Iso-array rewriting P systems with context-free iso-array rules

A new computing model called P system is a highly distributed and parallel theoretical model, which is proposed in the area of membrane computing. Ceterchi et al. initially proposed array rewriting P systems by extending the notion of string rewriting P systems to arrays (2003). A theoretical model for picture generation using context-free iso-array grammar rules and puzzle iso-array grammar rules are introduced by Kalyani et al. (2004, 2006). Also iso-array rewriting P systems for iso-picture languages have been studied by Annadurai et al. (2008). In this paper we consider the context-free iso-array rules and context-free puzzle iso-array rules in iso-array rewriting P systems and examine the generative powers of these P systems

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

A well-defined notion of chemical compound space (CCS) is essential for gaining rigorous control of properties through variation of elemental composition and atomic configurations. Here, we review an atomistic first principles perspective on CCS. First, CCS is discussed in terms of variational nuclear charges in the context of conceptual density functional and molecular grand-canonical ensemble theory. Thereafter, we revisit the notion of compound pairs, related to each other via "alchemical" interpolations involving fractional nuclear chargens in the electronic Hamiltonian. We address Taylor expansions in CCS, property non-linearity, improved predictions using reference compound pairs, and the ounce-of-gold prize challenge to linearize CCS. Finally, we turn to machine learning of analytical structure property relationships in CCS. These relationships correspond to inferred, rather than derived through variational principle, solutions of the electronic Schr\"odinger equation

Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0

Increased lifetime of Organic Photovoltaics (OPVs) and the impact of degradation, efficiency and costs in the LCOE of Emerging PVs

Emerging photovoltaic (PV) technologies such as organic photovoltaics (OPVs) and perovskites (PVKs) have the potential to disrupt the PV market due to their ease of fabrication (compatible with cheap roll-to-roll processing) and installation, as well as their significant efficiency improvements in recent years. However, rapid degradation is still an issue present in many emerging PVs, which must be addressed to enable their commercialisation. This thesis shows an OPV lifetime enhancing technique by adding the insulating polymer PMMA to the active layer, and a novel model for quantifying the impact of degradation (alongside efficiency and cost) upon levelized cost of energy (LCOE) in real world emerging PV installations. The effect of PMMA morphology on the success of a ternary strategy was investigated, leading to device design guidelines. It was found that either increasing the weight percent (wt%) or molecular weight (MW) of PMMA resulted in an increase in the volume of PMMA-rich islands, which provided the OPV protection against water and oxygen ingress. It was also found that adding PMMA can be effective in enhancing the lifetime of different active material combinations, although not to the same extent, and that processing additives can have a negative impact in the devices lifetime. A novel model was developed taking into account realistic degradation profile sourced from a literature review of state-of-the-art OPV and PVK devices. It was found that optimal strategies to improve LCOE depend on the present characteristics of a device, and that panels with a good balance of efficiency and degradation were better than panels with higher efficiency but higher degradation as well. Further, it was found that low-cost locations were more favoured from reductions in the degradation rate and module cost, whilst high-cost locations were more benefited from improvements in initial efficiency, lower discount rates and reductions in install costs

Development and Application of Pseudoreceptor Modeling

Quantitative Structure-Activity Relationship (QSAR) methods are a commonly used tool in the drug discovery process. These methods attempt to form a statistical model that relates descriptor properties of a ligand to the activity of that ligand compound towards a specific desired physiological response. QSAR methods are known as a ligand-based method, as they specifically use information from ligands and not protein structural data. However, a derivation of QSAR methods are pseudoreceptor methods. Pseudoreceptor methods go beyond standard QSAR by building a model representation of the protein pocket. However, the ability of pseudoreceptors to accurately replicate natural protein surfaces has not been studied. The goal of this thesis work is to investigate the necessary descriptors to map a protein binding pocket and a method to accurately recreate the 3-D spatial structure of the binding pocket. In addition, additional applications of existing pseudoreceptor methods are explored

Center for Space Microelectronics Technology. 1993 Technical Report

The 1993 Technical Report of the Jet Propulsion Laboratory Center for Space Microelectronics Technology summarizes the technical accomplishments, publications, presentations, and patents of the Center during the past year. The report lists 170 publications, 193 presentations, and 84 New Technology Reports and patents. The 1993 Technical Report of the Jet Propulsion Laboratory Center for Space Microelectronics Technology summarizes the technical accomplishments, publications, presentations, and patents of the Center during the past year. The report lists 170 publications, 193 presentations, and 84 New Technology Reports and patents

Searching for life in the Universe: unconventional methods for an unconventional problem

The search for life, on and off our planet, can be done by conventional methods with which we are all familiar. These methods are sensitive and specific, and are often capable of detecting even single cells. However, if the search broadens to include life that may be different (even subtly different) in composition, the methods and even the approach must be altered. Here we discuss the development of what we call non-earthcentric life detection – detecting life with methods that could detect life no matter what its form or composition. To develop these methods, we simply ask, can we define life in terms of its general properties and particularly those that can be measured and quantified? Taking such an approach we can search for life using physics and chemistry to ask questions about structure, chemical composition, thermodynamics, and kinetics. Structural complexity can be searched for using computer algorithms that recognize complex structures. Once identified, these structures can be examined for a variety of chemical traits, including elemental composition, chirality, and complex chemistry. A second approach involves defining our environment in terms of energy sources (i.e., reductants), and oxidants (e.g. what is available to eat and breathe), and then looking for areas in which such phenomena are inexplicably out of chemical equilibrium. These disequilibria, when found, can then be examined in detail for the presence of the structural and chemical complexity that presumably characterizes any living systems. By this approach, we move the search for life to one that should facilitate the detection of any earthly life it encountered, as well as any non-conventional life forms that have structure, complex chemistry, and live via some form of redox chemistry

Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes

Microglia are the CNS resident immune cells that react to misfolded proteins through pattern recognition receptor ligation and activation of inflammatory pathways. Here, we studied how microglia handle and cope with alpha-synuclein (alpha-syn) fibrils and their clearance. We found that microglia exposed to alpha-syn establish a cellular network through the formation of F-actin-dependent intercellular connections, which transfer alpha-syn from overloaded microglia to neighboring naive microglia where the alpha-syn cargo got rapidly and effectively degraded. Lowering the alpha-syn burden attenuated the inflammatory profile of microglia and improved their survival. This degradation strategy was compromised in cells carrying the LRRK2 G2019S mutation. We confirmed the intercellular transfer of alpha-syn assemblies in microglia using organotypic slice cultures, 2-photon microscopy, and neuropathology of patients. Together, these data identify a mechanism by which microglia create an on-demand functional network in order to improve pathogenic alpha-syn clearance