Evidence for a black hole in a radio-quiet quasar nucleus

We present the first milli-arcsecond resolution radio images of a radio-quiet quasar, detecting a high brightness temperature core with data from the VLBA. On maps made with lower-frequency data from MERLIN and the VLA jets appear to emanate from the core in opposite directions, which correspond to radio-emission on arcsecond scales seen with the VLA at higher frequencies. These provide strong evidence for a black-hole--based jet-producing central engine, rather than a starburst, being responsible for the compact radio emission in this radio-quiet quasar.Comment: 10 pages including 1 postscript figure; uses aaspp4.sty. Accepted for publication in Ap. J. Lett. Also available from http://www-astro.physics.ox.ac.uk/research/preprints

Hex Player—a virtual musical controller

In this paper, we describe a playable musical interface for tablets and multi-touch tables. The interface is a generalized keyboard, inspired by the Thummer, and consists of an array of virtual buttons. On a generalized keyboard, any given interval always has the same shape (and therefore fingering); furthermore, the fingering is consistent over a broad range of tunings. Compared to a physical generalized keyboard, a virtual version has some advantages—notably, that the spatial location of the buttons can be transformed by shears and rotations, and their colouring can be changed to reflect their musical function in different scales. We exploit these flexibilities to facilitate the playing not just of conventional Western scales but also a wide variety of microtonal generalized diatonic scales known as moment of symmetry, or well-formed, scales. A user can choose such a scale, and the buttons are automatically arranged so their spatial height corresponds to their pitch, and buttons an octave apart are always vertically above each other. Furthermore, the most numerous scale steps run along rows, while buttons within the scale are light-coloured, and those outside are dark or removed. These features can aid beginners; for example, the chosen scale might be the diatonic, in which case the piano’s familiar white and black colouring of the seven diatonic and five chromatic notes is used, but only one scale fingering need ever be learned (unlike a piano where every key needs a different fingering). Alternatively, it can assist advanced composers and musicians seeking to explore the universe of unfamiliar microtonal scales

A Simple Theory of Complex Valuation

Complex valuations of assets, companies, government programs, damages, and the like cannot be done without expertise, yet judges routinely pick an arbitrary value that falls somewhere between the extreme numbers suggested by competing experts. This creates costly uncertainty and undermines the legitimacy of the court. Proposals to remedy this well-recognized difficulty have become increasingly convoluted. As a result, no solution has been effectively adopted and the problem persists. This Article suggests that the valuation dilemma stems from a misconception of the inquiry involved. Courts have treated valuation as its own special type of inquiry distinct from traditional fact-finding. We show that reintroducing fundamental principles of fact-finding can provide a simpler and more accurate method of complex valuation. Our conclusion rests on the premise that valuations are nothing more than exercises in routine fact-finding. Valuation is not an ethereal question with no right answer. Rather, valuation is a process of inferring the value that a relevant community places on an asset. This basic point has been ignored in practice and received almost no attention in the academy. Recognizing this foundational point can both restore the legitimacy of the process and reduce the costs of uncertainty and biased testimony. We demonstrate that a return to traditional evidentiary rules, including attention to burdens of proof, will discourage courts from resorting to ad hoc calculations and will encourage courts to arrive at valuations through vetted methodologies that are shown to be reasonably accurate and, most importantly, supported by the record. We further show that this will lead to an improvement in the quality of information provided by expert witnesses

Evaluation of IRI's seasonal climate forecasts for the extreme 15% tails

This paper evaluates the quality of real-time seasonal probabilistic forecasts of the extreme 15% tails of the climatological distribution of temperature and precipitation issued by the International Research Institute for Climate and Society (IRI) from 1998 through 2009. IRI’s forecasts have been based largely on a two-tiered multimodel dynamical prediction system. Forecasts of the 15% extremes have been consistent with the corresponding probabilistic forecasts for the standard tercile-based categories; however, nonclimatological forecasts for the extremes have been issued sparingly. Results indicate positive skill in terms of resolution and discrimination for the extremes forecasts, particularly in the tropics. Additionally, with the exception of some overconfidence for extreme above-normal precipitation and a strong cool bias for temperature, reliability analyses suggest generally good calibration. Skills for temperature are generally higher than those for precipitation, due both to correct forecasts of increased probabilities of extremely high (above the upper 15th percentile) temperatures associated with warming trends, and to better discrimination of interannual variability. However, above-normal temperature extremes were substantially underforecast, as noted also for the IRI’s tercile forecasts

mTOR inhibition and levels of the DNA repair protein MGMT in T98G glioblastoma cells

