| 1. |
- Faatz, B., et al.
(author)
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Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
- 2016
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Journal article (peer-reviewed)abstract
- Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs-dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.
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| 2. |
- Haycock, Philip C., et al.
(author)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Journal article (peer-reviewed)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Neves-Petersen, Maria Teresa, et al.
(author)
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Flash Photolysis of Cutinase: Identification and Decay Kinetics of Transient Intermediates Formed upon UV Excitation of Aromatic Residues
- 2009
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In: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 97:1, s. 211-226
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Journal article (peer-reviewed)abstract
- Aromatic amino acids play an important role in ultraviolet (UV)-induced photochemical reactions in proteins. In this work, we aim at gaining insight into the photochemical reactions induced by near-UV light excitation of aromatic residues that lead to breakage of disulfide bridges in our model enzyme, Fusarium solani pisi cutinase, a lipolytic enzyme. With this purpose, we acquired transient absorption data of cutinase, with supplemental experimental data on tryptophan (Trp) and lysozyme as reference molecules. We here report formation kinetics and lifetimes of transient chemical species created upon UV excitation of aromatic residues in proteins. Two proteins, lysozyme and cutinase, as well as the free amino acid Trp, were studied under acidic, neutral, and alkaline conditions. The shortest-lived species is assigned to solvated electrons (lifetimes of a few microseconds to nanoseconds), whereas the longer-lived species are assigned to aromatic neutral and ionic radicals, Trp triplet states, and radical ionic disulphide bridges. The pH-dependent lifetimes of each species are reported. Solvated electrons ejected from the side chain of free Trp residues and aromatic residues in proteins were observed 12 ns after excitation, reaching a maximum yield after similar to 40 ns. It is interesting to note that the formation kinetics of solvated electrons is not pH-dependent and is similar in the different samples. On the other hand, a clear increase of the solvated electron lifetime is observed with increasing pH. This observation is correlated with H3O+ being an electron scavenger. Prolonged UV illumination of cutinase leads to a larger concentration of solvated electrons and to greater absorption at 410 nm (assigned to disulphide electron adduct RSSR center dot-), with concomitant faster decay kinetics and near disappearance of the Trp(center dot) radical peak at 330 nm, indicating possible additional formation of TyrO(center dot) formed upon reaction of Trp(center dot) with Tyr residues. Prolonged UV illumination of cutinase also leads to a larger concentration of free thiol groups, known to originate from the dissociation of RSSR center dot-. Additional mechanisms that may lead to the near disappearance of Trp(center dot) are discussed. Our study provides insight into one key UV-light-induced reaction in cutinase, i.e., light-induced disruption of disulphide bridges mediated by the excitation of aromatic residues. Knowledge about the nature of the formed species and their lifetimes is important for the understanding of UV-induced reactions in humans that lead to light-induced diseases, e.g., skin cancer and cataract formation.
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| 4. |
- Nilsson, Anna, et al.
(author)
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Tryptophan-tagged cutinase studied by steady state fluorescence for understanding of tag interactions in aqueous two-phase systems
- 2003
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In: Biochimica et Biophysica Acta - Proteins and Proteomics. - 1570-9639. ; 1646:1-2, s. 57-66
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Journal article (peer-reviewed)abstract
- Genetic engineering has been used to construct fusion proteins of Fusarium solani pisi cutinase and tryptophan-based tags, expressed in Saccharomyces cerevisiae, to increase the partitioning in aqueous two-phase systems. The separation systems were composed of thermoseparating polymers (random copolymers of ethylene oxide and propylene oxide, EOPO) and detergents (C12EOn). In this study, the fluorescence behaviour of the peptide-tagged protein, free peptide tag and tryptophan was investigated. The tryptophan-tagged proteins, cutinase-(WP)4 and cutinase-TGGSGG-(WP)4, showed emission spectra similar to the free peptides and tryptophan, indicating solvent exposure of the tag. The influence of polymers and detergents on the fluorescence of tagged proteins was examined. When peptides and tagged proteins were exposed to polymer, a slight blue shift of the emission maximum was observed. Larger blue shifts of the emission maximum were observed when C12EOn detergents were utilised. The results correlate with aqueous two-phase partitioning where addition of C12EOn detergents results in more extreme partitioning compared to systems containing only polymers. Dynamic light scattering (DLS) measurements of the EOPO copolymers were carried out, showing that the polymers did not aggregate at concentrations used in aqueous two-phase systems. Quenching of fluorescence with iodide for both proteins and peptide tags was studied. Plots according to the Stern-Volmer equation resulted in a linear fit, indicating exposed tryptophan residues for both free peptides and fusion proteins. The quenching constants were similar for both tagged protein and free peptide tag. The fluorescence results indicated that the tryptophan residues in the tag were exposed to the solvent and could interact with detergents and polymers in the two-phase systems.
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| 5. |
- Petersen, Steffen E, et al.
(author)
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Cardiovascular Magnetic Resonance for Patients With COVID-19
- 2022
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In: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1876-7591 .- 1936-878X. ; 15:4, s. 685-699
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Research review (peer-reviewed)abstract
- COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19-related myocarditis is likely infrequent, COVID-19-related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post-COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19-related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19.
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| 6. |
- Goncalves, Odete Sofia Lopes, et al.
(author)
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The repeated 36 amino acid motif of Chlamydia trachomatis Hc2 protein binds to the major groove of DNA
- 2019
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In: Research in Microbiology. - : ELSEVIER. - 0923-2508 .- 1769-7123. ; 170:6-7, s. 256-262
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Journal article (peer-reviewed)abstract
- The gram-negative, obligate intracellular human pathogen, Chlamydia trachomatis has a bi-phasic developmental cycle. The histone H1-like C. trachomatis DNA binding protein, Hc2, is produced late during the developmental cycle when the dividing reticulate body transforms into the smaller, metabolically inactive elementary body. Together with Hc1, the two proteins compact the chlamydial chromosome and arrest replication and transcription. Hc2 is heterogeneous in length due to variation in the number of lysine rich pentamers. Six pentamers and one hexamer constitute a 36 amino acid long repetitive unit that, in spite of variations, is unique for Chlamydiaceae. Using synthetic peptides, the DNA-binding capacity of the 36 amino acid peptide and that of a randomized peptide was analyzed. Both peptides bound and compacted plasmid DNA, however, electron microscopy of peptide/DNA complexes showed major differences in the resulting aggregated structures. Fluorescence spectroscopy was used to analyze the binding. After complexing plasmid DNA with each of three different intercalating dyes, increasing amounts of peptides were added and fluorescence spectroscopy performed. The major groove binder, methyl green, was displaced by both peptides at low concentrations, while the minor groove binder, Hoechts, and the intercalating dye, Ethidium Bromide, were displaced only at high concentrations of peptides. (C) 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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| 7. |
- Petersen, Steffen E, et al.
(author)
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Differentiation of athlete's heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance.
- 2005
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In: Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance. - 1097-6647. ; 7:3, s. 551-8
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Journal article (peer-reviewed)abstract
- PURPOSE: Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging. METHODS: A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined. RESULTS: Left ventricular (LV) mass indices were similar for all forms of LVH (p > 0.05), which were at least 35% higher than those obtained in healthy volunteers (p < 0.05). Multiple logistic regression showed that the percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive heart disease. Using a receiver operating curve-determined cut-off value for diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes' hearts could be differentiated from all forms of pathological cardiac hypertrophy with 99% specificity. CONCLUSIONS: Athlete's heart can be reliably distinguished from all forms of pathological cardiac hypertrophy using CMR-derived LV volume and geometric indices, but pathological forms of LVH present with overlapping cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical value.
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