| 1. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 2. |
- Aarts, B., et al.
(författare)
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DNActivity: International cooperation in activity level interpretation of forensic DNA evidence.
- 2015
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Ingår i: Abstract book, 7<sup>th</sup> European Academy of Forensic Science, EAFS, Prag, Tjeckien, 2015.. ; , s. 555-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activitity level (i.e. ‘how did the DNA get there?’). The answers to these questions are usually formulated as the probability of the evidence under alternative scenarios. As activity level questions are part of investigative and legal considerations it is of paramount importance that expert witnesses are provided with knowledge and tools to address these questions.To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects. There is a paucity of empirical data on these topics, but the number of studies is increasing both through in-house experiments and experimental data published in international scientific journals.Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.Moreover, if existing data and data generated from future experiments are made available to the (forensic) community, knowledge is needed on the key factors that underlie potential interlaboratory variation.The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientificdata. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation.
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| 3. |
- Bosmans, Laura A., et al.
(författare)
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Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:5, s. 1146-1160
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Tidskriftsartikel (refereegranskat)abstract
- Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/− , respect-Results ively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
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| 4. |
- Felce, JH, et al.
(författare)
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Single-Molecule, Super-Resolution, and Functional Analysis of G Protein-Coupled Receptor Behavior Within the T Cell Immunological Synapse
- 2021
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Ingår i: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 8, s. 608484-
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Tidskriftsartikel (refereegranskat)abstract
- A central process in immunity is the activation of T cells through interaction of T cell receptors (TCRs) with agonistic peptide-major histocompatibility complexes (pMHC) on the surface of antigen presenting cells (APCs). TCR-pMHC binding triggers the formation of an extensive contact between the two cells termed the immunological synapse, which acts as a platform for integration of multiple signals determining cellular outcomes, including those from multiple co-stimulatory/inhibitory receptors. Contributors to this include a number of chemokine receptors, notably CXC-chemokine receptor 4 (CXCR4), and other members of the G protein-coupled receptor (GPCR) family. Although best characterized as mediators of ligand-dependent chemotaxis, some chemokine receptors are also recruited to the synapse and contribute to signaling in the absence of ligation. How these and other GPCRs integrate within the dynamic structure of the synapse is unknown, as is how their normally migratory Gαi-coupled signaling is terminated upon recruitment. Here, we report the spatiotemporal organization of several GPCRs, focusing on CXCR4, and the G protein Gαi2 within the synapse of primary human CD4+ T cells on supported lipid bilayers, using standard- and super-resolution fluorescence microscopy. We find that CXCR4 undergoes orchestrated phases of reorganization, culminating in recruitment to the TCR-enriched center. This appears to be dependent on CXCR4 ubiquitination, and does not involve stable interactions with TCR microclusters, as viewed at the nanoscale. Disruption of this process by mutation impairs CXCR4 contributions to cellular activation. Gαi2 undergoes active exclusion from the synapse, partitioning from centrally-accumulated CXCR4. Using a CRISPR-Cas9 knockout screen, we identify several diverse GPCRs with contributions to T cell activation, most significantly the sphingosine-1-phosphate receptor S1PR1, and the oxysterol receptor GPR183. These, and other GPCRs, undergo organization similar to CXCR4; including initial exclusion, centripetal transport, and lack of receptor-TCR interactions. These constitute the first observations of GPCR dynamics within the synapse, and give insights into how these receptors may contribute to T cell activation. The observation of broad GPCR contributions to T cell activation also opens the possibility that modulating GPCR expression in response to cell status or environment may directly regulate responsiveness to pMHC.
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| 5. |
- Kerstis, Birgitta, et al.
