Emerging Trade Patterns in a 3-Region Linear NEG Model: Three Examples

This chapter draws attention to a specific feature of a NEG model that uses linear (and not iso-elastic) demand functions, namely its ability to account for zero trade. Thus, it represents a suitable framework to study how changes in parameters that are typical for NEG models, such as trade costs and regional market size, not only shape the regional distribution of economic activity, but at the same time determine the emergence of additional trade links between formerly autarkic regions. We survey some related papers and present a three-region framework that potentially nests many possible trade patterns. To focus the analysis, we study in more detail three specific trade patterns frequently found in the EU trade network. We start with three autarkic regions; then we introduce the possibility that two regions trade with each other; and, finally, we allow for one region trading with the other two, but the latter are still not trading with each other. We find a surprising plethora of long-run equilibria each involving a specific regional distribution of economic activity and a specific pattern of trade links. We show how a reduction in trade costs shapes simultaneously industry location and the configuration of the trade network

Mitochondrial Pathway Mediates the Antileukemic Effects of Hemidesmus Indicus, a Promising Botanical Drug

Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades. The interest in further development of botanical drugs has been increasing steadily and the FDA recently approved the first new botanical prescription drug. The present study is designed to explore the potential antileukemic properties of Hemidesmus indicus with a view to contributing to further development of botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical evaluation.A variety of cellular assays and flow cytometry, as well as a phytochemical screening, were performed on different leukemic cell lines. We have demonstrated that Hemidesmus modulated many components of intracellular signaling pathways involved in cell viability and proliferation and altered the protein expression, eventually leading to tumor cell death, mediated by a loss of mitochondrial transmembrane potential and increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus significantly enhanced the antitumor activity of three commonly used chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically relevant observation is that its cytotoxic activity was also recorded in primary cells from acute myeloid leukemic patients.These results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its anticancer activity. On these bases, we conclude that Hemidesmus can represent a valuable tool in the anticancer pharmacology, and should be considered for further investigations