Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135

Transformações químicas, caracterizações e estudo de modelagem molecular do clerodano bioativo trans-desidrocrotonina

In this work it were developed synthetic and theoretical studies for clerodane-type diterpenes obtained from Croton cajucara Benth which represents one of the most important medicinal plant of the Brazil amazon region. Specifically, the majoritary biocompound 19-nor-clerodane trans-dehydrocrotonin (t-DCTN) isolated from the bark of this Croton, was used as target molecule. Semi-synthetic derivatives were obtained from t-DCTN by using the followed synthetic procedures: 1) catalytic reduction with H2, 2) reduction using NaBH4 and 3) reduction using NaBH4/CeCl3. The semi-synthetic 19-nor-furan-clerodane alcohol-type derivatives were denominated such as t-CTN, tCTN-OL, t-CTN-OL, t-DCTN-OL, t-DCTN-OL, being all of them characterized by NMR. The furan-clerodane alcohol derivatives t-CTN-OL and tCTN-OL were obtained form the semi-synthetic t-CTN, which can be isolated from the bark of C. cajucara. A theoretical protocol (DFT/B3LYP) involving the prevision of geometric and magnetic properties such as bond length and angles, as well as chemical shifts and coupling constants, were developed for the target t-DCTN in which was correlated NMR theoretical data with structural data, with satisfactory correlation with NMR experimental data (coefficients ranging from 0.97 and 0.99) and X-ray diffraction data. This theoretical methodology was also validated for all semi-synthetic derivatives described in this work. In addition, topological data from the Quantum Theory of Atoms in Molecules (QTAIM) showed the presence of H-H and (C)O--H(C) intramolecular stabilized interactions types for t-DCTN e t-CTN, contributing to the understanding of the different reactivity of this clerodanes in the presence of NaBH4.

Novos adsorventes para aplicação na remoção de enxofre de combustíveis

Currently the market requires increasingly pure oil derivatives and, with that, comes the need for new methods for obtaining those products that are more efficient and economically viable. Considering the removal of sulfur from diesel, most refineries uses catalytic hydrogenation process, the hydrodesulfurization. These processes needs high energy content and high cost of production and has low efficiency in removing sulfur at low concentrations (below 500 ppm). The adsorption presents itself as an efficient and economically viable alternative in relation to the techniques currently used. With that, the main purpose of this work is to develop and optimize the obtaining of new adsorbents based on diatomite, modified with two non ionic surfactants microemulsions, adding efficiency to the material, to its application on removal of sulfur present in commercial diesel. Analyses were undertaken of scanning electron microscopy (SEM), x-ray diffraction (XRD), x-ray fluorescence (XRF), thermogravimetry (TG) and N2 adsorption (BET) for characterization of new materials obtained. The variables used for diatomite modification were: microemulsion points for each surfactant (RNX 95 and UNTL 90), microemulsion aqueous phase through the use or non-use of salts (CaCl2 and BaCl2), the contact time during the modification and the contact form. The study of adsorption capacity of materials obtained was performed using a statistical modeling to evaluate the influence of salt concentration in the aqueous phase (20 ppm to 1500 ppm), finite bath temperature (25 to 60° C) and the concentration of sulphur in diesel. It was observed that the temperature and the concentration of sulphur (300 to 1100 ppm) were the most significant parameters, in which increasing their values increase the ability of modified clay to adsorb the sulphur in diesel fuel. Adsorption capacity increased from 0.43 to mg/g 1.34 mg/g with microemulsion point optimization and with the addition of salts.

Remoção de nitratos em água utilizando diferentes materiais e processos

The need to preserve the environment has led to the search for new materials for efficient disposal of chemical compounds that alter the stability of our natural resources. Among these resources, stands in first place the water, as a precious commodity and scarce, leading to the proper use and reuse. As a result, the World Health Organization has established maximum permissible values in drinking water, such as: 50 mg/L, 0, 1 mg/L and 0, 5 mg/L to at-3, at-2, NH 4, respectively. For these reasons, assesses the implementation of new materials and water treatment processes aiming at the removal of these compounds, such as alumina, in the form of powder or as a support for a catalytic system using inorganic membranes capable of supporting more severe conditions of temperature and pressure by opening new possibilities for applications of membrane reactors; and also for electrochemical treatments with doped diamond bobo electrodes (BDD) as anode and copper as cathode. For such purpose, was conducted the study of adsorption of nitrate in different times to assess the time required to achieve equilibrium by employing three commercial alumina called: acidic, basic and neutral alumina, with subsequent treatment only in the acidic alumina impregnating metals (PdCu/Al2O3) for the catalytic reaction. The materials were previously characterized by XRD, SEM techniques and ABET. Aluminas presented a considerable adsortive capacity of nitrate in the first thirty minutes, equivalent to 50% of removal reaching equilibrium in that time. After treatment, using alumina as catalyst for the reaction in batch reactor (Pd-Cu/Al2O3), the results were more favourable, totalling 64% reduction of ion NO3-at the end of three hours. On the other hand, the results for the catalytic reaction using the catalytic support Pd-Cu/TiO2 in membrane reactor proved to be low. -if, in this way, improve the conditions of catalytic system to optimize the process. Already, for the electrochemical tests using DDB1 electrodes as anode, and Cu, as cathode, there was a fairly significant nitrate reduction, approximately 80% of ion removal during three hours and cost viable applications.

Catalisadores bifuncionais à base de silicoaluminofosfato e fosfatos de nióbio para emprego em reações de hidroisomerização e hidrocraqueamento do n-hexadecano

Lubricants and cutting middle distillates typically have large amounts of n-paraffins to increase its freezing point and fluidity. Accordingly, the removal of n-paraffins of long chain lubricants oils and diesel is essential to get a product with good cold flow properties. The development of new catalysts, which exhibit thermal stability and catalytic activity for the hydroisomerization reaction is still a challenge. Thus, silicoaluminophosphates (SAPO) were synthesized by different routes. Have been used also post-synthesis treatment for obtaining hybrid structures and others synthesis have been carried out with mesoporous template (soft and hard-template). Therefore, SAPO have been impregnated with H2PtCl6 solution by the incipient wetness method. Then assessments of catalytic activities in hydroisomerization and hydrocracking reactions of hexadecane have been held. Besides SAPO, niobium phosphate - NbP - were also impregnated with platinum and evaluated in the same reaction. After impregnation, these catalysts have been characterized by X-ray diffraction (XRD), nitrogen adsorption, infrared spectroscopy with adsorbed pyridine (IV-PY), scanning electron microscopy (SEM) and resonance nuclear magnetic 29Si (29Si-NMR). The characterization results by XRD have shown that it has been possible to obtain mesoporous SAPOs. However, for the syntheses with soft template there was collapse of the structure after removal of the organic template. Even so, these catalysts have been actives. It was possible to obtain hybrid materials through the synthesis of SAPO-11 made with hard templates and by means of post-synthesis treatments samples of SAPO-11. Moreover, NbP has shown characteristic XRD of amorphous materials, with high acidity and were active in the conversion of hexadecane.

Catalisadores bifuncionais à base de silicoaluminofosfato e fosfatos de nióbio para emprego em reações de hidroisomerização e hidrocraqueamento do n-hexadecano

Lubricants and cutting middle distillates typically have large amounts of n-paraffins to increase its freezing point and fluidity. Accordingly, the removal of n-paraffins of long chain lubricants oils and diesel is essential to get a product with good cold flow properties. The development of new catalysts, which exhibit thermal stability and catalytic activity for the hydroisomerization reaction is still a challenge. Thus, silicoaluminophosphates (SAPO) were synthesized by different routes. Have been used also post-synthesis treatment for obtaining hybrid structures and others synthesis have been carried out with mesoporous template (soft and hard-template). Therefore, SAPO have been impregnated with H2PtCl6 solution by the incipient wetness method. Then assessments of catalytic activities in hydroisomerization and hydrocracking reactions of hexadecane have been held. Besides SAPO, niobium phosphate - NbP - were also impregnated with platinum and evaluated in the same reaction. After impregnation, these catalysts have been characterized by X-ray diffraction (XRD), nitrogen adsorption, infrared spectroscopy with adsorbed pyridine (IV-PY), scanning electron microscopy (SEM) and resonance nuclear magnetic 29Si (29Si-NMR). The characterization results by XRD have shown that it has been possible to obtain mesoporous SAPOs. However, for the syntheses with soft template there was collapse of the structure after removal of the organic template. Even so, these catalysts have been actives. It was possible to obtain hybrid materials through the synthesis of SAPO-11 made with hard templates and by means of post-synthesis treatments samples of SAPO-11. Moreover, NbP has shown characteristic XRD of amorphous materials, with high acidity and were active in the conversion of hexadecane.

Preparação de catalisadores para reações de esterificação do ácido oleico baseados em matrizes polímericas sulfonadas POLI(1- FENILETILENO) (PS) e POLI(1-CLOROETILENO) (PVC)

Chemical modification of polymer matrices is an alternative way to change its surface properties. The introduction of sulfonic acid groups in polymer matrices alter properties such as adhesion, wettability, biocampatibility, catalytic activity, among others. This paper describes the preparation of polymeric solid acid based on the chemical modification of poly (1-fenietileno) (PS) and Poly (1-chloroethylene) (PVC) by the introduction of sulfonic acid groups and the application of these polymers as catalysts in the esterification reaction of oleic acid with methanol. The modified materials were characterized by Infrared Spectroscopy, Elemental Analysis and titration acid-base of the acid groups. All techniques confirmed the chemical changes and the presence of sulfur associated with sulfonic acid groups or sulfates. The modified polymers excellent performance in the esterification reaction of oleic acid with methanol a degree of conversion higher than 90% for all investigated polymers (modified PS and PVC (5% w / w)), with a mass ratio of oleic acid: methanol 1:10 to 100 ° C. The best performance was observed for the modified PVC catalyst (PVCS) which showed low degree of swelling during the reactions is recovered by filtration different from that observed for polystyrene sulfonate (PSS). Given these facts, the PVCS was employed as a catalyst in the esterification reaction of oleic acid in different times and different temperatures to obtain the kinetic parameters of the reaction. Experimental data show a great fit for pseudo-homogeneous model of second order and activation energy value of 41.12 kJ mol -1, below that found in the literature for the uncatalyzed reaction, 68.65 kJ mol -1 .The PVCS exhibits good catalytic activity for 3 times of reuse, with a slight decrease in the third cycle, but with a conversion of about 78%. The results show that solid polymeric acid has good chemical stability for the application in esterification reaction of commercial importance with possible application in the biodiesel production. The advantages in use of this system are the increased reaction rate at about 150 times, at these test conditions, the replacement of sulfuric acid as a catalyst for this being the most corrosive and the possibility of reuse of the polymer for several cycles.

Aplicación del sistema de recombinación específica de secuencia β-six al estudio de la regulación de la expresión génica en células eucariotas y modelos animales

Las recombinasas específicas de secuencia son herramientas muy valiosas en la generación de modificaciones génicas condicionales. Estos sistemas permiten controlar la recombinación de forma específica de tejido, temporalmente, o ambas, y sortean diversas limitaciones de los sistemas de knockout (KO) convencionales, como la letalidad embrionaria o la generación de mecanismos compensatorios. Actualmente los sistemas Cre/loxP y Flp/FRT son los más empleados tanto en modelos animales como vegetales. La necesidad de realizar modificaciones más complejas en un mismo organismo hace que sea primordial caracterizar otras recombinasas que complementen a las existentes. La b recombinasa (b-rec) es originaria del plásmido pSM19035 de Streptococcus pyogenes. A diferencia de Cre y Flp, que en ausencia de factores adicionales catalizan la integración en un nuevo sustrato, la b-rec necesita un sustrato superenrollado y un cofactor de la reacción, una proteína asociada a la cromatina (como la procariota Hbsu o la eucariota HMG1). Se ha demostrado que la b-rec cataliza de forma específicamente intramolecular (resolución o inversión) la recombinación en células eucariotas, tanto de sustratos episomales como integrados en la cromatina, lo que indica que el entorno eucariota es capaz de proveer del cofactor y del superenrollamiento necesarios para que la b-rec realice su función. En este trabajo hemos determinado que la tasa de recombinación mediada por la b-rec no se ve afectada en absoluto por la deficiencia en el cofactor HMG1, alcanzando el mismo valor de recombinación en MEF KO en HMG1 que en wt. Este y otros datos confirman que en el entorno eucariota hay otras proteínas accesorias que pueden actuar de cofactores y sugiere que estas reacciones pueden ocurrir en la mayor parte de tejidos y tipos celulares. Para estudiar detalladamente el potencial de la b-rec en eucariotas desarrollamos un sistema de RAGE (activación génica mediada por recombinación) dependiente de la actividad b-rec; este sistema ha resultado funcional tanto en sustratos episomales como en sustratos integrados en la cromatina. También hemos generado un vector retroviral que porta la proteína de fusión b-Egfp, permitiendo de forma rápida y eficiente la integración y expresión funcional de nuestra proteína...

