Interaction matrix element fluctuations in quantum dots

In the Coulomb blockade regime of a ballistic quantum dot, the distribution of conductance peak spacings is well known to be incorrectly predicted by a single-particle picture; instead, matrix element fluctuations of the residual electronic interaction need to be taken into account. In the normalized random-wave model, valid in the semiclassical limit where the number of electrons in the dot becomes large, we obtain analytic expressions for the fluctuations of two-body and one-body matrix elements. However, these fluctuations may be too small to explain low-temperature experimental data. We have examined matrix element fluctuations in realistic chaotic geometries, and shown that at energies of experimental interest these fluctuations generically exceed by a factor of about 3-4 the predictions of the random wave model. Even larger fluctuations occur in geometries with a mixed chaotic-regular phase space. These results may allow for much better agreement between the Hartree-Fock picture and experiment. Among other findings, we show that the distribution of interaction matrix elements is strongly non-Gaussian in the parameter range of experimental interest, even in the random wave model. We also find that the enhanced fluctuations in realistic geometries cannot be computed using a leading-order semiclassical approach, but may be understood in terms of short-time dynamics.Comment: 12 pages, 6 figures; submitted for conference proceedings of Workshop on Nuclei and Mesoscopic Physics (WNMP07), October 20-22, 2007, East Lansing, Michigan (Pawel Danielewicz, Editor

Beam mismatch effects in Cosmic Microwave Background polarization measurements

Measurement of cosmic microwave background polarization is today a major goal of observational cosmology. The level of the signal to measure, however, makes it very sensitive to various systematic effects. In the case of Planck, which measures polarization by combining data from various detectors, the beam asymmetry can induce a temperature leakage or a polarization mode mixing. In this paper, we investigate this effect using realistic simulated beams and propose a first-order method to correct the polarization power spectra for the induced systematic effect.Comment: Accepted by Astronomy & Astrophysic

Data-Driven Prediction and Design of bZIP Coiled-Coil Interactions

Selective dimerization of the basic-region leucine-zipper (bZIP) transcription factors presents a vivid example of how a high degree of interaction specificity can be achieved within a family of structurally similar proteins. The coiled-coil motif that mediates homo- or hetero-dimerization of the bZIP proteins has been intensively studied, and a variety of methods have been proposed to predict these interactions from sequence data. In this work, we used a large quantitative set of 4,549 bZIP coiled-coil interactions to develop a predictive model that exploits knowledge of structurally conserved residue-residue interactions in the coiled-coil motif. Our model, which expresses interaction energies as a sum of interpretable residue-pair and triplet terms, achieves a correlation with experimental binding free energies of R = 0.68 and significantly out-performs other scoring functions. To use our model in protein design applications, we devised a strategy in which synthetic peptides are built by assembling 7-residue native-protein heptad modules into new combinations. An integer linear program was used to find the optimal combination of heptads to bind selectively to a target human bZIP coiled coil, but not to target paralogs. Using this approach, we designed peptides to interact with the bZIP domains from human JUN, XBP1, ATF4 and ATF5. Testing more than 132 candidate protein complexes using a fluorescence resonance energy transfer assay confirmed the formation of tight and selective heterodimers between the designed peptides and their targets. This approach can be used to make inhibitors of native proteins, or to develop novel peptides for applications in synthetic biology or nanotechnology.National Institutes of Health (U.S.) (Award GM067681

Atomic Force Microscopy and Optical Studies of Organic Thin Films with Hydrogen-Bonded Networks

Brewster angle microscopy and atomic force microscopy were used to characterize the surface morphology of thin films in situ or after transfer onto solid supports. Two acids were studied, differing in carboxylic acid head groups, resulting in significantly different morphological features for thin films formed from these two amphiphiles on a Langmuir trough. Differences in self-assembly and domain sizes were correlated with the formation of hydrogen-bonded networks. The influence of surface hydrophobicity or hydrophilicity during deposition on morphology was also characterized, with spherulitic features appearing in some samples

Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

<p>Abstract</p> <p>Background</p> <p>Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.</p> <p>Results</p> <p>In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells.</p> <p>Conclusions</p> <p>Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.</p

Uncertainty explicit assessment of off-the-shelf software: A Bayesian approach

Assessment of software COTS components is an essential part of component-based software development. Poorly chosen components may lead to solutions of low quality and that are difficult to maintain. The assessment may be based on incomplete knowledge about the COTS component itself and other aspects (e.g. vendor’s credentials, etc.), which may affect the decision of selecting COTS component(s). We argue in favor of assessment methods in which uncertainty is explicitly represented (‘uncertainty explicit’ methods) using probability distributions. We provide details of a Bayesian model, which can be used to capture the uncertainties in the simultaneous assessment of two attributes, thus, also capturing the dependencies that might exist between them. We also provide empirical data from the use of this method for the assessment of off-the-shelf database servers which illustrate the advantages of ‘uncertainty explicit’ methods over conventional methods of COTS component assessment which assume that at the end of the assessment the values of the attributes become known with certainty

Patient- and physician-related risk factors for hyperkalaemia in potassium-increasing drug-drug interactions

Purpose: Hyperkalaemia due to potassium-increasing drug-drug interactions (DDIs) is a clinically important adverse drug event. The purpose of this study was to identify patient- and physician-related risk factors for the development of hyperkalaemia. Methods: The risk for adult patients hospitalised in the University Hospital Zurich between 1 December 2009 and 31 December 2011 of developing hyperkalaemia was correlated with patient characteristics, number, type and duration of potassium-increasing DDIs and frequency of serum potassium monitoring. Results: The 76,467 patients included in this study were prescribed 8,413 potentially severe potassium-increasing DDIs. Patient-related characteristics associated with the development of hyperkalaemia were pulmonary allograft [relative risk (RR) 5.1; p 48h: RR 1.6; p < 0.01). Conclusion: Strategies for reducing the risk of hyperkalaemia during potassium-increasing DDIs should consider both patient- and physician-related risk factors

Limitations of the heavy-baryon expansion as revealed by a pion-mass dispersion relation

The chiral expansion of nucleon properties such as mass, magnetic moment, and magnetic polarizability are investigated in the framework of chiral perturbation theory, with and without the heavy-baryon expansion. The analysis makes use of a pion-mass dispersion relation, which is shown to hold in both frameworks. The dispersion relation allows an ultraviolet cutoff to be implemented without compromising the symmetries. After renormalization, the leading-order heavy-baryon loops demonstrate a stronger dependence on the cutoff scale, which results in weakened convergence of the expansion. This conclusion is tested against the recent results of lattice quantum chromodynamics simulations for nucleon mass and isovector magnetic moment. In the case of the polarizability, the situation is even more dramatic as the heavy-baryon expansion is unable to reproduce large soft contributions to this quantity. Clearly, the heavy-baryon expansion is not suitable for every quantity.Comment: Accepted for publication in EPJ C. Made changes based on referee comments: clarifying sentences to conclusion 1. of Section IV, beginning of Section V, and new footnote in Section VI, page 8. Added more detailed explanation in paragraph 4 of Section III. Added citations of Phys.Rev. D60, 034014, and Phys.Lett. B716, 33

Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6)

Aims Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. Methods and results The electrocardiogram of the affected member of a single family revealed a QT interval of 317 ms (QTc 329 ms) with tall, narrow, and symmetrical T-waves. Invasive electrophysiological testing showed short ventricular refractory periods and increased vulnerability to induce ventricular fibrillation. DNA screening of the patient identified no mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p.Ser755Thr), coding for the Cavα2δ-1 subunit of the L-type calcium channel. The pathogenic role of the p.Ser755Thr variant of the CACNA2D1 gene was analysed by using co-expression of the two other L-type calcium channel subunits, Cav1.2α1 and Cavβ2b, in HEK-293 cells. Barium currents (IBa) were recorded in these cells under voltage-clamp conditions using the whole-cell configuration. Co-expression of the p.Ser755Thr Cavα2δ-1 subunit strongly reduced the IBa by more than 70% when compared with the co-expression of the wild-type (WT) variant. Protein expression of the three subunits was verified by performing western blots of total lysates and cell membrane fractions of HEK-293 cells. The p.Ser755Thr variant of the Cavα2δ-1 subunit was expressed at a similar level compared with the WT subunit in both fractions. Since the mutant Cavα2δ-1 subunit did not modify the expression of the pore-forming subunit of the L-type calcium channel, Cav1.2α1, it suggests that single channel biophysical properties of the L-type channel are altered by this variant. Conclusion In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS. It remains to be determined whether mutations in this gene lead to other manifestations of the J-wave syndrom

p73 Regulates Neurodegeneration and Phospho-Tau Accumulation during Aging and Alzheimer's Disease

SummaryThe genetic mechanisms that regulate neurodegeneration are only poorly understood. We show that the loss of one allele of the p53 family member, p73, makes mice susceptible to neurodegeneration as a consequence of aging or Alzheimer's disease (AD). Behavioral analyses demonstrated that old, but not young, p73+/− mice displayed reduced motor and cognitive function, CNS atrophy, and neuronal degeneration. Unexpectedly, brains of aged p73+/− mice demonstrated dramatic accumulations of phospho-tau (P-tau)-positive filaments. Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. The increase in P-tau was likely mediated by JNK; in p73+/− neurons, the activity of the p73 target JNK was enhanced, and JNK regulated P-tau levels. Thus, p73 is essential for preventing neurodegeneration, and haploinsufficiency for p73 may be a susceptibility factor for AD and other neurodegenerative disorders