Planejamento estrat??gico governamental em contexto democr??tico: li????es da Am??rica Latina

Livro sobre Planejamento Estrat??gico, decorrente de curso do mesmo nome, realizado na ENAP em 2013, em parceria com o Centro Latino Americano de Administra????o para o Desenvolvimento (CLAD)

La brecha entre el reconocimiento y la implementaci��n de los derechos territoriales de los pueblos ind��genas: an��lisis sobre su configuraci��n en las normas, las pol��ticas y los jueces, tras la aprobaci��n de la Constituci��n Pol��tica de 1991

La del acceso a la tierra y su distribuci��n, ha sido una problem��tica transversal a la historia de los conflictos sociales en el pa��s. En el caso de los pueblos ind��genas, la existencia de todo un marco jur��dico nacional e internacional que reconoce sus derechos territoriales, as�� como de importantes avances que a este punto se han producido en cuanto a titulaci��n de tierras de resguardo en nuestro pa��s, fueron dos factores que invitaron a preguntarnos en este trabajo por las din��micas que, a pesar de ello, subyacen a un permanente desconocimiento de tales derechos. Con este objeto, en ��l se caracterizan las disputas que, desarrolladas en el marco del ordenamiento jur��dico e institucional de la Constituci��n Pol��tica de 1991, han llevado a la existencia de una contraposici��n entre el reconocimiento y la eficacia de los derechos territoriales de los pueblos ind��genas en Colombia. Desde una perspectiva cr��tica, la mirada propuesta presenta un abordaje a tales disputas que abarca una aproximaci��n a sus antecedentes hist��ricos y posterior configuraci��n a instancias de la expedici��n de las normas, la formulaci��n de las pol��ticas y el ejercicio del control judicial constitucional, en los a��os posteriores a 1991. Resultado de tal caracterizaci��n, se demuestra de qu�� manera dichas pugnas, que tienen expresiones normativas, administrativas y judiciales, y a su vez son determinadas por factores sociales, pol��ticos, econ��micos y culturales, han llevado a la existencia en nuestro pa��s, de una brecha de implementaci��n de tales derechos.

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement(1), increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively(2,3). Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement(4). Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

A homo-proline tetrazole as an improved organocatalyst for the asymmetric Michael addition of carbonyl compounds to nitro-olefins

A new homo-proline tetrazole derivative 7 has been prepared and shown to have improved properties for achieving asymmetric Michael addition of carbonyl compounds to nitro-olefins.

Organocatalysis with proline derivatives: improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions

Tetrazole and acylsulfonamide organocatalysts derived from proline have been synthesised and applied to the asymmetric Mannich, nitro-Michael and aldol reactions to give results that are superior to the proline-catalysed counterpart.

Trapping of palindromic ligands within native transthyretin prevents amyloid formation

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2���-(4,4���-(heptane 1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2���-(4,4���-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was con���rmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis.

Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal���Knorr pyrrole formation and gas concentration measurement by inline flow titration

Using a simple and accessible Teflon AF-2400 based tube-intube reactor, a series of pyrroles were synthesised in flow using the Paal���Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

Continuous-flow processing of gaseous ammonia using a Teflon AF-2400 tube-in-tube reactor: synthesis of thioureas and in-line titrations

A simple tube-in-tube reactor based on the gas-permeable membrane Teflon AF-2400 was used in the continuous flow reaction of gaseous ammonia with isothiocyanates and one isocyanate. A colourimetric in-line titration technique is also reported as a simple method to quantify the amount of ammonia taken up by the solvent in the system.

Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent

Here we describe general ���ow processes for the synthesis of alkyl and aryl azides, and the development of a new monolithic triphenylphosphine reagent, which provides a convenient format for the use of this versatile reagent in ���ow. The utility of these new tools was demonstrated by their application to a ���ow Staudinger aza-Wittig reaction sequence. Finally, a multistep aza-Wittig, reduction and puri���cation ���ow process was designed, allowing access to amine products in an automated fashion.

Tagged phosphine reagents to assist reaction work-up by phase-switched scavenging using a modular flow reactor

The use of three orthogonally tagged phosphine reagents to assist chemical work-up via phase-switch scavenging in conjunction with a modular flow reactor is described. These techniques (acidic, basic and Click chemistry) are used to prepare various amides and tri-substituted guanidines from in situ generated iminophosphoranes.

[3 + 2] Cycloaddition of acetylenes with azides to give 1,4-disubstituted 1,2,3-triazoles in a modular flow reactor

The cycloaddition of acetylenes with azides to give the corresponding 1,4-disubstituted 1,2,3-triazoles is reported using immobilised reagents and scavengers in pre-packed glass tubes in a modular flow reactor.

A modular flow reactor for performing Curtius rearrangements as a continuous flow process

The use of a mesofluidic flow reactor is described for performing Curtius rearrangement reactions of carboxylic acids in the presence of diphenylphosphoryl azide and trapping of the intermediate isocyanates with various nucleophiles.

Azide monoliths as convenient flow reactors for efficient Curtius rearrangement reactions

The preparation and use of an azide-containing monolithic reactor is described for use in a flow chemistry device and in particular for conducting Curtius rearrangement reactions via acid chloride inputs.