Isogeometric Boundary-Element Analysis for the Wave-Resistance Problem using T-splines

In this paper we couple collocated Boundary Element Methods (BEM) with unstructured analysis suitable T-spline surfaces for solving a linear Boundary Integral Equation (BIE) arising in the context of a ship-hydrodynamic problem, namely the so-called Neumann-Kelvin problem, following the formulation by Brard (1972) [1] and Baar & Price (1988) [2]. The local-refinement capabilities of the adopted T-spline bases, which are used for representing both the geometry of the hull and approximating the solution of the associated BIE, in accordance with the Isogeometric concept proposed by Hughes et al. (2005) [3], lead to a solver that achieves the same error level for many fewer degrees of freedom as compared with the corresponding NURBS-based Isogeometric-BEM solver recently developed in Belibassakis et al. (2013) [4]. In this connection, this paper makes a step towards integrating modern CAD representations for ship-hulls with hydrodynamic solvers of improved accuracy and efficiency, which is a prerequisite for building efficient ship-hull optimizers

A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding

In bacterial c-type cytochromes, the haem cofactor is covalently attached via two cysteine residues organized in a haem c-binding motif. Here, a novel octa-haem c protein, MccA, is described that contains only seven conventional haem c-binding motifs (CXXCH), in addition to several single cysteine residues and a conserved CH signature. Mass spectrometric analysis of purified MccA from Wolinella succinogenes suggests that two of the single cysteine residues are actually part of an unprecedented CX15CH sequence involved in haem c binding. Spectroscopic characterization of MccA identified an unusual high-potential haem c with a red-shifted absorption maximum, not unlike that of certain eukaryotic cytochromes c that exceptionally bind haem via only one thioether bridge. A haem lyase gene was found to be specifically required for the maturation of MccA in W. succinogenes. Equivalent haem lyase-encoding genes belonging to either the bacterial cytochrome c biogenesis system I or II are present in the vicinity of every known mccA gene suggesting a dedicated cytochrome c maturation pathway. The results necessitate reconsideration of computer-based prediction of putative haem c-binding motifs in bacterial proteomes

Resonant transmission through an open quantum dot

We have measured the low-temperature transport properties of a quantum dot formed in a one-dimensional channel. In zero magnetic field this device shows quantized ballistic conductance plateaus with resonant tunneling peaks in each transition region between plateaus. Studies of this structure as a function of applied perpendicular magnetic field and source-drain bias indicate that resonant structure deriving from tightly bound states is split by Coulomb charging at zero magnetic field.Comment: To be published in Phys. Rev. B (1997). 8 LaTex pages with 5 figure

In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds

The calcium/calmodulin‐dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The deregulation of CAMKK2 is linked to several diseases, suggesting the utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work, we demonstrate that STO‐609, frequently described as a selective inhibitor for CAMKK2, potently inhibits a significant number of other kinases. Through an analysis of literature and public databases, we have identified other potent CAMKK2 inhibitors and verified their activities in differential scanning fluorimetry and enzyme inhibition assays. These inhibitors are potential starting points for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology.252CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465651/2014-32013/50724-5; 2014/50897-0; 2019/14275-

Towards a New Standard Model for Black Hole Accretion

We briefly review recent developments in black hole accretion disk theory, emphasizing the vital role played by magnetohydrodynamic (MHD) stresses in transporting angular momentum. The apparent universality of accretion-related outflow phenomena is a strong indicator that large-scale MHD torques facilitate vertical transport of angular momentum. This leads to an enhanced overall rate of angular momentum transport and allows accretion of matter to proceed at an interesting rate. Furthermore, we argue that when vertical transport is important, the radial structure of the accretion disk is modified at small radii and this affects the disk emission spectrum. We present a simple model demonstrating how energetic, magnetically-driven outflows modify the emergent disk emission spectrum with respect to that predicted by standard accretion disk theory. A comparison of the predicted spectra against observations of quasar spectral energy distributions suggests that mass accretion rates inferred using the standard disk model may severely underestimate their true values.Comment: To appear in the Fifth Stromlo Symposium Proceedings special issue of ApS

Automated echocardiographic detection of heart failure with preserved ejection fraction using artificial intelligence

