Design and study of self-assembled functional organic and hybrid systems for biological applications

The focus of self-assembly as a strategy for the synthesis has been confined largely to molecules, because of the importance of manipulating the structure of matter at the molecular scale. We have investigated the influence of temperature and pH, in addition to the concentration of the capping agent used for the formation of the nano-bio conjugates. For example, the formation of the narrower size distribution of the nanoparticles was observed with the increase in the concentration of the protein, which supports the fact that γ-globulin acts both as a controller of nucleation as well as stabiliser. As analyzed through various photophysical, biophysical and microscopic techniques such as TEM, AFM, C-AFM, SEM, DLS, OPM, CD and FTIR, we observed that the initial photoactivation of γ-globulin at pH 12 for 3 h resulted in small protein fibres of ca. Further irradiation for 24 h, led to the formation of selfassembled long fibres of the protein of ca. 5-6 nm and observation of surface plasmon resonance band at around 520 nm with the concomitant quenching of luminescence intensity at 680 nm. The observation of light triggered self-assembly of the protein and its effect on controlling the fate of the anchored nanoparticles can be compared with the naturally occurring process such as photomorphogenesis.Furthermore,our approach offers a way to understand the role played by the self-assembly of the protein in ordering and knock out of the metal nanoparticles and also in the design of nano-biohybrid materials for medicinal and optoelectronic applications. Investigation of the potential applications of NIR absorbing and water soluble squaraine dyes 1-3 for protein labeling and anti-amyloid agents forms the subject matter of the third chapter of the thesis. The study of their interactions with various proteins revealed that 1-3 showed unique interactions towards serum albumins as well as lysozyme. 69%, 71% and 49% in the absorption spectra as well as significant quenching in the fluorescence intensity of the dyes 1-3, respectively. Half-reciprocal analysis of the absorption data and isothermal titration calorimetric (ITC) analysis of the titration experiments gave a 1:1 stoichiometry for the complexes formed between the lysozyme and squaraine dyes with association constants (Kass) in the range 104-105 M-1. We have determined the changes in the free energy (ΔG) for the complex formation and the values are found to be -30.78, -32.31 and -28.58 kJmol-1, respectively for the dyes 1, 2 and 3. Furthermore, we have observed a strong induced CD (ICD) signal corresponding to the squaraine chromophore in the case of the halogenated squaraine dyes 2 and 3 at 636 and 637 nm confirming the complex formation in these cases. To understand the nature of interaction of the squaraine dyes 1-3 with lysozyme, we have investigated the interaction of dyes 1-3 with different amino acids. These results indicated that the dyes 1-3 showed significant interactions with cysteine and glutamic acid which are present in the side chains of lysozyme. In addition the temperature dependent studies have revealed that the interaction of the dye and the lysozyme are irreversible. Furthermore, we have investigated the interactions of these NIR dyes 1-3 with β- amyloid fibres derived from lysozyme to evaluate their potential as inhibitors of this biologically important protein aggregation. These β-amyloid fibrils were insoluble protein aggregates that have been associated with a range of neurodegenerative diseases, including Huntington, Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob diseases. We have synthesized amyloid fibres from lysozyme through its incubation in acidic solution below pH 4 and by allowing to form amyloid fibres at elevated temperature. To quantify the binding affinities of the squaraine dyes 1-3 with β-amyloids, we have carried out the isothermal titration calorimetric (ITC) measurements. The association constants were determined and are found to be 1.2 × 105, 3.6× 105 and 3.2 × 105 M-1 for the dyes, 1-3, respectively. To gain more insights into the amyloid inhibiting nature of the squaraine dyes under investigations, we have carried out thioflavin assay, CD, isothermal titration calorimetry and microscopic analysis. The addition of the dyes 1-3 (5μM) led to the complete quenching in the apparent thioflavin fluorescence, thereby indicating the destabilization of β-amyloid fibres in the presence of the squaraine dyes. Further, the inhibition of the amyloid fibres by the squaraine dyes 1-3, has been evidenced though the DLS, TEM AFM and SAED, wherein we observed the complete destabilization of the amyloid fibre and transformation of the fibre into spherical particles of ca. These results demonstrate the fact that the squaraine dyes 1-3 can act as protein labeling agents as well as the inhibitors of the protein amyloidogenesis. The last chapter of the thesis describes the synthesis and investigation of selfassembly as well as bio-imaging aspects of a few novel tetraphenylethene conjugates 4-6.Expectedly, these conjugates showed significant solvatochromism and exhibited a hypsochromic shift (negative solvatochromism) as the solvent polarity increased, and these observations were justified though theoretical studies employing the B3LYP/6-31g method. We have investigated the self-assembly properties of these D-A conjugates though variation in the percentage of water in acetonitrile solution due to the formation of nanoaggregates. Further the contour map of the observed fluorescence intensity as a function of the fluorescence excitation and emission wavelength confirmed the formation of J-type aggregates in these cases. To have a better understanding of the type of self-assemblies formed from the TPE conjugates 4-6, we have carried out the morphological analysis through various microscopic techniques such as DLS, SEM and TEM. 70%, we observed rod shape architectures having ~ 780 nm in diameter and ~ 12 μM in length as evidenced through TEM and SEM analysis. We have made similar observations with the dodecyl conjugate 5 at ca. 70% and 50% water/acetonitrile mixtures, the aggregates formed from 4 and 5 were found to be highly crystalline and such structures were transformed to amorphous nature as the water fraction was increased to 99%. To evaluate the potential of the conjugate as bio-imaging agents, we have carried out their in vitro cytotoxicity and cellular uptake studies though MTT assay, flow cytometric and confocal laser scanning microscopic techniques. Thus nanoparticle of these conjugates which exhibited efficient emission, large stoke shift, good stability, biocompatibility and excellent cellular imaging properties can have potential applications for tracking cells as well as in cell-based therapies. In summary we have synthesized novel functional organic chromophores and have studied systematic investigation of self-assembly of these synthetic and biological building blocks under a variety of conditions. The investigation of interaction of water soluble NIR squaraine dyes with lysozyme indicates that these dyes can act as the protein labeling agents and the efficiency of inhibition of β-amyloid indicate, thereby their potential as anti-amyloid agents.

