Hierarchical hyperbolicity of graphs of multicurves

We show that many graphs naturally associated to a connected, compact, orientable surface are hierarchically hyperbolic spaces in the sense of Behrstock, Hagen and Sisto. They also automatically have the coarse median property defined by Bowditch. Consequences for such graphs include a distance formula analogous to Masur and Minsky's distance formula for the mapping class group, an upper bound on the maximal dimension of quasiflats, and the existence of a quadratic isoperimetric inequality. The hierarchically hyperbolic structure also gives rise to a simple criterion for when such graphs are Gromov hyperbolic.Comment: 27 pages, 4 figures. Minor changes from previous version. Addition of appendix describing a hierarchically hyperbolic structure on the arc grap

Thickness and relative hyperbolicity for graphs of multicurves

We prove that any graph of multicurves satisfying certain natural properties is either hyperbolic, relatively hyperbolic, or thick. Further, this geometric characterization is determined by the set of subsurfaces that intersect every vertex of the graph. This extends previously established results for the pants graph and the separating curve graph to a broad family of graphs associated to surfaces.Comment: Version accepted for publication by the Journal of Topolog

Large scale geometry of curve complexes

We study the coarse geometry of curve graphs and related graphs for connected, compact, orientable surfaces. We prove that the separating curve graph of a surface is a hierarchically hyperbolic space, as defined by Behrstock, Hagen and Sisto, whenever it is connected. It also automatically has the coarse median property defined by Bowditch. Consequences for the separating curve graph include a distance formula analogous to Masur and Minsky's distance formula for the mapping class group, an upper bound on the maximal dimension of quasiflats, and the existence of a quadratic isoperimetric inequality. We also describe surgery arguments for studying the coarse geometry of curve graphs and similar graphs. Specifically, we give a new proof of the uniform hyperbolicity of the curve graphs, extending methods of Przytycki and Sisto. We also give an elementary proof of Masur and Minsky's result that the disc graphs are quasi-convex in the curve graphs. Moreover, we show that the constant of quasiconvexity is independent of the surface, as also shown in work of Hamenstädt

Differential responsiveness of MET inhibition in non-small-cell lung cancer with altered CBL.

Casitas B-lineage lymphoma (CBL) is an E3 ubiquitin ligase and a molecule of adaptor that we have shown is important for non-small-cell lung cancer (NSCLC). We investigated if MET is a target of CBL and if enhanced in CBL-altered NSCLC. We showed that CBL wildtype cells have lower MET expression than CBL mutant cells. Ubiquitination of MET was also decreased in CBL mutant cells compared to wildtype cells. Mutant cells were also more sensitive to MET inhibitor SU11274 than wild-type cells. sh-RNA-mediated knockdown of CBL enhanced cell motility and colony formation in NSCLC cells, and these activities were inhibited by SU11274. Assessment of the phospho-kinome showed decreased phosphorylation of pathways involving MET, paxillin, EPHA2, and VEGFR. When CBL was knocked down in the mutant cell line H1975 (erlotinib-resistant), it became sensitive to MET inhibition. Our findings suggest that CBL status is a potential positive indicator for MET-targeted therapeutics in NSCLC

Razors and lasers : an undergraduate experiment to determine thermal expansion coefficients using single slit diffraction measurements

Single slit diffraction and the thermal expansion of materials are common components of an undergraduate physics course, though these topics are often taught independently in both lectures and laboratory based courses. Higher levels of cognitive domains can be achieved by building on these established topics and combining them into a single experiment that also introduces new tools and techniques for data handling and analysis. Here we describe an experiment where the thermal expansion of a metal bar shifts an attached razor blade such that the separation between this blade and another fixed blade decreases. This decrease in blade separation allows for changes in the peak separation for single slit diffraction to be measured and the expansion coefficient of three metal bars (copper, steel and aluminium) is determined to good agreement with accepted values. The use of multiple peak fitting allows students to develop more sophisticated analysis techniques that are applicable beyond this experiment and are transferable to different areas of experimental physics

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism

Context: Reduced health-related quality of life (HRQoL) is common in patients with hypoparathyroidism on conventional therapy with calcium and active vitamin D supplements. Objective: To examine the effects of recombinant human parathyroid hormone (rhPTH[1-84]) on HRQoL as measured by the 36-Item Short Form Health Survey (SF-36) during the multinational, randomized, placebo-controlled REPLACE study. Patients: 122 adults with chronic hypoparathyroidism. Intervention(s): Following an optimization period when calcium and/or active vitamin D supplements were adjusted to reach target serum calcium levels (8.0-9.0 mg/dL; 2.0-2.2 mmol/L), patients were randomized to receive placebo (n=39) or rhPTH(1-84) (n=83) (starting dose 50 mug/day, could be titrated up to 100 mug/day); supplement doses were adjusted to maintain target serum calcium levels. Main Outcome Measure(s): Change from baseline (post-optimization, at randomization) to Week 24 in HRQoL as assessed by the SF-36v2 health survey. Results: Overall, the between-group differences were not statistically significant. However, in the rhPTH(1-84) group, there were significant improvements in the physical component summary score (P=0.004) and in body pain (P<0.05), general health (P<0.05), and vitality (P<0.001) domains as compared with baseline values. In the placebo group, there were no significant changes for any of the domains. The magnitude of change between 0 and 24 weeks in SF-36 scores was negatively correlated with baseline scores, such that patients with lower HRQoL at baseline were more likely to experience improvement in response to treatment. Conclusions: Treatment with rhPTH(1-84) may improve HRQoL in adults with hypoparathyroidism