752 research outputs found
Quasars with PV broad absorption in BOSS data release 9
Broad absorption lines (BALs) found in a significant fraction of quasar
spectra identify high-velocity outflows that might be present in all quasars
and could be a major factor in feedback to galaxy evolution. Understanding the
nature of these flows requires further constraints on their physical
properties, including their column densities, for which well-studied BALs, such
as CIV 1548,1551, typically provide only a lower limit because of saturation
effects. Low-abundance lines, such as PV 1118,1128, indicate large column
densities, implying outflows more powerful than measurements of CIV alone would
indicate. We search through a sample of 2694 BAL quasars from the SDSS-III/BOSS
DR9 quasar catalog for such absorption, and we identify 81 `definite' and 86
`probable' detections of PV broad absorption, yielding a firm lower limit of
3.0-6.2% for the incidence of such absorption among BAL quasars. The
PV-detected quasars tend to have stronger CIV and SiIV absorption, as well as a
higher incidence of LoBAL absorption, than the overall BAL quasar population.
Many of the PV-detected quasars have CIV troughs that do not reach zero
intensity (at velocities where PV is detected), confirming that the outflow gas
only partially covers the UV continuum source. PV appears significantly in a
composite spectrum of non-PV-detected BAL quasars, indicating that PV
absorption (and large column densities) are much more common than indicated by
our search results. Our sample of PV detections significantly increases the
number of known PV detections, providing opportunities for follow-up studies to
better understand BAL outflow energetics.Comment: 18 pages, 12 figures. All spectral plots available at
http://www.dancapellupo.com/boss-pv-bal-spectral-plots.htm
Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection
Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts
Coherent combining of two high-brightness laser diodes phase-locked by a Michelson-type external cavity (Orale)
International audienceWe describe a new coherent beam combin- ing architecture based on the passive phase- locking of two laser diodes in a Michelson external cavity on their rear side, and their coherent combination on their front side
The Differential Efficacy of Pemetrexed According to NSCLC Histology: A Review of Two Phase III Studies
Abstract
Background.
Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of pemetrexed according to histology in two large, phase III NSCLC trials.
Methods.
One study tested pemetrexed versus docetaxel in previously treated patients (n = 571) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n = 1,725) with advanced NSCLC. Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan–Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs).
Results.
In both studies, treatment arms were well balanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups.
Conclusions.
The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology. These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma, but, because of efficacy and safety advantages, pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC
Natural Resistance-Associated Macrophage Protein Is a Cellular Receptor for Sindbis Virus in Both Insect and Mammalian Hosts
SummaryAlphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multipass membrane proteins for infection
Zebrafish type I collagen mutants faithfully recapitulate human type I collagenopathies
The type I collagenopathies are a group of heterogeneous connective tissue disorders, that are caused by mutations in the genes encoding type I collagen and include specific forms of osteogenesis imperfecta (OI) and the Ehlers-Danlos syndrome (EDS). These disorders present with a broad disease spectrum and large clinical variability of which the underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes in a large set of zebrafish, with diverse mutations in the genes encoding type I collagen, representing different genetic forms of human OI, and a zebrafish model resembling human EDS, which harbors a number of soft connective tissues defects, typical of EDS. Furthermore, we provide insight into how zebrafish and human type I collagen are compositionally and functionally related, which is relevant in the interpretation of human type I collagen-related disease models. Our studies reveal a high degree of intergenotype variability in phenotypic expressivity that closely correlates with associated OI severity. Furthermore, we demonstrate the potential for select mutations to give rise to phenotypic variability, mirroring the clinical variability associated with human disease pathology. Therefore, our work suggests the future potential for zebrafish to aid in identifying unknown genetic modifiers and mechanisms underlying the phenotypic variability in OI and related disorders. This will improve diagnostic strategies and enable the discovery of new targetable pathways for pharmacological intervention
Natural Resistance-associated Macrophage Protein (NRAMP) is a cellular receptor for Sindbis virus in both insect and mammalian hosts
Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of for this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter Natural Resistance-Associated Macrophage Protein (NRAMP), as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were non-permissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multi-pass membrane proteins for infection
Observation of Josephson harmonics in tunnel junctions
Approaches to developing large-scale superconducting quantum
processors must cope with the numerous microscopic degrees of freedom
that are ubiquitous in solid-state devices. State-of-the-art superconducting
qubits employ aluminium oxide (AlO) tunnel Josephson junctions as
the sources of nonlinearity necessary to perform quantum operations.
Analyses of these junctions typically assume an idealized, purely sinusoidal
current–phase relation. However, this relation is expected to hold only in the
limit of vanishingly low-transparency channels in the AlO barrier. Here we
show that the standard current–phase relation fails to accurately describe
the energy spectra of transmon artificial atoms across various samples
and laboratories. Instead, a mesoscopic model of tunnelling through
an inhomogeneous AlO barrier predicts percent-level contributions
from higher Josephson harmonics. By including these in the transmon
Hamiltonian, we obtain orders of magnitude better agreement between
the computed and measured energy spectra. The presence and impact of
Josephson harmonics has important implications for developing AlOx-based
quantum technologies including quantum computers and parametric
amplifiers. As an example, we show that engineered Josephson harmonics
can reduce the charge dispersion and associated errors in transmon qubits
by an order of magnitude while preserving their anharmonicity
Observation of Josephson Harmonics in Tunnel Junctions
Superconducting quantum processors have a long road ahead to reach
fault-tolerant quantum computing. One of the most daunting challenges is taming
the numerous microscopic degrees of freedom ubiquitous in solid-state devices.
State-of-the-art technologies, including the world's largest quantum
processors, employ aluminum oxide (AlO) tunnel Josephson junctions (JJs) as
sources of nonlinearity, assuming an idealized pure current-phase
relation (CR). However, this celebrated CR is
only expected to occur in the limit of vanishingly low-transparency channels in
the AlO barrier. Here we show that the standard CR fails to
accurately describe the energy spectra of transmon artificial atoms across
various samples and laboratories. Instead, a mesoscopic model of tunneling
through an inhomogeneous AlO barrier predicts %-level contributions from
higher Josephson harmonics. By including these in the transmon Hamiltonian, we
obtain orders of magnitude better agreement between the computed and measured
energy spectra. The reality of Josephson harmonics transforms qubit design and
prompts a reevaluation of models for quantum gates and readout, parametric
amplification and mixing, Floquet qubits, protected Josephson qubits, etc. As
an example, we show that engineered Josephson harmonics can reduce the charge
dispersion and the associated errors in transmon qubits by an order of
magnitude, while preserving anharmonicity
- …