| 1. |
- Abreu, P., et al.
(författare)
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Search for sleptons in e+e- collisions at √s = 183 to 189 GeV
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 29-42
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Tidskriftsartikel (refereegranskat)abstract
- Data taken by the DELPHI experiment at centre-of-mass energies of 183 GeV and 189 GeV with a total integrated luminosity of 212 pb-1 have been used to search for the supersymmetric partners of the electrons, muons, and taus in the context of the Minimal Supersymmetric Standard Model (MSSM). The decay topologies searched for were the direct decay (ℓ̃ → ℓx̃), producing acoplanar lepton pairs plus missing energy, and the cascade decay (ℓ → ℓx̃0 2 → ℓγx̃0 1), producing acoplanar lepton and photon pairs plus missing energy. The observed number of events is in agreement with Standard Model predictions. The 95% CL excluded mass limits for selectrons, smuons and staus are mẽ ≤ 87 GeV/c2, mμ̃ ≤ 80 GeV/c2 and mτ̃ 75 GeV/c2, respectively, for values of μ=-200 GeV/c2 and tanβ=1.5.
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| 2. |
- Anney, R. J. L., et al.
(författare)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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| 3. |
- Weiner, D. J., et al.
(författare)
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Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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| 4. |
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| 5. |
- Legall, H., et al.
(författare)
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Compact X-ray microscope for the water window based on a high brightness laser plasma source
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:16, s. 18362-18369
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Tidskriftsartikel (refereegranskat)abstract
- We present a laser plasma based x-ray microscope for the water window employing a high-average power laser system for plasma generation. At 90 W laser power a brightness of 7.4 x 10(11) photons/(s x sr x mu m(2)) was measured for the nitrogen Ly alpha line emission at 2.478 nm. Using a multilayer condenser mirror with 0.3 % reflectivity 10(6) photons/(mu m(2) x s) were obtained in the object plane. Microscopy performed at a laser power of 60 W resolves 40 nm lines with an exposure time of 60 s. The exposure time can be further reduced to 20 s by the use of new multilayer condenser optics and operating the laser at its full power of 130 W.
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| 6. |
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| 7. |
- Martz, Dale H., et al.
(författare)
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High average brightness water window source for short-exposure cryomicroscopy
- 2012
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Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 37:21, s. 4425-4427
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory water window cryomicroscopy has recently demonstrated similar image quality as synchrotron-based microscopy but still with much longer exposure times, prohibiting the spread to a wider scientific community. Here we demonstrate high-resolution laboratory water window imaging of cryofrozen cells with 10 s range exposure times. The major improvement is the operation of a lambda = 2.48 nm, 2 kHz liquid nitrogen jet laser plasma source with high spatial and temporal stability at high average brightness >1.5 x 10(12) ph/(s x sr x mu m(2) x line), i.e., close to that of early synchrotrons. Thus, this source enables not only biological x-ray microscopy in the home laboratory but potentially other applications previously only accessible at synchrotron facilities.
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| 8. |
- Pearce, Neil E, et al.
(författare)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 9. |
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| 10. |
- Shameer, S., et al.
(författare)
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TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:D1, s. D637-D644
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic network of a cell represents thecatabolic and anabolic reactions that interconvertsmall molecules (metabolites) through the activity ofenzymes, transporters and non-catalyzed chemicalreactions. Our understanding of individual metabolicnetworks is increasing as we learn more aboutthe enzymes that are active in particular cells underparticular conditions and as technologies advanceto allow detailed measurements of the cellularmetabolome. Metabolic network databases areof increasing importance in allowing us to contextualisedata sets emerging from transcriptomic,proteomic and metabolomic experiments. Here wepresent a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describesthe generic and condition-specific metabolic networkof Trypanosoma brucei, a parasitic protozoan responsiblefor human and animal African trypanosomiasis.In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have alsoimplemented a network-based representation of theinformation through MetExplore, yielding a novel environmentin which to visualise the metabolism ofthis important parasite.
