400 research outputs found

    Near-to mid-IR spectral purity transfer with a tunable frequency comb: methanol frequency metrology over a record frequency span

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    We report the development and operation of a frequency-comb-assisted high-resolution mid-infrared molecular spectrometer combining high spectral purity, SI-traceability, wide tunability and high sensitivity. An optical frequency comb is used to transfer the spectral purity of a SI-traceable 1.54 μ\mum metrology-grade frequency reference to a 10.3 μ\mum quantum cascade laser (QCL). The near-infrared reference is operated at the French time/frequency metrology institute, calibrated there to primary frequency standards, and transferred to Laboratoire de Physique des Lasers via the REFIMEVE fiber network. The QCL exhibits a sub-10 --15 frequency stability from 0.1 to 10 s and its frequency is traceable to the SI with a total uncertainty better than 4 x 10 --14 after 1-s averaging time. We have developed the instrumentation allowing comb modes to be continuously tuned over 9 GHz resulting in a QCL of record spectral purity uninterruptedly tunable at the precision of the reference over an unprecedented span of 1.4 GHz. We have used our apparatus to conduct sub-Doppler spectroscopy of methanol in a multi-pass cell, demonstrating state-of-art frequency uncertainties down to the few kilohertz level. We have observed weak intensity resonances unreported so far, resolved subtle doublets never seen before and brought to light discrepancies with the HITRAN database. This demonstrates the potential of our apparatus for probing subtle internal molecular processes, building accurate spectroscopic models of polyatomic molecules of atmospheric or astrophysical interest, and carrying out precise spectroscopic tests of fundamental physics

    Identifying Contributing Factors Associated With Dental Adverse Events Through a Pragmatic Electronic Health Record-Based Root Cause Analysis

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    OBJECTIVE: This study assessed contributing factors associated with dental adverse events (AEs). METHODS: Seven electronic health record-based triggers were deployed identifying potential AEs at 2 dental institutions. From 4106 flagged charts, 2 reviewers examined 439 charts selected randomly to identify and classify AEs using our dental AE type and severity classification systems. Based on information captured in the electronic health record, we analyzed harmful AEs to assess potential contributing factors; harmful AEs were defined as those that resulted in temporary moderate to severe harm, required hospitalization, or resulted in permanent moderate to severe harm. We classified potential contributing factors according to (1) who was involved (person), (2) what were they doing (tasks), (3) what tools/technologies were they using (tools/technologies), (4) where did the event take place (environment), (5) what organizational conditions contributed to the event? (organization), (6) patient (including parents), and (7) professional-professional collaboration. A blinded panel of dental experts conducted a second review to confirm the presence of an AE. RESULTS: Fifty-nine cases had 1 or more harmful AEs. Pain occurred most frequently (27.1%), followed by nerve injury (16.9%), hard tissue injury (15.2%), and soft tissue injury (15.2%). Forty percent of the cases were classified as temporary not moderate to severe harm. Person (training, supervision, and fatigue) was the most common contributing factor (31.5%), followed by patient (noncompliance, unsafe practices at home, low health literacy, 17.1%), and professional-professional collaboration (15.3%). CONCLUSIONS: Pain was the most common harmful AE identified. Person, patient, and professional-professional collaboration were the most frequently assessed factors associated with harmful AEs

    Intracellular localisation and extracellular release of Y RNA and Y RNA binding proteins

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    Cells can communicate via the release and uptake of extracellular vesicles (EVs), which are nano-sized membrane vesicles that can transfer protein and RNA cargo between cells. EVs contain microRNAs and various other types of non-coding RNA, of which Y RNA is among the most abundant types. Studies on how RNAs and their binding proteins are sorted into EVs have mainly focused on comparing intracellular (cytoplasmic) levels of these RNAs to the extracellular levels in EVs. Besides overall transcriptional levels that may regulate sorting of RNAs into EVs, the process may also be driven by local intracellular changes in RNA/RBP concentrations. Changes in extracellular Y RNA have been linked to cancer and cardiovascular diseases. Although the loading of RNA cargo into EVs is generally thought to be influenced by cellular stimuli and regulated by RNA binding proteins (RBP), little is known about Y RNA shuttling into EVs. We previously reported that immune stimulation alters the levels of Y RNA in EVs independently of cytosolic Y RNA levels. This suggests that Y RNA binding proteins, and/or changes in the local Y RNA concentration at EV biogenesis sites, may affect Y RNA incorporation into EVs. Here, we investigated the subcellular distribution of Y RNA and Y RNA binding proteins in activated and non-activated THP1 macrophages. We demonstrate that Y RNA and its main binding protein Ro60 abundantly co-fractionate in organelles involved in EV biogenesis and in EVs. Cellular activation led to an increase in Y RNA concentration at EV biogenesis sites and this correlated with increased EV-associated levels of Y RNA and Ro60. These results suggest that Y RNA incorporation into EVs may be controlled by local intracellular changes in the concentration of Y RNA and their protein binding partners

    The Team Keck Treasury Redshift Survey of the GOODS-North Field

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    We report the results of an extensive imaging and spectroscopic survey in the GOODS-North field completed using DEIMOS on the Keck II telescope. Observations of 2018 targets in a magnitude-limited sample of 2911 objects to R=24.4 yield secure redshifts for a sample of 1440 galaxies and AGN plus 96 stars. In addition to redshifts and associated quality assessments, our catalog also includes photometric and astrometric measurements for all targets detected in our R-band imaging survey of the GOODS-North region. We investigate various sources of incompleteness and find the redshift catalog to be 53% complete at its limiting magnitude. The median redshift of z=0.65 is lower than in similar deep surveys because we did not select against low-redshift targets. Comparison with other redshift surveys in the same field, including a complementary Hawaii-led DEIMOS survey, establishes that our velocity uncertainties are as low as 40 km/s for red galaxies and that our redshift confidence assessments are accurate. The distributions of rest-frame magnitudes and colors among the sample agree well with model predictions out to and beyond z=1. We will release all survey data, including extracted 1-D and sky-subtracted 2-D spectra, thus providing a sizable and homogeneous database for the GOODS-North field which will enable studies of large scale structure, spectral indices, internal galaxy kinematics, and the predictive capabilities of photometric redshifts.Comment: 17 pages, 18 figures, submitted to AJ; v2 minor changes; see survey database at http://www2.keck.hawaii.edu/realpublic/science/tksurvey

    Plasmid-mediated Quinolone Resistance among Non-TyphiSalmonella enterica Isolates, USA

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    We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6′)Ib-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism

    A single dose of ChAdOx1 Chik vaccine induces neutralising antibodies against four chikungunya virus lineages in a phase 1 clinical trial

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    Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and Tcell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose

    Electrospun Small-Diameter Silk Fibroin Vascular Grafts with Tuned Mechanical and Biocompatibility Properties as Tissue Engineered Scaffolds

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    Almost 9 million people in the U.S. have peripheral arterial disease (PAD). In severe cases of PAD, arterial bypass surgery is performed to redirect flow around the problem area. However, for many elderly patients, this surgery is not feasible using the preferred autologous grafts because of the limited availability of tissue to use for grafting, so there is a clinical need for engineered vascular grafts. Engineered grafts are intended to replace native blood vessels by manipulating biomaterials to mimic the properties of the native vessel. Despite success in large diameter cases, small diameter grafts are still prone to a number of issues such as occlusion, hyperplasia, and thrombosis. Silk fibroin is a promising biomaterial for creating vascular grafts because of its demonstrated mechanical strength and biocompatibility. Our research established a method for electrospinning the silk fibroin onto a rotating mandrel for seamless grafts. Mechanical testing, including burst pressure and tensile strength tests, compared the strength of our grafts to that of the autologous vessel. Finally, biochemical modifications, aimed at both recruiting and proliferating HUVECs on the grafts, increased cell proliferation on the grafts in vitro
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