A Diffusion-Based Approach to Geminate Recombination of Heme Proteins with Small Ligands

A model of postphotodissociative monomolecular (geminate) recombination of heme proteins with small ligands (NO, O2 or CO) is represented. The non-exponential decay with time for the probability to find a heme in unbound state is interpreted in terms of diffusion-like migration of ligabs physics/0212040 and between protein cavities. The temporal behavior for the probability is obtained from numerical simulation and specified by two parameters: the time \tau_{reb} of heme-ligand rebinding for the ligand localized inside the heme pocket and the time \tau_{esc} of ligand escape from the pocket. The model is applied in the analysis of available experimental data for geminate reoxygenation of human hemoglobin HbA. Our simulation is in good agreement with the measurements. The analysis shows that the variation in pH of the solution (6.0<pH<9.4) results in considerable changes for \tau_{reb} from 0.36 ns (at pH=8.5) up to 0.5 ns (pH=6.0) but effects slightly on the time \tau_{esc} (\tau_{esc} ~ 0.88 ns).Comment: 8 pages with 4 figures, submitted to Chem. Phy

The Maunakea Spectroscopic Explorer Book 2018

(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

Repeated exposure to socioeconomic disadvantage and health selection as life course pathways to mid-life depressive and anxiety disorders

The biomedical examination was funded by Medical Research Council [G0000934], awarded under the Health of the Public initiative. Charlotte Clark is supported by an Engineering and Physical Sciences Research Fellowship. Bryan Rodgers is supported by Research Fellowships Nos 148948 and 366758 and by Program Grant No. 179805 from the National Health and Medical Research Council of Australia. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu[superscript 230], located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.Glenn Foundation for Medical ResearchEllison Medical FoundationJuvenile Diabetes Research Foundation InternationalUnited Mitochondrial Disease FoundationNational Institutes of Health (U.S.)National Institute of Allergy and Infectious Diseases (U.S.

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument.Comment: Full report: 498 pages. Executive Summary: 14 pages. More information about HabEx can be found here: https://www.jpl.nasa.gov/habex

A framework to integrate design knowledge reuse and requirements management in engineering design

This paper presents a framework to integrate requirements management and design knowledge reuse. The research approach begins with a literature review in design reuse and requirements management to identify appropriate methods within each domain. A framework is proposed based on the identified requirements. The framework is then demonstrated using a case study example: vacuum pump design. Requirements are presented as a component of the integrated design knowledge framework. The proposed framework enables the application of requirements management as a dynamic process, including capture, analysis and recording of requirements. It takes account of the evolving requirements and the dynamic nature of the interaction between requirements and product structure through the various stages of product development. (C) 2007 Elsevier Ltd. All rights reserved

An engineering design knowledge reuse methodology using process modelling.

This paper describes an approach for reusing engineering design knowledge. Many previous design knowledge reuse systems focus exclusively on geometrical data, which is often not applicable in early design stages. The proposed methodology provides an integrated design knowledge reuse framework, bringing together elements of best practice reuse, design rationale capture and knowledge-based support in a single coherent framework. Best practices are reused through the process model. Rationale is supported by product information, which is retrieved through links to design process tasks. Knowledge-based methods are supported by a common design data model, which serves as a single source of design data to support the design process. By using the design process as the basis for knowledge structuring and retrieval, it serves the dual purpose of design process capture and knowledge reuse: capturing and formalising the rationale that underpins the design process, and providing a framework through which design knowledge can be stored, retrieved and applied. The methodology has been tested with an industrial sponsor producing high vacuum pumps for the semiconductor industry