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| 11. |
- Svanberg, Sune, et al.
(författare)
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Applications of terawatt lasers
- 1994
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Ingår i: LASER SPECTROSCOPY - XITH INTERNATIONAL CONFERENCE. - : AIP. - 1551-7616 .- 0094-243X. - 1563962624 ; :290, s. 264-269
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Konferensbidrag (refereegranskat)
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| 12. |
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| 13. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 14. |
- Legall, H., et al.
(författare)
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A compact laboratory transmission X-ray microscope for the water window
- 2013
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Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 463:1, s. 012013-
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Tidskriftsartikel (refereegranskat)abstract
- In the water window (2.2-4.4 nm) the attenuation of radiation in water is significantly smaller than in organic material. Therefore, intact biological specimen (e.g. cells) can be investigated in their natural environment. In order to make this technique accessible to users in a laboratory environment a Full-Field Laboratory Transmission X-ray Microscope (L-TXM) has been developed. The L-TXM is operated with a nitrogen laser plasma source employing an InnoSlab high power laser system for plasma generation. For microscopy the Ly α emission of highly ionized nitrogen at 2.48 nm is used. A laser plasma brightness of 5 × 1011 photons/(s × sr × μm2 in line at 2.48 nm) at a laser power of 70 W is demonstrated. In combination with a state-of-the-art Cr/V multilayer condenser mirror the sample is illuminated with 106 photons/(μm2 × s). Using objective zone plates 35-40 nm lines can be resolved with exposure times < 60 s. The exposure time can be further reduced to 20 s by the use of new multilayer condenser optics and operating the laser at its full power of 130 W. These exposure times enable cryo tomography in a laboratory environment.
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| 15. |
- Lundström, Ulf, et al.
(författare)
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X-ray phase contrast for CO2 microangiography
- 2012
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 57:9, s. 2603-2617
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a laboratory method for imaging small blood vessels using x-ray propagation-based phase-contrast imaging and carbon dioxide (CO2) gas as a contrast agent. The limited radiation dose in combination with CO2 being clinically acceptable makes the method promising for small-diameter vascular visualization. We investigate the possibilities and limitations of the method for small-animal angiography and compare it with conventional absorption-based x-ray angiography. Photon noise in absorption-contrast imaging prevents visualization of blood vessels narrower than 50 mu m at the highest radiation doses compatible with living animals, whereas our simulations and experiments indicate the possibility of visualizing 20 mu m vessels at radiation doses as low as 100 mGy. Experimental computed tomography of excised rat kidney shows blood vessels of diameters down to 60 mu m with improved image quality compared to absorption-based methods. With our present prototype x-ray source, the acquisition time for a tomographic dataset is approximately 1 h, which is long compared to the 1-20 min common for absorption-contrast micro-CT systems. Further development of the liquid-metal-jet microfocus x-ray sources used here and high-resolution x-ray detectors shows promise to reduce exposure times and make this high-resolution method practical for imaging of living animals.
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| 16. |
- McGrath, Patrick J., et al.
(författare)
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Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials : PedIMMPACT recommendations
- 2008
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 9:9, s. 771-83
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Tidskriftsartikel (refereegranskat)abstract
- Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. PERSPECTIVE: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment.
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| 17. |
- Opheim, G., et al.
(författare)
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7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice
- 2021
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 96:7, s. 327-341
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Tidskriftsartikel (refereegranskat)abstract
- Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
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| 18. |
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| 19. |
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| 20. |
- Uhlén, Fredrik, et al.
