A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

Purpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD), they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNAbased markers and CIDD was applied to a population of patients undergoing monitoring for recurrence. Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay. Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value) those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests. Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could lead to the more efficient triage of patients undergoing recurrence monitoring

Smectic ordering in liquid crystal - aerosil dispersions I. X-ray scattering

Comprehensive x-ray scattering studies have characterized the smectic ordering of octylcyanobiphenyl (8CB) confined in the hydrogen-bonded silica gels formed by aerosil dispersions. For all densities of aerosil and all measurement temperatures, the correlations remain short range, demonstrating that the disorder imposed by the gels destroys the nematic (N) to smectic-A (SmA) transition. The smectic correlation function contains two distinct contributions. The first has a form identical to that describing the critical thermal fluctuations in pure 8CB near the N-SmA transition, and this term displays a temperature dependence at high temperatures similar to that of the pure liquid crystal. The second term, which is negligible at high temperatures but dominates at low temperatures, has a shape given by the thermal term squared and describes the static fluctuations due to random fields induced by confinement in the gel. The correlation lengths appearing in the thermal and disorder terms are the same and show strong variation with gel density at low temperatures. The temperature dependence of the amplitude of the static fluctuations further suggests that nematic susceptibility become suppressed with increasing quenched disorder. The results overall are well described by a mapping of the liquid crystal-aerosil system into a three dimensional XY model in a random field with disorder strength varying linearly with the aerosil density.Comment: 14 pages, 13 figure

Self-dual noncommutative \phi^4-theory in four dimensions is a non-perturbatively solvable and non-trivial quantum field theory

We study quartic matrix models with partition function Z[E,J]=\int dM \exp(trace(JM-EM^2-(\lambda/4)M^4)). The integral is over the space of Hermitean NxN-matrices, the external matrix E encodes the dynamics, \lambda>0 is a scalar coupling constant and the matrix J is used to generate correlation functions. For E not a multiple of the identity matrix, we prove a universal algebraic recursion formula which gives all higher correlation functions in terms of the 2-point function and the distinct eigenvalues of E. The 2-point function itself satisfies a closed non-linear equation which must be solved case by case for given E. These results imply that if the 2-point function of a quartic matrix model is renormalisable by mass and wavefunction renormalisation, then the entire model is renormalisable and has vanishing \beta-function. As main application we prove that Euclidean \phi^4-quantum field theory on four-dimensional Moyal space with harmonic propagation, taken at its self-duality point and in the infinite volume limit, is exactly solvable and non-trivial. This model is a quartic matrix model, where E has for N->\infty the same spectrum as the Laplace operator in 4 dimensions. Using the theory of singular integral equations of Carleman type we compute (for N->\infty and after renormalisation of E,\lambda) the free energy density (1/volume)\log(Z[E,J]/Z[E,0]) exactly in terms of the solution of a non-linear integral equation. Existence of a solution is proved via the Schauder fixed point theorem. The derivation of the non-linear integral equation relies on an assumption which we verified numerically for coupling constants 0<\lambda\leq (1/\pi).Comment: LaTeX, 64 pages, xypic figures. v4: We prove that recursion formulae and vanishing of \beta-function hold for general quartic matrix models. v3: We add the existence proof for a solution of the non-linear integral equation. A rescaling of matrix indices was necessary. v2: We provide Schwinger-Dyson equations for all correlation functions and prove an algebraic recursion formula for their solutio

The Structure and Dynamics of the Upper Chromosphere and Lower Transition Region as Revealed by the Subarcsecond VAULT Observations

The Very high Angular resolution ULtraviolet Telescope (VAULT) is a sounding rocket payload built to study the crucial interface between the solar chromosphere and the corona by observing the strongest line in the solar spectrum, the Ly-a line at 1216 {\AA}. In two flights, VAULT succeeded in obtaining the first ever sub-arcsecond (0.5") images of this region with high sensitivity and cadence. Detailed analyses of those observations have contributed significantly to new ideas about the nature of the transition region. Here, we present a broad overview of the Ly-a atmosphere as revealed by the VAULT observations, and bring together past results and new analyses from the second VAULT flight to create a synthesis of our current knowledge of the high-resolution Ly-a Sun. We hope that this work will serve as a good reference for the design of upcoming Ly-a telescopes and observing plans.Comment: 28 pages, 11 figure

Neutron background in large-scale xenon detectors for dark matter searches

Simulations of the neutron background for future large-scale particle dark matter detectors are presented. Neutrons were generated in rock and detector elements via spontaneous fission and (alpha,n) reactions, and by cosmic-ray muons. The simulation techniques and results are discussed in the context of the expected sensitivity of a generic liquid xenon dark matter detector. Methods of neutron background suppression are investigated. A sensitivity of $10^{-9}-10^{-10}$ pb to WIMP-nucleon interactions can be achieved by a tonne-scale detector.Comment: 35 pages, 13 figures, 2 tables, accepted for publication in Astroparticle Physic

EUV Spectra of the Full Solar Disk: Analysis and Results of the Cosmic Hot Interstellar Plasma Spectrometer (CHIPS)

We analyze EUV spectra of the full solar disk from the Cosmic Hot Interstellar Plasma Spectrometer (CHIPS) spanning a period of two years. The observations were obtained via a fortuitous off-axis light path in the 140 -- 270 Angstrom passband. The general appearance of the spectra remained relatively stable over the two-year time period, but did show significant variations of up to 25% between two sets of Fe lines that show peak emission at 1 MK and 2 MK. The variations occur at a measured period of 27.2 days and are caused by regions of hotter and cooler plasma rotating into, and out of, the field of view. The CHIANTI spectral code is employed to determine plasma temperatures, densities, and emission measures. A set of five isothermal plasmas fit the full disk spectra well. A 1 -- 2 MK plasma of Fe contributes 85% of the total emission in the CHIPS passband. The standard Differential Emission Measures (DEMs) supplied with the CHIANTI package do not fit the CHIPS spectra well as they over-predict emission at temperatures below log(T) = 6.0 and above log(T) = 6.3. The results are important for cross-calibrating TIMED, SORCE, SOHO/EIT, and CDS/GIS, as well as the recently launched Solar Dynamics Observatory.Comment: 27 Pages, 13 Figure

Photo--assisted current and shot noise in the fractional quantum Hall effect

The effect of an AC perturbation on the shot noise of a fractional quantum Hall fluid is studied both in the weak and the strong backscattering regimes. It is known that the zero-frequency current is linear in the bias voltage, while the noise derivative exhibits steps as a function of bias. In contrast, at Laughlin fractions, the backscattering current and the backscattering noise both exhibit evenly spaced singularities, which are reminiscent of the tunneling density of states singularities for quasiparticles. The spacing is determined by the quasiparticle charge $\nu e$ and the ratio of the DC bias with respect to the drive frequency. Photo--assisted transport can thus be considered as a probe for effective charges at such filling factors, and could be used in the study of more complicated fractions of the Hall effect. A non-perturbative method for studying photo--assisted transport at $\nu=1/2$ is developed, using a refermionization procedure.Comment: 14 pages, 6 figure

Heliospheric Transport of Neutron-Decay Protons

We report on new simulations of the transport of energetic protons originating from the decay of energetic neutrons produced in solar flares. Because the neutrons are fast-moving but insensitive to the solar wind magnetic field, the decay protons are produced over a wide region of space, and they should be detectable by current instruments over a broad range of longitudes for many hours after a sufficiently large gamma-ray flare. Spacecraft closer to the Sun are expected to see orders-of magnitude higher intensities than those at the Earth-Sun distance. The current solar cycle should present an excellent opportunity to observe neutron-decay protons with multiple spacecraft over different heliographic longitudes and distances from the Sun.Comment: 12 pages, 4 figures, to be published in special issue of Solar Physic

Anisotropy at the end of the cosmic ray spectrum?

The starburst galaxies M82 and NGC253 have been proposed as the primary sources of cosmic rays with energies above $10^{18.7}$ eV. For energies \agt 10^{20.3} eV the model predicts strong anisotropies. We calculate the probabilities that the latter can be due to chance occurrence. For the highest energy cosmic ray events in this energy region, we find that the observed directionality has less than 1% probability of occurring due to random fluctuations. Moreover, during the first 5 years of operation at Auger, the observation of even half the predicted anisotropy has a probability of less than $10^{-5}$ to occur by chance fluctuation. Thus, this model can be subject to test at very small cost to the Auger priors budget and, whatever the outcome of that test, valuable information on the Galactic magnetic field will be obtained.Comment: Final version to be published in Physical Review

Phenomenology of Randall-Sundrum Black Holes

We explore the phenomenology of microscopic black holes in the $S^1/Z_2$ Randall-Sundrum (RS) model. We consider the canonical framework in which both gauge and matter fields are confined to the brane and only gravity spills into the extra dimension. The model is characterized by two parameters, the mass of the first massive graviton $(m_1)$, and the curvature $1/\ell$ of the RS anti-de Sitter space. We compute the sensitivity of present and future cosmic ray experiments to various regions of $\ell$ and $m_1,$ and compare with that of Runs I and II at the Tevatron. As part of our phenomenological analysis, we examine constraints placed on $\ell$ by AdS/CFT considerations.Comment: Version to appear in Physical Review D; contains additional analysis on sensitivity of OW