10,622 research outputs found
International Business Training In The 21st Century: How Do They Learn?
International business and the ‘global marketplace’ have captured the American mindset. This is evidenced throughout our media, and certainly on U.S. business school campuses. More and more universities require international business courses as core course requirements, and many now offer international business as separate majors. Business study abroad programs have been around for years. Programs range from direct enrollment at foreign universities to ‘packaged’ courses offered by U.S. universities in other countries. Although these programs are popular with students and faculty alike, one questions how much learning is actually accomplished in these in-tensive but often brief programs. Based on the results of tests we administered we concluded that students participating in a three week Study Abroad course learned more about understanding the importance cultural differences in international business operations than students who cover the topic in a required international business course on campus
Quantitative analysis of NRF2 pathway reveals key elements of the regulatory circuits underlying antioxidant response and proliferation of ovarian cancer cells
Cells are constantly exposed to Reactive Oxygen Species (ROS) produced both endogenously to meet physiological requirements and from exogenous sources. While endogenous ROS are considered as important signalling molecules, high uncontrollable ROS are detrimental. It is unclear how cells can achieve a balance between maintaining physiological redox homeostasis and robustly activate the antioxidant system to remove exogenous ROS. We have utilised a Systems Biology approach to understand how this robust adaptive system fulfils homeostatic requirements of maintaining steady-state ROS and growth rate, while undergoing rapid readjustment under challenged conditions. Using a panel of human ovarian and normal cell lines, we experimentally quantified and established interrelationships between key elements of ROS homeostasis. The basal levels of NRF2 and KEAP1 were cell line specific and maintained in tight correlation with their growth rates and ROS. Furthermore, perturbation of this balance triggered cell specific kinetics of NRF2 nuclear–cytoplasmic relocalisation and sequestration of exogenous ROS. Our experimental data were employed to parameterise a mathematical model of the NRF2 pathway that elucidated key response mechanisms of redox regulation and showed that the dynamics of NRF2-H2O2 regulation defines a relationship between half-life, total and nuclear NRF2 level and endogenous H2O2 that is cell line specific
Semiconductor effective charges from tight-binding theory
We calculate the transverse effective charges of zincblende compound
semiconductors using Harrison's tight-binding model to describe the electronic
structure. Our results, which are essentially exact within the model, are found
to be in much better agreement with experiment than previous
perturbation-theory estimates. Efforts to improve the results by using more
sophisticated variants of the tight-binding model were actually less
successful. The results underline the importance of including quantities that
are sensitive to the electronic wavefunctions, such as the effective charges,
in the fitting of tight-binding models.Comment: 4 pages, two-column style with 2 postscript figures embedded. Uses
REVTEX and epsf macros. Also available at
http://www.physics.rutgers.edu/~dhv/preprints/index.html#jb_t
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
Chesapeake Energy Corporation
Chesapeake is the second largest producer of natural gas in the United States, but the company is struggling financially. In addition, its CEO left the company amid governance concerns. This case provides a description of upstream, midstream and downstream energy production and trends in those segments, and how Chesapeake has shifted its emphasis in an effort to increase its performance. The extreme price volatility in this industry is also described, as are technological advances in areas such as “fracking.
Systems analysis of drug-induced receptor tyrosine kinase reprogramming following targeted mono- and combination anti-cancer therapy
The receptor tyrosine kinases (RTKs) are key drivers of cancer progression and targets for drug therapy. A major challenge in anti-RTK treatment is the dependence of drug effectiveness on co-expression of multiple RTKs which defines resistance to single drug therapy. Reprogramming of the RTK network leading to alteration in RTK co-expression in response to drug intervention is a dynamic mechanism of acquired resistance to single drug therapy in many cancers. One route to overcome this resistance is combination therapy. We describe the results of a joint in silico, in vitro, and in vivo investigations on the efficacy of trastuzumab, pertuzumab and their combination to target the HER2 receptors. Computational modelling revealed that these two drugs alone and in combination differentially suppressed RTK network activation depending on RTK co-expression. Analyses of mRNA expression in SKOV3 ovarian tumour xenograft showed up-regulation of HER3 following treatment. Considering this in a computational model revealed that HER3 up-regulation reprograms RTK kinetics from HER2 homodimerisation to HER3/HER2 heterodimerisation. The results showed synergy of the trastuzumab and pertuzumab combination treatment of the HER2 overexpressing tumour can be due to an independence of the combination effect on HER3/HER2 composition when it changes due to drug-induced RTK reprogramming
Public-private health sector partnerships for STD control in South Africa perspectives from the Hlabisa experience
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ERBE and AVHRR Cirrus cloud fire study
Understanding the impact of cirrus clouds on the global radiation budget is essential to determining the role of clouds in the process of climate change. The ongoing Earth Radiation Budget Experiment (ERBE) is charged with measuring the global radiation balance at the top of the atmosphere. The International Satellite Cloud Climatology Project (ISCCP) is measuring global cloud amounts and properties over a time frame similar to ERBE. Specific cloud properties are absent from the ERBE program, while ISCCP lacks the broadband radiances necessary to determine the total radiation fields. Together, results from these two global programs have the potential for improving the knowledge of the relationship between cirrus clouds and the Earth radiation balance. The First ISCCP Regional Experiment (FIRE), especially its cirrus Intensive Field Observations (IFO), provides opportunities for studying radiation measurements from the ERBE taken over areas with known cirrus cloud properties. Satellite measurements taken during the IFO are used to determine the broadband radiation fields over cirrus clouds and to examine the relationship between narrowband and broadband radiances over various known scenes. The latter constitutes the link between the ERBE and the ISCCP
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