(författare)
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Damage investigation on tungsten and diamond diffractive optics at a hard x-ray free-electron laser
- 2013
-
Ingår i: Optics Express. - : Optical Society America. - 1094-4087. ; 21:7, s. 8051-8061
-
Tidskriftsartikel (refereegranskat)abstract
- Focusing hard x-ray free-electron laser radiation with extremely high fluence sets stringent demands on the x-ray optics. Any material placed in an intense x-ray beam is at risk of being damaged. Therefore, it is crucial to find the damage thresholds for focusing optics. In this paper we report experimental results of exposing tungsten and diamond diffractive optics to a prefocused 8.2 keV free-electron laser beam in order to find damage threshold fluence levels. Tungsten nanostructures were damaged at fluence levels above 500 mJ/cm(2). The damage was of mechanical character, caused by thermal stress variations. Diamond nanostructures were affected at a fluence of 59 000 mJ/cm(2). For fluence levels above this, a significant graphitization process was initiated. Scanning Electron Microscopy (SEM) and mu-Raman analysis were used to analyze exposed nanostructures.
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| 21. |
- van Kuilenburg, André B P, et al.
(författare)
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Severe fluoropyrimidine toxicity due to novel and rare DPYD missense mutations, deletion and genomic amplification affecting DPD activity and mRNA splicing
- 2017
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1863:3, s. 721-730
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Tidskriftsartikel (refereegranskat)abstract
- Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Genetic variations in DPD have emerged as predictive risk factors for severe fluoropyrimidine toxicity. Here, we report novel and rare genetic variants underlying DPD deficiency in 9 cancer patients presenting with severe fluoropyrimidine-associated toxicity. All patients possessed a strongly reduced DPD activity, ranging from 9 to 53% of controls. Analysis of the DPD gene (DPYD) showed the presence of 21 variable sites including 4 novel and 4 very rare aberrations: 3 missense mutations, 2 splice-site mutations, 1 intronic mutation, a deletion of 21 nucleotides and a genomic amplification of exons 9-12. Two novel/rare variants (c.2843T>C, c.321+1G>A) were present in multiple, unrelated patients. Functional analysis of recombinantly-expressed DPD mutants carrying the p.I948T and p.G284V mutation showed residual DPD activities of 30% and 0.5%, respectively. Analysis of a DPD homology model indicated that the p.I948T and p.G284V mutations may affect electron transfer and the binding of FAD, respectively. cDNA analysis showed that the c.321+1G>A mutation in DPYD leads to skipping of exon 4 immediately upstream of the mutated splice-donor site in the process of DPD pre-mRNA splicing. A lethal toxicity in two DPD patients suggests that fluoropyrimidines combined with other therapies such as radiotherapy might be particularly toxic for DPD deficient patients. Our study advocates a more comprehensive genotyping approach combined with phenotyping strategies for upfront screening for DPD deficiency to ensure the safe administration of fluoropyrimidines.
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| 22. |
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| 23. |
- Burvall, Anna, et al.
(författare)
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Phase retrieval in X-ray phase-contrast imaging suitable for tomography
- 2011
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Ingår i: Optics Express. - 1094-4087. ; 19:11, s. 10359-10376
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Tidskriftsartikel (refereegranskat)abstract
- In-line phase-contrast X-ray imaging provides images where both absorption and refraction contribute. For quantitative analysis of these images, the phase needs to be retrieved numerically. There are many phase-retrieval methods available. Those suitable for phase-contrast tomography, i.e., non-iterative phase-retrieval methods that use only one image at each projection angle, all follow the same pattern though derived in different ways. We outline this pattern and use it to compare the methods to each other, considering only phase-retrieval performance and not the additional effects of tomographic reconstruction. We also outline derivations, approximations and assumptions, and show which methods are similar or identical and how they relate to each other. A simple scheme for choosing reconstruction method is presented, and numerical phase-retrieval performed for all methods.
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| 24. |
- Burvall, Anna, et al.
(författare)
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Phase-retrieval methods with applications in composite-material tomography
- 2013
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Ingår i: 11th International Conference On X-Ray Microscopy (XRM2012). - : Institute of Physics Publishing (IOPP). ; , s. 012015-
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Konferensbidrag (refereegranskat)abstract
- In-line phase-contrast x-ray imaging is emerging as a method for observing small details when the contrast in absorption x-ray imaging is low. It gives images with strong edge enhancement, and phase retrieval is necessary to obtain quantitative thickness information. In particular for tomography, clarity can be enhanced by phase retrieval, as here demonstrated on a 3D-weave reinforced composite material. Seven suitable phase-retrieval methods are identified and integrated into a single method, where each version is marked by variations in particular steps. The general method and its variations are outlined and a comparison shows which methods are most suitable in different situations.
