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Inferring behavioral models (e.g., state machines) of software systems is an important element of re-engineering activities. Model inference techniques can be categorized as active or passive learning, constructing models by (dynamically) interacting with systems or (statically) analyzing traces, respectively. Application of those techniques in the industry is, however, hindered by the trade-off between learning time and completeness achieved (active learning) or by incomplete input logs (passive learning). We investigate the learning time/completeness achieved trade-off of active learning with a pilot study at ASML, provider of lithography systems for the semiconductor industry. To resolve the trade-off we advocate extending active learning with execution logs and passive learning results.We apply the extended approach to eighteen components used in ASML TWINSCAN lithography machines. Compared to traditional active learning, our approach significantly reduces the active learning time. Moreover, it is capable of learning the behavior missed by the traditional active learning approach.

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Goed slapen is belangrijk voor een gezonde ontwikkeling. Jonge kinderen zijn voor het reguleren van hun slaap sterk afhankelijk van hun ouders. De manier waarop ouders hun kinderen gezond slaapgedrag aanleren, werkt door tot in de adolescentie. Uit onderzoek blijkt echter dat veel kinderen slaapproblemen ervaren en deze problemen lijken de laatste jaren alleen maar toe te nemen. Slaapproblemen bij jonge kinderen hebben vaak ook grote gevolgen voor het hele gezin. Hoe kunnen we deze problemen voorkomen of zo nodig behandelen?

Het onderzoeksproject ‘Optimizing Water Availability with Sentinel-1 Satellites’ heeft als doel te onderzoeken hoe satellietdata gebruikt kan worden in het Nederlandse waterbeheer. Het onderzoek laat zien dat de satelliet Sentinel-1 buiten het groeiseizoen om al een vrij goed beeld geeft van het bodemvochtgehalte. Hiermee kan bijvoorbeeld de berijdbaarheid van landbouwpercelen in kaart gebracht kan worden. Ook is met Deltares en HKV een data-assimilatietool ontwikkeld die ingezet kan worden om simulaties met het Landelijk Hydrologisch Model te verbeteren.

We answer an open question in the theory of degrees of infinite sequences with respect to transducibilityby finite-state transducers. An initial study of this partial order of degrees was carried out in [1], but many basic questions remain unanswered.One of the central questions concerns the existence of atom degrees, other than the degree of the ‘identity sequence’ 100101102103⋯ . A degree is called an ‘atom’ if below it there is only the bottom degree 00 , which consists of the ultimately periodic sequences. We show that also the degree of the ‘squares sequence’ 1001011041091016⋯ is an atom.As the main tool for this result we characterise the transducts of ‘spiralling’ sequences and their degrees. We use this to show that every transduct of a ‘polynomial sequence’ either is in 00 or can be transduced back to a polynomial sequence for a polynomial of the same order.

The engineering of supervisory controllers for large and complex cyber-physical systems requires dedicated engineering support. The Compositional Interchange Format language and toolset have been developed for this purpose. We highlight a model-based engineering framework for the engineering of supervisory controllers and explain how the CIF language and accompanying tools can be used for typical activities in that framework such as modeling, supervisory control synthesis, simulation-based validation, verification, and visualization, real-time testing, and code generation. We mention a number of case studies for which this approach was used in the recent past. We discuss future developments on the level of language and tools as well as research results that may be integrated in the longer term.

Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy. Such antibodies induced unprecedented long-term remissions in patients with advanced stage malignancies, most notably melanoma and lung cancer, that do not respond to conventional therapies. In this review, we will recapitulate the development of antibody-based therapy, and detail recent advances and new functions, particularly in the field of cancer immunotherapy. With the advent of recombinant DNA engineering, a number of rationally designed molecular formats of antibodies and antibody-derived agents have become available, and we will discuss various molecular formats including antibodies with improved effector functions, bispecific antibodies, antibody-drug conjugates, antibody-cytokine fusion proteins, and T cells genetically modified with chimeric antigen receptors. With these exciting advances, new antibody-based treatment options will likely enter clinical practice and pave the way toward more successful control of malignant diseases.

Riparian vegetation actively interacts with fluvial systems affecting river hydrodynamics, morphodynamics and groundwater. These interactions can be coupled because both vegetation and hydromorphology (i.e. the combined scientific study of hydrology and fluvial geomorphology) involve dynamic processes with similar temporal and spatial scales. To predict and assess the consequences of restoration measures, maintenance operations or human pressures in rivers, managers and planners may wish to model these interactions considering the different and interdisciplinary implications in the fields of ecology, geomorphology and hydrology. In this paper, we review models that are currently available and that incorporate the processes that relate riparian vegetation to hydromorphology. The models that are considered include those emphasizing hydraulic-geomorphological processes (such as flow resistance, sediment transport and bank dynamics) as well as those emphasizing ecological processes (seed dispersal, plant survival, growth, succession and mortality). Models interpreting the coupled evolution between riparian vegetation and river morphology and groundwater are also presented. The aim is to provide an overview of current modelling capabilities and limitations and to identify future modelling challenges.

We present a coinductive framework for defining infinitary analogues of equational reasoning and rewriting in a uniform way. We define the relation ∞=, a notion of infinitary equational reasoning, and →∞, the standard notion of infinitary rewriting as follows: ∞=:= νR. (=R ≊ R)→∞ := μR. νS.(→R ≊ R)o S where μ and ν are the least and greatest fixed-point operators, respectively, and where R := {f(s1, . . . , sn), f(t1, . . . , tn) f∈∑ s1 R t1, . . . , snR tn } ≊ Id . The setup captures rewrite sequences of arbitrary ordinal length, but it has neither the need for ordinals nor for metric convergence. This makes the framework especially suitable for formalizations in theorem provers.