Background: Glioblastoma multiforme (GBM), the most common and most aggressive type of primary adult brain tumour, responds poorly to conventional treatment. Temozolomide (TMZ) chemotherapy remains the most commonly used treatment, despite a large proportion of tumours displaying TMZ resistance. 60% of GBM tumours have unmethylated MGMT promoter regions, resulting in an overexpression of the DNA repair protein O6 -methylguanine-DNA methyltransferase (MGMT), which is responsible for tumour resistance to TMZ chemotherapy. Tumours also often exhibit hyperactive PI3-kinase/mTOR signalling, which enables them to resynthesise proteins quickly. Since MGMT is a suicide protein that is degraded upon binding to and repairing TMZ-induced O6-methylguanine adducts, it has been hypothesized that inhibition of translation via the mTOR signalling pathway could generate a tumour-specific reduction in MGMT protein and increase TMZ sensitivity. Methods: MGMT was monitored at the post-transcriptional, translational and protein levels, to determine what effect mTOR inhibition was having on MGMT protein expression in vitro. Results: We show that inhibiting mTOR signalling is indeed associated with acute inhibition of protein synthesis. Western blots show that despite this, relative to loading control proteins, steady state levels of MGMT protein increased and MGMT mRNA was retained in heavy polysomes. Whilst TMZ treatment resulted in maintained MGMT protein levels, concomitant treatment of T98G cells with TMZ and KU0063794 resulted in increased MGMT protein levels without changes in total mRNA levels. Conclusions: These in vitro data suggest that, counterintuitively, mTOR inhibition may not be a useful adjunct to TMZ therapy and that more investigation is needed before applying mTOR inhibitors in a clinical setting

Synthetic approaches to the C11-C27 fragments of bryostatins

Modified Julia reactions and reactions of lithated dithianes have been used to prepare intermediates for a synthesis of bryostatins.</p

An Integrated Tracker for STAR

The STAR experiment at the Relativistic Heavy Ion Collider RHIC studies the new state of matter produced in relativistic heavy ion collisions and the spin structure of the nucleon in collisions of polarized protons. In order to improve the capabilities for heavy flavor measurements and the reconstruction of charged vector bosons an upgrade of the tracking system both in the central and the forward region is pursued. The integrated system providing high resolution tracking and secondary vertex reconstruction capabilities will use silicon pixel, strip and GEM technology.Comment: 4 pages, 2 figures, to be published in the Proceedings of the 9th Conference on the Intersections of Particle and Nuclear Physics (CIPANP 2006), Rio Grande, Puerto Rico, May 30 - June 3, 200

Inclusive Hadron Production in p+p Collisions at STAR

The STAR experiment at RHIC has measured a variety of inclusive hadron cross sections in $p+p$ collisions at Sqrt(s) = 200 GeV. Measurements of the differential cross section for inclusive charged pion production at mid rapidity and for inclusive neutral pion production at forward rapidity (3.0 < eta < 4.2) as well as the first preliminary result from STAR for the differential cross section for inclusive neutral pion production near mid rapidity are presented. These cross sections are compared to next-to-leading order perturbative QCD calculations and can provide constraints on the pion fragmentation functions. Good agreement between data and pQCD has been found for all three cross sections.Comment: 4 pages, 1 figure, to be published in the Proceedings of the 9th Conference on the Intersections of Particle and Nuclear Physics (CIPANP 2006), Rio Grande, Puerto Rico, May 30 - June 3, 2006, v2 with updated reference

Phosphoregulation of Twist1 Provides a Mechanism of Cell Fate Control

Basic Helix-loop-Helix (bHLH) factors play a significant role in both development and disease. bHLH factors function as protein dimers where two bHLH factors compose an active transcriptional complex. In various species, the bHLH factor Twist has been shown to play critical roles in diverse developmental systems such as mesoderm formation, neurogenesis, myogenesis, and neural crest cell migration and differentiation. Pathologically, Twist1 is a master regulator of epithelial-to-mesenchymal transition (EMT) and is causative of the autosomal-dominant human disease Saethre Chotzen Syndrome (SCS). Given the wide spectrum of Twist1 expression in the developing embryo and the diverse roles it plays within these forming tissues, the question of how Twist1 fills some of these specific roles has been largely unanswered. Recent work has shown that Twist’s biological function can be regulated by its partner choice within a given cell. Our work has identified a phosphoregulatory circuit where phosphorylation of key residues within the bHLH domain alters partner affinities for Twist1; and more recently, we show that the DNA binding affinity of the complexes that do form is affected in a cis-element dependent manner. Such perturbations are complex as they not only affect direct transcriptional programs of Twist1, but they indirectly affect the transcriptional outcomes of any bHLH factor that can dimerize with Twist1. Thus, the resulting lineage-restricted cell fate defects are a combination of loss-of-function and gain-of-function events. Relating the observed phenotypes of defective Twist function with this complex regulatory mechanism will add insight into our understanding of the critical functions of this complex transcription factor

Antithrombotic therapy in palliative care

Management of venous thromboembolism (VTE) in patients in advanced cancer can be difficult due to the increased risk of recurrent and extending VTE despite therapeutic anticoagulation, and of bleeding due to or exacerbated by anticoagulation. Currently, best practice is long term administration of low molecular weight heparin (LMWH), but a recurrent VTE and bleeding rate remains, and some patients have contra-indications to anticoagulation. Newer anticoagulants such as oral anti-thrombin agents and biotinylated idrapurinux may have a role in the future.Management of venous thromboembolism (VTE) in patients in advanced cancer can be difficult due to the increased risk of recurrent and extending VTE despite therapeutic anticoagulation, and of bleeding due to or exacerbated by anticoagulation. Currently, best practice is long term administration of low molecular weight heparin (LMWH), but a recurrent VTE and bleeding rate remains, and some patients have contra-indications to anticoagulation. Newer anticoagulants such as oral anti-thrombin agents and biotinylated idrapurinux may have a role in the future