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| 25. |
- Eriksson, Fredrik, et al.
(författare)
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Enhanced soft x-ray reflectivity of Cr/Sc multilayers by ion assisted sputter deposition
- 2001
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 4506, s. 84-92
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cr/Sc multilayers have been grown on Si substrates using DC magnetron sputtering. The multilayers are intended as condenser mirrors in a soft x-ray microscope operating at the wavelength 3.374 nm. They were designed for normal reflection of the first and second order with multilayer periods of 1.692 nm and 3.381 nm, and layer thickness ratios of 0.471 and 0.237, respectively. At-wavelength soft x-ray reflectivity measurements were carried out using a reflectometer with a compact soft x-ray laser-plasma source. The multilayers were irradiated during growth with Ar ions, varying both in energy (9-113 eV) and flux, in order to stimulate the ad-atom mobility and improve the interface flatness. It was found that to obtain a maximum soft x-ray reflectivity with a low flux (Cr=0.76, Sc=2.5) of Ar ions a rather high energy of 53 eV was required. Such energy also caused intermixing of the layers. By the use of a solenoid surrounding the substrate, the arriving ion-to-metal flux ratio could be increased 10 times and the ion energy could be decreased. A high flux (Cr=7.1, Sc=23.1) of low energy (9 eV) Ar ions founded the most favourable growth condition in order to limit the intermixing with a subsistent surface flatness.
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| 26. |
- Faerch, Mia, et al.
(författare)
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Skewed X-chromosome inactivation causing diagnostic misinterpretation in congenital nephrogenic diabetes insipidus
- 2010
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 44:5, s. 324-330
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish the clinical phenotype and genetic background in a family with diabetes insipidus.MATERIAL AND METHODS: The subjects were a sister and brother, aged 34 and 27 years, respectively, with a history of polyuria since infancy. Clinical testing confirmed a diagnosis of congenital nephrogenic diabetes insipidus (CNDI) in both. Samples of purified genomic DNA were analysed.RESULTS: The sequence of the entire coding region of the AQP2 gene as well as the AVPR2 gene was determined. Sequence analysis revealed no variations in the AQP2 gene. A missense variation in exon 2 of the AVPR2 gene (g.685G>A), predicting a p.Asp85Asn substitution, was identified in the X-chromosome of the affected male and one allele in the sister and the asymptomatic mother. The p.Asp85Asn variation in AVPR2 is known to cause CNDI, and has previously been described as inducing a partial phenotype treatable with dDAVP. However, in this family dDAVP had no influence on urine osmolality, whereas combination therapy with indomethacin and hydrochlorothiazide increased urine osmolality to 299 mosm/l in the proband. A skewed X-inactivation pattern (93%) occurring in the normal X allele was recognized in the sister.CONCLUSIONS: This study demonstrates the effect of skewed X-chromosome inactivation associated with X-linked CNDI. Polydipsia in early childhood could be due to X-linked CNDI despite affecting both genders. The significant heterogeneity in the clinical phenotype in CNDI carries a risk of diagnostic misinterpretation and emphasizes the need for genetic characterization. Treatment combining indomethacin and hydrochlorothiazide results in a marked response on both urine output and urine osmolality.
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| 27. |
- Fogelqvist, Emelie, et al.
(författare)
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The Stockholm laboratory cryo x-ray microscope : towards cell-cell interaction studies
- 2013
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Ingår i: 11th International Conference On X-Ray Microscopy (XRM2012). - : Institute of Physics (IOP). ; , s. 012054-
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Konferensbidrag (refereegranskat)abstract
- We describe recent improvements in the Stockholm laboratory x-ray microscope and the first experiments aiming towards studies of cell-cell interaction. The shorter exposure time due to a higher brightness laser-plasma source will become of large importance for tomography while the reproducible cryo preparation of few-cell samples is essential for the interaction studies.
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| 28. |
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| 29. |
- Hansson, B. A. M., et al.
(författare)
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Characterisation of a liquid-xenon jet laser-plasma extreme-ultraviolet source
- 2004
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 75:6, s. 2122-2129
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Tidskriftsartikel (refereegranskat)abstract
- A liquid-xenon-jet laser-plasma source for extreme-ultraviolet (EUV) and soft-x-ray generation has been characterized. Being a source candidate for EUV lithography (EUVL), we especially focus on parameters important for the integration of the source in EUVL systems. The deep-ultraviolet (DUV) out-of-band radiation (=120–400 nm) was quantified, to within a factor of two, using a flying-circus tool together with a transmission-grating spectrograph resulting in a total DUV conversion efficiency (CE) of ~0.33%/2sr. The size and the shape of the xenon plasma was investigated using an in-band-only EUV microscope, based on a spherical Mo/Si multilayer mirror and a charge-coupled device detector. Scalability of the source size from 20–270 µm full width at half maximum was shown. The maximum repetition-rate sustainable by the liquid-xenon-jet target was simulated by a double-pulse experiment indicating feasibility of >17 kHz operation. The xenon-ion energy distribution from the plasma was determined in a time-of-flight experiment with a Faraday-cup detector showing the presence of multi-kilo-electron-volt ions. Sputtering of silicon witness plates exposed to the plasma was observed, while a xenon background of >1 mbar was shown to eliminate the sputtering. It is concluded that the source has potential to meet the requirements of future EUVL systems.
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| 30. |
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| 31. |
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| 32. |
- Hertz, H.M., et al.
(författare)
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High voltage measurement system based on a capacitively coupled Pockels cell
- 1987
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Ingår i: Proc. SPIE - Int. Soc. Opt. Eng. (USA). ; 701, s. 8-226
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A fiber-optical system for measurements of fast high voltage pulses has been developed. The system is based on capacitively coupled Pockels cell voltage sensor and features excellent rejection of electrical interference, large bandwidth and practically unlimited voltage range. The authors describe the principle of operation and give a preliminary discussion of the performance of the measurement system
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| 33. |
- Hertz, Hans M., et al.
(författare)
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Laboratory x-ray fluorescence tomography for high-resolution nanoparticle bio-imaging
- 2014
-
Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 39:9, s. 2790-2793
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that nanoparticle x-ray fluorescence computed tomography in mouse-sized objects can be performed with very high spatial resolution at acceptable dose and exposure times with a compact laboratory system. The method relies on the combination of the 24 keV line-emission from a high-brightness liquid-metal-jet x-ray source, pencil-beam-forming x-ray optics, photon-counting energy-dispersive detection, and carefully matched (Mo) nanoparticles. Phantom experiments and simulations show that the arrangement significantly reduces Compton background and allows 100 mu m detail imaging at dose and exposure times compatible with small-animal experiments. The method provides a possible path to in vivo molecular x-ray imaging at sub-100 mu m resolution in mice.
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| 34. |
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| 35. |
- Hertz, H.M, et al.
(författare)
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Optically trapped non-linear particles as probes for scanning near-field optical microscopy
- 1995
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Ingår i: Ultramicroscopy. - 0304-3991. ; 57:2-3, s. 309-312
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Tidskriftsartikel (refereegranskat)abstract
- We use the frequency doubled light from an optically trapped lithium niobate particle for non-intrusive scanning near-field optical microscopy. The detected power from this 50-100 nm diameter probe is currently tens of pW and is expected to approach nW with an improved detection system. The current experimental resolution is approximately 0.5 [mu]m, while the ultimate theoretical resolution is 70-90 nm. An acoustic trap which potentially allows higher resolution imaging is briefly described.
