Computational study of ligand binding in lipid transfer proteins: Structures, interfaces, and free energies of protein-lipid complexes

Plant nonspecific lipid transfer proteins (nsLTPs) bind a wide variety of lipids, which allows them to perform disparate functions. Recent reports on their multifunctionality in plant growth processes have posed new questions on the versatile binding abilities of these proteins. The lack of binding specificity has been customarily explained in qualitative terms on the basis of a supposed structural flexibility and nonspecificity of hydrophobic protein-ligand interactions. We present here a computational study of protein-ligand complexes formed between five nsLTPs and seven lipids bound in two different ways in every receptor protein. After optimizing geometries inmolecular dynamics calculations, we computed Poisson- Boltzmann electrostatic potentials, solvation energies, properties of the protein-ligand interfaces, and estimates of binding free energies of the resulting complexes. Our results provide the first quantitative information on the ligand abilities of nsLTPs, shed new light into protein-lipid interactions, and reveal new features which supplement commonly held assumptions on their lack of binding specificity.

Estudio de la fisuración de paneles sándwich de yeso laminado y alma de lana de roca = Study of the cracking of sandwich panels of plasterboard and rockwool

Este artículo presenta el estudio de la rotura de paneles sándwich de yeso laminado y lana de roca bajo solicitaciones de flexo-tracción dentro de su plano. Estos paneles se emplean para conformar tabiques interiores de edificación y con frecuencia se fisuran por flechas excesivas en los forjados. Actualmente no hay modelos de cálculo fiables ni datos experimentales que permitan estudiar este problema. Este trabajo presenta los resultados de una campaña experimental encaminada a caracterizar el comportamiento en rotura de los paneles sándwich y de sus componentes individuales. Además, se presenta un modelo cohesivo con fisura embebida que permite simular el comportamiento en rotura del panel sándwich conjunto. Por último se presentan los resultados de los ensayos de fractura en modo mixto (tracción/cortante) de paneles comerciales y se reproduce su comportamiento con el modelo cohesivo propuesto, obteniéndose un buen ajuste. This paper presents the study of plasterboard and rockwool sandwich panels cracking under flexural loading. These panels are usually used to perform interior partition walls and they frequently show cracking pathology due to excessive deflexion of the slabs. There are currently no reliable simulation models and experimental data for the study of this problem. This paper presents the results of an experimental campaign aimed to characterize the fracture behaviour of sandwich panels and their individual components. In addition, the paper presents a cohesive model with embedded crack to simulate the fracture behaviour of the panel. Finally we present the results of tests for mixed mode fracture (tensile / shear) commercial panels and their behaviour is reproduced with the cohesive model proposed, yielding a good fit.

A comparative study of SISO and MIMO control strategies for floor vibration damping

Civil engineering structures such as floor systems with open-plan layout or lightweight footbridges are susceptible to excessive level of vibrations caused by human loading. Active vibration control (AVC) via inertial mass actuators has been shown to be a viable technique to mitigate vibrations, allowing structures to satisfy vibration serviceability limits. Most of the AVC applications involve the use of SISO (single input single-output) strategies based on collocated control. However, in the case of floor structures, in which mostof the vibration modes are locally spatially distributed, SISO or multi-SISO strategies are quite inefficient. In this paper, a MIMO (multi-inputs multi-outputs) control in decentralised and centralised configuration is designed. The design process simultaneously finds the placement of multiple actuators and sensors and the output feedback gains. Additionally, actuator dynamics, actuator nonlinearities and frequency and time weightings are considered into the design process. Results with SISO and decentralised and centralised MIMO control (for a given number of actuators and sensors) are compared, showing the advantages of MIMO control for floor vibration control.

Coupled models for the dynamics of bridges under high-speed rail traffic

The dynamic effects of high-speed trains on viaducts are important issues for the design of the structures, as well as for determining safe running conditions of trains. In this work we start by reviewing the relevance of some basic moving load models for the dynamic action of vertical traffic loads. The study of lateral dynamics of running trains on bridges is of importance mainly for the safety of the traffic, and may be relevant for laterally compliant bridges. These studies require 3D coupled vehicle-bridge models and consideration of wheel to rail contact. We describe here a fully nonlinear coupled model, formulated in absolute coordinates and incorporated into a commercial finite element framework. An application example is presented for a vehicle subject to a strong wind gust traversing a bridge, showing the relevance of the nonlinear wheel-rail contact model as well as the interaction between bridge and vehicle.

