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It is argued that the competitive capacities from the regional and local point of view can be constructed, that in fact are tied to territorial policies and to the development of a territorial culture that integrates the local system of companies. Moreover a process of such nature can contribute to overcome the deterioration of backward territories. The construction of territorial competitiveness has to be one along the fundamental lines of action of sub-national governments. The existence of a solid service sector and some degree of specialisation in tertiary activities are among a number of territorial diversity of factors which need to be taken into account in relation to the creation of competitive capacities. In addition globalisation has presumably played a significant role in the productive restructuring of economies; within this the service sector has had over the years an increasing quantitative and qualitative importance in economic structures. This urges to evaluate the role of the third sector, in a context of economic globalisation, in the processes of constructing regional competitive capacities. This paper aims at providing a wide-ranging assessment of efficiency of the third sector at the regional level and its sources as well as an examination of the territorial structure of services and commerce in Mexico, specialisation patterns and productive structures. Our interest is to begin a line of study to analyse the efficiency of the Mexican tertiary sector by looking at the differences in regional performance and also the geographical determinants of these differentials. We will evaluate if there are clear patterns of concentration, specialisation and regional efficiency because of its impact on regional competitiveness. The regional efficiency of the service sector in Mexico in the period of NAFTA operation will be analysed. We employ state level data to examine technical efficiency's differentials across regions and their determinants. The methodology includes Data Envelopment Analysis to measure the efficiency of the third sector which is the dependent variable in a reduced form model that links regional performance with a number of proxies for various types of agglomeration economies such as specialisation, urbanisation and internal economies of scale.

The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

Helicobacter pylori is associated with peptic ulcer and gastric adenocarcinoma. Toll-like receptors (TLRs) participate in H. pylori recognition, and single-nucleotide polymorphisms (SNPs) in TLRs are associated with impaired immune response. We aimed to evaluate the association of TLR2/R753Q and TLR4/D299G/T399I SNPs with gastroduodenal diseases; and study the effect of SNPs on cytokine and chemokine expression in the gastric mucosa. Study included 450 Mexican patients with gastroduodenal diseases. SNPs in TLRs 2 and 4 genes were analyzed by allele-specific PCR. Cytokines and chemokines were assessed by qRT-PCR and immunoassay. TLR4/D299G/T399I polymorphisms were more frequent in duodenal ulcer and showed a trend in gastric cancer, when compared with non-atrophic gastritis. Patients with TLR4 polymorphisms expressed significantly lower levels of IL-1β, IL-6, IL-8 and GRO-α; and higher levels of TNF-α, IL-10, MCP-1 and MIP-1α . SNPs in TLR4 gene had an association with severe H. pylori -associated disease and with modified pattern of inflammatory cytokines and chemokines in the gastric mucosa. These results suggest that TLR4 SNPs contributes importantly to the clinical outcome of H. pylori infection.

A novel class of highly selective inhibitors of p38 MAP kinase was discovered from high throughput screening. The synthesis and optimization of a series of 5-amino-N-phenyl-1H-pyrazol-4-yl-3-phenylmethanones is described. An X-ray crystal structure of this series bound in the ATP binding pocket of unphosphorylated p38alpha established the presence of a unique hydrogen bond between the exocyclic amine of the inhibitor and threonine 106 which likely contributes to the selectivity for p38. The crystallographic information was used to optimize the potency and physicochemical properties of the series. The incorporation of the 2,3-dihydroxypropoxy moiety on the pyrazole scaffold resulted in a compound with excellent drug-like properties including high oral bioavailability. These efforts identified 63 (RO3201195) as an orally bioavailable and highly selective inhibitor of p38 which was selected for advancement into Phase I clinical trials.

Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38 was used to guide the optimization of the series. Specific focus was placed on modulating the physical properties of the core while maintaining potent inhibition of p38. These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies.

The synthesis of pyrazolo-pyridine, pyrimidine, pyrazine and pyridazine heterocycles is described. In addition, we report the utilization of 2,4-difluorophenoxide as a leaving group, to facilitate formation of the desired pyrazole adducts.

En este texto se revisa la evolución reciente de las zonas metropolitanas en México. Se presentan elementos de discusión teórica y conceptual acerca de la visión económica del fenómeno metropolitano y se describe la conformación y estructuración del sistema metropolitano en México. A partir de datos de los censos económicos (1998, 2003 y 2008) y de los censos de población y vivienda (1990, 2000 y 2010) se examina una serie de indicadores que dan cuenta de distintas dimensiones de las economías metropolitanas, de su población, así como del sistema metropolitano en su conjunto. Por un lado se encuentra un declive en varios aspectos del sistema de metrópolis; por otro, un reacomodo progresivo en el interior del sistema, donde la heterogeneidad urbana persiste. Los resultados, sin embargo, dependen de cada una de las variables consideradas.