Topological Structure of Dense Hadronic Matter

We present a summary of work done on dense hadronic matter, based on the Skyrme model, which provides a unified approach to high density, valid in the large $N_c$ limit. In our picture, dense hadronic matter is described by the {\em classical} soliton configuration with minimum energy for the given baryon number density. By incorporating the meson fluctuations on such ground state we obtain an effective Lagrangian for meson dynamics in a dense medium. Our starting point has been the Skyrme model defined in terms of pions, thereafter we have extended and improved the model by incorporating other degrees of freedom such as dilaton, kaons and vector mesons.Comment: 13 pages, 8 figures, Talk given at the KIAS-APCTP Symposium in Astro-Hadron Physics "Compact Stars: Quest for New States of Dense Matter", November 10-14, 2003, Seoul, Korea, published by World Scientific. Based on talk by B.-Y. Par

The pion velocity in dense skyrmion matter

We have developed a field theory formalism to calculate in-medium properties of hadrons within a unified approach that exploits a single Lagrangian to describe simultaneously both matter background and meson fluctuations. In this paper we discuss the consequences on physical observables of a possible phase transition of hadronic matter taking place in the chiral limit. We pay special attention to the pion velocity vπ, which controls, through a dispersion relation, the pion propagation in the hadronic medium. The vπ is defined in terms of parameters related to the matrix element in matter of the axial-vector current, namely, the in-medium pion decay constants, ft and fs. Both of the pion decay constants change dramatically with density and even vanish in the chiral limit when chiral symmetry is restored, but the pion velocity does not go to zero, decreasing at most 10% over the whole density range studied. A possible pseudogap structure is indicated

Early onset of colorectal cancer in a 13-year-old girl with Lynch syndrome

Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells

Unified Approach to Dense Matter

We apply the Skyrme model to dense hadronic matter, which provides a unified approach to high density, valid in the large Nc limit. In our picture, dense hadronic matter is described by the classical soliton configuration with minimum energy for the given baryon number density. By incorporating the meson fluctuations on such ground state we obtain an effective Lagrangian for meson dynamics in a dense medium. Our starting point has been the Skyrme model defined in terms of pions, thereafter we have extended and improved the model by incorporating other degrees of freedom such as dilaton, kaons and vector mesons.Comment: 6 pages, 4 figures, a talk given at the international conference QCD DOWN UNDER, March 10 - 19, Adelaide, Australi

Sliding Vacua in Dense Skyrmion Matter

In continuation of our systematic effort to understand hadronic matter at high density, we study dense skyrmion matter and its chiral phase structure in an effective field theory implemented with the trace anomaly of QCD applicable in the large $N_c$ limit. By incorporating a dilaton field $\chi$ associated with broken conformal symmetry of QCD into the simplest form of skyrmion Lagrangian, we simulate the effect of "sliding vacua" influenced by the presence of matter and obtain what could correspond to the ``intrinsic dependence" on the background of the system, i.e., matter density or temperature, that results when a generic chiral effective field theory of strong interactions is matched to QCD at a matching scale near the chiral scale $\Lambda_\chi \sim 4\pi f_\pi\sim 1$ GeV. The properties of the Goldstone pions and the dilaton scalar near the chiral phase transition are studied by looking at the pertinent excitations of given quantum numbers on top of a skyrmion matter and their behavior in the vicinity of the phase transition from Goldstone mode to Wigner mode characterized by the changeover from the FCC crystal to the half-skyrmion CC crystal. We recover from the model certain features that are connected to Brown-Rho scaling and that suggest how to give a precise meaning to the latter in the framework of an effective field theory that is matched to QCD .Comment: 23 pages, 8 figure

The Proton Spin in the Chiral Bag Model : Casimir Contribution and Cheshire Cat Principle

The flavor singlet axial charge has been a source of study in the last years due to its relation to the so called {\it Proton Spin Problem}. The relevant flavor singlet axial current is anomalous, i.e., its divergence contains a piece which is the celebrated $U_A(1)$ anomaly. This anomaly is intimately associated with the $\eta^\prime$ meson, which gets its mass from it. When the gauge degrees of freedom of QCD are confined within a volume as is presently understood, the $U_A(1)$ anomaly is known to induce color anomaly leading to "leakage" of the color out of the confined volume (or bag). For consistency of the theory, this anomaly should be canceled by a boundary term. This ``color boundary term" inherits part or most of the dynamics of the volume (i.e., QCD). In this paper, we exploit this mapping of the volume to the surafce via the color boundary condition to perform a complete analysis of the flavor singlet axial charge in the chiral bag model using the Cheshire Cat Principle. This enables us to obtain the hitherto missing piece in the axial charge associated with the gluon Casimir energies. The result is that the flavor singlet axial charge is small independent of the confinement (bag) size ranging from the skyrmion picture to the MIT bag picture, thereby confirming the (albeit approximate) Cheshire Cat phenomenon.Comment: 18 pages, 6 figure

A Unified Approach to High Density: Pion Fluctuations in Skyrmion Matter

As the first in a series of systematic work on dense hadronic matter, we study the properties of the pion in dense medium using Skyrme's effective Lagrangian as a unified theory of the hadronic interactions applicable in the large $N_c$ limit. Dense baryonic matter is described as the ground state of a skyrmion matter which appears in two differentiated phases as a function of matter density: i) at high densities as a stable cubic-centered (CC) half-skyrmion crystal; ii) at low densities as an unstable face-centered cubic (FCC) skyrmion crystal. We substitute the latter by a stable inhomogeneous phase of lumps of dense matter, which represents a naive Maxwell construction of the phase transition. This baryonic dense medium serves as a background for the pions whose effective {\em in-medium} Lagrangian we construct by allowing time-dependent quantum fluctuations on the classical dense matter field. We find that the same parameter which describes the phase transition for baryonic matter, the expectation value of the $\sigma$ field, also describes the phase transition for the dynamics of the {\em in-medium} pion. Thus, the structure of the baryonic ground state $crucially$ determines the behavior of the pion in the medium. As matter density increases, $$ decreases, a phenomenon which we interpret to signal, in terms of the parameters of the effective pion Lagrangian $f_\pi^*$ and $m_\pi^*$, the restoration of chiral symmetry at high density. Our calculation shows also the important role played by the higher powers in the density as it increases and chiral symmetry is being restored. This feature is likely to be generic at high density although our ground state may not be the true ground state

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Methods Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. Results The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. Conclusion P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement

Effects of an Intravitreal Bevacizumab Injection Combined With Panretinal Photocoagulation on High-Risk Proliferative Diabetic Retinopathy

PURPOSE: To investigate the short-term effects of panretinal photocoagulation (PRP) combined with an intravitreal injection of Avastin(bevacizumab) as an adjuvant to high-risk proliferative diabetic retinopathy (PDR). METHODS: The data was collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. One eye was treated with only PRP (PRP only group) and the fellow eye of same patient was treated with both PRP and intravitreal bevacizumab injection (Adjuvant group). Best corrected visual acuity (BCVA), IOP (intraocular pressure), and new vessel (NV) size in fluorescein angiography were recorded immediately and at the six-week follow-up visit. Adverse events associated with intravitreal injection were investigated. RESULTS: Of 12 patients with high-risk PDR, five were male and seven were female. There were no statistically significant BCVA or IOP changes after treatment in either group (p=0.916, 0.888). The reduction of NV size was found in both groups, but NV size in the adjuvant group showed a greater decrease than that of the PRP only group (p=0.038). Three patients had adverse events after intravitreal injection. Two patients had mild anterior uveitis and one patient had a serious complication of branched retinal artery obstruction (BRAO). CONCLUSIONS: Intravitreal bevacizumab injection with PRP resulted in marked regression of neovascularization compared with PRP alone. One serious side effect, BRAO, was noted in this study. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant