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1.
Ann Neurol ; 96(1): 46-60, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38624158

ABSTRACT

OBJECTIVE: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. METHODS: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. RESULTS: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels. INTERPRETATION: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60.


Subject(s)
Amyloid beta-Peptides , Polysomnography , Sleep, REM , Sleep, Slow-Wave , Humans , Middle Aged , Amyloid beta-Peptides/blood , Amyloid beta-Peptides/metabolism , Adult , Male , Aged , Female , Sleep, Slow-Wave/physiology , Young Adult , Sleep, REM/physiology , Hydrocortisone/blood , Peptide Fragments/blood
2.
Sci Adv ; 7(50): eabj6737, 2021 Dec 10.
Article in English | MEDLINE | ID: mdl-34890240

ABSTRACT

We present a three-periodic, chiral, tensegrity structure and demonstrate that it is auxetic. Our tensegrity structure is constructed using the chiral symmetry Π+ cylinder packing, transforming cylinders to elastic elements and cylinder contacts to incompressible rods. The resulting structure displays local reentrant geometry at its vertices and is shown to be auxetic when modeled as an equilibrium configuration of spatial constraints subject to a quasi-static deformation. When the structure is subsequently modeled as a lattice material with elastic elements, the auxetic behavior is again confirmed through finite element modeling. The cubic symmetry of the original structure means that the auxetic behavior is observed in both perpendicular directions and is close to isotropic in magnitude. This structure could be the simplest three-dimensional analog to the two-dimensional reentrant honeycomb. This, alongside the chirality of the structure, makes it an interesting design target for multifunctional materials.

3.
PLoS One ; 15(12): e0243692, 2020.
Article in English | MEDLINE | ID: mdl-33347458

ABSTRACT

OBJECTIVE: Rapid testing is paramount during a pandemic to prevent continued viral spread and excess morbidity and mortality. This study investigates whether testing strategies based on sample pooling can increase the speed and throughput of screening for SARS-CoV-2, especially in resource-limited settings. METHODS: In a mathematical modelling approach conducted in May 2020, six different testing strategies were simulated based on key input parameters such as infection rate, test characteristics, population size, and testing capacity. The situations in five countries were simulated, reflecting a broad variety of population sizes and testing capacities. The primary study outcome measurements were time and number of tests required, number of cases identified, and number of false positives. FINDINGS: The performance of all tested methods depends on the input parameters, i.e. the specific circumstances of a screening campaign. To screen one tenth of each country's population at an infection rate of 1%, realistic optimised testing strategies enable such a campaign to be completed in ca. 29 days in the US, 71 in the UK, 25 in Singapore, 17 in Italy, and 10 in Germany. This is ca. eight times faster compared to individual testing. When infection rates are lower, or when employing an optimal, yet more complex pooling method, the gains are more pronounced. Pool-based approaches also reduce the number of false positive diagnoses by a factor of up to 100. CONCLUSIONS: The results of this study provide a rationale for adoption of pool-based testing strategies to increase speed and throughput of testing for SARS-CoV-2, hence saving time and resources compared with individual testing.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Models, Theoretical , Clinical Laboratory Techniques , Humans , Mass Screening/methods
5.
Plant Methods ; 16: 82, 2020.
Article in English | MEDLINE | ID: mdl-32523612

ABSTRACT

BACKGROUND: Many metals are essential for plants and humans. Knowledge of metal distribution in plant tissues in vivo contributes to the understanding of physiological mechanisms of metal uptake, accumulation and sequestration. For those studies, X-rays are a non-destructive tool, especially suited to study metals in plants. RESULTS: We present microfluorescence imaging of trace elements in living plants using a customized benchtop X-ray fluorescence machine. The system was optimized by additional detector shielding to minimize stray counts, and by a custom-made measuring chamber to ensure sample integrity. Protocols of data recording and analysis were optimised to minimise artefacts. We show that Zn distribution maps of whole leaves in high resolution are easily attainable in the hyperaccumulator Noccaea caerulescens. The sensitivity of the method was further shown by analysis of micro- (Cu, Ni, Fe, Zn) and macronutrients (Ca, K) in non-hyperaccumulating crop plants (soybean roots and pepper leaves), which could be obtained in high resolution for scan areas of several millimetres. This allows to study trace metal distribution in shoots and roots with a wide overview of the object, and thus avoids making conclusions based on singular features of tiny spots. The custom-made measuring chamber with continuous humidity and air supply coupled to devices for imaging chlorophyll fluorescence kinetic measurements enabled direct correlation of element distribution with photosynthesis. Leaf samples remained vital even after 20 h of X-ray measurements. Subtle changes in some of photosynthetic parameters in response to the X-ray radiation are discussed. CONCLUSIONS: We show that using an optimized benchtop machine, with protocols for measurement and quantification tailored for plant analyses, trace metal distribution can be investigated in a reliable manner in intact, living plant leaves and roots. Zinc distribution maps showed higher accumulation in the tips and the veins of young leaves compared to the mesophyll tissue, while in the older leaves the distribution was more homogeneous.

6.
Anal Chem ; 86(19): 9774-80, 2014 Oct 07.
Article in English | MEDLINE | ID: mdl-25162502

ABSTRACT

Depth profiling with confocal micro-X-ray fluorescence spectroscopy (confocal micro-XRF) is a nondestructive analytical method for obtaining elemental depth profiles in the micrometer region. Up until now, the quantitative reconstruction of thicknesses and elemental concentration of stratified samples has been only possible with monochromatic, thus, synchrotron radiation. In this work, we present a new calibration and reconstruction procedure, which renders quantification in the laboratory feasible. The proposed model uses the approximation of an effective spot size of the optic in the excitation channel and relies on the calibration of the transmission of this lens beforehand. Calibration issues are discussed and validation measurements on thick multielement reference material and a stratified system are presented.

7.
Anal Bioanal Chem ; 402(4): 1505-15, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21928082

ABSTRACT

The aim of the research project "Typology of Dutch Drawing" was to establish an interdisciplinary approach for investigating heterogeneous drawing collections. To define a type common to a group of drawings, we determine elements that are common to them based on style and the use of identical materials. To that end, we investigated about 750 Dutch drawings from the sixteenth century at the Dresden Kupferstich-Kabinett using art historical and scientific methods. In this work, we present a detailed analysis of 30 drawings ascribed to the Egmont Master.

8.
Anal Bioanal Chem ; 402(4): 1493-503, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21805315

ABSTRACT

In this study, we address the question of the provenance and origin of the Dead Sea Scrolls manuscripts. A characteristic low ratio of chlorine to bromine, corresponding to that of the Dead Sea water, may serve as an indicator for local production. For this aim we developed a non-destructive procedure to determine the Cl/Br ratio in the parchment of these manuscripts. Micro-X-ray fluorescence (µ-XRF) measurements of a large number of parchment and leather fragments from the Dead Sea Scrolls were analyzed with a routine we developed based on fundamental parameter quantification. This routine takes into account the absorption of the collagen matrix and the influence of the different sample thicknesses. To calculate the representative Cl/Br ratio for each fragment, we investigated the lateral homogeneity and determined the total mass deposition using the intensity of the inelastically scattered, characteristic tube radiation. The distribution of the Cl/Br ratios thus obtained from the µ-XRF measurements make it possible to distinguish fragments whose origin lies within the Dead Sea region from those produced in other locations.

9.
Anal Chem ; 83(16): 6308-15, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21711051

ABSTRACT

A combination of 3D micro X-ray fluorescence spectroscopy (3D micro-XRF) and micro-XRF was utilized for the investigation of a small collection of highly heterogeneous, partly degraded Dead Sea Scroll parchment samples from known excavation sites. The quantitative combination of the two techniques proves to be suitable for the identification of reliable marker elements which may be used for classification and provenance studies. With 3D micro-XRF, the three-dimensional nature, i.e. the depth-resolved elemental composition as well as density variations, of the samples was investigated and bromine could be identified as a suitable marker element. It is shown through a comparison of quantitative and semiquantitative values for the bromine content derived using both techniques that, for elements which are homogeneously distributed in the sample matrix, quantification with micro-XRF using a one-layer model is feasible. Thus, the possibility for routine provenance studies using portable micro-XRF instrumentation on a vast amount of samples, even on site, is obtained through this work.

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