Synthetic Gene Circuits: Design with Directed Evolution

Synthetic circuits offer great promise for generating insights into nature's underlying design principles or forward engineering novel biotechnology applications. However, construction of these circuits is not straightforward. Synthetic circuits generally consist of components optimized to function in their natural context, not in the context of the synthetic circuit. Combining mathematical modeling with directed evolution offers one promising means for addressing this problem. Modeling identifies mutational targets and limits the evolutionary search space for directed evolution, which alters circuit performance without the need for detailed biophysical information. This review examines strategies for integrating modeling and directed evolution and discusses the utility and limitations of available methods

The role of falsification in the development of cognitive architectures: insights from a Lakatosian analysis

It has been suggested that the enterprise of developing mechanistic theories of the human cognitive architecture is flawed because the theories produced are not directly falsifiable. Newell attempted to sidestep this criticism by arguing for a Lakatosian model of scientific progress in which cognitive architectures should be understood as theories that develop over time. However, Newell’s own candidate cognitive architecture adhered only loosely to Lakatosian principles. This paper reconsiders the role of falsification and the potential utility of Lakatosian principles in the development of cognitive architectures. It is argued that a lack of direct falsifiability need not undermine the scientific development of a cognitive architecture if broadly Lakatosian principles are adopted. Moreover, it is demonstrated that the Lakatosian concepts of positive and negative heuristics for theory development and of general heuristic power offer methods for guiding the development of an architecture and for evaluating the contribution and potential of an architecture’s research program

Selective Oxidation: From a Still Immature Technology to the Roots of Catalysis Science

The design of heterogeneous selective oxidation catalysts based upon complex metal oxides is governed at present by a set of empirical rules known as “pillars of oxidation catalysis”. They serve as practical guidelines for catalyst development and guide the reasoning about the catalyst role in the process. These rules are, however, not based upon atomistic concepts and thus preclude their immediate application in for example computer-aided search strategies. The present work extends the ideas of the pillar rules and develops the concept of considering a selective oxidation catalyst as enabler for the execution of a reaction network. The enabling function is controlled by mutual interactions between catalyst and reactants. The electronic structure of the catalyst is defined as a bulk semiconductor with a surface state arising form a terminating over layer being different from the structure of the bulk. These components that can be identified by in situ analytical methods form a chemical system with feedback loops, which is responsible for generating selectivity during execution of the reaction network. This concept is based upon physical observables and could allow for a design strategy based upon a kinetic description that combines the processes between reactants with the processes between catalyst and reactants. Such kinetics is not available at present. Few of the constants required are known but many of them are accessible to experimental determination with in situ techniques

METABOLIC MODELING AND OMICS-INTEGRATIVE ANALYSIS OF SINGLE AND MULTI-ORGANISM SYSTEMS: DISCOVERY AND REDESIGN

Computations and modeling have emerged as indispensable tools that drive the process of understanding, discovery, and redesign of biological systems. With the accelerating pace of genome sequencing and annotation information generation, the development of computational pipelines for the rapid reconstruction of high-quality genome-scale metabolic networks has received significant attention. These models provide a rich tapestry for computational tools to quantitatively assess the metabolic phenotypes for various systems-level studies and to develop engineering interventions at the DNA, RNA, or enzymatic level by careful tuning in the biophysical modeling frameworks. in silico genome-scale metabolic modeling algorithms based on the concept of optimization, along with the incorporation of multi-level omics information, provides a diverse array of toolboxes for new discovery in the metabolism of living organisms (which includes single-cell microbes, plants, animals, and microbial ecosystems) and allows for the reprogramming of metabolism for desired output(s). Throughout my doctoral research, I used genome-scale metabolic models and omics-integrative analysis tools to study how microbes, plants, animal, and microbial ecosystems respond or adapt to diverse environmental cues, and how to leverage the knowledge gleaned from that to answer important biological questions. Each chapter in this dissertation will provide a detailed description of the methodology, results, and conclusions from one specific research project. The research works presented in this dissertation represent important foundational advance in Systems Biology and are crucial for sustainable development in food, pharmaceuticals and bioproduction of the future. Advisor: Rajib Sah

Recent advances in natural polymer-based hydroxyapatite scaffolds:Properties and applications

New materials that mimic natural bone properties, matching functional, mechanical, and biological properties have been continuously developed to rehabilitate bone defects. Desirably, 'tissue engineering' has been a multidisciplinary ground that uses the principles of life sciences and engineering for the biological replacements that restore or replace the tissue function or a whole organ. Nevertheless, the bone grafting treatment has numerous restrictions, counting the major hazards of morbidity from the sites where donor bone grafts are removed, the likelihood for an immune rejection or bacterial transport from the donor site (in case of allogeneic grafting), and the inadequate availability of donor bone grafts that can meet the current demands. Since the proper growth of synthetic materials for implantable bones encourages the reconstruction of bone tissues by providing strong structural support without any damages to the interferences of biological tissue. To serve for such behavior, the biodegradable matrices provide temporary scaffolds within which the bone tissues can be regenerated. Typically, the thermoplastic aliphatic polyesters are found to serve this purpose. The great significance of this field lies in the in vitro growth of precise cells on porous matrices (scaffolds) to generate three-dimensional (3D) tissues that can be entrenched into the location of tissue/bone damage. Numerous gifts have been gifted by our nature to advance and preserve the well-being of all living things either directly or indirectly. This review focuses on the recent advances in polymer-based hydroxyapatite scaffolds including their properties and applications

Ion Beam Techniques and Applications

A wide variety of ion beam techniques are being used in several versatile applications ranging from environmental science, nuclear physics, microdevice fabrication to materials science. In addition, new applications of ion beam techniques across a broad range of disciplines and fields are also being discovered frequently. In this book, the latest research and development on progress in ion beam techniques has been compiled and an overview of ion beam irradiation-induced applications in nanomaterial-focused ion beam applications, ion beam analysis techniques, as well as ion implantation application in cells is provided. Moreover, simulations of ion beam-induced damage to structural materials of nuclear fusion reactors are also presented in this book

Getting rid of Keynes ? A survey of the history of macroeconomics from Keynes to Lucas and beyond

The aim of this paper is to recount the ebbs and flows of Keynesianism over the history of macroeconomics. The bulk of the paper consists of a discussion of the main episodes of the unfolding of macroeconomics (Keynesian macroeconomics, monetarism, new classical macroeconomics, real business cycle models and new neoclassical synthesis models) against the background of a distinction between Keynesianism as a ‘moderately conservative’ (Keynes’s words) vision about the working of the market system and as a conceptual apparatus. Particular attention is given to the contrast between Keynesian and Lucasian macroeconomics. The paper ends with a few remarks about the impact of the present crisis on the development of macroeconomic theoryKeynes, Lucas, history of macroeconomics