Pressure Induced Change in the Magnetic Modulation of CeRhIn5

We report the results of a high pressure neutron diffraction study of the heavy fermion compound CeRhIn5 down to 1.8 K. CeRhIn5 is known to order magnetically below 3.8 K with an incommensurate structure. The application of hydrostatic pressure up to 8.6 kbar produces no change in the magnetic wave vector qm. At 10 kbar of pressure however, a sudden change in the magnetic structure occurs. Although the magnetic transition temperature remains the same, qm increases from (0.5, 0.5, 0.298) to (0.5, 0.5, 0.396). This change in the magnetic modulation may be the outcome of a change in the electronic character of this material at 10 kbar.Comment: 4 pages, 3 figures include

Antimetastatic Potential of PAI-1 Specific RNA Aptamers

The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is increased in several cancers, including breast, where it is associated with a poor outcome. Metastatic breast cancer has a dismal prognosis, as evidenced by treatment goals that are no longer curative but are largely palliative in nature. PAI-1 competes with integrins and the urokinase plasminogen activator receptor on the surface of breast cancer cells for binding to vitronectin. This results in the detachment of tumor cells from the extracellular matrix, which is critical to the metastatic process. For this reason, we sought to isolate RNA aptamers that disrupt the interaction between PAI-1 and vitronectin. Through utilization of combinatorial chemistry techniques, aptamers have been selected that bind to PAI-1 with high affinity and specificity. We identified two aptamers, WT-15 and SM-20, that disrupt the interactions between PAI-1 and heparin, as well as PAI-1 and vitronectin, without affecting the antiprotease activity of PAI-1. Furthermore, SM-20 prevented the detachment of breast cancer cells (MDA-MB-231) from vitronectin in the presence of PAI-1, resulting in an increase in cellular adhesion. Therefore, the PAI-1 aptamer SM-20 demonstrates therapeutic potential as an antimetastatic agent and could possibly be used as an adjuvant to traditional chemotherapy for breast cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78126/1/oli.2008.0177.pd

From D-Dbar Pairs to Branes in Motion

We investigate various supersymmetric brane intersections. Motivated by the recent results on supertubes, we investigate general constraints in which parallel brane-antibrane configurations are supersymmetric. Dual descriptions of these configurations involve systems of branes in relative motion. In particular, we find new supersymmetric configurations which are not related to a static brane intersection by a boost. In these new configurations, the intersection point moves at the speed of light. These systems provide interesting time dependent backgrounds for open strings.Comment: 28+1 pages, 8 figures, uses JHEP3.cl

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

'Disc-jet' coupling in black hole X-ray binaries and active galactic nuclei

In this chapter I will review the status of our phenomenological understanding of the relation between accretion and outflows in accreting black hole systems. This understanding arises primarily from observing the relation between X-ray and longer wavelength (infrared, radio) emission. The view is necessarily a biased one, beginning with observations of X-ray binary systems, and attempting to see if they match with the general observational properties of active galactic nuclei.Comment: 28 pages, 15 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Gauge/Gravity Duals with Holomorphic Dilaton

We consider configurations of D7-branes and whole and fractional D3-branes with N=2 supersymmetry. On the supergravity side these have a warp factor, three-form flux and a nonconstant dilaton. We discuss general IIB solutions of this type and then obtain the specific solutions for the D7/D3 system. On the gauge side the D7-branes add matter in the fundamental representation of the D3-brane gauge theory. We find that the gauge and supergravity metrics on moduli space agree. However, in many cases the supergravity curvature is large even when the gauge theory is strongly coupled. In these cases we argue that the useful supergravity dual must be a IIA configuration.Comment: 23 pages. Minor corrections to eqs. 2.6 and 4.8 v3: reference to non-Abelian BPS monopole solution corrected (Chamseddine-Volkov

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy