| 1. |
- Kann, D. A., et al.
(author)
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THE AFTERGLOWS OF SWIFT-ERA GAMMA-RAY BURSTS. I. COMPARING PRE-SWIFT AND SWIFT-ERA LONG/SOFT (TYPE II) GRB OPTICAL AFTERGLOWS
- 2010
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720:2, s. 1513-1558
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Journal article (peer-reviewed)abstract
- We have gathered optical photometry data from the literature on a large sample of Swift-era gamma-ray burst (GRB) afterglows including GRBs up to 2009 September, for a total of 76 GRBs, and present an additional three pre-Swift GRBs not included in an earlier sample. Furthermore, we publish 840 additional new photometry data points on a total of 42 GRB afterglows, including large data sets for GRBs 050319, 050408, 050802, 050820A, 050922C, 060418, 080413A, and 080810. We analyzed the light curves of all GRBs in the sample and derived spectral energy distributions for the sample with the best data quality, allowing us to estimate the host-galaxy extinction. We transformed the afterglow light curves into an extinction-corrected z = 1 system and compared their luminosities with a sample of pre-Swift afterglows. The results of a former study, which showed that GRB afterglows clustered and exhibited a bimodal distribution in luminosity space, are weakened by the larger sample. We found that the luminosity distribution of the two afterglow samples (Swift-era and pre-Swift) is very similar, and that a subsample for which we were not able to estimate the extinction, which is fainter than the main sample, can be explained by assuming a moderate amount of line-of-sight host extinction. We derived bolometric isotropic energies for all GRBs in our sample, and found only a tentative correlation between the prompt energy release and the optical afterglow luminosity at 1 day after the GRB in the z = 1 system. A comparative study of the optical luminosities of GRB afterglows with echelle spectra (which show a high number of foreground absorbing systems) and those without, reveals no indication that the former are statistically significantly more luminous. Furthermore, we propose the existence of an upper ceiling on afterglow luminosities and study the luminosity distribution at early times, which was not accessible before the advent of the Swift satellite. Most GRBs feature afterglows that are dominated by the forward shock from early times on. Finally, we present the first indications of a class of long GRBs, which form a bridge between the typical high-luminosity, high-redshift events and nearby low-luminosity events (which are also associated with spectroscopic supernovae) in terms of energetics and observed redshift distribution, indicating a continuous distribution overall.
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| 4. |
- Vilarino-Gueell, Carles, et al.
(author)
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VPS35 Mutations in Parkinson Disease
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 89:1, s. 162-167
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Journal article (peer-reviewed)abstract
- The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 +/- 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
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| 5. |
- Kupitz, Christopher, et al.
(author)
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Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7517, s. 261-265
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Journal article (peer-reviewed)abstract
- Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth's oxygenic atmosphere. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the 'dangler' Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.
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| 6. |
- Andersen, Gregers Stig Tig, et al.
(author)
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The DEXLIFE study methods : identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals
- 2014
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In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 383-389
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Journal article (peer-reviewed)abstract
- The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.
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| 7. |
- Puschmann, Andreas, et al.
(author)
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First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation.
- 2012
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In: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 18:4, s. 332-338
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Journal article (peer-reviewed)abstract
- The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined.
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| 8. |
- Germs, W. Chr., et al.
(author)
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Charge transport in amorphous InGaZnO thin-film transistors
- 2012
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In: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 86:15
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Journal article (peer-reviewed)abstract
- We investigate the mechanism of charge transport in indium gallium zinc oxide (a-IGZO), an amorphous metal-oxide semiconductor. We measured the field-effect mobility and the Seebeck coefficient (S = Delta V/Delta T) of a-IGZO in thin-film transistors as a function of charge-carrier density for different temperatures. Using these transistors, we further employed a scanning Kelvin probe-based technique to determine the density of states of a-IGZO that is used as the basis for the modeling. After comparing two commonly used models, the band transport percolation model and a mobility edge model, we find that both cannot describe the full properties of the charge transport in the a-IGZO semiconductor. We, therefore, propose a model that extends the mobility edge model to allow for variable range hopping below the mobility edge. The extended mobility edge model gives a superior description of the experimental results. We show that the charge transport is dominated by variable range hopping below, rather than by bandlike transport above the mobility edge.
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