EPR of Compound I: An Illustrated Revision of the Theoretical Model

Compound I has been postulated to be the reactive species in many heme catalysts, which performs different chemistry and shows different properties in different enzymes. The aim of this review is to present a comprehensive model which has been successfully used to interpret the EPR spectra of various Compound I species. The theoretical approach established by seminal articles will be revisited and its ability to explain experimental results will be illustrated by simulating selected spectra from the literature. Compound I stores two oxidizing equivalents, one in the paramagnetic iron(IV)-oxo moiety, and another one as a free radical on the porphyrin ligand or an amino acid in the protein. To describe the interactions of the two paramagnetic species with each other and with their local environment, the spin Hamiltonian of the system is built step by step. The Fe(IV) center is described using a two-hole model. The effect of the crystal-field and spin–orbit coupling on the energy levels is calculated with this simple approach, which allows to obtain spin Hamiltonian parameters like zero-field splitting and effective g-values for the iron. The magnetic interaction between the Fe(IV) center and the free radical is considered and allowed to vary in sign (ferromagnetic to antiferromagnetic) and magnitude to interpret the EPR of Compound I species in different systems. Since orbital overlap is crucial for exchange interaction, special emphasis is made in obtaining the orientation of Fe semi-occupied orbitals by extending the counter-rotation concept, which relates the directions of magnetic, electronic, and molecular axes

(Architectural) measures to control wave overtopping inside harbours

One of the weak zones in the safety of the coastal city Oostende, Belgium, are the quays in the inner harbour which are rather low. A storm wall is an easy and effective measure to reduce wave overtopping and prevent the city from flooding. The location of this storm wall (close by the quay wall (2m) versus further away from the quay wall (15m)), and architectural alternatives for better integration in the setting have been studied at Ghent University. This paper summarizes the results

Economic Impact of Illness with Health Insurance but without Income Insurance

__Abstract__ We examine economic vulnerability to illness when, as for informal sector workers in Thailand, there is universal coverage for health care but earnings losses are uninsured. Even with comprehensive health care entitlement, severe illness that strikes an initially healthy worker is found to raise out-of-pocket medical expenses by around two thirds and increase the probability that medical spending absorbs more than a tenth of the household budget by nine percentage points. Moreover, severe illness reduces the probability of remaining in employment by 18 points and precipitates a reduction in household labor income of almost one third. Despite the rise in medical expenses and fall in earnings, households are able to maintain expenditure on goods and services other than medical care by drawing on remittances and informal transfers, cutting back on saving, and by borrowing. In the short term, informal insurance fills gaps left uncovered by formal insurance but there is likely to be subst antial exposure to economic risks associated with long-term illness

A Seamless Convergence of the Digital and Physical Factory Aiming in Personalized Product Emergence Process (PPEP) for Smart Products within ESB Logistics Learning Factory at Reutlingen University

AbstractA seamless convergence of the digital and physical factory aiming in personalized Product Emergence Process (PPEP) for smart products within ESB Logistics Learning Factory at Reutlingen University.A completely new business model with reference to Industrie4.0 and facilitated by 3D Experience Software in today's networked society in which customers expect immediate responses, delightful experience and simple solutions is one of the mission scenarios in the ESB Logistics Learning Factory at ESB Business School (Reutlingen University).The business experience platform provides software solutions for every organization in the company respectively in the factory. An interface with dashboards, project management apps, 3D - design and construction apps with high end visualization, manufacturing and simulation apps as well as intelligence and social network apps in a collaborative interactive environment help the user to learn the creation of a value end to end process for a personalized virtual and later real produced product.Instead of traditional ways of working and a conventional operating factory real workers and robots work semi-intuitive together. Centerpiece in the self-planned interim factory is the smart personalized product, uniquely identifiable and locatable at all times during the production process – a scooter with an individual colored mobile phone – holder for any smart phone produced with a 3D printer in lot size one. Smart products have in the future solutions incorporated internet based services – designed and manufactured - at the costs of mass products. Additionally the scooter is equipped with a retrievable declarative product memory. Monitoring and control is handled by sensor tags and a raspberry positioned on the product. The engineering design and implementation of a changeable production system is guided by a self-execution system that independently find amongst others esplanade workplaces.The imparted competences to students and professionals are project management method SCRUM, customization of workflows by Industrie4.0 principles, the enhancements of products with new personalized intelligent parts, electrical and electronic self-programmed components and the control of access of the product memory information, to plan in a digital engineering environment and set up of the physical factory to produce customer orders. The gained action-orientated experience refers to the chances and requirements for holistic digital and physical systems

Explanation of inequality in utilization of ambulatory care before and after universal health insurance in Thailand

Thailand implemented a Universal Coverage Scheme (UCS) of national health insurance in April 2001 to finance equitable access to health care. This paper compares inequalities in health service use before and after the UCS, and analyses the trend and determinants of inequality

Data in support of UbSRD: The Ubiquitin Structural Relational Database

This article provides information to support the database article titled UbSRD: The Ubiquitin Structural Relational Database (Harrison et al., 2015) [1] . The ubiquitin-like homology fold (UBL) represents a large family that encompasses both post-translational modifications, like ubiquitin (UBQ) and SUMO, and functional domains on many biologically important proteins like Parkin, UHRF1 (ubiquitin-like with PDB and RING finger domains-1), and Usp7 (ubiquitin-specific protease-7) (Zhang et al., 2015; Rothbart et al., 2013; Burroughs et al., 2012; Wauer et al., 2015) [2], [3], [4], [5]. The UBL domain can participate in several unique protein-protein interactions (PPI) since protein adducts can be attached to and removed from amino groups of lysine side chains and the N-terminus of proteins. Given the biological significance of UBL domains, many have been characterized with high-resolution techniques, and for UBQ and SUMO, many protein complexes have been characterized. We identified all the UBL domains in the PDB and created a relational database called UbSRD (Ubiquitin Structural Relational Database) by using structural analysis tools in the Rosetta (Leaver et al., 2013; O\u27Meara et al., 2015; Leaver-fay et al., 2011) [1], [6], [7], [8]. Querying UbSRD permitted us to report many quantitative properties of UBQ and SUMO recognition at different types interfaces (noncovalent: NC, conjugated: CJ, and deubiquitanse: DB). In this data article, we report the average number of non-UBL neighbors, secondary structure of interacting motifs, and the type of inter-molecular hydrogen bonds for each residue of UBQ and SUMO. Additionally, we used PROMALS3D to generate a multiple sequence alignment used to construct a phylogram for the entire set of UBLs (Pei and Grishin, 2014) [9]. The data described here will be generally useful to scientists studying the molecular basis for recognition of UBQ or SUMO

Data in support of UbSRD: The Ubiquitin Structural Relational Database

This article provides information to support the database article titled UbSRD: The Ubiquitin Structural Relational Database (Harrison et al., 2015) [1] . The ubiquitin-like homology fold (UBL) represents a large family that encompasses both post-translational modifications, like ubiquitin (UBQ) and SUMO, and functional domains on many biologically important proteins like Parkin, UHRF1 (ubiquitin-like with PDB and RING finger domains-1), and Usp7 (ubiquitin-specific protease-7) (Zhang et al., 2015; Rothbart et al., 2013; Burroughs et al., 2012; Wauer et al., 2015) [2], [3], [4], [5]. The UBL domain can participate in several unique protein-protein interactions (PPI) since protein adducts can be attached to and removed from amino groups of lysine side chains and the N-terminus of proteins. Given the biological significance of UBL domains, many have been characterized with high-resolution techniques, and for UBQ and SUMO, many protein complexes have been characterized. We identified all the UBL domains in the PDB and created a relational database called UbSRD (Ubiquitin Structural Relational Database) by using structural analysis tools in the Rosetta (Leaver et al., 2013; O\u27Meara et al., 2015; Leaver-fay et al., 2011) [1], [6], [7], [8]. Querying UbSRD permitted us to report many quantitative properties of UBQ and SUMO recognition at different types interfaces (noncovalent: NC, conjugated: CJ, and deubiquitanse: DB). In this data article, we report the average number of non-UBL neighbors, secondary structure of interacting motifs, and the type of inter-molecular hydrogen bonds for each residue of UBQ and SUMO. Additionally, we used PROMALS3D to generate a multiple sequence alignment used to construct a phylogram for the entire set of UBLs (Pei and Grishin, 2014) [9]. The data described here will be generally useful to scientists studying the molecular basis for recognition of UBQ or SUMO

UbSRD: The Ubiquitin Structural Relational Database

The structurally defined ubiquitin-like homology fold (UBL) can engage in several unique protein–protein interactions and many of these complexes have been characterized with high-resolution techniques. Using Rosetta's structural classification tools, we have created the Ubiquitin Structural Relational Database (UbSRD), an SQL database of features for all 509 UBL-containing structures in the PDB, allowing users to browse these structures by protein–protein interaction and providing a platform for quantitative analysis of structural features. We used UbSRD to define the recognition features of ubiquitin (UBQ) and SUMO observed in the PDB and the orientation of the UBQ tail while interacting with certain types of proteins. While some of the interaction surfaces on UBQ and SUMO overlap, each molecule has distinct features that aid in molecular discrimination. Additionally, we find that the UBQ tail is malleable and can adopt a variety of conformations upon binding. UbSRD is accessible as an online resource at rosettadesign.med.unc.edu/ubsrd

Health related utility measurement in rheumatology: an introduction

Utility measures of health-related quality of life are preference values that patients attach to their overall health status. In clinical trials, utility measures summarize both positive and negative effects of an intervention into one single value between 0 (equal to death) and 1 (equal to perfect health). These measures allow for comparison of patient outcomes of different diseases and allow for comparison between various health care interventions. There are two different approaches to utility measurement. The first is to classify patients into categories based on their responses to a number of questions about their functional status, as for instance the Quality of Well-Being questionnaire. The second approach is to ask patients to assign a single rating to their overall health by means of rating scale, standard gamble, time trade-off, or willingness to pay. The Quality Adjusted Life Year (QALY) as outcome measure includes both effects in terms of quality and quantity of life. Utilities are used as weights to adjust life years for the quality of life in order to calculate QALYs. Both QALYs and utilities are useful in decision-making regarding appropriate procedures for groups of patients

Characterization of the heme pocket structure and ligand binding kinetics of non-symbiotic hemoglobins from the model legume lotus japonicus

Plant hemoglobins (Hbs) are found in nodules of legumes and actinorhizal plants but also in non-symbiotic organs of monocots and dicots. Non-symbiotic Hbs (nsHbs) have been classified into two phylogenetic groups. Class 1 nsHbs show an extremely high O2 affinity and are induced by hypoxia and nitric oxide (NO), whereas class 2 nsHbs have moderate O2 affinity and are induced by cold and cytokinins. The functions of nsHbs are still unclear, but some of them rely on the capacity of hemes to bind diatomic ligands and catalyze the NO dioxygenase (NOD) reaction (oxyferrous Hb + NO ? ferric Hb + nitrate). Moreover, NO may nitrosylate Cys residues of proteins. It is therefore important to determine the ligand binding properties of the hemes and the role of Cys residues. Here, we have addressed these issues with the two class 1 nsHbs (LjGlb1-1 and LjGlb1-2) and the single class 2 nsHb (LjGlb2) of Lotus japonicus, which is a model legume used to facilitate the transfer of genetic and biochemical information into crops. We have employed carbon monoxide (CO) as a model ligand and resonance Raman, laser flash photolysis, and stopped-flow spectroscopies to unveil major differences in the heme environments and ligand binding kinetics of the three proteins, which suggest non-redundant functions. In the deoxyferrous state, LjGlb1-1 is partially hexacoordinate, whereas LjGlb1-2 shows complete hexacoordination (behaving like class 2 nsHbs) and LjGlb2 is mostly pentacoordinate (unlike other class 2 nsHbs). LjGlb1-1 binds CO very strongly by stabilizing it through hydrogen bonding, but LjGlb1-2 and LjGlb2 show lower CO stabilization. The changes in CO stabilization would explain the different affinities of the three proteins for gaseous ligands. These affinities are determined by the dissociation rates and follow the order LjGlb1-1 > LjGlb1-2 > LjGlb2. Mutations LjGlb1-1 C78S and LjGlb1-2 C79S caused important alterations in protein dynamics and stability, indicating a structural role of those Cys residues, whereas mutation LjGlb1-1 C8S had a smaller effect. The three proteins and their mutant derivatives exhibited similarly high rates of NO consumption, which were due to NOD activity of the hemes and not to nitrosylation of Cys residues