Angiotensin-Converting Enzyme 2: The First Decade

The renin-angiotensin system (RAS) is a critical regulator of hypertension, primarily through the actions of the vasoactive peptide Ang II, which is generated by the action of angiotensin-converting enzyme (ACE) mediating an increase in blood pressure. The discovery of ACE2, which primarily metabolises Ang II into the vasodilatory Ang-(1-7), has added a new dimension to the traditional RAS. As a result there has been huge interest in ACE2 over the past decade as a potential therapeutic for lowering blood pressure, especially elevation resulting from excess Ang II. Studies focusing on ACE2 have helped to reveal other actions of Ang-(1-7), outside vasodilation, such as antifibrotic and antiproliferative effects. Moreover, investigations focusing on ACE2 have revealed a variety of roles not just catalytic but also as a viral receptor and amino acid transporter. This paper focuses on what is known about ACE2 and its biological roles, paying particular attention to the regulation of ACE2 expression. In light of the entrance of human recombinant ACE2 into clinical trials, we discuss the potential use of ACE2 as a therapeutic and highlight some pertinent questions that still remain unanswered about ACE2

Towards a Formal Verification Methodology for Collective Robotic Systems

We introduce a UML-based notation for graphically modeling systems’ security aspects in a simple and intuitive way and a model-driven process that transforms graphical specifications of access control policies in XACML. These XACML policies are then translated in FACPL, a policy language with a formal semantics, and the resulting policies are evaluated by means of a Java-based software tool

Evidence for a lineage of virulent bacteriophages that target Campylobacter.

BACKGROUND: Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. RESULTS: Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. CONCLUSIONS: Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other Campylobacter bacteriophages, forming a highly conserved lineage of bacteriophages that predate upon campylobacters and indicating that highly adapted bacteriophage genomes can be stable over prolonged periods of time

A Logical Verification Methodology for Service-Oriented Computing

We introduce a logical verification methodology for checking behavioural properties of service-oriented computing systems. Service properties are described by means of SocL, a branching-time temporal logic that we have specifically designed to express in an effective way distinctive aspects of services, such as, e.g., acceptance of a request, provision of a response, and correlation among service requests and responses. Our approach allows service properties to be expressed in such a way that they can be independent of service domains and specifications. We show an instantiation of our general methodology that uses the formal language COWS to conveniently specify services and the expressly developed software tool CMC to assist the user in the task of verifying SocL formulae over service specifications. We demonstrate feasibility and effectiveness of our methodology by means of the specification and the analysis of a case study in the automotive domain

Airborne sampling of aerosol particles: Comparison between surface sampling at Christmas Island and P-3 sampling during PEM-Tropics B

Bulk aerosol sampling of soluble ionic compounds from the NASA Wallops Island P-3 aircraft and a tower on Christmas Island during PEM-Tropics B provides an opportunity to assess the magnitude of particle losses in the University of New Hampshire airborne bulk aerosol sampling system. We find that most aerosol-associated ions decrease strongly with height above the sea surface, making direct comparisons between mixing ratios at 30 m on the tower and the lowest flight level of the P-3 (150 m) open to interpretation. Theoretical considerations suggest that vertical gradients of sea-salt aerosol particles should show exponential decreases with height. Observed gradients of Na+ and Mg2+, combining the tower observations with P-3 samples collected below 1 km, are well described by exponential decreases (r values of 0.88 and 0.87, respectively), though the curve fit underestimates average mixing ratios at the surface by 25%. Cascade impactor samples collected on the tower show that \u3e99% of the Na+ and Mg2+mass is on supermicron particles, 65% is in the 1–6 micron range, and just 20% resides on particles with diameters larger than 9 microns. These results indicate that our airborne aerosol sampling probes must be passing particles up to at least 6 microns with high efficiency. We also observed that nss SO42− and NH4+, which are dominantly on accumulation mode particles, tended to decrease between 150 and 1000 m, but they were often considerably higher at the lowest P-3 sampling altitudes than at the tower. This finding is presently not well understood

Inheritance of Temporal Logic Properties

Abstract. Inheritance is one of the key features for the success of object-oriented languages. Inheritance (or specialisation) supports incremental design and re-use of already written specifications or programs. In a for-mal approach to system design the interest does not only lie in re-use of class definitions but also in re-use of correctness proofs. If a provably correct class is specialised we like to know those correctness properties which are preserved in the subclass. This can avoid re-verification of already proven properties and may thus substantially reduce the verifi-cation effort. In this paper we study the question of inheritance of correctness prop-erties in the context of state-based formalisms, using a temporal logic (CTL) to formalise requirements on classes. Given a superclass and its specialised subclass we develop a technique for computing the set of for-mulas which are preserved in the subclass. For specialisation we allow addition of attributes, modification of existing as well as extension with new methods.

