Revised submission for MOF 2.0 query / views / transformations RFP.

This submission presents the QVT-Partners proposal for the MOF 2.0 QVT standard. The proposal consists of a number of key ingredients which we briefly discuss in this section. -Specification and implementation: A common scenario in the development of any artifact is to first create a specification of the form and behaviour of the the artifact, and then realise an implementation which satisfies the specification. The specification is characterised by a lack of implementation details, but having a close correspondence to the requirements; conversely an implementation may lack close correspondence to the requirements. This submission maintains this important distinction. Relations provide a specification oriented view of the relationship between models and are specified in a language that can be easily understood. They say what it means to translate between several models but without saying precisely how the translation is achieved. Those details are realised by mappings which characterise the means by which models are translated. It should be noted though, that while the mappings language is rich enough to provide an implementation of relations it also manages to maintain a requirements oriented focus. This may give rise to a scenario where developers prefer to omit relations and directly define mappings. -Scalability and reuse: Decomposition is a key approach to managing complexity. This submission provides a number of composition mechanisms whereby relations and mappings can be composed to form more complex specifications. These mechanisms also aid reuse since mappings and relations can be treated as reusable components which are composed for specific contexts. -Usability: Diagrammatic notations have been important to the success of many OMG standards. This proposal presents a diagrammatic notation which is an extension of collaboration object diagrams and is therefore familiar to many end users. A criticism often levelled at diagrammatic notations is their scalability. This submission also presents a textual syntax, constructs of the diagrammatic notations are closely aligned with its textual counterpart. Considering the domains of relations and mappings at the generic type level is often too limiting. Instead it often is specific-types of things that are of interest. This submission uses patterns to describe the domains of both relations and mappings. Patterns are a means of succinctly describing specific-types of model elements and enable domains of interest to be rapidly stated with ease. -Semantic soundness: By definition a standard should give rise to consistency across differing implementations. It is important that an end user can get the same results on two different implementations. For this reason, this submission goes to some effort to ensure that all the constructs have a well-defined semantic basis. This is achieved by treating the submission in two parts. The infrastructure part has a small number of constructs which can be easily and consistently understood from informal descriptions (although a mathematical semantics is given in Appendix B for the sake of completeness and rigour). The superstructure part uses the infrastructure as its semantic basis and defines the syntax that the end user deals with. The relationship between the superstructure and the infrastructure is expressed as a translation

Higher-order nonlinear modes and bifurcation phenomena due to degenerate parametric four-wave mixing

We demonstrate that weak parametric interaction of a fundamental beam with its third harmonic field in Kerr media gives rise to a rich variety of families of non-fundamental (multi-humped) solitary waves. Making a comprehensive comparison between bifurcation phenomena for these families in bulk media and planar waveguides, we discover two novel types of soliton bifurcations and other interesting findings. The later includes (i) multi-humped solitary waves without even or odd symmetry and (ii) multi-humped solitary waves with large separation between their humps which, however, may not be viewed as bound states of several distinct one-humped solitons.Comment: 9 pages, 17 figures, submitted to Phys. Rev.

Gravitational waves from Sco X-1: A comparison of search methods and prospects for detection with advanced detectors

The low-mass X-ray binary Scorpius X-1 (Sco X-1) is potentially the most luminous source of continuous gravitational-wave radiation for interferometers such as LIGO and Virgo. For low-mass X-ray binaries this radiation would be sustained by active accretion of matter from its binary companion. With the Advanced Detector Era fast approaching, work is underway to develop an array of robust tools for maximizing the science and detection potential of Sco X-1. We describe the plans and progress of a project designed to compare the numerous independent search algorithms currently available. We employ a mock-data challenge in which the search pipelines are tested for their relative proficiencies in parameter estimation, computational efficiency, robust- ness, and most importantly, search sensitivity. The mock-data challenge data contains an ensemble of 50 Scorpius X-1 (Sco X-1) type signals, simulated within a frequency band of 50-1500 Hz. Simulated detector noise was generated assuming the expected best strain sensitivity of Advanced LIGO and Advanced VIRGO ($4 \times 10^{-24}$ Hz$^{-1/2}$). A distribution of signal amplitudes was then chosen so as to allow a useful comparison of search methodologies. A factor of 2 in strain separates the quietest detected signal, at $6.8 \times 10^{-26}$ strain, from the torque-balance limit at a spin frequency of 300 Hz, although this limit could range from $1.2 \times 10^{-25}$ (25 Hz) to $2.2 \times 10^{-26}$ (750 Hz) depending on the unknown frequency of Sco X-1. With future improvements to the search algorithms and using advanced detector data, our expectations for probing below the theoretical torque-balance strain limit are optimistic.Comment: 33 pages, 11 figure

Replica theory for learning curves for Gaussian processes on random graphs

Statistical physics approaches can be used to derive accurate predictions for the performance of inference methods learning from potentially noisy data, as quantified by the learning curve defined as the average error versus number of training examples. We analyse a challenging problem in the area of non-parametric inference where an effectively infinite number of parameters has to be learned, specifically Gaussian process regression. When the inputs are vertices on a random graph and the outputs noisy function values, we show that replica techniques can be used to obtain exact performance predictions in the limit of large graphs. The covariance of the Gaussian process prior is defined by a random walk kernel, the discrete analogue of squared exponential kernels on continuous spaces. Conventionally this kernel is normalised only globally, so that the prior variance can differ between vertices; as a more principled alternative we consider local normalisation, where the prior variance is uniform

