Molecular Biomarkers for Celiac Disease:Past, Present and Future

Celiac disease (CeD) is a complex immune-mediated disorder that is triggered by dietary gluten in genetically predisposed individuals. CeD is characterized by inflammation and villous atrophy of the small intestine, which can lead to gastrointestinal complaints, malnutrition, and malignancies. Currently, diagnosis of CeD relies on serology (antibodies against transglutaminase and endomysium) and small-intestinal biopsies. Since small-intestinal biopsies require invasive upper-endoscopy, and serology cannot predict CeD in an early stage or be used for monitoring disease after initiation of a gluten-free diet, the search for non-invasive biomarkers is ongoing. Here, we summarize current and up-and-coming non-invasive biomarkers that may be able to predict, diagnose, and monitor the progression of CeD. We further discuss how current and emerging techniques, such as (single-cell) transcriptomics and genomics, can be used to uncover the pathophysiology of CeD and identify non-invasive biomarkers

Ground State and Spectral Properties of a Quantum Impurity in d-Wave Superconductors

The variational approach of Gunnarsson and Sch\"onhammer to the Anderson impurity model is generalized to study d-wave superconductors in the presence of dilute spin-1/2 impurities. We show that the local moment is screened when the hybridization exceeds a nonzero critical value at which the ground state changes from a spin doublet to a spin singlet. The electron spectral functions are calculated in both phases. We find that while a Kondo resonance develops above the Fermi level in the singlet phase, the spectral function exhibits a low-energy spectral peak below the Fermi level in the spin doublet phase. The origin of such a ``virtual Kondo resonance'' is the existence of low-lying collective excitations in the spin-singlet sector. We discuss our results in connection to recent spectroscopic experiments on Zn doped high-T$_c$ superconductors.Comment: 5 pages, 4figures, revised versio

Anomalous magnetic splitting of the Kondo resonance

The splitting of the Kondo resonance in the density of states of an Anderson impurity in finite magnetic field is calculated from the exact Bethe-ansatz solution. The result gives an estimate of the electron spectral function for nonzero magnetic field and Kondo temperature, with consequences for transport experiments on quantum dots in the Kondo regime. The strong correlations of the Kondo ground state cause a significant low-temperature reduction of the peak splitting. Explicit formulae are found for the shift and broadening of the Kondo peaks. A likely cause of the problems of large-N approaches to spin-1/2 impurities at finite magnetic field is suggested.Comment: 4 pages, 2 eps figures; published versio

Nonvanishing Local Moment in Triplet Superconductors

The Kondo effect in a $p_x + {\rm i} p_y$-wave superconductor is studied by applying the Wilson's numerical renormalization group method. In this type of superconductor with a full energy gap like a s-wave one, the ground state is always a spin doublet, while a local spin is shrunk by the Kondo effect. The calculated magnetic susceptibility indicates that the spin of the ground state is generated by the orbital effect of the $p_x + {\rm i} p_y$-wave Cooper pairs. The effect of spin polarization of the triplet superconductor is also discussed.Comment: 5 pages, 4 figures, to be published in J. Phys. Soc. Jp

Multichannel pseudogap Kondo model: Large-N solution and quantum-critical dynamics

We discuss a multichannel SU(N) Kondo model which displays non-trivial zero-temperature phase transitions due to a conduction electron density of states vanishing with a power law at the Fermi level. In a particular large-N limit, the system is described by coupled integral equations corresponding to a dynamic saddle point. We exactly determine the universal low-energy behavior of spectral densities at the scale-invariant fixed points, obtain anomalous exponents, and compute scaling functions describing the crossover near the quantum-critical points. We argue that our findings are relevant to recent experiments on impurity-doped d-wave superconductors.Comment: 4 pages, 3 figs; extended discussion of large-N spin representations, added references; accepted for publication in PR

Non Fermi Liquid Behaviour near a T=0T=0 spin-glass transition

In this paper we study the competition between the Kondo effect and RKKY interactions near the zero-temperature quantum critical point of an Ising-like metallic spin-glass. We consider the mean-field behaviour of various physical quantities. In the `quantum- critical regime' non-analytic corrections to the Fermi liquid behaviour are found for the specific heat and uniform static susceptibility, while the resistivity and NMR relaxation rate have a non-Fermi liquid dependence on temperature.Comment: 15 pages, RevTex 3.0, 1 uuencoded ps. figure at the en

Differential expression of DNA topoisomerase II alpha and -beta in P-gp and MRP-negative VM26, mAMSA and mitoxantrone-resistant sublines of the human SCLC cell line GLC4.

Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC4 with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC4/VM20x, GLC4/AM3x and GLC4/MIT60x, respectively) were derived to study the contribution of DNA topoisomerase II alpha and -beta (TopoII alpha and -beta) to resistance for TopoII-targeting drugs. The cell lines did not overexpress P-glycoprotein or the multidrug resistance-associated protein but were cross-resistant to other TopoII drugs. GLC4/VM20x showed a major decrease in TopoII alpha protein (54%; for all assays presented in this paper the GLC4 level was defined to be 100%) without reduction in TopoII beta protein; GLC4/AM3x showed only a major decrease in TopoII beta protein (to 18%) and not in TopoII alpha. In GLC4/MIT60x, the TopoII alpha and -beta protein levels were both decreased (TopoII alpha to 31%; TopoII beta protein was undetectable). The decrease in TopoII alpha protein in GLC4/VM20x and GLC4/MIT60x, was mediated by decreased TopoII alpha mRNA levels. Loss of TopoII alpha gene copies contributed to the mRNA decrease in these cell lines. Only in the GLC4/MIT60x cell line was an accumulation defect observed for the drug against which the cell line was made resistant. In conclusion, TopoII alpha and -beta levels were decreased differentially in the resistant cell lines, suggesting that resistance to these drugs may be mediated by a decrease in a specific isozyme

Ground State Properties of Anderson Impurity in a Gapless Host

Using the Bethe ansatz method, we study the ground state properties of a $U\to\infty$ Anderson impurity in a ``gapless'' host, where a density of band states vanishes at the Fermi level $\epsilon_F$ as $|\epsilon-\epsilon_F|$. As in metals, the impurity spin is proven to be screened at arbitrary parameters of the system. However, the impurity occupancy as a function of the bare impurity energy is shown to acquire novel qualitative features which demonstrate a nonuniversal behavior of the system. The latter explains why the Kondo screening is absent (or exists only at quite a large electron-impurity coupling) in earlier studies based on scaling arguments.Comment: 5 pages, no figure, RevTe

Local quantum phase transition in the pseudogap Anderson model: scales, scaling and quantum critical dynamics

The pseudogap Anderson impurity model provides a paradigm for understanding local quantum phase transitions, in this case between generalised fermi liquid and degenerate local moment phases. Here we develop a non-perturbative local moment approach to the generic asymmetric model, encompassing all energy scales and interaction strengths and leading thereby to a rich description of the problem. We investigate in particular underlying phase boundaries, the critical behaviour of relevant low-energy scales, and single-particle dynamics embodied in the local spectrum. Particular attention is given to the resultant universal scaling behaviour of dynamics close to the transition in both the GFL and LM phases, the scale-free physics characteristic of the quantum critical point itself, and the relation between the two.Comment: 39 pages, 19 figure

Bethe ansatz approach to thermodynamics of superconducting magnetic alloys

We derive thermodynamic Bethe ansatz equations for a model describing an $U\to\infty$ Anderson impurity embedded in a BCS superconductor. The equations are solved analytically in the zero-temperature limit, T=0. It is shown that the impurities depress superconductivity in the Kondo limit, however at T=0 the system remains in the superconducting state for any impurity concentration. In the mixed-valence regime, an impurity contribution to the density of states of the system near the Fermi level overcompensates a Cooper pairs weakening, and superconductivity is enhanced.Comment: 4 pages, RevTex, to appear in PR