Anafilaxia en urgencias: incidencia, diagnóstico y manejo clínico

La anafilaxia fue descrita en 1902, sin embargo, sigue sin existir una definición de anafilaxia universalmente aceptada. La más utilizada, en la actualidad, es la publicada en el documento de consenso del simposio sobre la definición y el manejo de la anafilaxia del año 2005, que la describe como “una reacción alérgica de inicio rápido que puede producir la muerte”. Actualmente, la anafilaxia se clasifica en inmunológica (IgE dependiente o independiente) y no inmunológica (por ejemplo, la originada por algunos contrastes iodados). Sus síntomas están causados por una liberación masiva de mediadores, principalmente de mastocitos y basófilos, que pueden tener como diana cualquier órgano. Los datos epidemiológicos acerca de la anafilaxia son escasos. La prevalencia se estima entre el 0,05% y el 2%, aunque su incidencia parece estar aumentando. En los últimos años, se han publicado varios estudios que han intentado establecer la incidencia de anafilaxia en los servicios de urgencias de diversos hospitales. Los datos publicados en estos estudios oscilan entre el 0,07% y el 0,4%. Esta variabilidad puede deberse a características de la población y zona geográfica, y también a limitaciones metodológicas, condicionadas principalmente por la falta de consenso en cuanto a su definición, las dificultades para la codificación de la anafilaxia mediante códigos CIE y el funcionamiento de los servicios de urgencias. Además, la mayor parte de estos estudios se centran en pacientes adultos, y en menos ocasiones analizan las características de los pacientes en edad pediátrica...

La demostración de la existencia del mundo externo en dos experiencias de enseñanza de la filosofía : La Escuela Primaria y la Universidad

Nuestro interés en este trabajo es llevar a cabo algunas reflexiones sobre el proceso de enseñanza-aprendizaje y lo que allí sucede, a partir de la experiencia de plantear un mismo problema filosófico en el marco de un taller de filosofía con niños de 8 años, y en el marco de una clase universitaria de filosofía para alumnos de primer año de la carrera de Psicología. Los puntos que contrastaremos son: el abordaje diferencial del disparador de la pregunta (algunos pasajes de las obras de Descartes y Hume), la reacción de los alumnos y el tipo de respuesta elaborado por ambos grupos, así como el rol del docente en cada caso. Para finalizar, esbozaremos algunas reflexiones referidas a la influencia de la instancia de evaluación de contenidos como factor de diferenciación en el proceso de enseñanza y aprendizaje en ambos espacios

La tutela jurídica de los bienes arqueológicos en la Roma pontificia: Del "Sacco" de Roma al Dominio francés (1527-1795)

El presente artículo es síntesis de un trabajo doctoral dedicado al interés por los restos del pasado y su conocimiento así como a los comienzos de la tutela jurídica del patrimonio arqueológico en el Estado Pontificio. Se trata de una primera entrega que tendrá continuidad con otras posteriores. Se analiza en ésta la reacción del papado al Sacco de Roma y las mediadas de protección que se pusieron en marcha, destacando la creación del cargo de Commissario dell’antichità primera autoridad creada en Europa para el control de las excavaciones arqueológicas, hallazgos y exportaciones. Al mismo tiempo se analizan las Proibizioni y Editti promulgados para el control de los bienes arqueológicos desde 1527 hasta 1795.

