Trade liberalization and horizontal merger

Dissertação de mestrado em Economia Industrial e da EmpressaTrade liberalization implies increased international competition between firms and increased opportunities for foreign market access. Firms can choose to meet increased international competition by merging horizontally, either domestically or cross-border. Foreign firms can also choose horizontal merger as a way to access foreign markets. In this thesis we analyse theoretically how trade liberalization affects incentives for (domestic versus international) mergers and the corresponding welfare implications of trade liberalization. The analytical framework is a two-stage model with endogenous merger formation among domestic and foreign owners prior to Cournot competition in the domestic market. We also assume that there are different sources of cost synergies that can be realized through various types of horizontal merger. We find that international mergers arise in equilibrium only if trade costs are sufficiently high. On the other hand, the fully decentralized market structure (without any mergers) arises only if foreign firms are sufficiently more cost efficient that domestic firms. The welfare analysis shows that equilibrium market structures and the market structures that maximize domestic welfare do not always coincide.A liberalização do comércio implica o aumento da concorrência internacional entre empresas e o aumento das oportunidades de acesso ao mercado externo. As empresas podem escolher a fusão horizontal ao invés do nível nacional ou internacional para enfrentar o aumento da concorrência internacional. As empresas estrangeiras também podem escolher fusão horizontal, como forma de acesso aos mercados estrangeiros. Nesta tese, iremos analisar teoricamente como a liberalização do negócio afeta os incentivos (autóctone versus internacional), as fusões e as implicações sociais correspondentes de liberalização do comércio. O quadro analítico é um modelo de dois estágios com a formação endógena de fusão entre os proprietários nacionais e estrangeiros antes da competição Cournot no mercado doméstico. Assumimos também que existem diferentes fontes de sinergias de custos que podem ser realizados através de vários tipos de fusão horizontal. Nós achamos que as fusões internacionais surgem em equilíbrio somente se os custos de comércio são suficientemente elevados. Por outro lado, a estrutura de mercado totalmente descentralizada (sem fusões) surge apenas se as empresas estrangeiras forem suficientemente mais eficientes que as empresas nacionais. A análise de bem-estar mostra que as estruturas do mercado de equilíbrio e as estruturas de mercado que maximizam o bem-estar doméstico nem sempre coincidem

Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery.

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties

Novel hybrids of natural β-elemene bearing isopropanolamine moieties: synthesis, enhanced anticancer profile, and improved aqueous solubility

A series of novel β-elemene isopropanolamine derivatives were synthesized and evaluated for their antitumor activity. The results indicated that all of the compounds showed stronger antiproliferative activities than β-elemene as well as improved aqueous solubility. In particular dimer 6q showed the strongest cytotoxicity against four tumor cell lines (SGC-7901, HeLa, U87 and A549) with IC50 values ranging from 4.37 to 10.20 μM. Moreover, combination of 6q with cisplatin exhibited a synergistic effect on these cell lines with IC50 values ranging from 1.21 to 2.94 μM, and reversed the resistance of A549/DPP cells with an IC50 value of 2.52 μM. The mechanism study revealed that 6q caused cell cycle arrest at the G2 phase and induced apoptosis of SGC-7901 cells through a mitochondrial-dependent apoptotic pathway. Further in vivo study in H22 liver cancer xenograft mouse model validated the antitumor activity of 6q with a tumor inhibitory ratio (TIR) of 60.3%, which was higher than that of β-elemene (TIR, 49.1%) at a dose of 60 mg/kg. Altogether, the potent antitumor activity of 6qin vitro and in vivo warranted further preclinical investigation for potential anticancer chemotherapy

Regression Compatible Listwise Objectives for Calibrated Ranking

As Learning-to-Rank (LTR) approaches primarily seek to improve ranking quality, their output scores are not scale-calibrated by design -- for example, adding a constant to the score of each item on the list will not affect the list ordering. This fundamentally limits LTR usage in score-sensitive applications. Though a simple multi-objective approach that combines a regression and a ranking objective can effectively learn scale-calibrated scores, we argue that the two objectives can be inherently conflicting, which makes the trade-off far from ideal for both of them. In this paper, we propose a novel regression compatible ranking (RCR) approach to achieve a better trade-off. The advantage of the proposed approach is that the regression and ranking components are well aligned which brings new opportunities for harmonious regression and ranking. Theoretically, we show that the two components share the same minimizer at global minima while the regression component ensures scale calibration. Empirically, we show that the proposed approach performs well on both regression and ranking metrics on several public LTR datasets, and significantly improves the Pareto frontiers in the context of multi-objective optimization. Furthermore, we evaluated the proposed approach on YouTube Search and found that it not only improved the ranking quality of the production pCTR model, but also brought gains to the click prediction accuracy

Discovery of novel antitumor nitric oxide-donating b-elemene hybrids through inhibiting the PI3K/Akt pathway

A series of novel furoxan-based NO-donating b-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural b-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound b-elemene. Interestingly, these compounds displayed excellent sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which was superior to that of b-elemene (TIR, 49.6%) at the same dose of 60 mg/kg. Together, the remarkable biological profiles of these novel NO-donating b-elemene derivatives may make them promising candidates for the intervention of human cancers