The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer

Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications

Stress analysis of a simplified compression plate fixation system for fractured bones

AbstractA three-dimensional finite element model was generated of a plexiglass tube with an attached six-hole stainless steel compression plate to study the mechanics of internal fixation of fractured long bones. To demonstrate the importance of the plate-bone interface, this interface was represented three different ways in the finite element model. A plated tube with a uniform transverse osteotomy gap was also examined to study the mechanics of plated fractured bones. To validate the model, the results for the intact plated tube were compared to composite beam theory and strain gauge data from an instrumented physical model. Applications of the finite element model data included the prediction of screw failure modes, plate-induced osteopenia, and multi-axial strains in an interfragmentary region. The addition of sliding motion between the plate and tube resulted in a deviation from composite beam theory and improved correspondence with strain gage data when compared to a model having the plate and tube securely bonded. Sliding motion resulted in a much smaller region of bone subjected to reduced axial stress levels, which may decrease the extent of plate-induced osteopenia. The complex nature of induced strains in an osteotomy gap was also demonstrated, along with the tendency for failure of the screws nearest the fracture site

Photoemission Spectra in t-J Ladders with Two Legs

Photoemission spectra for the isotropic two-leg t-J ladder are calculated at various hole-doping levels using exact diagonalization techniques. Low-energy sharp features caused by short-range antiferromagnetic correlations are observed at finite doping levels close to half-filling, above the naive Fermi momentum. These features should be observable in angle-resolved photoemission experiments. In addition, the formation of a d-wave pairing condensate as the ratio J/t is increased leads to dynamically generated spectral weight for momenta close to $k_F$ where the $d_{x^2-y^2 }$-order parameter is large.Comment: 9 pages, RevTex, to be published in Phys. Rev. B (RC

Density-Matrix Algorithm for Phonon Hilbert Space Reduction in the Numerical Diagonalization of Quantum Many-Body Systems

Combining density-matrix and Lanczos algorithms we propose a new optimized phonon approach for finite-cluster diagonalizations of interacting electron-phonon systems. To illustrate the efficiency and reliability of our method, we investigate the problem of bipolaron band formation in the extended Holstein Hubbard model.Comment: 14 pages, 6 figures, Workshop on High Performance Computing in Science and Engineering, Stuttgart 200

Effect of Stripes on Electronic States in Underdoped La_{2-x}Sr_xCuO_4

We investigate the electronic states of underdoped La_{2-x}Sr_xCuO_4 (LSCO) by using a microscopic model, i.e., t-t'-t''-J model, containing vertical charge stripes. The numerically exact diagonalization calculation on small clusters shows the consistent explanation of the physical properties in the angle-resolved photoemission, neutron magnetic scattering and optical conductivity experiments such as the antiphase domain and quasi-one-dimensional charge transport. The pair correlation function of the d-channel is suppressed by the stripes. These results demonstrate a crucial role of the stripes in LSCOComment: 4 pages, 4 EPS figures, revised version, to appear in Phys. Rev. Lett. Vol.82, No.25, 199

Electronic States in the Antiferromagnetic Phase of Electron-Doped High-Tc Cuprates

We investigate the electronic states in the antiferromagnetic (AF) phase of electron-doped cuprates by using numerically exact diagonalization technique for a t-t'-t''-J model. When AF correlation develops with decreasing temperature, a gaplike behavior emerges in the optical conductivity. Simultaneously, the coherent motion of carriers due to the same sublattice hoppings is enhanced. We propose that the phase is characterized as an AF state with small Fermi surface around the momentum k=(\pi,0) and (0,\pi). This is a remarkable contrast to the behavior of hole-doped cuprates.Comment: RevTeX, 5 pages, 4 figures, to appear in Phys. Rev. B Brief Report

Using Sputter Deposition to Increase CO Tolerance in a Proton-Exchange Membrane Fuel Cell

Placing a layer of Ru atop a Pt anode increases the carbon monoxide tolerance of proton-exchange membrane fuel cells when oxygen is added to the fuel stream. Sputter-deposited Ru filter anodes composed of a single Ru layer and three Ru layers separated by Nafion-carbon ink, respectively, were compared to Pt, Pt:Ru alloy, and an ink-based Ru filter anodes. The amount of Pt in each anode was 0.15 mg/cm2 and the amount of Ru in each Ru-containing anode was 0.080 mg/cm2. For an anode feed consisting of hydrogen, 200 ppm CO, and 2% O2 (in the form of an air bleed), all Ru filter anodes outperformed the Pt:Ru alloy. The performance of the Pt + single-layer sputtered Ru filter was double that of the Pt:Ru alloy (0.205 vs. 0.103 A/cm2 at 0.6 V). The performance was also significantly greater than that of the ink-based Ru filter (0.149 A/cm2 at 0.6 V). Within the filter region of the anode, it is likely that the decreased hydrogen kinetics of the Ru (compared to Pt) allow for more of the OHads formed from oxygen in the fuel stream to oxidize adsorbed CO to CO2

