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

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

NGC 2770: high supernova rate due to interaction

Galaxies which hosted many core-collapse supernovae (SN) explosions can be used to study the conditions necessary for the formation of massive stars. NGC 2770 was dubbed a SN factory, because it hosted four core-collapse SNe in 20 years (three type Ib and one type IIn). Its star formation rate (SFR) was reported not to be enhanced and therefore not compatible with such a high SN rate. We aim at explaining the high SN rate of NGC 2770. We used archival HI line data for NGC 2770 and reinterpret the Halpha and optical continuum data. Even though the continuum-based SFR indicators do not yield high values, the dust-corrected Halpha luminosity implies a high SFR, consistent with the high SN rate. Such disparity between the SFR estimators is an indication of recently enhanced star formation activity, because the continuum indicators trace long timescale of the order of 100 Myr, unlike the line indicators, which trace timescales of the order of 10 Myr. Hence, the unique feature of NGC 2770 compared to other galaxies is the fact that it is observed very recently after the enhancement of the SFR. It also has high dust extinction, E(B-V) above 1 mag. We provide support for the hypothesis that the increased SFR in NGC 2770 is due to the interaction with its companion galaxies. We report an HI bridge between NGC 2770 and its closest companion and the existence of a total of four companions within 100 kpc (one identified for the first time). There are no clear HI concentrations close to the positions of SNe in NGC 2770 such as those detected for hosts of gamma-ray bursts (GRBs) and broad-lined SNe type Ic (IcBL). This suggests that the progenitors of type Ib SNe are not born out of recently accreted atomic gas, as was suggested for GRB and IcBL SN progenitors.Comment: Astronomy & Astrophysics, in press, 8 pages, 3 figures, 1 tabl

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

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

Sweetened Drink and Snacking Cues in Adolescents. A Study Using Ecological Momentary Assessment

The objective of this study was to identify physical, social, and intrapersonal cues that were associated with the consumption of sweetened beverages and sweet and salty snacks among adolescents from lower SES neighborhoods. Students were recruited from high schools with a minimum level of 25% free or reduced cost lunches. Using ecological momentary assessment, participants (N=158) were trained to answer brief questionnaires on handheld PDA devices: (a) each time they ate or drank, (b) when prompted randomly, and (c) once each evening. Data were collected over 7days for each participant. Participants reported their location (e.g., school grounds, home), mood, social environment, activities (e.g., watching TV, texting), cravings, food cues (e.g., saw a snack), and food choices. Results showed that having unhealthy snacks or sweet drinks among adolescents was associated with being at school, being with friends, feeling lonely or bored, craving a drink or snack, and being exposed to food cues. Surprisingly, sweet drink consumption was associated with exercising. Watching TV was associated with consuming sweet snacks but not with salty snacks or sweet drinks. These findings identify important environmental and intrapersonal cues to poor snacking choices that may be applied to interventions designed to disrupt these food-related, cue-behavior linked habits

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