Theoretical study on receptor-G protein recognition: new insights into the mechanisms of the alpha1b-adrenergic recptor activation

This work compares the structural/dynamics features of the wild-type alb-adrenergic receptor (AR) with those of the D142A active mutant and the agonist-bound state. The two active receptor forms were compared in their isolated states as well as in their ability to form homodimers and to recognize the G alpha q beta 1 gamma 2 heterotrimer. The analysis of the isolated structures revealed that, although the mutation- and agonist-induced active states of the alpha 1b-AR are different, they, however, share several structural peculiarities including (a) the release of some constraining interactions found in the wild-type receptor and (b) the opening of a cytosolic crevice formed by the second and third intracellular loops and the cytosolic extensions of helices 5 and 6. Accordingly, also their tendency to form homodimers shows commonalties and differences. In fact, in both the active receptor forms, helix 6 plays a crucial role in mediating homodimerization. However, the homodimeric models result from different interhelical assemblies. On the same line of evidence, in both of the active receptor forms, the cytosolic opened crevice recognizes similar domains on the G protein. However, the docking solutions are differently populated and the receptor-G protein preorientation models suggest that the final complexes should be characterized by different interaction patterns.

Theoretical study of the electrostatically driven step of receptor-G protein recognition.

This study proposes a theoretical model describing the electrostatically driven step of the alpha 1 b-adrenergic receptor (AR)-G protein recognition. The comparative analysis of the structural-dynamics features of functionally different receptor forms, i.e., the wild type (ground state) and its constitutively active mutants D142A and A293E, was instrumental to gain insight on the receptor-G protein electrostatic and steric complementarity. Rigid body docking simulations between the different forms of the alpha 1 b-AR and the heterotrimeric G alpha q, G alpha s, G alpha i1, and G alpha t suggest that the cytosolic crevice shared by the active receptor and including the second and the third intracellular loops as well as the cytosolic extension of helices 5 and 6, represents the receptor surface with docking complementarity with the G protein. On the other hand, the G protein solvent-exposed portions that recognize the intracellular loops of the activated receptors are the N-terminal portion of alpha 3, alpha G, the alpha G/alpha 4 loop, alpha 4, the alpha 4/beta 6 loop, alpha 5, and the C-terminus. Docking simulations suggest that the two constitutively active mutants D142A and A293E recognize different G proteins with similar selectivity orders, i.e., G alpha q approximately equal to G alpha s > G alpha i > G alpha t. The theoretical models herein proposed might provide useful suggestions for new experiments aiming at exploring the receptor-G protein interface.

Estudi del comportament sísmic d'una estructura de formigó armat amb forjats de llosa massissa i dissipadors d'energia

Anàlisi de la resposta estructural d’un edifici d’oficines de formigó armat amb pilars i forjats de llosa massissa situat en una zona de sismicitat elevada segons diferents variants constructives. L’emplaçament teòric de l’obra és la ciutat de Granada, per tant, li serà d’aplicació la normativa española vigent. L’estudi es basa especialment en la Normativa Sismorresistent Espanyola (NCSE-02) i el Codi Tècnic de l’Edificació (CTE), entre d’altres

Disseny, anàlisi del comportament i fabricació d’un nou dissipador d’energia per a edificis sismorresistents

Definició, disseny, anàlisi del comportament i procés de fabricació d’un nou dissipador d’energia amb la finalitat de poder ser utilitzat en edificis sotmesos a situacions de moviment sísmic

Aplicacions de la fibra òptica a la monitorització d'estructures

Davant la gran necessitat que es té per reduir al mínim els costs relacionats amb el manteniment, prevenció i seguretat, la monitorització en el camp de les estructures civils és una activitat que ha anat adquirint un paper cada cop més important. Dins el camp de l’enginyeria civil, la instrumentació d’estructures d’edificació i obra civil ha experimentat una profunda expansió. Les aplicacions més habituals en aquest tipus d’ activitat, solen estar associades a l’avaluació d’esforços en estructures existents, i/o el seguiment de l’estat tenso-deformacional durant el procés de construcció. Hi ha una gran diversitat de dispositius de mesura que permeten realitzar aquest seguiment. Els sistemes basats en la tecnologia de fibra òptica ja ho permeten. La resistència a la corrosió i a la fatiga, la immunitat a les interferències electromagnètiques o la possibilitat de prendre mesures discretes al llarg del temps, podent referir-les en tot moment a l’origen, són alguns dels seus avantatges. Tot i els múltiples avantatges, aquest sistema també té els seus inconvenients. En tota seguretat el més important és l’influencia de la temperatura en els valors mesurats. El projecte es centre en aquest últim punt , concretament en les mesures de deformació. Els objectius que s’han dut a terme al llarg de la durada del treball han estat els següents: - Aprendre les bases teòriques d’aquesta tecnologia. - Determinar en quin grau, la temperatura afecta a les mesures adquirides mitjançant sensors de fibra òptica. - Establir els mecanismes adients per quantificar, corregir o minimitzar aquests efectes. - Comparar la fiabilitat d’aquest tipus de mesura respecte a la dels sensors basats en extensometria

Disseny, anàlisi del comportament i fabricació d’un nou dissipador d’energia per a edificis sismorresistents

Definició, disseny, anàlisi del comportament i procés de fabricació d’un nou dissipador d’energia amb la finalitat de poder ser utilitzat en edificis sotmesos a situacions de moviment sísmic

Estudi del comportament sísmic d'una estructura de formigó armat amb forjats de llosa massissa i dissipadors d'energia

Anàlisi de la resposta estructural d’un edifici d’oficines de formigó armat amb pilars i forjats de llosa massissa situat en una zona de sismicitat elevada segons diferents variants constructives. L’emplaçament teòric de l’obra és la ciutat de Granada, per tant, li serà d’aplicació la normativa española vigent. L’estudi es basa especialment en la Normativa Sismorresistent Espanyola (NCSE-02) i el Codi Tècnic de l’Edificació (CTE), entre d’altres

Strategic use of private standards to enhance international competitiveness: Vegetable exports from Kenya and elsewhere

The paper examines how European retailers are using private standards for food safety and,quality as risk management and competitive tools and the strategic responses of leading Kenyan and other developing country supplier/exporters to such standards. Despite measures to harmonize a 'single market', the European fresh produce market is very diverse in terms of consumer preferences, structural dynamics and attention to and enforcement of food safety and other standards. Leading Kenyan fresh produce suppliers have re-positioned themselves at the high end, including 'high care', segments of the market - precisely those that are most demanding in terms of quality assurance and food safety systems. An array of factors have influenced this strategic positioning, including relatively high international freight costs, the emergence of more effective competition in mainstream product lines, relatively low labor costs for produce preparation, and strong market relationships with selected retail chains. To succeed in this demanding market segment, the industry has had to invest substantially in improved production and procurement systems, upgraded pack house facilities, and quality assurance/food safety management systems. (C) 2005 Elsevier Ltd. All rights reserved.

Using of model updating considering damped frequency response function

The search for better performance in the structural systems has been taken to more refined models, involving the analysis of a growing number of details, which should be correctly formulated aiming at defining a representative model of the real system. Representative models demand a great detailing of the project and search for new techniques of evaluation and analysis. Model updating is one of this technologies, it can be used to improve the predictive capabilities of computer-based models. This paper presents a FRF-based finite element model updating procedure whose the updating variables are physical parameters of the model. It includes the damping effects in the updating procedure assuming proportional and none proportional damping mechanism. The updating parameters are defined at an element level or macro regions of the model. So, the parameters are adjusted locally, facilitating the physical interpretation of the adjusting of the model. Different tests for simulated and experimental data are discussed aiming at defining the characteristics and potentialities of the methodology.

How C-terminal carboxyamidation alters the biological activity of peptides from the venom of the eumenine solitary wasp

Inflammatory peptides display different types of post-transcriptional modifications, such as C-terminal amidation, that alter their biological activity. Here we describe the structural and molecular dynamics features of the mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF-NH2), found in the venom of the solitary wasp, and of its carboxyl-free C-terminal form (EMP-AF-COO-) characterized by a reduced activity. Circular dichroism indicates that both peptides switch from a random coil conformation in water to a helical structure in TFE and SDS micelles. NMR data, in 30% TFE, reveal that the two peptides fold into an alpha-helix spanning most of their length, while they differ in terms of molecular rigidity. To understand the origins of the conformational flexibility observed in the case of EMP-AF-COO-, a 5 ns MD simulation was carried out for each peptide, in an explicit water/TFE environment. The results show that the two peptides differ in an H-bond between Leu14 NH2 and the backbone carbonyl of Ile11. The loss of that H-bond in EMP-AF-COO- leads to a significant modification of its structural dynamics. In fact, as evidenced by essential dynamics analysis, while EMP-AF-NH2 exists mainly as a rigid structure, EMP-AF-COO- presents two helical stretches that fluctuate in some sort of independent fashion. We conclude that the diverse biological activity of the two peptides is not simply due to the reduction of the net positive charge, as generally suggested, but also to a structural perturbation of the amphipathic alpha-helix that affects their ability to perturb the cell membrane.

Revisão sobre técnicas de controle em estruturas inteligentes

One of the great challenges of structural dynamics is to ally structures lighther and stronger. The great difficulty is that light systems, in general, have a low inherent damping. Besides, they contain resonance frequencies in the low frequency range. So, any external disturbance can excite the system in some resonance and the resulting effect can be drastic. The methodologies of active damping, with control algorithms and piezoelectric sensors and actuators coupled in a base structure, are attractive in current days, in order to overcome the contradictory features of these requeriments. In this sense, this article contributes with a bibliographical review of the literature on the importance of active noise and vibration control in engineering applications, models of smart structures, techniques of optimal placement of piezoelectric sensors and actuators and methodologies of structural active control. Finally, it is discussed the future perspectives in this area.

Robust control applications for smart truss structure

A finite element modeling of an intelligent truss structure with piezoelectric stack actuators for the purpose of active damping and structural vibration attenuation is presented. This paper concerns with the following issues aspects: the design of intelligent truss structure considering electro-mechanical coupling between the host structure and piezoelectric stack actuators; the H 2 norm approach to search for optimal placement of actuators and sensors; and finally some aspects in robust control techniques. The electro-mechanical behavior of piezoelectric elements is directly related to the successful application of the actuators in truss structures. In order to achieve the desired damping in the interested bandwidth frequency it is used the H ∞ output feedback solved by convex optimization. The constraints to be reached are written by linear matrix inequalities (LMI). The paper concludes with a numerical example, using Matlab and Simulink, in a cantilevered, 2-bay space truss structure. The results demonstrated the approach applicability.

Optimal placement of sensors/actuators in truss structures with known disturbances

An important stage in the solution of active vibration control in flexible structures is the optimal placement of sensors and actuators. In many works, the positioning of these devices in systems governed for parameter distributed is, mainly, based, in controllability approach or criteria of performance. The positions that enhance such parameters are considered optimal. These techniques do not take in account the space variation of disturbances. An way to enhance the robustness of the control design would be to locate the actuators considering the space distribution of the worst case of disturbances. This paper is addressed to include in the formulation of problem of optimal location of sensors and piezoelectric actuators the effect of external disturbances. The paper concludes with a numerical simulation in a truss structure considering that the disturbance is applied in a known point a priori. As objective function the C norm system is used. The LQR (Linear Quadratic Regulator) controller was used to quantify performance of different sensors/actuators configurations.

Experimental damage detection using system norms

Nowadays there is great interest in structural damage detection in systems using nondestructive tests. Once the failure is detected, as for instance a crack, it is possible to take providences. There are several different approaches that can be used to obtain information about the existence, location and extension of the fault in the system by non-destructive tests. Among these methodologies, one can mention different optimization techniques, as for instance classical methods, genetic algorithms, neural networks, etc. Most of these techniques, which are based on element-byelement adjustments of a finite element (FE) model, take advantage of the dynamic behavior of the model. However, in practical situations, usually, is almost impossible to obtain an accuracy model. In this paper, it is proposed an experimental technique for damage location. This technique is based on H: norm to obtain the damage location. The dynamic properties of the structure were identified using experimental data by eigensystem realization algorithm (ERA). The experimental test was carried out in a beam structure through varying the mass of an element. For the output signal was used a piezoelectric sensor. The signal of input of sine form was generated through SignalCalc® software.