Background: Detection of heart failure with preserved ejection fraction (HFpEF) involves integration of multiple imaging and clinical features which are often discordant or indeterminate. Objectives: We applied artificial intelligence (AI) to analyze a single apical four-chamber (A4C) transthoracic echocardiogram videoclip to detect HFpEF. Methods: A three-dimensional convolutional neural network was developed and trained on A4C videoclips to classify patients with HFpEF (diagnosis of HF, EF≥50%, and echocardiographic evidence of increased filling pressure; cases) versus without HFpEF (EF≥50%, no diagnosis of HF, normal filling pressure; controls). Model outputs were classified as HFpEF, no HFpEF, or non-diagnostic (high uncertainty). Performance was assessed in an independent multi-site dataset and compared to previously validated clinical scores. Results: Training and validation included 2971 cases and 3785 controls (validation holdout, 16.8% patients), and demonstrated excellent discrimination (AUROC:0.97 [95%CI:0.96-0.97] and 0.95 [0.93-0.96] in training and validation, respectively). In independent testing (646 cases, 638 controls), 94 (7.3%) were non-diagnostic; sensitivity (87.8%; 84.5-90.9%) and specificity (81.9%; 78.2-85.6%) were maintained in clinically relevant subgroups, with high repeatability and reproducibility. Of 701 and 776 indeterminate outputs from the HFA-PEFF and H2FPEF scores, the AI HFpEF model correctly reclassified 73.5 and 73.6%, respectively. During follow-up (median [IQR]:2.3 [0.5-5.6] years), 444 (34.6%) patients died; mortality was higher in patients classified as HFpEF by AI (hazard ratio [95%CI]:1.9 [1.5-2.4]). Conclusion: An AI HFpEF model based on a single, routinely acquired echocardiographic video demonstrated excellent discrimination of patients with versus without HFpEF, more often than clinical scores, and identified patients with higher mortality

De Sitter and Schwarzschild-De Sitter According to Schwarzschild and De Sitter

When de Sitter first introduced his celebrated spacetime, he claimed, following Schwarzschild, that its spatial sections have the topology of the real projective space RP^3 (that is, the topology of the group manifold SO(3)) rather than, as is almost universally assumed today, that of the sphere S^3. (In modern language, Schwarzschild was disturbed by the non-local correlations enforced by S^3 geometry.) Thus, what we today call "de Sitter space" would not have been accepted as such by de Sitter. There is no real basis within classical cosmology for preferring S^3 to RP^3, but the general feeling appears to be that the distinction is in any case of little importance. We wish to argue that, in the light of current concerns about the nature of de Sitter space, this is a mistake. In particular, we argue that the difference between "dS(S^3)" and "dS(RP^3)" may be very important in attacking the problem of understanding horizon entropies. In the approach to de Sitter entropy via Schwarzschild-de Sitter spacetime, we find that the apparently trivial difference between RP^3 and S^3 actually leads to very different perspectives on this major question of quantum cosmology.Comment: 26 pages, 8 figures, typos fixed, references added, equation numbers finally fixed, JHEP versio

A Step Beyond the Bounce: Bubble Dynamics in Quantum Phase Transitions

We study the dynamical evolution of a phase interface or bubble in the context of a \lambda \phi^4 + g \phi^6 scalar quantum field theory. We use a self-consistent mean-field approximation derived from a 2PI effective action to construct an initial value problem for the expectation value of the quantum field and two-point function. We solve the equations of motion numerically in (1+1)-dimensions and compare the results to the purely classical evolution. We find that the quantum fluctuations dress the classical profile, affecting both the early time expansion of the bubble and the behavior upon collision with a neighboring interface.Comment: 12 pages, multiple figure

Shape-optimization of 2D hydrofoils using an isogeometric BEM solver

In this paper, an optimization procedure, based on an Isogeometric BEM solver for the potential flow, is developed and used for the shape optimization of hydrofoils. The formulation of the exterior potential-flow problem reduces to a Boundary-Integral Equation (BIE) for the associated velocity potential exploiting the null-pressure jump Kutta condition at the trailing edge. The numerical solution of the BIE is performed by an Isogeometric Boundary-Element Method (BEM) combining a generic B-splines parametric modeler for generating hydrofoil shapes, using a set of eight parameters, the very same basis of the geometric representation for representing the velocity potential and collocation at the Greville abscissas of the knot vector of the hydrofoil's B-splines representation. Furthermore, the optimization environment is developed based on the geometric parametric modeler for the hydrofoil, the Isogeometric BEM solver and an optimizer employing a controlled elitist genetic algorithm. Multi-objective hydrofoil shape optimization examples are demonstrated with respect to the criteria (i) maximum lift coefficient and (ii) minimum deviation of the hydrofoil area from a reference area