Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer

We have studied a set of 40 human lobular breast cancers for loss of heterozygosity (LOH) at various chromosome locations and for mutations in the coding region plus flanking intron sequences of the E-cadherin gene. We found a high frequency of LOH (100%, 31/31) at 16q21–q22.1. A significantly higher level of LOH was detected in ductal breast tumours at chromosome arms 1p, 3p, 9p, 11q, 13q and 18q compared to lobular breast tumours. Furthermore, we found a significant association between LOH at 16 q containing the E-cadherin locus and lobular histological type. Six different somatic mutations were detected in the E-cadherin gene, of which three were insertions, two deletions and one splice site mutation. Mutations were found in combination with LOH of the wild type E-cadherin locus and loss of or reduced E-cadherin expression detected by immunohistochemistry. The mutations described here have not previously been reported. We compared LOH at different chromosome regions with E-cadherin gene mutations and found a significant association between LOH at 13 q and E-cadherin gene mutations. A significant association was also detected between LOH at 13q and LOH at 7q and 11q. Moreover, we found a significant association between LOH at 3 p and high S phase, LOH at 9p and low ER and PgR content, LOH at 17p and aneuploidy. We conclude that LOH at 16q is the most frequent chromosome alteration and E-cadherin is a typical tumour suppressor gene in lobular breast cancer. © 1999 Cancer Research Campaig

Design and development of a low temperature, inductance based high frequency ac susceptometer

We report on the development of an induction based low temperature high frequency ac susceptometer capable of measuring at frequencies up to 3.5 MHz and at temperatures between 2 K and 300 K. Careful balancing of the detection coils and calibration have allowed a sample magnetic moment resolution of $5\times10^{-10} Am^2$ at 1 MHz. We will discuss the design and characterization of the susceptometer, and explain the calibration process. We also include some example measurements on the spin ice material CdEr$_2$S$_4$ and iron oxide based nanoparticles to illustrate functionality

Reconstruction of Random Colourings

Reconstruction problems have been studied in a number of contexts including biology, information theory and and statistical physics. We consider the reconstruction problem for random $k$-colourings on the $\Delta$-ary tree for large $k$. Bhatnagar et. al. showed non-reconstruction when $\Delta \leq \frac12 k\log k - o(k\log k)$ and reconstruction when $\Delta \geq k\log k + o(k\log k)$. We tighten this result and show non-reconstruction when $\Delta \leq k[\log k + \log \log k + 1 - \ln 2 -o(1)]$ and reconstruction when $\Delta \geq k[\log k + \log \log k + 1+o(1)]$.Comment: Added references, updated notatio

BRCA2 mutation carriers, reproductive factors and breast cancer risk

BACKGROUND: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear. METHODS: In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis. RESULTS: An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years. CONCLUSION: The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast

Strict inequalities of critical values in continuum percolation

We consider the supercritical finite-range random connection model where the points $x,y$ of a homogeneous planar Poisson process are connected with probability $f(|y-x|)$ for a given $f$. Performing percolation on the resulting graph, we show that the critical probabilities for site and bond percolation satisfy the strict inequality $p_c^{\rm site} > p_c^{\rm bond}$. We also show that reducing the connection function $f$ strictly increases the critical Poisson intensity. Finally, we deduce that performing a spreading transformation on $f$ (thereby allowing connections over greater distances but with lower probabilities, leaving average degrees unchanged) {\em strictly} reduces the critical Poisson intensity. This is of practical relevance, indicating that in many real networks it is in principle possible to exploit the presence of spread-out, long range connections, to achieve connectivity at a strictly lower density value.Comment: 38 pages, 8 figure

Phase Transitions on Nonamenable Graphs

We survey known results about phase transitions in various models of statistical physics when the underlying space is a nonamenable graph. Most attention is devoted to transitive graphs and trees

Fragility of the Free-Energy Landscape of a Directed Polymer in Random Media

We examine the sensitiveness of the free-energy landscape of a directed polymer in random media with respect to various kinds of infinitesimally weak perturbation including the intriguing case of temperature-chaos. To this end, we combine the replica Bethe ansatz approach outlined in cond-mat/0112384, the mapping to a modified Sinai model and numerically exact calculations by the transfer-matrix method. Our results imply that for all the perturbations under study there is a slow crossover from a weakly perturbed regime where rare events take place to a strongly perturbed regime at larger length scales beyond the so called overlap length where typical events take place leading to chaos, i.e. a complete reshuffling of the free-energy landscape. Within the replica space, the evidence for chaos is found in the factorization of the replicated partition function induced by infinitesimal perturbations. This is the reflex of explicit replica symmetry breaking.Comment: 29 pages, Revtex4, ps figure

Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R).

To access full text version of this article. Please click on the hyperlink "View/open" at the bottom of this pageWe aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. The study population consisted of 4,994 persons aged ≥ 67 years, who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA(1c) ≥ 6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA(1c), insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.NIH N01-AG-12100 NIH/NIA, National Eye Institute (NEI) of the NIH ZIAEY000401, Hjartavernd (the Icelandic Heart Association), Althingi (the Icelandic Parliament), University of Iceland

The repulsive lattice gas, the independent-set polynomial, and the Lov\'asz local lemma

We elucidate the close connection between the repulsive lattice gas in equilibrium statistical mechanics and the Lovasz local lemma in probabilistic combinatorics. We show that the conclusion of the Lovasz local lemma holds for dependency graph G and probabilities {p_x} if and only if the independent-set polynomial for G is nonvanishing in the polydisc of radii {p_x}. Furthermore, we show that the usual proof of the Lovasz local lemma -- which provides a sufficient condition for this to occur -- corresponds to a simple inductive argument for the nonvanishing of the independent-set polynomial in a polydisc, which was discovered implicitly by Shearer and explicitly by Dobrushin. We also present some refinements and extensions of both arguments, including a generalization of the Lovasz local lemma that allows for "soft" dependencies. In addition, we prove some general properties of the partition function of a repulsive lattice gas, most of which are consequences of the alternating-sign property for the Mayer coefficients. We conclude with a brief discussion of the repulsive lattice gas on countably infinite graphs.Comment: LaTex2e, 97 pages. Version 2 makes slight changes to improve clarity. To be published in J. Stat. Phy