From labelling to social aid for immigrants in the 21st Century

Migration is as old as humanity, but since the 1990s migration flows in Western Europe have led to societies that are not just multicultural but so-called «super-diverse». As a result, Western towns now have very complex social structures, with amongst others large amounts of small immigrant communities that are in constant change. In this paper we argue that for social workers to be able to offer adequate professional help to non-native residents in town, they will need balanced view of ‘culture’ and of the role culture plays in social aid. Culture is never static, but is continually changing. By teaching social workers about how to look at cultural backgrounds of immigrant groups and about the limitations of then role that culture plays in communication, they will be better equipped to provide adequate aid and will contribute to making various groups grow towards each other and to avoid people thinking in terms of ‘out-group-homogeneity’. Nowadays, inclusion is a priority in social work that almost every social worker supports. Social workers should have an open attitude to allow them to approach every individual as a unique person. They will see the other person as the person they are, and not as a part of a specific cultural group. Knowledge about the others makes them see the cultural heterogeneity in every group. The social sector, though, must be aware not to fall into the trap of the ‘inclusion mania’! This will cause the social deprivation of a particular group to be forgotten. An inclusive policy requires an inclusive society. Otherwise, this could result in even more deprivation of other groups, already discriminated against. Emancipation of deprived people demands a certain target-group policymaking. Categorized aid will raise efficiency of working with immigrants and of acknowledging the cultural identity of the non-natives group. It will also create the possibility to work on fighting social deprivation, in which most immigrants can be found.

Aproximación al clítico 的 de en chino

Debido a las características intrínsecas de la lengua china, los clíticos juegan un papel imprescindible en la estructura sintáctica del idioma. Sin ellos, las oraciones no llegan a construirse, ya que son estos, entre otros recursos, los que cargan las informaciones gramaticales; es más, cada clítico en chino ocupa un hueco en la gramática, por lo que es difícil remplazarlos sin cambiar el sentido de la oración. De todos los clíticos, la palabra «的» es la que se presenta con mayor frecuencia. Esta palabra, como muchas otras “palabras vacías”, desempeña diversas funciones gramaticales, por lo que constituye un punto de investigación muy interesante en la gramática china. Desde los años 20 del siglo pasado, generaciones de eruditos se han dedicado a su estudio, entre otros, figuran Li Jinxi（黎锦熙), Gao Mingkai（高名凯),Chen Qiongzan（陈琼瓒), Fan Jiyan（范继淹）y Zhu Dexi（朱德熙). Un artículo de este último Sobre “的 (De)” ha provocado una amplia reacción y una profunda influencia en las investigaciones posteriores. A pesar de todo y hasta hoy en día, el uso de esta palabra sigue siendo un escollo tanto para los profesores de chino como para sus alumnos. Las ambigüedades que puede causar y la diferencia semántica y pragmática de su uso y desuso han sido un rompecabezas no sólo para los extranjeros, sino también para los nativos. En este artículo, intentaremos delimitar sus usos y analizar sus valores semánticos y pragmáticos.

El Norte de Africa y el Sahel y la Estrategia Global de Seguridad de la Unión Europea

El objetivo del artículo es exponer una adecuada y necesaria redefinición de la política de la UE hacia el Norte de África y el Sahel, tanto en términos geográficos como en términos estratégicos de acuerdo con lo expuesto en la nueva Estrategia Global Europea. En este sentido, se revisarán los postulados y la evolución de la antigua Estrategia Europea de Seguridad (EES) y su consiguiente Política de Vecindad (ENP), en comparación con la recién lanzada Estrategia. La nueva Estrategia es concebida como una guía para el desarrollo de la política exterior y de seguridad que la UE ha de llevar a cabo, inter alia, en su periferia. Lamentablemente su concepción de esta zona regional resulta anclada en el pasado.

Contact dermatitis from shoes: an update

Contact dermatitis is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions that occur after contact with a foreign substance. There are two forms of contact dermatitis: irritant and allergic. Irritant contact dermatitis is caused by the non–immune-modulated irritation of the skin by a substance, leading to skin changes. Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur after reexposure to the substance. A medical condition referred to as “shoe dermatitis” is a form of contact dermatitis caused by the contact of the foot with parts of the shoe due to these materials. Shoe dermatitis is a diagnostic and therapeutic challenge and is a common type of contact dermatitis. It is imperative the foot and ankle physician become familiar with recognizing signs and symptoms of shoe dermatitis so that their patients can be accurately diagnosis and appropriately treated to avoid secondary infections and disability. This review will first present causative factors for the etiology of shoe contact dermatitis supported by clinical-based evidence as found in the medical literature. Secondly, a description of the signs and symptoms of shoe contact dermatitis will be presented in a narrative fashion. Finally, both treatment options and preventative measures to avoid shoe.