PROTOTYPICAL CASES FOR RETRIEVAL, REUSE, AND KNOWLEDGE MAINTENANCE IN BIOMEDICAL CASE-BASED REASONING

Representing biomedical knowledge is an essential task in biomedical informatics intelligent systems. Case-based reasoning (CBR) holds the promise to represent contextual knowledge in a way that was not possible before with traditional knowledge-based methods. One main issue in biomedical CBR is dealing with the rate of generation of new knowledge in biomedical fields, which often makes the content of a case base partially obsolete. This article proposes to make use of the concept of prototypical case to ensure that a CBR system would keep update with current research advances in the biomedical field. Prototypical cases have served various purposes in biomedical CBR systems, among which to organize and structure the memory, to guide the retrieval as well as the reuse of cases, and to serve as bootstrapping a CBR system memory when real cases are not available in sufficient quantity and/or quality. This paper emphasizes the different roles prototypical cases can play in CBR systems, and presents knowledge maintenance as a very important novel role for these prototypical cases.     

Principal motion components for one-shot gesture recognition

This paper introduces principal motion components (PMC), a new method for one-shot gesture recognition. In the considered scenario a single training video is available for each gesture to be recognized, which limits the application of traditional techniques (e.g., HMMs). In PMC, a 2D map of motion energy is obtained per each pair of consecutive frames in a video. Motion maps associated to a video are processed to obtain a PCA model, which is used for recognition under a reconstruction-error approach. The main benefits of the proposed approach are its simplicity, easiness of implementation, competitive performance and efficiency. We report experimental results in one-shot gesture recognition using the ChaLearn Gesture Dataset; a benchmark comprising more than 50,000 gestures, recorded as both RGB and depth video with a Kinect?camera. Results obtained with PMC are competitive with alternative methods proposed for the same data set.     

Stabilization of the inverted pendulum around its homoclinic orbit

The inverted pendulum has been used as a benchmark for motivating the study of nonlinear control techniques. We propose a simple controller for balancing the inverted pendulum and raise it to its upper equilibrium position while the cart displacement is brought to zero. The control strategy is based on an energy approach of the cart and pendulum system.     

An MDA approach to knowledge engineering

This paper proposes an MDA approach to knowledge engineering, centered on the CommonKADS knowledge model. The latter corresponds to the CIM level of MDA whereas PRR, which represents production rules and rulesets, corresponds to the PIM level. The paper explores the mapping between CommonKADS knowledge models and production rules and rulesets based on PRR. Mapping CommonKADS knowledge models into PRR is very useful, due to the fact that the CIM level remains relatively unexplored, despite its key role in MDA. This motivates our choice to focus on the CIM and PIM levels. Furthermore, the mapping between PIM and PSM (i.e. the implementation of production rules in specific rule-based systems) constitutes less of an issue. To map CommonKADS knowledge models into PRR production rules and rulesets, we propose and illustrate a set of transformations. To ease these transformations, we start by grouping elements of the CommonKADS knowledge models into so-called “inference groups”. We propose and illustrate an algorithm that defines these inference groups automatically. The definition of transformations between models (CIM to PIM levels) requires a specific metamodel for CommonKADS as well as a dedicated metamodel for PRR. Unlike PRR, there is no published CommonKADS metamodel. This paper proposes a comprehensive CommonKADS knowledge metamodel. We describe and discuss an example, applying the whole approach.     

In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators

ABCB11 is responsible for biliary bile acid secretion at the canalicular membrane of hepatocytes. Variations in the ABCB11 gene cause a spectrum of rare liver diseases. The most severe form is progressive familial intrahepatic cholestasis type 2 (PFIC2). Current medical treatments have limited efficacy. Here, we report the in vitro study of Abcb11 missense variants identified in PFIC2 patients and their functional rescue using cystic fibrosis transmembrane conductance regulator potentiators. Three ABCB11 disease-causing variations identified in PFIC2 patients (i.e., A257V, T463I and G562D) were reproduced in a plasmid encoding an Abcb11-green fluorescent protein. After transfection, the expression and localization of the variants were studied in HepG2 cells. Taurocholate transport activity and the effect of potentiators were studied in Madin–Darby canine kidney (MDCK) clones coexpressing Abcb11 and the sodium taurocholate cotransporting polypeptide (Ntcp/Slc10A1). As predicted using three-dimensional structure analysis, the three variants were expressed at the canalicular membrane but showed a defective function. Ivacaftor, GLP1837, SBC040 and SBC219 potentiators increased the bile acid transport of A257V and T463I and to a lesser extent, of G562D Abcb11 missense variants. In addition, a synergic effect was observed when ivacaftor was combined with SBC040 or SBC219. Such potentiators could represent new pharmacological approaches for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the function of the transporter.     

Aphid BCR4 Structure and Activity Uncover a New Defensin Peptide Superfamily

Aphids (Hemiptera: Aphidoidea) are among the most detrimental insects for agricultural plants, and their management is a great challenge in agronomical research. A new class of proteins, called Bacteriocyte-specific Cysteine-Rich (BCR) peptides, provides an alternative to chemical insecticides for pest control. BCRs were initially identified in the pea aphid Acyrthosiphon pisum. They are small disulfide bond-rich proteins expressed exclusively in aphid bacteriocytes, the insect cells that host intracellular symbiotic bacteria. Here, we show that one of the A. pisum BCRs, BCR4, displays prominent insecticidal activity against the pea aphid, impairing insect survival and nymphal growth, providing evidence for its potential use as a new biopesticide. Our comparative genomics and phylogenetic analyses indicate that BCRs are restricted to the aphid lineage. The 3D structure of BCR4 reveals that this peptide belongs to an as-yet-unknown structural class of peptides and defines a new superfamily of defensins.     

Spatial–Spectral Analysis of Hyperspectral Images Reveals Early Detection of Downy Mildew on Grapevine Leaves

Downy mildew is a highly destructive disease of grapevine. Currently, monitoring for its symptoms is time-consuming and requires specialist staff. Therefore, an automated non-destructive method to detect the pathogen before the visible symptoms appear would be beneficial for early targeted treatments. The aim of this study was to detect the disease early in a controlled environment, and to monitor the disease severity evolution in time and space. We used a hyperspectral image database following the development from 0 to 9 days post inoculation (dpi) of three strains of Plasmopara viticola inoculated on grapevine leaves and developed an automatic detection tool based on a Support Vector Machine (SVM) classifier. The SVM obtained promising validation average accuracy scores of 0.96, a test accuracy score of 0.99, and it did not output false positives on the control leaves and detected downy mildew at 2 dpi, 2 days before the clear onset of visual symptoms at 4 dpi. Moreover, the disease area detected over time was higher than that when visually assessed, providing a better evaluation of disease severity. To our knowledge, this is the first study using hyperspectral imaging to automatically detect and show the spatial distribution of downy mildew on grapevine leaves early over time.     

Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.     

Individual and combined effects of subclinical doses of deoxynivalenol and fumonisins in piglets

Scope: Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species and most commonly co‐occur in animal diets. These mycotoxins were studied for their toxicity in piglets on several parameters including plasma biochemistry, organ histopathology and immune response. Methods and results: Twenty‐four 5‐wk‐old animals were randomly assigned to four different groups, receiving separate diets for 5 wk, a control diet, a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg) or both toxins. At days 4 and 16 of the trial, the animals were subcutaneously immunized with ovalbumin to assess their specific immune response. The different diets did not affect animal performance and had minimal effect on hematological and biochemical blood parameters. By contrast, DON and FB induced histopathological lesions in the liver, the lungs and the kidneys of exposed animals. The liver was significantly more affected when the two mycotoxins were present simultaneously. The contaminated diets also altered the specific immune response upon vaccination as measured by reduced anti‐ovalbumin IgG level in the plasma and reduced lymphocyte proliferation upon antigenic stimulation. Because cytokines play a key role in immunity, the expression levels of IL‐8, IL‐1β, IL‐6 and macrophage inflammatory protein‐1β were measured by RT‐PCR at the end of the experiment. The expression of these four cytokines was significantly decreased in the spleen of piglets exposed to multi‐contaminated diet. Conclusion: Taken together, our data indicate that ingestion of multi‐contaminated diet induces greater histopathological lesions and higher immune suppression than ingestion of mono‐contaminated diets.