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Acknowledgement The authors thank James Worrell, Achilles Beros and Uli Fahrenberg for advice and discussions. ...arXiv:1407.1513v1 fatcat:a7vso5cut5golp2hwrocckhhji
Lecture Notes in Computer Science
When creating execution-level process models from conceptual to-be process models, challenges are to find implementations for process activities and to use these implementations correctly. Carrying out these activities manually can be time consuming, since it involves searching in large service repositories and cycles of testing and re-designing. We present Maestro for BPMN, a tool that allows to annotate and automatically compose activities within business processes, and to verify the consistency of an annotated process.doi:10.1007/978-3-642-00887-0_67 fatcat:oofx3ewsyzcqhjhkjkmoi2cxbq
The task of unsupervised induction of probabilistic context-free grammars (PCFGs) has attracted a lot of attention in the field of computational linguistics. Although it is a difficult task, work in this area is still very much in demand since it can contribute to the advancement of language parsing and modelling. In this work, we describe a new algorithm for PCFG induction based on a principled approach and capable of inducing accurate yet compact artificial natural language grammars anddoi:10.3115/v1/d14-1141 dblp:conf/emnlp/SciclunaH14 fatcat:7mwrhfeymzhczntgjtaxbufm4i
more »... l context-free grammars. Moreover, this algorithm can work on large grammars and datasets and infers correctly even from small samples. Our analysis shows that the type of grammars induced by our algorithm are, in theory, capable of modelling natural language. One of our experiments shows that our algorithm can potentially outperform the state-of-the-art in unsupervised parsing on the WSJ10 corpus. * ⇒ w} and the language generated by a grammar G is L(G) = S∈I L(S). A CFG is in Chomsky Normal Form (CNF) if ev-
Automatic web service composition (WSC) is a key component of flexible SOAs. We address WSC at the profile/capability level, where preconditions and effects of services are described in an ontology. In its most expressive formulation, WSC has two sources of complexity: (A) a combinatorial explosion of the services composition space, and (B) worst-case exponential reasoning is needed to determine whether the underlying ontology implies that a particular composition is a solution. Any WSCdoi:10.1109/icwe.2008.8 dblp:conf/icwe/HoffmannWSKA08 fatcat:mvt6ejgrubc3lnwryw35hovndi
more »... gy must hence choose a trade-off between scalability and expressivity. We devise new methods for finding better trade-offs. We address (A) by techniques for the automatic generation of heuristic functions. We address (B) by approximate reasoning techniques for the fully expressive case, and by identifying a sub-class where the required reasoning is tractable. We show empirically that our approach scales gracefully to large pools of pre-discovered services, in several test cases.
Lecture Notes in Computer Science
Choreography (chair: James Scicluna) The Choreography part of SESA is meant to provide a process language which should allow for formal specifications of interactions and processes between the service ...doi:10.1007/978-3-540-77028-2_22 fatcat:tueiwlavszd2pbw6ifda4yre4e
The microtubule-associated protein tau has a critical role in Alzheimer disease and related tauopathies. There is accumulating evidence that tau aggregates spread and replicate in a prionlike manner, with the uptake of pathological tau seeds causing misfolding and aggregation of monomeric tau in recipient cells. Here we focused on small extracellular vesicles enriched for exosomes that were isolated from the brains of tau transgenic rTg4510 and control mice. We found that these extracellulardoi:10.1074/jbc.m115.709485 pmid:27030011 pmcid:PMC4933440 fatcat:v2ote2vkmzcipcklgawhmqgt44
more »... icles contained tau, although the levels were significantly higher in transgenic mice that have a pronounced tau pathology. Tau in the vesicles was differentially phosphorylated, although to a lower degree than in the brain cells from which they were derived. Several phospho-epitopes (AT8, AT100, and AT180) thought to be critical for tau pathology were undetected in extracellular vesicles. Despite this, when assayed with FRET tau biosensor cells, extracellular vesicles derived from transgenic mice were capable of seeding tau aggregation in a threshold-dependent manner. We also observed that the dye used to label extracellular vesicle membranes was still present during nucleation and formation of tau inclusions, suggesting either a role for membranes in the seeding or in the process of degradation. Together, we clearly demonstrate that extracellular vesicles can transmit tau pathology. This indicates a role for extracellular vesicles in the transmission and spreading of tau pathology. The characteristics of tau in extracellular vesicles and the seeding threshold we identified may explain why tau pathology develops very slowly in neurodegenerative diseases such as Alzheimer disease.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission)doi:10.1073/pnas.2011574118 pmid:33879606 pmcid:PMC8092379 fatcat:vtaixfetvjcghey7ctf4dcu7wi
more »... atients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.
AbstractTuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathwaydoi:10.1007/s10571-021-01157-5 pmid:34709498 fatcat:evg7oeg7p5ek5pjgyn5qzttoru
more »... extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.
Emergent informed consent for clinical trials in acute myocardial infarction (AMI) and stroke is challenging. The role and value of consent are controversial, and insufficient data exist regarding patients' and surrogates' experiences. Methods and Results We conducted structured interviews with patients (or surrogates) enrolled in AMI or acute stroke trials at 6 sites between 2011 and 2016. Primary domains included trial recall, consent experiences, and preferences regarding involvement.doi:10.1161/jaha.118.010905 pmid:30663498 pmcid:PMC6497349 fatcat:7rae2gwgxrgodd72453wa32sx4
more »... tive and test statistics were used to characterize responses and explore relationships between key domains and characteristics. Multivariable logistic regression was used to examine associations between key covariates and consent preferences. There were 176 (84 stroke, 92 AMI) completed interviews. Most stroke respondents (82%) were surrogates; all AMI respondents were patients. Average time from trial enrollment to interview was 1.9 years (stroke) and 2.8 years (AMI); 89% of stroke and 62% of AMI respondents remembered being in the trial, and among these respondents, 80% (stroke) and 44% (AMI) remembered reading some of the consent form. Over 90% reported not feeling pressure to enroll, being treated in a caring way, and being treated with dignity. A minority (16% stroke and 26% AMI) reported they would have preferred not to be asked for consent. Just over half (61% stroke and 53% AMI) recalled a postenrollment conversation about the study. Conclusions Most respondents felt they were treated respectfully and were glad they had been asked for consent. Trial recall was relatively low, and many respondents recalled little postenrollment discussion. Further development of context-sensitive approaches to consent is important.
Systemic inflammation is a whole body reaction having an infection-positive (i.e., sepsis) or infection-negative origin. It is important to distinguish between these two etiologies early and accurately because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on peripheral blood RNAs could be discovered that would (1) determine which patients with systemic inflammation had sepsis, (2) be robust across independent patientdoi:10.1371/journal.pmed.1001916 pmid:26645559 pmcid:PMC4672921 fatcat:3qicwxr4szeqrjf5tdbrujz424
more »... cohorts, (3) be insensitive to disease severity, and (4) provide diagnostic utility. The goal of this study was to identify and validate such a molecular classifier. Methods and Findings We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICUs). Biomarker discovery utilized an Australian cohort PLOS Medicine | (n = 105) consisting of 74 cases (sepsis patients) and 31 controls (post-surgical patients with infection-negative systemic inflammation) recruited at five tertiary care settings in Brisbane, Australia, from June 3, 2008, to December 22, 2011. A four-gene classifier combining CEACAM4, LAMP1, PLA2G7, and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was validated using reverse transcription quantitative PCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Patients for validation were selected from the Molecular Diagnosis and Risk Stratification of Sepsis study (ClinicalTrials.gov, NCT01905033), which recruited ICU patients from the Academic Medical Center in Amsterdam and the University Medical Center Utrecht. Patients recruited from November 30, 2012, to August 5, 2013, were eligible for inclusion in the present study. Validation cohort 1 (n = 59) consisted entirely of unambiguous cases and controls; SeptiCyte Lab gave an area under curve (AUC) of 0.95 (95% CI 0.91-1.00) in this cohort. ROC curve analysis of an independent, more heterogeneous group of patients (validation cohorts 2-5; 249 patients after excluding 37 patients with an infection likelihood of "possible") gave an AUC of 0.89 (95% CI 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility of SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters available to a clinician within 24 h of ICU admission. Sep-tiCyte Lab was significantly better at differentiating cases from controls than all tested parameters, both singly and in various logistic combinations, and more than halved the diagnostic error rate compared to procalcitonin in all tested cohorts and cohort combinations. Limitations of this study relate to (1) cohort compositions that do not perfectly reflect the composition of the intended use population, (2) potential biases that could be introduced as a result of the current lack of a gold standard for diagnosing sepsis, and (3) lack of a complete, unbiased comparison to C-reactive protein.
variability in submillimeter dust emission, "The JCMT Transient Survey" (Herczeg et al. 2017 ) is monitoring eight star-forming regions with the SCUBA-2 (Holland et al. 2013) submillimeter bolometer on the James ...doi:10.3847/1538-4357/aaa764 fatcat:snfzwmkv55fndmizaxsrbd7phq
The James Clerk Maxwell Telescope is operated by the East Asian Observatory on behalf of the National Astronomical Observatory of Japan, Academia Sinica Institute of Astronomy and Astrophysics, the Korea ... The benefit of observing variability at submillimeter wavelengths is that ground-based instruments such as the James Clerk Maxwell Telescope (JCMT) are available to monitor large areas of the sky at a ...doi:10.3847/1538-4357/aa9225 fatcat:w76s43jlvvcnjbzkksxos32gnq
.; Scicluna, B.P.; Aronica, E. Aronica, E. (2017). Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: implications for pathophysiology and treatment. ...doi:10.1038/s41598-017-06145-8 pmid:28808237 pmcid:PMC5556011 fatcat:ufxjrmog2rckhafvpio23rsrpm
Tuberous sclerosis complex (TSC), a rare genetic disorder caused by a mutation in the TSC1 or TSC2 gene, is characterized by the growth of hamartomas in several organs. This includes the growth of low-grade brain tumors, known as subependymal giant cell astrocytomas (SEGA). Previous studies have shown differential expression of genes related to the extracellular matrix in SEGA. Matrix metalloproteinases (MMPs), and their tissue inhibitors (TIMPs) are responsible for remodeling the extracellulardoi:10.1093/jnen/nlaa040 pmid:32472129 fatcat:6zabhxguqfgg7jvlhmaklzp62e
more »... matrix and are associated with tumorigenesis. This study aimed to investigate the MMP/TIMP proteolytic system in SEGA and the regulation of MMPs by microRNAs, which are important post-transcriptional regulators of gene expression. We investigated the expression of MMPs and TIMPs using previously produced RNA-Sequencing data, real-time quantitative PCR and immunohistochemistry in TSC-SEGA samples and controls. We found altered expression of several MMPs and TIMPs in SEGA compared to controls. We identified the lowly expressed miR-320d in SEGA as a potential regulator of MMPs, which can decrease MMP2 expression in human fetal astrocyte cultures. This study provides evidence of a dysregulated MMP/TIMP proteolytic system in SEGA of which MMP2 could be rescued by microRNA-320d. Therefore, further elucidating microRNA-mediated MMP regulation may provide insights into SEGA pathogenesis and identify novel therapeutic targets.
Lecture Notes in Computer Science
One of the main problems when creating execution-level process models is finding implementations for process activities. Carrying out this activity manually can be time consuming, since it involves searching in large service repositories. We present Maestro for BPMN, a tool that allows to annotate and automatically compose activities within business processes. We explain the main assumptions and algorithms underlying the tool, and we overview what will be demonstrated at ESWC.doi:10.1007/978-3-540-68234-9_56 dblp:conf/esws/BornHKKMSWZ08 fatcat:xdhpmgunhbexbgxgh6alnzz7t4
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