CurlySMILES: a chemical language to customize and annotate encodings of molecular and nanodevice structures

CurlySMILES is a chemical line notation which extends SMILES with annotations for storage, retrieval and modeling of interlinked, coordinated, assembled and adsorbed molecules in supramolecular structures and nanodevices. Annotations are enclosed in curly braces and anchored to an atomic node or at the end of the molecular graph depending on the annotation type. CurlySMILES includes predefined annotations for stereogenicity, electron delocalization charges, extra-molecular interactions and connectivity, surface attachment, solutions, and crystal structures and allows extensions for domain-specific annotations. CurlySMILES provides a shorthand format to encode molecules with repetitive substructural parts or motifs such as monomer units in macromolecules and amino acids in peptide chains. CurlySMILES further accommodates special formats for non-molecular materials that are commonly denoted by composition of atoms or substructures rather than complete atom connectivity

Rationale and Architecture Principles for Medical Application Platforms

The concept of “system of systems” architecture is increasingly prevalent in many critical domains. Such systems allow information to be pulled from a variety of sources, analyzed to discover correlations and trends, stored to enable realtime and post-hoc assessment, mined to better inform decisionmaking, and leveraged to automate control of system units. In contrast, medical devices typically have been developed as monolithic stand-alone units. However, a vision is emerging of a notion of a medical application platform (MAP) that would provide device and health information systems (HIS) interoperability, safety critical network middleware, and an execution environment for clinical applications (“apps”) that offer numerous advantages for safety and effectiveness in health care delivery. In this paper, we present the clinical safety/effectiveness and economic motivations for MAPs, and describe key characteristics of MAPs that are guiding the search for appropriate technology, regulatory, and ecosystem solutions. We give an overview of the Integrated Clinical Environment (ICE) – one particular achitecture for MAPs, and the Medical Device Coordination Framework – a prototype implementation of the ICE architecture

Hole transfer equilibrium in rigidly linked bichromophoric molecules

Two bichromophoric molecules consisting of anthracene and diphenylpolyene moieties linked by two fused norbornyl bridges undergo photoionization upon ultraviolet (UV) pulsed laser irradiation. The simultaneous observation of the cation radicals of both anthracene and polyene groups points to a rapid (nanosecond or faster) intramolecular hole transfer equilibrium between the two chromophores. The existence of an equilibrium is supported by the results of one- and two-laser transient absorption and electrochemical experiments. Equilibrium constants (293 K) were determined by both transient absorption and cyclic voltammetry measurements and were independent of the method used within experimental error. For A-sp-VB, which contains anthracene and vinyldiphenylbutadiene chromophores, Keq = 4.0 ? 2 (transient absorption) and 3.2 ? 2 (electrochemical), favoring the anthracene cation radical. For A-sp-VS, containing anthracene and vinylstilbene groups, Keq = 70 ? 30 (transient absorption) and 105 ? 50 (electrochemical), favoring the anthracene cation radical.Peer reviewed: YesNRC publication: Ye

Credibility Evidence for Computational Patient Models Used in the Development of Physiological Closed-Loop Controlled Devices for Critical Care Medicine

Physiological closed-loop controlled medical devices automatically adjust therapy delivered to a patient to adjust a measured physiological variable. In critical care scenarios, these types of devices could automate, for example, fluid resuscitation, drug delivery, mechanical ventilation, and/or anesthesia and sedation. Evidence from simulations using computational models of physiological systems can play a crucial role in the development of physiological closed-loop controlled devices; but the utility of this evidence will depend on the credibility of the computational model used. Computational models of physiological systems can be complex with numerous non-linearities, time-varying properties, and unknown parameters, which leads to challenges in model assessment. Given the wide range of potential uses of computational patient models in the design and evaluation of physiological closed-loop controlled systems, and the varying risks associated with the diverse uses, the specific model as well as the necessary evidence to make a model credible for a use case may vary. In this review, we examine the various uses of computational patient models in the design and evaluation of critical care physiological closed-loop controlled systems (e.g., hemodynamic stability, mechanical ventilation, anesthetic delivery) as well as the types of evidence (e.g., verification, validation, and uncertainty quantification activities) presented to support the model for that use. We then examine and discuss how a credibility assessment framework (American Society of Mechanical Engineers Verification and Validation Subcommittee, V&V 40 Verification and Validation in Computational Modeling of Medical Devices) for medical devices can be applied to computational patient models used to test physiological closed-loop controlled systems

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities

<p>Abstract</p> <p>Background</p> <p>Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups.</p> <p>Results</p> <p>We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects.</p> <p>Conclusions</p> <p>The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.</p

Visual Network Analysis of Dynamic Metabolic Pathways

Abstract. We extend our previous work on the exploration of static metabolic networks to evolving, and therefore dynamic, pathways. We apply our visualization software to data from a simulation of early metabolism. Thereby, we show that our technique allows us to test and argue for or against different scenarios for the evolution of metabolic pathways. This supports a profound and efficient analysis of the structure and properties of the generated metabolic networks and its underlying components, while giving the user a vivid impression of the dynamics of the system. The analysis process is inspired by Ben Shneiderman’s mantra of information visualization. For the overview, user-defined diagrams give insight into topological changes of the graph as well as changes in the attribute set associated with the participating enzymes, substances and reactions. This way, “interesting features” in time as well as in space can be recognized. A linked view implementation enables the navigation into more detailed layers of perspective for in-depth analysis of individual network configuration

Functional Group and Substructure Searching as a Tool in Metabolomics

BACKGROUND: A direct link between the names and structures of compounds and the functional groups contained within them is important, not only because biochemists frequently rely on literature that uses a free-text format to describe functional groups, but also because metabolic models depend upon the connections between enzymes and substrates being known and appropriately stored in databases. METHODOLOGY: We have developed a database named "Biochemical Substructure Search Catalogue" (BiSSCat), which contains 489 functional groups, >200,000 compounds and >1,000,000 different computationally constructed substructures, to allow identification of chemical compounds of biological interest. CONCLUSIONS: This database and its associated web-based search program (http://bisscat.org/) can be used to find compounds containing selected combinations of substructures and functional groups. It can be used to determine possible additional substrates for known enzymes and for putative enzymes found in genome projects. Its applications to enzyme inhibitor design are also discussed