Asymmetric Information, Trading Volume, and Portfolio Performance

In dealership markets, asymmetric information feeds through to higher transaction costs as dealers adjust their bid-ask spreads to compensate for anticipated losses. In this paper, we show that the presence of asymmetric information can also provide a positive externality to those market participants who operate in multiple markets-portfolio managers. Specifically, insiders lower the estimation errors of portfolio selection methods, thus improving asset allocation. We develop multiple artificial markets, in which portfolio managers trade alongside informed and uniformed speculators, and we contrast the performance of 'volatility timing'-a method that relies on efficient price discovery - with that of 'naive diversification'. Volatility timing is shown to consistently outperform naive diversification on a risk-adjusted basis

The Globular Cluster System of NGC 3115

The evolution of galaxies through cosmic time remains a key question in Extra- galactic Astronomy. Globular Clusters (GCs) are believed to be good tracers of this evolution as they form during large star formation events. In this thesis we use spectroscopic data of GCs, taken using the FORS2 instrument on the Very Large Telescope, to create a catalogue of kinematics and metallicities for GCs in the S0 galaxy of NGC 3115. In order to do this the data was reduced using the ESO RE- FLEX program, creating 1D spectra for each of the GC targets. These were then fed into a modified version of the full spectrum fitting method ’pPXF’ to extract the kinematics, metallicities and ages of each target. The dataset created via this method was then compared to, and combined with, supplementary data from other surveys to create a more complete catalogue of GCs in NGC 3115. From this cata- logue there is evidence that the bimodal colour distribution is caused by a underlying bimodal metallicity distribution. Implying that at least two major star formation events have occurred in the history of NGC 3115

The chicken B-cell line DT40 proteome, beadome and interactomes.

In developing a new quantitative AP-MS method for exploring interactomes in the chicken B-cell line DT40, we also surveyed the most abundant proteins in this organism and explored the likely contaminants that bind to a variety of affinity resins that would later be confirmed quantitatively [1]. We present the 'Top 150 abundant DT40 proteins list', the DT40 beadomes as well as protein interaction lists for the Phosphatidyl inositol 5-phosphate 4-kinase 2β and Fanconi anaemia protein complexes.We thanks Prof. R. Irvine for providing the JPR3 cell line, to Dr. E. Rajendra for providing the FANCC cell line, FANC antibodies and helpful discussions, to Dr. M. Deery and J. Howard for assistance with MS. This work was funded by the Biotechnology and Biological Sciences Research Council (UK) Grant BB/H024085/1.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.dib.2014.12.00

Protein neighbors and proximity proteomics

Within cells, proteins can co-assemble into functionally integrated and spatially restricted multicomponent complexes. Often, the affinities between individual proteins are relatively weak, and proteins within such clusters may interact only indirectly with many of their other protein neighbors. This makes proteomic characterization difficult using methods such as immunoprecipitation or cross-linking. Recently, several groups have described the use of enzyme-catalyzed proximity labeling reagents that covalently tag the neighbors of a targeted protein with a small molecule such as fluorescein or biotin. The modified proteins can then be isolated by standard pulldown methods and identified by mass spectrometry. Here we will describe the techniques as well as their similarities and differences. We discuss their applications both to study protein assemblies and to provide a new way for characterizing organelle proteomes. We stress the importance of proteomic quantitation and independent target validation in such experiments. Furthermore, we suggest that there are biophysical and cell-biological principles that dictate the appropriateness of enzyme-catalyzed proximity labeling methods to address particular biological questions of interest.This work was supported by Biotechnology and Biological Sciences Research Council (UK) Grant BB/J021091/1. XWL & SP supported by Chinese Ministry of Science and Technology 973 Program Grants 2012CB911000 and 2013CB910700 and National Natural Science Foundation of China Grant 31110103914.This is the final version of the article. It was first available from ASBMB via http://dx.doi.org/10.1074/mcp.R115.05290

Characterization of a Temperature-Sensitive Vertebrate Clathrin Heavy Chain Mutant as a Tool to Study Clathrin-Dependent Events In Vivo

Clathrin and clathrin-dependent events are evolutionary conserved although it is believed that there are differences in the requirement for clathrin in yeast and higher vertebrates. Clathrin is a long-lived protein and thus, with clathrin knockdowns only long-term consequences of clathrin depletion can be studied. Here, we characterize the first vertebrate temperature-sensitive clathrin heavy chain mutant as a tool to investigate responses to rapid clathrin inactivation in higher eukaryotes. Although we created this mutant using a clathrin cryo-electron microscopy model and a yeast temperature-sensitive mutant as a guide, the resulting temperature-sensitive clathrin showed an altered phenotype compared to the corresponding yeast temperature-sensitive clathrin. First, it seemed to form stable triskelions at the non-permissive temperature although endocytosis was impaired under these conditions. Secondly, as a likely consequence of the stable triskelions at the non-permissive temperature, clathrin also localized correctly to its target membranes. Thirdly, we did not observe missorting of the lysosomal enzyme beta-glucuronidase which could indicate that the temperature-sensitive clathrin is still operating at the non-permissive temperature at the Golgi or, that, like in yeast, more than one TGN trafficking pathway exists. Fourthly, in contrast to yeast, actin does not appear to actively compensate in general endocytosis. Thus, there seem to be differences between vertebrates and yeast which can be studied in further detail with this newly created tool

An investment case analysis for the prevention and treatment of adolescent mental disorders and suicide in England

BackgroundAdolescent mental health (AMH) needs in England have increased dramatically and needs exceed treatment availability. This study undertook a comparative assessment of the health and economic return on investment (ROI) of interventions to prevent and treat mental disorders among adolescents (10–19 years) and examined intervention affordability and readiness.MethodsInterventions were identified following a review of published and grey literature. A Markov model followed a simulated adolescent cohort to estimate implementation costs and health, education, and economic benefits. Intervention affordability was assessed, comparing annual cost per adolescent with NHS England per capita spending, and an expert panel assessed intervention readiness using a validated framework.ResultsOver 10- and 80-year horizons, interventions to treat mild anxiety and mild depression were most cost-effective, with the highest individual lifetime ROI (GBP 5822 GBP 1 and GBP 257: GBP 1). Preventing anxiety and depression was most affordable and ‘implementation ready’ and offered the highest health and economic benefits. A priority package (anxiety and depression prevention; mild anxiety and mild depression treatment) would avert 5 million disability-adjusted life-years (DALYS) and achieve an ROI of GBP 15: GBP 1 over 10 years or 11.5 million DALYs (ROI of GBP 55: GBP 1) over 80 years.ConclusionThe economic benefits from preventing and treating common adolescent mental disorders equivalent to 25% of NHS England’s annual spending in 2021 over 10 years and 91% over 80 years. Preventing and early treatment for anxiety and depression had the highest ROIs and strong implementation readiness.<br/

SDF-1 chemokine signalling modulates the apoptotic responses to iron deprivation of clathrin-depleted DT40 cells.

We have previously deleted both endogenous copies of the clathrin heavy-chain gene in the chicken pre B-cell-line DT40 and replaced them with clathrin under the control of a tetracycline-regulatable promoter (Tet-Off). The originally derived cell-line DKO-S underwent apoptosis when clathrin expression was repressed. We have also described a cell-line DKO-R derived from DKO-S cells that was less sensitive to clathrin-depletion. Here we show that the restriction of transferrin uptake, resulting in iron deprivation, is responsible for the lethal consequence of clathrin-depletion. We further show that the DKO-R cells have up-regulated an anti-apoptotic survival pathway based on the chemokine SDF-1 and its receptor CXCR4. Our work clarifies several puzzling features of clathrin-depleted DT40 cells and reveals an example of how SDF-1/CXCR4 signalling can abrogate pro-apoptotic pathways and increase cell survival. We propose that the phenomenon described here has implications for the therapeutic approach to a variety of cancers.The work was supported by the following: Department of Biochemistry, University of Cambridge, BBSRC, and Marie Curie Fellowship (FRMW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.pone.010627

Factors which influence the cardiac surgeon's decision not to operate on patients referred for consideration of surgery

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to document what proportion of patients referred for consideration of cardiac surgery are turned down, the reasons given for not operating and also to evaluate what happens to those patients who do not undergo surgery.</p> <p>Methods</p> <p>382 elective patients referred for consideration of cardiac surgery to one of six consultant cardiac surgeons at Wythenshawe Hospital during a one year period from were included in the study. Data for those patients who underwent an operation were collected prospectively in a cardiac surgery database. The case notes of those patients who did not undergo an operation were reviewed to establish reasons given by surgeons for not operating. Patients were followed up to determine vital status at the end of the study period.</p> <p>Results</p> <p>333 (87.2%) patients underwent an operation and 49 (12.8%) did not. 68% of patients turned down were thought to be too high-risk. 14% of patients did not fulfill symptomatic or prognostic criteria for surgery and in 8% of patients coronary artery surgery was thought ineffective due to poor distal vessels. 6% of patients declined an operation and 4% were thought to be more suitable for coronary angioplasty. Patients turned down for surgery had more renal dysfunction (p = 0.017), respiratory disease (p < 0.001) and peripheral vascular disease (p < 0.001), were more likely to have undergone prior heart surgery (p < 0.001) and to have poor left ventricular function (p = 0.003). Patients turned down for surgery had significantly higher EuroSCORE values compared to patients who underwent an operation: 5 versus 4 (p = 0.006). Freedom from death in the patients turned down for surgery at 1-, 6-, 12- and 24-months was 95.9%, 91.8%, 83.7% and 71.4% respectively, compared with 97.9%, 96.7%, 96.4% and 94.5% for the patients who underwent an operation (p < 0.001 [log-rank]). 14 of the 15 deaths that occurred in the turned down group occurred in the category considered too high-risk for surgery.</p> <p>Conclusion</p> <p>12.8% of patients referred for consideration of cardiac surgery did not undergo an operation. Two thirds of patients not accepted for surgery were thought too high risk. Those patients who did not undergo an operation had a significantly worse mortality.</p