650 research outputs found
Antiviral Strategies for Pandemic and Seasonal Influenza
While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein
Kinematic classifications of local interacting galaxies: implications for the merger/disk classifications at high-z
The classification of galaxy mergers and isolated disks is key for
understanding the relative importance of galaxy interactions and secular
evolution during the assembly of galaxies. The kinematic properties of galaxies
as traced by emission lines have been used to suggest the existence of a
significant population of high-z star-forming galaxies consistent with isolated
rotating disks. However, recent studies have cautioned that post-coalescence
mergers may also display disk-like kinematics. To further investigate the
robustness of merger/disk classifications based on kinematic properties, we
carry out a systematic classification of 24 local (U)LIRGs spanning a range of
galaxy morphologies: from isolated spiral galaxies, ongoing interacting
systems, to fully merged remnants. We artificially redshift the WiFeS
observations of these local (U)LIRGs to z=1.5 to make a realistic comparison
with observations at high-z, and also to ensure that all galaxies have the same
spatial sampling of ~900 pc. Using both kinemetry-based and visual
classifications, we find that the reliability of kinematic classification shows
a strong trend with the interaction stage of galaxies. Mergers with two nuclei
and tidal tails have the most distinct kinematic properties compared to
isolated disks, whereas a significant population of the interacting disks and
merger remnants are indistinguishable from isolated disks. The high fraction of
late-stage mergers showing disk-like kinematics reflects the complexity of the
dynamics during galaxy interactions. However, the exact fractions of
misidentified disks and mergers depend on the definition of kinematic
asymmetries and the classification threshold when using kinemetry-based
classifications. Our results suggest that additional indicators such as
morphologies traced by stars or molecular gas are required to further constrain
the merger/disk classifications at high-z.Comment: 16 pages, 5 figures, ApJ accepte
Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation
Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs. For example, vascular patency and appropriate cell distribution and expansion are critical components in the production of successful BELs. Proper solutions to these components of BELs have challenged its development. Several strategies, such as heparin immobilization, heparin-gelatin, REDV peptide, and anti-CD31 aptamer have been developed to extend the vascular patency of revascularized bioengineered livers (rBELs). Other novel methods have been developed to enhance cell seeding of parenchymal cells and to increase graft functionality during both bench and in vivo perfusion. These enhanced methods have been associated with up to 15 days of survival in large animal (porcine) models of heterotopic transplantation but have not yet permitted extended survival after implantation of BELs in the orthotopic position. This review will highlight both the remaining challenges and the potential for clinical application of functional bioengineered grafts
Orbital Instabilities in a Triaxial Cusp Potential
This paper constructs an analytic form for a triaxial potential that
describes the dynamics of a wide variety of astrophysical systems, including
the inner portions of dark matter halos, the central regions of galactic
bulges, and young embedded star clusters. Specifically, this potential results
from a density profile of the form , where the radial
coordinate is generalized to triaxial form so that . Using the resulting analytic form of the potential, and the
corresponding force laws, we construct orbit solutions and show that a robust
orbit instability exists in these systems. For orbits initially confined to any
of the three principal planes, the motion in the perpendicular direction can be
unstable. We discuss the range of parameter space for which these orbits are
unstable, find the growth rates and saturation levels of the instability, and
develop a set of analytic model equations that elucidate the essential physics
of the instability mechanism. This orbit instability has a large number of
astrophysical implications and applications, including understanding the
formation of dark matter halos, the structure of galactic bulges, the survival
of tidal streams, and the early evolution of embedded star clusters.Comment: 50 pages, accepted for publication in Ap
Altered Lung Morphogenesis, Epithelial Cell Differentiation and Mechanics in Mice Deficient in the Wnt/β-Catenin Antagonist Chibby