Design and Synthesis of Donor-Acceptor Low Band Gap Copolymers for Photoconductive and Non-linear Optical Applications

The main focus of the present study was to develop ideal low band gap D-A copolymers for photoconducting and non-linear optical applications. This chapter summarizes the overall research work done. Designed copolymers were synthesized via direct arylation or Suzuki coupling reactions. Copolymers were characterized by theoretical and experimental methods. The suitability of these copolymers in photoconducting and optical limiting devices has been investigated.The results suggest that the copolymers investigated in the present study have a good non-linear optical response and are comparable to or even better than the D-A copolymers reported in the literature and hence could be chosen as ideal candidates with potential applications for non-linear optics. The results also show that the structures of the polymers have great impact on NLO properties. Copolymers studied here exhibits good optical limiting property at 532 nm wavelength due to two-photon absorption (TPA) process. The results revealed that the two copolymers, (P(EDOT-BTSe) and P(PH-TZ)) exhibited strong two-photon absorption and superior optical power limiting properties, which are much better than that of others.

Micro-electromechanical structural design and optimization of vertical cavity photonic devices with wide continuous tuning

Diese Arbeit umfaßt das elektromechanische Design und die Designoptimierung von weit durchstimmbaren optischen multimembranbasierten Bauelementen, mit vertikal orientierten Kavitäten, basierend auf der Finiten Element Methode (FEM). Ein multimembran InP/Luft Fabry-Pérot optischer Filter wird dargestellt und umfassend analysiert. In dieser Arbeit wird ein systematisches strukturelles Designverfahren dargestellt. Genaue analytische elektromechanischer Modelle für die Bauelemente sind abgeleitet worden. Diese können unschätzbare Werkzeuge sein, um am Anfang der Designphase schnell einen klaren Einblick zur Verfügung zu stellen. Mittels des FEM Programms ist der durch die nicht-lineare Verspannung hervorgerufene versteifende Effekt nachgeforscht und sein Effekt auf die Verlängerung der mechanischen Durchstimmungsstrecke der Bauelemente demonstriert worden. Interessant war auch die Beobachtung, dass die normierte Relation zwischen Ablenkung und Spannung ein unveränderliches Profil hat. Die Deformation der Membranflächen der in dieser Arbeit dargestellten Bauelementformen erwies sich als ein unerwünschter, jedoch manchmal unvermeidbarer Effekt. Es zeigt sich aber, dass die Wahl der Größe der strukturellen Dimensionen den Grad der Membrandeformation im Falle der Aktuation beeinflusst. Diese Arbeit stellt ein elektromechanisches in FEMLAB implementierte quasi-3D Modell, das allgemein für die Modellierung dünner Strukturen angewendet werden kann, dar; und zwar indem man diese als 2D-Objekte betrachtet und die dritte Dimension als eine konstante Größe (z.B. die Schichtdicke) oder eine Größe, welche eine mathematische Funktion ist, annimmt. Diese Annahme verringert drastisch die Berechnungszeit sowie den erforderlichen Arbeitsspeicherbedarf. Weiter ist es für die Nachforschung des Effekts der Skalierung der durchstimmbaren Bauelemente verwendet worden. Eine neuartige Skalierungstechnik wurde abgeleitet und verwendet. Die Ergebnisse belegen, dass das daraus resultierende, skalierte Bauelement fast genau die gleiche mechanische Durchstimmung wie das unskalierte zeigt. Die Einbeziehung des Einflusses von axialen Verspannungen und Gradientenverspannungen in die Berechnungen erforderte die Änderung der Standardimplementierung des 3D Mechanikberechnungsmodus, der mit der benutzten FEM Software geliefert wurde. Die Ergebnisse dieser Studie zeigen einen großen Einfluss der Verspannung auf die Durchstimmungseigenschaften der untersuchten Bauelemente. Ferner stimmten die Ergebnisse der theoretischen Modellrechnung mit den experimentellen Resultaten sehr gut überein.

Research through DESIGN through research - a problem statement and a conceptual sketch

This paper re-addresses the issue of a lacking genuine design research paradigm. It tries to sketch an operational model of such a paradigm, based upon a generic design process model, which is derived from basic notions of evolution and learning in different domains of knowing (and turns out to be not very different from existing ones). It does not abandon the scientific paradigm but concludes that the latter has to be embedded into / subordinated under a design paradigm.

Design, implementation and application of a generic framework for integrated regional land-use modeling

Land use is a crucial link between human activities and the natural environment and one of the main driving forces of global environmental change. Large parts of the terrestrial land surface are used for agriculture, forestry, settlements and infrastructure. Given the importance of land use, it is essential to understand the multitude of influential factors and resulting land use patterns. An essential methodology to study and quantify such interactions is provided by the adoption of land-use models. By the application of land-use models, it is possible to analyze the complex structure of linkages and feedbacks and to also determine the relevance of driving forces. Modeling land use and land use changes has a long-term tradition. In particular on the regional scale, a variety of models for different regions and research questions has been created. Modeling capabilities grow with steady advances in computer technology, which on the one hand are driven by increasing computing power on the other hand by new methods in software development, e.g. object- and component-oriented architectures. In this thesis, SITE (Simulation of Terrestrial Environments), a novel framework for integrated regional sland-use modeling, will be introduced and discussed. Particular features of SITE are the notably extended capability to integrate models and the strict separation of application and implementation. These features enable efficient development, test and usage of integrated land-use models. On its system side, SITE provides generic data structures (grid, grid cells, attributes etc.) and takes over the responsibility for their administration. By means of a scripting language (Python) that has been extended by language features specific for land-use modeling, these data structures can be utilized and manipulated by modeling applications. The scripting language interpreter is embedded in SITE. The integration of sub models can be achieved via the scripting language or by usage of a generic interface provided by SITE. Furthermore, functionalities important for land-use modeling like model calibration, model tests and analysis support of simulation results have been integrated into the generic framework. During the implementation of SITE, specific emphasis was laid on expandability, maintainability and usability. Along with the modeling framework a land use model for the analysis of the stability of tropical rainforest margins was developed in the context of the collaborative research project STORMA (SFB 552). In a research area in Central Sulawesi, Indonesia, socio-environmental impacts of land-use changes were examined. SITE was used to simulate land-use dynamics in the historical period of 1981 to 2002. Analogous to that, a scenario that did not consider migration in the population dynamics, was analyzed. For the calculation of crop yields and trace gas emissions, the DAYCENT agro-ecosystem model was integrated. In this case study, it could be shown that land-use changes in the Indonesian research area could mainly be characterized by the expansion of agricultural areas at the expense of natural forest. For this reason, the situation had to be interpreted as unsustainable even though increased agricultural use implied economic improvements and higher farmers' incomes. Due to the importance of model calibration, it was explicitly addressed in the SITE architecture through the introduction of a specific component. The calibration functionality can be used by all SITE applications and enables largely automated model calibration. Calibration in SITE is understood as a process that finds an optimal or at least adequate solution for a set of arbitrarily selectable model parameters with respect to an objective function. In SITE, an objective function typically is a map comparison algorithm capable of comparing a simulation result to a reference map. Several map optimization and map comparison methodologies are available and can be combined. The STORMA land-use model was calibrated using a genetic algorithm for optimization and the figure of merit map comparison measure as objective function. The time period for the calibration ranged from 1981 to 2002. For this period, respective reference land-use maps were compiled. It could be shown, that an efficient automated model calibration with SITE is possible. Nevertheless, the selection of the calibration parameters required detailed knowledge about the underlying land-use model and cannot be automated. In another case study decreases in crop yields and resulting losses in income from coffee cultivation were analyzed and quantified under the assumption of four different deforestation scenarios. For this task, an empirical model, describing the dependence of bee pollination and resulting coffee fruit set from the distance to the closest natural forest, was integrated. Land-use simulations showed, that depending on the magnitude and location of ongoing forest conversion, pollination services are expected to decline continuously. This results in a reduction of coffee yields of up to 18% and a loss of net revenues per hectare of up to 14%. However, the study also showed that ecological and economic values can be preserved if patches of natural vegetation are conservated in the agricultural landscape. -----------------------------------------------------------------------