Background: Inflammatory bowel disease-unclassified (IBD-U) is diagnosed in ∼10% of pediatric and adolescent onset IBD patients. The EUROKIDS registry (2004) initiated by the Porto IBD working group of ESPGHAN prospectively monitors diagnostic workup of newly diagnosed pediatric and adolescent onset IBD patients. We aimed to describe diagnostic workup, phenotype, and change of diagnosis over time in pediatric IBD-U patients. Methods: Data were collected on children from 52 centers across 20 European countries and Israel, diagnosed with IBD from May 2005 through November 2013. Full endoscopy plus small bowel radiology was considered complete diagnostic workup. Participating centers reporting IBD-U patients were queried in 2014 for follow-up data. Results: IBD-U was the provisional first diagnosis in 265 of 3461 children (7.7%) (91/158 [58%] with pancolitis; 140 [53%] male), diagnosed more frequently under the age of 10 (median age 12.3 years, 89 [34%] under 10 years). Half (48%) had undergone complete diagnostic workup. Lack of small bowel radiology was the prevailing reason for incomplete workup. As a result of reinvestigations (endoscopy in 54%, radiology in 38%) during a median follow-up of 5.7 years (interquartile range, 2.5-7.8), a change in diagnosis from IBD-U to Crohn's disease (12%) or ulcerative colitis (20%) was reported. Conclusions: Only half of patients reported as IBD-U in EUROKIDS had undergone complete diagnostic workup. Follow-up with reinvestigations resulted in a reduction of IBD-U rate to 5.6%. A diagnosis of IBD-U becomes less likely in case of complete diagnostic workup. Implementation of clear diagnostic criteria will further reduce the rate of IBD-U in the future. © 2015 Crohn's & Colitis Foundation of America, Inc.

We answer an open question in the theory of degrees of infinite sequences with respect to transducibility by finite-state transducers. An initial study of this partial order of degrees was carried out in (Endrullis, Hendriks, Klop, 2011), but many basic questions remain unanswered. One of the central questions concerns the existence of atom degrees, other than the degree of the `identity sequence' 1 0^0 1 0^1 1 0^2 1 0^3 .... A degree is called an `atom' if below it there is only the bottom degree 0, which consists of the ultimately periodic sequences. We show that also the degree of the `squares sequence' 1 0^0 1 0^1 1 0^4 1 0^9 1 0^{16} ... is an atom. As the main tool for this result we characterise the transducts of `spiralling' sequences and their degrees. We use this to show that every transduct of a `polynomial sequence' either is in 0 or can be transduced back to a polynomial sequence for a polynomial of the same order.

We present a coinductive framework for defining infinitary analogues of equational reasoning and rewriting in a uniform way. We define the relation 1=, a hitherto unknown notion of infinitary equational reasoning, and !1, the standard notion of infinitary rewriting as follows: 1= := R. (=E [ R) !1 := μR. S. (!R [ R) S where μ and are the least and greatest fixed-point operators, respectively, and where R := { hf(s1, . . . , sn), f(t1, . . . , tn)i | f 2 , s1 R t1, . . . , sn R tn } [ Id . The setup captures rewrite sequences of arbitrary ordinal length, but it has neither the need for ordinals nor for metric convergence. This makes the framework especially suitable for formalizations in theorem provers.

The research objective for Deliverable 2.1 is to develop a process-based, multi-scale, hierarchical framework to support river managers in assessing the hydromorphological character of rivers, exploring the causes of hydromorphological problems, and devising sustainable management solutions.

A semi-quantitative risk assessment is presented for the storage of gas oil in depleted salt caverns in the Twente region, the Netherlands. It is based on a bow-tie model, in which an incident, leakage of gas oil from the storage system (cavern and wells), is evaluated by assessing its possible causes and effects. The causes are all the events thatmay lead to leakage fromthe storage system. The effects are the consequences of the leakage. It is considered that themost serious of the subsurface risks is contamination of the groundwater due to upward migration of the gas oil to the surface. A unique aspect of our risk assessment is the combination of causes and effects. The effects of containment/failure are quantified at multiple time scales using a numerical flow model for multiphase flow through porous medium, based on the geohydrological properties of the subsurface of the Twente area. The probability of occurrence of loss of containment/failure (causes) is quantified semi-quantitatively, using the causal relationships between the causes and effects. Modelling of the leakage shows that, as expected, leakage from the well above the hydrogeological base in the phreatic aquifer produces an immediate risk of contamination of the upper groundwater. However, leakage at a deeper level does not pose a risk of contamination of groundwater, because the low porosity and permeability of the geological layers prevent the upward migration of leaking gas oil. The semi-quantitative approach to the probability of failure finds that for multiple scenarios (e.g. well failure, unstable cavern, high pressure) and in the absence of human intervention, the probabilities of failure are medium to high. If human intervention is assumed, these probabilities of failure diminish considerably, especially those associated with the well. These findings are consistent with those from other hazard studies on storage in salt caverns. The causes (probabilities of failure) and effects (modelling of leakage) together indicate that for most scenarios the risk is low when human intervention (e.g. monitoring of the well) is assumed. Notwithstanding our conclusion that the risk of leakage associated with gas oil injection and storage in salt caverns is low, an extensive monitoring plan should be formulated to monitor the containment of the gas oil in the storage system and its long-term stability, to ensure timely human intervention that reduces the risk considerably

Contains fulltext : 122925.pdf (Author’s version preprint ) (Open Access) Workshop on Infinitary Rewriting 2013 Friday June 28, Eindhoven, The Netherlands