Collective Organization of Complex Networks: Emergent Scales, Vulnerability, and Targeting of Desired Dynamics

Cuando una colectividad de sistemas dinámicos acoplados mediante una estructura irregular de interacciones evoluciona, se observan dinámicas de gran complejidad y fenómenos emergentes imposibles de predecir a partir de las propiedades de los sistemas individuales. El objetivo principal de esta tesis es precisamente avanzar en nuestra comprensión de la relación existente entre la topología de interacciones y las dinámicas colectivas que una red compleja es capaz de mantener. Siendo este un tema amplio que se puede abordar desde distintos puntos de vista, en esta tesis se han estudiado tres problemas importantes dentro del mismo que están relacionados entre sí. Por un lado, en numerosos sistemas naturales y artificiales que se pueden describir mediante una red compleja la topología no es estática, sino que depende de la dinámica que se desarrolla en la red: un ejemplo son las redes de neuronas del cerebro. En estas redes adaptativas la propia topología emerge como consecuencia de una autoorganización del sistema. Para conocer mejor cómo pueden emerger espontáneamente las propiedades comúnmente observadas en redes reales, hemos estudiado el comportamiento de sistemas que evolucionan según reglas adaptativas locales con base empírica. Nuestros resultados numéricos y analíticos muestran que la autoorganización del sistema da lugar a dos de las propiedades más universales de las redes complejas: a escala mesoscópica, la aparición de una estructura de comunidades, y, a escala macroscópica, la existencia de una ley de potencias en la distribución de las interacciones en la red. El hecho de que estas propiedades aparecen en dos modelos con leyes de evolución cuantitativamente distintas que siguen unos mismos principios adaptativos sugiere que estamos ante un fenómeno que puede ser muy general, y estar en el origen de estas propiedades en sistemas reales. En segundo lugar, proponemos una medida que permite clasificar los elementos de una red compleja en función de su relevancia para el mantenimiento de dinámicas colectivas. En concreto, estudiamos la vulnerabilidad de los distintos elementos de una red frente a perturbaciones o grandes fluctuaciones, entendida como una medida del impacto que estos acontecimientos externos tienen en la interrupción de una dinámica colectiva. Los resultados que se obtienen indican que la vulnerabilidad dinámica es sobre todo dependiente de propiedades locales, por tanto nuestras conclusiones abarcan diferentes topologías, y muestran la existencia de una dependencia no trivial entre la vulnerabilidad y la conectividad de los elementos de una red. Finalmente, proponemos una estrategia de imposición de una dinámica objetivo genérica en una red dada e investigamos su validez en redes con diversas topologías que mantienen regímenes dinámicos turbulentos. Se obtiene como resultado que las redes heterogéneas (y la amplia mayora de las redes reales estudiadas lo son) son las más adecuadas para nuestra estrategia de targeting de dinámicas deseadas, siendo la estrategia muy efectiva incluso en caso de disponer de un conocimiento muy imperfecto de la topología de la red. Aparte de la relevancia teórica para la comprensión de fenómenos colectivos en sistemas complejos, los métodos y resultados propuestos podrán dar lugar a aplicaciones en sistemas experimentales y tecnológicos, como por ejemplo los sistemas neuronales in vitro, el sistema nervioso central (en el estudio de actividades síncronas de carácter patológico), las redes eléctricas o los sistemas de comunicaciones. ABSTRACT The time evolution of an ensemble of dynamical systems coupled through an irregular interaction scheme gives rise to dynamics of great of complexity and emergent phenomena that cannot be predicted from the properties of the individual systems. The main objective of this thesis is precisely to increase our understanding of the interplay between the interaction topology and the collective dynamics that a complex network can support. This is a very broad subject, so in this thesis we will limit ourselves to the study of three relevant problems that have strong connections among them. First, it is a well-known fact that in many natural and manmade systems that can be represented as complex networks the topology is not static; rather, it depends on the dynamics taking place on the network (as it happens, for instance, in the neuronal networks in the brain). In these adaptive networks the topology itself emerges from the self-organization in the system. To better understand how the properties that are commonly observed in real networks spontaneously emerge, we have studied the behavior of systems that evolve according to local adaptive rules that are empirically motivated. Our numerical and analytical results show that self-organization brings about two of the most universally found properties in complex networks: at the mesoscopic scale, the appearance of a community structure, and, at the macroscopic scale, the existence of a power law in the weight distribution of the network interactions. The fact that these properties show up in two models with quantitatively different mechanisms that follow the same general adaptive principles suggests that our results may be generalized to other systems as well, and they may be behind the origin of these properties in some real systems. We also propose a new measure that provides a ranking of the elements in a network in terms of their relevance for the maintenance of collective dynamics. Specifically, we study the vulnerability of the elements under perturbations or large fluctuations, interpreted as a measure of the impact these external events have on the disruption of collective motion. Our results suggest that the dynamic vulnerability measure depends largely on local properties (our conclusions thus being valid for different topologies) and they show a non-trivial dependence of the vulnerability on the connectivity of the network elements. Finally, we propose a strategy for the imposition of generic goal dynamics on a given network, and we explore its performance in networks with different topologies that support turbulent dynamical regimes. It turns out that heterogeneous networks (and most real networks that have been studied belong in this category) are the most suitable for our strategy for the targeting of desired dynamics, the strategy being very effective even when the knowledge on the network topology is far from accurate. Aside from their theoretical relevance for the understanding of collective phenomena in complex systems, the methods and results here discussed might lead to applications in experimental and technological systems, such as in vitro neuronal systems, the central nervous system (where pathological synchronous activity sometimes occurs), communication systems or power grids.

Computational Study of the Fe(CN)(2)CO Cofactor and Its Binding to HypC Protein.

In the intricate maturation process of [NiFe]-hydrogenases, the Fe(CN)2CO cofactor is first assembled in a HypCD complex with iron coordinated by cysteines from both proteins and CO is added after ligation of cyanides. The small accessory protein HypC is known to play a role in delivering the cofactor needed for assembling the hydrogenase active site. However, the chemical nature of the Fe(CN)2CO moiety and the stability of the cofactor–HypC complex are open questions. In this work, we address geometries, properties, and the nature of bonding of all chemical species involved in formation and binding of the cofactor by means of quantum calculations. We also study the influence of environmental effects and binding to cysteines on vibrational frequencies of stretching modes of CO and CN used to detect the presence of Fe(CN)2CO. Carbon monoxide is found to be much more sensitive to sulfur binding and the polarity of the medium than cyanides. The stability of the HypC–cofactor complex is analyzed by means of molecular dynamics simulation of cofactor-free and cofactor-bound forms of HypC. The results show that HypC is stable enough to carry the cofactor, but since its binding cysteine is located at the N-terminal unstructured tail, it presents large motions in solution, which suggests the need for a guiding interaction to achieve delivery of the cofactor.

Aerodynamic Study of Airfoils with Leading Edge Imperfections at Low Reynolds Number

A study has been made on the influence of the leading edge imperfections in airfoils used in different devices relating their aerodynamic performances. Wind tunnel tests have been made at different Reynolds numbers and angle of attacks in order to show this effect. Later, a quantitative study of the aerodynamic properties has been made based on the different leading edge imperfections and their size.

Nonlinear models for lateral dynamics of railway vehicles on bridges subject to wind action

The study of lateral dynamics of running trains on bridges is of importance mainly for the safety of the traffic, and may be relevant for laterally compliant bridges. These studies require threedimensional coupled vehicle-bridge models, wheree consideration of wheel to rail contact is a key aspect. Furthermore, an adequate evaluation of safety of rail traffic requires nonlinear models. A nonlinear coupled model is proposed here for vehicle-structure vertical and lateral dynamics. Vehicles are considered as fully three-dimensional multibody systems including gyroscopic terms and large rotation effects. The bridge structure is modeled by means of finite elements which may be of beam, shell or continuum type and may include geometric or material nonlinearities. The track geometry includes distributed track alignment irregularities. Both subsystems (bridge and vehicles) are described with coordinates in absolute reference frames, as opposed to alternative approaches which describe the multibody system with coordinates relative to the base bridge motion. The wheelrail contact employed is a semi-Hertzian model based on realistic wheel-rail profiles. It allows a detailed geometrical description of the contact patch under each wheel including multiple-point contact, flange contact and uplift. Normal and tangential stresses in each contact are integrated at each time-step to obtain the resultant contact forces. The models have been implemented within an existing finite element analysis software with multibody capabilities, Abaqus (Simulia Ltd., 2010). Further details of the model are presented in Antolín et al. (2012). Representative applications are presented for railway vehicles under lateral wind action on laterally compliant viaducts, showing the relevance of the nonlinear wheel-rail contact model as well as the interaction between bridge and vehicle.

One-dimensional self-similar solution of the dynamics of axisymmetric slender liquid bridges

In this paper the dynamics of axisymmetric, slender, viscous liquid bridges having volume close to the cylindrical one, and subjected to a small gravitational field parallel to the axis of the liquid bridge, is considered within the context of one-dimensional theories. Although the dynamics of liquid bridges has been treated through a numerical analysis in the inviscid case, numerical methods become inappropriate to study configurations close to the static stability limit because the evolution time, and thence the computing time, increases excessively. To avoid this difficulty, the problem of the evolution of these liquid bridges has been attacked through a nonlinear analysis based on the singular perturbation method and, whenever possible, the results obtained are compared with the numerical ones.

Numerical study of ultrasound induced non-linear shape and size bubble oscillations in viscoelastic media

The theoretical study of forced bubble oscillations is motivated by the importance of cavitation bubbles and oscillating encapsulated microbubbles (i.e. contrast agents) in medical sciences. In more details,theoretical studies on bubble dynamics addressing the sound-bubble interaction phenomenon provide the basis for understanding the dynamics of contrast agent microbubbles used in medical diagnosis and of non-linearly oscillating cavitation bubbles in the case of high-intensity ultrasound therapy. Moreover, the inclusion of viscoelasticity is of vital importance for an accurate theoretical analysis since most biological tissues and fluids exhibit non-Newtonian behavior.

The importance of reactant positioning in enzyme catalysis: A hybrid quantum mechanics/molecular mechanics study of a haloalkane dehalogenase

Hybrid quantum mechanics/molecular mechanics calculations using Austin Model 1 system-specific parameters were performed to study the SN2 displacement reaction of chloride from 1,2-dichloroethane (DCE) by nucleophilic attack of the carboxylate of acetate in the gas phase and by Asp-124 in the active site of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10. The activation barrier for nucleophilic attack of acetate on DCE depends greatly on the reactants having a geometry resembling that in the enzyme or an optimized gas-phase structure. It was found in the gas-phase calculations that the activation barrier is 9 kcal/mol lower when dihedral constraints are used to restrict the carboxylate nucleophile geometry to that in the enzyme relative to the geometries for the reactants without dihedral constraints. The calculated quantum mechanics/molecular mechanics activation barriers for the enzymatic reaction are 16.2 and 19.4 kcal/mol when the geometry of the reactants is in a near attack conformer from molecular dynamics and in a conformer similar to the crystal structure (DCE is gauche), respectively. This haloalkane dehalogenase lowers the activation barrier for dehalogenation of DCE by 2–4 kcal/mol relative to the single point energies of the enzyme's quantum mechanics atoms in the gas phase. SN2 displacements of this sort in water are infinitely slower than in the gas phase. The modest lowering of the activation barrier by the enzyme relative to the reaction in the gas phase is consistent with mutation experiments.

Intraspecific Behavioural Diversity in a Freshwater Zooplankton: A study of the fitness consequences of vertical migration behaviour for distinct morphs of Daphnia pulicaria

The literature on niche separation and coexistence between species is large, but there is widespread variation in behavioural strategy between individuals of the same species that has received much less attention. Understanding what maintains this diversity is important because intraspecific behavioural diversity can affect population dynamics and community interactions. Multiple behavioural strategies can arise either as phenotype-dependent ‘conditional strategies’, where phenotypic variation causes individuals to adopt different strategies for optimizing fitness, or as internally-independent ‘alternative strategies’, where multiple fitness peaks exist for individuals and strategic ‘choice’ remains plastic. Though intraspecific variation in stable phenotypes is known to maintain intraspecific behavioural diversity through conditional strategies, when internal conditions are highly plastic or reversible, it is not clear whether individual behaviours are maintained as conditional strategies, or as alternative strategies of equal fitness. In this study, I combine an observational and experimental approach to identify the likely mechanisms maintaining behavioural diversity between hemoglobin-rich and hemoglobin-poor morphs in a natural population of Daphnia pulicaria. In Round Lake, individuals with low hemoglobin migrate daily from the hypolimnion to the epilimnion, whereas individuals with high hemoglobin remain in the hypolimnion. Using high-resolution depth and time sampling, I discovered behavioural diversity both within and among hemoglobin phenotypes. I tested the role of hemoglobin phenotype in maintaining behavioural diversity using automated migration robots that move individuals across the natural environmental gradients in the lake. By measuring the fitness of each morph undergoing either a natural migration behaviour, or the migration of the opposite morph, I found that the fitness of hemoglobin rich and poor morphs in their natural behaviour does not differ, but that Hb-rich individuals can obtain equal fitness from either behaviour, while Hb-poor morphs suffer substantial drops in survivorship in the alternate migration behaviour. Thus, migration behaviour in this system exists as a conditional strategy for some individuals, and as alternative strategies of equal fitness for others. The results of this study suggest that individual limits in the expression of highly flexible internal conditions can reinforce intraspecific behavioural diversity. Few studies have measured the fitness consequences of switching migration strategies and this study provides a rare example in the field.

A feasibility study of a sealed safety monitor for trucks carrying LNG and other hazardous materials. Final report.

Energy Department, Office of Operational Safety Programs, Washington, D.C.

The Moscow peace offensive and its revolutionary potential (a study in political dynamics)

Bibliography: p. 80-85.

A study of the aerodynamic effects and stability characteristics of buses. Summary report. Volume 1. Final report.

National Highway Traffic Safety Administration, Washington, D.C.