Monoclonal antibody against cadherin-17 as a potential treatment for liver cancer

This journal suppl. entitled: Abstracts of The International Liver Congress™ 2012 – 47th annual meeting of the European Association for the Study of the Liver / Poster AbstractsBACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major type of liver cancer associated with high mortality. Prognosis is poor in HCC patients largely because of late diagnosis and limitations in treatment options. Therefore, this study aims to identify alternative target for HCC in hope to offer new treatments to patients. Cadherin-17 (CDH17) has been identified as an oncofetal molecule of HCC and that a suppression of its expression by RNA interference (RNAi) leads to anti-tumorigenesis. To supplement the drawbacks associated with the use of RNAi approach in biotherapy, we developed specific antibody against CDH17 for achieving similar purpose. METHODS: Hybridoma cell clones capable of secreting antibodies ...postprin

Neogene-Quaternary post-rift tectonic reactivation of the Bohai Bay Basin, eastern China

Bohai Bay Basin, located in eastern China, is considered a Cenozoic rifted basin. The basin is atypical in terms of its Neogene–Quaternary postrift subsidence history in that it experienced intensive tectonic reactivation, rather than the relative tectonic quiescence experienced during this stage by most rift basins. This Neogene–Quaternary tectonic reactivation arose principally in response to two tectonic events: (1) activity on a dense array of shallow faults and (2) accelerated tectonic subsidence that occurred during the postrift stage. These two events were neither strictly temporally nor spatially equivalent. The dense array of shallow faults form a northwest–southeast-trending belt in the central part of the basin, with displacement induced by the reactivation of older northeast- and northwest-trending basement faults and an associated substantial component of strike-slip displacement occurring after 5.3 Ma. The intensive reactivation of these faults contributed to the atypically accelerated rate of postrift tectonic subsidence of the basin that commenced ca. . However, this was not the sole cause of this accelerated tectonic subsidence: A combination of geological activity deep within the crust led to the buildup of intraplate stresses, and this, combined with ongoing thermal subsidence, acted as an additional contributory factor that drove unusually high rates of subsidence for this basin. This episode of accelerated postrift tectonic reactivation resulted in conditions favorable for hydrocarbon accumulation

Cell sorting in a Petri dish controlled by computer vision.

Fluorescence-activated cell sorting (FACS) applying flow cytometry to separate cells on a molecular basis is a widespread method. We demonstrate that both fluorescent and unlabeled live cells in a Petri dish observed with a microscope can be automatically recognized by computer vision and picked up by a computer-controlled micropipette. This method can be routinely applied as a FACS down to the single cell level with a very high selectivity. Sorting resolution, i.e., the minimum distance between two cells from which one could be selectively removed was 50-70 micrometers. Survival rate with a low number of 3T3 mouse fibroblasts and NE-4C neuroectodermal mouse stem cells was 66 +/- 12% and 88 +/- 16%, respectively. Purity of sorted cultures and rate of survival using NE-4C/NE-GFP-4C co-cultures were 95 +/- 2% and 62 +/- 7%, respectively. Hydrodynamic simulations confirmed the experimental sorting efficiency and a cell damage risk similar to that of normal FACS

Spin correlations in the electron-doped high-transition-temperature superconductor Nd{2-x}Ce{x}CuO{4+/-delta}

High-transition-temperature (high-Tc) superconductivity develops near antiferromagnetic phases, and it is possible that magnetic excitations contribute to the superconducting pairing mechanism. To assess the role of antiferromagnetism, it is essential to understand the doping and temperature dependence of the two-dimensional antiferromagnetic spin correlations. The phase diagram is asymmetric with respect to electron and hole doping, and for the comparatively less-studied electron-doped materials, the antiferromagnetic phase extends much further with doping [1, 2] and appears to overlap with the superconducting phase. The archetypical electron-doped compound Nd{2-x}Ce{x}CuO{4\pm\delta} (NCCO) shows bulk superconductivity above x \approx 0.13 [3, 4], while evidence for antiferromagnetic order has been found up to x \approx 0.17 [2, 5, 6]. Here we report inelastic magnetic neutron-scattering measurements that point to the distinct possibility that genuine long-range antiferromagnetism and superconductivity do not coexist. The data reveal a magnetic quantum critical point where superconductivity first appears, consistent with an exotic quantum phase transition between the two phases [7]. We also demonstrate that the pseudogap phenomenon in the electron-doped materials, which is associated with pronounced charge anomalies [8-11], arises from a build-up of spin correlations, in agreement with recent theoretical proposals [12, 13].Comment: 5 pages, 4 figure

Some Field Theoretic Issues Regarding the Chiral Magnetic Effect

In this paper, we shall address some field theoretic issues regarding the chiral magnetic effect. The general structure of the magnetic current consistent with the electromagnetic gauge invariance is obtained and the impact of the infrared divergence is examined. Some subtleties on the relation between the chiral magnetic effect and the axial anomaly are clarified through a careful examination of the infrared limit of the relevant thermal diagrams.Comment: 19 pages, 4 figures in Latex. Typos fixed, version accepted to be published in JHE

Holographic Anomalous Conductivities and the Chiral Magnetic Effect

We calculate anomaly induced conductivities from a holographic gauge theory model using Kubo formulas, making a clear conceptual distinction between thermodynamic state variables such as chemical potentials and external background fields. This allows us to pinpoint ambiguities in previous holographic calculations of the chiral magnetic conductivity. We also calculate the corresponding anomalous current three-point functions in special kinematic regimes. We compare the holographic results to weak coupling calculations using both dimensional regularization and cutoff regularization. In order to reproduce the weak coupling results it is necessary to allow for singular holographic gauge field configurations when a chiral chemical potential is introduced for a chiral charge defined through a gauge invariant but non-conserved chiral density. We argue that this is appropriate for actually addressing charge separation due to the chiral magnetic effect.Comment: 17 pages, 1 figure. v2: 18 pages, 1 figure, discussion clarified throughout the text, references added, version accepted for publication in JHE

Challenges to the development of antigen-specific breast cancer vaccines

Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor

The nature of the pseudogap phase is a central problem in the quest to understand high-Tc cuprate superconductors. A fundamental question is what symmetries are broken when that phase sets in below a temperature T*. There is evidence from both polarized neutron diffraction and polar Kerr effect measurements that time- reversal symmetry is broken, but at temperatures that differ significantly. Broken rotational symmetry was detected by both resistivity and inelastic neutron scattering at low doping and by scanning tunnelling spectroscopy at low temperature, but with no clear connection to T*. Here we report the observation of a large in-plane anisotropy of the Nernst effect in YBa2Cu3Oy that sets in precisely at T*, throughout the doping phase diagram. We show that the CuO chains of the orthorhombic lattice are not responsible for this anisotropy, which is therefore an intrinsic property of the CuO2 planes. We conclude that the pseudogap phase is an electronic state which strongly breaks four-fold rotational symmetry. This narrows the range of possible states considerably, pointing to stripe or nematic orders.Comment: Published version. Journal reference and DOI adde

Electron-Spin Excitation Coupling in an Electron Doped Copper Oxide Superconductor

High-temperature (high-Tc) superconductivity in the copper oxides arises from electron or hole doping of their antiferromagnetic (AF) insulating parent compounds. The evolution of the AF phase with doping and its spatial coexistence with superconductivity are governed by the nature of charge and spin correlations and provide clues to the mechanism of high-Tc superconductivity. Here we use a combined neutron scattering and scanning tunneling spectroscopy (STS) to study the Tc evolution of electron-doped superconducting Pr0.88LaCe0.12CuO4-delta obtained through the oxygen annealing process. We find that spin excitations detected by neutron scattering have two distinct modes that evolve with Tc in a remarkably similar fashion to the electron tunneling modes in STS. These results demonstrate that antiferromagnetism and superconductivity compete locally and coexist spatially on nanometer length scales, and the dominant electron-boson coupling at low energies originates from the electron-spin excitations.Comment: 30 pages, 12 figures, supplementary information include

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate