Probing the interface magnetism in the FeMn/NiFe exchange bias system using magnetic second harmonic generation

Second harmonic generation magneto-optic Kerr effect (SHMOKE) experiments, sensitive to buried interfaces, were performed on a polycrystalline NiFe/FeMn bilayer in which areas with different exchange bias fields were prepared using 5 KeV He ion irradiation. Both reversible and irreversible uncompensated spins are found in the antiferromagnetic layer close to the interface with the ferromagnetic layer. The SHMOKE hysteresis loop shows the same exchange bias field as obtained from standard magnetometry. We demonstrate that the exchange bias effect is controlled by pinned uncompensated spins in the antiferromagnetic layer.Comment: submitted to Phys. Rev. Let

Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours

We recently discovered that stathmin was overexpressed in a subgroup of human breast carcinomas. Stathmin is a cytosolic phosphoprotein proposed to act as a relay integrating diverse cell signalling pathways, notably during the control of cell growth and differentiation. It may also be considered as one of the key regulators of cell division for its ability to destabilize microtubules in a phosphorylation-dependent manner. To assess the significance of stathmin overexpression in breast cancer, we evaluated the correlation of stathmin expression, quantified by reverse transcription polymerase chain reaction, with several disease parameters in a large series of human primary breast cancer (n = 133), obtained in strictly followed up women, whose clinico-pathological data were fully available. In agreement with our preliminary survey, stathmin was found overexpressed in a subgroup of tumours (22%). In addition, overexpression was correlated to the loss of steroid receptors (oestrogen, P = 0.0006; progesterone, P = 0.008), and to the Scarff–Bloom–Richardson histopathological grade III (P = 0.002), this latter being ascribable to the mitotic index component (P = 0.02). Furthermore studies at the DNA level indicated that stathmin is overexpressed irrespective of its genomic status. Our findings raise important questions concerning the causes and consequences of stathmin overexpression, and the reasons of its inability to counteract cell proliferation in the overexpression group. © 2000 Cancer Research Campaig

Field dependence of the temperature at the peak of the ZFC magnetization

The effect of an applied magnetic field on the temperature at the maximum of the ZFC magnetization, $M_{ZFC}$, is studied using the recently obtained analytic results of Coffey et al. (Phys. Rev. Lett. {\bf 80}(1998) 5655) for the prefactor of the N\'{e}el relaxation time which allow one to precisely calculate the prefactor in the N\'{e}el-Brown model and thus the blocking temperature as a function of the coefficients of the Taylor series expansion of the magnetocrystalline anisotropy. The present calculations indicate that even a precise determination of the prefactor in the N\'{e}el-Brown theory, which always predicts a monotonic decrease of the relaxation time with increasing field, is insufficient to explain the effect of an applied magnetic field on the temperature at the maximum of the ZFC magnetization. On the other hand, we find that the non linear field-dependence of the magnetization along with the magnetocrystalline anisotropy appears to be of crucial importance to the existence of this maximum.Comment: 14 LaTex209 pages, 6 EPS figures. To appear in J. Phys.: Condensed Matte

On the non-abelian Brumer-Stark conjecture and the equivariant Iwasawa main conjecture

We show that for an odd prime p, the p-primary parts of refinements of the (imprimitive) non-abelian Brumer and Brumer-Stark conjectures are implied by the equivariant Iwasawa main conjecture (EIMC) for totally real fields. Crucially, this result does not depend on the vanishing of the relevant Iwasawa mu-invariant. In combination with the authors' previous work on the EIMC, this leads to unconditional proofs of the non-abelian Brumer and Brumer-Stark conjectures in many new cases.Comment: 33 pages; to appear in Mathematische Zeitschrift; v3 many minor updates including new title; v2 some cohomological arguments simplified; v1 is a revised version of the second half of arXiv:1408.4934v

Cancer risk management strategies and perceptions of unaffected women 5 years after predictive genetic testing for BRCA1/2 mutations

In a French national cohort of unaffected females carriers/non-carriers of a BRCA1/2 mutation, long-term preventive strategies and breast/ovarian cancer risk perceptions were followed up to 5 years after test result disclosure, using self-administered questionnaires. Response rate was 74%. Carriers (N=101) were younger (average age±SD=37±10) than non-carriers (N=145; 42±12). There were four management strategies that comprised 88% of the decisions made by the unaffected carriers: 50% opted for breast surveillance alone, based on either magnetic resonance imaging (MRI) and other imaging (31%) or mammography alone (19%); 38% opted for either risk reducing salpingo-oophorectomy (RRSO) and breast surveillance, based on MRI and other imaging (28%) or mammography alone (10%). The other three strategies were: risk reducing mastectomy (RRM) and RRSO (5%), RRM alone (2%) and neither RRM/RRSO nor surveillance (6%). The results obtained for various age groups are presented here. Non-carriers often opted for screening despite their low cancer risk. Result disclosure increased carriers' short-term high breast/ovarian cancer risk perceptions (P⩽0.02) and decreased non-carriers' short- and long-term perceptions (P<0.001). During follow-up, high breast cancer risk perceptions increased with time among those who had no RRM and decreased in the opposite case; high ovarian cancer risk perceptions increased further with time among those who had no RRSO and decreased in the opposite case; RRSO did not affect breast cancer risk perceptions. Informed decision-making involves letting women know whether opting for RRSO and breast MRI surveillance is as effective in terms of survival as RRM and RRSO

The combinatorics of plane curve singularities. How Newton polygons blossom into lotuses