Analytical Pluralism in Qualitative Research: A Meta-Study

Recent interest in analytical pluralism – the application of more than one qualitative analytical method to a single data set – has demonstrated its potential to produce multiple, complex and varied understandings of phenomena. However tensions remain regarding the commensurability of findings produced from diverse theoretical frameworks, the practical application of multiple methods of analysis and the capacity of pluralism to contribute to knowledge in psychology. This study addresses these issues, through a critical interpretation of existing qualitative studies that utilised analytical pluralism. Using a meta-study design, we examined the use of theory, application of methods and production of findings in studies that had adopted qualitative analytical pluralism. Following comprehensive database searches, 10 articles were included in the analysis. Epistemological and ontological considerations, the influence of decisions made in the practical application of pluralism and approaches to interpreting findings produced from multiple analyses are discussed, and implications for future research are considered

Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain

AbstractAngiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin–angiotensin system (RAS) and a receptor for the causative agent of severe-acute respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF-α converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors

Patients Undergoing Ileoanal Pouch Surgery Experience a Constellation of Symptoms and Consequences Representing a Unique Syndrome: A Report from the Patient-Reported Outcomes After Pouch Surgery (PROPS) Delphi Consensus Study

Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research.The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function.This was a Delphi consensus study.Three rounds of surveys were used to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement.Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients, including patients, colorectal surgeons, and gastroenterologists or other clinicians.A consensus statement was the main outcome.patients, 62 colorectal surgeons, and 48 gastroenterologists or nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement.The study was limited by online recruitment bias.This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function. See Video Abstract at http://links.lww.com/DCR/B571.Un Informe de los Resultados Reportados por los Pacientes Posterior a la Cirugía de Reservorio (PROPS) Estudio de Consenso DelphiANTECEDENTES:Los resultados funcionales después de la creación del reservorio ileoanal han sido estudiados; sin embargo, existe una gran variabilidad en la forma en que se definen y reportan los resultados relevantes. Más importante aún, la perspectiva de los pacientes no se ha representado a la hora de decidir qué resultados deberían ser el foco de investigación.OBJETIVO:El objetivo principal era crear en el paciente una definición centrada de los síntomas principales que debería incluirse en los estudios futuros de la función del reservorio.DISEÑO:Estudio de consenso Delphi.ENTORNO CLINICO:Se emplearon tres rondas de encuestas para seleccionar elementos de alta prioridad. La votación de la encuesta fue seguida por una serie de reuniones de consulta de pacientes en línea que se utilizan para aclarar las tendencias de votación. Se realizo una reunión de consenso final en línea con representación de los tres paneles de expertos para finalizar una declaración de consenso.PACIENTES:Se eligieron partes interesadas expertas para correlacionar con el escenario clínico del equipo multidisciplinario que atiende a los pacientes con reservorio: pacientes, cirujanos colorrectales, gastroenterólogos / otros médicos.PRINCIPALES MEDIDAS DE VALORACION:Declaración de consenso.RESULTADOS:Ciento noventa y cinco pacientes, 62 cirujanos colorrectales y 48 gastroenterólogos / enfermeras especialistas completaron las tres rondas Delphi. 53 pacientes participaron en grupos focales en línea. 161 interesados participaron en la reunión de consenso final. Al concluir la reunión de consenso, siete síntomas intestinales y siete consecuencias de someterse a una cirugía de reservorio ileoanal se incluyeron en la declaración de consenso final.LIMITACIONES:Sesgo de reclutamiento en línea.CONCLUSIONES:Este estudio es el primero en identificar resultados funcionales claves después de la cirugía de reservorio con información directa de un gran panel de pacientes con reservorio ileoanal. La inclusión de pacientes en todas las etapas del proceso de consenso permitió un verdadero enfoque centrado en el paciente para definir los dominios principales en los que debería centrarse los estudios futuros de la función del reservorio. Consulte Video Resumen en http://links.lww.com/DCR/B571