10 research outputs found

    Pulsed Triple Frequency Modulation for Frequency Stabilization and Control of Two Lasers to an Optical Cavity

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    We present a method to stabilize two lasers to an optical cavity using pulsed triple frequency modulation. The setup allows simultaneous Pound–Drever–Hall stabilization, as well as independent frequency control, while removing interference terms that limit the frequency scan range and allowing for smaller modulation depths. A review of single, dual, and triple frequency modulation is also presented in addition to a discussion of how to effectively turn pulsed triple frequency modulation into independent dual frequency modulation for each laser. This method would increase the scan range to half the free spectral range

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Spectroscopic study of the 7p J=1/2 and 7p J=3/2 states in neutral cesium-133

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    I will start with a few observations of connections between spectroscopy and other (seemingly unrelated) research topics, then focus on Doppler free spectroscopy on the 7p J=1/2 and 7p J=3/2 states in neutral cesium-133. A frequency doubled titanium sapphire laser stabilized to a temperature stabilized ultra-low expansion optical cavity was used to find the absolute frequencies for the centers of gravity of the two cesium states. These measurements are an improvement of a factor of 650 and 500 over previously reported measurements. The magnetic dipole and electric quadrupole constants were also measured and found to be consistent with previously published values

    Cork oak physiological responses to manipulated water availability in a Mediterranean woodland

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    tThis study details the physiological responses of cork oak (Quercus suber L.) to manipulated water inputs.Treatments named as dry, ambient and wet, which received 80, 100 and 120% of the annual precipitation,respectively, were applied to a Mediterranean woodland in southern Portugal. Tree ecophysiology andgrowth were monitored from 2003 to 2005.The impacts of the water manipulation were primarily observed in tree transpiration, especially dur-ing summer drought. Rainfall exclusion reduced the annual stand canopy transpiration by 10% over the2-year study period, while irrigation increased it by 11%. The accumulated tree transpiration matchedprecipitation in spring 2004 and 2005 at the stand level, suggesting that cork oak trees rely on precip-itation water sources during the peak of the growing season. However, during the summer droughts,groundwater was the main water source for trees.Despite the significant differences in soil water content and tree transpiration, no treatment effectscould be detected in leaf water potential and leaf gas exchange, except for a single event after spring irri-gations in the very dry year 2005. These irrigations were intentionally delayed to reduce dry spell durationduring the peak of tree growing season. They resulted in an acute positive physiological response of treesfrom the wet treatment one week after the last irrigation event leading to a 32% raise of stem diame-ter increment the following months. Our results suggest that in a semi-arid environment precipitationchanges in spring (amount and timing) have a stronger impact on cork oak physiology and growth thanan overall change in the total annual precipitation.The extreme drought of 2005 had a negative impact on tree growth. The annual increment of treetrunk diameter in the ambient and dry treatments was reduced, while it increased for trees from the wettreatment. Water shortage also significantly reduced leaf area. The latter dropped by 10.4% in responseto the extreme drought of 2005 in trees from the ambient treatment. The reduction was less pronouncedin trees of the wet treatment (−7.6%), and more pronounced in trees of the dry treatment (−14.7%).Cork oak showed high resiliency to inter-annual precipitation variability. The annual accumulated treetranspiration, the minimum midday leaf water potential and the absolute amount of groundwater usedinfo:eu-repo/semantics/publishedVersio

    Ultrasonic backscatter coefficients for weakly scattering, agar spheres in agar phantoms

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    Applicability of ultrasound phantoms to biological tissue has been limited because most phantoms have generally used strong scatterers. The objective was to develop very weakly scattering phantoms, whose acoustic scattering properties are likely closer to those of tissues and then compare theoretical simulations and experimental backscatter coefficient (BSC) results. The phantoms consisted of agar spheres of various diameters (nominally between 90 and 212 μm), containing ultrafiltered milk, suspended in an agar background. BSC estimates were performed at two institutions over the frequency range 1–13 MHz, and compared to three models. Excellent agreement was shown between the two laboratory results as well as with the three models

    Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE

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    BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486

    The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

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    Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations(1-4) in addition to numerous lower frequency genetic events of uncertain significance(5). Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis(6,7) in a mouse model of pancreatic ductal preneoplasia(8) to identify genes that cooperate with oncogenic Kras(G12D) to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia(9), we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with Kras(G12D) to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA
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