Using global analysis, partial specifications, and an extensible assertion language for program validation and debugging

We discuss a framework for the application of abstract interpretation as an aid during program development, rather than in the more traditional application of program optimization. Program validation and detection of errors is first performed statically by comparing (partial) specifications written in terms of assertions against information obtained from (global) static analysis of the program. The results of this process are expressed in the user assertion language. Assertions (or parts of assertions) which cannot be checked statically are translated into run-time tests. The framework allows the use of assertions to be optional. It also allows using very general properties in assertions, beyond the predefined set understandable by the static analyzer and including properties defined by user programs. We also report briefly on an implementation of the framework. The resulting tool generates and checks assertions for Prolog, CLP(R), and CHIP/CLP(fd) programs, and integrates compile-time and run-time checking in a uniform way. The tool allows using properties such as types, modes, non-failure, determinacy, and computational cost, and can treat modules separately, performing incremental analysis.

Using global analysis, partial specifications, and an extensible assertion language for program validation and debugging

We present a framework for the application of abstract interpretation as an aid during program development, rather than in the more traditional application of program optimization. Program validation and detection of errors is first performed statically by comparing (partial) specifications written in terms of assertions against information obtained from static analysis of the program. The results of this process are expressed in the user assertion language. Assertions (or parts of assertions) which cannot be verified statically are translated into run-time tests. The framework allows the use of assertions to be optional. It also allows using very general properties in assertions, beyond the predefined set understandable by the static analyzer and including properties defined by means of user programs. We also report briefly on an implementation of the framework. The resulting tool generates and checks assertions for Prolog, CLP(R), and CHIP/CLP(fd) programs, and integrates compile-time and run-time checking in a uniform way. The tool allows using properties such as types, modes, non-failure, determinacy, and computational cost, and can treat modules separately, performing incremental analysis. In practice, this modularity allows detecting statically bugs in user programs even if they do not contain any assertions.

solaR: Solar Radiation and Photovoltaic Systems with R

The solaR package allows for reproducible research both for photovoltaics (PV) systems performance and solar radiation. It includes a set of classes, methods and functions to calculate the sun geometry and the solar radiation incident on a photovoltaic generator and to simulate the performance of several applications of the photovoltaic energy. This package performs the whole calculation procedure from both daily and intradaily global horizontal irradiation to the final productivity of grid-connected PV systems and water pumping PV systems. It is designed using a set of S4 classes whose core is a group of slots with multivariate time series. The classes share a variety of methods to access the information and several visualization methods. In addition, the package provides a tool for the visual statistical analysis of the performance of a large PV plant composed of several systems. Although solaR is primarily designed for time series associated to a location defined by its latitude/longitude values and the temperature and irradiation conditions, it can be easily combined with spatial packages for space-time analysis.

Decoupling of soil nutrient cycles as a function of aridity in global drylands

The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems. It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes. Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability. The increase in aridity predicted for the twenty-first century in many drylands worldwide may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients. Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition. Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequences

Assessment of diastolic chamber properties of the right ventricle by global fitting of pressure-volume data and conformational analysis of 3D + T echocardiographic sequences

El nuevo escenario global y un modelo de negocio para la industria naval militar del 2025

Los retos y oportunidades a los que se enfrentan las organizaciones y administraciones de las primeras décadas del siglo XXI se caracterizan por una serie de fuerzas perturbadoras como la globalización, el avance de las tecnologías emergentes y el desequilibrio económico, que están actuando como impulsores de la transformación del mercado. La acción conjunta de estos factores está obligando a todas las empresas industriales a tener que trabajar con mayores y más exigentes niveles de productividad planteándose continuamente como mejorar y lograr satisfacer los requerimientos de los clientes. De esta situación surge la necesidad de volver a plantearse de nuevo ¿quién es el cliente?, ¿qué valora el cliente? y ¿cómo se pueden generan beneficios sostenibles? La aplicación de esta reflexión a la industria naval militar marca los objetivos a los que esta tesis doctoral busca dar respuesta. El primer objetivo, de carácter general, consiste en la definición de un modelo de negocio sostenible para la industria naval militar del 2025 que se adapte a los requisitos del cliente y al nuevo escenario político, económico, social, tecnológico y ambiental que rodea esta industria. El segundo objetivo, consecuencia del modelo general, trata de desarrollar una metodología para ejecutar programas de apoyo al ciclo de vida del “buque militar”. La investigación se estructura en cuatro partes: en la primera se justifica, por un lado, la necesidad del cambio de modelo y por otro se identifican los factores estructurantes para la definición del modelo. La segunda parte revisa la literatura existente sobre uno de los aspectos básicos para el nuevo modelo, el concepto Producto-Servicio. La tercera parte se centra totalmente en la industria naval militar estudiando los aspectos concretos del sector y, en base al trabajo de campo realizado, se identifican los puntos que más valoran las Marinas de Guerra y como estas gestionan al buque militar durante todo su ciclo de vida. Por último se presentan los principios del modelo propuesto y se desarrollan los pilares básicos para la ejecución de proyectos de Apoyo al Ciclo de Vida (ACV). Como resultado de la investigación, el modelo propuesto para la industria naval militar se fundamenta en once principios: 1. El buque militar (producto de alto valor añadido) debe ser diseñado y construido en un astillero del país que desarrolla el programa de defensa. 2. El diseño tiene que estar orientado al valor para el cliente, es decir, se tiene que diseñar el buque militar para que cumpla su misión, eficaz y eficientemente, durante toda su vida operativa, asegurando la seguridad del buque y de las personas y protegiendo el medio ambiente de acuerdo con las regulaciones vigentes. 3. La empresa debe suministrar soluciones integrales de apoyo al ciclo de vida al producto. 4. Desarrollar y mantener las capacidades de integración de sistemas complejos para todo el ciclo de vida del buque militar. 5. Incorporar las tecnologías digitales al producto, a los procesos, a las personas y al propio modelo de negocio. 6. Desarrollar planes de actuación con el cliente domestico a largo plazo. Estos planes tienen que estar basados en tres premisas: (i) deben incluir el ciclo de vida completo, desde la fase de investigación y desarrollo hasta la retirada del buque del servicio; (ii) la demanda debe ser sofisticada, es decir las exigencias del cliente, tanto desde la óptica de producto como de eficiencia, “tiran” del contratista y (iii) permitir el mantenimiento del nivel tecnológico y de las capacidades industriales de la compañía a futuro y posicionarla para que pueda competir en el mercado de exportación. 7. Impulsar el sector militar de exportación mediante una mayor actividad comercial a nivel internacional. 8. Fomentar la multilocalización ya que representa una oportunidad de crecimiento y favorece la exportación posibilitando el suministro de soluciones integrales en el país destino. 9. Reforzar la diplomacia institucional como palanca para la exportación. 10. Potenciar el liderazgo tecnológico tanto en producto como en procesos con políticas activas de I + D+ i. 11. Reforzar la capacidad de financiación con soluciones innovadoras. El segundo objetivo de esta tesis se centra en el desarrollo de soluciones integrales de Apoyo al Ciclo de Vida (ACV). La metodología planteada trata de minimizar la brecha entre capacidades y necesidades a lo largo de la vida operativa del barco. Es decir, el objetivo principal de los programas de ACV es que la unidad conserve durante toda su vida operativa, en términos relativos a las tecnologías existentes, las capacidades equivalentes a las que tendrá cuando entre en servicio. Los ejes de actuación para conseguir que un programa de Apoyo al Ciclo de Vida cumpla su objetivo son: el diseño orientado al valor, la ingeniería de Apoyo al Ciclo de Vida, los proyectos de refresco de tecnología, el mantenimiento Inteligente y los contratos basados en prestaciones. ABSTRACT On the first decades of the 21st century, organizations and administrations face challenges and come across opportunities threatened by a number of disruptive forces such as globalization, the ever-changing emerging technologies and the economic imbalances acting as drivers of the market transformation. This combination of factors is forcing all industrial companies to have more and higher demanding productivity levels, while bearing always in mind how to improve and meet the customer’s requirements. In this situation, we need to question ourselves again: Who is the customer? What does the customer value? And how can we deliver sustainable economic benefits? Considering this matter in a military naval industry framework sets the goals that this thesis intends to achieve. The first general goal is the definition of a new sustainable business model for the 2025 naval industry, adapted to the customer requirements and the new political, economic, social, technological and environmental scenario. And the second goal that arises as a consequence of the general model develops a methodology to implement “warship” through life support programs. The research is divided in four parts: the first one justifies, on the one hand, the need to change the existing model and, on the other, identifies the model structural factors. On the second part, current literature regarding one of the key issues on the new model (the Product-Service concept) is reviewed. Based on field research, the third part focuses entirely on military shipbuilding, analyzing specific key aspects of this field and identifying which of them are valued the most by Navies and how they manage through life cycles of warships. Finally, the foundation of the proposed model is presented and also the basic grounds for implementing a Through Life Support (TLS) program are developed. As a result of this research, the proposed model for the naval industry is based on eleven (11) key principles: 1. The warship (a high added value product) must be designed and built in a shipyard at the country developing the defense program. 2. Design must be customer value oriented, i.e.warship must be designed to effectively fulfill its mission throughout its operational life, ensuring safety at the ship and for the people and protecting the environment in accordance with current regulations. 3. The industry has to provide integrated Through Life Support solutions. 4. Develop and maintain integrated complex systems capabilities for the entire warship life cycle. 5. Introduce the product, processes, people and business model itself to digital technologies. 6. Develop long-term action plans with the domestic customer. These plans must be based on three premises: (i) the complete life cycle must be included, starting from the research and development stage throughout the ship’s disposal; (ii) customer demand has to be sophisticated, i.e. customer requirements, both from the efficiency and product perspective, "attract" the contractor and (iii) technological level and manufacturing capabilities of the company in the future must be maintained and a competitive position on the export market has to be achieved. 7. Promote the military exporting sector through increased international business. 8. Develop contractor multi-location as it entails an opportunity for growth and promote export opportunities providing integrated solutions in the customer's country. 9. Strengthen institutional diplomacy as a lever for export. 10. Promote technological leadership in both product and processes with active R & D & I policies (Research & Development & Innovation) 11. Strengthen financing capacity through innovative solutions. The second goal of this thesis is focused on developing integrated Through Life Support (TLS) solutions. The proposed methodology tries to minimize the gap between needs and capabilities through the ship operational life. It means, the main TLS program objective is to maintain the ship’s performance and capabilities during operational life, in relative terms to current technologies, equivalent to those the ship had when it entered service. The main actions to fulfill the TLS program objectives are: value-oriented design, TLS engineering, technology updating projects, intelligent maintenance and performance based contracts.

Aurintricarboxylic acid prevents GLUR2 mRNA down-regulation and delayed neurodegeneration in hippocampal CA1 neurons of gerbil after global ischemia

Aurintricarboxylic acid (ATA), an inhibitor of endonuclease activity and other protein–nucleic acid interactions, blocks apoptosis in several cell types and prevents delayed death of hippocampal pyramidal CA1 neurons induced by transient global ischemia. Global ischemia in rats and gerbils induces down-regulation of GluR2 mRNA and increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced Ca2+ influx in CA1 before neurodegeneration. This result and neuroprotection by antagonists of AMPA receptors suggests that formation of AMPA receptors lacking GluR2, and therefore Ca2+ permeable, leads to excessive Ca2+ influx in response to endogenous glutamate; the resulting delayed neuronal death in CA1 exhibits many characteristics of apoptosis. In this study, we examined the effects of ATA on expression of mRNAs encoding glutamate receptor subunits in gerbil hippocampus after global ischemia. Administration of ATA by injection into the right cerebral ventricle 1 h before (but not 6 h after) bilateral carotid occlusion prevented the ischemia-induced decrease in GluR2 mRNA expression and the delayed neurodegeneration. These findings suggest that ATA is neuroprotective in ischemia by blocking the transcriptional changes leading to down-regulation of GluR2, rather than by simply blocking endonucleases, which presumably act later after Ca2+ influx initiates apoptosis. Maintaining formation of Ca2+ impermeable, GluR2 containing AMPA receptors could prevent delayed death of CA1 neurons after transient global ischemia, and block of GluR2 down-regulation may provide a further strategy for neuroprotection.

Multi-component assessment of chronic obstructive pulmonary disease : an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets

Funding The International Primary Care Respiratory Group (IPCRG) provided funding for this research project as an UNLOCK group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. The latter funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Database access for the OPCRD was provided by the Respiratory Effectiveness Group (REG) and Research in Real Life; the OPCRD statistical analysis was funded by REG. The Bocholtz Study was funded by PICASSO for COPD, an initiative of Boehringer Ingelheim, Pfizer and the Caphri Research Institute, Maastricht University, The Netherlands.

Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans

We thank Karim Gharbi and Urmi Trivedi for their assistance with RNA sequencing, carried out in the GenePool genomics facility (University of Edinburgh). We also thank Susan Fairley and Eduardo De Paiva Alves (Centre for Genome Enabled Biology and Medicine, University of Aberdeen) for help with the initial bioinformatics analysis. We thank Aaron Mitchell for kindly providing the ALS3 mutant, Julian Naglik for the gift of TR146 cells, and Jon Richardson for technical assistance. We thank the Genomics and Bioinformatics core of the Faculty of Health Sciences for Next Generation Sequencing and Bioinformatics support, the Information and Communication Technology Office at the University of Macau for providing access to a High Performance Computer and Jacky Chan and William Pang for their expert support on the High Performance Computer. Finally, we thank Amanda Veri for generating CaLC2928. M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), R.A.F. by a Wellcome Trust-Massachusetts Institute of Technology (MIT) Postdoctoral Fellowship, L.E.C. by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Canadian Institutes of Health Research Grants MOP-119520 and MOP-86452, A.J. P.B. was supported by the UK Biotechnology and Biological Sciences Research Council (BB/F00513X/1) and by the European Research Council (ERC-2009-AdG-249793-STRIFE), KHW is supported by the Science and Technology Development Fund of Macau S.A.R (FDCT) (085/2014/A2) and the Research and Development Administrative Office of the University of Macau (SRG2014-00003-FHS) and R.T.W. by the Burroughs Wellcome fund and NIH R15AO094406. Data availability RNA-sequencing data sets are available at ArrayExpress (www.ebi.ac.uk) under accession code E-MTAB-4075. ChIP-seq data sets are available at the NCBI SRA database (http://www.ncbi.nlm.nih.gov) under accession code SRP071687. The authors declare that all other data supporting the findings of this study are available within the article and its supplementary information files, or from the corresponding author upon request.

The Contribution of Agriculture, Forestry and other Land Use activities to Global Warming, 1990-2012

Date of Acceptance: 16/12/2014 Acknowledgements: This work was carried out with generous funding by the Governments of Germany (GCP/GLO/286/GER) and Norway (GCP/GLO/325/NOR) to the ‘Monitoring and Assessment of GHG Emissions and Mitigation Potential from Agriculture’ Project of the FAO Climate, Energy and Tenure Division. P. Smith is a Royal Society Wolfson Merit Award holder, and his input contributes to the University of Aberdeen Environment and Food Security Theme and to Scotland's ClimateXChange. J. House was funded by a Leverhulme Research Fellowship. The FAO Statistics Division maintains the FAOSTAT Emissions database with regular program funds allocated through Strategic Objective 6. © 2015 John Wiley & Sons Ltd.

A global budget for fine root biomass, surface area, and nutrient contents

Global biogeochemical models have improved dramatically in the last decade in their representation of the biosphere. Although leaf area data are an important input to such models and are readily available globally, global root distributions for modeling water and nutrient uptake and carbon cycling have not been available. This analysis provides global distributions for fine root biomass, length, and surface area with depth in the soil, and global estimates of nutrient pools in fine roots. Calculated root surface area is almost always greater than leaf area, more than an order of magnitude so in grasslands. The average C:N:P ratio in living fine roots is 450:11:1, and global fine root carbon is more than 5% of all carbon contained in the atmosphere. Assuming conservatively that fine roots turn over once per year, they represent 33% of global annual net primary productivity.

Can ozone depletion and global warming interact to produce rapid climate change?

The atmosphere displays modes of variability whose structures exhibit a strong longitudinally symmetric (annular) component that extends from the surface to the stratosphere in middle and high latitudes of both hemispheres. In the past 30 years, these modes have exhibited trends that seem larger than their natural background variability, and may be related to human influences on stratospheric ozone and/or atmospheric greenhouse gas concentrations. The pattern of climate trends during the past few decades is marked by rapid cooling and ozone depletion in the polar lower stratosphere of both hemispheres, coupled with an increasing strength of the wintertime westerly polar vortex and a poleward shift of the westerly wind belt at the earth's surface. Annular modes of variability are fundamentally a result of internal dynamical feedbacks within the climate system, and as such can show a large response to rather modest external forcing. The dynamics and thermodynamics of these modes are such that strong synergistic interactions between stratospheric ozone depletion and greenhouse warming are possible. These interactions may be responsible for the pronounced changes in tropospheric and stratospheric climate observed during the past few decades. If these trends continue, they could have important implications for the climate of the 21st century.

