50 research outputs found

    Efficient magneto-optical trapping of Yb atoms with a violet laser diode

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    We report the first efficient trapping of rare-earth Yb atoms with a high-power violet laser diode (LD). An injection-locked violet LD with a 25 mW frequency-stabilized output was used for the magneto-optical trapping (MOT) of fermionic as well as bosonic Yb isotopes. A typical number of 4×1064\times 10^6 atoms for 174^{174}Yb with a trap density of 1×108/\sim 1\times10^8/cm3^3 was obtained. A 10 mW violet external-cavity LD (ECLD) was used for the one-dimensional (1D) slowing of an effusive Yb atomic beam without a Zeeman slower resulting in a 35-fold increase in the number of trapped atoms. The overall characteristics of our compact violet MOT, e.g., the loss time of 1 s, the loading time of 400 ms, and the cloud temperature of 0.7 mK, are comparable to those in previously reported violet Yb MOTs, yet with a greatly reduced cost and complexity of the experiment.Comment: 5 pages, 3 figures, 1 table, Phys. Rev. A (to be published

    Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

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    The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

    Experimental progress in positronium laser physics

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    Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

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    The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

    Accelarated immune ageing is associated with COVID-19 disease severity

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    Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

    High-resolution Spectroscopy With Femtosecond Optical Combs

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    A stabilized femtosecond frequency comb has ∼106 stable optical modes spanning hundreds of terahertz, making it an ideal tool for high-resolution spectroscopy. We demonstrate some features of frequency-comb spectroscopy using experiments involving calcium and cesium. © OSA.Oskay, W.H., Diddams, S.A., Donley, E.A., Fortier, T.M., Heavner, T.P., Hollberg, L., Itano, W.M., Bergquist, J.C., Single-atom optical clock with high accuracy (2006) Phys. Rev. Lett, 97, pp. 020801/1-020801/4Fortier, T.M., Bartels, A., Diddams, S.A., Octave-spanning Ti:sapphire laser with a repetition rate >1 GHz for optical frequency measurements and comparisons (2006) Opt. Lett, 31, pp. 1011-1013Jones, D.J., Diddams, S.A., Ranka, J.K., Stentz, A., Windeler, R.S., Hall, J.L., Cundiff, S.T., Carrier-envelope phase control of femtosecond mode-locked lasers and direct optical frequency synthesis (2000) Science, 288, pp. 635-639Fortier, T.M., Le Coq, Y., Stalnaker, J.E., Ortega, D., Diddams, S.A., Oates, C.W., Hollberg, L., Kilohertz-resolution spectroscopy of cold atoms with an optical frequency comb (2006) Phys. Rev. Lett, 97, pp. 163905/1-163905/4Oates, C.W., Bondu, F., Fox, R.W., Hollberg, L., A diode-laser optical frequency standard based on laser-cooled Ca atoms: Sub-kilohertz spectroscopy by optical shelving detection (1999) Eur. Phys. J. D, 7, pp. 449-460Degenhardt, C., Stoehr, H., Lisdat, C., Wilpers, G., Schnatz, H., Lipphardt, B., Nazarova, T., Riehle, F., Calcium optical frequency standard with ultracold atoms: Approaching 10-15 relative uncertainty (2005) Phys. Rev. A, 72, pp. 062111/1-062111/1
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