The effects of pre- and postnatal administration of propionic acid and lipopolysaccharide on the behaviour of adolescent male and female rats

The gut microbiome plays an important role in immune functioning and neurodevelopment. Altered microbiome composition, leading to short chain fatty acid, and/or immune system dysfunction has been observed in children with autism spectrum disorders (ASD). This thesis describes the developmental influence of prenatal exposure to propionic acid (PPA), a metabolic fermentation product of enteric bacteria, or prenatal exposure to lipopolysaccharide (LPS), a bacterial mimetic and product of enteric bacteria, on a range of behaviours in male and female neonatal, adolescent and adult rats. Study one evaluated the effects of prenatal PPA and LPS, and postnatal PPA, on developmental milestones in early life and on subsequent locomotor activity and anxiety-related behaviours. Study two examined acoustic startle response (ASR) and prepulse inhibition, while the third examined social behaviours. Overall, prenatal and postnatal treatments subtly altered behaviour in a sex- and test-specific manner. Male and female rats showed developmental delay in the day of eye opening and in acquiring a nest seeking odor discrimination. Prenatal and postnatal PPA treatments increased anxiety-related behaviour and altered ASR. Male rats displayed alterations in social behaviour and locomotor activity that was not observed in female rats, supporting the male bias seen in autism. However, female rats also showed augmented sensitivity to PPA, displaying repetitive behaviour, altered ASR, and decreased prepulse inhibition, in agreement with the evidence that these behaviours are more severe in females with ASD. Together, these findings demonstrate that the metabolic products of enteric bacteria, PPA and LPS, may alter development in ways resembling ASD

Ability, Parental Valuation of Education and the High School Dropout Decision

We use a large, rich Canadian micro-level dataset to examine the channels through which family socio-economic status and unobservable characteristics affect children's decisions to drop out of high school. First, we document the strength of observable socio-economic factors: our data suggest that teenage boys with two parents who are themselves high school dropouts have a 16% chance of dropping out, compared to a dropout rate of less than 1% for boys whose parents both have a university degree. We examine the channels through which this socio-economic gradient arises using an extended version of the factor model set out in Carneiro, Hansen, and Heckman (2003). Specifically, we consider the impact of cognitive and non-cognitive ability and the value that parents place on education. Our results support three main conclusions. First, cognitive ability at age 15 has a substantial impact on dropping out. Second, parental valuation of education has an impact of approximately the same size as cognitive ability effects for medium and low ability teenagers. A low ability teenager has a probability of dropping out of approximately .03 if his parents place a high value on education but .36 if their education valuation is low. Third, parental education has no direct effect on dropping out once we control for ability and parental valuation of education. Our results point to the importance of whatever determines ability at age 15 (including, potentially, early childhood interventions) and of parental valuation of education during the teenage years. We also make a small methodological contribution by extending the standard factor based estimator to allow a non-linear relationship between the factors and a covariate of interest. We show that allowing for non-linearities has a substantial impact on estimated effects.Idiosyncratic Shocks, Disability, Insurance, Marriage

Ability, parental valuation of education and the high school dropout decision

We use a large, rich Canadian micro-level dataset to examine the channels through which family socio-economic status and unobservable characteristics affect children's decisions to drop out of high school. First, we document the strength of observable socio-economic factors: our data suggest that teenage boys with two parents who are themselves high school dropouts have a 16 per cent chance of dropping out, compared to a dropout rate of less than 1 per cent for boys whose parents both have a university degree. We examine the channels through which this socio-economic gradient arises using an extended version of the factor model set out in Carneiro, Hansen, and Heckman (2003). Specifically, we consider the impact of cognitive and non-cognitive ability and the value that parents place on education. Our results support three main conclusions. First, cognitive ability at age 15 has a substantial impact on dropping out. The highest ability individuals are predicted never to drop out regardless of parental education or parental valuation of education. In contrast, the lowest ability teenagers have a probability of dropping out of approximately .36 if their parents have a low valuation of education. Second, parental valuation of education has a substantial impact on medium and low ability teenagers. A low ability teenager has a probability of dropping out of approximately .03 if his parents place a high value on education but .36 if their educational valuation is low. These effects are estimated while conditioning on ability at age 15. Thus, under some assumptions, they reflect parental influences during the upper teenage years and are in addition to any impact they might have in the early childhood years leading up to age 15. Third, parental education has no direct effect on dropping out once we control for ability and parental valuation of education. Overall, our results point to the importance of whatever determines ability at age 15 (including, potentially, early childhood interventions) and of parental valuation of education during the teenage years. Our work also provides a small methodological contribution by extending the standard factor based estimator to allow a more non-linear relationship between the factors and a co-variate of interest. We show that allowing for non-linearities has a substantial impact on estimated effects.

In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails

This document is the Accepted Manuscript of the following article: Aditya K. Gupta, et al, 'In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails', Journal of Dermatological Treatment, Jan 2018. Under embargo until 10 January 2019. The final, published version is available online at doi: https://doi.org/10.1080/09546634.2017.1422078.Background: Topical antifungal treatments for onychomycosis are applied to clean, unpolished nails for 48 weeks or longer. Patients often wish to mask their infection with nail polish yet there is no evidence to suggest antifungal efficacy in the presence of nail polish. Objective: To determine if tavaborole retains the ability to penetrate the nail plate and inhibit fungal growth in the presence of nail polish. Method: Tavaborole was applied to human fingernails painted with 2 or 4 coats of nail polish, and unpainted nails in an ex vivo model. Nails were mounted on TurChub ® chambers seeded with Trichophyton rubrum and allowed to incubate for 7 days. Antifungal activity was assessed by measuring zones of inhibition. Results and conclusion: Tavaborole exhibited antifungal activity in all experimental groups. The zones of inhibition of T. rubrum for all experimental groups (2 or 4 coats of polish, unpolished) were greater than infected controls (polished and unpolished), p s <.001. Tavaborole penetrates polished nails and kills T. rubrum in this ex vivo model.Peer reviewe

A Mismatch in the Ultraviolet Spectra between Low-Redshift and Intermediate-Redshift Type Ia Supernovae as a Possible Systematic Uncertainty for Supernova Cosmology

We present Keck high-quality rest-frame ultraviolet (UV) through optical spectra of 21 Type Ia supernovae (SNe Ia) in the redshift range 0.11 < z < 0.37 and a mean redshift of 0.22 that were discovered during the Sloan Digital Sky Survey-II (SDSS-II) SN Survey. Using the broad-band photometry of the SDSS survey, we are able to reconstruct the SN host-galaxy spectral energy distributions (SEDs), allowing for a correction for the host-galaxy contamination in the SN Ia spectra. Comparison of composite spectra constructed from a subsample of 17 high-quality spectra to those created from a low-redshift sample with otherwise similar properties shows that the Keck/SDSS SNe Ia have, on average, extremely similar rest-frame optical spectra but show a UV flux excess. This observation is confirmed by comparing synthesized broad-band colors of the individual spectra, showing a difference in mean colors at the 2.4 - 4.4 sigma level for various UV colors. We further see a slight difference in the UV spectral shape between SNe with low-mass and high-mass host galaxies. Additionally, we detect a relationship between the flux ratio at 2770 and 2900 A and peak luminosity that differs from that observed at low redshift. We find that changing the UV SED of an SN Ia within the observed dispersion can change the inferred distance moduli by ~0.1 mag. This effect only occurs when the data probe the rest-frame UV. We suggest that this discrepancy could be due to differences in the host-galaxy population of the two SN samples or to small-sample statistics.Comment: 28 pages, 21 figures, accepted by AJ, spectra are available at http://www.cfa.harvard.edu/~rfoley/data

SN Refsdal: Classification as a Luminous and Blue SN 1987A-like Type II Supernova

We have acquired Hubble Space Telescope (HST) and Very Large Telescope near-infrared spectra and images of supernova (SN) Refsdal after its discovery as an Einstein cross in Fall 2014. The HST light curve of SN Refsdal matches the distinctive, slowly rising light curves of SN 1987A-like supernovae (SNe), and we find strong evidence for a broad H-alpha P-Cygni profile in the HST grism spectrum at the redshift (z = 1.49) of the spiral host galaxy. SNe IIn, powered by circumstellar interaction, could provide a good match to the light curve of SN Refsdal, but the spectrum of a SN IIn would not show broad and strong H-alpha absorption. From the grism spectrum, we measure an H-alpha expansion velocity consistent with those of SN 1987A-like SNe at a similar phase. The luminosity, evolution, and Gaussian profile of the H-alpha emission of the WFC3 and X-shooter spectra, separated by ~2.5 months in the rest frame, provide additional evidence that supports the SN 1987A-like classification. In comparison with other examples of SN 1987A-like SNe, SN Refsdal has a blue B-V color and a high luminosity for the assumed range of potential magnifications. If SN Refsdal can be modeled as a scaled version of SN 1987A, we estimate it would have an ejecta mass of 20+-5 solar masses. The evolution of the light curve at late times will provide additional evidence about the potential existence of any substantial circumstellar material (CSM). Using MOSFIRE and X-shooter spectra, we estimate a subsolar host-galaxy metallicity (8.3+-0.1 dex and <8.4 dex, respectively) near the explosion site.Comment: Submitted to ApJ; 26 page

The High-Metallicity Explosion Environment of the Relativistic Supernova 2009bb

We investigate the environment of the nearby (d ~ 40Mpc) broad-lined Type Ic supernova SN 2009bb. This event was observed to produce a relativistic outflow likely powered by a central accreting compact object. While such a phenomenon was previously observed only in long-duration gamma-ray bursts (LGRBs), no LGRB was detected in association with SN 2009bb. Using an optical spectrum of the SN 2009bb explosion site, we determine a variety of ISM properties for the host environment, including metallicity, young stellar population age, and star formation rate. We compare the SN explosion site properties to observations of LGRB and broad-lined SN Ic host environments on optical emission line ratio diagnostic diagrams. Based on these analyses, we find that the SN 2009bb explosion site has a very high metallicity of ~2x solar, in agreement with other broad-lined SN Ic host environments and at odds with the low-redshift LGRB host environments and recently proposed maximum metallicity limits for relativistic explosions. We consider the implications of these findings and the impact that SN 2009bb's unusual explosive properties and environment have on our understanding of the key physical ingredient that enables some SNe to produce a relativistic outflow.Comment: 7 pages, 4 figures, 1 table; accepted for publication in ApJ Letters (replaced to include missing figure

The Spectroscopic Diversity of Type Ia Supernovae

We present 2603 spectra of 462 nearby Type Ia supernovae (SN Ia) obtained during 1993-2008 through the Center for Astrophysics Supernova Program. Most of the spectra were obtained with the FAST spectrograph at the FLWO 1.5m telescope and reduced in a consistent manner, making data set well suited for studies of SN Ia spectroscopic diversity. We study the spectroscopic and photometric properties of SN Ia as a function of spectroscopic class using the classification schemes of Branch et al. and Wang et al. The width-luminosity relation appears to be steeper for SN Ia with broader lines. Based on the evolution of the characteristic Si II 6355 line, we propose improved methods for measuring velocity gradients, revealing a larger range than previously suspected, from ~0 to ~400 km/s/day considering the instantaneous velocity decline rate at maximum light. We find a weaker and less significant correlation between Si II velocity and intrinsic B-V color at maximum light than reported by Foley et al., owing to a more comprehensive treatment of uncertainties and host galaxy dust. We study the extent of nuclear burning and report new detections of C II 6580 in 23 early-time spectra. The frequency of C II detections is not higher in SN Ia with bluer colors or narrower light curves, in conflict with the recent results of Thomas et al. Based on nebular spectra of 27 SN Ia, we find no relation between the FWHM of the iron emission feature at ~4700 A and Dm15(B) after removing the two low-luminosity SN 1986G and SN 1991bg, suggesting that the peak luminosity is not strongly dependent on the kinetic energy of the explosion for most SN Ia. Finally, we confirm the correlation of velocity shifts in some nebular lines with the intrinsic B-V color of SN Ia at maximum light, although several outliers suggest a possible non-monotonic behavior for the largest blueshifts.Comment: 36 pages (emulateapj), 23 figures. Accepted for publication in AJ. Spectroscopic data available at http://www.cfa.harvard.edu/supernova/SNarchive.html . New SNID template set available at http://marwww.in2p3.fr/~blondin/software/snid/index.html . Minor changes from v1 to conform to published versio

The Fairness Challenge in Computer Networks

In this paper, the concept of fairness in computer networks is investigated. We motivate the need of examining fairness issues by providing example future application scenarios where fairness support is needed in order to experience sufficient service quality. Fairness definitions from political science and their application to computer networks are described and a state-of-the-art overview of research activities in fairness, from issues such a queue management and tcp-friendliness to issues like fairness in layered multi-rate multicast scenarios, is given. We contribute with this paper to the ongoing research activities by defining the fairness challenge with the purpose of helping direct future investigations to with spots on the map of research in fairness

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