915 resultados para Affordance-Based Design
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Modern sensor technologies and simulators applied to large and complex dynamic systems (such as road traffic networks, sets of river channels, etc.) produce large amounts of behavior data that are difficult for users to interpret and analyze. Software tools that generate presentations combining text and graphics can help users understand this data. In this paper we describe the results of our research on automatic multimedia presentation generation (including text, graphics, maps, images, etc.) for interactive exploration of behavior datasets. We designed a novel user interface that combines automatically generated text and graphical resources. We describe the general knowledge-based design of our presentation generation tool. We also present applications that we developed to validate the method, and a comparison with related work.
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Optical communications receivers using wavelet signals processing is proposed in this paper for dense wavelength-division multiplexed (DWDM) systems and modal-division multiplexed (MDM) transmissions. The optical signal-to-noise ratio (OSNR) required to demodulate polarization-division multiplexed quadrature phase shift keying (PDM-QPSK) modulation format is alleviated with the wavelet denoising process. This procedure improves the bit error rate (BER) performance and increasing the transmission distance in DWDM systems. Additionally, the wavelet-based design relies on signal decomposition using time-limited basis functions allowing to reduce the computational cost in Digital-Signal-Processing (DSP) module. Attending to MDM systems, a new scheme of encoding data bits based on wavelets is presented to minimize the mode coupling in few-mode (FWF) and multimode fibers (MMF). The Shifted Prolate Wave Spheroidal (SPWS) functions are proposed to reduce the modal interference.
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Passive energy dissipation devices are increasingly implemented in frame structures to improve their performance under seismic loading. Most guidelines for designing this type of system retain the requirements applicable to frames without dampers, and this hinders taking full advantage of the benefits of implementing dampers. Further, assessing the extent of damage suffered by the frame and by the dampers for different levels of seismic hazard is of paramount importance in the framework of performance-based design. This paper presents an experimental investigation whose objectives are to provide empirical data on the response of reinforced concrete (RC) frames equipped with hysteretic dampers (dynamic response and damage) and to evaluate the need for the frame to form a strong column-weak beam mechanism and dissipate large amounts of plastic strain energy. To this end, shake-table tests were conducted on a 2/5-scale RC frame with hysteretic dampers. The frame was designed only for gravitational loads. The dampers provided lateral strength and stiffness, respectively, three and 12 times greater than those of the frame. The test structure was subjected to a sequence of seismic simulations that represented different levels of seismic hazard. The RC frame showed a performance level of "immediate occupancy", with maximum rotation demands below 20% of the ultimate capacity. The dampers dissipated most of the energy input by the earthquake. It is shown that combining hysteretic dampers with flexible reinforced concrete frames leads to structures with improved seismic performance and that requirements of conventional RC frames (without dampers) can be relieved.
