Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine

Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.     

Acceptability of genetically modified cheese presented as real product alternative

European consumers, in general, have negative attitudes towards the use of gene technology in food production. The objective of this study was to examine whether taste and health benefits influence the acceptability of genetically modified (gm) products when they are presented as real product alternatives. Consumers in Denmark, Finland, Norway and Sweden (n=738) assessed two cheeses: one was labelled as genetically modified (preferred in an earlier product test) and the other as conventional (neutral in an earlier product test). A smaller control group received two cheeses with blind codes. Labelling decreased consumers' intentions to buy the originally preferred gm-labelled cheese, but still the intentions were at the same level with the conventionally labelled option. Participants chose two gm cheeses out of five possible when given the option to take cheese home after tasting. Intentions to buy gm cheese could best be explained by respondents' attitudes towards gene technology and perceived taste benefits. General health interest was also a reinforcer of intentions for gm cheese with reduced fat content.     

Visualizing transport structures of time-dependent flow fields

This article focuses on the transport characteristics of physical properties in fluids-in particular, visualizing the finite-time transport structure of property advection. Applied to a well-chosen set of property fields, the proposed approach yields structures giving insights into the underlying flow's dynamic processes.     

Topology‐based Smoothing of 2D Scalar Fields with C1‐Continuity

Data sets coming from simulations or sampling of real‐world phenomena often contain noise that hinders their processing and analysis. Automatic filtering and denoising can be challenging: when the nature of the noise is unknown, it is difficult to distinguish between noise and actual data features; in addition, the filtering process itself may introduce “artificial” features into the data set that were not originally present. In this paper, we propose a smoothing method for 2D scalar fields that gives the user explicit control over the data features. We define features as critical points of the given scalar function, and the topological structure they induce (i.e., the Morse‐Smale complex). Feature significance is rated according to topological persistence. Our method allows filtering out spurious features that arise due to noise by means of topological simplification, providing the user with a simple interface that defines the significance threshold, coupled with immediate visual feedback of the remaining data features. In contrast to previous work, our smoothing method guarantees a C¹‐continuous output scalar field with the exact specified features and topological structures.     

Smooth Shape‐Aware Functions with Controlled Extrema

Functions that optimize Laplacian‐based energies have become popular in geometry processing, e.g. for shape deformation, smoothing, multiscale kernel construction and interpolation. Minimizers of Dirichlet energies, or solutions of Laplace equations, are harmonic functions that enjoy the maximum principle, ensuring no spurious local extrema in the interior of the solved domain occur. However, these functions are only C⁰ at the constrained points, which often causes smoothness problems. For this reason, many applications optimize higher‐order Laplacian energies such as biharmonic or triharmonic. Their minimizers exhibit increasing orders of continuity but lose the maximum principle and show oscillations. In this work, we identify characteristic artifacts caused by spurious local extrema, and provide a framework for minimizing quadratic energies on manifolds while constraining the solution to obey the maximum principle in the solved region. Our framework allows the user to specify locations and values of desired local maxima and minima, while preventing any other local extrema. We demonstrate our method on the smoothness energies corresponding to popular polyharmonic functions and show its usefulness for fast handle‐based shape deformation, controllable color diffusion, and topologically‐constrained data smoothing.     

采用新型QUICC Engine技术的PowerQUICC Ⅱ处理器瞄准IP融合市场解决兼容和成本问题

通信行业正在迅速从电路交换网络迁移到基于互联网协议(IP)的分组交换网络.IP融合实现了宽带部署、"三网合一"(语音/视频/数据)业务、3G无线和其它通信业务,它们正在为消费者、服务提供商和设备制造商创造令人激动的新机遇.     

Spatiotemporal EEG/MEG source analysis based on a parametric noise covariance model

A method is described to incorporate the spatiotemporal noise covariance matrix into a spatiotemporal source analysis. The essential feature is that the estimation problem is split into two parts. First, a model is fitted to the observed noise covariance matrix. This model is a Kronecker product of a spatial and a temporal matrix. The spatial matrix models the spatial covariances by a function dependent on sensor distance. The temporal matrix models the temporal covariances as lag dependent. In the second part, sources are estimated given this noise model, which can be done very efficiently due to the Kronecker formulation. An application to real electroencephalogram (EEG) data shows that the noise model fits the data very well. Simulation results show that the resulting source estimates are more precise than those obtained from a standard analysis neglecting the noise covariance. In addition, the estimated standard errors of the source parameter estimates are far more precise than those obtained from a standard analysis. Finally, the source parameter standard errors are used to investigate the effects of temporal sampling. It is shown that increasing the sampling by a factor x, decreases the standard errors of all source parameters with the square root of x.     

Kinematics of the heart: strain-rate imaging from time-resolved three-dimensional phase contrast MRI

A four-dimensional mapping (three spatial dimensions + time) of myocardial strain-rate would help to describe the mechanical properties of the myocardium, which affect important physiological factors such as the pumping performance of the ventricles. Strain-rate represents the local instantaneous deformation of the myocardium and can be calculated from the spatial gradients of the velocity field. Strain-rate has previously been calculated using one-dimensional (ultrasound) or two-dimensional (2-D) magnetic resonance imaging) techniques. However, this assumes that myocardial motion only occurs in one direction or in one plane, respectively. This paper presents a method for calculation of the time-resolved three-dimensional (3-D) strain-rate tensor using velocity vector information in a 3-D spatial grid during the whole cardiac cycle. The strain-rate tensor provides full information of both magnitude and direction of the instantaneous deformation of the myocardium. A method for visualization of the full 3-D tensor is also suggested. The tensors are visualized using ellipsoids, which display the principal directions of strain-rate and the ratio between strain-rate magnitude in each direction. The presented method reveals the principal strain-rate directions without a priori knowledge of myocardial motion directions.