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- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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| 8. |
- Kujala, M, et al.
(författare)
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Expression of ion transport-associated proteins in human efferent and epididymal ducts
- 2007
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Ingår i: Reproduction (Cambridge, England). - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 133:4, s. 775-784
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Tidskriftsartikel (refereegranskat)abstract
- Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na+/H+exchanger 3 (NHE3), the Cl−channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na+/H+exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.
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| 9. |
- Mustjoki, S., et al.
(författare)
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Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
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Tidskriftsartikel (refereegranskat)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
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- Tong, M., et al.
(författare)
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An integrated framework for multi-scale multi-physics numerical modelling of interface evolution in welding
- 2012
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Ingår i: IOP Conf. Ser. Mater. Sci. Eng..
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Konferensbidrag (refereegranskat)abstract
- The project Modelling of Interface evolution in advanced Welding (MIntWeld) is a 4-year international research project funded by the European Commission under their FP7 programme. Its main target is to develop a numerical toolbox which can be used to predict the evolution of interfaces during welding. There are various interfaces involving multiple phenomena and different spatial scales, which can be simulated using corresponding numerical modelling methods respectively. The modelling methods include quantum dynamics, molecular dynamics, phase field, phase field crystal, computational fluid dynamics, phase transformation and heat transfer, thermodynamics, continuum mechanics and life and defects prediction. Although each modelling method is based on different physical theories and involves different scales, they are not isolated. Therefore, this project aims to design a common framework which couples each model with the upstream and/or downstream model at the relevant neighbouring length scales. The data exchange framework which underpins the coupling of the models is described, and typical examples addressing the solution to the challenges faced, such as those of data interpolation between one discretisation of the computational domain and another, are discussed. Initial successes from the model-linking efforts of the authors are also presented.
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| 14. |
- Backis, A., et al.
(författare)
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Time- and energy-resolved effects in the boron-10 based multi-grid and helium-3 based thermal neutron detectors
- 2021
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Ingår i: Measurement science and technology. - : IOP PUBLISHING LTD. - 0957-0233 .- 1361-6501. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- The boron-10 based multi-grid detector is being developed as an alternative to helium-3 based neutron detectors. At the European Spallation Source, the detector will be used for time-of-flight neutron spectroscopy at cold to thermal neutron energies. The objective of this work is to investigate fine time- and energy-resolved effects of the Multi-Grid detector, down to a few mu eV, while comparing it to the performance of a typical helium-3 tube. Furthermore, it is to characterize differences between the detector technologies in terms of internal scattering, as well as the time reconstruction of similar to mu s short neutron pulses. The data were taken at the Helmholtz Zentrum Berlin, where the Multi-Grid detector and a helium-3 tube were installed at the ESS test beamline, V20. Using a Fermi-chopper, the neutron beam of the reactor was chopped into a few tens of mu s wide pulses before reaching the detector, located a few tens of cm downstream. The data of the measurements show an agreement between the derived and calculated neutron detection efficiency curve. The data also provide fine details on the effect of internal scattering, and how it can be reduced. For the first time, the chopper resolution was comparable to the timing resolution of the Multi-Grid detector. This allowed a detailed study of time- and energy resolved effects, as well as a comparison with a typical helium-3 tube.
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| 15. |
- Birgersson, Sofia, 1976, et al.
(författare)
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Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: An open label trial [version 2; peer review: 2 approved]
- 2020
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008). © 2020 Birgersson S et al.
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| 24. |
- Hoglund, J, et al.
(författare)
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Microsatellite markers reveal the potential for kin selection on black grouse leks
- 1999
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Ingår i: PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES. - : ROYAL SOC LONDON. - 0962-8452. ; 266:1421, s. 813-816
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The evolution of social behaviour has puzzled biologists since Darwin. Since Hamilton's theoretical work in the 1960s it has been realized that social behaviour may evolve through the effects of kinship. By helping relatives, an individual may pass on its
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| 32. |
- Nilsson, J., et al.
(författare)
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Non Ischemic Heart Preservation
- 2018
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Ingår i: The Journal of Heart and Lung Transplantation. - 1053-2498. ; 37:4, s. 13-13
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Konferensbidrag (refereegranskat)
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| 33. |
- Ostadkarampour, M., et al.
(författare)
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Higher levels of interleukin IL-17 and antigen-specific IL-17 responses in pulmonary sarcoidosis patients with Lofgren's syndrome
- 2014
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 178:2, s. 342-352
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Tidskriftsartikel (refereegranskat)abstract
- Sarcoidosis is a granulomatous disorder of unknown aetiology. The presence of Mycobacterium tuberculosis catalase-peroxidase (mKatG) in sarcoidosis tissue has been reported. T helper type 1 (Th1) responses against mKatG have previously been observed. However, little is known about interleukin (IL)-17 and Th17 responses in sarcoidosis. Here, we investigated the levels of IL-17 and frequencies of IL-17-producing cells responding to mKatG in sarcoidosis patients with different prognosis. Peripheral blood and bronchoalveolar lavage (BAL) cells were obtained from sarcoidosis patients with or without Lofgren's syndrome (often associated with spontaneous recovery), and also stratified according to human leucocyte antigen (HLA) type. Cells producing IL-17 and interferon (IFN)-gamma after stimulation with mKatG were enumerated by enzyme-linked immunospot (ELISPOT). The level of IL-17 in the BAL fluid of sarcoidosis patients and healthy controls was measured by quantitative immuno-polymerase chain reaction (qIPCR). We also performed flow cytometry and immunohistochemistry for further characterization of IL-17 expression. Patients with Lofgren's syndrome had a higher frequency of IL-17-producing cells responding to mKatG in BAL fluid compared to patients without Lofgren's syndrome (P < 0.05). The HLA-DR3(+) sarcoidosis patients with Lfgren's syndrome (known to have a particularly good prognosis) also had a clearly higher level of IL-17 in BAL fluid compared to healthy controls and sarcoidosis patients without Lofgren's syndrome (P < 0.01) and (P < 0.05), respectively. No such difference between patient groups was observed with regard to IFN-gamma and not with regard to either cytokine in peripheral blood. These findings suggest that IL-17-producing cells may be a useful biomarker for the prognosis of sarcoidosis and play a role in the spontaneous recovery typical of patients with Lfgren's syndrome.
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| 35. |
- Rintamäki, PT, et al.
(författare)
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Combs and sexual selection in black grouse (Tetrao tetrix)
- 2000
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Ingår i: BEHAVIORAL ECOLOGY. - : OXFORD UNIV PRESS INC. - 1045-2249. ; 11:5, s. 465-471
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Tidskriftsartikel (refereegranskat)abstract
- We studied supra-orbital combs in lekking black grouse (Telrao tetrix) in relation to sexual selection at five leks in Finland 1991-1998 and four leks in Sweden 1992-1995. Comb size was estimated in two ways: by observing its natural size in the field at
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| 36. |
- Shorey, L, et al.
(författare)
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Fine-scale genetic structuring on Manacus manacus leks
- 2000
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Ingår i: NATURE. - : MACMILLAN PUBLISHERS LTD. - 0028-0836. ; 408:6810, s. 352-353
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Tidskriftsartikel (refereegranskat)abstract
- Leks have traditionally been considered as arenas where males compete to attract females and secure matings. Thus, direct fitness benefits mediated through competition between males to fertilize females have been considered to be the primary force driving
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| 38. |
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| 39. |
- Wedenoja, S, et al.
(författare)
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A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 14208-
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Tidskriftsartikel (refereegranskat)abstract
- Chloride absorption and bicarbonate excretion through exchange by the solute carrier family 26 member 3 (SLC26A3) and cystic fibrosis transmembrane conductance regulator (CFTR) are crucial for many tissues including sperm and epithelia of the male reproductive tract. Homozygous SLC26A3 mutations cause congenital chloride diarrhea with male subfertility, while homozygous CFTR mutations cause cystic fibrosis with male infertility. Some homozygous or heterozygous CFTR mutations only manifest as male infertility. Accordingly, we studied the influence of SLC26A3 on idiopathic infertility by sequencing exons of SLC26A3 in 283 infertile and 211 control men. A heterozygous mutation c.2062 G > C (p.Asp688His) appeared in nine (3.2%) infertile men, and additionally, in two (0.9%) control men, whose samples revealed a sperm motility defect. The p.Asp688His mutation is localized in the CFTR-interacting STAS domain of SLC26A3 and enriched in Finland, showing a significant association with male infertility in comparison with 6,572 Finnish (P < 0.05) and over 120,000 global alleles (P < 0.0001) (ExAC database). Functional studies showed that while SLC26A3 is a strong activator of CFTR-dependent anion transport, SLC26A3-p.Asp688His mutant retains normal Cl−/HCO3− exchange activity but suppresses CFTR, despite unaffected domain binding and expression. These results suggest a novel mechanism for human male infertility─impaired anion transport by the coupled SLC26A3 and CFTR.
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| 40. |
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| 41. |
- Yougbare, I, et al.
(författare)
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Activated NK cells cause placental dysfunction and miscarriages in fetal alloimmune thrombocytopenia
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 224-
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Tidskriftsartikel (refereegranskat)abstract
- Miscarriage and intrauterine growth restriction (IUGR) are devastating complications in fetal/neonatal alloimmune thrombocytopenia (FNAIT). We previously reported the mechanisms for bleeding diatheses, but it is unknown whether placental, decidual immune cells or other abnormalities at the maternal–fetal interface contribute to FNAIT. Here we show that maternal immune responses to fetal platelet antigens cause miscarriage and IUGR that are associated with vascular and immune pathologies in murine FNAIT models. Uterine natural killer (uNK) cell recruitment and survival beyond mid-gestation lead to elevated NKp46 and CD107 expression, perforin release and trophoblast apoptosis. Depletion of NK cells restores normal spiral artery remodeling and placental function, prevents miscarriage, and rescues hemorrhage in neonates. Blockade of NK activation receptors (NKp46, FcɣRIIIa) also rescues pregnancy loss. These findings shed light on uNK antibody-dependent cell-mediated cytotoxicity of invasive trophoblasts as a pathological mechanism in FNAIT, and suggest that anti-NK cell therapies may prevent immune-mediated pregnancy loss and ameliorate FNAIT.
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| 47. |
- Andersson, J. O., et al.
(författare)
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THERMO-CALC & DICTRA, computational tools for materials science
- 2002
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Ingår i: Calphad. - 0364-5916 .- 1873-2984. ; 26:2, s. 273-312
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Tidskriftsartikel (refereegranskat)abstract
- Software for calculation of phase diagrams and thermodynamic properties have been developed since the 1970's. Software and computers have now developed to a level where such calculations can be used as tools for material and process development. In the present paper some of the latest software developments at Thermo-Calc Software are presented together with application examples. It is shown how advanced thermodynamic calculations have become more accessible since: - A more user-friendly windows version of Thermo-Calc, TCW, has been developed. - There is an increasing amount of thermodynamic databases for different materials available. - Thermo-Calc can be accessed from user-written software through several different programming interfaces are available which enables access to the thermodynamic software from a user-written software. Accurate data for thermodynamic properties and phase equilibria can then easily be incorporated into software written in e.g. C++, Matlab and FORTRAN. Thermo-Calc Software also produces DICTRA, a software for simulation of diffusion controlled phase transformations. Using DICTRA it is possible to simulate processes such as homogenization, carburising, microsegregation and coarsening in multicomponent alloys. The different models in the DICTRA software are briefly presented in the present paper together with some application examples.
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| 48. |
- Andersson, J. Y., et al.
(författare)
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Quantum structure based infrared detector research and development within Acreo's centre of excellence IMAGIC
- 2010
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Ingår i: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 53:4, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- Acreo has a long tradition of working with quantum structure based infrared (IR) detectors and arrays. This includes QWIP (quantum well infrared photodetector), QDIP (quantum dot infrared photodetector), and InAs/GaInSb based photon detectors of different structure and composition. It also covers R&D on uncooled microbolometers. The integrated thermistor material of such detectors is advantageously based on quantum structures that are optimised for high temperature coefficient and low noise. Especially the SiGe material system is preferred due to the compatibility with silicon technology. The R&D work on IR detectors is a prominent part of Acreo's centre of excellence "IMAGIC" on imaging detectors and systems for non-visible wavelengths. IMAGIC is a collaboration between Acreo, several industry partners and universities like the Royal Institute of Technology (KTH) and Linkoping University. (C) 2010 Elsevier B.V. All rights reserved.
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