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Sökning: WFRF:(Kamphuis J.)

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  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
  • Michalowski, M. J., et al. (författare)
  • Massive stars formed in atomic hydrogen reservoirs : H i observations of gamma-ray burst host galaxies
  • 2015
  • Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 582
  • Tidskriftsartikel (refereegranskat)abstract
    • Long gamma-ray bursts (GRBs), among the most energetic events in the Universe, are explosions of massive and short-lived stars, so they pinpoint locations of recent star formation. However, several GRB host galaxies have recently been found to be deficient in molecular gas (H-2), believed to be the fuel of star formation. Moreover, optical spectroscopy of GRB afterglows implies that the molecular phase constitutes only a small fraction of the gas along the GRB line of sight. Here we report the first ever 21 cm line observations of GRB host galaxies, using the Australia Telescope Compact Array, implying high levels of atomic hydrogen (HI), which suggests that the connection between atomic gas and star formation is stronger than previously thought. In this case, it is possible that star formation is directly fuelled by atomic gas (or that the HI- to- H-2 conversion is very efficient, which rapidly exhaust molecular gas), as has been theoretically shown to be possible. This can happen in low-metallicity gas near the onset of star formation because cooling of gas (necessary for star formation) is faster than the HI- to- H-2 conversion. Indeed, large atomic gas reservoirs, together with low molecular gas masses, stellar, and dust masses are consistent with GRB hosts being preferentially galaxies which have very recently started a star formation episode after accreting metal-poor gas from the intergalactic medium. This provides a natural route for forming GRBs in low-metallicity environments. The gas inflow scenario is also consistent with the existence of the companion HI object with no optical counterpart similar to 19 kpc from the GRB 060505 host, and with the fact that the HI centroids of the GRB 980425 and 060505 hosts do not coincide with optical centres of these galaxies, but are located close to the GRB positions.
  • Richards, Stephen, et al. (författare)
  • Genome sequence of the pea aphid Acyrthosiphon pisum
  • 2010
  • Ingår i: PLoS Biology. - Public Library of Science. - 1545-7885. ; 8:2, s. 1-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
  • Michalowski, Michal J., et al. (författare)
  • Molecular gas masses of gamma-ray burst host galaxies
  • 2018
  • Ingår i: Astronomy and Astrophysics. - 0004-6361. ; 617
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Long gamma-ray bursts (GRBs) can potentially be used as a tool to study star formation and recent gas accretion onto galaxies. However, the information about gas properties of GRB hosts is scarce. In particular, very few carbon monoxide (CO) line detections of individual GRB hosts have been reported. It has also been suggested that GRB hosts have lower molecular gas masses than expected from their star formation rates (SFRs). Aims. The objectives of this paper are to analyse molecular gas properties of the first substantial sample of GRB hosts and test whether they are deficient in molecular gas. Methods. We obtained CO(2-1) observations of seven GRB hosts with the APEX and IRAM 30 m telescopes. We analysed these data together with all other hosts with previous CO observations. From these observations we calculated the molecular gas masses of these galaxies and compared them with the expected values based on their SFRs and metallicities. Reults. We obtained detections for 3 GRB hosts (980425, 080207, and 111005A) and upper limits for the remaining 4 (031203, 060505, 060814, and 100316D). In our entire sample of 12 CO-observed GRB hosts, 3 are clearly deficient in molecular gas, even taking into account their metallicity (980425, 060814, and 080517). Four others are close to the best-fit line for other star-forming galaxies on the SFR-M-H2 plot (051022, 060505, 080207, and 100316D). One host is clearly molecule rich (111005A). Finally, the data for 4 GRB hosts are not deep enough to judge whether they are molecule deficient (000418, 030329, 031203, and 090423). The median value of the molecular gas depletion time, M-H2/SFR, of GRB hosts is similar to 0.3 dex below that of other star-forming galaxies, but this result has low statistical significance. A Kolmogorov-Smirnov test performed on M-H2/SFR shows an only similar to 2 sigma difference between GRB hosts and other galaxies. This difference can partly be explained by metallicity effects, since the significance decreases to similar to 1 sigma for M-H2/SFR versus metallicity. Conclusions. We found that any molecular gas deficiency of GRB hosts has low statistical significance and that it can be attributed to their lower metallicities; and thus the sample of GRB hosts has molecular properties that are consistent with those of other galaxies, and they can be treated as representative star-forming galaxies. However, the molecular gas deficiency can be strong for GRB hosts if they exhibit higher excitations and/or a lower CO-to-H-2 conversion factor than we assume, which would lead to lower molecular gas masses than we derive. Given the concentration of atomic gas recently found close to GRB and supernova sites, indicating recent gas inflow, our results about the weak molecular deficiency imply that such an inflow does not enhance the SFRs significantly, or that atomic gas converts efficiently into the molecular phase, which fuels star formation. Only if the analysis of a larger GRB host sample reveals molecular deficiency (especially close to the GRB position) would this support the hypothesis of star formation that is directly fuelled by atomic gas.
