Feasibility of low-dose coronary CT angiography: first experience with prospective ECG-gating

AIMS: To determine the feasibility of prospective electrocardiogram (ECG)-gating to achieve low-dose computed tomography coronary angiography (CTCA). METHODS AND RESULTS: Forty-one consecutive patients with suspected (n = 35) or known coronary artery disease (n = 6) underwent 64-slice CTCA using prospective ECG-gating. Individual radiation dose exposure was estimated from the dose-length product. Two independent readers semi-quantitatively assessed the overall image quality on a five-point scale and measured vessel attenuation in each coronary segment. One patient was excluded for atrial fibrillation. Mean effective radiation dose was 2.1 +/- 0.6 mSv (range, 1.1-3.0 mSv). Image quality was inversely related to heart rate (HR) (57.3 +/- 6.2, range 39-66 b.p.m.; r = 0.58, P 63 b.p.m. (P < 0.001). CONCLUSION: This first experience documents the feasibility of prospective ECG-gating for CTCA with diagnostic image quality at a low radiation dose (1.1-3.0 mSv), favouring HR <63 b.p.

Feasibility of low-dose coronary CT angiography: first experience with prospective ECG-gating

AIMS: To determine the feasibility of prospective electrocardiogram (ECG)-gating to achieve low-dose computed tomography coronary angiography (CTCA). METHODS AND RESULTS: Forty-one consecutive patients with suspected (n = 35) or known coronary artery disease (n = 6) underwent 64-slice CTCA using prospective ECG-gating. Individual radiation dose exposure was estimated from the dose-length product. Two independent readers semi-quantitatively assessed the overall image quality on a five-point scale and measured vessel attenuation in each coronary segment. One patient was excluded for atrial fibrillation. Mean effective radiation dose was 2.1 +/- 0.6 mSv (range, 1.1-3.0 mSv). Image quality was inversely related to heart rate (HR) (57.3 +/- 6.2, range 39-66 b.p.m.; r = 0.58, P 63 b.p.m. (P < 0.001). CONCLUSION: This first experience documents the feasibility of prospective ECG-gating for CTCA with diagnostic image quality at a low radiation dose (1.1-3.0 mSv), favouring HR <63 b.p.

Metal-insulator Crossover Behavior at the Surface of NiS_2

We have performed a detailed high-resolution electron spectroscopic investigation of NiS$_2$ and related Se-substituted compounds NiS$_{2-x}$Se$_x$, which are known to be gapped insulators in the bulk at all temperatures. A large spectral weight at the Fermi energy of the room temperature spectrum, in conjunction with the extreme surface sensitivity of the experimental probe, however, suggests that the surface layer is metallic at 300 K. Interestingly, the evolution of the spectral function with decreasing temperature is characterized by a continuous depletion of the single-particle spectral weight at the Fermi energy and the development of a gap-like structure below a characteristic temperature, providing evidence for a metal-insulator crossover behavior at the surfaces of NiS$_2$ and of related compounds. These results provide a consistent description of the unusual transport properties observed in these systems.Comment: 12 pages, 3 figure

Scaling of the Conductivity with Temperature and Uniaxial Stress in Si:B at the Metal-Insulator Transition

Using uniaxial stress to tune Si:B through the metal-insulator transition we find the conductivity at low temperatures shows an excellent fit to scaling with temperature and stress on both sides of the transition. The scaling functions yield the conductivity in the metallic and insulating phases, and allow a reliable determination of the temperature dependence in the critical regions on both sides of the transition

Disorder effects in electronic structure of substituted transition metal compounds

Investigating LaNi(1-x)M(x)O3 (M = Mn and Fe), we identify a characteristic evolution of the spectral function with increasing disorder in presence of strong interaction effects across the metal-insulator transition. We discuss these results vis-a-vis existing theories of electronic structure in simultaneous presence of disorder and interaction.Comment: Revtex, 4 pages, 3 postscript figures (To appear in Phys. Rev. Lett

K^0 pi^0 Sigma^+ and K^*0 Sigma^+ photoproduction off the proton

The exclusive reactions $\gamma p \to K^{*0} \Sigma^+(1189)$ and $\gamma p \to K^{0} \pi^{0}\Sigma^+(1189)$, leading to the p 4$\pi^{0}$ final state, have been measured with a tagged photon beam for incident energies from threshold up to 2.5 GeV. The experiment has been performed at the tagged photon facility of the ELSA accelerator (Bonn). The Crystal Barrel and TAPS detectors were combined to a photon detector system of almost 4$\pi$ geometrical acceptance. Differential and total cross sections are reported. At energies close to the threshold, a flat angular distribution has been observed for the reaction $\gamma p\to K^{0} \pi^{0}\Sigma^+$ suggesting dominant s-channel production. $\Sigma^*(1385)$ and higher lying hyperon states have been observed. An enhancement in the forward direction in the angular distributions of the reaction $\gamma p \to K^{*0}\Sigma^+$ indicates a $t$-channel exchange contribution to the reaction mechanism. The experimental data are in reasonable agreement with recent theoretical predictions.Comment: 11 pages, 13 figures, submitted to EPJ

Overexpression of Cathepsin Z Contributes to Tumor Metastasis by Inducing Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

The aim of this study was to characterize the oncogenic function and mechanism of Cathepsin Z (CTSZ) at 20q13.3, a frequently amplified region in hepatocellular carcinoma (HCC). Real-time PCR were used to compare CTSZ expression between paired HCC tumor and non-tumor specimens. CTSZ gene was stably transfected into HCC line QGY-7703 cells and its role in tumorigenicity and cell motility was characterized by soft agar, wound-healing, transwell invasion and cell adhesion assay, and tumor xenograft mouse model. Western blot analysis was used to study expression of proteins associated with epithelial-mesenchymal transition (EMT)

Pro-autophagic signal induction by bacterial pore-forming toxins

Pore-forming toxins (PFT) comprise a large, structurally heterogeneous group of bacterial protein toxins. Nucleated target cells mount complex responses which allow them to survive moderate membrane damage by PFT. Autophagy has recently been implicated in responses to various PFT, but how this process is triggered is not known, and the significance of the phenomenon is not understood. Here, we show that S. aureus α-toxin, Vibrio cholerae cytolysin, streptolysin O and E. coli haemolysin activate two pathways leading to autophagy. The first pathway is triggered via AMP-activated protein kinase (AMPK). AMPK is a major energy sensor which induces autophagy by inhibiting the target of rapamycin complex 1 (TORC1) in response to a drop of the cellular ATP/AMP-ratio, as is also observed in response to membrane perforation. The second pathway is activated by the conserved eIF2α-kinase GCN2, which causes global translational arrest and promotes autophagy in response to starvation. The latter could be accounted for by impaired amino acid transport into target cells. Notably, PKR, an eIF2α-kinase which has been implicated in autophagy induction during viral infection, was also activated upon membrane perforation, and evidence was obtained that phosphorylation of eIF2α is required for the accumulation of autophagosomes in α-toxin-treated cells. Treatment with 3-methyl-adenine inhibited autophagy and disrupted the ability of cells to recover from sublethal attack by S. aureus α-toxin. We propose that PFT induce pro-autophagic signals through membrane perforation–dependent nutrient and energy depletion, and that an important function of autophagy in this context is to maintain metabolic homoeostasis

Hypoxia and the Hypoxic Response Pathway Protect against Pore-Forming Toxins in C. elegans

Pore-forming toxins (PFTs) are by far the most abundant bacterial protein toxins and are important for the virulence of many important pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although many cellular responses to PFTs have been recorded, little is understood about their relevance to pathological or defensive outcomes. To shed light on this important question, we have turned to the only genetic system for studying PFT-host interactions—Caenorhabditis elegans intoxication by Crystal (Cry) protein PFTs. We mutagenized and screened for C. elegans mutants resistant to a Cry PFT and recovered one mutant. Complementation, sequencing, transgenic rescue, and RNA interference data demonstrate that this mutant eliminates a gene normally involved in repression of the hypoxia (low oxygen response) pathway. We find that up-regulation of the C. elegans hypoxia pathway via the inactivation of three different genes that normally repress the pathway results in animals resistant to Cry PFTs. Conversely, mutation in the central activator of the hypoxia response, HIF-1, suppresses this resistance and can result in animals defective in PFT defenses. These results extend to a PFT that attacks mammals since up-regulation of the hypoxia pathway confers resistance to Vibrio cholerae cytolysin (VCC), whereas down-regulation confers hypersusceptibility. The hypoxia PFT defense pathway acts cell autonomously to protect the cells directly under attack and is different from other hypoxia pathway stress responses. Two of the downstream effectors of this pathway include the nuclear receptor nhr-57 and the unfolded protein response. In addition, the hypoxia pathway itself is induced by PFT, and low oxygen is protective against PFT intoxication. These results demonstrate that hypoxia and induction of the hypoxia response protect cells against PFTs, and that the cellular environment can be modulated via the hypoxia pathway to protect against the most prevalent class of weapons used by pathogenic bacteria