1,596 research outputs found

    Femtosecond frequency comb measurement of absolute frequencies and hyperfine coupling constants in cesium vapor

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    We report measurements of absolute transition frequencies and hyperfine coupling constants for the 8S_{1/2}, 9S_{1/2}, 7D_{3/2}, and 7D_{5/2} states in ^{133}Cs vapor. The stepwise excitation through either the 6P_{1/2} or 6P_{3/2} intermediate state is performed directly with broadband laser light from a stabilized femtosecond laser optical-frequency comb. The laser beam is split, counter-propagated and focused into a room-temperature Cs vapor cell. The repetition rate of the frequency comb is scanned and we detect the fluorescence on the 7P_{1/2,3/2} -> 6S_{1/2} branches of the decay of the excited states. The excitations to the different states are isolated by the introduction of narrow-bandwidth interference filters in the laser beam paths. Using a nonlinear least-squares method we find measurements of transition frequencies and hyperfine coupling constants that are in agreement with other recent measurements for the 8S state and provide improvement by two orders of magnitude over previously published results for the 9S and 7D states.Comment: 14 pages, 14 figure

    Phase-Contrast OCT Imaging of Transverse Flows in the Mouse Retina and Choroid

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    Purpose. To test the hypothesis that a novel phase-contrast optical coherence tomography (OCT) system can image retinal and choroidal vessels in the living mouse. Methods. A high-speed spectral domain optical coherence tomography (SDOCT) system, which measures the reflections for the entire depth of the retina at once with each axial scan (A-scan), was developed for mouse retinal imaging. Acquiring multiple A-scans over a transverse line across the mouse retina offers a two-dimensional cross-sectional image (B-scan); several neighboring B-scans can be assembled into a three-dimensional OCT image. To visualize mobility and transverse flow in retinal vessels, the statistical variance of phase for each location was calculated from multiple B-scans acquired successively for the same retinal cross-section. Such measures of phase variance offer a direct measure of motions over a large dynamic range of flow velocities. Results. Three-dimensional phase-contrast images of the live mouse retina were created using multiple two-dimensional cross-sectional image slices through the retina. For the data presented here, each cross-sectional phase-contrast slice resulted from five images of 100 or 200 transverse pixels, acquired over 25 ms or 50 ms, respectively. The approach offered clear identification of motion regions at different depths, including flow in the retinal microvasculature and in the choroidal vessels. Conclusions. Phase-contrast OCT enables three-dimensional visualization of retinal and choroidal vasculature in vivo

    Physical and Emotional States as Memory-Relevant Factors: Cognitive Monitoring by Young Children

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    The Flavell (l981) model of cognitive monitoring and metamnemonic development was tested by four experiments conducted to determine whether preschool children (1) recognize that mood, fatigue, and fear are variables that influence learning; and (2) self-monitor their internal states and adjust their study behavior when they are sad or tired

    Combinatorial Analysis of mRNA Expression Patterns in Mouse Embryos Using Hybridization Chain Reaction

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    Multiplexed fluorescent hybridization chain reaction (HCR) and advanced imaging techniques can be used to evaluate combinatorial gene expression patterns in whole mouse embryos with unprecedented spatial resolution. Using HCR, DNA probes complementary to mRNA targets trigger chain reactions in which metastable fluorophore-labeled DNA HCR hairpins self-assemble into tethered fluorescent amplification polymers. Each target mRNA is detected by a probe set containing one or more DNA probes, with each probe carrying two HCR initiators. For multiplexed experiments, probe sets for different target mRNAs carry orthogonal initiators that trigger orthogonal DNA HCR amplification cascades labeled by spectrally distinct fluorophores. As a result, in situ amplification is performed for all targets simultaneously, and the duration of the experiment is independent of the number of target mRNAs. We have used multiplexed fluorescent in situ HCR and advanced imaging technologies to address questions of cell heterogeneity and tissue complexity in craniofacial patterning and anterior neural development. In the sample protocol presented here, we detect three different mRNA targets: Tg(egfp), encoding the enhanced green fluorescent protein (GFP) transgene (typically used as a control); Twist1, encoding a transcription factor involved in cell lineage determination and differentiation; and Pax2, encoding a transcription factor expressed in the mid-hindbrain region of the mouse embryo

    Adherence counseling practices of generalist and specialist physicians caring for people living with HIV/AIDS in North Carolina

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    National guidelines recommend that practitioners assess and reinforce patient adherence when prescribing antiretroviral (ART) medications, but the extent to which physicians do this routinely is unknown

    Period-1 Encodes an ATP-Dependent RNA Helicase that Influences Nutritional Compensation of the Neurospora Circadian Clock

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    Mutants in the period-1 (prd-1) gene, characterized by a recessive allele, display a reduced growth rate and period lengthening of the developmental cycle controlled by the circadian clock. We refined the genetic location of prd-1 and used whole genome sequencing to find the mutation defining it, confirming the identity of prd-1 by rescuing the mutant circadian phenotype via transformation. PRD-1 is an RNA helicase whose orthologs, DDX5 [DEAD (Asp-Glu-Ala-Asp) Box Helicase 5] and DDX17 in humans and DBP2 (Dead Box Protein 2) in yeast, are implicated in various processes, including transcriptional regulation, elongation, and termination, ribosome biogenesis, and mRNA decay. Although prd-1 mutants display a long period (∼25 h) circadian developmental cycle, they interestingly display a WT period when the core circadian oscillator is tracked using a frq-luciferase transcriptional fusion under conditions of limiting nutritional carbon; the core oscillator in the prd-1 mutant strain runs with a long period under glucose-sufficient conditions. Thus, PRD-1 clearly impacts the circadian oscillator and is not only part of a metabolic oscillator ancillary to the core clock. PRD-1 is an essential protein, and its expression is neither light-regulated nor clock-regulated. However, it is transiently induced by glucose; in the presence of sufficient glucose, PRD-1 is in the nucleus until glucose runs out, which elicits its disappearance from the nucleus. Because circadian period length is carbon concentration-dependent, prd-1 may be formally viewed as a clock mutant with defective nutritional compensation of circadian period length

    Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

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    BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of 16,298,correspondingtoanincrementalcost−effectivenessratioof16,298, corresponding to an incremental cost-effectiveness ratio of 61,984 (95% CI 34,087−34,087-135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was 100,000/LYG.Thecost−effectivenessratiowasmostfavourableforpatientslessthan60yearsold(100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old (31,800/LYG) but increased to 80,600/LYGforpatients60−79yearsoldand80,600/LYG for patients 60-79 years old and 110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug

    Comparative Ultrastructure Of Digestive Diverticulae In Bathymodiolin Mussels: Discovery Of An Unknown Spherical Inclusion (Six) In Digestive Cells Of A Seep Mussel

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    Mussels in the genus Bathymodiolus host endosymbiotic bacteria in their gills, from which the mussel derives much of its nutrition. Bathymodiolin mussels also have functional digestive systems and, as in shallow-water mytilid mussels, cells of the digestive diverticulae are of two types: basophilic secretory cells and columnar digestive cells. Cellular contents of secretory and digestive cells of Bathymodiolus thermophilus and Bathymodiolus brevior from deep-sea hydrothermal vents are comparable to cellular contents of these cell types observed in shallow-water mytilids. In the seep mussel Bathymodiolus heckerae, cellular contents of columnar cells were anomalous, being dominated by an unknown cellular inclusion herein called spherical inclusion unknown or SIX. SIX was observed in all digestive cells and some basophilic cells of B. heckerae examined with TEM. It is a large (2-10-mu m diameter) and abundant (7 +/- 1.5 inclusions per epithelial cell section) inclusion, with a double external membrane and stacked internal lamellae. No microbial DNA was detected in digestive tubules of B. heckerae using molecular probes, preferential DNA amplification techniques, or DAPI staining, suggesting that SIX is not a unicellular parasite or symbiont. The ubiquity and abundance of SIX within cells of the digestive diverticula suggest that it has an important cellular function (positive or negative), yet to be determined
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