Quantum spin fluctuations in the dipolar Heisenberg-like rare earth pyrochlores

The magnetic pyrochlore oxide materials of general chemical formula R2Ti2O7 and R2Sn2O7 (R = rare earth) display a host of interesting physical behaviours depending on the flavour of rare earth ion. These properties depend on the value of the total magnetic moment, the crystal field interactions at each rare earth site and the complex interplay between magnetic exchange and long-range dipole-dipole interactions. This work focuses on the low temperature physics of the dipolar isotropic frustrated antiferromagnetic pyrochlore materials. Candidate magnetic ground states are numerically determined at zero temperature and the role of quantum spin fluctuations around these states are studied using a Holstein-Primakoff spin wave expansion to order 1/S. The results indicate the strong stability of the proposed classical ground states against quantum fluctuations. The inclusion of long range dipole interactions causes a restoration of symmetry and a suppression of the observed anisotropy gap leading to an increase in quantum fluctuations in the ground state when compared to a model with truncated dipole interactions. The system retains most of its classical character and there is little deviation from the fully ordered moment at zero temperature.Comment: Latex2e, 18 pages, 4 figures, IOP forma

Quantum Griffiths effects and smeared phase transitions in metals: theory and experiment

In this paper, we review theoretical and experimental research on rare region effects at quantum phase transitions in disordered itinerant electron systems. After summarizing a few basic concepts about phase transitions in the presence of quenched randomness, we introduce the idea of rare regions and discuss their importance. We then analyze in detail the different phenomena that can arise at magnetic quantum phase transitions in disordered metals, including quantum Griffiths singularities, smeared phase transitions, and cluster-glass formation. For each scenario, we discuss the resulting phase diagram and summarize the behavior of various observables. We then review several recent experiments that provide examples of these rare region phenomena. We conclude by discussing limitations of current approaches and open questions.Comment: 31 pages, 7 eps figures included, v2: discussion of the dissipative Ising chain fixed, references added, v3: final version as publishe

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man

Ezrin Ubiquitylation by the E3 Ubiquitin Ligase, WWP1, and Consequent Regulation of Hepatocyte Growth Factor Receptor Activity

The membrane cytoskeleton linker ezrin participates in several functions downstream of the receptor Met in response to Hepatocyte Growth Factor (HGF) stimulation. Here we report a novel interaction of ezrin with a HECT E3 ubiquitin ligase, WWP1/Aip5/Tiul1, a potential oncogene that undergoes genomic amplification and overexpression in human breast and prostate cancers. We show that ezrin binds to the WW domains of WWP1 via the consensus motif PPVY477 present in ezrin’s C-terminus. This association results in the ubiquitylation of ezrin, a process that requires an intact PPVY477 motif. Interestingly ezrin ubiquitylation does not target the protein for degradation by the proteasome. We find that ezrin ubiquitylation by WWP1 in epithelial cells leads to the upregulation of Met level in absence of HGF stimulation and increases the response of Met to HGF stimulation as measured by the ability of the cells to heal a wound. Interestingly this effect requires ubiquitylated ezrin since it can be rescued, after depletion of endogenous ezrin, by wild type ezrin but not by a mutant of ezrin that cannot be ubiquitylated. Taken together our data reveal a new role for ezrin in Met receptor stability and activity through its association with the E3 ubiquitin ligase WWP1. Given the role of Met in cell proliferation and tumorigenesis, our results may provide a mechanistic basis for understanding the role of ezrin in tumor progression

Expression of high p53 levels in colorectal cancer: a favourable prognostic factor

The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0–52 ng mg−1). Using an arbitrary cut-off value of 2.7 ng mg−1, 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis. © 1999 Cancer Research Campaig

Breast MRI: guidelines from the European Society of Breast Imaging

The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)