216 research outputs found

    A hybrid dynamic logic for event/data-based systems

    Get PDF
    We propose E↓ -logic as a formal foundation for the specification and development of event-based systems with local data states. The logic is intended to cover a broad range of abstraction levels from abstract requirements specifications up to constructive specifications. Our logic uses diamond and box modalities over structured actions adopted from dynamic logic. Atomic actions are pairs Open image in new window where e is an event and /ψ a state transition predicate capturing the allowed reactions to the event. To write concrete specifications of recursive process structures we integrate (control) state variables and binders of hybrid logic. The semantic interpretation relies on event/data transition systems; specification refinement is defined by model class inclusion. For the presentation of constructive specifications we propose operational event/data specifications allowing for familiar, diagrammatic representations by state transition graphs. We show that E↓-logic is powerful enough to characterise the semantics of an operational specification by a single E↓-sentence. Thus the whole development process can rely on E↓-logic and its semantics as a common basis. This includes also a variety of implementation constructors to support, among others, event refinement and parallel composition.publishe

    Complex Processes from Dynamical Architectures with Time-Scale Hierarchy

    Get PDF
    The idea that complex motor, perceptual, and cognitive behaviors are composed of smaller units, which are somehow brought into a meaningful relation, permeates the biological and life sciences. However, no principled framework defining the constituent elementary processes has been developed to this date. Consequently, functional configurations (or architectures) relating elementary processes and external influences are mostly piecemeal formulations suitable to particular instances only. Here, we develop a general dynamical framework for distinct functional architectures characterized by the time-scale separation of their constituents and evaluate their efficiency. Thereto, we build on the (phase) flow of a system, which prescribes the temporal evolution of its state variables. The phase flow topology allows for the unambiguous classification of qualitatively distinct processes, which we consider to represent the functional units or modes within the dynamical architecture. Using the example of a composite movement we illustrate how different architectures can be characterized by their degree of time scale separation between the internal elements of the architecture (i.e. the functional modes) and external interventions. We reveal a tradeoff of the interactions between internal and external influences, which offers a theoretical justification for the efficient composition of complex processes out of non-trivial elementary processes or functional modes

    The origin and development of nonlymphoid tissue CD103+ DCs

    Get PDF
    CD103+ dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c+MHCII+ cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103+ DCs are related to lymphoid organ CD8+ DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103+ DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c+MHCII+ cells in tissues, which is CD103−CD11b+, is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103+ DCs and lymphoid organ CD8+ DCs derive from the same precursor and follow a related differentiation program

    Increased aortic stiffness and blood pressure in non-classic Pompe disease

    Get PDF
    Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20 %), more Pompe patients had a history of hypertension (36 %, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly

    Transfer of learning between unimanual and bimanual rhythmic movement coordination: transfer is a function of the task dynamic.

    Get PDF
    Under certain conditions, learning can transfer from a trained task to an untrained version of that same task. However, it is as yet unclear what those certain conditions are or why learning transfers when it does. Coordinated rhythmic movement is a valuable model system for investigating transfer because we have a model of the underlying task dynamic that includes perceptual coupling between the limbs being coordinated. The model predicts that (1) coordinated rhythmic movements, both bimanual and unimanual, are organised with respect to relative motion information for relative phase in the coupling function, (2) unimanual is less stable than bimanual coordination because the coupling is unidirectional rather than bidirectional, and (3) learning a new coordination is primarily about learning to perceive and use the relevant information which, with equal perceptual improvement due to training, yields equal transfer of learning from bimanual to unimanual coordination and vice versa [but, given prediction (2), the resulting performance is also conditioned by the intrinsic stability of each task]. In the present study, two groups were trained to produce 90° either unimanually or bimanually, respectively, and tested in respect to learning (namely improved performance in the trained 90° coordination task and improved visual discrimination of 90°) and transfer of learning (to the other, untrained 90° coordination task). Both groups improved in the task condition in which they were trained and in their ability to visually discriminate 90°, and this learning transferred to the untrained condition. When scaled by the relative intrinsic stability of each task, transfer levels were found to be equal. The results are discussed in the context of the perception–action approach to learning and performance

    Composition and Hierarchical Organisation of a Spider Silk

    Get PDF
    Albeit silks are fairly well understood on a molecular level, their hierarchical organisation and the full complexity of constituents in the spun fibre remain poorly defined. Here we link morphological defined structural elements in dragline silk of Nephila clavipes to their biochemical composition and physicochemical properties. Five layers of different make-ups could be distinguished. Of these only the two core layers contained the known silk proteins, but all can vitally contribute to the mechanical performance or properties of the silk fibre. Understanding the composite nature of silk and its supra-molecular organisation will open avenues in the production of high performance fibres based on artificially spun silk material

    Stable Genetic Effects on Symptoms of Alcohol Abuse and Dependence from Adolescence into Early Adulthood

    Get PDF
    Relatively little is known about how genetic influences on alcohol abuse and dependence (AAD) change with age. We examined the change in influence of genetic and environmental factors which explain symptoms of AAD from adolescence into early adulthood. Symptoms of AAD were assessed using the four AAD screening questions of the CAGE inventory. Data were obtained up to six times by self-report questionnaires for 8,398 twins from the Netherlands Twin Register aged between 15 and 32 years. Longitudinal genetic simplex modeling was performed with Mx. Results showed that shared environmental influences were present for age 15–17 (57%) and age 18–20 (18%). Unique environmental influences gained importance over time, contributing 15% of the variance at age 15–17 and 48% at age 30–32. At younger ages, unique environmental influences were largely age-specific, while at later ages, age-specific influences became less important. Genetic influences on AAD symptoms over age could be accounted for by one factor, with the relative influence of this factor differing across ages. Genetic influences increased from 28% at age 15–17 to 58% at age 21–23 and remained high in magnitude thereafter. These results are in line with a developmentally stable hypothesis that predicts that a single set of genetic risk factors acts on symptoms of AAD from adolescence into young adulthood

    The role of the complement system in traumatic brain injury: a review

    Get PDF
    Traumatic brain injury (TBI) is an important cause of disability and mortality in the western world. While the initial injury sustained results in damage, it is the subsequent secondary cascade that is thought to be the significant determinant of subsequent outcomes. The changes associated with the secondary injury do not become irreversible until some time after the start of the cascade. This may present a window of opportunity for therapeutic interventions aiming to improve outcomes subsequent to TBI. A prominent contributor to the secondary injury is a multifaceted inflammatory reaction. The complement system plays a notable role in this inflammatory reaction; however, it has often been overlooked in the context of TBI secondary injury. The complement system has homeostatic functions in the uninjured central nervous system (CNS), playing a part in neurodevelopment as well as having protective functions in the fully developed CNS, including protection from infection and inflammation. In the context of CNS injury, it can have a number of deleterious effects, evidence for which primarily comes not only from animal models but also, to a lesser extent, from human post-mortem studies. In stark contrast to this, complement may also promote neurogenesis and plasticity subsequent to CNS injury. This review aims to explore the role of the complement system in TBI secondary injury, by examining evidence from both clinical and animal studies. We examine whether specific complement activation pathways play more prominent roles in TBI than others. We also explore the potential role of complement in post-TBI neuroprotection and CNS repair/regeneration. Finally, we highlight the therapeutic potential of targeting the complement system in the context of TBI and point out certain areas on which future research is needed
    corecore