Synthetic Circuits for Feedback and Detection in Bacteria

Synthetic biology, by co-opting molecular machinery from existing organisms, can be used as a tool for building new genetic systems from scratch, for understanding natural networks through perturbation, or for hybrid circuits that piggy-back on existing cellular infrastructure. Although the toolbox for genetic circuits has greatly expanded in recent years, it is still difficult to separate the circuit function from its specific molecular implementation. In this thesis, we discuss the function-driven design of two synthetic circuit modules, and use mathematical models to understand the fundamental limits of circuit topology versus operating regimes as determined by the specific molecular implementation. First, we describe a protein concentration tracker circuit that sets the concentration of an output protein relative to the concentration of a reference protein. The functionality of this circuit relies on a single negative feedback loop that is implemented via small programmable protein scaffold domains. We build a mass-action model to understand the relevant timescales of the tracking behavior and how the input/output ratios and circuit gain might be tuned with circuit components. Second, we design an event detector circuit with permanent genetic memory that can record order and timing between two chemical events. This circuit was implemented using bacteriophage integrases that recombine specific segments of DNA in response to chemical inputs. We simulate expected population-level outcomes using a stochastic Markov-chain model, and investigate how inferences on past events can be made from differences between single-cell and population-level responses. Additionally, we present some preliminary investigations on spatial patterning using the event detector circuit as well as the design of stationary phase promoters for growth-phase dependent activation. These results advance our understanding of synthetic gene circuits, and contribute towards the use of circuit modules as building blocks for larger and more complex synthetic networks.

Self-defeating austerity? Assessing the impact of fiscal consolidations on unemployment

The great recession of 2008/2009 has had a huge impact on unemployment and public finances in most advanced countries, and these impacts were magnified in the southern Euro area countries by the sovereign debt crisis of 2010/2011. The fiscal consolidation imposed by the European Union on highly indebted countries was based on the assumptions of the so-called expansionary austerity. However, the reality so far shows proof to the contrary, and the results of this paper support the opposing view of a self- defeating austerity. Based on the input-output relations of the productive system, an unemployment rate/budget balance trade-off equation is derived, as well as the impact of a strong fiscal consolidation based on social transfers and the notion of neutral budget balance. An application to the Portuguese case confirms the huge costs of a strong fiscal consolidation, both in terms of unemployment and social policy regress, and it allows one to conclude that too much consolidation in one year makes consolidation more difficult in the following year.

Foreign direct investment determinants revisited in the context of global value chains

In this paper, we aim at contributing to the new field of research that intends to bring up-to-date the tools and statistics currently used to look to the current reality given by Global Value Chains (GVC) in international trade and Foreign Direct Investment (FDI). Namely, we make use of the most recent data published by the World Input-Output Database to suggest indicators to measure the participation and net gains of countries by being a part of GVC; and use those indicators in a pooled-regression model to estimate determinants of FDI stocks in Organization for Economic Co-operation and Development (OECD)-member countries. We conclude that one of the measures proposed proves to be statistically significant in explaining the bilateral stock of FDI in OECD countries, meaning that the higher the transnational income generated between two given countries by GVC, taken as a proxy to the participation of those countries in GVC, the higher one could expect the FDI entering those countries to be. The regression also shows the negative impact of the global financial crisis that started in 2009 in the world’s bilateral FDI stocks and, additionally, the particular and significant role played by the People’s Republic of China in determining these stocks.

Inter-industry analysis and monetary policy evaluations in the Korean flow of funds accounts

This study mainly aims to provide an inter-industry analysis through the subdivision of various industries in flow of funds (FOF) accounts. Combined with the Financial Statement Analysis data from 2004 and 2005, the Korean FOF accounts are reconstructed to form "from-whom-to-whom" basis FOF tables, which are composed of 115 institutional sectors and correspond to tables and techniques of input–output (I–O) analysis. First, power of dispersion indices are obtained by applying the I–O analysis method. Most service and IT industries, construction, and light industries in manufacturing are included in the first quadrant group, whereas heavy and chemical industries are placed in the fourth quadrant since their power indices in the asset-oriented system are comparatively smaller than those of other institutional sectors. Second, investments and savings, which are induced by the central bank, are calculated for monetary policy evaluations. Industries are bifurcated into two groups to compare their features. The first group refers to industries whose power of dispersion in the asset-oriented system is greater than 1, whereas the second group indicates that their index is less than 1. We found that the net induced investments (NII)–total liabilities ratios of the first group show levels half those of the second group since the former's induced savings are obviously greater than the latter.

Undermined climate policies : a study on the impact of regulatory and financial discrimination across heterogeneous firms in China

Firms in China within the same industry but with different ownership and size have very different production functions and can face very different emission regulations and financial conditions. This fact has largely been ignored in most of the existing literature on climate change. Using a newly augmented Chinese input–output table in which information about firm size and ownership are explicitly reported, this paper employs a dynamic computable general equilibrium (CGE) model to analyze the impact of alternative climate policy designs with respect to regulation and financial conditions on heterogeneous firms. The simulation results indicate that with a business-as-usual regulatory structure, the effectiveness and economic efficiency of climate policies is significantly undermined. Expanding regulation to cover additional firms has a first-order effect of improving efficiency. However, over-investment in energy technologies in certain firms may decrease the overall efficiency of investments and dampen long-term economic growth by competing with other fixed-capital investments for financial resources. Therefore, a market-oriented arrangement for sharing emission reduction burden and a mechanism for allocating green investment is crucial for China to achieve a more ambitious emission target in the long run.

Productivity growth and the structure of production

In this study, interactions between potential hierarchical value chains existing in the production structure and industry-wise productivity growths are sought. We applied generalized Chenery-Watanabe heuristics for matrix linearity maximization to triangulate the input-output incidence matrix for both Japan and the Republic of Korea, finding the potential directed flow of values spanning the industrial sectors of the basic (disaggregated) industry classifications for both countries. Sector specific productivity growths were measured by way of the Trönquvist index, using the 2000-2005 linked input-output tables for both Japan and Korea.

Modelo de gestión del conocimiento para el impacto económico. Aplicación al sector defensa

En el escenario actual macro económico la toma de decisiones en materia económica de cualquier entidad pública debe de estar sustentada por una adecuada inteligencia económica. Es prioritario disponer de modelos, procesos, técnicas y herramientas que permitan garantizar un control adecuado de todas sus inversiones. En la presente tesis exponemos un modelo de gestión del conocimiento basado en el marco Input-Output (IO), que nos permite conocer el impacto económico de los programas públicos. Este modelo está soportado por un sistema de información que coadyuvará a los analistas económicos para la toma de decisiones en el campo de las inversiones públicas. El principal objetivo de la tesis es la creación y desarrollo de este modelo denominado MOCIE (Modelo del Conocimiento para el Impacto Económico). No obstante, en la tesis además de profundizar sobre este modelo y la gestión del conocimiento en materia económica de los grandes programas públicos, se ha realizado un estudio que ha abarcado diferentes líneas de investigación complementarias como el análisis IO, la ingeniería y la arquitectura de sistemas de la información, la economía de la Defensa o la computación genética. El modelo propuesto en esta tesis se ha puesto en práctica en un sector económico muy específico dentro de la economía nacional: el sector de la defensa. Por tanto, ha sido también necesario realizar un estudio en profundidad del propio sector y de la gestión de los programas públicos en el ámbito de la Defensa. MOCIE se estructura a través de tres capas de gestión del conocimiento que nos permiten, por un lado, la percepción de los componentes existentes en el entorno de las inversiones públicas y la comprensión de su significado en términos de impacto económico y su relación con el resto de variables macroeconómicas nacionales y, por otro, la proyección y monitorización de su estado a lo largo de todo el ciclo de vida de los programas públicos...

Thermally induced all-optical inverter and dynamic hysteresis loops in graphene oxide dispersions

We experimentally study the temporal dynamics of amplitude-modulated laser beams propagating through a water dispersion of graphene oxide sheets in a fiber-to-fiber U-bench. Nonlinear refraction induced in the sample by thermal effects leads to both phase reversing of the transmitted signals and dynamic hysteresis in the input- output power curves. A theoretical model including beam propagation and thermal lensing dynamics reproduces the experimental findings. © 2015 Optical Society of America.

La articulación productiva como elemento clave para el desarrollo económico: la experiencia de España, Corea del Sur y México frente al proceso de internacionalización de la producción, 1980-2000

La articulación productiva, como una característica esencial de la estructura económica, es un tema poco analizado por la teoría económica. Por lo tanto, esta tesis pretende incorporarla en el análisis económico de manera explícita, para estudiar los efectos que tienen sobre las características de las estructuras económicas la actual forma de organización de la producción y el comercio a nivel mundial. La investigación analiza las repercusiones de la producción fragmentada sobre las características de las estructuras económicas y los posibles efectos para el desarrollo económico. Se estudian tres países – Corea del Sur, España y México –, caracterizados por una fuerte integración internacional. Con el fin de evaluar el desempeño económico bajo modelos de desarrollo disímiles, se comparan el año de 1980 con al primer decenio del 2000, con el empleo de tablas input-output (TIO)...

Bienes de capital, flujos tecnológicos y cambio estructural: los casos de Estados Unidos, Japón y Alemania, 1980-2005

La innovación tecnológica se encuentra estrechamente vinculada con el desenvolvimiento de la estructura productiva. Durante mucho tiempo, esta relación era muy evidente, ya que la tecnología como fuente impulsora del crecimiento se asociaba a la inversión en maquinaria y equipo. Ésta última, integraba el componente de innovación que generaba el incremento en productividad. El modelo neoclásico ortodoxo centro el estudio del crecimiento económico en el estudio de Solow (1957), quien explica que la fuente del crecimiento se encuentra en un factor exógeno, que identifica como cambio tecnológico y, de esta manera, resta importancia a la inversión como un determinante del incremento en el producto. En consecuencia, los aportes teóricos recientes, particularmente el neoclásico, centran su atención en los factores que inciden en la generación y desarrollo de innovaciones, pero dejan de lado la vinculación con la estructura económica. En este trabajo se analiza la importancia de los bienes de capital en Alemania, Japón y Estados Unidos, empleando tablas input-output, durante 1980 y 2005, definiendo la vinculación entre cambio tecnológico y la estructura productiva. 1. Síntesis El objetivo es demostrar que la industria de bienes de capital vincula la dinámica tecnológica y los procesos de innovación con el desenvolvimiento de la estructura productiva, por ser clave en el desarrollo económico como fuerza motriz del sistema al generar cambio tecnológico, transferir innovaciones y articular el cambio tecnológico con la estructura productiva. De la Tesis se extraen los siguientes resultados: a) Desde una visión teórica Nathan Rosenberg justifica la importancia de los bienes de capital, por su capacidad de generar cambio tecnológico incorporado, así como por su carácter articulador con otros sectores productivos, favoreciendo el proceso de desarrollo económico. Por el lado metodológico, el análisis input-output resulta ser el más idóneo para el propósito de la investigación. b) La importancia del cambio tecnológico Mediante el estudio de patentes, se demostró que la dinámica de innovación del sector está relacionada con los flujos de conocimiento, al crear y difundir innovaciones, y por su habilidad de asimilar los avances generados en otros sectores. Con el empleo del “Análisis de Flujo Mínimo”, se determina que los bienes de capital juegan un papel destacado por sus efectos de propagación del esfuerzo innovador; asimismo, por ser generadores de innovaciones, su inversión en I+D se traduce en una alta capacidad para impactar a los sectores con los que se vincula...