  • Mulay, A. L., et al. (författare)
  • Borderline personality disorder diagnosis in a new key
  • 2019
  • Ingår i: Borderline Personality Disorder and Emotion Dysregulation. - 2051-6673. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Conceptualizations of personality disorders (PD) are increasingly moving towards dimensional approaches. The definition and assessment of borderline personality disorder (BPD) in regard to changes in nosology are of great importance to theory and practice as well as consumers. We studied empirical connections between the traditional DSM-5 diagnostic criteria for BPD and Criteria A and B of the Alternative Model for Personality Disorders (AMPD). Method Raters of varied professional backgrounds possessing substantial knowledge of PDs (N = 20) characterized BPD criteria with the four domains of the Level of Personality Functioning Scale (LPFS) and 25 pathological personality trait facets. Mean AMPD values of each BPD criterion were used to support a nosological cross-walk of the individual BPD criteria and study various combinations of BPD criteria in their AMPD translation. The grand mean AMPD profile generated from the experts was compared to published BPD prototypes that used AMPD trait ratings and the DSM-5-III hybrid categorical-dimensional algorithm for BPD. Divergent comparisons with DSM-5-III algorithms for other PDs and other published PD prototypes were also examined. Results Inter-rater reliability analyses showed generally robust agreement. The AMPD profile for BPD criteria rated by individual BPD criteria was not isomorphic with whole-person ratings of BPD, although they were highly correlated. Various AMPD profiles for BPD were generated from theoretically relevant but differing configurations of BPD criteria. These AMPD profiles were highly correlated and showed meaningful divergence from non-BPD DSM-5-III algorithms and other PD prototypes. Conclusions Results show that traditional DSM BPD diagnosis reflects a common core of PD severity, largely composed of LPFS and the pathological traits of anxiousness, depressively, emotional lability, and impulsivity. Results confirm the traditional DSM criterion-based BPD diagnosis can be reliably cross-walked with the full AMPD scheme, and both approaches share substantial construct overlap. This relative equivalence suggests the vast clinical and research literatures associated with BPD may be brought forward with DSM-5-III diagnosis of BPD.
  • Timmers, E. R., et al. (författare)
  • Non-motor symptoms and quality of life in dopa-responsive dystonia patients
  • 2017
  • Ingår i: Parkinsonism and Related Disorders. - Elsevier. - 1353-8020. ; 45, s. 57-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In patients with GTP-cyclohydrolase deficient dopa-responsive dystonia (DRD) the occurrence of associated non-motor symptoms (NMS) is to be expected. Earlier studies report conflicting results with regard to the nature and severity of NMS. The aim of our study was to investigate the prevalence of psychiatric disorders, sleep problems, fatigue and health-related quality of life (HR-QoL) in a Dutch DRD cohort. Methods Clinical characteristics, motor symptoms, type and severity of psychiatric co-morbidity, sleep problems, fatigue and HR-QoL were assessed in DRD patients with a confirmed GCH1 mutation and matched controls. Results Twenty-eight patients were included (18 adults and 10 children), from 10 families. Dystonia symptoms were well-controlled in all patients. According to the DSM IV patients significantly more often met the criteria for a lifetime psychiatric disorder than controls (61% vs. 29%, p < 0.05). In particular the frequencies of generalized anxiety and agoraphobia were higher in patients (both 29% vs. 4%, p < 0.05). Patients scored significantly higher on daytime sleepiness than controls (ESS, 11.2 vs 5.7, p < 0.05). Adult patients had significantly lower scores on the mental component of the HR-QoL (47 vs. 54, p < 0.05) than controls mainly associated with (worse) quality of sleep. Conclusion NMS were highly prevalent in our cohort of DRD patients, despite adequate treatment of motor symptoms. Our findings support the accumulating evidence of an important non-motor phenotype in DRD, with possible involvement of serotonergic mechanisms. This highlights the need to address NMS and the underlying neurobiology in patients with DRD.
  • Carlsson, Per, et al. (författare)
  • Better Grid Integration of Distributed Generation Using Supply - Demand Matching
  • 2005
  • Konferensbidrag (populärvet., debatt m.m.)abstract
    • In the future electricity grids it is expected that the share of Distributed Generation and intermittent generators will rise. Because of that the conventional top-down-approach of grid control is no longer sufficient and the need arises to find new mechanisms for balancing supply and demand of electricity.Using new developments in ICT technology ECN and EnerSearch have developed an alternative concept of balancing supply and demand of electricity, supply-demand matching. This facilitates the introduction of a large amount of small scale distributed generation (including RES) within the lower levels of the power grid.We show several scenarios that may benefit from supply-demand matching. One scenario investigates the impact of distributed supply - demand matching (SDM) in a residential area. In the scenario a cluster of 40 houses, all connected to the same low-voltage distribution grid cell (LV-cell), is simulated. The LV-cell is externally connected to a medium voltage network. Through this connection power can be obtained from and delivered to other parts of the network. The influence of the SDM has been evaluated in terms of the possibilities to improve the overall match of local demand and supply (i.e. improvement of the local match), and decrease the dependency upon externally supplied power. The added value of SDM has been evaluated in terms of financial value of the locally generated power, and in terms of compliance to user preferences.Another scenario investigates the case of a program responsible partner having intermittent production such as a wind turbine. Due to uncertainty in the power forecast financial risk is at stake when trading the power. We add different suppliers and consumers to the portfolio, who have elasticity in their load patterns, such as a CHP-installation controlling the building temperature of a cooling device controlling a cold store. We use this elasticity as a local reserve capacity to be controlled by the program responsible partner in order to overcome the uncertainty of its intermittent production.At the conference we will present the simulation results for these scenarios within the above sketched distributed power market. The case studies will show the benefits for cost effective operation of distributed energy resources (DER); reduction of power flow through substations, thus avoiding distribution and transmission cost; controlling unbalance in intermittent renewables generation such as PV or wind. To validate the results of the simulations an experiment is being prepared.
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