Immunodetectable cyclin D 1 is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancerous breast lesions

Cyclin D1 is associated with cell cycle regulation and has more recently been shown to stimulate the transcriptional functions of the oestrogen receptor (ER). Furthermore, in normal breast there is a negative association between expression of ER and the proliferation marker Ki67 indicating that either ER positive cells are non-dividing or that the receptor is down-regulated as cells enter cycle. This important relationship breaks down in many ER-positive cancers and precancerous breast lesions where the receptor is often detected on proliferating cells. The aims of the present study were to determine the interplay between ER, Ki67 and cyclin D 1 in individual cells within the spectrum of human breast lesions ranging from normal to invasive carcinoma by using dual staining immunofluorescence. We found that in normal breast there was a strong positive association between ER and cyclin D 1 expression. In contrast there was a strong negative association between cyclin D 1 and Ki67 expression. Similar findings were seen for the other precancerous and cancerous breast lesions. Thus immunodetectable cyclin D 1 within individual cells does not appear to be associated with cell cycle progression in the benign or malignant breast but instead may have important interactions with ER. © 2001 Cancer Research Campaign http://www.bjcancer.co

Structural Controls on Crustal Fluid Circulation and Hot Spring Geochemistry Above a Flat‐Slab Subduction Zone, Peru

Hot spring geochemistry from the Cordillera Blanca and Cordillera Huayhuash, Peru, reveal the influence of crustal‐scale structures on geothermal fluid circulation in an amagmatic region located above a flat‐slab subduction zone. To test the influence of contrasting modes of faulting in these regions, springs were targeted along the Cordillera Blanca detachment fault, within its hanging wall, in the footwall of the detachment, and in the Cordillera Huayhuash. Hot springs along the Cordillera Blanca detachment fault zone are associated with recent extension and normal faulting, and those in its footwall and the Cordillera Huayhuash are located in the Marañon fold and thrust belt where compressional structures dominate. Springs along and in the hanging wall of the Cordillera Blanca detachment fault yield brackish‐saline, alkaline‐chloride waters, with oxygen, hydrogen, carbon, and chlorine stable isotope values that suggest mixing between meteoric groundwater and saline brine affected by high water‐rock interaction. Geothermometry reservoir temperature estimates (RTEs) of 91–226°C indicate maximum flow path depths of 8.7 or 11 km, depending on geothermal gradient, associated with the Cordillera Blanca detachment fault. In contrast, springs in the footwall and in the Cordillera Huayhuash exhibit a wide range of water types with an isotopic affinity to meteoric water, suggesting a greater influence from shallow groundwater and less water‐rock interaction. For these springs, RTEs of 40–98°C correspond to much shallower circulation (1.6–4 km). Results indicate that the Cordillera Blanca detachment system accommodates significantly deeper circulation of crustal fluids compared to other regional compressional structures

Gene expression profiling in bladder cancer identifies potential therapeutic targets

Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation

A Sparse Stress Model

Force-directed layout methods constitute the most common approach to draw general graphs. Among them, stress minimization produces layouts of comparatively high quality but also imposes comparatively high computational demands. We propose a speed-up method based on the aggregation of terms in the objective function. It is akin to aggregate repulsion from far-away nodes during spring embedding but transfers the idea from the layout space into a preprocessing phase. An initial experimental study informs a method to select representatives, and subsequent more extensive experiments indicate that our method yields better approximations of minimum-stress layouts in less time than related methods.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

A variational method based on weighted graph states

In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a class of states which is suitable as a variational set to find ground states in spin systems of arbitrary spatial dimension and with long-range entanglement. Here, we continue the exposition of our technique, extend from spin 1/2 to higher spins and use the boson Hubbard model as a non-trivial example to demonstrate our scheme.Comment: 36 pages, 13 figure

A New Paradigm for Large Earthquakes in Stable Continental Plate Interiors

Large earthquakes within stable continental regions (SCR) show that significant amounts of elastic strain can be released on geological structures far from plate boundary faults, where the vast majority of the Earth's seismic activity takes place. SCR earthquakes show spatial and temporal patterns that differ from those at plate boundaries and occur in regions where tectonic loading rates are negligible. However, in the absence of a more appropriate model, they are traditionally viewed as analogous to their plate boundary counterparts, occuring when the accrual of tectonic stress localized at long-lived active faults reaches failure threshold. Here we argue that SCR earthquakes are better explained by transient perturbations of local stress or fault strength that release elastic energy from a pre-stressed lithosphere. As a result, SCR earthquakes can occur in regions with no previous seismicity and no surface evidence for strain accumulation. They need not repeat, since the tectonic loading rate is close to zero. Therefore, concepts of recurrence time or fault slip rate do not apply. As a consequence, seismic hazard in SCRs is likely more spatially distributed than indicated by paleoearthquakes, current seismicity, or geodetic strain rates