Cyclin D1 and p16 expression in recurrent nasopharyngeal carcinoma

Abstract Background Cyclin D1 and p16 are involved in the regulation of G1 checkpoint and may play an important role in the tumorigenesis of nasopharyngeal carcinoma (NPC). Previous studies have examined the level of expression of cyclin D1 and p16 in primary untreated NPC but no such information is available for recurrent NPC. We set out in this study to examine the expression level of cyclin D1 and p16 in recurrent NPC that have failed previous treatment with radiation +/- chemotherapy. Patients and methods A total of 42 patients underwent salvage nasopharyngectomy from 1984 to 2001 for recurrent NPC after treatment failure with radiation +/- chemotherapy. Twenty-seven pathologic specimens were available for immunohistochemical study using antibodies against cyclin D1 and p16. Results Positive expression of cyclin D1 was observed in 7 of 27 recurrent NPC specimens (26%) while positive p16 expression was seen in only 1 of 27 recurrent NPC (4%). Conclusion While the level of expression of cyclin D1 in recurrent NPC was similar to that of previously untreated head and neck cancer, the level of p16 expression in recurrent NPC samples was much lower than that reported for previously untreated cancer. The finding that almost all (96%) of the recurrent NPC lack expression of p16 suggested that loss of p16 may confer a survival advantage by making cancer cells more resistant to conventional treatment with radiation +/- chemotherapy. Further research is warranted to investigate the clinical use of p16 both as a prognostic marker and as a potential therapeutic target

Quantum transport theory for nanostructures with Rashba spin-orbital interaction

We report on a general theory for analyzing quantum transport through devices in the Metal-QD-Metal configuration where QD is a quantum dot or the device scattering region which contains Rashba spin-orbital and electron-electron interactions. The metal leads may or may not be ferromagnetic, they are assumed to weakly couple to the QD region. Our theory is formulated by second quantizing the Rashba spin-orbital interaction in spectral space (instead of real space), and quantum transport is then analyzed within the Keldysh nonequilibrium Green's function formalism. The Rashba interaction causes two main effects to the Hamiltonian: (i) it gives rise to an extra spin-dependent phase factor in the coupling matrix elements between the leads and the QD; (ii) it gives rise to an inter-level spin-flip term but forbids any intra-level spin-flips. Our formalism provides a starting point for analyzing many quantum transport issues where spin-orbital effects are important. As an example, we investigate transport properties of a Aharnov-Bohm ring in which a QD having Rashba spin-orbital and e-e interactions is located in one arm of the ring. A substantial spin-polarized conductance or current emerges in this device due to a combined effect of a magnetic flux and the Rashba interaction. The direction and strength of the spin-polarization are shown to be controllable by both the magnetic flux and a gate voltage.Comment: 12 pages, 8 figure

Determination of material properties in the Chaboche unified viscoplasticity model

An experimental programme of cyclic mechanical testing of a 316 stainless steel, at temperatures up to 600°C, under isothermal conditions, for the identification of material constitutive constants, has been carried out using a thermo-mechanical fatigue (TMF) test machine with induction coil heating. The constitutive model adopted is a modified Chaboche unified viscoplasticity model, which can deal with both cyclic effects, such as combined isotropic and kinematic hardening, and rate-dependent effects, associated with viscoplasticity. The characterization of 316 stainless steel is presented and compared with results from cyclic isothermal tests. A least-squares optimization algorithm has been developed and implemented for determining the material constants in order to further improve the general fit of the model to experimental data, using the initially obtained material constants as the starting point in this optimization process. The model predictions using both the initial and optimized material constants are compared to experimental data

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Magnetism and Faraday Rotation in Oxygen-Deficient Polycrystalline and Single-Crystal Iron-Substituted Strontium Titanate

Both polycrystalline and single-crystal films of iron-substituted strontium titanate, Sr(Ti[subscript 0.65]Fe[subscript 0.35])O[subscript 3−δ], prepared by pulsed laser deposition, show room-temperature magnetism and Faraday rotation, with the polycrystalline films exhibiting higher saturation magnetization and Faraday rotation. The magnetic properties vary with the oxygen pressure at which the films are grown, showing a maximum at pressures of approximately 4  μ Torr at which the unit-cell volume is largest. The results are discussed in terms of the oxygen stoichiometry and corresponding Fe valence states, the structure and strain state, and the presence of small-volume fractions of metallic Fe in single-crystal films grown at the optimum deposition pressure. Integration of magneto-optical polycrystalline films on an optical-waveguide device demonstrates a nonreciprocal phase shift.National Science Foundation (U.S.) (Grants DMR1419807 and ECCS1607865)Semiconductor Research Corporation. Function Accelerated nanoMaterial Engineerin

Vascular Smooth Muscle Cell Stiffness and Adhesion to Collagen I Modified by Vasoactive Agonists

In vascular smooth muscle cells (VSMCs) integrin-mediated adhesion to extracellular matrix (ECM) proteins play important roles in sustaining vascular tone and resistance. The main goal of this study was to determine whether VSMCs adhesion to type I collagen (COL-I) was altered in parallel with the changes in the VSMCs contractile state induced by vasoconstrictors and vasodilators. VSMCs were isolated from rat cremaster skeletal muscle arterioles and maintained in primary culture without passage. Cell adhesion and cell E-modulus were assessed using atomic force microscopy (AFM) by repetitive nano-indentation of the AFM probe on the cell surface at 0.1 Hz sampling frequency and 3200 nm Z-piezo travelling distance (approach and retraction). AFM probes were tipped with a 5 μm diameter microbead functionalized with COL-I (1mg\ml). Results showed that the vasoconstrictor angiotensin II (ANG-II; 10−6 ) significantly increased (p<0.05) VSMC E-modulus and adhesion probability to COL-I by approximately 35% and 33%, respectively. In contrast, the vasodilator adenosine (ADO; 10−4 ) significantly decreased (p<0.05) VSMC E-modulus and adhesion probability by approximately −33% and −17%, respectively. Similarly, the NO donor (PANOate, 10−6 M), a potent vasodilator, also significantly decreased (p<0.05) the VSMC E-modulus and COL-I adhesion probability by −38% and −35%, respectively. These observations support the hypothesis that integrin-mediated VSMC adhesion to the ECM protein COL-I is dynamically regulated in parallel with VSMC contractile activation. These data suggest that the signal transduction pathways modulating VSMC contractile activation and relaxation, in addition to ECM adhesion, interact during regulation of contractile state

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized

Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference