Spin Reduction Transition in Spin-3/2 Random Heisenberg Chains

Random spin-3/2 antiferromagnetic Heisenberg chains are investigated using an asymptotically exact renormalization group. Randomness is found to induce a quantum phase transition between two random-singlet phases. In the strong randomness phase the effective spins at low energies are S_eff=3/2, while in the weak randomness phase the effective spins are S_eff=1/2. Separating them is a quantum critical point near which there is a non-trivial mixture of S=1/2, S=1, and S=3/2 effective spins at low temperatures.Comment: 4 pages, 3 figures. Typos correcte

Variation in use of targeted therapies for metastatic renal cell carcinoma

__Background:__ For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS). __Methods:__ Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008-2010 Cohort (n = 645) and a 2011-2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies. __Results:__ Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008-2010 Cohort; 35 % in the 2011-2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84-0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005). __Conclusions:__ Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully

Heterotic SO(32) model building in four dimensions

Four dimensional heterotic SO(32) orbifold models are classified systematically with model building applications in mind. We obtain all Z3, Z7 and Z2N models based on vectorial gauge shifts. The resulting gauge groups are reminiscent of those of type-I model building, as they always take the form SO(2n_0)xU(n_1)x...xU(n_{N-1})xSO(2n_N). The complete twisted spectrum is determined simultaneously for all orbifold models in a parametric way depending on n_0,...,n_N, rather than on a model by model basis. This reveals interesting patterns in the twisted states: They are always built out of vectors and anti--symmetric tensors of the U(n) groups, and either vectors or spinors of the SO(2n) groups. Our results may shed additional light on the S-duality between heterotic and type-I strings in four dimensions. As a spin-off we obtain an SO(10) GUT model with four generations from the Z4 orbifold.Comment: 1+37 pages LaTeX, some typos in table 4 corrected, and we have included some discussion on exceptional shift vectors which ignored in the previous version

Phase separation in t-J ladders

The phase separation boundary of isotropic t-J ladders is analyzed using density matrix renormalization group techniques. The complete boundary to phase separation as a function of J/t and doping is determined for a chain and for ladders with two, three and four legs. Six-chain ladders have been analyzed at low hole doping. We use a direct approach in which the phase separation boundary is determined by measuring the hole density in the part of the system which contains both electrons and holes. In addition we examine the binding energy of multi-hole clusters. An extrapolation in the number of legs suggests that the lowest J/t for phase separation to occur in the two dimensional t-J model is J/t~1.Comment: 8 pages in revtex format including 13 embedded figures, one reference adde

Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma

__Purpose:__ Based on improvements of progression-free survival (PFS), new agents for metastatic renal cell carcinoma (mRCC) have been approved. It is assumed that one of the benefits is a delay in health-related quality of life (HRQoL) deterioration as a result of a delay in progression of disease. However, little data are available supporting this relationship. This study aims to provide insight into the most important determinants of HRQoL (including progression of disease) of patients with mRCC. __Methods:__ A patient registry (PERCEPTION) was created to evaluate treatment of patients with (m)RCC in the Netherlands. HRQoL was measured, using the EORTC QLQ-C30 and EQ-5D-5L, every 3 months in the first year of participation in the study, and every 6 months in the second year. Participation started as soon as possible following a diagnosis of (m)RCC. Random effects models were used to study associations between HRQoL and patient and disease characteristics, symptoms and treatment. __Results:__ Eighty-seven patients with mRCC completed 304 questionnaires. The average EORTC QLQ-C30 global health status was 69 (SD, 19) before progression and 61 (SD, 22) after progression of disease. Similarly, the average EQ-5D utility was 0.75 (SD, 0.19) before progression and 0.66 (SD, 0.30) after progression of disease. The presence of fatigue, pain, dyspnoea, and the application of radiotherapy were associated with significantly lower EQ-5D utilities. __Conclusions:__ Key drivers for reduced HRQoL in mRCC are disease symptoms. Since symptoms increase with progression of disease, targeted therapies that increase PFS are expected to postpone reductions in HRQoL in mRCC

Ceres' spectral link to carbonaceous chondrites - Analysis of the dark background materials

Ceres’ surface has commonly been linked with carbonaceous chondrites (CCs) by ground‐based telescopic observations, because of its low albedo, flat to red‐sloped spectra in the visible and near‐infrared (VIS/NIR) wavelength region, and the absence of distinct absorption bands, though no currently known meteorites provide complete spectral matches to Ceres. Spatially resolved data of the Dawn Framing Camera (FC) reveal a generally dark surface covered with bright spots exhibiting reflectance values several times higher than Ceres’ background. In this work, we investigated FC data from High Altitude Mapping Orbit (HAMO) and Ceres eXtended Juling (CXJ) orbit (~140 m/pixel) for global spectral variations. We found that the cerean surface mainly differs by spectral slope over the whole FC wavelength region (0.4–1.0 μm). Areas exhibiting slopes <−10% μm−1 constitute only ~3% of the cerean surface and mainly occur in the bright material in and around young craters, whereas slopes ≥−10% μm−1 occur on more than 90% of the cerean surface; the latter being denoted as Ceres’ background material in this work. FC and Visible and Infrared Spectrometer (VIR) spectra of this background material were compared to the suite of CCs spectrally investigated so far regarding their VIS/NIR region and 2.7 μm absorption, as well as their reflectance at 0.653 μm. This resulted in a good match to heated CI Ivuna (heated to 200–300 °C) and a better match for CM1 meteorites, especially Moapa Valley. This possibly indicates that the alteration of CM2 to CM1 took place on Ceres

Genetic Selection for Enhanced Folding In Vivo Targets the Cys14-Cys38 Disulfide Bond in Bovine Pancreatic Trypsin Inhibitor

The periplasm provides a strongly oxidizing environment; however, periplasmic expression of proteins with disulfide bonds is often inefficient. Here, we used two different tripartite fusion systems to perform in vivo selections for mutants of the model protein bovine pancreatic trypsin inhibitor (BPTI) with the aim of enhancing its expression in Escherichia coli. This trypsin inhibitor contains three disulfides that contribute to its extreme stability and protease resistance. The mutants we isolated for increased expression appear to act by eliminating or destabilizing the Cys14-Cys38 disulfide in BPTI. In doing so, they are expected to reduce or eliminate kinetic traps that exist within the well characterized in vitro folding pathway of BPTI. These results suggest that elimination or destabilization of a disulfide bond whose formation is problematic in vitro can enhance in vivo protein folding. The use of these in vivo selections may prove a valuable way to identify and eliminate disulfides and other rate-limiting steps in the folding of proteins, including those proteins whose in vitro folding pathways are unknown. Antioxid. Redox Signal. 14, 973-984.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90494/1/ars-2E2010-2E3712.pd

Inhomogeneously doped two-leg ladder systems

A chemical potential difference between the legs of a two-leg ladder is found to be harmful for Cooper pairing. The instability of superconductivity in such systems is analyzed by compairing results of various analytical and numerical methods. Within a strong coupling approach for the t-J model, supplemented by exact numerical diagonalization, hole binding is found unstable beyond a finite, critical chemical potential difference. The spinon-holon mean field theory for the t-J model shows a clear reduction of the the BCS gaps upon increasing the chemical potential difference leading to a breakdown of superconductivity. Based on a renormalization group approach and Abelian bosonization, the doping dependent phase diagram for the weakly interacting Hubbard model with different chemical potentials was determined.Comment: Revtex4, 11 pages, 7 figure

Excitation Spectra and Thermodynamic Response of Segmented Heisenberg Spin Chains

The spectral and thermodynamic response of segmented quantum spin chains is analyzed using a combination of numerical techniques and finite-size scaling arguments. Various distributions of segment lengths are considered, including the two extreme cases of quenched and annealed averages. As the impurity concentration is increased, it is found that (i) the integrated spectral weight is rapidly reduced, (ii) a pseudo-gap feature opens up at small frequencies, and (iii) at larger frequencies a discrete peak structure emerges, dominated by the contributions of the smallest cluster segments. The corresponding low-temperature thermodynamic response has a divergent contribution due to the odd-site clusters and a sub-dominant exponentially activated component due to the even-site segments whose finite-size gap is responsible for the spectral weight suppression at small frequencies. Based on simple scaling arguments, approximate low-temperature expressions are derived for the uniform susceptibility and the heat capacity. These are shown to be in good agreement with numerical solutions of the Bethe ansatz equations for ensembles of open-end chains.Comment: RevTex, 9 pages with 6 figure

Comprehensive characterization of circulating tumor cells and cell-free DNA in patients with metastatic melanoma

Advances in therapeutic approaches for melanoma urge the need for biomarkers that can identify patients at risk for recurrence and to guide treatment. The potential use of liquid biopsies in identifying biomarkers is increasingly being recognized. Here, we present a head-to-head comparison of several techniques to analyze circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in 20 patients with metastatic melanoma. In this study, we investigated whether diagnostic leukapheresis (DLA) combined with multimarker flow cytometry (FCM) increased the detection of CTCs in blood compared to the CellSearch platform. Additionally, we characterized cfDNA at the level of somatic mutations, extent of aneuploidy and genome-wide DNA methylation. Both CTCs and cfDNA measures were compared to tumor markers and extracranial tumor burden on radiological imaging. Compared to the CellSearch method applied on peripheral blood, DLA combined with FCM increased the proportion of patients with detectable CTCs from 35% to 70% (P = 0.06). However, the median percentage of cells that could be recovered by the DLA procedure was 29%. Alternatively, cfDNA mutation and methylation analysis detected tumor load in the majority of patients (90% and 93% of samples successfully analyzed, respectively). The aneuploidy score was positive in 35% of all patients. From all tumor measurements in blood, lactate dehydrogenase (LDH) levels were significantly correlated to variant allele frequency (P = 0.004). Furthermore, the presence of CTCs in DLA was associated with tumor burden (P &lt; 0.001), whereas the presence of CTCs in peripheral blood was associated with number of lesions on radiological imaging (P &lt; 0.001). In conclusion, DLA tended to increase the proportion of patients with detectable CTCs but was also associated with low recovery. Both cfDNA and CTCs were correlated with clinical parameters such as LDH levels and extracranial tumor burden.</p