TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer.

Tumor antigen-driven selection may expand T cells having T cell receptors (TCRs) of shared antigen specificity but different amino acid or nucleotide sequence in a process known as TCR convergence. Substitution sequencing errors introduced by TCRβ (TCRB) repertoire sequencing may create artifacts resembling TCR convergence. Given the anticipated differences in substitution error rates across different next-generation sequencing platforms, the choice of platform could be consequential. To test this, we performed TCRB sequencing on the same peripheral blood mononuclear cells (PBMC) from individuals with cancer receiving anti-CTLA-4 or anti-PD-1 using an Illumina-based approach (Sequenta) and an Ion Torrent-based approach (Oncomine TCRB-LR). While both approaches found similar TCR diversity, clonality, and clonal overlap, we found that Illumina-based sequencing resulted in higher TCR convergence than with the Ion Torrent approach. To build upon this initial observation we conducted a systematic comparison of Illumina-based TCRB sequencing assays, including those employing molecular barcodes, with the Oncomine assay, revealing differences in the frequency of convergent events, purportedly artifactual rearrangements, and sensitivity of detection. Finally, we applied the Ion Torrent-based approach to evaluate clonality and convergence in a cohort of individuals receiving anti-CTLA-4 blockade for cancer. We found that clonality and convergence independently predicted response and could be combined to improve the accuracy of a logistic regression classifier. These results demonstrate the importance of the sequencing platform in assessing TCRB convergence

Toward the PSTN/Internet Inter-Networking--Pre-PINT Implementations

This document contains the information relevant to the development of the inter-networking interfaces underway in the Public Switched Telephone Network (PSTN)/Internet Inter-Networking (PINT) Working Group. It addresses technologies, architectures, and several (but by no means all) existing pre-PINT implementations of the arrangements through which Internet applications can request and enrich PSTN telecommunications services. The common denominator of the enriched services (a.k.a. PINT services) is that they combine the Internet and PSTN services in such a way that the Internet is used for non-voice interactions, while the voice (and fax) are carried entirely over the PSTN. One key observation is that the pre-PINT implementations, being developed independently, do not inter-operate. It is a task of the PINT Working Group to define the inter-networking interfaces that will support inter-operation of the future implementations of PINT services

Systematic variation of the stellar Initial Mass Function with velocity dispersion in early-type galaxies

An essential component of galaxy formation theory is the stellar initial mass function (IMF), that describes the parent distribution of stellar mass in star forming regions. We present observational evidence in a sample of early-type galaxies (ETGs) of a tight correlation between central velocity dispersion and the strength of several absorption features sensitive to the presence of low-mass stars. Our sample comprises ~40,000 ETGs from the SPIDER survey (z<0.1). The data, extracted from the Sloan Digital Sky Survey, are combined, rejecting both noisy data, and spectra with contamination from telluric lines, resulting in a set of 18 stacked spectra at high signal-to-noise ratio (S/N> 400 per A). A combined analysis of IMF-sensitive line strengths and spectral fitting is performed with the latest state-of the art population synthesis models (an extended version of the MILES models). A significant trend is found between IMF slope and velocity dispersion, towards an excess of low-mass stars in the most massive galaxies. Although we emphasize that accurate values of the IMF slope will require a detailed analysis of chemical composition (such as [a/Fe] or even individual element abundance ratios), the observed trends suggest that low-mass ETGs are better fit by a Kroupa-like IMF, whereas massive galaxies require bottom-heavy IMFs, exceeding the Salpeter slope at velocity dispersions above 200km/s.Comment: 5 pages, 4 figures, accepted for publication in MNRAS Letter

Near Infrared spectroscopy of post-starburst galaxies: a limited impact of TP-AGB stars on galaxy SEDs

We present VLT-ISAAC NIR spectro-photometric observations of 16 post-starburst (PSB) galaxies aimed at constraining the debated influence of TP-AGB stars on the SED of galaxies with stellar ages of 0.5-2 Gyr, critical for high-redshift studies. PSB galaxies have negligible on-going star formation and a SED dominated by the stars formed in a recent (<2 Gyr) burst. By spectroscopically selecting PSB galaxies with mean luminosity-weighted ages between 0.5 and 1.5 Gyr and a broad range of metallicities, we explore the parameter space around the peak of the relative energy output of TP-AGB stars. Crucially, we target galaxies at z~0.2, so that two main spectral features of TP-AGB stars (C-molecule band-head drops at 1.41 and 1.77mum), which are heavily absorbed by our atmosphere for targets at z~0, move inside the H and K atmospheric windows and can be constrained for the first time to high accuracy. Our findings provide key constraints to stellar population synthesis models: i) The NIR regions around 1.41 and 1.77mum (rest-frame) are featureless for all galaxies in our sample over the whole range of relevant ages and metallicities at variance with the Maraston (2005) TP-AGB heavy models, which exhibit marked drops there; ii) No flux boosting is observed in the NIR. The optical-NIR SEDs of most of our PSB galaxies can be consistently reproduced with Bruzual & Charlot (2003) models, using either simple stellar populations of corresponding light-weighted ages and metallicities, or a more realistic burst plus an old population containing <~60% of the total stellar mass. In contrast, all combinations of this kind based on the Maraston (2005) models are unable to simultaneously reproduce the smoothness of the NIR spectra and the relatively blue optical-NIR colours in the observations. The data collected in this study appear to disfavour TP-AGB heavy models with respect to TP-AGB light ones.Comment: MNRAS accepted. 21 pages, 11 figures. New version improves mainly on clarity of figures and discussion of burst fraction/SF

Extragalactic Background Light Inferred from AEGIS Galaxy SED-type Fractions

The extragalactic background light (EBL) is of fundamental importance both for understanding the entire process of galaxy evolution and for gamma-ray astronomy, but the overall spectrum of the EBL between 0.1-1000 microns has never been determined directly from galaxy spectral energy distribution (SED) observations over a wide redshift range. The evolving, overall spectrum of the EBL is derived here utilizing a novel method based on observations only. This is achieved from the observed evolution of the rest-frame K-band galaxy luminosity function up to redshift 4 (Cirasuolo et al. 2010), combined with a determination of galaxy SED-type fractions. These are based on fitting SWIRE templates to a multiwavelength sample of about 6000 galaxies in the redshift range from 0.2 to 1 from the All-wavelength Extended Groth Strip International Survey (AEGIS). The changing fractions of quiescent galaxies, star-forming galaxies, starburst galaxies and AGN galaxies in that redshift range are estimated, and two alternative extrapolations of SED-types to higher redshifts are considered. This allows calculation of the evolution of the luminosity densities from the UV to the IR, the evolving star formation rate density of the universe, the evolving contribution to the bolometric EBL from the different galaxy populations including AGN galaxies and the buildup of the EBL. Our EBL calculations are compared with those from a semi-analytic model, from another observationally-based model and observational data. The EBL uncertainties in our modeling based directly on the data are quantified, and their consequences for attenuation of very high energy gamma-rays due to pair production on the EBL are discussed. It is concluded that the EBL is well constrained from the UV to the mid-IR, but independent efforts from infrared and gamma-ray astronomy are needed in order to reduce the uncertainties in the far-IR.Comment: 25 pages, 18 figures, 4 tables; accepted for publication in MNRAS on September 3, 2010. Online material available at http://side.iaa.es/EB

Confronting theoretical models with the observed evolution of the galaxy population out to z=4

[abridged] We construct lightcones for the semi-analytic galaxy formation simulation of Guo et al. (2011) and make mock catalogues for comparison with deep high-redshift surveys. Photometric properties are calculated with two different stellar population synthesis codes (Bruzual & Charlot 2003; Maraston 2005) in order to study sensitivity to this aspect of the modelling. The catalogues are publicly available and include photometry for a large number of observed bands from 4000{\deg}A to 6{\mu}m, as well as rest-frame photometry and intrinsic properties of the galaxies. Guo et al. (2011) tuned their model to fit the low-redshift galaxy population but noted that at z > 1 it overpredicts the abundance of galaxies below the "knee" of the stellar mass function. Here we extend the comparison to deep galaxy counts in the B, i, J, K and IRAC 3.6{\mu}m, 4.5{\mu}m and 5.8{\mu}m bands, to the redshift distributions of K and 5.8{\mu}m selected galaxies, and to the evolution of rest-frame luminosity functions in the B and K bands. The B, i and J counts are well reproduced, but at longer wavelengths the overabundant high-redshift galaxies produce excess faint counts. The predicted redshift distributions for K and 5.8{\mu}m selected samples highlight the effect of emission from thermally pulsing AGB stars. The full treatment of Maraston (2005) predicts three times as many z~2 galaxies in faint 5.8{\mu}m selected samples as the model of Bruzual & Charlot (2003), whereas the two models give similar predictions for K-band selected samples. Although luminosity functions are adequately reproduced out to z~3 in rest-frame B, the same is true at rest-frame K only if TP-AGB emission is included, and then only at high luminosity. Fainter than L* the two synthesis models agree but overpredict the number of galaxies, another reflection of the overabundance of ~10^10M\odot model galaxies at z > 1.Comment: 13 pages, 6 figures, accepted by MNRA

Morphological variation of genetically confirmed Alouatta Pigra × A. palliata hybrids from a natural hybrid zone in Tabasco, Mexico

While hybridization has been reported for a large number of primate taxa, there is a general lack of data on hybrid morphology for wild individuals with known genetic ancestry. A confirmed hybrid zone for the closely related Neotropical primates Alouatta palliata and A. pigra has provided a unique opportunity to study primate hybrid morphological variation. Here we used molecular evidence based on mitochondrial, Y‐chromosome, and autosomal data to assess hybrid ancestry. We conducted univariate and multivariate statistical comparisons of morphometric data collected from individuals both outside and within the hybrid zone in Tabasco, Mexico. Our results show that of all the hybrids detected ( N = 128), only 12% of them were approximately genetically intermediate, and none of them were first generation hybrids. Univariate pairwise comparisons among parental individuals, multigenerational backcrossed hybrids, and intermediate hybrids showed that overall, multigenerational backcrossed hybrids resemble the parental species with which they share most of their alleles. Conversely, intermediates were highly variable. Similarly, principal component analysis depicts an overlap between the parental species and their backcrosses when considering overall morphological differences. Finally, discriminant function analysis of the morphological variables was overall unreliable for classifying individuals into their assigned genotypic classes. Taken together, our results suggest that primate natural hybridization studies should incorporate molecular methods for determining ancestry, because morphology may not always be a reliable indicator of hybrid status. Hybrid zones could comprise a large number of multigenerational backcrossed hybrids that are indistinguishable from the parental species. The implications for studying hybridization in the primate fossil record are discussed. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96397/1/22196_ftp.pd

A new method for classifying galaxy SEDs from multiwavelength photometry

We present a new method to classify the broad-band optical–near-infrared spectral energy distributions (SEDs) of galaxies using three shape parameters (super-colours) based on a principal component analysis of model SEDs. As well as providing a compact representation of the wide variety of SED shapes, the method allows for easy visualization of information loss and biases caused by the incomplete sampling of the rest-frame SED as a function of redshift. We apply the method to galaxies in the United Kingdom Infrared Telescope Infrared Deep Sky Survey Ultra Deep Survey with 0.9 11, declining steadily to 13 per cent at logM∗/M_ = 10. The properties and mass function of the poststarburst galaxies are consistent with a scenario in which gas-rich mergers contribute to the growth of the low- and intermediate-mass range of the red sequence

Empirical determination of the shape of dust attenuation curves in star-forming galaxies