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| 36. |
- Hertz, Hans M., et al.
(författare)
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Propagation-based phase-contrast imaging with laboratory sources
- 2016
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Ingår i: Optics InfoBase Conference Papers. - Washington, D.C. : OSA - The Optical Society. - 9781943580095
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Konferensbidrag (refereegranskat)abstract
- We demonstrate that propagation-based phase-contrast x-ray imaging with state-of-the art laboratory microfocus sources allows imaging of thick biomedical objects with very high spatial resolution.
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| 37. |
- Hertz, Hans M., et al.
(författare)
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Table-top X-ray microscopy : Sources, optics and applications
- 2003
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Ingår i: Journal de Physique IV. - : EDP Sciences. - 1155-4339 .- 1764-7177. ; 104, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- We have developed the first operative compact sub-visible-resolution x-ray microscope for the water-window region (lambda = 2.3 - 4.4 nm). The microscope is based on a 100 Hz liquid-jet-target laser-plasma x-ray source, normal-incidence multilayer condenser optics, diffractive zone plate optics and CCD detection. In the present article we emphasize the system's aspects and summarize the recent progress on the components, all aiming at the reduction of the exposure time of a few seconds, i.e., similar to bending-magnet based microscopes. This primarily includes improved laser-plasma source, improved condenser optics using Cr/Sc multilayers, and improved image handling capability using wavelet algorithms. Such compact short-exposure time microscopes would significantly increase the applicability of the technology.
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| 38. |
- Hertz-Picciotto, I., et al.
(författare)
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Polybrominated dipheny ehters in relation to autism and developmental delay : A case-control study
- 2011
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Ingår i: Environmental Health. - 1476-069X. ; 10, s. 1-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polybrominated diphenyl ethers (PBDEs) are flame retardants used widely and in increasing amounts in the U.S. over the last few decades. PBDEs and their metabolites cross the placenta and studies in rodents demonstrate neurodevelopmental toxicity from prenatal exposures. PBDE exposures occur both via breastfeeding and hand-to-mouth activities in small children. Methods: Participants were 100 children from the CHARGE (CHildhood Autism Risk from Genetics and the Environment) Study, a case-control epidemiologic investigation of children with autism/autism spectrum disorder, with developmental delay and from the general population. Diagnoses of autism were confirmed by the Autism Diagnostic Observation Schedule and Autism Diagnostic Inventory-Revised, and of developmental delay using the Mullen's Scales of Early Learning and the Vineland Adaptive Behavior Scales. Typically developing controls were those with no evidence of delay, autism, or autism spectrum disorder. Eleven PBDE congeners were measured by gas chromatography/mass spectrometry from serum specimens collected after children were assessed. Logistic regression was used to evaluate the association between plasma PBDEs and autism. Results: Children with autism/autism spectrum disorder and developmental delay were similar to typically developing controls for all PBDE congeners, but levels were high for all three groups. Conclusions: Plasma samples collected post-diagnosis in this study may not represent early life exposures due to changes in diet and introduction of new household products containing PBDEs. Studies with direct measurements of prenatal or infant exposures are needed to assess the possible causal role for these compounds in autism spectrum disorders.
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| 39. |
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| 40. |
- Hoppe, R., et al.
(författare)
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Full characterization of a focused wavefield with sub 100 nm resolution
- 2013
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Ingår i: Advances In X-Ray Free-Electron Lasers II. - : SPIE - International Society for Optical Engineering. - 9780819495808 ; , s. 87780G-
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Konferensbidrag (refereegranskat)abstract
- A hard x-ray free-electron laser (XFEL) provides an x-ray source with an extraordinary high peak-brilliance, a time structure with extremely short pulses and with a large degree of coherence, opening the door to new scientific fields. Many XFEL experiments require the x-ray beam to be focused to nanometer dimensions or, at least, benefit from such a focused beam. A detailed knowledge about the illuminating beam helps to interpret the measurements or is even inevitable to make full use of the focused beam. In this paper we report on focusing an XFEL beam to a transverse size of 125nm and how we applied ptychographic imaging to measure the complex wavefield in the focal plane in terms of phase and amplitude. Propagating the wavefield back and forth we are able to reconstruct the full caustic of the beam, revealing aberrations of the nano-focusing optic. By this method we not only obtain the averaged illumination but also the wavefield of individual XFEL pulses.
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| 41. |
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| 42. |
- Jais, JP, et al.
(författare)
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X-linked Alport syndrome: Natural history and genotype-phenotype correlations in girls and women belonging to 195 families: A "European community Alport syndrome concerted action" study
- 2003
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673. ; 14:10, s. 2603-2610
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Tidskriftsartikel (refereegranskat)abstract
- Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disease in girls and women. A "European Community Alport Syndrome Concerted Action" (ECASCA) group was established to delineate the Alport syndrome phenotype in each gender and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of heterozygous girls and women belonging to the 195 families with proven COL4A5 mutation are compared with those of hemizygous boys and men. Hematuria was observed in 95% of carriers and consistently absent in the others. Proteinuria, hearing loss, and ocular defects developed in 75%, 28%, and 15%, respectively. The probability of developing end-stage renal disease or deafness before the age of 40 yr was 12% and 10%, respectively, in girls and women versus 90 and 80%, respectively, in boys and men. The risk of progression to end-stage renal disease appears to increase after the age of 60 yr in women. Because of the absence of genotype-phenotype correlation and the large intrafamilial phenotypic heterogeneity, early prognosis of the disease in X-linked Alport syndrome carriers remains moot. Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect.
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| 43. |
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| 44. |
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| 45. |
- Kauranen, P, et al.
(författare)
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Tomographic imaging of fluid flows by the use of two-tone frequency-modulation spectroscopy
- 1994
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Ingår i: Optics Letters. - 0146-9592. ; 19:18, s. 1489-1491
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Tidskriftsartikel (refereegranskat)abstract
- Diode laser absorption measurements obtained with two-tone frequency-modulation spectroscopy (TTFMS) are combined with tomography to produce spatially resolved quantitative images of fluid flows. The high sensitivity, good accuracy, and high stability of TTFMS absorption measurements permit optical-absorption tomography to be performed with low noise on extremely weakly absorbing objects. The method is demonstrated on a small oxygen flow with a GaAlAs diode laser operating near 760 nm and with an absorption sensitivity of 1:106.
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| 46. |
- Larsson, Daniel H., et al.
(författare)
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A 24 keV liquid-metal-jet x-ray source for biomedical applications
- 2011
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Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 82:12, s. 123701-
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Tidskriftsartikel (refereegranskat)abstract
- We present a high-brightness 24-keV electron-impact microfocus x-ray source based on continuous operation of a heated liquid-indium/gallium-jet anode. The 30–70 W electron beam is magnetically focused onto the jet, producing a circular 7–13 μm full width half maximum x-ray spot. The measured spectral brightness at the 24.2 keV In Kα line is 3 × 109 photons/(s × mm2 × mrad2 × 0.1% BW) at 30 W electron-beam power. The high photon energy compared to existing liquid-metal-jet sources increases the penetration depth and allows imaging of thicker samples. The applicability of the source in the biomedical field is demonstrated by high-resolution imaging of a mammography phantom and a phase-contrast angiography phantom.
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| 47. |
- Larsson, Daniel H., et al.
(författare)
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First application of liquid-metal-jet sources for small-animal imaging : High-resolution CT and phase-contrast tumor demarcation
- 2013
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Ingår i: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 40:2, s. 021909-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Small-animal studies require images with high spatial resolution and high contrast due to the small scale of the structures. X-ray imaging systems for small animals are often limited by the microfocus source. Here, the authors investigate the applicability of liquid-metal-jet x-ray sources for such high-resolution small-animal imaging, both in tomography based on absorption and in soft-tissue tumor imaging based on in-line phase contrast. Methods: The experimental arrangement consists of a liquid-metal-jet x-ray source, the small-animal object on a rotating stage, and an imaging detector. The source-to-object and object-to-detector distances are adjusted for the preferred contrast mechanism. Two different liquid-metal-jet sources are used, one circulating a Ga/In/Sn alloy and the other an In/Ga alloy for higher penetration through thick tissue. Both sources are operated at 40-50 W electron-beam power with similar to 7 mu m x-ray spots, providing high spatial resolution in absorption imaging and high spatial coherence for the phase-contrast imaging. Results: High-resolution absorption imaging is demonstrated on mice with CT, showing 50 mu m bone details in the reconstructed slices. High-resolution phase-contrast soft-tissue imaging shows clear demarcation of mm-sized tumors at much lower dose than is required in absorption. Conclusions: This is the first application of liquid-metal-jet x-ray sources for whole-body small-animal x-ray imaging. In absorption, the method allows high-resolution tomographic skeletal imaging with potential for significantly shorter exposure times due to the power scalability of liquid-metal-jet sources. In phase contrast, the authors use a simple in-line arrangement to show distinct tumor demarcation of few-mm-sized tumors. This is, to their knowledge, the first small-animal tumor visualization with a laboratory phase-contrast system.
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| 48. |
- Larsson, Daniel H., et al.
(författare)
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High-resolution short- exposure small-animal laboratory x-ray phase-contrast tomography
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten mu m spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.
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| 49. |
- Larsson, Daniel H., et al.
(författare)
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Small-animal tomography with a liquid-metal-jet x-ray source
- 2012
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE - International Society for Optical Engineering. - 9780819489623 ; , s. 83130N-
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Konferensbidrag (refereegranskat)abstract
- X-ray tomography of small animals is an important tool for medical research. For high-resolution x-ray imaging of few-cm-thick samples such as, e.g., mice, high-brightness x-ray sources with energies in the few-10-keV range are required. In this paper we perform the first small-animal imaging and tomography experiments using liquid-metal-jet-anode x-ray sources. This type of source shows promise to increase the brightness of microfocus x-ray systems, but present sources are typically optimized for an energy of 9 keV. Here we describe the details of a high-brightness 24-keV electron-impact laboratory microfocus x-ray source based on continuous operation of a heated liquid-In/Ga-jet anode. The source normally operates with 40 W of electron-beam power focused onto the metal jet, producing a 7×7 μm 2 FWHM x-ray spot. The peak spectral brightness is 4 × 10 9 photons/( s × mm 2 × mrad 2 × 0.1%BW) at the 24.2 keV In K α line. We use the new In/Ga source and an existing Ga/In/Sn source for high-resolution imaging and tomography of mice.
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| 50. |
- Larsson, Jakob C., et al.
(författare)
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High-spatial-resolution nanoparticle X-ray fluorescence tomography
- 2016
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Ingår i: MEDICAL IMAGING 2016. - : SPIE. - 9781510600188
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Konferensbidrag (refereegranskat)abstract
- X-ray fluorescence tomography (XFCT) has potential for high-resolution 3D molecular x-ray bio-imaging. In this technique the fluorescence signal from targeted nanoparticles (NPs) is measured, providing information about the spatial distribution and concentration of the NPs inside the object. However, present laboratory XFCT systems typically have limited spatial resolution (>1 mm) and suffer from long scan times and high radiation dose even at high NP concentrations, mainly due to low efficiency and poor signal-to-noise ratio. We have developed a laboratory XFCT system with high spatial resolution (sub-100 mu m), low NP concentration and vastly decreased scan times and dose, opening up the possibilities for in-vivo small-animal imaging research. The system consists of a high-brightness liquid-metal-jet microfocus x-ray source, x-ray focusing optics and an energy-resolving photon-counting detector. By using the source's characteristic 24 keV line-emission together with carefully matched molybdenum nanoparticles the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the Mo nanoparticles. A filtered back-projection method is used to produce the final XFCT image.
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