TDR-based water content estimation on globigerina limestone through permittivity measurements

Most monuments and historical buildings in the Maltese Islands are made of the local Globigerina Limestone (GL). This type of stone, however, is very delicate and prone to degradation caused by the environmental conditions of the islands. Hence, for the preservation of the Cultural Heritage monuments, it is necessary to promptly assess the health status of these structures and, in particular, their water content (which represents one of the major causes of degradation). Starting from these considerations, in this work, a time domain reflectometry (TDR)-based method for estimating water content of GL is presented. More specifically, the proposed method relies on estimating the water content value of the GL structure from TDR-based dielectric permittivity measurements. To verify the suitability of this system, experimental tests were carried out on a GL sample. The results anticipate the strong potential of the proposed method for practical applications in the Cultural Heritage diagnostics

Atrial flutter and fibrillation in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension in the ASPIRE registry: comparison of rate versus rhythm control approaches

Background The development of atrial flutter and fibrillation (AFL/AF) in patients with pre-capillary pulmonary hypertension has been associated with an increased risk of morbidity and mortality. Rate and rhythm control strategies have not been directly compared. Methods Eighty-four patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with new-onset AFL/AF were identified in the ASPIRE registry. First, baseline characteristics and rates of sinus rhythm (SR) restoration of 3 arrhythmia management strategies (rate control, medical rhythm control and DC cardioversion, DCCV) in an early (2009–13) and later (2014–19) cohort were compared. Longer-term outcomes in patients who achieved SR versus those who did not were then explored. Results Sixty (71%) patients had AFL and 24 (29%) AF. Eighteen (22%) patients underwent rate control, 22 (26%) medical rhythm control and 44 (52%) DCCV. SR was restored in 33% treated by rate control, 59% medical rhythm control and 95% DCCV (p < 0.001). Restoration of SR was associated with greater improvement in functional class (FC) and Incremental Shuttle Walk Distance (p both <0.05). It also independently predicted superior survival (3-year survival 62% vs 23% in those remaining in AFL/AF, p < 0.0001). In addition, FC III/IV independently predicted higher mortality (HR 2.86, p = 0.007). Right atrial area independently predicted AFL/AF recurrence (OR 1.08, p = 0.01). DCCV was generally well tolerated with no immediate major complications. Conclusions Restoration of SR is associated with superior functional improvement and survival in PAH/CTEPH compared with rate control. DCCV is generally safe and is more effective than medical therapy at achieving SR

The Pfam protein families database

Pfam is a comprehensive collection of protein domains and families, represented as multiple sequence alignments and as profile hidden Markov models. The current release of Pfam (22.0) contains 9318 protein families. Pfam is now based not only on the UniProtKB sequence database, but also on NCBI GenPept and on sequences from selected metagenomics projects. Pfam is available on the web from the consortium members using a new, consistent and improved website design in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/), as well as from mirror sites in France (http://pfam.jouy.inra.fr/) and South Korea (http://pfam.ccbb.re.kr/)

Isoflurane Preconditioning at Clinically Relevant Doses Induce Protective Effects of Heme Oxygenase-1 on Hepatic Ischemia Reperfusion in Rats

<p>Abstract</p> <p>Background</p> <p>Activation of heme oxygenase-1 (HO-1) has been proved to reduce damages to the liver in ischemia reperfusion injury. The objective of present study was to determine whether clinic relevant doses of isoflurane treatment could be sufficient to activate HO-1 inducing, which confers protective effect against hepatic ischemia-reperfusion injury.</p> <p>Methods</p> <p>The hepatic artery and portal vein to the left and the median liver lobes of forty male Sprague-Dawley rats were occluded for 60 minutes. Reperfusion was allowed for 4 hours before the animal subjects were sacrificed. Six groups (n = 12) were included in the study. A negative control group received sham operation and positive control group a standard ischemia-reperfusion regimen. The third group was pretreated with isoflurane prior to the ischemia-reperfusion. The fourth group received an HO-1 inhibitor zinc protoporphyrin (Znpp) prior to the isoflurane pretreatment and the ischemia-reperfusion. The fifth group received Znpp alone before ischemia-reperfusion procedure, and the sixth group was administrated with a HO-1 inducer hemin prior to IR. HO-1 in the liver was measured using an enzymatic activity assay, a Western blot analysis, as well as immunohistochemical method. Extent of liver damage was estimated by determination of the serum transaminases, liver lipid peroxidation and hepatic histology. Infiltration of the liver by neutrophils was measured using a myeloperoxidase activity assay. TNFα mRNA in the liver was measured using RT-PCR.</p> <p>Results</p> <p>Isoflurane pretreatment significantly attenuated the hepatic injuries and inflammatory responses caused by the ischemia reperfusion. Selectively inhibiting HO-1 with ZnPP completed blocked the protective effects of isoflurane. Inducing HO-1 with hemin alone produced protective effects similar in magnitude to that of isoflurane.</p> <p>Conclusions</p> <p>Clinic relevant doses of isoflurane attenuate ischemia reperfusion injury in rats by increasing the HO-1 expression and activity.</p

Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

(c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year