The canonical Wnt/β-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/β-catenin antagonist Chibby (Cby). In support of its inhibitory role in canonical Wnt signaling, expression of β-catenin target genes is elevated in the Cby−/− lung. Notably, Cby protein is prominently associated with the centrosome/basal body microtubule structures in embryonic lung epithelial progenitor cells, and later enriches as discrete foci at the base of motile cilia in airway ciliated cells. At birth, Cby−/− lungs are grossly normal but spontaneously develop alveolar airspace enlargement with reduced proliferation and abnormal differentiation of lung epithelial cells, resulting in altered pulmonary function. Consistent with the Cby expression pattern, airway ciliated cells exhibit a marked paucity of motile cilia with apparent failure of basal body docking. Moreover, we demonstrate that Cby is a direct downstream target for the master ciliogenesis transcription factor Foxj1. Collectively, our results demonstrate that Cby facilitates proper postnatal lung development and function
Inhibition of Neuraminidase Inhibitor-Resistant Influenza Virus by DAS181, a Novel Sialidase Fusion Protein
Antiviral drug resistance for influenza therapies remains a concern due to the high prevalence of H1N1 2009 seasonal influenza isolates which display H274Y associated oseltamivir-resistance. Furthermore, the emergence of novel H1N1 raises the potential that additional reassortments can occur, resulting in drug resistant virus. Thus, additional antiviral approaches are urgently needed. DAS181 (Fludase®), a sialidase fusion protein, has been shown to have inhibitory activity against a large number of seasonal influenza strains and a highly pathogenic avian influenza (HPAI) strain (H5N1). Here, we examine the in vitro activity of DAS181 against a panel of 2009 oseltamivir-resistant seasonal H1N1 clinical isolates. The activity of DAS181 against nine 2009, two 2007, and two 2004 clinical isolates of seasonal IFV H1N1 was examined using plaque number reduction assay on MDCK cells. DAS181 strongly inhibited all tested isolates. EC50 values remained constant against isolates from 2004, 2007, and 2009, suggesting that there was no change in DAS181 sensitivity over time. As expected, all 2007 and 2009 isolates were resistant to oseltamivir, consistent with the identification of the H274Y mutation in the NA gene of all these isolates. Interestingly, several of the 2007 and 2009 isolates also exhibited reduced sensitivity to zanamivir, and accompanying HA mutations near the sialic acid binding site were observed. DAS181 inhibits IFV that is resistant to NAIs. Thus, DAS181 may offer an alternative therapeutic option for seasonal or pandemic IFVs that become resistant to currently available antiviral drugs
MUSTANG 3.3 Millimeter Continuum Observations of Class 0 Protostars
We present observations of six Class 0 protostars at 3.3 mm (90 GHz) using
the 64-pixel MUSTANG bolometer camera on the 100-m Green Bank Telescope. The
3.3 mm photometry is analyzed along with shorter wavelength observations to
derive spectral indices (S_nu ~ nu^alpha) of the measured emission. We utilize
previously published dust continuum radiative transfer models to estimate the
characteristic dust temperature within the central beam of our observations. We
present constraints on the millimeter dust opacity index, beta, between 0.862
mm, 1.25 mm, and 3.3 mm. Beta_mm typically ranges from 1.0 to 2.4 for Class 0
sources. The relative contributions from disk emission and envelope emission
are estimated at 3.3 mm. L483 is found to have negligible disk emission at 3.3
mm while L1527 is dominated by disk emission within the central beam. The
beta_mm^disk <= 0.8 - 1.4 for L1527 indicates that grain growth is likely
occurring in the disk. The photometry presented in this paper may be combined
with future interferometric observations of Class 0 envelopes and disks.Comment: 19 pages, 3 figures, AJ accepted, in pres
As a Pediatrician, I Don’t Know the Second, Third, or Fourth Thing to Do: A Qualitative Study of Pediatric Residents’ Training and Experiences in Behavioral Health
Despite a mandated 1-month rotation in developmental-behavioral pediatrics (DBP), pediatric residents report inadequate training in behavioral health care. As a first step in much needed curriculum development in this area, this study sought to assess learner experiences regarding the management of behavioral health problems during residency. Four focus groups were conducted for residents in years 1-3 of training in 2 residency programs in a northeastern state. Transcripts were analyzed and coded by researchers through qualitative classical content analysis. The exploratory analysis revealed 9 key themes: time requirements, rapport building, resources and referrals for behavioral health, psychiatric medications, diagnosis vs. treatment, working with families, the importance of behavioral health, fears of working with a pediatric population, and training issues. These qualitative data further identify gaps in the behavioral health training of pediatric residents and may inform future innovations in training curricula
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