Quarkonium at finite temperature

Lattice QCD studies on charmonium at finite temperature are presented After a discussion about problems for the Maximum Entropy Method applied to finite temperature lattice QCD, I show several results on charmonium spectral functions. The ``wave function'' of charmonium is also discussed to study the spatial correlation between quark and anti-quark in deconfinement phase.Comment: 8pages, 4figures, talk presented at Hard Probes 200

Frequency-dependent spin susceptibility in the two-dimensional Hubbard model

A Quantum Monte Carlo calculation of dynamical spin susceptibility in the half-filled 2D Hubbard model is presented for temperature $T=0.2t$ and an intermediate on-site repulsion $U=4t$. Using the singular value decomposition technique we succeed in analytically continuing the Matsubara Green's function into the real frequency domain and in deriving the spectral representation for the longitudinal and transverse spin susceptibility. The simulation results, while contradicting the random-phase approximation prediction of antiferromagnetic long-range order at this temperature, are in agreement with an extension of a self-consistent renormalization approach of Moriya. The static susceptibility calculated using this technique is qualitatively consistent with the $\omega \rightarrow 0$ simulation results.Comment: 4 pages, Revtex, encoded figs.uu file with 3 figures enclose

Results on Finite Density QCD

A brief summary of the formulation of QCD at finite chemical potental, $\mu$, is presented. The failure of the quenched approximation to the problem is reviewed. Results are presented for dynamical simulations of the theory at strong and intermediate couplings. We find that the problems associated with the quenched theory persist: the onset of non-zero quark number does seem to occur at a chemical potential $\approx { {m_{\pi}} \over 2}$. However analysis of the Lee-Yang zeros of the grand canonical partition function in the complex fugacity plane, ($e^{\mu/T}$), does show signals of critical behaviour in the expected region of chemical potential. Results are presented for a simulation at finite density of the Gross-Neveu model on a $16^3$ lattice near to the chiral limit. Contrary to our simulations of QCD no pathologies were found when $\mu$ passed through the value m_{\pi}/2}.Comment: 14 pages, Latex, 18 eps figures, Review for Tsukuba worksho

Spectral weight function for the half-filled Hubbard model: a singular value decomposition approach

The singular value decomposition technique is used to reconstruct the electronic spectral weight function for a half-filled Hubbard model with on-site repulsion $U=4t$ from Quantum Monte Carlo data. A two-band structure for the single-particle excitation spectrum is found to persist as the lattice size exceeds the spin-spin correlation length. The observed bands are flat in the vicinity of the $(0,\pi),(\pi,0)$ points in the Brillouin zone, in accordance with experimental data for high-temperature superconducting compounds.Comment: 4 pages, Revtex

Density-Induced Breaking of Pairs in the Attractive Hubbard Model

A conserving T-matrix approximation is applied to the two-dimensional attractive Hubbard model in the low-density regime. A set of self-consistent equations is solved in the real-frequency domain to avoid the analytic continuation procedure. By tuning the chemical potential the particle density was varied in the limits 0.01 < n < 0.18. For the value of the attractive potential U=8t the binding energy of pairs monotonically decreases with increasing n, from its zero-density limit 2.3t and vanishes at a critical density n=0.19. A pairing-induced pseudogap in the single-particle density of states is found at low densities and temperatures.Comment: 5 pages, 4 figures, accepted for publication in Phys. Rev. Let

Conformation-specific inhibitory anti-MMP-7 monoclonal antibody sensitizes pancreatic ductal adenocarcinoma cells to chemotherapeutic cell kill

Matrix metalloproteases (MMPs) undergo post-translational modifications including pro-domain shedding. The activated forms of these enzymes are effective drug targets, but generating potent biological inhibitors against them remains challenging. We report the generation of anti-MMP-7 inhibitory monoclonal antibody (GSM-192), using an alternating immunization strategy with an active site mimicry antigen and the activated enzyme. Our protocol yielded highly selective anti-MMP-7 monoclonal antibody, which specifically inhibits MMP-7′ s enzyme activity with high affinity (IC50 = 132 ± 10 nM). The atomic model of the MMP-7-GSM-192 Fab complex exhibited antibody binding to unique epitopes at the rim of the enzyme active site, sterically preventing entry of substrates into the catalytic cleft. In human PDAC biopsies, tissue staining with GSM-192 showed characteristic spatial distribution of activated MMP-7. Treatment with GSM-192 in vitro induced apoptosis via stabilization of cell surface Fas ligand and retarded cell migration. Co-treatment with GSM-192 and chemotherapeutics, gemcitabine and oxaliplatin elicited a synergistic effect. Our data illustrate the advantage of precisely targeting catalytic MMP-7 mediated disease specific activity

Complement as a biological tool to control tumor growth

Deposits of complement components have been documented in several human tumors suggesting a potential involvement of the complement system in tumor immune surveillance. In vitro and in vivo studies have revealed a double role played by this system in tumor progression. Complement activation in the cancer microenvironment has been shown to promote cancer growth through the release of the chemotactic peptide C5a recruiting myeloid suppressor cells. There is also evidence that tumor progression can be controlled by complement activated on the surface of cancer cells through one of the three pathways of complement activation. The aim of this review is to discuss the protective role of complement in cancer with special focus on the beneficial effect of complement-fixing antibodies that are efficient activators of the classical pathway and contribute to inhibit tumor expansion as a result of MAC-mediated cancer cell killing and complement-mediated inflammatory process. Cancer cells are heterogeneous in their susceptibility to complement-induced killing that generally depends on stable and relatively high expression of the antigen and the ability of therapeutic antibodies to activate complement. A new generation of monoclonal antibodies are being developed with structural modification leading to hexamer formation and enhanced complement activation. An important progress in cancer immunotherapy has been made with the generation of bispecific antibodies targeting tumor antigens and able to neutralize complement regulators overexpressed on cancer cells. A great effort is being devoted to implementing combined therapy of traditional approaches based on surgery, chemotherapy and radiotherapy and complement-fixing therapeutic antibodies. An effective control of tumor growth by complement is likely to be obtained on residual cancer cells following conventional therapy to reduce the tumor mass, prevent recurrences and avoid disabilities

In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell - endothelial cell interaction

<p>Abstract</p> <p>Background</p> <p>Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer.</p> <p>Methods</p> <p>Anaesthetized CD rats were mechanically ventilated and 10⁶human HT-29LMM and T84 colon cancer cells were injected intracardially as single cell suspensions. Quantitative in vivo microscopy of the lung was performed in 10 minute intervals for a total of 40 minutes beginning with the time of injection.</p> <p>Results</p> <p>After vehicle treatment of HT-29LMM controls 15.2 ± 5.3; 14.2 ± 7.5; 11.4 ± 5.5; and 15.4 ± 6.5 cells/20 microscopic fields were found adherent within the pulmonary microvasculature in each 10 minute interval. Similar numbers were found after injection of the lung metastasis derived T84 cell line and after treatment of HT-29LMM with unspecific mouse control-IgG. Subsequently, HT-29LMM cells were treated with function blocking antibodies against β1-, β4-, and αv-integrins wich also did not impair tumor cell adhesion in the lung. In contrast, after hydrolization of sialylated glycoproteins on the cells' surface by neuraminidase, we observed impairment of tumor cell adhesion by more than 50% (p < 0.05). The same degree of impairment was achieved by inhibition of P- and L-selectins via animal treatment with fucoidan (p < 0.05) and also by inhibition of the Thomson-Friedenreich (TF)-antigen (p < 0.05).</p> <p>Conclusions</p> <p>These results demonstrate that the initial colon cancer cell adhesion in the capillaries of the lung is predominantly mediated by tumor cell - endothelial cell interactions, possibly supported by platelets. In contrast to reports of earlier studies that metastatic tumor cell adhesion occurs through integrin mediated binding of extracellular matrix proteins in liver, in the lung, the continuously lined endothelium appears to be specifically targeted by circulating tumor cells.</p