Collaborative design procedures for architects and engineers

This book argues for novel strategies to integrate engineering design procedures and structural analysis data into architectural design. Algorithmic procedures that recently migrated into the architectural practice are utilized to improve the interface of both disciplines. Architectural design is predominately conducted as a negotiation process of various factors but often lacks rigor and data structures to link it to quantitative procedures. Numerical structural design on the other hand could act as a role model for handling data and robust optimization but it often lacks the complexity of architectural design. The goal of this research is to bring together robust methods from structural design and complex dependency networks from architectural design processes. The book presents three case studies of tools and methods that are developed to exemplify, analyze and evaluate a collaborative work flow.

Extracting Urban Food Potential: design-based methods for digital and bodily cartography

Sweden’s recent report on Urban Sustainable Development calls out a missing link between the urban design process and citizens. This paper investigates if engaging citizens as design agents by providing a platform for alternate participation can bridge this gap, through the transfer of spatial agency and new modes of critical cartography. To assess whether this is the case, the approaches are applied to Stockholm’s urban agriculture movement in a staged intervention. The aim of the intervention was to engage citizens in locating existing and potential places for growing food and in gathering information from these sites to inform design in urban agriculture. The design-based methodologies incorporated digital and bodily interfaces for this cartography to take place. The Urban CoMapper, a smartphone digital app, captured real-time perspectives through crowd-sourced mapping. In the bodily cartography, participant’s used their bodies to trace the site and reveal their sensorial perceptions. The data gathered from these approaches gave way to a mode of artistic research for exploring urban agriculture, along with inviting artists to be engaged in the dialogues. In sum, results showed that a combination of digital and bodily approaches was necessary for a critical cartography if we want to engage citizens holistically into the urban design process as spatial agents informing urban policy. Such methodologies formed a reflective interrogation and encouraged a new intimacy with nature, in this instance, one that can transform our urban conduct by questioning our eating habits: where we get our food from and how we eat it seasonally.

A Theory of Quantitative Inference Applied to a Mechanical Design Compiler

This thesis presents the ideas underlying a computer program that takes as input a schematic of a mechanical or hydraulic power transmission system, plus specifications and a utility function, and returns catalog numbers from predefined catalogs for the optimal selection of components implementing the design. Unlike programs for designing single components or systems, the program provides the designer with a high level "language" in which to compose new designs. It then performs some of the detailed design process. The process of "compilation" is based on a formalization of quantitative inferences about hierarchically organized sets of artifacts and operating conditions. This allows the design compilation without the exhaustive enumeration of alternatives.

The Architect's Collaborator: Toward Intelligent Tools for Conceptual Design

In early stages of architectural design, as in other design domains, the language used is often very abstract. In architectural design, for example, architects and their clients use experiential terms such as "private" or "open" to describe spaces. If we are to build programs that can help designers during this early-stage design, we must give those programs the capability to deal with concepts on the level of such abstractions. The work reported in this thesis sought to do that, focusing on two key questions: How are abstract terms such as "private" and "open" translated into physical form? How might one build a tool to assist designers with this process? The Architect's Collaborator (TAC) was built to explore these issues. It is a design assistant that supports iterative design refinement, and that represents and reasons about how experiential qualities are manifested in physical form. Given a starting design and a set of design goals, TAC explores the space of possible designs in search of solutions that satisfy the goals. It employs a strategy we've called dependency-directed redesign: it evaluates a design with respect to a set of goals, then uses an explanation of the evaluation to guide proposal and refinement of repair suggestions; it then carries out the repair suggestions to create new designs. A series of experiments was run to study TAC's behavior. Issues of control structure, goal set size, goal order, and modification operator capabilities were explored. In addition, TAC's use as a design assistant was studied in an experiment using a house in the process of being redesigned. TAC's use as an analysis tool was studied in an experiment using Frank Lloyd Wright's Prairie houses.

Intelligence by Design: Principles of Modularity and Coordination for Engineerin

All intelligence relies on search --- for example, the search for an intelligent agent's next action. Search is only likely to succeed in resource-bounded agents if they have already been biased towards finding the right answer. In artificial agents, the primary source of bias is engineering. This dissertation describes an approach, Behavior-Oriented Design (BOD) for engineering complex agents. A complex agent is one that must arbitrate between potentially conflicting goals or behaviors. Behavior-oriented design builds on work in behavior-based and hybrid architectures for agents, and the object oriented approach to software engineering. The primary contributions of this dissertation are: 1.The BOD architecture: a modular architecture with each module providing specialized representations to facilitate learning. This includes one pre-specified module and representation for action selection or behavior arbitration. The specialized representation underlying BOD action selection is Parallel-rooted, Ordered, Slip-stack Hierarchical (POSH) reactive plans. 2.The BOD development process: an iterative process that alternately scales the agent's capabilities then optimizes the agent for simplicity, exploiting tradeoffs between the component representations. This ongoing process for controlling complexity not only provides bias for the behaving agent, but also facilitates its maintenance and extendibility. The secondary contributions of this dissertation include two implementations of POSH action selection, a procedure for identifying useful idioms in agent architectures and using them to distribute knowledge across agent paradigms, several examples of applying BOD idioms to established architectures, an analysis and comparison of the attributes and design trends of a large number of agent architectures, a comparison of biological (particularly mammalian) intelligence to artificial agent architectures, a novel model of primate transitive inference, and many other examples of BOD agents and BOD development.

A HOLISTIC APPROACH TO MANUFACTURING SYSTEM DESIGN IN THE DEFENSE AEROSPACE INDUSTRY

Manufacturing has evolved to become a critical element of the competitive skill set of defense aerospace firms. Given the changes in the acquisition environment and culture; traditional “thrown over the wall” means of developing and manufacturing products are insufficient. Also, manufacturing systems are complex systems that need to be carefully designed in a holistic manner and there are shortcomings with available tools and methods to assist in the design of these systems. This paper outlines the generation and validation of a framework to guide this manufacturing system design process.

Electrical Design: A Problem for Artificial Intelligence Research

This report outlines the problem of intelligent failure recovery in a problem-solver for electrical design. We want our problem solver to learn as much as it can from its mistakes. Thus we cast the engineering design process on terms of Problem Solving by Debugging Almost-Right Plans, a paradigm for automatic problem solving based on the belief that creation and removal of "bugs" is an unavoidable part of the process of solving a complex problem. The process of localization and removal of bugs called for by the PSBDARP theory requires an approach to engineering analysis in which every result has a justification which describes the exact set of assumptions it depends upon. We have developed a program based on Analysis by Propagation of Constraints which can explain the basis of its deductions. In addition to being useful to a PSBDARP designer, these justifications are used in Dependency-Directed Backtracking to limit the combinatorial search in the analysis routines. Although the research we will describe is explicitly about electrical circuits, we believe that similar principles and methods are employed by other kinds of engineers, including computer programmers.

Assembly Design and Evaluation in an Augmented Reality Environment

The technologies and methodologies of assembly design and evaluation in the early design stage are highly significant to product development. This paper looks at a promising technology to mix real components (e.g. physical prototypes, assembly tools, machines, etc.) with virtual components to create an Augmented Reality (AR) interface for assembly process evaluation. The goal of this paper is to clarify the methodologies and enabling technologies of how to establish an AR assembly simulation and evaluation environment. The architecture of an AR assembly system is proposed and the important functional modules including AR environment set-up, design for assembly (DFA) analysis and AR assembly sequence planning in an AR environment are discussed in detail.

Facilitating Mechanical Design with Augmented Reality

By enhancing a real scene with computer generated objects, Augmented Reality (AR), has proven itself as a valuable Human-Computer Interface (HCI) in numerous application areas such as medical, military, entertainment and manufacturing. It enables higher performance of on-site tasks with seamless presentation of up-to-date, task-related information to the users during the operation. AR has potentials in design because the current interface provided by Computer-aided Design (CAD) packages is less intuitive and reports show that the presence of physical objects help design thinking and communication. This research explores the use of AR to improve the efficiency of a design process, specifically in mechanical design.

Logistics Network Design with Differentiated Delivery Lead-Time: Benefits and Insights

Most logistics network design models assume exogenous customer demand that is independent of the service time or level. This paper examines the benefits of segmenting demand according to lead-time sensitivity of customers. To capture lead-time sensitivity in the network design model, we use a facility grouping method to ensure that the different demand classes are satisfied on time. In addition, we perform a series of computational experiments to develop a set of managerial insights for the network design decision making process.