296 research outputs found

    Characterization of Power Induced Heating and Damage in Fiber Optic Probes for Near-Field Scanning Optical Microscopy

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    Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ~55–60°C as output powers reach ~50 nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ~450 nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminum coating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4 ± 1.7 and 20.7 ± 6.9 mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∌15° for etched and ~6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ~6ÎŒm. These stress fractures, arising from the differential heating expansion of the dielectric and the metal coating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminum coating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

    Characterization of power induced heating and damage in fiber optic probes for near-field scanning optical microscopy

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    This is the published version, also available here: http://dx.doi.org/10.1063/1.2740133.Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ∌55–60°C as output powers reach ∌50nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ∌450nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminumcoating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4±1.7 and 20.7±6.9mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∌15° for etched and ∌6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ∌6ÎŒm. These stress fractures, arising from the differential heating expansion of the dielectric and the metalcoating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminumcoating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

    Effects of diet on resource utilization by a model human gut microbiota containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome

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    The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism's 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight into how gut microbes adapt to dietary perturbations at both a community level and from the perspective of a well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate the value of artificial communities

    The role of TcdB and TccC subunits in secretion of the photorhabdus Tcd toxin complex

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    The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5:1:1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man

    Shocked monazite chronometry: integrating microstructural and in situ isotopic age data for determining precise impact ages

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    Monazite is a robust geochronometer and occurs in a wide range of rock types. Monazite also records shock deformation from meteorite impact but the effects of impact-related microstructures on the U–Th–Pb systematics remain poorly constrained. We have, therefore, analyzed shock-deformed monazite grains from the central uplift of the Vredefort impact structure, South Africa, and impact melt from the Araguainha impact structure, Brazil, using electron backscatter diffraction, electron microprobe elemental mapping, and secondary ion mass spectrometry (SIMS). Crystallographic orientation mapping of monazite grains from both impact structures reveals a similar combination of crystal-plastic deformation features, including shock twins, planar deformation bands and neoblasts. Shock twins were documented in up to four different orientations within individual monazite grains, occurring as compound and/or type one twins in (001), (100), (10 1 ÂŻ) , {110}, { 212 } , and type two (irrational) twin planes with rational shear directions in [ 0 1 ÂŻ 1 ÂŻ ] and [ 1 ÂŻ 1 ÂŻ 0 ]. SIMS U–Th–Pb analyses of the plastically deformed parent domains reveal discordant age arrays, where discordance scales with increasing plastic strain. The correlation between discordance and strain is likely a result of the formation of fast diffusion pathways during the shock event. Neoblasts in granular monazite domains are strain-free, having grown during the impact events via consumption of strained parent grains. Neoblastic monazite from the Inlandsee leucogranofels at Vredefort records a 207Pb/206Pb age of 2010 ± 15 Ma (2σ, n = 9), consistent with previous impact age estimates of 2020 Ma. Neoblastic monazite from Araguainha impact melt yield a Concordia age of 259 ± 5 Ma (2σ, n = 7), which is consistent with previous impact age estimates of 255 ± 3 Ma. Our results demonstrate that targeting discrete microstructural domains in shocked monazite, as identified through orientation mapping, for in situ U–Th–Pb analysis can date impact-related deformation. Monazite is, therefore, one of the few high-temperature geochronometers that can be used for accurate and precise dating of meteorite impacts

    What makes you not a Buddhist? : a preliminary mapping of values

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    This study sets out to establish which Buddhist values contrasted with or were shared by adolescents from a non-Buddhist population. A survey of attitude toward a variety of Buddhist values was fielded in a sample of 352 non-Buddhist schoolchildren aged between 13 and 15 in London. Buddhist values where attitudes were least positive concerned the worth of being a monk/nun or meditating, offering candles & incense on the Buddhist shrine, friendship on Sangha Day, avoiding drinking alcohol, seeing the world as empty or impermanent and Nirvana as the ultimate peace. Buddhist values most closely shared by non-Buddhists concerned the Law of Karma, calming the mind, respecting those deserving of respect, subjectivity of happiness, welfare work, looking after parents in old age and compassion to cuddly animals. Further significant differences of attitude toward Buddhism were found in partial correlations with the independent variables of sex, age and religious affiliation. Correlation patterns paralleled those previously described in theistic religions. Findings are applied to spiritual, moral, social and cultural development and for the teaching of religious to pupils of no faith adherence. The study recommends that quantitative psychometrics employed to conceptualize Buddhist values by discriminant validity in this study could be extended usefully to other aspects of the study of Buddhism, particularly in quest of validity in the conceptualization of Buddhist identity within specifically Buddhist populations

    Prevalence and Clinical Implications of a ÎČ-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

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    IMPORTANCE: Knowledge is lacking on the prevalence and prognosis of individuals with a ÎČ-amyloid-negative, tau-positive (A-T+) cerebrospinal fluid (CSF) biomarker profile. OBJECTIVE: To estimate the prevalence of a CSF A-T+ biomarker profile and investigate its clinical implications. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020). This was a multicenter study, with data collected from referral centers in clinical routine (UGOT) and research settings (ADNI and WISC). Eligible individuals had 1 lumbar puncture (all cohorts), 2 or more cognitive assessments (ADNI and WISC), and imaging (ADNI only) performed on 2 separate occasions. Data were analyzed on August 2022 to April 2023. EXPOSURES: Baseline CSF AÎČ42/40 and phosphorylated tau (p-tau)181; cognitive tests (ADNI: modified preclinical Alzheimer cognitive composite [mPACC]; WISC: modified 3-test PACC [PACC-3]). Exposures in the ADNI cohort included [18F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [18F]-flortaucipir, WISC: [18F]-MK6240). MAIN OUTCOMES AND MEASURES: Primary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A-T+ vs A-T- groups. Secondary outcomes included cross-sectional tau-PET. RESULTS: A total of 7679 individuals (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) were included in the UGOT cohort, 970 individuals (mean [SD] age, 73 [7.0] years; 526 male [54%]) were included in the ADNI cohort, and 519 individuals (mean [SD] age, 60 [7.3] years; 346 female [67%]) were included in the WISC cohort. The prevalence of an A-T+ profile in the UGOT cohort was 4.1% (95% CI, 3.7%-4.6%), being less common than the other patterns. Longitudinally, no significant differences in rates of worsening were observed between A-T+ and A-T- profiles for cognition or imaging biomarkers. Cross-sectionally, A-T+ had similar tau-PET uptake to individuals with an A-T- biomarker profile. CONCLUSION AND RELEVANCE: Results suggest that the CSF A-T+ biomarker profile was found in approximately 5% of lumbar punctures and was not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals

    Resolving catastrophic error bursts from cosmic rays in large arrays of superconducting qubits

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    Scalable quantum computing can become a reality with error correction, provided coherent qubits can be constructed in large arrays. The key premise is that physical errors can remain both small and sufficiently uncorrelated as devices scale, so that logical error rates can be exponentially suppressed. However, energetic impacts from cosmic rays and latent radioactivity violate both of these assumptions. An impinging particle ionizes the substrate, radiating high energy phonons that induce a burst of quasiparticles, destroying qubit coherence throughout the device. High-energy radiation has been identified as a source of error in pilot superconducting quantum devices, but lacking a measurement technique able to resolve a single event in detail, the effect on large scale algorithms and error correction in particular remains an open question. Elucidating the physics involved requires operating large numbers of qubits at the same rapid timescales as in error correction, exposing the event's evolution in time and spread in space. Here, we directly observe high-energy rays impacting a large-scale quantum processor. We introduce a rapid space and time-multiplexed measurement method and identify large bursts of quasiparticles that simultaneously and severely limit the energy coherence of all qubits, causing chip-wide failure. We track the events from their initial localised impact to high error rates across the chip. Our results provide direct insights into the scale and dynamics of these damaging error bursts in large-scale devices, and highlight the necessity of mitigation to enable quantum computing to scale

    Selection of suitable reference genes for quantitative real-time polymerase chain reaction in human meningiomas and arachnoidea

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    <p>Abstract</p> <p>Findings</p> <p>At first 32 housekeeping genes were analyzed in six randomly chosen meningiomas, brain and dura mater using geNorm, NormFinder, Bestkeeper-1 software and the comparative ΔCt method. Reference genes were ranked according to an integration tool for analyzing reference genes expression based on those four algorithms. Eight highest ranked reference genes (CASC3, EIF2B1, IPO8, MRPL19, PGK1, POP4, PPIA, and RPL37A) plus GAPDH and ACTB were then analyzed in 35 meningiomas, arachnoidea, dura mater and normal brain. NormFinder and Bestkeeper-1 identified RPL37A as the most stable expressed gene in meningiomas and their normal control tissue. NormFinder also determined the best combination of genes: RPL37A and EIF2B1. Commonly used reference genes GAPDH and ACTB were considered least stable genes. The critical influence of reference genes on qPCR data analysis is shown for VEGFA transcription patterns.</p> <p>Background</p> <p>In meningiomas quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is most frequently used for accurate determination of gene expression using various reference genes. Although meningiomas are a heterogeneous group of tissue, no data have been reported to validate reference genes for meningiomas and their control tissues.</p> <p>Conclusions</p> <p>RPL37A is the optimal single reference gene for normalization of gene expression in meningiomas and their control tissues, although the use of the combination of RPL37A and EIF2B1 would provide more stable results.</p
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