Enhanced conductance near zero voltage bias in mesoscopic superconductor-semiconductor junctions

We have studied the conductance enhancement near zero voltage bias of double-barrier Nb-p++Si-E junctions, where we chose for the counterelectrode E either Nb, Al, or W. The experiments show a large correction, ΔG ≈ 0.1GN, on the classical superconductor–insulator–normal-metal (SIN) conductance. We present measurements of the temperature, magnetic-field, and voltage dependence, and we interpret the observed results within the available theoretical models for coherent Andreev reflection, as provided by several authors.

Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2 syndrome

Adrenal medullary hyperplasias (AMHs) are adrenal medullary proliferations with a size b1cm, while larger lesions are considered as pheochromocytoma (PCC). This arbitrary distinction has been proposed decades ago, although the biological relationship between AMH and PCC has never been investigated. Both lesions are frequently diagnosed in multiple endocrine neoplasia type 2 (MEN2) patients in whom they are considered as two unrelated clinical entities. In this study, we investigated the molecular relationship between AMH and PCC in MEN2 patients. Molecular aberrations of 19 AMHs and 13 PCCs from 18 MEN2 patients were determined by rearranged during transfection (RET) proto-oncogene mutation analysis and loss of heterozygosity (LOH) analysis for chromosomal regions 1p13, 1p36, 3p, and 3q, genomic areas covering commonly altered regions in RET-related PCC. Identical molecular aberrations were found in all AMHs and PCCs, at similar frequencies. LOH was seen for chromosomes 1p13 in 8 of 18 (44%), 1p36 in 9 of 15 (60%), 3p12-13 in 12 of 18 (67%), and 3q23-24 in 10 of 16 (63%) of AMHs, and for chromosome 1p13 in 13 of 13 (100%), 1p36 in 7 of 11 (64%), 3p12-13 in 4 of 11 (36%), and 3q23-24 in 11 of 12 (92%) of PCCs. Our results indicate that AMHs are not hyperplasias and, in clinical practice, should be regarded as PCCs, which has an impact on diagnosis and treatment of MEN2 patients. We therefore propose to replace the term AMH by micro-PCC to indicate adrenal medullary proliferations of less than 1cm

Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency

The microsomal enzyme cytochrome P450c17 is an important regulator of steroidogenesis. The enzyme has two functions: 17alpha-hydroxylase and 17,20-lyase activities. These functions determine the ability of adrenal glands and gonads to synthesize 17alpha-hydroxylated glucocorticoids (17alpha-hydroxylase activity) and/or sex steroids (17,20-lyase activity). Both enzyme functions depend on correct steroid binding, but it was recently shown that isolated lyase deficiency can also be caused by mutations located in the redox partner interaction domain. In this article we present the clinical history and molecular analysis of two patients with combined 17alpha-hydroxylase/17,20-lyase deficiency and four patients with isolated 17,20-lyase deficiency. In these six patients, four missense CYP17 mutations were identified. Two mutations were located in the steroid-binding domain (F114V and D116V), and the other two mutations were found in the redox partner interaction domain (R347C and R347H). We investigated the activity of these mutated proteins by transfection experiments in COS-1 cells using pregnenolone, progesterone, or their hydroxylated products as a substrate and measuring 17alpha-hydroxylase- and 17,20-lyase-dependent metabolites in the medium. The mutations in the steroid-binding domain (F114V and D116V) of P450c17 caused combined, complete (F114V), or partial (D116V) 17alpha-hydroxylase and 17,20-lyase deficiencies, whereas mutations in the redox partner interaction domain (R347C and R347H) displayed less severe 17alpha-hydroxylase deficiency, but complete 17,20-lyase deficiency. These findings are consistent with the clinical data and support the observation that the redox partner interaction domain is essential for normal 17,20-lyase function of P450c17

Non-Equilibrium Quasiclassical Theory for Josephson Structures

We present a non-equilibrium quasiclassical formalism suitable for studying linear response ac properties of Josephson junctions. The non-equilibrium self-consistency equations are satisfied, to very good accuracy, already in zeroth iteration. We use the formalism to study ac Josephson effect in a ballistic superconducting point contact. The real and imaginary parts of the ac linear conductance are calculated both analytically (at low frequencies) and numerically (at arbitrary frequency). They show strong temperature, frequency, and phase dependence. Many anomalous properties appear near phi = pi. We ascribe them to the presence of zero energy bound states.Comment: 11 pages, 9 figures, Final version to appear in PR

Full Counting Statistics of Multiple Andreev Reflections in incoherent diffusive superconducting junctions

We present a theory for the full distribution of current fluctuations in incoherent diffusive superconducting junctions, subjected to a voltage bias. This theory of full counting statistics of incoherent multiple Andreev reflections is valid for arbitrary applied voltage. We present a detailed discussion of the properties of the first four cumulants as well as the low and high voltage regimes of the full counting statistics. The work is an extension of the results of Pilgram and the author, Phys. Rev. Lett. 94, 086806 (2005).Comment: Included in special issue Spin Physics of Superconducting heterostructures of Applied Physics A: Materials Science & Processin

Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiologi

Quantum Theory in Accelerated Frames of Reference

The observational basis of quantum theory in accelerated systems is studied. The extension of Lorentz invariance to accelerated systems via the hypothesis of locality is discussed and the limitations of this hypothesis are pointed out. The nonlocal theory of accelerated observers is briefly described. Moreover, the main observational aspects of Dirac's equation in noninertial frames of reference are presented. The Galilean invariance of nonrelativistic quantum mechanics and the mass superselection rule are examined in the light of the invariance of physical laws under inhomogeneous Lorentz transformations.Comment: 25 pages, no figures, contribution to Springer Lecture Notes in Physics (Proc. SR 2005, Potsdam, Germany, February 13 - 18, 2005

Expert consensus recommendations on the cardiogenetic care for patients with thoracic aortic disease and their first-degree

Background: Thoracic aortic aneurysm (TAA) is a potentially life-threatening disorder with a strong genetic component. The number of genes implicated in TAA has increased exponentially over the last decade. Approximately 20% of patients with TAA have a positive family history. As most TAA remain asymptomatic for a long time, screening of at risk relatives is warranted to prevent complications. Existing international guidelines lack detailed instructions regarding genetic evaluation and family screening of TAA patients. We aimed to develop a consensus document to provide medical guidance for all health care professionals involved in the recognition, diagnosis and treatment of patients with thoracic aortic disease and their relatives. Methods: A multidisciplinary panel of experts including cardiologists, cardiothoracic surgeons, clinical geneticists and general practitioners, convened to review and discuss the current literature, guidelines and clinical practice on genetic testing and family screening in TAA. Results: There is a lack of high-quality evidence in the literature. This consensus statement, based on the available literature and expert opinions, summarizes our recommendations in order to standardize and optimize the cardiogenetic care for patients and families with thoracic aortic disease. In particular, we provide criteria to identify those patients most likely to have a genetic predisposition, and discuss the preferred modality and frequency of screening in their relatives. Conclusions: Age, family history, aortic size and syndromic features determine who is advised to have genetic testing as well as screening of first-degree relatives. There is a need for more prospective multicenter studies to optimize current recommendations