This survey may be seen as an introduction to the use of toric and tropical geometry in the analysis of plane curve singularities, which are germs $(C,o)$ of complex analytic curves contained in a smooth complex analytic surface $S$. The embedded topological type of such a pair $(S, C)$ is usually defined to be that of the oriented link obtained by intersecting $C$ with a sufficiently small oriented Euclidean sphere centered at the point $o$, defined once a system of local coordinates $(x,y)$ was chosen on the germ $(S,o)$. If one works more generally over an arbitrary algebraically closed field of characteristic zero, one speaks instead of the combinatorial type of $(S, C)$. One may define it by looking either at the Newton-Puiseux series associated to $C$ relative to a generic local coordinate system $(x,y)$, or at the set of infinitely near points which have to be blown up in order to get the minimal embedded resolution of the germ $(C,o)$ or, thirdly, at the preimage of this germ by the resolution. Each point of view leads to a different encoding of the combinatorial type by a decorated tree: an Eggers-Wall tree, an Enriques diagram, or a weighted dual graph. The three trees contain the same information, which in the complex setting is equivalent to the knowledge of the embedded topological type. There are known algorithms for transforming one tree into another. In this paper we explain how a special type of two-dimensional simplicial complex called a lotus allows to think geometrically about the relations between the three types of trees. Namely, all of them embed in a natural lotus, their numerical decorations appearing as invariants of it. This lotus is constructed from the finite set of Newton polygons created during any process of resolution of $(C,o)$ by successive toric modifications.Comment: 104 pages, 58 figures. Compared to the previous version, section 2 is new. The historical information, contained before in subsection 6.2, is distributed now throughout the paper in the subsections called "Historical comments''. More details are also added at various places of the paper. To appear in the Handbook of Geometry and Topology of Singularities I, Springer, 202

Prognostic value of CCND1 gene status in sporadic breast tumours, as determined by real-time quantitative PCR assays

The CCND1 gene, a key cell-cycle regulator, is often altered in breast cancer, but the mechanisms underlying CCND1 dysregulation and the clinical significance of CCND1 status are unclear. We used real-time quantitative PCR and RT–PCR assays based on fluorescent TaqMan methodology to quantify CCND1 gene amplification and expression in a large series of breast tumours. CCND1 overexpression was observed in 44 (32.8%) of 134 breast tumour RNAs, ranging from 3.3 to 43.7 times the level in normal breast tissues, and correlated significantly with positive oestrogen receptor status (P=0.0003). CCND1 overexpression requires oestrogen receptor integrity and is exacerbated by amplification at 11q13 (the site of the CCND1 gene), owing to an additional gene dosage effect. Our results challenge CCND1 gene as the main 11q13 amplicon selector. The relapse-free survival time of patients with CCND1-amplified tumours was shorter than that of patients without CCND1 alterations, while that of patients with CCND1-unamplified-overexpressed tumours was longer (P=0.011). Only the good prognostic significance of CCND1-unamplified-overexpression status persisted in Cox multivariate regression analysis. This study confirms that CCND1 is an ER-responsive or ER-coactivator gene in breast cancer, and points to the CCND1 gene as a putative molecular marker predictive of hormone responsiveness in breast cancer. Moreover, CCND1 amplification status dichotomizes the CCND1-overexpressing tumors into two groups with opposite outcomes

An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition

<p>Abstract</p> <p>Background</p> <p>Germ-line mutations in the <it>BRCA1 </it>and <it>BRCA2 </it>genes are major contributors to hereditary breast/ovarian cancer. Large rearrangements are less frequent in the <it>BRCA2 </it>gene than in <it>BRCA1</it>. We report, here, the first total deletion of exon 3 in the <it>BRCA2 </it>gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for <it>BRCA2 </it>large rearrangements. Deletion of exon 3, which is in phase, does not alter the reading frame. Low levels of alternative transcripts lacking exon 3 (Δ3 delta3 transcript) have been reported in normal tissues, which raises the question whether deletion of exon 3 is pathogenic.</p> <p>Methods</p> <p>Large <it>BRCA2 </it>rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the <it>BRCA2 </it>gene and sequencing. To determine the effect of exon 3 deletion and assess its pathogenic effect, three methods of transcript quantification were used: fragment analysis of FAM-labelled PCR products, specific allelic expression using an intron 2 polymorphism and competitive quantitative RT-PCR.</p> <p>Results</p> <p>Large rearrangements of <it>BRCA2 </it>were detected in six index cases out of 2058 tested (3% of all deleterious <it>BRCA2 </it>mutations). This study reports the first large rearrangement of the <it>BRCA2 </it>gene that includes all of exon 3 and leads to an <it>in frame </it>deletion of exon 3 at the transcriptional level. Thirty five variants in exon 3 and junction regions of <it>BRCA2 </it>are also reported, that contribute to the interpretation of the pathogenicity of the deletion. The quantitative approaches showed that there are three classes of delta3 <it>BRCA2 </it>transcripts (low, moderate and exclusive). Exclusive expression of the delta3 transcript by the mutant allele and segregation data provide evidence for a causal effect of the exon 3 deletion.</p> <p>Conclusion</p> <p>This paper highlights that large rearrangements and total deletion of exon 3 in the <it>BRCA2 </it>gene could contribute to hereditary breast and/or ovarian cancer. In addition, our findings suggest that, to interpret the pathogenic effect of any variants of exon 3, both accurate transcript quantification and co-segregation analysis are required.</p