Mechanising syntax with binders in Coq

Mechanising binders in general-purpose proof assistants such as Coq is cumbersome and difficult. Yet binders, substitutions, and instantiation of terms with substitutions are a critical ingredient of many programming languages. Any practicable mechanisation of the meta-theory of the latter hence requires a lean formalisation of the former. We investigate the topic from three angles: First, we realise formal systems with binders based on both pure and scoped de Bruijn algebras together with basic syntactic rewriting lemmas and automation. We automate this process in a compiler called Autosubst; our final tool supports many-sorted, variadic, and modular syntax. Second, we justify our choice of realisation and mechanise a proof of convergence of the sigma calculus, a calculus of explicit substitutions that is complete for equality of the de Bruijn algebra corresponding to the lambda calculus. Third, to demonstrate the practical usefulness of our approach, we provide concise, transparent, and accessible mechanised proofs for a variety of case studies refined to de Bruijn substitutions.Die Mechanisierung von Bindern in universellen Beweisassistenten wie Coq ist arbeitsaufwändig und schwierig. Binder, Substitutionen und die Instantiierung von Substitutionen sind jedoch kritischer Bestandteil vieler Programmiersprachen. Deshalb setzt eine praktikable Mechanisierung der Metatheorie von Programmiersprachen eine elegante Formalisierung von Bindern voraus. Wir nähern uns dem Thema aus drei Richtungen an: Zuerst realisieren wir formale Systeme mit Bindern mit Hilfe von reinen und indizierten de Bruijn Algebren, zusammen mit grundlegenden syntaktischen Gleichungen und Automatisierung. Wir automatisieren diesen Prozess in einem Kompilierer namens Autosubst. Unser finaler Kompilierer unterstützt Sortenlogik, variadische Syntax und modulare Syntax. Zweitens rechtfertigen wir unsere Repräsentation und mechanisieren einen Beweis der Konvergenz des SP-Kalküls, einem Kalkül expliziter Substitutionen der bezüglich der Gleichheit der puren de Bruijn Algebra des -Kalküls vollständig ist. Drittens entwickeln wir kurze, transparente und leicht zugängliche mechanisierte Beweise für diverse Fallstudien, die wir an de Bruijn Substitutionen angepasst haben. Wir weisen so die praktische Anwendbarkeit unseres Ansatzes nach

Differential Object Marking in Corsican: Regularities and triggering factors

The paper deals with Differential Object Marking in Corsican. After a short introduction, it gives an overview of the main local triggering factors for marking direct objects in general (animacy, referentiality). It then presents the few main assumptions about Corsican DOM in the literature as well as findings of a new corpus study, based on written Corsican texts. Strong personal pronouns and proper names for human referents are consistently marked by the DOM marker à, but toponyms and metonymically used proper names are marked as well. Universal and negative quantifiers with a human denotation are also DOM-marked, whereas all other pronouns are not; thus animacy plays only a minor role in Corsican. The presence of determiners, quantifiers or numerals within nominals excludes the presence of à, irrespective of the nominals' denotation. Non-specific bare nominals are never DOM-marked, also irrespective of the nominals' denotation. The discussion then explains that the Corsican DOM is triggered much more by syntactic definiteness than animacy, a hypothesis strengthened by the most prominent morphosyntactic regularity at work in Corsican: nominals in combination with determiners and quantifiers cannot be marked by the DOM-marker à, even if they denote human beings. The complementary distribution of à and prenominal functional elements requires a further detailed syntactic analysi

Akzeptanzanalyse zum Einsatz von Hybriden Prototypen und Extended Reality in der Produktentstehung

Anhand einer Befragung zu virtuellen und hybriden Prototypen, einem multimodalen Lösungsansatz zur Beurteilung von virtuellen Prototypen (Buchholz 2017), werden Erwartungshaltungen, Erfahrungswerte und Prioritäten von Experten in der Produktentwicklung dargestellt und analysiert. Die qualitative Expertenbefragung spiegelt ein aktuelles Meinungsbild der deutschen Industrie zur Verwendung solcher Prototypen wieder und eröffnet eine detaillierte Sicht auf Hürden, die es bei der Entwicklung und Planung zu bewältigen gilt, um die Hemmschwellen für den Einsatz mindern zu können. Im Zuge des Verbundprojekts „RobVRAR - Funktionale virtuelle Prüfsysteme für die roboterbasierte Qualitätsprüfung“ ist in Zusammenarbeit mit der Firma Battenberg ROBOTIC GmbH & Co. KG ein Heckklappen-Demonstrator gebaut worden, der sich als repräsentatives Beispiel eignet. Die Expertenbefragung enthält allgemeine Fragen zu hybriden Prototypen und Fragen, die sich konkret mit dem Heckklappen-Demonstrator befassen

A heuristic framework for video-based teaching and learning scenarios in higher education

Video has been proven to be an effective tool for enhancing the professional vision of higher education students, which is a crucial situation-specific skill within their professional competence. To ensure the successful integration of video in higher education teaching and learning, several implementation actions and processes need to be considered. This paper proposes a heuristic framework for implementing video-based teaching and learning scenarios across various disciplines in higher education. The framework combines existing research strands on professional vision, video implementation, technological pedagogical content knowledge (TPACK), and interactive, constructive, active, and passive (ICAP) learning activities. To highlight the interdisciplinary nature of the framework, examples from four different higher education disciplines (Catholic moral theology, Communication science, German as a second and foreign language, Medicine) are provided. These examples serve to underscore the framework’s applicability across a range of academic fields

Identification of Hypoxia-Induced Genes in Human SGBS Adipocytes by Microarray Analysis

Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation, which in obesity can further lead to insulin resistance. The effect of hypoxia on gene expression in adipocytes appears to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. Microarray analysis showed more than 500 significantly differentially regulated mRNAs after incubation of the cells under low oxygen levels. To gain further insight into the biological processes, hypoxia-regulated genes after 16 hours of hypoxia were classified according to their function. We identified an enrichment of genes involved in important biological processes such as glycolysis, response to hypoxia, regulation of cellular component movement, response to nutrient levels, regulation of cell migration, and transcription regulator activity. Real-time PCR confirmed eight genes to be consistently upregulated in response to 3, 6 and 16 hours of hypoxia. For adipocytes the hypoxia-induced regulation of these genes is shown here for the first time. Moreover in six of these eight genes we identified HIF response elements in the proximal promoters, specific for the HIF transcription factor family members HIF1A and HIF2A. In the present study, we demonstrated that hypoxia has an extensive effect on gene expression of SGBS adipocytes. In addition, the identified hypoxia-regulated genes are likely involved in the regulation of obesity, the incidence of type 2 diabetes, and the metabolic syndrome

Anti-Thymocyte Globulin Treatment Augments 1,25-Dihydroxyvitamin D3 Serum Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation

Application of anti-thymocyte globulin (ATG) is a widely used strategy for the prevention of graftversus-host disease (GvHD). As vitamin D3 serum levels are also discussed to affect hematopoietic stem cell transplantation (HSCT) outcome and GvHD development, we analysed a possible interplay between ATG treatment and serum levels of 25-hydroxyvitamin D3and 1,25-dihydroxyvitaminD3in 4HSCT cohorts withdifferent vitaminD3supplementation. ATG is significantly associated with higher serum level of 1,25 dihydroxyvitamin D3 around HSCT (day -2 to 7, peri-transplant), however only in patients with adequate levels of its precursor 25-hydroxyvitamin D3. ATG exposure had no impact on overall survival in patients supplemented with high dose vitamin D3, but was associated with higher risk of one-year treatment-related mortality (log rank test p=0.041) in patients with no/low vitamin D3 supplementation. However, the difference failed to reach significance applying a Cox-model regression without and with adjustment for baseline risk factors (unadjusted P=0,058, adjusted p=0,139). To shed some light on underlying mechanisms, we investigated the impact of ATG on 1,25-DihydroxyvitaminD3 production by human dendritic cells (DCs) in vitro.ATGincreased gene expression ofCYP27B1, the enzyme responsible for the conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3, which was accompanied by higher 1,25-dihydroxyvitamin D3levels in ATG-treatedDCculture supernatants.Our data demonstrate a cooperative effect of 25-hydroxyvitamin D3 and ATG in the regulation of 1,25-dihydroxyvitamin D3 production. This finding may be of importance in the context of HSCT, where early high levels of 1,25- dihydroxyvitamin D3 levels have been shown to be predictive for lower transplant related mortality and suggest that vitamin D3 supplementation may especially be important in patients receiving ATG for GvHD prophylaxis

Improvement of antibiotic prescription in outpatient care: a cluster-randomized intervention study using a sentinel surveillance network of physicians

Objectives To assess the effectiveness of implementing guidelines, coupled with individual feedback, on antibiotic prescribing behaviour of primary care physicians in Switzerland. Methods One hundred and forty general practices from a representative Swiss sentinel network of primary care physicians participated in this cluster-randomized prospective intervention study. The intervention consisted of providing guidelines on treatment of respiratory tract infections (RTIs) and uncomplicated lower urinary tract infections (UTIs), coupled with sustained, regular feedback on individual antibiotic prescription behaviour during 2 years. The main aims were: (i) to increase the percentage of prescriptions of penicillins for all RTIs treated with antibiotics; (ii) to increase the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics; (iii) to decrease the percentage of quinolone prescriptions for all cases of exacerbated COPD (eCOPD) treated with antibiotics; and (iv) to decrease the proportion of sinusitis and other upper RTIs treated with antibiotics. The study was registered at ClinicalTrials.gov (NCT01358916). Results While the percentage of antibiotics prescribed for sinusitis or other upper RTIs and the percentage of quinolones prescribed for eCOPD did not differ between the intervention group and the control group, there was a significant increase in the percentage of prescriptions of penicillins for all RTIs treated with antibiotics [57% versus 49%, OR = 1.42 (95% CI 1.08-1.89), P = 0.01] and in the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics [35% versus 19%, OR = 2.16 (95% CI 1.19-3.91), P = 0.01] in the intervention group. Conclusions In our setting, implementing guidelines, coupled with sustained individual feedback, was not able to reduce the proportion of sinusitis and other upper RTIs treated with antibiotics, but increased the use of recommended antibiotics for RTIs and UTIs, as defined by the guideline

Parametric Integration by Magic Point Empirical Interpolation

We derive analyticity criteria for explicit error bounds and an exponential rate of convergence of the magic point empirical interpolation method introduced by Barrault et al. (2004, An empirical interpolation method: application to efficient reduced-basis discretization of partial differential equations. C. R. Math.,339, 667–672). Furthermore, we investigate its application to parametric integration. We find that the method is well-suited to Fourier transforms and has a wide range of applications in such diverse fields as probability and statistics, signal and image processing, physics, chemistry and mathematical finance. To illustrate the method, we apply it to the evaluation of probability densities by parametric Fourier inversion. Our numerical experiments display convergence of exponential order, even in cases where the theoretical results do not apply. The magic point integration performs considerably well, when compared with Clenshaw–Curtis quadrature and with Chebyshev interpolation in the parameter space

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies