Progressive leukoencephalopathy impairs neurobehavioral development in sialin-deficient mice

Slc17a5−/− mice represent an animal model for the infantile form of sialic acid storage disease (SASD). We analyzed genetic and histological time-course expression of myelin and oligodendrocyte (OL) lineage markers in different parts of the CNS, and related this to postnatal neurobehavioral development in these mice. Sialin-deficient mice display a distinct spatiotemporal pattern of sialic acid storage, CNS hypomyelination and leukoencephalopathy. Whereas few genes are differentially expressed in the perinatal stage (p0), microarray analysis revealed increased differential gene expression in later postnatal stages (p10–p18). This included progressive upregulation of neuroinflammatory genes, as well as continuous down-regulation of genes that encode myelin constituents and typical OL lineage markers. Age-related histopathological analysis indicates that initial myelination occurs normally in hindbrain regions, but progression to more frontal areas is affected in Slc17a5−/− mice. This course of progressive leukoencephalopathy and CNS hypomyelination delays neurobehavioral development in sialin-deficient mice. Slc17a5−/− mice successfully achieve early neurobehavioral milestones, but exhibit progressive delay of later-stage sensory and motor milestones. The present findings may contribute to further understanding of the processes of CNS myelination as well as help to develop therapeutic strategies for SASD and other myelination disorders

Verification of XRL:An XML-based workflow language

XRL (eXchangeable Routing Language) is an instance-based workflow language that uses XML for the representation of process definitions and Petri nets for its semantics. Since XRL is instance-based, workflow definitions can be changed on the fly and sent across organizational boundaries. These features are vital for today's dynamic and networked economy. However, the features also enable subtle, but highly disruptive, cross-organizational errors. On-the-fly changes and one-of-a-kind processes are destined to result in errors. Moreover, errors of a cross-organizational nature are difficult to repair. In this paper, we show soundness properties of XRL constructs by using a novel, constructive approach. We also describe a software tool based on XML and Petri-net technologies for verifying XRL workflows.</p

YAWL in the cloud: Supporting process sharing and variability

The cloud is at the centre of attention in various fields, including that of BPM. However, all BPM systems in the cloud seem to be nothing more than an installation in the cloud with a web-interface for a single organisation, while cloud technology offers an excellent platform for cooperation on an intra- and inter-organisational level. In this paper, we show how cloud technology can be used for supporting different variants of the same process (due to “couleur locale”), and how these organisations can aid each other in achieving the completion of a running case. In this paper we describe how we have brought a BPM system (YAWL) into the cloud that supports variants

YAWL in the Cloud

In the context of the CoSeLoG project (which involves 10 Dutch municipalities), we realised a proof-of-concept implementation based on YAWL. The municipalities want to share a common IT infras- tructure and learn from one another, but also allow for local differences. Therefore, we extended YAWL to run in a cloud-based environment lever-aging on existing configuration possibilities. To support "YAWL in the Cloud" we developed load-balancing capabilities that allow for the distribution of work over multiple YAWL engines. Moreover, we extended YAWL with multi-tenancy capabilities: one municipality may effectively use multiple engines without knowing it and one engine may safely run the processes of multiple municipalities

Incremental computation of synthesis rules for free-choice Petri nets

In this paper, we propose a novel approach that calculates all the possible applications of synthesis rules, for well-formed free-choice Petri nets [8], in a speedy way to enable an interactive editing system. The proposed approach uses a so-called incremental synthesis structure, which can be used to extract all the synthesis rules, corresponding to a given net. Furthermore, this structure is updated incrementally, i.e. after usage of a synthesis rule, to obtain the incremental synthesis structure of the newly synthesized net. We prove that the proposed approach is correct and complete in order to synthesize any well-formed free-choice Petri net, starting with an initial well-formed atomic net and the corresponding incremental synthesis structure. A variant of the proposed approach has been implemented that allows interactive modeling (discovery) of sound business processes (from event logs). Experimental results show that the proposed approach is fast, and outperforms the baseline, and hence is well-suited for enabling interactive synthesis of very large nets

XES tools

Process mining has emerged as a new way to analyze business processes based on event logs. These events logs need to be extracted from operational systems and can subsequently be used to discover or check the conformance of processes. ProM is a widely used tool for process mining. In earlier versions of ProM, MXML was used as an input format. In future releases of ProM, a new logging format will be used: The eXtensible Event Stream (XES) format. This format has several advantages over MXML. The paper presents two tools that use this format - XESMa and ProM6 - and highlights the main innovations and the role of XES. XESMa enables domain experts to specify how the event log should be extracted from existing systems and converted to XES. ProM6 is a completely new process mining framework based on XES and enabling innovative process mining functionality

Plasma Amyloid-beta Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study

Item does not contain fulltextBACKGROUND: Plasma amyloid-beta (Abeta) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Abeta isoforms, i.e., Abeta1-40 and Abeta1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Abeta levels including novel Abeta1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementiaObjective:To examine the association of plasma Abeta levels (i.e., Abeta1-38, Abeta1-40, and Abeta1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. METHODS: We analyzed plasma Abeta1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Abeta levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-analysis with fixed effects. RESULTS: Higher levels of plasma Abeta1-38, Abeta1-40, Abeta1-42, and Abeta1-40/ Abeta1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels of Abeta1-40 and Abeta1-40/ Abeta1-42 were significantly associated with larger WMH volumes. With regard to cognition, a higher level of Abeta1-38 Abeta1-40 and Abeta1-40/ Abeta1-42 was related to worse performance on cognitive test specifically in memory domain. CONCLUSION: Higher plasma levels of Abeta levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Abeta levels thus mark the presence of vascular brain pathology