Field desorption ion source development for neutron generators

A new approach to deuterium ion sources for deuterium-tritium neutron generators is being developed. The source is based upon the field desorption of deuterium from the surfaces of metal tips. Field desorption studies of microfabricated field emitter tip arrays have been conducted for the first time. Maximum fields of 30 V/nm have been applied to the array tip surfaces to date, although achieving fields of 20 V/nm to possibly 25 V/nm is more typical. Both the desorption of atomic deuterium ions and the gas phase field ionization of molecular deuterium has been observed at fields of roughly 20 V/nm and 20-30 V/nm, respectively, at room temperature. The desorption of common surface adsorbates, such as hydrogen, carbon, water, and carbon monoxide is observed at fields exceeding ~10 V/nm. In vacuo heating of the arrays to temperatures of the order of 800 C can be effective in removing many of the surface contaminants observed

Race and smoking status associated with paclitaxel drug response in patient-derived lymphoblastoid cell lines

The use of ex-vivo model systems to provide a level of forecasting for in-vivo characteristics remains an important need for cancer therapeutics. The use of lymphoblastoid cell lines (LCLs) is an attractive approach for pharmacogenomics and toxicogenomics, due to their scalability, efficiency, and cost-effectiveness. There is little data on the impact of demographic or clinical covariates on LCL response to chemotherapy. Paclitaxel sensitivity was determined in LCLs from 93 breast cancer patients from the University of North Carolina Lineberger Comprehensive Cancer Center Breast Cancer Database to test for potential associations and/or confounders in paclitaxel dose-response assays. Measures of paclitaxel cell viability were associated with patient data included treatment regimens, cancer status, demographic and environmental variables, and clinical outcomes. We used multivariate analysis of variance to identify the in-vivo variables associated with ex-vivo dose-response. In this unique dataset that includes both in-vivo and ex-vivo data from breast cancer patients, race (P = 0.0049) and smoking status (P = 0.0050) were found to be significantly associated with ex-vivo dose-response in LCLs. Racial differences in clinical dose-response have been previously described, but the smoking association has not been reported. Our results indicate that in-vivo smoking status can influence ex-vivo dose-response in LCLs, and more precise measures of covariates may allow for more precise forecasting of clinical effect. In addition, understanding the mechanism by which exposure to smoking in-vivo effects ex-vivo dose-response in LCLs may open up new avenues in the quest for better therapeutic prediction

CYP2D6 Genotype is Not Associated with Survival in Breast Cancer Patients Treated with Tamoxifen: Results from a Population-based Study

Purpose: A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Methods: Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). Results: CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). Conclusions: This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice

Further analysis of the quantum critical point of Ce1−x_{1-x}Lax_{x}Ru2_{2}Si2_{2}

New data on the spin dynamics and the magnetic order of Ce$_{1-x}$La$_{x}$Ru$_{2}$Si$_{2}$ are presented. The importance of the Kondo effect at the quantum critical point of this system is emphasized from the behaviour of the relaxation rate at high temperature and from the variation of the ordered moment with respect to the one of the N\'eel temperature for various $x$.Comment: Contribution for the Festschrift on the occasion of Hilbert von Loehneysen 60 th birthday. To be published as a special issue in the Journal of Low Temperature Physic

Relationship between single and bulk mechanical properties for zeolite ZSM5 spray-dried particles

In this work typical mechanical properties for a catalyst support material, ZSM5 (a spray-dried granular zeolite), have been measured in order to relate the bulk behaviour of the powder material to the single particle mechanical properties. Particle shape and size distribution of the powders, determined by laser diffraction and scanning electron microscopy (SEM), confirmed the spherical shape of the spray-dried particles. The excellent flowability of the material was assessed by typical methods such as the Hausner ratio and the Carr index. This was confirmed by bulk measurements of the particle–particle internal friction parameter and flow function using a Schulze shear cell, which also illustrated the low compressibility of the material. Single particle compression was used to characterize single particle mechanical proper-ties such as reduced elastic modulus and strength from Hertz contact mechanics theory. Comparison with surface properties obtained from nanoindentation suggests heterogeneity, the surface being harder than the core. In order to evaluate the relationship between single particle mechanical properties and bulk compression behaviour, uniaxial confined compression was carried out. It was determined that the Adams model was suitable for describing the bulk compression and furthermore that the Adams model parameter, apparent strength of single particles, was in good agreement with the single particle strength determined from single particle compression test

Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment

Objectives Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations. Patients and methods Comprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients. Predicted activity phenotype for 19 enzymes and transporters were analyzed for univariate association with endoxifen concentration, and then adjusted for CYP2D6 and clinical covariates. Results In univariate analysis, higher activity of CYP2C8 (regression β=0.22, P=0.020) and CYP2C9 (β=0.20, P=0.04), lower body weight (β=-0.014, P<0.0001), and endoxifen measurement during winter (each β< -0.39, P=0.002) were associated with higher endoxifen concentrations. After adjustment for the CYP2D6 diplotype, weight, and season, CYP2C9 remained significantly associated with higher concentrations (P=0.02), but only increased the overall model R2 by 1.3%. Conclusion Our results further support a minor contribution of CYP2C9 genetic variability toward steadystate endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes

Competing orders in a magnetic field: spin and charge order in the cuprate superconductors

We describe two-dimensional quantum spin fluctuations in a superconducting Abrikosov flux lattice induced by a magnetic field applied to a doped Mott insulator. Complete numerical solutions of a self-consistent large N theory provide detailed information on the phase diagram and on the spatial structure of the dynamic spin spectrum. Our results apply to phases with and without long-range spin density wave order and to the magnetic quantum critical point separating these phases. We discuss the relationship of our results to a number of recent neutron scattering measurements on the cuprate superconductors in the presence of an applied field. We compute the pinning of static charge order by the vortex cores in the `spin gap' phase where the spin order remains dynamically fluctuating, and argue that these results apply to recent scanning tunnelling microscopy (STM) measurements. We show that with a single typical set of values for the coupling constants, our model describes the field dependence of the elastic neutron scattering intensities, the absence of satellite Bragg peaks associated with the vortex lattice in existing neutron scattering observations, and the spatial extent of charge order in STM observations. We mention implications of our theory for NMR experiments. We also present a theoretical discussion of more exotic states that can be built out of the spin and charge order parameters, including spin nematics and phases with `exciton fractionalization'.Comment: 36 pages, 33 figures; for a popular introduction, see http://onsager.physics.yale.edu/superflow.html; (v2) Added reference to new work of Chen and Ting; (v3) reorganized presentation for improved clarity, and added new appendix on microscopic origin; (v4) final published version with minor change

Theory of Two-Dimensional Quantum Heisenberg Antiferromagnets with a Nearly Critical Ground State

We present the general theory of clean, two-dimensional, quantum Heisenberg antiferromagnets which are close to the zero-temperature quantum transition between ground states with and without long-range N\'{e}el order. For N\'{e}el-ordered states, `nearly-critical' means that the ground state spin-stiffness, $\rho_s$, satisfies $\rho_s \ll J$, where $J$ is the nearest-neighbor exchange constant, while `nearly-critical' quantum-disordered ground states have a energy-gap, $\Delta$, towards excitations with spin-1, which satisfies $\Delta \ll J$. Under these circumstances, we show that the wavevector/frequency-dependent uniform and staggered spin susceptibilities, and the specific heat, are completely universal functions of just three thermodynamic parameters. Explicit results for the universal scaling functions are obtained by a $1/N$ expansion on the $O(N)$ quantum non-linear sigma model, and by Monte Carlo simulations. These calculations lead to a variety of testable predictions for neutron scattering, NMR, and magnetization measurements. Our results are in good agreement with a number of numerical simulations and experiments on undoped and lightly-doped $La_{2-\delta} Sr_{\delta}Cu O_4$.Comment: 81 pages, REVTEX 3.0, smaller updated version, YCTP-xxx

An experimental investigation of laser scabbling of concrete

Laser scabbling of concrete is the process of removal of surface material using a high power laser beam. The main aim of this investigation was to establish an experimental procedure for assessing the effects of various parameters that may be critical for the effectiveness of the process, such as material composition and initial moisture content. The study shows that the key characteristics of the process can be detected by monitoring surface temperature variations. This experimental procedure is used to provide data on the effects of each parameter to explain the mechanisms that drive the process. The results suggest that scabbling is mainly driven by pore pressures in the cement paste, but strongly affected by other factors. Reducing permeability by adding PFA to the cement paste resulted in significant increase in volume removal; but reducing moisture content by air-drying of the material did not result in the expected reduction in volume removal

Transition from a strong-coupling fixed point to an intermediate-coupling fixed point in a single-channel SU(N) Kondo model: role of the filling and two-stage screening

We study an extended SU(N) single-impurity Kondo model in which the impurity spin is described by a combination of Abrikosov fermions and Schwinger bosons. Our aim is to describe both the quasiparticle-like excitations and the locally critical modes observed in various physical situations, including non-Fermi liquid behavior in heavy fermion systems in the vicinity of a quantum critical point. We identify the strong coupling fixed point of the model and study its stability within second order perturbation theory. Already in the single channel case and in contrast with either the pure bosonic or the pure fermionic case, the strong coupling fixed point is unstable against the conduction electron kinetic term as soon as the amount of Abrikosov fermions reaches a critical value. In the stability region, the partially screened, dressed impurity at site 0 repels the conduction electrons on adjacent sites. In the instability region, the impurity tends to attract $(N-1)$ conduction electrons to the neighboring sites, giving rise to a two-stage Kondo effect with additional screening.This result opens the route to the existence of an intermediate coupling fixed point, characterized by non-Fermi liquid behavior