148 research outputs found
The GATT and the Uruguay Round: An Exercise in Real Politik
No full textThe author explores the present status of the Uruguay Round. Banerji then reviews the discussions in the 15 major areas, all of which may not be of immediate interest to India. The author then moves on to analyse the progress in discussions in areas that are of interest to India. These are tariffs, non-tariff measures, GATT article, safeguards, functioning of the CATT system, MTN agreements and arrangements, subsidies, countervailing measures and dispute settlement. The author ends by outlining some polemical issues, viz., textiles and clothing, agriculture, TRIPS and TRIMS and services. The author endorses the multitiered flexible approach to the final deal as proposed by Prof. Jagdish Bhagwati. (Editor’s abstract.
The GATT and the Uruguay Round: An Exercise in Real Politik
No full textThe author explores the present status of the Uruguay Round. Banerji then reviews the discussions in the 15 major areas, all of which may not be of immediate interest to India. The author then moves on to analyse the progress in discussions in areas that are of interest to India. These are tariffs, non-tariff measures, GATT article, safeguards, functioning of the CATT system, MTN agreements and arrangements, subsidies, countervailing measures and dispute settlement. The author ends by outlining some polemical issues, viz., textiles and clothing, agriculture, TRIPS and TRIMS and services. The author endorses the multitiered flexible approach to the final deal as proposed by Prof. Jagdish Bhagwati. (Editor’s abstract.
Galaxy Zoo:reproducing galaxy morphologies via machine learning
No full textWe present morphological classifications obtained using machine learning for objects in SDSS DR6 that have been classified by Galaxy Zoo into three classes, namely early types, spirals and point sources/artifacts. An artificial neural network is trained on a subset of objects classified by the human eye and we test whether the machine learning algorithm can reproduce the human classifications for the rest of the sample. We find that the success of the neural network in matching the human classifications depends crucially on the set of input parameters chosen for the machine-learning algorithm. The colours and parameters associated with profile-fitting are reasonable in separating the objects into three classes. However, these results are considerably improved when adding adaptive shape parameters as well as concentration and texture. The adaptive moments, concentration and texture parameters alone cannot distinguish between early type galaxies and the point sources/artifacts. Using a set of twelve parameters, the neural network is able to reproduce the human classifications to better than 90% for all three morphological classes. We find that using a training set that is incomplete in magnitude does not degrade our results given our particular choice of the input parameters to the network. We conclude that it is promising to use machine- learning algorithms to perform morphological classification for the next generation of wide-field imaging surveys and that the Galaxy Zoo catalogue provides an invaluable training set for such purposes
Political regimes, trade, and labor policies in developing countries
No full textWhat, if any, is the link between labor market policies that benefit insiders - for example, regulations guaranteeing high minimum wages and strict job security - and political regimes. Is it true that in a democracy outsiders vote and impose limits on what insiders can achieve, whereas in a dictatorship the government need worry only about insiders who have real power? Or are democratic governments more likely to succumb to trade union pressure and use labor policies to give them special privileges? To test these competing hypotheses, the authors designed a two-sector political economy model that demonstrates that labor market distortions depend directly on the trade regime: the more open the trade regime, the fewer distortions in the labor market. They use cross-country regressions to test the relationship between political and civil liberties and trade and labor policies. Using data for 90 developing countries, they apply existing indices of openness and political freedom and two different constructed measures of labor market distortion. Their conclusions, based on the regression results: authoritarian systems that repress labor are more likely than democratic systems to adopt inefficient labor policies inimical to development.Economic Theory&Research,Environmental Economics&Policies,Labor Policies,Health Economics&Finance,Banks&Banking Reform,Environmental Economics&Policies,Health Economics&Finance,Banks&Banking Reform,Labor Standards,Economic Theory&Research
Targeting Metabolism and Autophagy in the Context of Haematologic Malignancies
No full textAutophagy is a cellular process that maintains the homeostasis of the normal cell. It not only allows for cell survival in times of metabolic stress with nutrient recycling but also is able to lead to cell death when required. During malignant transformation the cell is able to proliferate and survive. This is due to altered cell metabolism and the presence of altered genetic changes that maintain the cell survival. Metabolism was considered an innocent bystander that was a consequence of the increased nutrient requirement for the survival and proliferation of haematological malignancies. The interdependency of metabolism and cellular mechanisms such as autophagy are becoming more evident and important. This interdependence contributes to increased cancer progression and drug resistance. In this paper we aim to discuss autophagy, how it pertains to metabolism in the context of hematologic malignancies, and the implications for therapy.Peer Reviewe
Targeting Metabolism and Autophagy in the Context of Haematologic Malignancies
No full textAutophagy is a cellular process that maintains the homeostasis of the normal cell. It not only allows for cell survival in times of metabolic stress with nutrient recycling but also is able to lead to cell death when required. During malignant transformation the cell is able to proliferate and survive. This is due to altered cell metabolism and the presence of altered genetic changes that maintain the cell survival. Metabolism was considered an innocent bystander that was a consequence of the increased nutrient requirement for the survival and proliferation of haematological malignancies. The interdependency of metabolism and cellular mechanisms such as autophagy are becoming more evident and important. This interdependence contributes to increased cancer progression and drug resistance. In this paper we aim to discuss autophagy, how it pertains to metabolism in the context of hematologic malignancies, and the implications for therapy
Targeting Mitochondrial Bioenergetics as a Therapeutic Strategy for Chronic Lymphocytic Leukemia
No full textAltered cellular metabolism is considered a hallmark of cancer and is fast becoming an avenue for therapeutic intervention. Mitochondria have recently been viewed as an important cellular compartment that fuels the metabolic demands of cancer cells. Mitochondria are the major source of ATP and metabolites necessary to fulfill the bioenergetics and biosynthetic demands of cancer cells. Furthermore, mitochondria are central to cell death and the main source for generation of reactive oxygen species (ROS). Overall, the growing evidence now suggests that mitochondrial bioenergetics, biogenesis, ROS production, and adaptation to intrinsic oxidative stress are elevated in chronic lymphocytic leukemia (CLL). Hence, recent studies have shown that mitochondrial metabolism could be targeted for cancer therapy. This review focuses the recent advancements in targeting mitochondrial metabolism for the treatment of CLL.</jats:p
Developing a 3D chronic lymphocytic leukemia (CLL) microenvironment
No full textChronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal B lymphocytes in the blood, lymph nodes, bone marrow and spleen. These microenvironments provide a protective niche for CLL cells that promote CLL cell survival and drug resistance. The dependence of CLL cells on their microenvironments in vivo is depicted by the spontaneous apoptosis CLL cells undergo when cultured alone in vitro. Co-culture of CLL cells with accessory cells or other components of the microenvironment such as cytokines, has been shown to counteract this spontaneous apoptosis of CLL cells, and has also been shown to be effective at preventing apoptosis from a variety of treatments. The dependence of CLL cells on their 3D microenvironment illustrates the need to develop a three-dimensional (3D) cell culture system for CLL, that incorporates components of their microenvironment in vivo, in order to develop research tools to explore new therapeutic targets. There are limited methods to study the CLL microenvironment, such as adaptations of two-dimensional (2D) cell culture and animal models. The objective of this thesis is to develop a 3D cell culture model for CLL that incorporates the microenvironment. Drug resistance remains a significant clinical barrier to treat CLL patients, where treatments are initially effective, but the disease often relapses. By understanding the role microenvironment factors play in promoting CLL cell survival during treatment, effective therapeutic strategies could be developed to overcome drug resistance.February 202
B-cell metabolic reprogramming through Hexokinase-II
No full textB-cell activation occurs via antigen binding to its membrane immunoglobulin along with T-cell help to initiate intracellular signaling cascades. B cell activation enhances glucose uptake, the phosphoinositide-3-kinase (PI3K) pathway, and glycolysis and oxidative phosphorylation in a balanced manner relative to resting B-cells. The enzyme Hexokinase (HK) is central to B cell activation as it catalyzes the first step of glucose metabolism by phosphorylating glucose to become glucose-6-phosphate, which then serves as an entry point for several metabolic pathways. Hexokinase-II (HKII) is one of four HK isoforms and is particularly interesting as the only isoform that can translocate between the cytoplasm and mitochondria. It is unknown if HKII, in comparison to the other isoforms, preferentially guides glucose-6-P down a particular metabolic pathway which may depend on the B-cell’s activation status and HKII’s cellular localization. B-cell activation through the T-cell dependent signals and the PI3K pathway reprograms resting B-cell metabolism by the modification of HKII expression and subcellular localization to meet the B-cell’s new activated metabolic program. B-cells with unusual HKII expression or subcellular localization may be a feature of B-cell metabolic dysregulation, such as that observed in Chronic Lymphocytic Leukemia (CLL).
A novel intracellular staining and flow cytometry assay was developed to measure HKII expression levels across B-cell subsets throughout the body and a fluorescence microscopy based assay quantified HKII mitochondrial localization. A biological mechanism is presented herein, where B-cell activation dependent on the PI3K pathway significantly increased HKII expression and along with the presence of glucose enhanced HKII mitochondrial localization. CLL B-cells failed to increase HKII expression following in vitro B-cell activation and expressed significantly less HKII, which decreased with advanced clinical Rai stage, compared to control B-cells; suggesting CLL B-cells may decrease HKII expression beyond normal levels as an anergic metabolic response to limit chronic B-cell activation.
A B-cell specific HKII knockout mouse model assessed the impact of HKII deletion on B-cell subset frequencies, antibody production, and metabolism. HKII deficiency significantly reduced activated B-cells, germinal centre B-cells, and plasma cell frequencies post sheep red blood cell immunization. Plasma blasts and immunization induced plasma cells had the highest HKII expression levels across B-cell subsets and HKII played a functional role during a B-cell immune response since HKII deficiency significantly reduced antibody production in vitro and in vivo. The impact that HKII expression and localization has on B-cell metabolism during resting and activated conditions is evaluated by mass spectrometry metabolite profiling, carbon tracing using 13C labelled glucose, and a seahorse assay to quantify the ATP production rate from glycolysis and oxidative phosphorylation. HKII acted as an energy switch guiding the transition from rest to B-cell activation by fine tuning the activation of catabolic and anabolic pathways. During rest, when glucose is scare, HKII promoted glycogen breakdown for energy but facilitated the anabolic production of nucleotides and hexosamine biosynthetic pathway metabolites. During B-cell activation, when intracellular glucose is in excess, HKII promoted glycogen synthesis for energy storage and played a catabolic role in elevating the glycolytic and total ATP production rate and citric acid cycle metabolite levels. HKII is a functionally important component of B cell metabolic reprogramming dependent on the PI3K pathway and may act as an energy sensor to guide the transition from B-cell rest to activation that coincides with a switch from glycogen breakdown to synthesis depending on glucose availability.The University of Manitoba Tri-Council Master's Supplement AwardFebruary 202
The welfare effects of a large depreciation : the case of Egypt, 2000-05
No full textThe Egyptian pound depreciated sharply between 2000 and 2005, declining by 26 percent in nominal trade-weighted terms. The author investigates the effect of the large depreciation on household welfare operating through exchange rate-induced changes in consumer prices. He estimates exchange rate pass-through regressions using disaggregated monthly consumer price indices to isolate the impact of the exchange rate changes on consumer prices. Then he uses household-level data from the 2000 and 2005 Egyptian household surveys to quantify the welfare effects of these consumer price changes at the household level. The average welfare loss due to exchange rate-induced price increases was equivalent to 7.4 percent of initial expenditure. Stronger estimated exchange rate pass-through for food items imply that this effect disproportionately affected poorer households.Markets and Market Access,Access to Markets,Economic Theory&Research,Poverty Lines,Commodities
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