Evaluating probability forecasts

Probability forecasts of events are routinely used in climate predictions, in forecasting default probabilities on bank loans or in estimating the probability of a patient's positive response to treatment. Scoring rules have long been used to assess the efficacy of the forecast probabilities after observing the occurrence, or nonoccurrence, of the predicted events. We develop herein a statistical theory for scoring rules and propose an alternative approach to the evaluation of probability forecasts. This approach uses loss functions relating the predicted to the actual probabilities of the events and applies martingale theory to exploit the temporal structure between the forecast and the subsequent occurrence or nonoccurrence of the event.Comment: Published in at http://dx.doi.org/10.1214/11-AOS902 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Carbon and Strontium Abundances of Metal-Poor Stars

We present carbon and strontium abundances for 100 metal-poor stars measured from R$\sim$7000 spectra obtained with the Echellette Spectrograph and Imager at the Keck Observatory. Using spectral synthesis of the G-band region, we have derived carbon abundances for stars ranging from [Fe/H]$=-1.3$ to [Fe/H]$=-3.8$. The formal errors are $\sim 0.2$ dex in [C/Fe]. The strontium abundance in these stars was measured using spectral synthesis of the resonance line at 4215 {\AA}. Using these two abundance measurments along with the barium abundances from our previous study of these stars, we show it is possible to identify neutron-capture-rich stars with our spectra. We find, as in other studies, a large scatter in [C/Fe] below [Fe/H]$= -2$. Of the stars with [Fe/H]$<-2$, 9$\pm$4% can be classified as carbon-rich metal-poor stars. The Sr and Ba abundances show that three of the carbon-rich stars are neutron-capture-rich, while two have normal Ba and Sr. This fraction of carbon enhanced stars is consistent with other studies that include this metallicity range.Comment: ApJ, Accepte

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin.

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types

Filling some black holes: modeling the connection between urbanization, infrastructure, and global service intensity

This empirical article combines insights from previous research on the level of knowledge-intensive service in metropolitan areas with the aim to develop an understanding of the spatial structure of the global service economy. We use a stepwise regression model with the Globalization and World Cities research network's measure of globalized service provisioning as the dependent variable and a range of variables focusing on population, infrastructure, urban primacy, and national regulation as independent variables. The discussion of the results focuses on model parameters as well as the meaning of outliers and is used to explore some avenues for future research

A CaVβ SH3/Guanylate Kinase Domain Interaction Regulates Multiple Properties of Voltage-gated Ca2+ Channels

Auxiliary Ca2+ channel β subunits (CaVβ) regulate cellular Ca2+ signaling by trafficking pore-forming α1 subunits to the membrane and normalizing channel gating. These effects are mediated through a characteristic src homology 3/guanylate kinase (SH3–GK) structural module, a design feature shared in common with the membrane-associated guanylate kinase (MAGUK) family of scaffold proteins. However, the mechanisms by which the CaVβ SH3–GK module regulates multiple Ca2+ channel functions are not well understood. Here, using a split-domain approach, we investigated the role of the interrelationship between CaVβ SH3 and GK domains in defining channel properties. The studies build upon a previously identified split-domain pair that displays a trans SH3–GK interaction, and fully reconstitutes CaVβ effects on channel trafficking, activation gating, and increased open probability (Po). Here, by varying the precise locations used to separate SH3 and GK domains and monitoring subsequent SH3–GK interactions by fluorescence resonance energy transfer (FRET), we identified a particular split-domain pair that displayed a subtly altered configuration of the trans SH3–GK interaction. Remarkably, this pair discriminated between CaVβ trafficking and gating properties: α1C targeting to the membrane was fully reconstituted, whereas shifts in activation gating and increased Po functions were selectively lost. A more extreme case, in which the trans SH3–GK interaction was selectively ablated, yielded a split-domain pair that could reconstitute neither the trafficking nor gating-modulation functions, even though both moieties could independently engage their respective binding sites on the α1C (CaV1.2) subunit. The results reveal that CaVβ SH3 and GK domains function codependently to tune Ca2+ channel trafficking and gating properties, and suggest new paradigms for physiological and therapeutic regulation of Ca2+ channel activity

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). © 2006 Nature Publishing Group

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.The main fundingwas provided by the Alzheimer’s SocietyUK and the BUPA Foundation. The research in Newcastle was supported in part by the Dunhill Medical Trust (R173/1110). Tissue for this study was provided by (i) the Newcastle Brain Tissue Resource; (ii) the London Neurodegenerative Brain Bank; and (iii) the Thomas Willis Oxford Brain Collection. All three resources are funded in part by grants from the UK Medical Research Council and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK. In Singapore, funding was provided by a Centre grant (NMRC/CG/NUHS/2010) and a Clinical Scientist Award (NMRC/CSA/032/2011) from the National Medical Research Council.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/bpa.12182/abstract

Increased Yield of ttbb at Hadron Colliders in Low-Energy Supersymmetry

Light bottom squarks and gluinos have been invoked to explain the b quark pair production excess at the Tevatron. We investigate the associated production of ttbb at hadron colliders in this scenario, and find that the rates for this process are enhanced over the Standard Model prediction. If light gluinos exist, it may be possible to detect them at the Tevatron, and they could easily be observed at the LHC.Comment: 5p, references added, version accepted to PR

Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that MetQ is a lipoprotein

NmMetQ is a substrate binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To address the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the absence and presence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function/topology, playing a role in NmMetNI-mediated transport at the inner-membrane in addition to moonlighting functions on the bacterial surface