that used is library research where the data obtained from sources that are relevant to the research problems are discussed. This research uses the perspective of mercantilism, and theories of foreign policy and theories export as well as the concept of national interest according to Jack. Plano and Roy Olton.The result of this research indicate that the purpose of Indonesia stop the export of breeding lobster to Vietnam is to reduce the export volume of breeding lobster because the population of lobster in the wild has declined

NRF2 regulates HER1 signaling pathway to modulate the sensitivity of ovarian cancer cells to lapatinib and erlotinib

NF-E2-related factor 2 (NRF2) regulates the transcription of a battery of metabolic and cytoprotective genes. NRF2 and epidermal growth factor receptors (EGFRs/HERs) are regulators of cellular proliferation and determinants of cancer initiation and progression. NRF2 and HERs confer cancers with resistance to several therapeutic agents. Nevertheless, there is limited understanding of the regulation of HER expression and activation and the link between NRF2 and HER signalling pathways. We show that NRF2 regulates both basal and inducible expression of HER1, as treatment of ovarian cancer cells (PEO1, OVCAR3, and SKOV3) with NRF2 activator tBHQ inducing HER1, while inhibition of NRF2 by siRNA knockdown or with retinoid represses HER1. Furthermore, treatment of cells with tBHQ increased total and phosphorylated NRF2, HER1, and AKT levels and compromised the cytotoxic effect of lapatinib or erlotinib. Treatment with siRNA or retinoid antagonised the effect of tBHQ on NRF2 and HER1 levels and enhanced the sensitivity of ovarian cancer cells to lapatinib or erlotinib. Pharmacological or genetic inhibition of NRF2 and/or treatment with lapatinib or erlotinib elevated cellular ROS and depleted glutathione. This extends the understanding of NRF2 and its regulation of HER family receptors and opens a strategic target for improving cancer therapy

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2. HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target

Techno-economic evaluation of utilizing a small-scale microgrid

Microgrid deployment has offered technical and economical benefits such as improving grid reliability, maximizing penetration of intermittent renewable energy sources, reducing the cost of energy production, etc. However, to realize those advantages, the costs of microgrid implementation may be bloated as microgrid need additional investment for the enabling technologies. Therefore, an appropriate approach to determine the economic viability of microgrid to quantify the values of microgrid benefits is needed. This study performs a techno-economic analysis of a small-scale grid-connected microgrid deployment which consists of photovoltaic (PV) and energy storage system. The analysis is done by considering the possible bussines models available in Indonesia where the microgrid test case is located, i.e, net metering for electricity bill, feed-in tariff for utilizing renewable energy, demand response (DR) implementation by exploiting battery roles in response of price variation during peak and off-peak period and assuming compensation is given every time microgrid is in islanded mode due to fault event occur in the main grid. The feasibility of each model is indicated by the microgrid’s net present value (NPV) and internal rate of return (IRR). The results show that further incentives from the utility or Government is required to make the small-scale microgrid deployment economically sustainable

Relation proximal point with some dynamical properties

In this paper we discussed relation proximal points with many of  dynamical properties through studied topological transformation group , and it will given  necessary condition for proximal relation to be minimal set ,and introduce  new define replete set and semi-replete set by using concept of the replete set and semi-replete set as well as  we introduce that many of  new  relations  and theorem. Key words: Proximal point, replete proximal point, syndetic set, semi-replete set, minimal set, almost periodic point             .