434 research outputs found
Recommended from our members
On the Difficulty of Measuring Forecasting Skill in Financial Markets
The use of correlation between forecasts and actual returns is commonplace in the literature, often used as a measurement of investors’ skill. A prominent application of this is the concept of the Information Coefficient (IC). Not only can IC be used as a tool to rate analysts and fund managers but it also represents an important parameter in the asset allocation and portfolio construction process. Nevertheless, theoretical understanding of it has typically been limited to the partial equilibrium context where the investing activities of each agent have no effect on other market participants. In this paper we show that this can be an undesirable oversimplification and we demonstrate plausible circumstances in which conventional empirical measurements of IC can be highly misleading. We suggest that improved understanding of IC in a general equilibrium setting can lead to refined portfolio decision making ex ante and more informative analysis of performance ex post.Information Rati
Recommended from our members
Social Welfare Issues of Financial Literacy
In the matter of financial literacy it is often supposed that more is automatically preferable to less. This paper considers to what extent this may be true generally, and specifically focuses on the case of investment forecasting skill (a significant component of an individual's financial literacy). We show that the while improved forecasting skill can increase an individual's own utility, the resulting increase in trading volume leads to higher asset price volatility. Under the plausible assumption that this volatility imposes disutility on non-investors, an interesting trade-off is exposed between the benefits of skill improvement which accrue to investors, and the costs suffered more broadly by society. The paper constructs a formal analytic framework in which to discuss these issues, examines under what conditions the marginal utility of skill is in fact monotonic for the individual and considers implications for policy-makers
Synthesis of oligodeoxyribonucleotides containing a tricyclic thio analogue of O6-methylguanine and their recognition by MGMT and Atl1
Promutagenic O6-alkylguanine adducts in DNA are repaired in humans by O6-methylguanine-DNA-methyltransferase (MGMT) in an irreversible reaction. Here we describe the synthesis of a phosphoramidite that allows the preparation of oligodeoxyribonucleotides (ODNs) containing a novel tricyclic thio analogue of O6-methylguanine in which the third ring bridges the 6-thio group and C7 of a 7-deazapurine. These ODNs are very poor substrates for MGMT and poorly recognised by the alkyltransferase-like protein, Atl1. Examination of the active sites of both MGMT and Atl1 suggest large steric clashes hindering binding of the analogue. Such analogues, if mutagenic, are likely to be highly toxic
The Fall of Stringy de Sitter
Kachru, Kallosh, Linde, & Trivedi recently constructed a four-dimensional de
Sitter compactification of IIB string theory, which they showed to be
metastable in agreement with general arguments about de Sitter spacetimes in
quantum gravity. In this paper, we describe how discrete flux choices lead to a
closely-spaced set of vacua and explore various decay channels. We find that in
many situations NS5-brane meditated decays which exchange NSNS 3-form flux for
D3-branes are comparatively very fast.Comment: 35 pp (11 pp appendices), 5 figures, v3. fixed minor typo
Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O6-Alkylguanines
Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O6-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O6-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O6-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER
Mass spectrometric analysis of the active site tryptic peptide of recombinant O6-methylguanine-DNA methyltransferase following incubation with human colorectal DNA reveals the presence of an O6-alkylguanine adductome
Human exposure to DNA alkylating agents is poorly characterized, partly because only a limited range of specific alkyl DNA adducts have been quantified. The human DNA repair protein, O6-methylguanine O6-methyltransferase (MGMT), irreversibly transfers the alkyl group from DNA O6-alkylguanines (O6-alkGs) to an acceptor cysteine, allowing the simultaneous detection of multiple O6-alkG modifications in DNA by mass spectrometric analysis of the MGMT active site peptide (ASP). Recombinant MGMT was incubated with oligodeoxyribonucleotides (ODNs) containing different O6-alkGs, Temozolomide-methylated calf thymus DNA (Me-CT-DNA), or human colorectal DNA of known O6-MethylG (O6-MeG) levels. It was digested with trypsin, and ASPs were detected and quantified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. ASPs containing S-methyl, S-ethyl, S-propyl, S-hydroxyethyl, S-carboxymethyl, S-benzyl, and S-pyridyloxobutyl cysteine groups were detected by incubating MGMT with ODNs containing the corresponding O6-alkGs. The LOQ of ASPs containing S-methylcysteine detected after MGMT incubation with Me-CT-DNA was <0.05 pmol O6-MeG per mg CT-DNA. Incubation of MGMT with human colorectal DNA produced ASPs containing S-methylcysteine at levels that correlated with those of O6-MeG determined previously by HPLC-radioimmunoassay (r2 = 0.74; p = 0.014). O6-CMG, a putative O6-hydroxyethylG adduct, and other potential unidentified MGMT substrates were also detected in human DNA samples. This novel approach to the identification and quantitation of O6-alkGs in human DNA has revealed the existence of a human DNA alkyl adductome that remains to be fully characterized. The methodology establishes a platform for characterizing the human DNA O6-alkG adductome and, given the mutagenic potential of O6-alkGs, can provide mechanistic information about cancer pathogenesis
Notch-IGF1 signalling in biliary epithelial cells drives their expansion and inhibits hepatocyte differentiation
[no abstract available
The First VERITAS Telescope
The first atmospheric Cherenkov telescope of VERITAS (the Very Energetic
Radiation Imaging Telescope Array System) has been in operation since February
2005. We present here a technical description of the instrument and a summary
of its performance. The calibration methods are described, along with the
results of Monte Carlo simulations of the telescope and comparisons between
real and simulated data. The analysis of TeV -ray observations of the
Crab Nebula, including the reconstructed energy spectrum, is shown to give
results consistent with earlier measurements. The telescope is operating as
expected and has met or exceeded all design specifications.Comment: Accepted by Astroparticle Physic
The Milky Way Bulge: Observed properties and a comparison to external galaxies
The Milky Way bulge offers a unique opportunity to investigate in detail the
role that different processes such as dynamical instabilities, hierarchical
merging, and dissipational collapse may have played in the history of the
Galaxy formation and evolution based on its resolved stellar population
properties. Large observation programmes and surveys of the bulge are providing
for the first time a look into the global view of the Milky Way bulge that can
be compared with the bulges of other galaxies, and be used as a template for
detailed comparison with models. The Milky Way has been shown to have a
box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an
additional spheroidal component. In this review we summarise the global
chemical abundances, kinematics and structural properties that allow us to
disentangle these multiple components and provide constraints to understand
their origin. The investigation of both detailed and global properties of the
bulge now provide us with the opportunity to characterise the bulge as observed
in models, and to place the mixed component bulge scenario in the general
context of external galaxies. When writing this review, we considered the
perspectives of researchers working with the Milky Way and researchers working
with external galaxies. It is an attempt to approach both communities for a
fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen
E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure
The Relationship Between Discrimination and Missed HIV Care Appointments Among Women Living with HIV
Receiving regular HIV care is crucial for maintaining good health among persons with HIV. However, racial and gender disparities in HIV care receipt exist. Discrimination and its impact may vary by race/ethnicity and gender, contributing to disparities. Data from 1578 women in the Women’s Interagency HIV Study ascertained from 10/1/2012 to 9/30/2016 were used to: (1) estimate the relationship between discrimination and missing any scheduled HIV care appointments and (2) assess whether this relationship is effect measure modified by race/ethnicity. Self-reported measures captured discrimination and the primary outcome of missing any HIV care appointments in the last 6 months. Log-binomial models accounting for measured sources of confounding and selection bias were fit. For the primary outcome analyses, women experiencing discrimination typically had a higher prevalence of missing an HIV care appointment. Moreover, there was no statistically significant evidence for effect measure modification by race/ethnicity. Interventions to minimize discrimination or its impact may improve HIV care engagement among women
- …