A simple rule for axon outgrowth and synaptic competition generates realistic connection lengths and filling fractions

Neural connectivity at the cellular and mesoscopic level appears very specific and is presumed to arise from highly specific developmental mechanisms. However, there are general shared features of connectivity in systems as different as the networks formed by individual neurons in Caenorhabditis elegans or in rat visual cortex and the mesoscopic circuitry of cortical areas in the mouse, macaque, and human brain. In all these systems, connection length distributions have very similar shapes, with an initial large peak and a long flat tail representing the admixture of long-distance connections to mostly short-distance connections. Furthermore, not all potentially possible synapses are formed, and only a fraction of axons (called filling fraction) establish synapses with spatially neighboring neurons. We explored what aspects of these connectivity patterns can be explained simply by random axonal outgrowth. We found that random axonal growth away from the soma can already reproduce the known distance distribution of connections. We also observed that experimentally observed filling fractions can be generated by competition for available space at the target neurons--a model markedly different from previous explanations. These findings may serve as a baseline model for the development of connectivity that can be further refined by more specific mechanisms.Comment: 31 pages (incl. supplementary information); Cerebral Cortex Advance Access published online on May 12, 200

Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter

Recently, four genes (TAP1, TAP2, LMP2, LMP7) involved or potentially involved in the processing and transport of major histocompatibility complex class I-associated antigen to the endoplasmic reticulum have been identified. We now report the initial characterization of the bidirectional promoter for the human transporter associated with antigen processing 1 (TAP1) and low molecular mass polypeptide 2 (LMP2) genes. These genes are divergently transcribed from a central promoter region of only 593 bp. Functional analysis using a bidirectional reporter system demonstrates the minimal 593-bp promoter is sufficient for concurrent expression in both directions. There is no TATA box homology at either end but there is a prevalence of GC boxes. Transcription is initiated at multiple sites for each gene without any of the TAP1 transcripts overlapping with the LMP2 transcripts. The region proximal to the TAP1 gene is required for maximal basal level expression of not only TAP1 but also LMP2. Furthermore, this region is necessary for tumor necrosis factor alpha (TNF-alpha) induction of both genes. Site-specific mutations of an NF-kappa B element in the TAP1 proximal region blocked induction by TNF-alpha in both the TAP1 and LMP2 directions. An adjacent GC box was required for basal expression of both genes as well as augmenting the TNF-alpha induction of the distal LMP2 gene. In vivo genomic foot-printing of this region revealed strong protein/DNA interactions at the NF-kappa B and GC box consensus sequences. In vitro binding studies confirmed the capacity of the NF- kappa B site to bind p50/p65 and p52/p65 heterodimers and of the GC box to bind Sp1. Thus, the promoter elements proximal to the TAP1 gene play a significant role in regulating basal and induced expression of both TAP1 and LMP2. The findings presented in this report clearly link LMP2 expression with TAP1 expression and provide additional suggestive evidence linking LMP2 to class I antigen presentation

Quantum Monte Carlo Study of Hole Binding and Pairing Correlations in the Three-Band Hubbard Model

We simulated the 3-band Hubbard model using the Constrained Path Monte Carlo (CPMC) method in search for a possible superconducting ground state. The CPMC is a ground state method which is free of the exponential scaling of computing time with system size. We calculated the binding energy of a pair of holes for systems up to $6 \times 4$ unit cells. We also studied the pairing correlation functions versus distance for both the d-wave and extended s-wave channels in systems up to $6 \times 6$. We found that holes bind for a wide range of parameters and that the binding increased as the system size is increased. However, the pairing correlation functions decay quickly with distance. For the extended s channel, we found that as the Coulomb interaction $U_d$ on the Cu sites is increased, the long-range part of the correlation functions is suppressed and fluctuates around zero. For the $d_{x^2 - y^2}$ channel, we found that the correlations decay rapidly with distance towards a small positive value. However, this value becomes smaller as the interaction $U_d$ or the system size is increased.Comment: 21 pages, 13 Postscript figures, Submitted to Phys. Rev.