Multinational Activity in the Modern World

Multinational corporations are the global goliaths of modern times. These entities collectively are responsible for large portions of world production, employment, investment, international trade, research, and innovation. Although their economic impact is most pronounced in high-income countries, where their activities have been concentrated historically, their reach increasingly extends to every corner of the world. Decisions made by these firms affect not only those who work for them, buy from them, do business with them, and compete with them, but also communities and countries in which they are located. As a result, their operations and activities are subjects of considerable interest and heated speculation

MendelianRandomization v0.5.0: updates to an R package for performing Mendelian randomization analyses using summarized data.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added to the package or updated in recent years. These features can be divided into four categories: robust methods for Mendelian randomization, methods for multivariable Mendelian randomization, functions for data visualization, and the ability to load data into the package seamlessly from the PhenoScanner web-resource. We provide examples of the graphical output produced by the data visualization commands, as well as syntax for obtaining suitable data and performing a Mendelian randomization analysis in a single line of code

The UV/optical spectra of the Type Ia supernova SN 2010jn: a bright supernova with outer layers rich in iron-group elements

Radiative transfer studies of Type Ia supernovae (SNe Ia) hold the promise of constraining both the time-dependent density profile of the SN ejecta and its stratification by element abundance which, in turn, may discriminate between different explosion mechanisms and progenitor classes. Here we present a detailed analysis of Hubble Space Telescope ultraviolet (UV) and ground-based optical spectra and light curves of the SN Ia SN 2010jn (PTF10ygu). SN 2010jn was discovered by the Palomar Transient Factory (PTF) 15 days before maximum light, allowing us to secure a time-series of four UV spectra at epochs from -11 to +5 days relative to B-band maximum. The photospheric UV spectra are excellent diagnostics of the iron-group abundances in the outer layers of the ejecta, particularly those at very early times. Using the method of 'Abundance Tomography' we have derived iron-group abundances in SN 2010jn with a precision better than in any previously studied SN Ia. Optimum fits to the data can be obtained if burned material is present even at high velocities, including significant mass fractions of iron-group elements. This is consistent with the slow decline rate (or high 'stretch') of the light curve of SN 2010jn, and consistent with the results of delayed-detonation models. Early-phase UV spectra and detailed time-dependent series of further SNe Ia offer a promising probe of the nature of the SN Ia mechanism.Comment: 17 pages, 9 figures (v3: several small updates to content including models; v2: metadata fixed), MNRAS, in pres

Supernova Simulations and Strategies For the Dark Energy Survey

We present an analysis of supernova light curves simulated for the upcoming Dark Energy Survey (DES) supernova search. The simulations employ a code suite that generates and fits realistic light curves in order to obtain distance modulus/redshift pairs that are passed to a cosmology fitter. We investigated several different survey strategies including field selection, supernova selection biases, and photometric redshift measurements. Using the results of this study, we chose a 30 square degree search area in the griz filter set. We forecast 1) that this survey will provide a homogeneous sample of up to 4000 Type Ia supernovae in the redshift range 0.05<z<1.2, and 2) that the increased red efficiency of the DES camera will significantly improve high-redshift color measurements. The redshift of each supernova with an identified host galaxy will be obtained from spectroscopic observations of the host. A supernova spectrum will be obtained for a subset of the sample, which will be utilized for control studies. In addition, we have investigated the use of combined photometric redshifts taking into account data from both the host and supernova. We have investigated and estimated the likely contamination from core-collapse supernovae based on photometric identification, and have found that a Type Ia supernova sample purity of up to 98% is obtainable given specific assumptions. Furthermore, we present systematic uncertainties due to sample purity, photometric calibration, dust extinction priors, filter-centroid shifts, and inter-calibration. We conclude by estimating the uncertainty on the cosmological parameters that will be measured from the DES supernova data.Comment: 46 pages, 30 figures, resubmitted to ApJ as Revision 2 (final author revision), which has subtle editorial differences compared to the published paper (ApJ, 753, 152). Note that this posting includes PDF only due to a bug in either the latex macros or the arXiv submission system. The source files are available in the DES document database: http://des-docdb.fnal.gov/cgi-bin/ShowDocument?docid=624

Hubble Space Telescope studies of low-redshift Type Ia supernovae: Evolution with redshift and ultraviolet spectral trends

We present an analysis of the maximum light, near ultraviolet (NUV; 2900-5500 A) spectra of 32 low redshift (0.001<z<0.08) Type Ia supernovae (SNe Ia), obtained with the Hubble Space Telescope (HST). We combine this spectroscopic sample with high-quality gri light curves obtained with robotic telescopes to measure photometric parameters, such as stretch, optical colour, and brightness. By comparing our data to a comparable sample of SNe Ia at intermediate-z (0.4<z<0.9), we detect modest spectral evolution (3-sigma), in the sense that our mean low-z NUV spectrum has a depressed flux compared to its intermediate-z counterpart. We also see a strongly increased dispersion about the mean with decreasing wavelength, confirming the results of earlier surveys. These trends are consistent with changes in metallicity as predicted by contemporary SN Ia spectral models. We also examine the properties of various NUV spectral diagnostics in the individual spectra. We find a general correlation between stretch and the velocity (or position) of many NUV spectral features. In particular, we observe that higher stretch SNe have larger Ca II H&K velocities, that also correlate with host galaxy stellar mass. This latter trend is probably driven by the well-established correlation between stretch and stellar mass. We find no trends between UV spectral features and optical colour. Mean spectra constructed according to whether the SN has a positive or negative Hubble residual show very little difference at NUV wavelengths, indicating that the NUV evolution and variation we identify do not directly correlate with Hubble residuals. Our work confirms and strengthens earlier conclusions regarding the complex behaviour of SNe Ia in the NUV spectral region, but suggests the correlations we find are more useful in constraining progenitor models than improving the use of SNe Ia as cosmological probes.Comment: 22 pages, 14 figures, accepted in MNRAS with minor changes - Spectra are available on WISeREP, http://www.weizmann.ac.il/astrophysics/wiserep

A rare variant in EZH2 is associated with prostate cancer risk

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10−5). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target

Constraining Cosmic Evolution of Type Ia Supernovae

We present the first large-scale effort of creating composite spectra of high-redshift type Ia supernovae (SNe Ia) and comparing them to low-redshift counterparts. Through the ESSENCE project, we have obtained 107 spectra of 88 high-redshift SNe Ia with excellent light-curve information. In addition, we have obtained 397 spectra of low-redshift SNe through a multiple-decade effort at Lick and Keck Observatories, and we have used 45 UV spectra obtained by HST/IUE. The low-redshift spectra act as a control sample when comparing to the ESSENCE spectra. In all instances, the ESSENCE and Lick composite spectra appear very similar. The addition of galaxy light to the Lick composite spectra allows a nearly perfect match of the overall spectral-energy distribution with the ESSENCE composite spectra, indicating that the high-redshift SNe are more contaminated with host-galaxy light than their low-redshift counterparts. This is caused by observing objects at all redshifts with the same slit width, which corresponds to different projected distances. After correcting for the galaxy-light contamination, subtle differences in the spectra remain. We have estimated the systematic errors when using current spectral templates for K-corrections to be ~0.02 mag. The variance in the composite spectra give an estimate of the intrinsic variance in low-redshift maximum-light SN spectra of ~3% in the optical and growing toward the UV. The difference between the maximum light low and high-redshift spectra constrain SN evolution between our samples to be < 10% in the rest-frame optical.Comment: 22 pages, 22 figures, submitted to ApJ. Composite spectra can be downloaded from http://astro.berkeley.edu/~rfoley/composite

Ultracontinuous single haplotype genome assemblies for the domestic cat (Felis catus) and Asian leopard cat (Prionailurus bengalensis)

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase \u3e99.9% of the reads into the two species’ haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in one or two large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation and speciation

Forest disturbance and vector transmitted diseases in thelowland tropical rainforest of central Panama

objective To explore possible changes in the community attributes of haematophagous insects as afunction of forest disturbance. We compare the patterns of diversity and abundance, plus thebehavioural responses of three epidemiologically distinct vector assemblages across sites depictingvarious levels of forest cover.methods Over a 3-year period, we sampled mosquitoes, sandflies and biting-midges in forestedhabitats of central Panama. We placed CDC light traps in the forest canopy and in the understorey togather blood-seeking females.results We collected 168 405 adult haematophagous dipterans in total, including 26 genera and 86species. Pristine forest settings were always more taxonomically diverse than the disturbed forest sites,confirming that disturbance has a negative impact on species richness. Species of Phlebotominae andCulicoides were mainly classified as climax (i.e. forest specialist) or disturbance-generalist, which tendto decrease in abundance along with rising levels of disturbance. In contrast, a significant portion ofmosquito species, including primary and secondary disease vectors, was classified as colonists (i.e.disturbed-areas specialists), which tend to increase in numbers towards more disturbed forest habitats.At pristine forest, the most prevalent species of Phlebotominae and Culicoides partitioned the verticalniche by being active at the forest canopy or in the understorey; yet this pattern was less clear indisturbed habitats. Most mosquito species were not vertically stratified in their habitat preference.conclusion We posit that entomological risk and related pathogen exposure to humans is higher inpristine forest scenarios for Culicoides and Phlebotominae transmitted diseases, whereas forestdisturbance poses a higher entomological risk for mosquito-borne infections. This suggests that theDilution Effect Hypothesis (DEH) does not apply in tropical rainforests where highly abundant, yetunrecognised insect vectors and neglected zoonotic diseases occur. Comprehensive, community levelentomological surveillance is, therefore, the key for predicting potential disease spill over in scenariosof pristine forest intermixed with anthropogenic habitats. We suggest that changes in forest qualityshould also be considered when assessing arthropod-borne disease transmission risk.objective To explore possible changes in the community attributes of haematophagous insects as afunction of forest disturbance. We compare the patterns of diversity and abundance, plus thebehavioural responses of three epidemiologically distinct vector assemblages across sites depictingvarious levels of forest cover.methods Over a 3-year period, we sampled mosquitoes, sandflies and biting-midges in forestedhabitats of central Panama. We placed CDC light traps in the forest canopy and in the understorey togather blood-seeking females.results We collected 168 405 adult haematophagous dipterans in total, including 26 genera and 86species. Pristine forest settings were always more taxonomically diverse than the disturbed forest sites,confirming that disturbance has a negative impact on species richness. Species of Phlebotominae andCulicoides were mainly classified as climax (i.e. forest specialist) or disturbance-generalist, which tendto decrease in abundance along with rising levels of disturbance. In contrast, a significant portion ofmosquito species, including primary and secondary disease vectors, was classified as colonists (i.e.disturbed-areas specialists), which tend to increase in numbers towards more disturbed forest habitats.At pristine forest, the most prevalent species of Phlebotominae and Culicoides partitioned the verticalniche by being active at the forest canopy or in the understorey; yet this pattern was less clear indisturbed habitats. Most mosquito species were not vertically stratified in their habitat preference.conclusion We posit that entomological risk and related pathogen exposure to humans is higher inpristine forest scenarios for Culicoides and Phlebotominae transmitted diseases, whereas forestdisturbance poses a higher entomological risk for mosquito-borne infections. This suggests that theDilution Effect Hypothesis (DEH) does not apply in tropical rainforests where highly abundant, yetunrecognised insect vectors and neglected zoonotic diseases occur. Comprehensive, community levelentomological surveillance is, therefore, the key for predicting potential disease spill over in scenariosof pristine forest intermixed with anthropogenic habitats. We suggest that changes in forest qualityshould also be considered when assessing arthropod-borne disease transmission risk

Sosa on Knowledge, Judgment and Guessing

In Chapter 3 of Judgment and Agency, Sosa (Judgment and Agency, 2015) explicates the concept of a fully apt performance. In the course of doing so, he draws from illustrative examples of practical performances and applies lessons drawn to the case of cognitive performances, and in particular, to the cognitive performance of judging. Sosa’s examples in the practical sphere are rich and instructive. But there is, I will argue, an interesting disanalogy between the practical and cognitive examples he relies on. Ultimately, I think the source of the disanalogy is a problematic picture of the cognitive performance of guessing and its connection to knowledge and defeat. Once this critical line of argument is advanced, an alternative picture of guessing, qua cognitive performance, is articulated, one which avoids the problems discussed, and yet remains compatible with Sosa’s broader framework