Participation of portuguese manufacturing industry in global value chains

Portugal’s manufacturing sector has a significant importance both in national income and employment. As has been pointed out by several researchers, the traditional methods of analysis fail to grasp all the dimensions of economic competitiveness. This dissertation is then, at its core, an analysis of Portugal’s manufacturing industry in terms of the latter’s value added to production and impact to employment under the framework of global value chains. The current dissertation seeks to study in which way the Portuguese manufacturing industry, and its respective sectors, has a direct and indirect impact on the creation of value added and employment and how this impact can be measured. For development of this work the input-output approach for calculation of multipliers and the new framework proposed by Timmer et al. (2013) for calculation of GVC income and GVC jobs indicators were used, elaborated on the basis of the WIOD project dataset. Moreover, to illustrate the application of the provided methodology the Portuguese textile industry was used as an example. It was found that the changes in final demand of such sectors as Pulp, Paper, Printing and Publishing; Machinery, Nec and Textiles and Textile Products would have a larger impact on generated value added than other manufacturing sectors. At the same time, employment created by the changes in final demand would be more impacted by such sectors as Food, Beverages and Tobacco; Wood and Products of Wood and Cork and Textiles and Textile Products. In this regard, the number of low-skilled workers in Portugal seems to be more effected by changes in final demand, than those occupied by higher -skilled individuals. Moreover, it was found that the distribution of GVC income and GVC jobs for the Portuguese manufacturing industry shares a similar outlook. However, upon closer inspection of GVC labour distribution by skill levels there seems to exist a general progression in which low-skilled jobs requirements are met by local resources, while the need for higher skilled jobs require a greater “off-shoring” of work The results obtained through calculations of presented multipliers provide a powerful tool for policy makers in strategic planning of development of national economy. Using the provided methodology and obtained results, a government and supranational organizations could define which industry would have the greatest impact for an additional unit of output generated through the economy, and thus define the sectors for further investments.

“Análise da Eficiência, Eficácia e Mortalidade Empresarial”

Este artigo analisa a eficácia e a eficiência do Programa Leader + e a mortalidade das empresas que beneficiaram de apoio financeiro no âmbito desta política pública, nas regiões Norte e Alentejo, no período de 2000 a 2006. A análise da eficácia e da eficiência incide sobre a totalidade dos projetos de investimento financiados e o estudo da mortalidade empresarial inclui apenas as empresas do sector privado, com atividade e/ou sede nas regiões citadas, que beneficiaram de financiamento. A avaliação da eficácia e da eficiência sustentou-se em indicadores de realização, indicadores de resultado e no rácio input-output. A sustentabilidade da política pública foi avaliada com base nas taxa de mortalidade das empresas e no estudo da relação entre a mortalidade empresarial e as variáveis região de pertença, atividade da empresa e número de sócios. O estudo permitiu encontrar diferenças entre as duas regiões ao nível da eficácia e da eficiência da política pública, bem como ao nível da mortalidade empresarial.

Multi-output buck-boost converter with enhanced dynamic response to load and input voltage changes

This paper presents a new multi-output DC/DC converter topology that has step-up and step-down conversion capabilities. In this topology, several output voltages can be generated which can be used in different applications such as multilevel converters with diode-clamped topology or power supplies with several voltage levels. Steady state and dynamic equations of the proposed multi-output converter have been developed, that can be used for steady state and transient analysis. Two control techniques have been proposed for this topology based on constant and dynamic hysteresis band height control to address different applications. Simulations have been performed for different operating modes and load conditions to verify the proposed topology and its control technique. Additionally, a laboratory prototype is designed and implemented to verify the simulation results.

Early and late electrophysiological effects of distractor frequency in picture naming: Reconciling input and output accounts

The “distractor-frequency effect” refers to the finding that high-frequency (HF) distractor words slow picture naming less than low-frequency distractors in the picture–word interference paradigm. Rival input and output accounts of this effect have been proposed. The former attributes the effect to attentional selection mechanisms operating during distractor recognition, whereas the latter attributes it to monitoring/decision mechanisms operating on distractor and target responses in an articulatory buffer. Using high-density (128-channel) EEG, we tested hypotheses from these rival accounts. In addition to conducting stimulus- and response-locked whole-brain corrected analyses, we investigated the correct-related negativity, an ERP observed on correct trials at fronto-central electrodes proposed to reflect the involvement of domain general monitoring. The wholebrain ERP analysis revealed a significant effect of distractor frequency at inferior right frontal and temporal sites between 100 and 300-msec post-stimulus onset, during which lexical access is thought to occur. Response-locked, region of interest (ROI) analyses of fronto-central electrodes revealed a correct-related negativity starting 121 msec before and peaking 125 msec after vocal onset on the grand averages. Slope analysis of this component revealed a significant difference between HF and lowfrequency distractor words, with the former associated with a steeper slope on the time windowspanning from100 msec before to 100 msec after vocal onset. The finding of ERP effects in time windows and components corresponding to both lexical processing and monitoring suggests the distractor frequency effect is most likely associated with more than one physiological mechanism.