In de boot genomen: genotsderving komt niet vanzelfsprekend in aanmerking voor vergoeding als vermogensschade

De koper draagt het risico van kleine gebreken in de aan hem geleverde zaken, indien de zaak adequaat is hersteld en de schade voorts uitsluitend bestaat uit gemist onstoffelijk voordeel ten gevolge van het tijdelijk niet beschikbaar zijn van de conforme zaak. Daarmee vult de Hoge Raad de regel uit het arrest Burger/Brouwer Motors verder in

Motive Matters! An exploration of the notion ‘deliberate breach of contract’ and its consequences for the application of remedies

This thesis explores the notion of deliberate breach of contract and its potential remedial consequences. In the major jurisdictions in Europe and in the United States the notion of deliberate breach of contract is generally not coherently and officially defined and acknowledged as an independent legal phenomenon. The ultimate added value of this thesis intends to be a first coherent comparative research on deliberate breach of contract and its potential consequences for the core standard remedies after breach of contract

Boobytraps, valkuilen en instinkers in het burgerlijk recht

Voorwoord: Dit boek bevat dertien opstellen van masterstudenten van de Erasmus School of Law. Met het schrijven van hun bijdrage aan dit boek voltooiden zij – onder begeleiding van de redacteuren – hun Master Privaatrecht, Master Aansprakelijkheid en Verzekering of Togamaster. Het boek is alweer het zesde deel in de rij van scriptieboeken die de Rotterdamse sectie burgerlijk recht sinds 2007 heeft verzorgd. Na de titels ‘Privaatrecht ondersteund’ (2007), ‘Autonomie en paternalisme in het privaatrecht’ (2008), ‘Waar gehakt wordt...’ (2009), ‘Rake Remedies’ (2010) en ‘Fundamentele rechten en vermogensrechten’ (2011), is het nu tijd om de nieuwste generatie Rotterdamse civilisten aan het woord te laten over ‘Boobytraps, valkuilen en instinkers in het burgerlijk recht’. Wij maken van de gelegenheid gebruik om de masterstudenten te danken voor hun grote inzet. Een speciaal woord van dank zijn we verschuldigd aan Emma Krikke, die behulpzaam was bij het verzorgen van de teksten. Ook veel dank gaat uit naar Ann-Sophie Vandenberghe en Gerhard Wagner voor hun medewerking aan de groepsbijeenkomsten

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands