Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus.

We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0-2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human antibody response to foreign Ags and for generating human mAbs of predetermined specificity and high affinity

Charting the main sequence of star-forming galaxies out to redshifts z~7

We present a new determination of the star-forming main sequence (MS), obtained through stacking 100k K-band-selected galaxies in the far-IR Herschel and James Clerk Maxwell Telescope (JCMT) imaging. By fitting the dust emission curve to the stacked far-IR photometry, we derive the IR luminosities (LIR) and, hence, star formation rates (SFR) out to z~7. The functional form of the MS is found, with the linear SFR-M* relation that flattens at high stellar masses and the normalization that increases exponentially with redshift. We derive the corresponding redshift evolution of the specific star formation rate (sSFR) and compare our findings with the recent literature. We find our MS to be exhibiting slightly lower normalization at z<=2 and to flatten at larger stellar masses at high redshifts. By deriving the relationship between the peak dust temperature (Td) and redshift, where Td increases linearly from ~20K at z=0.5 to ~50 K at z=6, we conclude that the apparent inconsistencies in the shapes of the MS are most likely caused by the different dust temperatures assumed when deriving SFRs in the absence of far-IR data. Finally, we investigate the derived shape of the star-forming MS by simulating the time evolution of the observed galaxy stellar mass function (GSMF). While the simulated GSMF is in good agreement with the observed one, some inconsistencies persist. In particular, we find the simulated GSMF to be somewhat overpredicting the number density of low-mass galaxies at z>2.Comment: 16 pages, 11 figures, 2 tables, submitted to A&

The even darker side of the eastern gray squirrel (Sciurus carolinensis): a review of global introductions, invasion biology, and pest management strategies

Huynh, H.M., Bertolino, S., Lurz, P.W.W., Koprowski, J.L., Williams, G.R., Thompson, C.W., McAlpine, D.F

Classification tree to analyze factors connected with post operative complications of cataract surgery in a teaching hospital

Background: Artificial intelligence (AI) is becoming ever more frequently applied in medicine and, consequently, also in ophthalmology to improve both the quality of work for physicians and the quality of care for patients. The aim of this study is to use AI, in particular classification tree, for the evaluation of both ocular and systemic features involved in the onset of complications due to cataract surgery in a teaching hospital. Methods: The charts of 1392 eyes of 1392 patients, with a mean age of 71.3 ± 8.2 years old, were reviewed to collect the ocular and systemic data before, during and after cataract surgery, including post-operative complications. All these data were processed by a classification tree algorithm, producing more than 260 million simulations, aiming to develop a predictive model. Results: Postoperative complications were observed in 168 patients. According to the AI analysis, the pre-operative characteristics involved in the insurgence of complications were: ocular comorbidities, lower visual acuity, higher astigmatism and intra-operative complications. Conclusions: Artificial intelligence application may be an interesting tool in the physician’s hands to develop customized algorithms that can, in advance, define the post-operative complication risk. This may help in improving both the quality and the outcomes of the surgery as well as in preventing patient dissatisfaction

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (>75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P<0.001). Using specific thresholds, patients with ⩾25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P<0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease

A resolved map of the infrared excess in a Lyman Break Galaxy at z=3

The version of record, © 2016 The American Astronomical Society, M. P. Koprowski, K. E. K. Coppin, J. E. Geach, N. K. Hine, M. Bremer, S. Chapman, L. J. M. Davies, T. Hayashino, K. K. Knudsen, M. Kubo, B. D. Lehmer, Y. Matsuda, D. J. B. Smith, P. P. van der Werf, G. Violino, and T. Yamada, ‘A RESOLVED MAP OF THE INFRARED EXCESS IN A LYMAN BREAK GALAXY AT z = 3’, The Astrophysical Journal Letters, Vol 828(2), is available via doi: 10.3847/2041-8205/828/2/L21We have observed the dust continuum of ten z=3.1 Lyman Break Galaxies with the Atacama Large Millimeter/Submillimeter Array at ~450 mas resolution in Band 7. We detect and resolve the 870um emission in one of the targets with an integrated flux density of S(870)=(192+/-57) uJy, and measure a stacked 3-sigma signal of S(870)=(67+/-23) uJy for the remaining nine. The total infrared luminosities estimated from full spectral energy distribution fits are L(8-1000um)=(8.4+/-2.3)x10^10 Lsun for the detection and L(8-1000um)=(2.9+/-0.9)x10^10 Lsun for the stack. With HST ACS I-band imaging we map the rest-frame UV emission on the same scale as the dust, effectively resolving the 'infrared excess' (IRX=L_FIR/L_UV) in a normal galaxy at z=3. Integrated over the galaxy we measure IRX=0.56+/-0.15, and the galaxy-averaged UV slope is beta=-1.25+/-0.03. This puts the galaxy a factor of ~10 below the IRX-beta relation for local starburst nuclei of Meurer et al. (1999). However, IRX varies by more than a factor of 3 across the galaxy, and we conclude that the complex relative morphology of the dust relative to UV emission is largely responsible for the scatter in the IRX-beta relation at high-z. A naive application of a Meurer-like dust correction based on the UV slope would dramatically over-estimate the total star formation rate, and our results support growing evidence that when integrated over the galaxy, the typical conditions in high-z star-forming galaxies are not analogous to those in the local starburst nuclei used to establish the Meurer relation.Peer reviewe

The evolving far-IR galaxy luminosity function and dust-obscured star-formation rate density out to z~5

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2017 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We present a new measurement of the evolving galaxy far-IR luminosity function (LF) extending out to redshifts z~5, with resulting implications for the level of dust-obscured star-formation density in the young Universe. To achieve this we have exploited recent advances in sub-mm/mm imaging with SCUBA-2 on the James Clerk Maxwell Telescope (JCMT) and the Atacama Large Millimeter/Submillimeter Array (ALMA), which together provide unconfused imaging with sufficient dynamic range to provide meaningful coverage of the luminosity-redshift plane out to z>4. Our results support previous indications that the faint-end slope of the far-IR LF is sufficiently flat that comoving luminosity-density is dominated by bright objects (~L*). However, we find that the number-density/luminosity of such sources at high redshifts has been severely over-estimated by studies that have attempted to push the highly-confused Herschel SPIRE surveys beyond z~2. Consequently we confirm recent reports that cosmic star-formation density is dominated by UV-visible star formation at z>4. Using both direct (1/Vmax) and maximum likelihood determinations of the LF, we find that its high-redshift evolution is well characterized by continued positive luminosity evolution coupled with negative density evolution (with increasing redshift). This explains why bright sub-mm sources continue to be found at z>5, even though their integrated contribution to cosmic star-formation density at such early times is very small. The evolution of the far-IR galaxy LF thus appears similar in form to that already established for active galactic nuclei, possibly reflecting a similar dependence on the growth of galaxy mass.Peer reviewe

The SCUBA-2 Cosmology Legacy Survey: the nature of bright submm galaxies from 2 deg2 of 850-μm imaging

We present physical properties [redshifts (z), star-formation rates (SFRs) and stellar masses ( Mstar Mstar )] of bright (S850 ≥ 4 mJy) submm galaxies in the ≃2 deg2 COSMOS and UDS fields selected with SCUBA-2/JCMT. We complete the galaxy identification process for all (≃2000) S/N ≥ 3.5 850-μm sources, but focus our scientific analysis on a high-quality subsample of 651 S/N ≥ 4 sources with complete multiwavelength coverage including 1.1-mm imaging. We check the reliability of our identifications, and the robustness of the SCUBA-2 fluxes by revisiting the recent ALMA follow-up of 29 sources in our sample. Considering >4 mJy ALMA sources, our identification method has a completeness of ≃86 per cent with a reliability of ≃92 per cent, and only ≃15–20 per cent of sources are significantly affected by multiplicity (when a secondary component contributes >1/3 of the primary source flux). The impact of source blending on the 850-μm source counts as determined with SCUBA-2 is modest; scaling the single-dish fluxes by ≃0.9 reproduces the ALMA source counts. For our final SCUBA-2 sample, we find median z=2.40+0.10−0.04 z=2.40−0.04+0.10 , SFR = 287 ± 6 M⊙  yr− 1 and log(Mstar/M⊙)=11.12±0.02 log⁡(Mstar/M⊙)=11.12±0.02 (the latter for 349/651 sources with optical identifications). These properties clearly locate bright submm galaxies on the high-mass end of the ‘main sequence’ of star-forming galaxies out to z ≃ 6, suggesting that major mergers are not a dominant driver of the high-redshift submm-selected population. Their number densities are also consistent with the evolving galaxy stellar mass function. Hence, the submm galaxy population is as expected, albeit reproducing the evolution of the main sequence of star-forming galaxies remains a challenge for theoretical models/simulations

A Submillimeter Galaxy Illuminating its Circumgalactic Medium:Lyα Scattering in a Cold, Clumpy Outflow

We report the detection at 850 μm of the central source in SSA22-LAB1, the archetypal "Lyman-α Blob" (LAB), a 100 kpc scale radio-quiet emission-line nebula at z = 3.1. The flux density of the source, S 850 = 4.6 ± 1.1 mJy, implies the presence of a galaxy or group of galaxies with a total luminosity of L IR ≈ 1012 L ⊙. The position of an active source at the center of a ~50 kpc radius ring of linearly polarized Lyα emission detected by Hayes et al. suggests that the central source is leaking Lyα photons preferentially in the plane of the sky, which undergo scattering in H I clouds at a large galactocentric radius. The Lyα morphology around the submillimeter detection is reminiscent of a biconical outflow, and the average Lyα line profiles of the two "lobes" are dominated by a red peak, which is expected for a resonant line emerging from a medium with a bulk velocity gradient that is outflowing relative to the line center. Taken together, these observations provide compelling evidence that the central active galaxy (or galaxies) is responsible for a large fraction of the extended Lyα emission and morphology. Less clear is the history of the cold gas in the circumgalactic medium being traced by Lyα: is it mainly pristine material accreting into the halo that has not yet been processed through an interstellar medium (ISM), now being blown back as it encounters an outflow, or does it mainly comprise gas that has been swept-up within the ISM and expelled from the galaxy