Immunological assessment of plant-derived avian flu H5/HA1 variants.

Polypeptide variants of the HA1 antigenic domain of the H5N1 avian influenza virus hemagglutinin (HA) molecule were produced in plants using transient and stable expression systems and fused with His/c-myc tags or with mouse or human Fc antibody fragments. The resulting peptides were purified and used for intramuscular immunization of mice. While the recombinant HA1 variants induced a significant serum humoral immune response in the mice, none of the HA1 preparations induced virus-neutralizing antibodies. Fusion with the Fc fragment improved overall yield of the constructs and allowed purification requiring only a single step, but led to no detectable fusion-related enhancement of immunogenicity or quality of immune response

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

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

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Tracing the evolution of dust-obscured activity using sub-millimetre galaxy populations from STUDIES and AS2UDS

We analyse the physical properties of 121 SNR ≥ 5 sub-millimetre galaxies (SMGs) from the STUDIES 450 μm survey. We model their UV-to-radio spectral energy distributions using MAGPHYS+photo-z and compare the results to similar modelling of 850 μm-selected SMG sample from AS2UDS, to understand the fundamental physical differences between the two populations at the observed depths. The redshift distribution of the 450-μm sample has a median of z = 1.85 ± 0.12 and can be described by strong evolution of the far-infrared luminosity function. The fainter 450-μm sample has ∼14 times higher space density than the brighter 850-μm sample at z ≲ 2, and a comparable space density at z = 2–3, before rapidly declining, suggesting LIRGs are the main obscured population at z ∼ 1–2, while ULIRGs dominate at higher redshifts. We construct rest-frame ∼180-μm-selected and dust-mass-matched samples at z = 1–2 and z = 3–4 from the 450 and 850-μm samples, respectively, to probe the evolution of a uniform sample of galaxies spanning the cosmic noon era. Using far-infrared luminosity, dust masses, and an optically thick dust model, we suggest that higher redshift sources have higher dust densities due to inferred dust continuum sizes which are roughly half of those for the lower redshift population at a given dust mass, leading to higher dust attenuation. We track the evolution in the cosmic dust mass density and suggest that the dust content of galaxies is governed by a combination of both the variation of gas content and dust destruction time-scale

Cosmic evolution of the H2 mass density and the epoch of molecular gas

© 2021. The American Astronomical Society. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.3847/1538-4357/abec81We present new empirical constraints on the evolution of ρ H2, the cosmological mass density of molecular hydrogen, back to z ≈ 2.5. We employ a statistical approach measuring the average observed 850 μm flux density of near-infrared selected galaxies as a function of redshift. The redshift range considered corresponds to a span where the 850 μm band probes the Rayleigh-Jeans tail of thermal dust emission in the rest frame, and can therefore be used as an estimate of the mass of the interstellar medium. Our sample comprises of ≈150,000 galaxies in the UK InfraRed Telescope Infrared Deep Sky Survey Ultra-Deep Survey field with near-infrared magnitudes K AB ≤ 25 mag and photometric redshifts with corresponding probability distribution functions derived from deep 12-band photometry. With a sample approximately 2 orders of magnitude larger than in previous works we significantly reduce statistical uncertainties on ρ H2 to z ≈ 2.5. Our measurements are in broad agreement with recent direct estimates from blank field molecular gas surveys, finding that the epoch of molecular gas coincides with the peak epoch of star formation with ρ H2, 2×107,MȮ Mpc-3at z ≈ 2. We demonstrate that rho; H2, can be broadly modeled by inverting the star formation rate (SFR) density with a fixed or weakly evolving star formation efficiency. This "constant efficiency"model shows a similar evolution to our statistically derived ρ H2,, indicating that the dominant factor driving the peak star formation history at z ≈ 2 is a larger supply of molecular gas in galaxies rather than a significant evolution of the SFR efficiency within individual galaxies.Peer reviewe

Evolution of arboreality and fossoriality in squirrels and aplodontid rodents: Insights from the semicircular canals of fossil rodents

Reconstructing locomotor behaviour for fossil animals is typically done with postcranial elements. However, for species only known from cranial material, locomotor behaviour is difficult to reconstruct. The semicircular canals (SCCs) in the inner ear provide insight into an animal's locomotor agility. A relationship exists between the size of the SCCs relative to body mass and the jerkiness of an animal's locomotion. Additionally, studies have also demonstrated a relationship between SCC orthogonality and angular head velocity. Here, we employ two metrics for reconstructing locomotor agility, radius of curvature dimensions and SCC orthogonality, in a sample of twelve fossil rodents from the families Ischyromyidae, Sciuridae and Aplodontidae. The method utilizing radius of curvature dimensions provided a reconstruction of fossil rodent locomotor behaviour that is more consistent with previous studies assessing fossil rodent locomotor behaviour compared to the method based on SCC orthogonality. Previous work on ischyromyids suggests that this group displayed a variety of locomotor modes. Members of Paramyinae and Ischyromyinae have relatively smaller SCCs and are reconstructed to be relatively slower compared to members of Reithroparamyinae. Early members of the Sciuroidea clade including the sciurid Cedromus wilsoni and the aplodontid Prosciurus relictus are reconstructed to be more agile than ischyromyids, in the range of extant arboreal squirrels. This reconstruction supports previous inferences that arboreality was likely an ancestral trait for this group. Derived members of Sciuridae and Aplodontidae vary in agility scores. The fossil squirrel Protosciurus cf. rachelae is inferred from postcranial material as arboreal, which is in agreement with its high agility, in the range of extant arboreal squirrels. In contrast, the fossil aplodontid Mesogaulus paniensis has a relatively low agility score, similar to the fossorial Aplodontia rufa, the only living aplodontid rodent. This result is in agreement with its postcranial reconstruction as fossorial and with previous indications that early aplodontids were more arboreal than their burrowing descendants

Orally Delivered, Plant-Produced Tat Protein Primes Mice For a Challenge DNA Vaccine Expressing Tat

Oral Presentation