ERCC6, a gen involved in Cockayne's syndrome

Knowledge on the molecular mechanism of nucleotide excision repair (NER) in mammalian cells is rapidly increasing, but far from complete. The aim of the experimental work described in this thesis is to enrich our understanding of the NER process, through the identification and characterization of gene(s) involved. Hereto, the UV-sensitivity of a Chinese hamster ovary (CHO) mutant cell line from rodent complementation group 6 (UV61) was restored to normal levels by means of DNAmediated gene transfer. The correcting human gene, designated ERCC6, has been isolated and characterized -as described in Chapters III to VI. Mutations in the gene appeared to be responsible for (the most common form of) the hereditary DNA repair disorder Cockayne's syndrome. A brief overview of (mammalian) NER is given in Chapter II. Finally, in Chapter VII the current data on the molecular mechanism of (mammalian) NER are discussed

Algebraic totality, towards completeness

Finiteness spaces constitute a categorical model of Linear Logic (LL) whose objects can be seen as linearly topologised spaces, (a class of topological vector spaces introduced by Lefschetz in 1942) and morphisms as continuous linear maps. First, we recall definitions of finiteness spaces and describe their basic properties deduced from the general theory of linearly topologised spaces. Then we give an interpretation of LL based on linear algebra. Second, thanks to separation properties, we can introduce an algebraic notion of totality candidate in the framework of linearly topologised spaces: a totality candidate is a closed affine subspace which does not contain 0. We show that finiteness spaces with totality candidates constitute a model of classical LL. Finally, we give a barycentric simply typed lambda-calculus, with booleans ${\mathcal{B}}$ and a conditional operator, which can be interpreted in this model. We prove completeness at type ${\mathcal{B}}^n\to{\mathcal{B}}$ for every n by an algebraic method

A robust semantics hides fewer errors

In this paper we explore how formal models are interpreted and to what degree meaning is captured in the formal semantics and to what degree it remains in the informal interpretation of the semantics. By applying a robust approach to the definition of refinement and semantics, favoured by the event-based community, to state-based theory we are able to move some aspects from the informal interpretation into the formal semantics

Novosti u sprječavanju, dijagnostici i liječenju infektivnih bolesti

Rizični čimbenici za dugoročni mortalitet od bakterijemija koje je uzrokovao Staphylococcus aureus Infekcija virusom Zika u trudnica u Rio de Janeiru – preliminarni izvještaj Fekalni mikrobiom pri pojavi juvenilnog idiopatskog artritisa Treće međunarodne konsenzusne definicije sepse i septičkog šoka (Sepsis-3) Dijagnostička i prognostička korist prokalcitonina u pacijenata koji dolaze u hitne ambulante sa simtomom dispnej

On the computational content of Zorn's lemma

We give a computational interpretation to an abstract instance of Zorn's lemma formulated as a wellfoundedness principle in the language of arithmetic in all finite types. This is achieved through G\"odel's functional interpretation, and requires the introduction of a novel form of recursion over non-wellfounded partial orders whose existence in the model of total continuous functionals is proven using domain theoretic techniques. We show that a realizer for the functional interpretation of open induction over the lexicographic ordering on sequences follows as a simple application of our main results

Computational interpretations of analysis via products of selection functions

We show that the computational interpretation of full comprehension via two wellknown functional interpretations (dialectica and modified realizability) corresponds to two closely related infinite products of selection functions

Forcing-based cut-elimination for Gentzen-style intuitionistic sequent calculus

International audienceWe give a simple intuitionistic completeness proof of Kripke semantics for intuitionistic logic with implication and universal quantification with respect to cut-free intuitionistic sequent calculus. The Kripke semantics is ``simplified'' in the way that the domain remains constant. The proof has been formalised in the Coq proof assistant and by combining soundness with completeness, we obtain an executable cut-elimination procedure. The proof easily extends to the case of the absurdity connective using Kripke models with exploding nodes à la Veldman

Successful control of a hospital-wide outbreak of OXA-48 producing Enterobacteriaceae in the Netherlands, 2009 to 2011

On 31 May 2011, after notification of Klebsiella pneumoniae(KP)(OXA-48);(CTX-M-15) in two patients, nosocomial transmission was suspected in a Dutch hospital. Hospital-wide infection control measures and an outbreak investigation were initiated. A total of 72,147 patients were categorised into groups based on risk of OXA-48 colonisation or infection, and 7,527 were screened for Enterobacteriaceae(OXA-48) by polymerase chain reaction (PCR). Stored KP isolates (n=408) were retrospectively tested for OXA-48 and CTX-M-1 group extended-spectrum beta-lactamases (ESBL). 285 KP isolates from retrospective and prospective patient screening were genotyped by amplified fragment length polymorphism (AFLP). 41 isolates harbouring different Enterobacteriaceae species were analysed by plasmid multilocus sequence typing (pMLST). No nosocomial transmission of Enterobacteriaceae(OXA-48) was detected after 18 July 2011. Enterobacteriaceae(OXA-48) were found in 118 patients (KP (n=99), Escherichia coli (n=56), >= 1 Enterobacteriaceae(OXA-48) species (n=52)),of whom 21 had clinical infections. 39/41 (95%) of OXA-48 containing plasmids were identical in pMLST. Minimum inhibitory concentrations (MICs) of KPOXA-48 and E. coli(OXA-48) for imipenem and meropenem ranged from = 16 mg/L, and 153/157 (97%) had MIC >0.25mg/L for ertapenem. AFLP identified a cluster of 203 genetically linked isolates (62 KPOXA-48;(CTX-M15); 107 KPCTX-M-15; 34 KPOXA-48). The 'oldest' KPCTX-M-15 and KPOXA-48 clonal types originated from February 2009 and September 2010, respectively. The last presumed outbreak-related KPOXA-48 was detected in April 2012. Uncontrolled transmission of KP (CTX-M-15) evolved into a nosocomial outbreak of KPOXA-48; CTX-M15 with large phenotypical heterogeneity. Although the outbreak was successfully controlled, the contribution of individual containment measures and of the hospital relocating into a new building just before outbreak notification was impossible to quantify