Compound optics such as lens systems can overcome the limitations concerning resolution, efficiency, or aberrations which fabrication constraints would impose on any single optical element. In this ...work we demonstrate unprecedented sub-5 nm point focusing of hard x-rays, based on the combination of a high gain Kirkpatrick-Baez (KB) mirror system and a high resolution W/Si multilayer zone plate (MZP) for ultra-short focal length f. The pre-focusing allows limiting the MZP radius to below 2 μm, compatible with the required 5 nm structure width and essentially unlimited aspect ratios, provided by enabling fabrication technology based on pulsed laser deposition (PLD) and focused ion beam (FIB).
Abstract
Cavitation bubbles can be seeded from a plasma following optical breakdown, by focusing an intense laser in water. The fast dynamics are associated with extreme states of gas and liquid, ...especially in the nascent state. This offers a unique setting to probe water and water vapor far-from equilibrium. However, current optical techniques cannot quantify these early states due to contrast and resolution limitations. X-ray holography with single X-ray free-electron laser pulses has now enabled a quasi-instantaneous high resolution structural probe with contrast proportional to the electron density of the object. In this work, we demonstrate cone-beam holographic flash imaging of laser-induced cavitation bubbles in water with nanofocused X-ray free-electron laser pulses. We quantify the spatial and temporal pressure distribution of the shockwave surrounding the expanding cavitation bubble at time delays shortly after seeding and compare the results to numerical simulations.
We present a correlative microscopy approach for biology based on holographic X-ray imaging, X-ray scanning diffraction, and stimulated emission depletion (STED) microscopy. All modalities are ...combined into the same synchrotron endstation. In this way, labeled and unlabeled structures in cells are visualized in a complementary manner. We map out the fluorescently labeled actin cytoskeleton in heart tissue cells and superimpose the data with phase maps from X-ray holography. Furthermore, an array of local far-field diffraction patterns is recorded in the regime of small-angle X-ray scattering (scanning SAXS), which can be interpreted in terms of biomolecular shape and spatial correlations of all contributing scattering constituents. We find that principal directions of anisotropic diffraction patterns coincide to a certain degree with the actin fiber directions and that actin stands out in the phase maps from holographic recordings. In situ STED recordings are proposed to formulate models for diffraction data based on co-localization constraints.
Adipose tissue-derived factors link non-alcoholic fatty liver disease (NAFLD) with obesity, which has also been reported for circulating chemerin. On the other hand, hepatic chemerin and ...chemokine-like receptor 1 (CMKLR1) mRNA expression has not yet been studied in an extensively characterized patient collective.
This study was cross-sectional and experimental in design.
Liver tissue samples were harvested from 47 subjects and histologically examined according to the NAFLD activity score (NAS). The concentrations of chemerin and CMKLR1 were measured using semi-quantitative real-time PCR, and the concentration of serum chemerin was measured using ELISA. To evaluate potential effects of chemerin and CMKLR1, cultured primary human hepatocytes (PHHs) were exposed to selected metabolites known to play a role in NAFLD (insulin, glucagon, palmitoic acid, and interleukin-6 (IL6)).
Chemerin and CMKLR1 mRNA levels were elevated in the human liver. Their expression was correlated with the NAS (R(2)=0.543; P<0.001 and R(2)=0.355; P=0.014 respectively) and was significantly elevated in patients with definite non-alcoholic steatohepatitis (NASH) (P<0.05 respectively). Linear regression analysis confirmed an independent association of liver fibrosis, steatosis, inflammation, and hepatocyte ballooning with hepatic chemerin mRNA expression (P<0.05 respectively). The expression of hepatic chemerin and CMKLR1 was correlated with the measures of obesity (P<0.05). The incubation of PHHs with IL6 significantly increased the expression of CMKLR1 mRNA (P=0.027), while that of chemerin remained unaffected (P>0.05). None of the other metabolites showed an influence (P>0.05).
This is the first study to show that chemerin mRNA expression is significantly elevated in the liver of NASH patients and that CMKLR1 expression is upregulated in liver inflammation, whereby IL6 could play a causal role.
Abstract Purpose Mesenteric panniculitis (MP) is an underdiagnosed inflammatory condition of mesenteric adipose tissue. Prior studies suggested an association of MP with malignancy. To reassess this ...hypothesis, we performed the first matched case–control study comparing prevalence of malignancy and other disease in patients with and without MP. Material and methods With a keyword search we identified CT examinations of MP patients between 2010 and 2012. Each MP patient was matched with two control patients for age, gender, abdominal diameter and CT protocol. Manifestation and extent of mesenteric panniculitis was classified independently by two investigators according to established criteria. Concomitant disease, laboratory parameters and follow up CTs were recorded and analyzed for all patients. Results 77 of 13485 CT patients were diagnosed with MP (prevalence 0.58%). 50.6% of MP patients suffered from malignancy vs. 60.2% in the control group ( p = 0.157). Over up to 4 years of follow up in 35 of these 77 MP patients no association between development of MP and the course of tumor diseases could be identified. There was also no significant difference in the rate of frequent concomitant diseases such as hypertension, diabetes or previous surgery between the two groups. Conclusion In this first case–control-study we could show that, contrary to previous reports, mesenteric panniculitis is neither paraneoplastic nor is it associated with other diseases.
The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the ...circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters.
Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR.
The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1).
Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.
We study the propagation of hard x rays in single curved x-ray waveguide channels and observe waveguide effects down to surprisingly small radii of curvature R≃10 mm and a large contour length s≃5 ...mm, deflecting beams up to 30°. At these high angles, about 2 orders of magnitude above the critical angle of total reflection θ(c), most radiation modes are lost by "leaking" into the cladding, while certain "survivor" modes persist. This may open up a new form of integrated x-ray optics "on a chip," requiring curvatures mostly well below the extreme values studied here, e.g., to split and to delay x-ray pulses.
Curved graded multilayers for X-ray nano-focusing optics Morawe, Ch; Osterhoff, M.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2010, Letnik:
616, Številka:
2
Journal Article
Recenzirano
This work gives a comprehensive overview on the use of curved graded multilayers as nano-focusing elements on 3rd generation synchrotron sources. Particular emphasis is put on the Kirkpatrick–Baez ...(KB) focusing setup that has been developed at the ESRF. Initial estimates of the diffraction limit are derived from basic geometrical schemes and compared with total reflection mirrors. Both analytical and numerical approaches to characterize the focusing performance are presented. The essential role of the meridional multilayer d-spacing gradient is discussed as well as the involved technological obstacles and limitations. A short section is devoted to suitable deposition methods and equipment. Experimental data and examples of operational ESRF KB focusing devices complement the work.
Human dopaminergic system in general, and substantia nigra (SN) neurons, in particular, are implicated in the pathologies underlying the human brain aging. The interplay between aberrations in the ...structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress. In the present study, we demonstrate an integrated approach to the analysis of the structural organization, assembly, and metals’ accumulation in two distinct areas of SN: in the neuromelanin neurons and neuropil. By using the highly brilliant source of PETRA III and the Kirkpatrick-Baez nano-focus, large area histological brain slices are scanned at the sub-neuronal resolution, taking advantage of continuous motor movement and reduced acquisition time. Elemental analysis with synchrotron radiation based X-ray Fluorescence (SRXRF) is combined with X-ray Phase Contrast Imaging (XPCI) to correct for inherent aberrations in the samples’ density and thickness, often referred to as the mass thickness effect. Based on the raw SRXRF spectra, we observed the accumulation of P, S, Cl, K, Ca, Fe, Cu and Zn predominantly in the SN neurons. However, upon the mass thickness correction, the distributions of Cl became significantly more uniform. Simultaneously with the fluorescence signal, the Small Angle X-ray Scattering (SAXS) is recorded by a pixel detector positioned in the far-field, enabling fast online computation of the darkfield and differential phase contrast (DPC). The data has demonstrated the SN neurons and neuropil produces excellent contrast which is due to their different mass density and scattering strength, indicative of differences in local structure and assembly therein. In all, the results show that combined SRXRF-XPCI-SAXS experiments can robustly serve as a unique tool for understanding the interplay between the chemical composition and structural organization that may drive the biochemical age-related processes occurring in the human dopaminergic system.
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•Mass thickness effect poses a major limitation to quantitative imaging by SRXRF .•Human substantia nigra (SN) neurons and surrounding neuropil are of different mass density.•X-ray Phase Contrast Imaging allows for determination of the mass densities in SN.•Small Angle X-ray Scattering enables unraveling the structural properties of the SN tissue.
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