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

Effect of the source charge on charged-beam interferometry

We investigate quantal perturbations of the interferometric correlations of charged bosons by the Coulomb field of an instantaneous, charged source. The source charge increases the apparent source size by weakening the correlation at non-zero relative momenta. The effect is strongest for pairs with a small total momentum and is stronger for kaons than for pions of the same momenta. The experimental data currently available are well described by this effect without invoking Pratt's exploding source model. A simple expression is proposed to account for the effect.Comment: 9 pages TEX, 3 Postscript figures available at http://www.krl.caltech.edu/preprints/MAP.htm

Collective Flow from the Intranuclear Cascade Model

The phenomenon of collective flow in relativistic heavy ion collisions is studied using the hadronic cascade model ARC. Direct comparison is made to data gathered at the Bevalac, for Au+Au at $p=1-2$ GeV/c. In contrast to the standard lore about the cascade model, collective flow is well described quantitatively without the need for explicit mean field terms to simulate the nuclear equation of state. Pion collective flow is in the opposite direction to nucleon flow as is that of anti-nucleons and other produced particles. Pion and nucleon flow are predicted at AGS energies also, where, in light of the higher baryon densities achieved, we speculate that equation of state effects may be observable.Comment: 9 pages, 2 figures include

Percolation diffusion into self-assembled mesoporous silica microfibres

© 2014 by the authors. Percolation diffusion into long (11.5 cm) self-assembled, ordered mesoporous microfibres is studied using optical transmission and laser ablation inductive coupled mass spectrometry (LA-ICP-MS). Optical transmission based diffusion studies reveal rapid penetration ( 80 μm2·s−1) of Rhodamine B with very little percolation of larger molecules such as zinc tetraphenylporphyrin (ZnTPP) observed under similar loading conditions. The failure of ZnTPP to enter the microfibre was confirmed, in higher resolution, using LA-ICP-MS. In the latter case, LA-ICP-MS was used to determine the diffusion of zinc acetate dihydrate, D~3 × 10−4 nm2·s−1. The large differences between the molecules are accounted for by proposing ordered solvent and structure assisted accelerated diffusion of the Rhodamine B based on its hydrophilicity relative to the zinc compounds. The broader implications and applications for filtration, molecular sieves and a range of devices and uses are described

Neutrons from multiplicity-selected Au-Au collisions at 150, 250, 400, and 650 AMeV

We measured neutron triple-differential cross sections from multiplicity-selected Au-Au collisions at 150, 250, 400, and 650 \AMeV. The reaction plane for each collision was estimated from the summed transverse velocity vector of the charged fragments emitted in the collision. We examined the azimuthal distribution of the triple-differential cross sections as a function of the polar angle and the neutron rapidity. We extracted the average in--plane transverse momentum $\langle P_x\rangle$ and the normalized observable $\langle P_x/P_\perp\rangle$, where $P_\perp$ is the neutron transverse momentum, as a function of the neutron center-of-mass rapidity, and we examined the dependence of these observables on beam energy. These collective flow observables for neutrons, which are consistent with those of protons plus bound nucleons from the Plastic Ball Group, agree with the Boltzmann--Uehling--Uhlenbeck (BUU) calculations with a momentum--dependent interaction. Also, we calculated the polar-angle-integrated maximum azimuthal anisotropy ratio R from the value of $\langle P_x/P_\perp\rangle$.Comment: 20 LaTeX pages. 11 figures to be faxed on request, send email to sender's addres

The NuMI Neutrino Beam and Potential for an Off-Axis Experiment

The Neutrinos at the Main Injector (NuMI) facility at Fermilab is under construction and due to begin operations in late 2004. NuMI will deliver an intense $\nu_{\mu}$ beam of variable energy 2-20 GeV directed into the Earth at 58 mrad. Several aspects of the design are reviewed, and potential limitations to the ultimate neutrino flux are described. In addition, potential measurements of neutrino mixing properties are described.Comment: talk given at NuFact '02, Imperial College London, proceedings to appear in J. Phys. G, revised to add a referenc

Neutrons from multiplicity-selected La-La and Nb-Nb collisions at 400A MeV and La-La collisions at 250A MeV

Triple-differential cross sections for neutrons from high-multiplicity La-La collisions at 250 and 400 MeV per nucleon and Nb-Nb collisions at 400 MeV per nucleon were measured at several polar angles as a function of the azimuthal angle with respect to the reaction plane of the collision. The reaction plane was determined by a transverse-velocity method with the capability of identifying charged-particles with Z=1, Z=2, and Z > 2. The flow of neutrons was extracted from the slope at mid-rapidity of the curve of the average in-plane momentum vs the center-of-mass rapidity. The squeeze-out of the participant neutrons was observed in a direction normal to the reaction plane in the normalized momentum coordinates in the center-of-mass system. Experimental results of the neutron squeeze-out were compared with BUU calculations. The polar-angle dependence of the maximum azimuthal anisotropy ratio $r(\theta)$ was found to be insensitive to the mass of the colliding nuclei and the beam energy. Comparison of the observed polar-angle dependence of the maximum azimuthal anisotropy ratio $r(\theta)$ with BUU calculations for free neutrons revealed that $r(\theta)$ is insensitive also to the incompressibility modulus in the nuclear equation of state.Comment: ReVTeX, 16 pages, 17 figures. To be published in Physical Review

Causality in relativistic many body theory

The stability of the nuclear matter system with respect to density fluctuations is examined exploring in detail the pole structure of the electro-nuclear response functions. Making extensive use of the method of dispersion integrals we calculate the full polarization propagator not only for real energies in the spacelike and timelike regime but also in the whole complex energy plane. The latter proved to be necessary in order to identify unphysical causality violating poles which are the consequence of a neglection of vacuum polarization. On the contrary it is shown that Dirac sea effects stabilize the nuclear matter system shifting the unphysical pole from the upper energy plane back to the real axis. The exchange of strength between these real timelike collective excitations and the spacelike energy regime is shown to lead to a reduction of the quasielastic peak as it is seen in electron scattering experiments. Neglecting vacuum polarization one also obtains a reduction of the quasielastic peak but in this case the strength is partly shifted to the causality violating pole mentioned above which consequently cannot be considered as a physical reliable result. Our investigation of the response function in the energy region above the threshold of nucleon anti-nucleon production leads to another remarkable result. Treating the nucleons as point-like Dirac particles we show that for any isospin independent NN-interaction RPA-correlations provide a reduction of the production amplitude for $p\bar p$-pairs by a factor 2.Comment: 19 pages Latex including 12 postscript figure

Momentum--dependent nuclear mean fields and collective flow in heavy ion collisions

We use the Boltzmann-Uehling-Uhlenbeck model to simulate the dynamical evolution of heavy ion collisions and to compare the effects of two parametrizations of the momentum--dependent nuclear mean field that have identical properties in cold nuclear matter. We compare with recent data on nuclear flow, as characterized by transverse momentum distributions and flow ($F$) variables for symmetric and asymmetric systems. We find that the precise functional dependence of the nuclear mean field on the particle momentum is important. With our approach, we also confirm that the difference between symmetric and asymmetric systems can be used to pin down the density and momentum dependence of the nuclear self consistent one--body potential, independently. All the data can be reproduced very well with a momentum--dependent interaction with compressibility K = 210 MeV.Comment: 15 pages in ReVTeX 3.0; 12 postscript figures uuencoded; McGill/94-1

The energy dependence of flow in Ni induced collisions from 400 to 1970A MeV

We study the energy dependence of collective (hydrodynamic-like) nuclear matter flow in 400-1970 A MeV Ni+Au and 1000-1970 A MeV Ni+Cu reactions. The flow increases with energy, reaches a maximum, and then gradually decreases at higher energies. A way of comparing the energy dependence of flow values for different projectile-target mass combinations is introduced, which demonstrates a common scaling behaviour among flow values from different systems.Comment: 12 pages, 3 figures. Submitted to Physical Review Letter