Identification of a novel titin-cap/telethonin mutation in a Portuguese family with hypertrophic cardiomyopathy

INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease; there is still a large proportion of patients with no identified disease-causing mutation. Although the majority of mutations are found in the MYH7 and MYBPC3 genes, mutations in Z-disk-associated proteins have also been linked to HCM. METHODS: We assessed a small family with HCM based on family history, physical examination, 12-lead ECG, echocardiogram and magnetic resonance imaging. After exclusion of mutations in eleven HCM disease genes, we performed direct sequencing of the TCAP gene encoding the Z-disk protein titin-cap (also known as telethonin). RESULTS: We present a novel TCAP mutation in a small family affected by HCM. The identified p.C57W mutation showed a very low population frequency, as well as high conservation across species. All of the bioinformatic prediction tools used considered this mutation to be damaging/deleterious. Family members were screened for this new mutation and a co-segregation pattern was detected. Both affected members of this family presented with late-onset HCM, moderate asymmetric left ventricular hypertrophy, atrial fibrillation and heart failure with preserved ejection fraction and low risk of sudden cardiac death. CONCLUSIONS: We present evidence supporting the classification of the TCAP p.C57W mutation, encoding the Z-disk protein titin-cap/telethonin as a new likely pathogenic variant of hypertrophic cardiomyopathy, with a specific phenotype in the family under analysis

Analysis of transition forms towards more ecologically-oriented farming: the case of organic farming and integrated crop protection

Interdisciplinary approaches developed concerning the conversion to organic farming show that the types of conversion trajectories can be differentiated on the basis of the progression of crop protection changes within a larger framework where relationships to other “objects” are transformed – the soil, products, rotations, work organisation, marketing, social networks and knowledge acquisition. In the case of integrated plant production, the extent of changes depends on the degree of recomposition of agronomic practices. This transition implies major knowledge acquisition that relies on the support and contribution of advisors and on the group dynamics that develop within a group of farmers. Transitions towards integrated crop protection are, by their nature, more reversible and therefore more fragile than the conversion to organic farming. This is due to the fact that they are not stabilised by a certification or by the market, and analysis shows that their sustainability is linked in part to their integration within a group dynamics

The Equation of State and the Hugoniot of Laser Shock-Compressed Deuterium

The equation of state and the shock Hugoniot of deuterium are calculated using a first-principles approach, for the conditions of the recent shock experiments. We use density functional theory within a classical mapping of the quantum fluids [ Phys. Rev. Letters, {\bf 84}, 959 (2000) ]. The calculated Hugoniot is close to the Path-Integral Monte Carlo (PIMC) result. We also consider the {\it quasi-equilibrium} two-temperature case where the Deuterons are hotter than the electrons; the resulting quasi-equilibrium Hugoniot mimics the laser-shock data. The increased compressibility arises from hot $D^+-e$ pairs occuring close to the zero of the electron chemical potential.Comment: Four pages; One Revtex manuscript, two postscipt figures; submitted to PR

KNAPSACK PROBLEMS WITH SETUPS

RÉSUMÉ : We consider two variants of knapsack problems with setups arising as subproblems in a DantzigWolfe decomposition approach to more complex combinatorial optimization problems. In the multiple-class binary knapsack problem with setups, items are partitioned into classes whose use implies a setup cost and associated capacity consumption. Item weights are assumed to be a multiple of their class weight. The total weight of selected items and setups is bounded. The objective is to maximize the difference between the profits of selected items and the fixed costs incurred for setting-up classes. In the continuous knapsack problems with setups, each class holds a single item and a fraction of an item can be selected while incurring a full setup. The paper shows the extent to which classical results for the knapsack problem can be generalized to these variants. In particular, an extension of the branch-and-bound algorithm of Horowitz and Sahni is developed for problems with positive setup costs. Our direct approach is compared experimentally with the approach proposed in the literature consisting in converting the problem into a multiple choice knapsack with pseudo-polynomial size

Minimal work principle: proof and counterexamples

The minimal work principle states that work done on a thermally isolated equilibrium system is minimal for adiabatically slow (reversible) realization of a given process. This principle, one of the formulations of the second law, is studied here for finite (possibly large) quantum systems interacting with macroscopic sources of work. It is shown to be valid as long as the adiabatic energy levels do not cross. If level crossing does occur, counter examples are discussed, showing that the minimal work principle can be violated and that optimal processes are neither adiabatically slow nor reversible. The results are corroborated by an exactly solvable model.Comment: 13 pages, revtex, 2 eps figure