Measuring the response of human head and neck squamous cell carcinoma to irradiation in a microfluidic model allowing customized therapy

Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers. HNSCC biopsies from five newly-presenting patients [2 lymph node (LN); 3 primary tumour (PT)] were divided into parallel microfluidic devices and replicates of each tumour were subjected to single-dose irradiation (0, 5, 10, 15 and 20 Gy). Lactate dehydrogenase (LDH) release was measured and tissue sections were stained for cytokeratin (CK), cleaved-CK18 (cCK18), phosphorylated-H2AX (λH2AX) and Ki.67 by immunohistochemistry. In addition, fragmented DNA was detected using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Compared with non.irradiated controls, higher irradiation doses resulted in elevated CK18-labelling index in two lymph nodes [15 Gy; 34.8% on LN1 and 31.7% on LN2 (p=0.006)] and a single laryngeal primary tumour (20 Gy; 31.5%; p=0.014). Significantly higher levels of DNA fragmentation were also detected in both lymph node samples and one primary tumour but at varying doses of irradiation, i.e., LN1 (20 Gy; 27.6%; p=0.047), LN2 (15 Gy; 15.3%; p=0.038) and PT3 (10 Gy; 35.2%; p=0.01). The λH2AX expression was raised but not significantly in the majority of samples. The percentage of Ki.67 positive nuclei reduced dose-dependently following irradiation. In contrast no significant difference in LDH release was observed between irradiated groups and controls. There is clear interand intra-patient variability in response to irradiation when measuring a variety of parameters, which offers the potential for the approach to provide clinically valuable information

Atmospheric aerosol and Doppler lidar studies

Experimental and theoretical studies were performed of atmospheric aerosol backscatter and atmospheric dynamics with Doppler lidar as a primary tool. Activities include field and laboratory measurement and analysis efforts. The primary focus of activities related to understanding aerosol backscatter is the GLObal Backscatter Experiment (GLOBE) program. GLOBE is a multi-element effort designed toward developing a global aerosol model to describe tropospheric clean background backscatter conditions that Laser Atmospheric Wind Sounder (LAWS) is likely to encounter. Two survey missions were designed and flown in the NASA DC-8 in November 1989 and May to June 1990 over the remote Pacific Ocean, a region where backscatter values are low and where LAWS wind measurements could make a major contribution. The instrument complement consisted of pulsed and continuous-wave (CW) CO2 gas and solid state lidars measuring aerosol backscatter, optical particle counters measuring aerosol concentration, size distribution, and chemical composition, a filter/impactor system collecting aerosol samples for subsequent analysis, and integrating nephelometers measuring visible scattering coefficients. The GLOBE instrument package and survey missions were carefully planned to achieve complementary measurements under clean background backscatter conditions

Dynamics of a bubble formed in double stranded DNA

We study the fluctuational dynamics of a tagged base-pair in double stranded DNA. We calculate the drift force which acts on the tagged base-pair using a potential model that describes interactions at base pairs level and use it to construct a Fokker-Planck equation.The calculated displacement autocorrelation function is found to be in very good agreement with the experimental result of Altan-Bonnet {\it et. al.} Phys. Rev. Lett. {\bf 90}, 138101 (2003) over the entire time range of measurement. We calculate the most probable displacements which predominately contribute to the autocorrelation function and the half-time history of these displacements.Comment: 11 pages, 4 figures. submitted to Phys. Rev. Let

Direct Photons in Nuclear Collisions at FAIR Energies

Using the extrapolation of existing data estimations of prompt photon production at FAIR energies have been made. At $y=y_{c.m.}$ the rapidity density of prompt photons with $p_{t}>$ 1.5 GeV/c per central Au+Au event at 25 AGeV is estimated as $\sim 10^{-4}$ . With the planed beam intensity $10^{9}$ per second and 1% interaction probability, for 10% of most central events one can expect the prompt photon rate $\sim 10^{2}$ photons per second. Direct photons from the hadron scenario of ion collisions generated by the Hadron-String-Dynamics (HSD) transport approach with implemented meson scatterings $\pi\rho\to\pi\gamma, \pi\pi\to\rho\gamma$ have been analyzed. Photons from short-living resonances (e.g. $\omega \to \pi^{0} \gamma$) decaying during the dense phase of the collision should be considered as direct photons. They contribute significantly in the direct photon spectrum at $p_{t}=0.5 - 1$ GeV/c. At the FAIR energy 25 AGeV in Au+Au central collisions the HSD generator predicts, as a lower estimate, $\gamma_{direct}/\gamma_{\pi^{0}} \simeq$ 0.5% in the region $p_{t}=0.5 - 1$ GeV/c. At $p_{t}=1.5 - 2$ GeV/c $\gamma_{prompt}/\gamma_{\pi^{0}} \simeq$ 2%. Thermal direct photons have been evaluated with the Bjorken Hydro-Dynamics (BHD) model. The BHD spectra differ strongly from the HSD predictions. The direct photon spectrum is very sensitive to the initial temperature parameter $T_{0}$ of the model. The 10 MeV increase in the $T_{0}$ value leads to $\sim$ 2 times higher photon yield.Comment: 9 pages, 5 figures, Talk at the session of Russian Academy of Sciences, ITEP, Moscow, 26 - 30 November 200

Radiation of single photons from Pb+PbPb+Pb collisions at the CERN SPS and quark hadron phase transition

The production of single photons in $Pb+Pb$ collisions at the CERN SPS as measured by the WA98 experiment is analysed. A quark gluon plasma is assumed to be formed initially, which expands, cools, hadronizes, and undergoes freeze-out. A rich hadronic equation of state is used and the transverse expansion of the interacting system is taken into account. The recent estimates of photon production in quark-matter (at two loop level) along with the dominant reactions in the hadronic matter leading to photons are used. About 50% of the single photons are seen to have a thermal origin. An addition of the thermal and prompt photons is seen to provide a very good description of the data. Most of the thermal photons having large transverse momenta arise from the quark-matter, which contributes dominantly through the mechanism of annihilation of quarks with scattering, and which in turn is possible only in a hot and dense plasma of quarks and gluons. The results thus confirm the formation of quark gluon plasma and the existence of this mechanism of the production of single photons.Comment: 6 pages including 3 figures. Corrected 2-loop rates for photons are use

A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease

The rising incidence of chronic liver disease continues to be an increasing health burden. The morbidity and mortality associated with chronic liver disease typically occur in patients with advanced fibrosis. Hence, early identification of those at-risk is of vital importance to ensure appropriate ongoing management. Currently, tools for appropriate risk stratification remain limited. Increasing awareness of the limitations of liver biopsy has driven research into alternative non-invasive methods of fibrosis assessment including serological markers assessing functional changes. One such biomarker, the Enhanced Liver Fibrosis test, was initially validated in a cohort of 1021 patients with mixed aetiology chronic liver disease and shown to perform well. Since this pathfinder study, it has been independently validated in cohorts of hepatitis C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. In addition to performing well as a diagnostic tool, the Enhanced Liver Fibrosis test has been shown to outperform liver biopsy in prognostic studies and is the only non-invasive marker to do so. However, questions remain regarding the use of this test, particularly regarding the possible effect age and alcohol may have on test scores. This review examines the current literature published in relation to the Enhanced Liver Fibrosis test and its clinical utility and highlights areas requiring further study

Rare-gas solids under pressure: A path-integral Monte Carlo simulation

Rare-gas solids (Ne, Ar, Kr, and Xe) under hydrostatic pressure up to 30 kbar have been studied by path-integral Monte Carlo simulations in the isothermal-isobaric ensemble. Results of these simulations have been compared with available experimental data and with those obtained from a quasiharmonic approximation (QHA). This comparison allows us to quantify the overall anharmonicity of the lattice vibrations and its influence on several structural and thermodynamic properties of rare-gas solids. The vibrational energy increases with pressure, but this increase is slower than that of the elastic energy, which dominates at high pressures. In the PIMC simulations, the vibrational kinetic energy is found to be larger than the corresponding potential energy, and the relative difference between both energies decreases as the applied pressure is raised. The accuracy of the QHA increases for rising pressure.Comment: 9 pages, 6 figure

Penning trap and vacuum noise

A number of comments are provided on Rogers's model experiment to measure the circular Unruh vacuum noise by means of a hyperbolic Penning trap inside a microwave cavity. It is suggested that cylindrical Penning traps, being geometrically simpler, and controlled almost at the same level of accuracy as the hyperbolic trap, might be a better choice for such an experiment. Besides, the microwave modes of the trap itself, of known analytical structure, can be directly used in trying to obtain measurable results for such a tiny noise effect.Comment: 7 LaTex pages, published text and references with title

Equation of state for nuclear matter based on density dependent effective interaction

An interesting method of obtaining equation of state for nuclear matter, from a density dependent M3Y interaction, by minimizing the energy per nucleon is described. The density dependence parameters of the interaction are obtained by reproducing the saturation energy per nucleon and the saturation density of spin and isospin symmetric cold infinite nuclear matter. The nuclear matter equation of state thus obtained is then used to calculate the pressure, the energy density, the nuclear incompressibility and the velocity of sound in nuclear medium. The results obtained are in good agreement with experimental data and provide a unified description of radioactivity, scattering and nuclear matter.Comment: 10 pages including 2 figure