Representation of probabilistic scientific knowledge

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Soldatova et al; licensee BioMed Central Ltd.The theory of probability is widely used in biomedical research for data analysis and modelling. In previous work the probabilities of the research hypotheses have been recorded as experimental metadata. The ontology HELO is designed to support probabilistic reasoning, and provides semantic descriptors for reporting on research that involves operations with probabilities. HELO explicitly links research statements such as hypotheses, models, laws, conclusions, etc. to the associated probabilities of these statements being true. HELO enables the explicit semantic representation and accurate recording of probabilities in hypotheses, as well as the inference methods used to generate and update those hypotheses. We demonstrate the utility of HELO on three worked examples: changes in the probability of the hypothesis that sirtuins regulate human life span; changes in the probability of hypotheses about gene functions in the S. cerevisiae aromatic amino acid pathway; and the use of active learning in drug design (quantitative structure activity relation learning), where a strategy for the selection of compounds with the highest probability of improving on the best known compound was used. HELO is open source and available at https://github.com/larisa-soldatova/HELO.This work was partially supported by grant BB/F008228/1 from the UK Biotechnology & Biological Sciences Research Council, from the European Commission under the FP7 Collaborative Programme, UNICELLSYS, KU Leuven GOA/08/008 and ERC Starting Grant 240186

A Novel Hybrid CNN-AIS Visual Pattern Recognition Engine

Machine learning methods are used today for most recognition problems. Convolutional Neural Networks (CNN) have time and again proved successful for many image processing tasks primarily for their architecture. In this paper we propose to apply CNN to small data sets like for example, personal albums or other similar environs where the size of training dataset is a limitation, within the framework of a proposed hybrid CNN-AIS model. We use Artificial Immune System Principles to enhance small size of training data set. A layer of Clonal Selection is added to the local filtering and max pooling of CNN Architecture. The proposed Architecture is evaluated using the standard MNIST dataset by limiting the data size and also with a small personal data sample belonging to two different classes. Experimental results show that the proposed hybrid CNN-AIS based recognition engine works well when the size of training data is limited in siz

The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth.

Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observed during embryonic and early postnatal ages than in young adulthood. We obtained biochemical evidence indicating that the bulk of dysbindin from brain exists as a stable component of biogenesis of lysosome-related organelles complex-1 (BLOC-1), a multi-subunit protein complex involved in intracellular membrane trafficking and organelle biogenesis. Selective biochemical interaction between brain BLOC-1 and a few members of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) superfamily of proteins that control membrane fusion, including SNAP-25 and syntaxin 13, was demonstrated. Furthermore, primary hippocampal neurons deficient in BLOC-1 displayed neurite outgrowth defects. Taken together, these observations suggest a novel role for the dysbindin-containing complex, BLOC-1, in neurodevelopment, and provide a framework for considering potential effects of allelic variants in DTNBP1--or in other genes encoding BLOC-1 subunits--in the context of the developmental model of schizophrenia pathogenesis

A before and after study of integrated training sessions for children's health and care services

Recent UK policy drivers such as the National Collaboration for Integrated Care and Support and Making Every Contact Count prioritise integrated care, an approach that seeks to provide more coordinated and seamless health and social care. In children's services, despite many partners, there are challenges around integrating care. A deprived borough of London ran short training and networking sessions for services supporting children and young people. This study examined whether intersectoral training would improve participants' knowledge of local services and joint working (including communication, navigation and confidence in collaboration). As part of a service evaluation, the study utilised a pre–post Likert scale survey design for each training session, a 1‐month follow‐up survey, and telephone interviews with a subsample of participants. The educational intervention was three sets of 1.5 hr educational workshops from December 2016 to February 2017. There were 302 attendances from 202 individuals from the health (n = 99), education (n = 145), social care (n = 39) and voluntary (n = 19) sectors. The pre and post surveys found significant increases in self‐assessed knowledge of health/education/social care/voluntary services and in some elements of joint working. However, these increases were not sustained in any domain after 1 month of follow‐up. There was also no difference in self‐assessments amongst those who attended three sessions compared to those who attended one or two. Telephone interviewees highlighted networking as being helpful and suggested that informative tasks and diverse attendance would be beneficial in future. To conclude, this study suggests that although short‐learning sessions may seem to improve immediate knowledge and some elements of joint working in the short term, any gains are not sustained in the long term. The cost effectiveness of such schemes is in doubt but may be improved by a more targeted delivery of content

Profile and management of patients at a memory clinic

Increasing longevity and a growing older population are being accompanied by a higher prevalence of dementia and concomitant demand for care. In this connection, the University of Cape Town/Groote Schuur Hospital (UCT/ GSH) Memory Clinic provides a valuable service to patients, families and health professionals. High levels of behavioural and psychological symptoms of dementia need expert tertiary level assessment and management. Public education on dementia, early referral for assessment by primary care health professionals, and advanced training of health professionals are needed to encourage early recognition and appropriate management. Community-based care services too are needed to support caregivers of cognitively impaired older individuals

Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis.

Peptidylarginine deiminases (PADIs) are strongly associated with the development of autoimmunity, neurodegeneration and cancer but their physiological roles are ill-defined. The nuclear deiminase PADI4 regulates pluripotency in the mammalian pre-implantation embryo but its function in tissue development is unknown. PADI4 is primarily expressed in the bone marrow, as part of a self-renewal-associated gene signature. It has been shown to regulate the proliferation of multipotent haematopoietic progenitors and proposed to impact on the differentiation of haematopoietic stem cells (HSCs), suggesting that it controls haematopoietic development or regeneration. Using conditional in vivo models of steady state and acute Padi4 ablation, we examined the role of PADI4 in the development and function of the haematopoietic system. We found that PADI4 loss does not significantly affect HSC self-renewal or differentiation potential upon injury or serial transplantation, nor does it lead to HSC exhaustion or premature ageing. Thus PADI4 is dispensable for cell-autonomous HSC maintenance, differentiation and haematopoietic regeneration. This work represents the first study of PADI4 in tissue development and indicates that pharmacological PADI4 inhibition may be tolerated without adverse effects

Imaging spontaneous currents in superconducting arrays of pi-junctions

Superconductors separated by a thin tunneling barrier exhibit the Josephson effect that allows charge transport at zero voltage, typically with no phase shift between the superconductors in the lowest energy state. Recently, Josephson junctions with ground state phase shifts of pi proposed by theory three decades ago have been demonstrated. In superconducting loops, pi-junctions cause spontaneous circulation of persistent currents in zero magnetic field, analogous to spin-1/2 systems. Here we image the spontaneous zero-field currents in superconducting networks of temperature-controlled pi-junctions with weakly ferromagnetic barriers using a scanning SQUID microscope. We find an onset of spontaneous supercurrents at the 0-pi transition temperature of the junctions Tpi = 3 K. We image the currents in non-uniformly frustrated arrays consisting of cells with even and odd numbers of pi-junctions. Such arrays are attractive model systems for studying the exotic phases of the 2D XY-model and achieving scalable adiabatic quantum computers.Comment: Pre-referee version. Accepted to Nature Physic

Inelastic J/ΨJ/\Psi Photoproduction off Nuclei: Gluon Enhancement or Double Color Exchange?

The nuclear enhancement observed in inelastic photoproduction of $J/\Psi$ should not be interpreted as evidence for an increased gluon density in nuclei. The nuclear suppression of the production rate due to initial and final state interactions is calculated and a novel two-step color exchange process is proposed, which is able to explain the data.Comment: Latex file, 23 pages including 5 Postscript figure