Edit metric decoding: Return of the side effect machines

Side Effect Machines (SEMs) are an extension of finite state machines which place a counter on each node that is incremented when that node is visited. Previous studies examined a genetic algorithm to discover node connections in SEMs for edit metric decoding for biological applications, namely to handle sequencing errors. Edit metric codes, while useful for decoding such biologically created errors, have a structure which significantly differentiates them from other codes based on Hamming distance. Further, the inclusion of biologically- motivated restrictions on allowed words makes development of decoders a bespoke process based on the exact code used. This study examines the use of evolutionary programming for the creation of such decoders, thus allowing for the number of states to be evolved directly, not witnessed in previous approaches which used genetic algorithms. Both direct and fuzzy decoding are used, obtaining correct decoding rates of up to 95% in some SEMs.Natural Sciences and Engineering Research Council of Canad

Compression of Biological Networks using a Genetic Algorithm with Localized Merge

Network graphs appear in a number of important biological data problems, recording information relating to protein-protein interactions, gene regulation, transcription regulation and much more. These graphs are of such a significant size that they are impossible for a human to understand. Furthermore, the ever-expanding quantity of such information means that there are storage issues. To help address these issues, it is common for applications to compress nodes to form supernodes of similarly connected components. In previous graph compression studies it was noted that such supernodes often contain points from disparate parts of the graph. This study aims to correct this flaw by only allowing merges to occur within a local neighbourhood rather than across the entire graph. This restriction was found to not only produce more meaningful compressions, but also to reduce the overall distortion created by the compression for two out of three biological networks studied

Gravitational waves from scattering of stellar-mass black holes in galactic nuclei

Stellar mass black holes (BHs) are expected to segregate and form a steep density cusp around supermassive black holes (SMBHs) in galactic nuclei. We follow the evolution of a multi-mass system of BHs and stars by numerically integrating the Fokker-Planck energy diffusion equations for a variety of BH mass distributions. We find that the BHs "self-segregate'', and that the rarest, most massive BHs dominate the scattering rate closest to the SMBH (< 0.1 pc). BH--BH binaries form out of gravitational wave emission during BH encounters. We find that the expected rate of BH coalescence events detectable by Advanced LIGO is ~1 - 100/yr, depending on the initial mass function of stars in galactic nuclei and the mass of the most massive BHs. We find that the actual merger rate is likely ~10 times larger than this due to the intrinsic scatter of stellar densities in many different galaxies. The BH binaries that form this way in galactic nuclei have significant eccentricities as they enter the LIGO band (90% with e > 0.9), and are therefore distinguishable from other binaries, which circularise before becoming detectable. We also show that eccentric mergers can be detected to larger distances and greater BH masses than circular mergers, up to ~ 700 solar masses. Future ground-based gravitational wave observatories will be able to constrain both the mass function of BHs and stars in galactic nuclei.Comment: 22 pages, 13 figures. MNRAS accepted, in pres

Scalar field instability in de Sitter space-time

Starting from the equation of motion of the quantum operator of a real scalar field phi in de Sitter space-time, a simple differential equation is derived which describes the evolution of quantum fluctuations of this field. Full de Sitter invariance is assumed and no ad hoc infrared cutoff is introduced. This equation is solved explicitly and in massive case our result agrees with the standard one. In massless case the large time behavior of our solution differs by sign from the expression found in earlier papers. A possible cause of discrepancy may be a spontaneous breaking of de Sitter invariance.Comment: 20 pages, no figures, revtex4. V2: minor changes, references adde

Still getting it on online: Thirty years of queer male spaces brokered through digital technologies

Research across the social sciences testifies to an ongoing relationship between queerness and digital technology. This article tracks how different online spaces for queer men have changed as the internet has developed over the past 30 years. It argues that queer spaces have become increasingly dominated by, and predicated on, internet technology. I review early interpretations of cyberspace as a liberatory space freed from heteronormativity and later more critical assessments of its potential, positioning arguments for and against the internet's status as a protective space. I then evaluate the huge popularity of mobile phone-based dating and hook-up apps such as Grindr and Tinder. These platforms have developed from static desktop offerings including Gaydar and PlanetRomeo, but emphasise a distinctly hybridised socio-technical experience in partner seeking. Finally, I consider the impact of locative media on more traditional queer concepts of cruising and community, concluding that contemporary apps refigure both structures in distinctive ways reflecting larger changes in sexuality and space studies

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed

Integration and continuity of primary care: polyclinics and alternatives - a patient-centred analysis of how organisation constrains care co-ordination

Background An ageing population, the increasing specialisation of clinical services and diverse health-care provider ownership make the co-ordination and continuity of complex care increasingly problematic. The way in which the provision of complex health care is co-ordinated produces – or fails to produce – six forms of continuity of care (cross-sectional, longitudinal, flexible, access, informational and relational). Care co-ordination is accomplished by a combination of activities by patients themselves; provider organisations; care networks co-ordinating the separate provider organisations; and overall health-system governance. This research examines how far organisational integration might promote care co-ordination at the clinical level. Objectives To examine (1) what differences the organisational integration of primary care makes, compared with network governance, to horizontal and vertical co-ordination of care; (2) what difference provider ownership (corporate, partnership, public) makes; (3) how much scope either structure allows for managerial discretion and ‘performance’; (4) differences between networked and hierarchical governance regarding the continuity and integration of primary care; and (5) the implications of the above for managerial practice in primary care. Methods Multiple-methods design combining (1) the assembly of an analytic framework by non-systematic review; (2) a framework analysis of patients’ experiences of the continuities of care; (3) a systematic comparison of organisational case studies made in the same study sites; (4) a cross-country comparison of care co-ordination mechanisms found in our NHS study sites with those in publicly owned and managed Swedish polyclinics; and (5) the analysis and synthesis of data using an ‘inside-out’ analytic strategy. Study sites included professional partnership, corporate and publicly owned and managed primary care providers, and different configurations of organisational integration or separation of community health services, mental health services, social services and acute inpatient care. Results Starting from data about patients’ experiences of the co-ordination or under-co-ordination of care, we identified five care co-ordination mechanisms present in both the integrated organisations and the care networks; four main obstacles to care co-ordination within the integrated organisations, of which two were also present in the care networks; seven main obstacles to care co-ordination that were specific to the care networks; and nine care co-ordination mechanisms present in the integrated organisations. Taking everything into consideration, integrated organisations appeared more favourable to producing continuities of care than did care networks. Network structures demonstrated more flexibility in adding services for small care groups temporarily, but the expansion of integrated organisations had advantages when adding new services on a longer term and a larger scale. Ownership differences affected the range of services to which patients had direct access; primary care doctors’ managerial responsibilities (relevant to care co-ordination because of their impact on general practitioner workload); and the scope for doctors to develop special interests. We found little difference between integrated organisations and care networks in terms of managerial discretion and performance. Conclusions On balance, an integrated organisation seems more likely to favour the development of care co-ordination and, therefore, continuities of care than a system of care networks. At least four different variants of ownership and management of organisationally integrated primary care providers are practicable in NHS-like settings. Future research is therefore required, above all to evaluate comparatively the different techniques for coordinating patient discharge across the triple interface between hospitals, general practices and community health services; and to discover what effects increasing the scale and scope of general practice activities will have on continuity of care

On the physical basis of cosmic time

In this manuscript we initiate a systematic examination of the physical basis for the time concept in cosmology. We discuss and defend the idea that the physical basis of the time concept is necessarily related to physical processes which could conceivably take place among the material constituents available in the universe. It is common practice to link the concept of cosmic time with a space-time metric set up to describe the universe at large scales, and then define a cosmic time $t$ as what is measured by a comoving standard clock. We want to examine, however, the physical basis for setting up a comoving reference frame and, in particular, what could be meant by a standard clock. For this purpose we introduce the concept of a `core' of a clock (which, for a standard clock in cosmology, is a scale-setting physical process) and we ask if such a core can--in principle--be found in the available physics contemplated in the various `stages' of the early universe. We find that a first problem arises above the quark-gluon phase transition (which roughly occurs when the cosmological model is extrapolated back to $\sim 10^{-5}$ seconds) where there might be no bound systems left, and the concept of a physical length scale to a certain extent disappears. A more serious problem appears above the electroweak phase transition believed to occur at $\sim 10^{-11}$ seconds. At this point the property of mass (almost) disappears and it becomes difficult to identify a physical basis for concepts like length scale, energy scale and temperature -- which are all intimately linked to the concept of time in modern cosmology. This situation suggests that the concept of a time scale in `very early' universe cosmology lacks a physical basis or, at least, that the time scale will have to be based on speculative new physics.Comment: 44 pages. Submitted to Studies in History and Philosophy of Modern Physic