Remodeling of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit composition in hippocampal neurons after global ischemia

Transient global ischemia induces selective delayed cell death, primarily of principal neurons in the hippocampal CA1. However, the molecular mechanisms underlying ischemia-induced cell death are as yet unclear. The present study shows that global ischemia triggers a pronounced and cell-specific reduction in GluR2 [the subunit that limits Ca2+ permeability of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors] in vulnerable CA1 neurons, as evidenced by immunofluorescence of brain sections and Western blot analysis of microdissected hippocampal subfields. At 72 h after ischemia (a time before cell death), virtually all CA1 pyramidal neurons exhibited greatly reduced GluR2 immunolabeling throughout their somata and dendritic processes. GluR2 immunolabeling was unchanged in pyramidal cells of the CA3 and granule cells of the dentate gyrus, regions resistant to ischemia-induced damage. Immunolabeling of the AMPA receptor subunit GluR1 was unchanged in CA1, CA3, and dentate gyrus. Western analysis indicated that GluR2 subunit abundance was markedly reduced in CA1 at 60 and 72 h after the ischemic insult; GluR1 abundance was unchanged in all subfields at all times examined. These findings, together with the previous observation of enhanced AMPA-elicited Ca2+ influx in postischemic CA1 neurons, show that functional GluR2-lacking, Ca2+-permeable AMPA receptors are expressed in vulnerable neurons before cell death. Thus, the present study provides an important link in the postulated causal chain between global ischemia and delayed death of CA1 pyramidal neurons.

Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia

The inducible isoform of the enzyme cyclooxygenase-2 (COX2) is an immediate early gene induced by synaptic activity in the brain. COX2 activity is an important mediator of inflammation, but it is not known whether COX2 activity is pathogenic in brain. To study the role of COX2 activity in ischemic injury in brain, expression of COX2 mRNA and protein and the effect of treatment with a COX2 inhibitor on neuronal survival in a rat model of global ischemia were determined. Expression of both COX2 mRNA and protein was increased after ischemia in CA1 hippocampal neurons before their death. There was increased survival of CA1 neurons in rats treated with the COX2-selective inhibitor SC58125 {1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazole} before or after global ischemia compared with vehicle controls. Furthermore, hippocampal prostaglandin E2 concentrations 24 h after global ischemia were decreased in drug-treated animals compared with vehicle-treated controls. These results suggest that COX2 activity contributes to CA1 neuronal death after global ischemia.

Recent improvements in prediction of protein structure by global optimization of a potential energy function

Recent improvements of a hierarchical ab initio or de novo approach for predicting both α and β structures of proteins are described. The united-residue energy function used in this procedure includes multibody interactions from a cumulant expansion of the free energy of polypeptide chains, with their relative weights determined by Z-score optimization. The critical initial stage of the hierarchical procedure involves a search of conformational space by the conformational space annealing (CSA) method, followed by optimization of an all-atom model. The procedure was assessed in a recent blind test of protein structure prediction (CASP4). The resulting lowest-energy structures of the target proteins (ranging in size from 70 to 244 residues) agreed with the experimental structures in many respects. The entire experimental structure of a cyclic α-helical protein of 70 residues was predicted to within 4.3 Å α-carbon (Cα) rms deviation (rmsd) whereas, for other α-helical proteins, fragments of roughly 60 residues were predicted to within 6.0 Å Cα rmsd. Whereas β structures can now be predicted with the new procedure, the success rate for α/β- and β-proteins is lower than that for α-proteins at present. For the β portions of α/β structures, the Cα rmsd's are less than 6.0 Å for contiguous fragments of 30–40 residues; for one target, three fragments (of length 10, 23, and 28 residues, respectively) formed a compact part of the tertiary structure with a Cα rmsd less than 6.0 Å. Overall, these results constitute an important step toward the ab initio prediction of protein structure solely from the amino acid sequence.