(författare)
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Association between parental depressive symptoms and impaired bonding with the infant
- 2016
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Ingår i: Archives of Women's Mental Health. - : Springer. - 1434-1816 .- 1435-1102. ; 19:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Impaired bonding with the infant is associated with maternal postpartum depression but has not been investigated extensively in fathers. The primary study aim was to evaluate associations between maternal and paternal depressive symptoms and impaired bonding with their infant. A secondary aim was to determine the associations between parents’ marital problems and impaired bonding with the infant. The study is part of a population-based cohort project (UPPSAT) in Uppsala, Sweden. The Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks and 6 months postpartum and the Postpartum Bonding Questionnaire at 6 months postpartum were completed by 727 couples. The prevalence of impaired bonding was highest among couples in which both spouses had depressive symptoms. Impaired bonding was associated with higher EPDS scores in both mothers and fathers, as well as with experiencing a deteriorated marital relationship. The association between maternal and paternal impaired bonding and the mothers’ and fathers’ EPDS scores remained significant even after adjustment for relevant confounding factors. Depressive symptoms at 6 weeks postpartum are associated with impaired bonding with the infant at 6 months postpartum for both mothers and fathers. It is critical to screen for and prevent depressive symptoms in both parents during early parenthood.
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| 6. |
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| 7. |
- Kokshoorn, B., et al.
(författare)
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DNActivity: International cooperation in activity level interpretation of forensic DNA evidence : .
- 2015
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Ingår i: Abstracts ISFG. ; , s. 148-
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Konferensbidrag (refereegranskat)abstract
- Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activity level (i.e. ‘how did the DNA get there?’).To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects.Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientific data. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation. This project is funded by the European Union TVEFS-2020 program.
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| 8. |
- Kokshoorn, Bas, et al.
(författare)
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Sharing data on DNA transfer, persistence, prevalence and recovery : Arguments for harmonization and standardization
- 2018
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Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 37, s. 260-269
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Tidskriftsartikel (refereegranskat)abstract
- Sharing data between forensic scientists on DNA transfer, persistence, prevalence and recovery (TPPR) is crucial to advance the understanding of these issues in the criminal justice community. We present the results of a collaborative exercise on reporting forensic genetics findings given activity level propositions. This exercise outlined differences in the methodology that was applied by the participating laboratories, as well as limitations to the use of published data on DNA TPPR. We demonstrate how publication of experimental results in scientific journals can be further improved to allow for an adequate use of these data. Steps that can be taken to share and use these data for research and casework purposes are outlined, and the prospects for future sharing of data through publicly accessible databases are discussed. This paper also explores potential avenues to proceed with implementation and is intended to fuel the discussion on sharing data pertaining to DNA TPPR issues. It is further suggested that international standardization and harmonization on these topics will benefit the forensic DNA community as it has been achieved in the past with the harmonization of STR typing systems.
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| 9. |
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| 10. |
- Rudisch, J., et al.
(författare)
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Kinematic parameters of hand movement during a disparate bimanual movement task in children with unilateral Cerebral Palsy
- 2016
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Ingår i: Human Movement Science. - : Elsevier. - 0167-9457 .- 1872-7646. ; 46, s. 239-250
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Tidskriftsartikel (refereegranskat)abstract
- Children with unilateral Cerebral Palsy (uCP) experience problems performing tasks requiring the coordinated use of both hands (bimanual coordination; BC). Additionally, some children with uCP display involuntary symmetrical activation of the opposing hand (mirrored movements). Measures, used to investigate therapy-related improvements focus on the functionality of the affected hand during unimanual or bimanual tasks. None however specifically address spatiotemporal integration of both hands. We explored the kinematics of hand movements during a bimanual task to identify parameters of BC. Thirty-seven children (aged 10.9. ±. 2.6. years, 20 male) diagnosed with uCP participated. 3D kinematic motion analysis was performed during the task requiring opening of a box with their affected- (AH) or less-affected hand (LAH), and pressing a button inside with the opposite hand. Temporal and spatial components of data were extracted and related to measures of hand function and level of impairment. Total task duration was correlated with the Jebsen-Taylor Test of Hand Function in both conditions (either hand leading with the lid-opening). Spatial accuracy of the LAH when the box was opened with their AH was correlated with outcomes on the Children's Hand Use Experience Questionnaire. Additionally, we found a subgroup of children displaying non-symmetrical movement interference associated with greater movement overlap when their affected hand opened the box. This subgroup also demonstrated decreased use of the affected hand during bimanual tasks. Further investigation of bimanual interference, which goes beyond small scaled symmetrical mirrored movements, is needed to consider its impact on bimanual task performance following early unilateral brain injury.
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