Mechanisms underlying mutational outcomes of DNA double-strand break repair

This thesis addresses the repair of DNA double-strand breaks (DSBs) that arise in different contexts, both artificially inflicted DNA damage and spontaneously arising breaks. We have found that the (mutational) repair outcome of a DSB depends on the context in which it occurs. When cells are not replicating, DSBs are repaired via non-homologous end-joining (NHEJ). NHEJ efficiency can be affected by defective RNA processing. In replicating cells, the preferable mechanism for DSB repair is homologous recombination (HR). When canonical HR cannot be executed, because the repair template is not available (at G4-induced breaks, for example) or when not all HR factors are present (in BRCA1 deficient situations), alternative annealing is needed. This is carried out via polymerase theta-mediated end-joining (TMEJ), or when homologous nucleotides are available, via HELQ-1 mediated annealing of these homologous stretches. Finally, we have found that large tandem duplications can arise when break ends cannot anneal properly after the extension step in HR.LUMC / Geneeskund

Actors, actions, and initiative in normative system specification

The logic of norms, called deontic logic, has been used to specify normative constraints for information systems. For example, one can specify in deontic logic the constraints that a book borrowed from a library should be returned within three weeks, and that if it is not returned, the library should send a reminder. Thus, the notion of obligation to perform an action arises naturally in system specification. Intuitively, deontic logic presupposes the concept of anactor who undertakes actions and is responsible for fulfilling obligations. However, the concept of an actor has not been formalized until now in deontic logic. We present a formalization in dynamic logic, which allows us to express the actor who initiates actions or choices. This is then combined with a formalization, presented earlier, of deontic logic in dynamic logic, which allows us to specify obligations, permissions, and prohibitions to perform an action. The addition of actors allows us to expresswho has the responsibility to perform an action. In addition to the application of the concept of an actor in deontic logic, we discuss two other applications of actors. First, we show how to generalize an approach taken up by De Nicola and Hennessy, who eliminate from CCS in favor of internal and external choice. We show that our generalization allows a more accurate specification of system behavior than is possible without it. Second, we show that actors can be used to resolve a long-standing paradox of deontic logic, called the paradox of free-choice permission. Towards the end of the paper, we discuss whether the concept of an actor can be combined with that of an object to formalize the concept of active objects

An example of active learning in Aerospace Engineering

This paper is a showcase for an on-going active learning capstone design project in the BSe. programme at the Faculty of Aerospace Engineering at Delft University of Technology. In multi-disciplinary teams supervised by tutors from different backgrounds students work towards an Aerospace (related) design. In the exercise students learn about applying knowledge, working in teams, sustainable development, project management, reporting, presenting and design in a semi-professional environment

An example of active learning in Aerospace Engineering

This paper is a showcase for an on-going active learning capstone design project in the BSe. programme at the Faculty of Aerospace Engineering at Delft University of Technology. In multi-disciplinary teams supervised by tutors from different backgrounds students work towards an Aerospace (related) design. In the exercise students learn about applying knowledge, working in teams, sustainable development, project management, reporting, presenting and design in a semi-professional environment

Impact of moisture and grinding on yield, physical, chemical and thermal properties of wholegrain flour obtained from hydrothermally treated sorghum grains

The present work evaluates the potential of sorghum with high content of tannins for wholegrain flour production. Two types of mills were used: a roller mill (RM) and a blade (BM) mill. The impact of moisture and grinding on yield, physical, chemical and thermal properties were evaluated. Maximum yield was obtained using a BM with 25% moisture in the grain, resulting in 60.9% versus 28% (g flour g−1 of wholegrain sorghum) for the RM. Grain moisture and milling type affected flour colour and ashes. For both mills, the pasting and thermal properties of flour with grain moisture variation were significantly different from the untreated control sample. By studying the procedures for flour production and quality characteristics, it is possible to produce flour with good physical attributes, which can contribute to the development of gluten‐free foods based on sorghum for the coeliac population.Fil: Acquisgrana, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina. Universidad Tecnológica Nacional. Facultad Regional Resistencia. Departamento de Ingeniería Química. Laboratorio de Química Teórica y Experimental; ArgentinaFil: Gómez Pamies, Laura Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina. Universidad Tecnológica Nacional. Facultad Regional Resistencia. Departamento de Ingeniería Química. Laboratorio de Química Teórica y Experimental; ArgentinaFil: Martinez Amezaga, Nancy María Jimena. Universidad Tecnológica Nacional. Facultad Regional Resistencia. Departamento de Ingeniería Química. Laboratorio de Química Teórica y Experimental; ArgentinaFil: Quiroga, Fernanda Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Química Aplicada; ArgentinaFil: Ribotta, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Benitez, Elisa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina. Universidad Tecnológica Nacional. Facultad Regional Resistencia. Departamento de Ingeniería Química. Laboratorio de Química Teórica y Experimental; Argentin

Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications

DNA double-strand breaks are a major threat to cellular survival and genetic integrity. In addition to high fidelity repair, three intrinsically mutagenic DNA break repair routes have been described, i.e. single-strand annealing (SSA), polymerase theta-mediated end-joining (TMEJ) and residual ill-defined microhomology-mediated end-joining (MMEJ) activity. Here, we identify C. elegans Helicase Q (HELQ-1) as being essential for MMEJ as well as for SSA. We also find HELQ-1 to be crucial for the synthesis-dependent strand annealing (SDSA) mode of homologous recombination (HR). Loss of HELQ-1 leads to increased genome instability: patchwork insertions arise at deletion junctions due to abortive rounds of polymerase theta activity, and tandem duplications spontaneously accumulate in genomes of helq-1 mutant animals as a result of TMEJ of abrogated HR intermediates. Our work thus implicates HELQ activity for all DSB repair modes guided by complementary base pairs and provides mechanistic insight into mutational signatures common in HR-defective cancers.Microhomology-mediated end-joining (MMEJ) is a poorly defined mutagenic DNA break repair pathway. Here the authors show that the helicase HELQ is essential for polymerase theta-independent MMEJ, single-strand annealing and homologous recombination through synthesis dependent strand annealing in C. elegans.Genome Instability and Cance

Infinitely many local higher symmetries without recursion operator or master symmetry: integrability of the Foursov--Burgers system revisited

We consider the Burgers-type system studied by Foursov, w_t &=& w_{xx} + 8 w w_x + (2-4\alpha)z z_x, z_t &=& (1-2\alpha)z_{xx} - 4\alpha z w_x + (4-8\alpha)w z_x - (4+8\alpha)w^2 z + (-2+4\alpha)z^3, (*) for which no recursion operator or master symmetry was known so far, and prove that the system (*) admits infinitely many local generalized symmetries that are constructed using a nonlocal {\em two-term} recursion relation rather than from a recursion operator.Comment: 10 pages, LaTeX; minor changes in terminology; some references and definitions adde

Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

0.001). CONCLUSIONS: In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolis