| 1. |
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| 2. |
- Faatz, B., et al.
(författare)
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Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
- 2016
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Vogel, G. F., et al.
(författare)
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Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants
- 2023
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 25:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow-up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals; 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. Conclusion: In most patients, TRMU-associated ALF was a transient, reversible disease and cysteine supplementation improved survival.
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| 7. |
- Maas, R. R., et al.
(författare)
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Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
- 2017
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 82:6, s. 1004-1015
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Tidskriftsartikel (refereegranskat)abstract
- Objective: 3-Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. Methods: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic “putaminal eye” was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. Interpretation: MEGDHEL syndrome is a progressive deafness–dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004–1015. © 2017 American Neurological Association
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| 8. |
- Hikmat, O., et al.
(författare)
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Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease
- 2021
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:11, s. 2155-2165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype-phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.
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| 9. |
- Holtmann, J., et al.
(författare)
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Three-branched dendritic dipolar nonlinear optical chromophores, more than three times a single-strand chromophore?
- 2008
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 112:47, s. 14751-14761
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the dependence of the nonlinear optical (NLO) response on the conformation of triply branched derivatives, a new series of D-pi-A dendrimers has been synthesized. A combined approach of experiments (UV-vis and EOA measurements) and computational predictions (semiempirical and ab initio) was applied both on the dendrimers and on the corresponding single-strand chromophores. It has been shown that depending on the surrounding media the NLO activity of a flexible dendrimer can be very different. Two limiting cases are proposed: (i) the dendrimer resembles a solution of the corresponding single-strand chromophores with about 3-fold concentration, where the hyperpolarizability is the sum of the effect of three noninteracting single-strand subunits ("independent chromophores" limit); (ii) the dendrimers show nearly parallel or helical alignments of the single-strand subunits. Because of this change of conformation the NLO activity can be enhanced up to nine times the value of the "independent chromophores" limit and, thus, are more than a single strand chromophore. Conformers of dendrimers with interacting single-strand chromophores have been identified experimentally in nonpolar solutions by the EOA spectroscopy and possible structures have been revealed by numerical calculations, which could moreover show the tendency of the effects on the hyperpolarizability due to structural changes of the flexible dendritic architecture. Implications for future research developments are given to implement the "more than three times" concept.
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| 10. |
- Chan, P., et al.
(författare)
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Multicentennial record of Labrador Sea primary productivity and sea-ice variability archived in coralline algal barium
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated warming and melting of Arctic sea-ice has been associated with significant increases in phytoplankton productivity in recent years. Here, utilizing a multiproxy approach, we reconstruct an annually resolved record of Labrador Sea productivity related to sea-ice variability in Labrador, Canada that extends well into the Little Ice Age (LIA; 1646 AD). Barium-to-calcium ratios (Ba/Ca) and carbon isotopes (delta C-13) measured in long-lived coralline algae demonstrate significant correlations to both observational and proxy records of sea-ice variability, and show persistent patterns of co-variability broadly consistent with the timing and phasing of the Atlantic Multidecadal Oscillation (AMO). Results indicate reduced productivity in the Subarctic Northwest Atlantic associated with AMO cool phases during the LIA, followed by a step-wise increase from 1910 to present levels-unprecedented in the last 363 years. Increasing phytoplankton productivity is expected to fundamentally alter marine ecosystems as warming and freshening is projected to intensify over the coming century.
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| 11. |
- Chien, Yin-Hsiu, et al.
(författare)
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Mudd's disease (MAT I/III deficiency) : a survey of data for MAT1A homozygotes and compound heterozygotes
- 2015
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper summarizes the results of a group effort to bring together the worldwide available data on patients who are either homozygotes or compound heterozygotes for mutations in MAT1A. MAT1A encodes the subunit that forms two methionine adenosyltransferase isoenzymes, tetrameric MAT I and dimeric MAT III, that catalyze the conversion of methionine and ATP to S-adenosylmethionine (AdoMet). Subnormal MAT I/III activity leads to hypermethioninemia. Individuals, with hypermethioninemia due to one of the MAT1A mutations that in heterozygotes cause relatively mild and clinically benign hypermethioninemia are currently often being flagged in screening programs measuring methionine elevation to identify newborns with defective cystathionine beta-synthase activity. Homozygotes or compound heterozygotes for MAT1A mutations are less frequent. Some but not all, such individuals have manifested demyelination or other CNS abnormalities. Purpose of the study: The goals of the present effort have been to determine the frequency of such abnormalities, to find how best to predict whether they will occur, and to evaluate the outcomes of the variety of treatment regimens that have been used. Data have been gathered for 64 patients, of whom 32 have some evidence of CNS abnormalities (based mainly on MRI findings), and 32 do not have such evidence. Results and Discussion: The results show that mean plasma methionine concentrations provide the best indication of the group into which a given patient will fall: those with means of 800 mu M or higher usually have evidence of CNS abnormalities, whereas those with lower means usually do not. Data are reported for individual patients for MAT1A genotypes, plasma methionine, total homocysteine (tHcy), and AdoMet concentrations, liver function studies, results of 15 pregnancies, and the outcomes of dietary methionine restriction and/or AdoMet supplementation. Possible pathophysiological mechanisms that might contribute to CNS damage are discussed, and tentative suggestions are put forth as to optimal management.
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| 12. |
- Del Dotto, V., et al.
(författare)
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SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder
- 2020
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 130:1, s. 108-125
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Tidskriftsartikel (refereegranskat)abstract
- Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.
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| 13. |
- Jolak, Rodi, et al.
(författare)
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Software engineering whispers: The effect of textual vs. graphical software design descriptions on software design communication
- 2020
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Ingår i: Empirical Software Engineering. - : Springer Science and Business Media LLC. - 1382-3256 .- 1573-7616. ; 25, s. 4427-4471
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Tidskriftsartikel (refereegranskat)abstract
- Context Software engineering is a social and collaborative activity. Communicating and sharing knowledge between software developers requires much effort. Hence, the quality of communication plays an important role in influencing project success. To better understand the effect of communication on project success, more in-depth empirical studies investigating this phenomenon are needed. Objective We investigate the effect of using a graphical versus textual design description on co-located software design communication. Method Therefore, we conducted a family of experiments involving a mix of 240 software engineering students from four universities. We examined how different design representations (i.e., graphical vs. textual) affect the ability toExplain,Understand,Recall, andActively Communicateknowledge. Results We found that the graphical design description is better than the textual in promotingActive Discussionbetween developers and improving theRecallof design details. Furthermore, compared to its unaltered version, a well-organized and motivated textual design description-that is used for the same amount of time-enhances the recall of design details and increases the amount of active discussions at the cost of reducing the perceived quality of explaining.
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| 16. |
- Pisesky, Andrea, et al.
(författare)
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Adverse fibrosis remodeling and aortopulmonary collateral flow are associated with poor Fontan outcomes
- 2021
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Ingår i: Journal of Cardiovascular Magnetic Resonance. - : Springer Science and Business Media LLC. - 1097-6647 .- 1532-429X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The extent and significance in of cardiac remodeling in Fontan patients are unclear and were the subject of this study. Methods: This retrospective cohort study compared cardiovascular magnetic resonance (CMR) imaging markers of cardiac function, myocardial fibrosis, and hemodynamics in young Fontan patients to controls. Results: Fifty-five Fontan patients and 44 healthy controls were included (median age 14 years (range 7–17 years) vs 13 years (range 4–14 years), p = 0.057). Fontan patients had a higher indexed end-diastolic ventricular volume (EDVI 129 ml/m2 vs 93 ml/m2, p < 0.001), and lower ejection fraction (EF 45% vs 58%, p < 0.001), circumferential (CS − 23.5% vs − 30.8%, p < 0.001), radial (6.4% vs 8.2%, p < 0.001), and longitudinal strain (− 13.3% vs − 24.8%, p < 0.001). Compared to healthy controls, Fontan patients had higher extracellular volume fraction (ECV) (26.3% vs 20.6%, p < 0.001) and native T1 (1041 ms vs 986 ms, p < 0.001). Patients with a dominant right ventricle demonstrated larger ventricles (EDVI 146 ml/m2 vs 120 ml/m2, p = 0.03), lower EF (41% vs 47%, p = 0.008), worse CS (− 20.1% vs − 25.6%, p = 0.003), and a trend towards higher ECV (28.3% versus 24.1%, p = 0.09). Worse EF and CS correlated with longer cumulative bypass (R = − 0.36, p = 0.003 and R = 0.46, p < 0.001), cross-clamp (R = − 0.41, p = 0.001 and R = 0.40, p = 0.003) and circulatory arrest times (R = − 0.42, p < 0.001 and R = 0.27, p = 0.03). T1 correlated with aortopulmonary collateral (APC) flow (R = 0.36, p = 0.009) which, in the linear regression model, was independent of ventricular morphology (p = 0.9) and EDVI (p = 0.2). The composite outcome (cardiac readmission, cardiac reintervention, Fontan failure or any clinically significant arrhythmia) was associated with increased native T1 (1063 ms vs 1026 ms, p = 0.029) and EDVI (146 ml/m2 vs 118 ml/m2, p = 0.013), as well as decreased EF (42% vs 46%, p = 0.045) and worse CS (− 22% vs − 25%, p = 0.029). APC flow (HR 5.5 CI 1.9–16.2, p = 0.002) was independently associated with the composite outcome, independent of ventricular morphology (HR 0.71 CI 0.30–1.69 p = 0.44) and T1 (HR1.006 CI 1.0–1.13, p = 0.07). Conclusions: Pediatric Fontan patients have ventricular dysfunction, altered myocardial mechanics and increased fibrotic remodeling. Cumulative exposure to cardiopulmonary bypass and increased aortopulmonary collateral flow are associated with myocardial dysfunction and fibrosis. Cardiac dysfunction, fibrosis, and collateral flow are associated with adverse outcomes.
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| 17. |
- Rajhans, Supriya, et al.
(författare)
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Post-compression of multi-millijoule picosecond pulses to few-cycles approaching the terawatt regime
- 2023
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Ingår i: Optics Letters. - 0146-9592. ; 48:18, s. 4753-4756
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Tidskriftsartikel (refereegranskat)abstract
- Advancing ultrafast high-repetition-rate lasers to shortest pulse durations comprising only a few optical cycles while pushing their energy into the multi-millijoule regime opens a route toward terawatt-class peak powers at unprecedented average power. We explore this route via efficient post-compression of high-energy 1.2 ps pulses from an ytterbium InnoSlab laser to 9.6 fs duration using gas-filled multi-pass cells (MPCs) at a repetition rate of 1 kHz. Employing dual-stage compression with a second MPC stage supporting a close-to-octave-spanning bandwidth enabled by dispersion-matched dielectric mirrors, a record compression factor of 125 is reached at 70% overall efficiency, delivering 6.7 mJ pulses with a peak power of ∼0.3 TW. Moreover, we show that post-compression can improve the temporal contrast at multi-picosecond delay by at least one order of magnitude. Our results demonstrate efficient conversion of multi-millijoule picosecond lasers to high-peak-power few-cycle sources, prospectively opening up new parameter regimes for laser plasma physics, high energy physics, biomedicine, and attosecond science.
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| 18. |
- Seidel, M., et al.
(författare)
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Multi-pass Cell Based Nonlinear Pulse Compression of Yb : YAG Pump-Probe Lasers at FLASH
- 2023
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Ingår i: X-Ray Free-Electron Lasers : Advances in Source Development and Instrumentation VI - Advances in Source Development and Instrumentation VI. - 1996-756X .- 0277-786X. - 9781510662827 ; 12581
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Konferensbidrag (refereegranskat)abstract
- The majority of user experiments at the high repetition-rate free electron laser (FEL) facility FLASH are of pump-probe type, combining the extreme ultraviolet (XUV) or soft x-ray radiation from the FEL with ultrashort pulses generated by optical lasers. In this contribution, we demonstrate the advantages of using high-power Yb:YAG lasers with subsequent nonlinear pulse compression stages based on multi-pass cells (MPC). The approach enables the combination of hundreds of kHz to MHz repetition-rates, hundreds of watts of average powers and excellent intensity stabilities. We present the characteristics of the MPC-based pump-probe laser at the FLASH plane-grating beamlines. Furthermore, we report pulse compression to 8.2 fs pulse duration and the seeding of an optical parametric amplifier generating mid-IR radiation tunable from 1.4 µm to 16 µm.
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| 19. |
- Wylensek, David, et al.
(författare)
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A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called 'Pig intestinal bacterial collection' (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota. The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.
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