We present a systematic study of the shape of the dust attenuation curve in star-forming galaxies from the far ultraviolet to the near infrared (0.15-2microns), as a function of specific star formation rate (sSFR) and axis ratio (b/a), for galaxies with and without a significant bulge. Our sample comprises 23,000 (15,000) galaxies with a median redshift of 0.07, with photometric entries in the SDSS, UKIDSS-LAS (and GALEX-AIS) survey catalogues and emission line measurements from the SDSS spectroscopic survey. We develop a new pair-matching technique to isolate the dust attenuation curves from the stellar continuum emission. The main results are: (i) the slope of the attenuation curve in the optical varies weakly with sSFR, strongly with b/a, and is significantly steeper than the Milky Way extinction law in bulge-dominated galaxies; (ii) the NIR slope is constant, and matches the slope of the Milky Way extinction law; (iii) the UV has a slope change consistent with a dust bump at 2175AA which is evident in all samples and varies strongly in strength with b/a in the bulge-dominated sample; (iv) there is a strong increase in emission line-to-continuum dust attenuation with both decreasing sSFR and increasing b/a; (v) radial gradients in dust attenuation increase strongly with increasing sSFR, and the presence of a bulge does not alter the strength of the gradients. These results are consistent with the picture in which young stars are surrounded by dense `birth clouds' with low covering factor which disperse on timescales of ~1e7 years and the diffuse interstellar dust is distributed in a centrally concentrated disk with a smaller scaleheight than the older stars that contribute the majority of the red and NIR light. [abridged]Comment: 22 pages, 13 figures + appendices with SQL queries and IDL code to perform dust correction of galaxy SEDs. Resubmitted to MNRAS after minor corrections suggested by the referee. Comments welcom

Repetitive task training for improving functional ability after stroke

Background Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation. Objectives Primary objective: To determine if RTT improves upper limb function/reach and lower limb function/balance in adults after stroke. Secondary objectives: 1) To determine the effect of RTT on secondary outcome measures including activities of daily living, global motor function, quality of life/health status and adverse events. 2) To determine the factors that could influence primary and secondary outcome measures, including the effect of 'dose' of task practice; type of task (whole therapy, mixed or single task); timing of the intervention and type of intervention. Search methods We searched the Cochrane Stroke Group Trials Register (4 March 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 5: 1 October 2006 to 24 June 2016); MEDLINE (1 October 2006 to 8 March 2016); Embase (1 October 2006 to 8 March 2016); CINAHL (2006 to 23 June 2016); AMED (2006 to 21 June 2016) and SPORTSDiscus (2006 to 21 June 2016). Selection criteria Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal. Data collection and analysis Two review authors independently screened abstracts, extracted data and appraised trials. We determined the quality of evidence within each study and outcome group using the Cochrane 'Risk of bias' tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We did not assess follow-up outcome data using GRADE. We contacted trial authors for additional information. Main results We included 33 trials with 36 intervention-control pairs and 1853 participants. The risk of bias present in many studies was unclear due to poor reporting; the evidence has therefore been rated 'moderate' or 'low' when using the GRADE system. There is low-quality evidence that RTT improves arm function (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) 0.01 to 0.49; 11 studies, number of participants analysed = 749), hand function (SMD 0.25, 95% CI 0.00 to 0.51; eight studies, number of participants analysed = 619), and lower limb functional measures (SMD 0.29, 95% CI 0.10 to 0.48; five trials, number of participants analysed = 419). There is moderate-quality evidence that RTT improves walking distance (mean difference (MD) 34.80, 95% CI 18.19 to 51.41; nine studies, number of participants analysed = 610) and functional ambulation (SMD 0.35, 95% CI 0.04 to 0.66; eight studies, number of participants analysed = 525). We found significant differences between groups for both upper-limb (SMD 0.92, 95% CI 0.58 to 1.26; three studies, number of participants analysed = 153) and lower-limb (SMD 0.34, 95% CI 0.16 to 0.52; eight studies, number of participants analysed = 471) outcomes up to six months post treatment but not after six months. Effects were not modified by intervention type, dosage of task practice or time since stroke for upper or lower limb. There was insufficient evidence to be certain about the risk of adverse events. Authors' conclusions There is low- to moderate-quality evidence that RTT improves upper and lower limb function; improvements were sustained up to six months post treatment. Further research should focus on the type and amount of training, including ways of measuring the number of repetitions actually performed by participants. The definition of RTT will need revisiting prior to further updates of this review in order to ensure it remains clinically meaningful and distinguishable from other interventions