A Design-for-Yield Algorithm to Assess and Improve the Structural and Energetic Robustness of Proteins and Drugs

Robustness is a property that pervades all aspects of nature. The ability of a system to adapt to perturbations due to internal and external agents, aging, wear, or to environmental changes is one of the driving forces of evolution. At the molecular level, understanding the robustness of a protein has a great impact on the in-silico design of polypeptide chains and drugs. The chance of computationally checking the ability of a protein to preserve its structure in the native state may lead to the design of new compounds that can work in a living cell more effectively. Inspired by the well known robustness analysis framework used in Electronic Design Automation, we introduce a formal definition of robustness for proteins and a dimensionless quantity, called yield, to quantify the robustness of a protein. Then, we introduce a new robustness-centered protein design algorithm called Design-For-Yield. The aim of the algorithm is to discover new conformations with a specific functionality and high yield values. We present extensive characterizations of the robustness properties of many peptides, proteins, and drugs. Finally, we apply the DFY algorithm on the Crambin protein (1CRN) and on the Oxicitin drug (DB00107). The obtained results confirm that the algorithm is able to discover a Crambin-like protein that is 23.61% more robust than the wild type. Concerning the Oxicitin drug a new protein sequence and the corresponding protein structure was discovered with an improved robustness of 3% at the global level. © 2009 Springer Berlin Heidelberg

Global Dynamics, Domestic Coalitions and a Reactive State: Major Policy Shifts in Post-War Turkish Economic Development

The main objective of this study is to propose an analytical framework to explain the major policy shifts that has characterized post-war Turkish economic development; divided into four phases, starting respectively in 1950, 1960, 1980, and 2001. Its main contribution is to incorporate external and internal factors into this framework within a broadly political economy perspective, attaching particular significance to the role of economic crises in moving from one phase to the other. While the role of external agents is identified as the main factor behind policy shifts, the role of domestic coalitions in support of policy regime in each phase is also recognized. Drawing attention to the role of state in the impressive recent growth of countries such as China, India, and Ireland, the paper argues that there is still room for the state taking on a developmental role. The paper recommends that Turkey follows a similar path by improving state capacity not only with respect to its regulatory role but also in more developmental spheres, encompassing its redistributive and transformative role on the basis of a domestically-determined industrialization strategy.Publisher's Versio

Soft Fault Clustering in Analog Electronic Circuits with the Use of Self Organizing Neural Network

The paper presents a methodology for parametric fault clustering in analog electronic circuits with the use of a self-organizing artificial neural network. The method proposed here allows fast and efficient circuit diagnosis on the basis of time and/or frequency response which may lead to higher production yield. A self-organizing map (SOM) has been applied in order to cluster all circuit states into possible separate groups. So, it works as a feature selector and classifier. SOM can be fed by raw data (data comes from the time or frequency response) or some pre-processing is done at first. The author proposes conversion of a circuit response with the use of e.g. gradient and differentiation. The main goal of the SOM is to distribute all single faults on a two-dimensional map without state overlapping. The method is aimed for the development stage because the tolerances of elements are not taken into account, however single but parametric faults are considered. Efficiency analyses of fault clustering have been made on several examples e.g. a Sallen-Key BPF and an ECG amplifier. Testing procedure is performed in time and frequency domains for the Sallen-Key BPF with limited number of test points i.e. it is assumed that only input and output pins are available. A similar procedure has been applied to a real ECG amplifier in the frequency domain. Results prove a high efficiency in acceptable time which makes th