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El presente trabajo aborda el análisis de la idea de monumentalidad, así como el diseño y la construcción de monumentos concretos, a la finalización de la Segunda Guerra Mundial, prestando especial atención al intento del Movimiento Moderno de introducirse en un campo que hasta entonces le había sido ajeno. Entendiendo que el monumento es ante todo un artefacto para la memoria, y analizando las teorías de sociólogos como Émile Durkheim, Maurice Halbwachs, Jan Assmann o Iwona Irwin-Zarecka, la tesis se propone explicar el papel que juegan los monumentos en la creación de una memoria colectiva que, a diferencia de la historia, es una recopilación selectiva de acontecimientos del pasado cuyo fin es procurar y celebrar la permanencia del grupo social. También se propone analizar el papel del monumento como elemento de estabilidad en el paisaje urbano que genera de forma natural el apego de los ciudadanos, puesto que forma parte destacada del marco espacial en el que se han desarrollado sus vidas. Desde estas dos facetas se pretende justificar la necesidad de monumentos que experimenta cualquier grupo social, y por qué las guerras, que ponen en peligro la estructura, e incluso la propia vida del grupo, son acontecimientos que generan una tendencia especial a la construcción de monumentos que conjuren el peligro al que éste se ha visto sometido. Se explicarán las razones por las que la conmemoración de la Segunda Guerra Mundial se volvió especialmente problemática. Entre las principales, la desaparición de fronteras entre frente y retaguardia, entre objetivos militares y civiles; por otra parte la despersonalización de la acción bélica como consecuencia de la aplicación de la tecnología; en tercer lugar el papel de los medios de comunicación de masas, que por primera vez en la historia irrumpieron de forma masiva en una guerra, y ofrecían imágenes instantáneas, más impactantes y con un aura de realidad con la que el monumento convencional no era capaz de competir; en cuarto lugar el inicio de la era atómica, que enfrentaba por primera vez a la humanidad a la posibilidad de su destrucción total; y finalmente la experiencia del Holocausto, en cuanto que aniquilación carente de objetivo e ideología, que se servía del progreso de la ciencia para ganar en eficiencia, y que puso de manifiesto la manipulabilidad de la tecnología al servicio de unos intereses particulares. Como respuesta a esta dificultad para la conmemoración, se popularizaron dos fórmulas hasta entonces marginales que podemos considerar características del momento: una de ellas es el living memorial, que trataba de ofrecer una lectura constructiva de la guerra poniendo de relieve determinadas funciones prácticas de carácter democrático, cultural, deportivo, etc. que se presentaban como los frutos por los que se había combatido en la guerra. En esta fórmula es donde el Movimiento Moderno encontró la posibilidad de abordar nuevos proyectos, en los que la función estaba presente pero no era el ingrediente determinante, lo que obligaría a un enriquecimiento del lenguaje con el que responder a la dimensión emotiva del monumento. Y si bien hay en esta época edificios modernos que podemos calificar justamente de monumentos, el desplazamiento del centro del debate teórico hacia cuestiones estilísticas y expresivas limitó considerablemente la claridad de los enunciados anteriores y la posibilidad de consenso. Dentro de los living memorials, las sedes de la Organización de Naciones Unidas y sus correspondientes agencias representaron la mayor esperanza del Movimiento Moderno por construir un auténtico monumento. Sin embargo, el sistema de trabajo en grupo, con su correspondiente conflicto de personalidades, la ausencia de proyección de los edificios sobre el espacio urbano anexo, y sobre todo el propio descrédito que comenzaron a sufrir las instituciones con el comienzo de la Guerra Fría, frustraron esta posibilidad. La segunda fórmula conmemorativa sería el monumento de advertencia o mahnmal, que renuncia a cualquier rasgo de heroísmo o romanticismo, y se concentra simplemente en advertir de los riesgos que implica la guerra. Dicha fórmula se aplicó fundamentalmente en los países vencidos, y generalmente no por iniciativa propia, sino como imposición de los vencedores, que de alguna forma aprovechaban la ocasión para hacer examen de conciencia lejos de la opinión pública de sus respectivos países. ABSTRACT This paper explores the idea of monumentality through the analysis of the design and construction of several monuments at the end ofWorldWar II. It pays particular attention to the attempt of the Modern Movement to enter a field that had been ignored until this moment. With the assumption that a monument is primarily a mnemonic device, this thesis focuses on the thinking of sociologists like Émile Durkheim, Maurice Halbwachs, Jan Assmann or Iwona Irwin-Zarecka, with the aim of explaining the role of monuments in the creation of a collective memory which, unlike history, consists of past events selected in order to secure and celebrate the permanence of a social group. It also considers the role of monuments as elements of stability in the urban landscape that naturally get assimilated by society, since they are prominent elements in the shared spaces of daily life. These two features explain the need felt by any society for monuments, and how wars, events that endanger the structure and even the existence of that same society, generate a special tendency to build monuments to conjure that inherent danger. The reasons why the memorializing of World War II became especially problematic will be explained. Primary among them is the blurring of boundaries between the front line and the domestic front, between military and civilian targets; moreover, the depersonalization of warfare as a result of advances in technology; thirdly, the role of mass media, which for the first time in history extensively covered a war, instantly broadcasting images of such power and with such an aura of reality that conventional monuments became obsolete; fourthly, the beginning of the atomic age, which meant that mankind faced the possibility of complete destruction; and finally the Holocaust, a racial annihilation devoid of purpose and ideology, which took advantage of scientific progress to gain efficiency, manipulating technology to serve particular interests. In response to this difficulty in commemorating wars, two formulas hitherto marginal gained such popularity as to become prototypes: one was the living memorial, offering a constructive reading of the war by hosting certain practical functions of democratic, cultural or sporting nature. Living memorials presented themselves as the image of the outcome for which the war had been fought. The Modern Movement found in this formula the opportunity for tackling new projects, in which function was present but not as the determining ingredient; in turn, they would require an enhancement of language in order to account for the emotional dimension of the monument. And while there are modern buildings at this time that we can justly describe as monuments, the displacement of the focus of the theoretical debate to stylistic and expressive issues considerably limited the clarity of previous statements and the possibility of consensus. Among all living memorials, the headquarters of the United Nations Organization and its satellite agencies represented the ultimate hope of the Modern Movement to build an authentic monument. However, the group-based design process, the fight of egos it caused, the lack of presence of these buildings over the adjacent urban space, and especially the very discredit that these institutions began to suffer with the onset of the Cold War, all thwarted this expectation. The second commemorative formula was the warning monument or Mahnmal, which rejects any trace of heroism or romanticism, and simply focuses on warning about the risks of war. This formula was mainly used in defeated countries, and generally not on their own initiative, but as an imposition of the victors, which seized the opportunity to do some soul-searching far away from the public opinion of their respective countries.
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Most known archaeal DNA polymerases belong to the type B family, which also includes the DNA replication polymerases of eukaryotes, but maintain high fidelity at extreme conditions. We describe here the 2.5 Å resolution crystal structure of a DNA polymerase from the Archaea Thermococcus gorgonarius and identify structural features of the fold and the active site that are likely responsible for its thermostable function. Comparison with the mesophilic B type DNA polymerase gp43 of the bacteriophage RB69 highlights thermophilic adaptations, which include the presence of two disulfide bonds and an enhanced electrostatic complementarity at the DNA–protein interface. In contrast to gp43, several loops in the exonuclease and thumb domains are more closely packed; this apparently blocks primer binding to the exonuclease active site. A physiological role of this “closed” conformation is unknown but may represent a polymerase mode, in contrast to an editing mode with an open exonuclease site. This archaeal B DNA polymerase structure provides a starting point for structure-based design of polymerases or ligands with applications in biotechnology and the development of antiviral or anticancer agents.
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Increased expression of the serine protease urokinase-type plasminogen activator (uPA) in tumor tissues is highly correlated with tumor cell migration, invasion, proliferation, progression, and metastasis. Thus inhibition of uPA activity represents a promising target for antimetastatic therapy. So far, only the x-ray crystal structure of uPA inactivated by H-Glu-Gly-Arg-chloromethylketone has been reported, thus limited data are available for a rational structure-based design of uPA inhibitors. Taking into account the trypsin-like arginine specificity of uPA, (4-aminomethyl)phenylguanidine was selected as a potential P1 residue and iterative derivatization of its amino group with various hydrophobic residues, and structure–activity relationship-based optimization of the spacer in terms of hydrogen bond acceptor/donor properties led to N-(1-adamantyl)-N′-(4-guanidinobenzyl)urea as a highly selective nonpeptidic uPA inhibitor. The x-ray crystal structure of the uPA B-chain complexed with this inhibitor revealed a surprising binding mode consisting of the expected insertion of the phenylguanidine moiety into the S1 pocket, but with the adamantyl residue protruding toward the hydrophobic S1′ enzyme subsite, thus exposing the ureido group to hydrogen-bonding interactions. Although in this enzyme-bound state the inhibitor is crossing the active site, interactions with the catalytic residues Ser-195 and His-57 are not observed, but their side chains are spatially displaced for steric reasons. Compared with other trypsin-like serine proteases, the S2 and S3/S4 pockets of uPA are reduced in size because of the 99-insertion loop. Therefore, the peculiar binding mode of the new type of uPA inhibitors offers the possibility of exploiting optimized interactions at the S1′/S2′ subsites to further enhance selectivity and potency. Because crystals of the uPA/benzamidine complex allow inhibitor exchange by soaking procedures, the structure-based design of new generations of uPA inhibitors can rely on the assistance of x-ray analysis.
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To test whether the structure of a protein is determined in a manner akin to the assembly of a jigsaw puzzle, up to 10 adjacent residues within the core of T4 lysozyme were replaced by methionine. Such variants are active and fold cooperatively with progressively reduced stability. The structure of a seven-methionine variant has been shown, crystallographically, to be similar to wild type and to maintain a well ordered core. The interaction between the core residues is, therefore, not strictly comparable with the precise spatial complementarity of the pieces of a jigsaw puzzle. Rather, a certain amount of give and take in forming the core structure is permitted. A simplified hydrophobic core sequence, imposed without genetic selection or computer-based design, is sufficient to retain native properties in a globular protein.
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We present a systematic approach to minimizing the Z-domain of protein A, a three-helix bundle (59 residues total) that binds tightly (Kd = 10 nM) to the Fc portion of an immunoglobin IgG1. Despite the fact that all the contacts seen in the x-ray structure of the complex with the IgG are derived from residues in the first two helices, when helix 3 is deleted, binding affinity is reduced > 10(5)-fold (Kd > 1 mM). By using structure-based design and phage display methods, we have iteratively improved the stability and binding affinity for a two-helix derivative, 33 residues in length, such that it binds IgG1, with a Kd of 43 nM. This was accomplished by stepwise selection of random mutations from three regions of the truncated Z-peptide: the 4 hydrophobic residues from helix 1 and helix 2 that contacted helix 3 (the exoface), followed by 5 residues between helix 1 and helix 2 (the intraface), and lastly by 19 residues at or near the interface that interacts with Fc (the interface). As selected mutations from each region were compiled (12 in total), they led to progressive increases in affinity for IgG, and concomitant increases in alpha-helical content reflecting increased stabilization of the two-helix scaffold. Thus, by sequential increases in the stability of the structure and improvements in the quality of the intermolecular contacts, one can reduce larger binding domains to smaller ones. Such mini-protein binding domains are more amenable to synthetic chemistry and thus may be useful starting points for the design of smaller organic mimics. Smaller binding motifs also provide simplified and more tractable models for understanding determinants of protein function and stability.
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Thesis (Master's)--University of Washington, 2016-06
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West Nile Virus (WNV) is a mosquito-borne flavivirus with a rapidly expanding global distribution. Infection causes severe neurological disease and fatalities in both human and animal hosts. The West Nile viral protease (NS2B-NS3) is essential for post-translational processing in host-infected cells of a viral polypeptide precursor into structural and functional viral proteins, and its inhibition could represent a potential treatment for viral infections. This article describes the design, expression, and enzymatic characterization of a catalytically active recombinant WNV protease, consisting of a 40-residue component of cofactor NS2B tethered via a noncleavable nonapeptide (G(4)SG(4)) to the N-terminal 184 residues of NS3. A chromogenic assay using synthetic para-nitroanilide (pNA) hexapeptide substrates was used to identify optimal enzyme-processing conditions (pH 9.5, I < 0.1 M, 30% glycerol, 1 mM CHAPS), preferred substrate cleavage sites, and the first competitive inhibitor (Ac-FASGKR- H, IC50 &SIM; 1 μM). A putative three-dimensional structure of WNV protease, created through homology modeling based on the crystal structures of Dengue-2 and Hepatitis C NS3 viral proteases, provides some valuable insights for structure-based design of potent and selective inhibitors of WNV protease.
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This research is concerned with the development of distributed real-time systems, in which software is used for the control of concurrent physical processes. These distributed control systems are required to periodically coordinate the operation of several autonomous physical processes, with the property of an atomic action. The implementation of this coordination must be fault-tolerant if the integrity of the system is to be maintained in the presence of processor or communication failures. Commit protocols have been widely used to provide this type of atomicity and ensure consistency in distributed computer systems. The objective of this research is the development of a class of robust commit protocols, applicable to the coordination of distributed real-time control systems. Extended forms of the standard two phase commit protocol, that provides fault-tolerant and real-time behaviour, were developed. Petri nets are used for the design of the distributed controllers, and to embed the commit protocol models within these controller designs. This composition of controller and protocol model allows the analysis of the complete system in a unified manner. A common problem for Petri net based techniques is that of state space explosion, a modular approach to both the design and analysis would help cope with this problem. Although extensions to Petri nets that allow module construction exist, generally the modularisation is restricted to the specification, and analysis must be performed on the (flat) detailed net. The Petri net designs for the type of distributed systems considered in this research are both large and complex. The top down, bottom up and hybrid synthesis techniques that are used to model large systems in Petri nets are considered. A hybrid approach to Petri net design for a restricted class of communicating processes is developed. Designs produced using this hybrid approach are modular and allow re-use of verified modules. In order to use this form of modular analysis, it is necessary to project an equivalent but reduced behaviour on the modules used. These projections conceal events local to modules that are not essential for the purpose of analysis. To generate the external behaviour, each firing sequence of the subnet is replaced by an atomic transition internal to the module, and the firing of these transitions transforms the input and output markings of the module. Thus local events are concealed through the projection of the external behaviour of modules. This hybrid design approach preserves properties of interest, such as boundedness and liveness, while the systematic concealment of local events allows the management of state space. The approach presented in this research is particularly suited to distributed systems, as the underlying communication model is used as the basis for the interconnection of modules in the design procedure. This hybrid approach is applied to Petri net based design and analysis of distributed controllers for two industrial applications that incorporate the robust, real-time commit protocols developed. Temporal Petri nets, which combine Petri nets and temporal logic, are used to capture and verify causal and temporal aspects of the designs in a unified manner.
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Conventional methods in horizontal drilling processes incorporate magnetic surveying techniques for determining the position and orientation of the bottom-hole assembly (BHA). Such means result in an increased weight of the drilling assembly, higher cost due to the use of non-magnetic collars necessary for the shielding of the magnetometers, and significant errors in the position of the drilling bit. A fiber-optic gyroscope (FOG) based inertial navigation system (INS) has been proposed as an alternative to magnetometer -based downhole surveying. The utilizing of a tactical-grade FOG based surveying system in the harsh downhole environment has been shown to be theoretically feasible, yielding a significant BHA position error reduction (less than 100m over a 2-h experiment). To limit the growing errors of the INS, an in-drilling alignment (IDA) method for the INS has been proposed. This article aims at describing a simple, pneumatics-based design of the IDA apparatus and its implementation downhole. A mathematical model of the setup is developed and tested with Bloodshed Dev-C++. The simulations demonstrate a simple, low cost and feasible IDA apparatus.
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The various questions of creation of integrated development environment for computer training systems are considered in the given paper. The information technologies that can be used for creation of the integrated development environment are described. The different didactic aspects of realization of such systems are analyzed. The ways to improve the efficiency and quality of learning process with computer training systems for distance education are pointed.