An Over-Massive Black Hole in the Compact Lenticular Galaxy NGC1277

All massive galaxies likely have supermassive black holes at their centers, and the masses of the black holes are known to correlate with properties of the host galaxy bulge component. Several explanations have been proposed for the existence of these locally-established empirical relationships; they include the non-causal, statistical process of galaxy-galaxy merging, direct feedback between the black hole and its host galaxy, or galaxy-galaxy merging and the subsequent violent relaxation and dissipation. The empirical scaling relations are thus important for distinguishing between various theoretical models of galaxy evolution, and they further form the basis for all black hole mass measurements at large distances. In particular, observations have shown that the mass of the black hole is typically 0.1% of the stellar bulge mass of the galaxy. The small galaxy NGC4486B currently has the largest published fraction of its mass in a black hole at 11%. Here we report observations of the stellar kinematics of NGC 1277, which is a compact, disky galaxy with a mass of 1.2 x 10^11 Msun. From the data, we determine that the mass of the central black hole is 1.7 x 10^10 Msun, or 59% its bulge mass. Five other compact galaxies have properties similar to NGC 1277 and therefore may also contain over-sized black holes. It is not yet known if these galaxies represent a tail of a distribution, or if disk-dominated galaxies fail to follow the normal black hole mass scaling relations.Comment: 7 pages. 6 figures. Nature. Animation at http://www.mpia.de/~bosch/blackholes.htm

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Modern Modal Testing: A Cautionary Tale

Over the past 50 years, great advances have been achieved in both analytical modal analysis (i.e. finite element models and analysis) and experimental modal analysis (i.e. modal testing) in aerospace and other fields. With the advent of more powerful computers, higher performance instrumentation and data acquisition systems, and powerful linear modal extraction tools, analysts and test engineers have a breadth and depth of technical resources only dreamed of by our predecessors. However, some observed recent trends indicate that hard lessons learned are being forgotten or ignored, and possibly fundamental concepts are not being understood. These trends have the potential of leading to the degradation of the quality of and confidence in both analytical and test results. These trends are a making of our own doing, and directly related to having ever more powerful computers, programmatic budgetary pressures to limit analysis and testing, and technical capital loss due to the retirement of the senior component of a bimodal workforce. This paper endeavors to highlight some of the most important lessons learned, common pitfalls to hopefully avoid, and potential steps that may be taken to help reverse this trend

Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

<p>Abstract</p> <p>Background</p> <p>Extracts of chicory root have anti-inflammatory properties <it>in vitro </it>and in animal models of arthritis. The primary objective of this investigator-initiated, Phase 1, placebo-controlled, double blind, dose-escalating trial was to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis (OA). Secondary objectives were to assess effects on the signs and symptoms of this disorder.</p> <p>Methods</p> <p>Individuals greater than 50 years of age with OA of the hip or knee were eligible for trial entry. A total of 40 patients were enrolled in 3 cohorts and were treated with escalating chicory doses of 600 mg/day, 1200 mg/day and 1800 mg/day for 1 month. The ratio of active treatment to placebo was 5:3 in cohorts 1 and 2 (8 patients) each and 16:8 in cohort 3 (24 patients). Safety evaluations included measurement of vital signs and routine lab tests at baseline and the end of the treatment period. Efficacy evaluations at baseline and final visits included self-assessment questionnaires and measurement of the 25-foot walking time.</p> <p>Results</p> <p>In the highest dose cohort, 18 patients who completed treatment per protocol were analyzed for efficacy. In this group, 13 patients showed at least 20% improvement in the defined response domains of pain, stiffness and global assessment: 9 of 10 (90%) patients randomized to active treatment with chicory and 4 of 8 (50%) patients randomized to placebo (P = 0.06). In general, the treatment was well-tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event.</p> <p>Conclusions</p> <p>The results of this pilot study suggest that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. Clinicaltrials.gov identifier: NCT 01010919.</p

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

Spatial Variation in Foraging Behaviour of a Marine Top Predator (Phoca vitulina) Determined by a Large-Scale Satellite Tagging Program

The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Short-Term Memory Maintenance of Object Locations during Active Navigation: Which Working Memory Subsystem Is Essential?

The goal of the present study was to examine the extent to which working memory supports the maintenance of object locations during active spatial navigation. Participants were required to navigate a virtual environment and to encode the location of a target object. In the subsequent maintenance period they performed one of three secondary tasks that were designed to selectively load visual, verbal or spatial working memory subsystems. Thereafter participants re-entered the environment and navigated back to the remembered location of the target. We found that while navigation performance in participants with high navigational ability was impaired only by the spatial secondary task, navigation performance in participants with poor navigational ability was impaired equally by spatial and verbal secondary tasks. The visual secondary task had no effect on navigation performance. Our results extend current knowledge by showing that the differential engagement of working memory subsystems is determined by navigational ability