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Sökning: WFRF:(Frisk Per)

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1.
  • Frisk, Per, et al. (författare)
  • Cataracts after autologous bone marrow transplantation in children
  • 2000
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 89:7, s. 814-819
  • Tidskriftsartikel (refereegranskat)abstract
    • We recorded the incidence and degree of posterior subcapsular cataract (PSC) in 29 children who had undergone autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) due to haematologic or lymphoid malignancy. Conditioning prior to transplantation consisted either of a combination of chemotherapy and total body irradiation (TBI) (n = 21) or of chemotherapy only (n = 8). TBI was given in one fraction of 7.5 Gy. Nine patients had received previous cranial irradiation. The patients were followed for 4-10 y (median 8y) after transplantation. Of 29 patients, 22 developed PSC, all within 4 y after BMT. With the exception of one patient who developed unilateral PSC, all had received TBI. Conversely, 100% of those who received TBI developed PSC. In this group (+TBI), eight patients (38%) developed significant PSC, defined as best corrected visual acuity < 0.8 in either eye. Six patients (10 eyes) have since needed surgical repair consisting of extracapsular cataract extraction and intraocular lens implantation. There was no clear relationship between previous cranial irradiation and cataract development, nor any other obvious baseline differences between those in the +TBI group who developed significant PSC and those who did not. Although effects of previous therapy cannot be ruled out, TBI appears to be the main cause of PSC in this group of patients. Twelve patients in the +TBI group had well-preserved visual acuity throughout the study, reflecting a slow progression of PSC. This compares favourably with previous reports of allogeneic BMT, possibly owing to less need for corticosteroids after autologous BMT. We conclude that the incidence of PSC was high after autologous BMT where the conditioning regimen included total body irradiation.
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3.
  • Jackmann, Natalja, et al. (författare)
  • Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
  • 2024
  • Ingår i: JBMR PLUS. - : OXFORD UNIV PRESS. - 2473-4039. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2-17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45 degrees and 45 degrees. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
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4.
  • Jackmann, Natalja, 1968-, et al. (författare)
  • Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases
  • 2024
  • Ingår i: JBMR Plus. - : Oxford University Press. - 2473-4039. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease.This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2–17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen.Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes −45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure.In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.
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5.
  • Rodriguez-Wallberg, Kenny A., et al. (författare)
  • ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden : a phase III randomised double-blinded placebo-controlled study
  • 2023
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.Methods and analysis A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.Ethics and dissemination This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.Study registration The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.Trial registration number NCT05328258; EudraCT number:2020-004780-71.
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6.
  • Tesi, Bianca, et al. (författare)
  • Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
  • 2024
  • Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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7.
  • Tesi, Bianca, et al. (författare)
  • Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
  • 2024
  • Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
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8.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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10.
  • Aref, Thomas, 1980, et al. (författare)
  • Quantum Acoustics with Surface Acoustic Waves
  • 2016
  • Ingår i: Superconducting Devices in Quantum Optics. - Cham : Springer International Publishing. - 9783319240916 ; , s. 217-244
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • It has recently been demonstrated that surface acoustic waves (SAWs) can interact with superconducting qubits at the quantum level. SAW resonators in the GHz frequency range have also been found to have low loss at temperatures compatible with superconducting quantum circuits. These advances open up new possibilities to use the phonon degree of freedom to carry quantum information. In this chapter, we give a description of the basic SAW components needed to develop quantum circuits, where propagating or localized SAW-phonons are used both to study basic physics and to manipulate quantum information. Using phonons instead of photons offers new possibilities which make these quantum acoustic circuits very interesting. We discuss general considerations for SAW experiments at the quantum level and describe experiments both with SAW resonators and with interaction between SAWs and a qubit. We also discuss several potential future developments.
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11.
  • Axelsson, Robert, et al. (författare)
  • The Challenge of Transdisciplinary Research : A Case Study of Learning by Evaluation for Sustainable Transport Infrastructures
  • 2020
  • Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 12:17, s. 1-24
  • Tidskriftsartikel (refereegranskat)abstract
    • While transdisciplinary (TD) research is desired in order to solve real world sustainability issues, this may be challenging for both academic and non-academic participants. Supporting learning through evaluation, we analyzed a project aiming at sustainable transport infrastructures. After developing a TD research framework as a benchmark, two external independent evaluators interviewed all project researchers, representatives for end-users, and donors. The evaluators compared results with the framework, and evaluators and participants critically reflected on the results together. There were three inconsistencies relative to the framework: (1) limited understanding of TD research among project management, end-users, and most of the researchers; (2) no structured learning process among end-users; instead, they expressed very diverse opinions about what they expected from the project; (3) project leaders had limited understanding of the special challenges of TD research, did not fully understand the status of the project's social system, and thus did not act as facilitators of the required collaborative learning process. Non-academic participants saw themselves as customers and not as partners in the knowledge production process. We conclude that TD problem-solving research requires much time and needs facilitation and training. A preparatory phase with a lower level of funding would be helpful in preparing for TD processes.
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12.
  • Bengtsson, Andreas, 1991, et al. (författare)
  • Improved Success Probability with Greater Circuit Depth for the Quantum Approximate Optimization Algorithm
  • 2020
  • Ingår i: Physical Review Applied. - 2331-7019. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Present-day, noisy, small or intermediate-scale quantum processors-although far from fault tolerant-support the execution of heuristic quantum algorithms, which might enable a quantum advantage, for example, when applied to combinatorial optimization problems. On small-scale quantum processors, validations of such algorithms serve as important technology demonstrators. We implement the quantum approximate optimization algorithm on our hardware platform, consisting of two superconducting transmon qubits and one parametrically modulated coupler. We solve small instances of the NP (nondeterministic polynomial time)-complete exact-cover problem, with 96.6% success probability, by iterating the algorithm up to level two.
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13.
  • Bjerkeli, Per, 1977, et al. (författare)
  • Odin observations of water in molecular outflows and shocks
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 507:3, s. 1455-1466
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: We investigate the ortho-water abundance in outflows and shocks in order to improve our knowledge of shock chemistry and of the physics behind molecular outflows.Methods: We used the Odin space observatory to observe the H2O(110-101) line. We obtain strip maps and single pointings of 13 outflows and two supernova remnants where we report detections for eight sources. We used RADEX to compute the beam averaged abundances of o-H2O relative to H2. In the case of non-detection, we derive upper limits on the abundance.Results: Observations of CO emission from the literature show that the volume density of H2 can vary to a large extent, a parameter that puts severe uncertainties on the derived abundances. Our analysis shows a wide range of abundances reflecting the degree to which shock chemistry affects the formation and destruction of water. We also compare our results with recent results from the SWAS team.Conclusions: Elevated abundances of ortho-water are found in several sources. The abundance reaches values as high as what would be expected from a theoretical C-type shock where all oxygen, not in the form of CO, is converted to water. However, the high abundances we derive could also be due to the low densities (derived from CO observations) that we assume. The water emission may in reality stem from high density regions much smaller than the Odin beam. We do not find any relationship between the abundance and the mass loss rate. On the other hand, there is a relation between the derived water abundance and the observed maximum outflow velocity.Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Étude Spatiale (CNES).The Swedish ESO Submillimetre Telescope (SEST) located at La Silla, Chile was funded by the Swedish Research Council (VR) and the European Southern Observatory. It was decommissioned in 2003. Appendix B is only available in electronic form at http://www.aanda.org
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14.
  • Chen, Liangyu, 1994, et al. (författare)
  • Transmon qubit readout fidelity at the threshold for quantum error correction without a quantum-limited amplifier
  • 2023
  • Ingår i: npj Quantum Information. - : Springer Science and Business Media LLC. - 2056-6387. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • High-fidelity and rapid readout of a qubit state is key to quantum computing and communication, and it is a prerequisite for quantum error correction. We present a readout scheme for superconducting qubits that combines two microwave techniques: applying a shelving technique to the qubit that reduces the contribution of decay error during readout, and a two-tone excitation of the readout resonator to distinguish among qubit populations in higher energy levels. Using a machine-learning algorithm to post-process the two-tone measurement results further improves the qubit-state assignment fidelity. We perform single-shot frequency-multiplexed qubit readout, with a 140 ns readout time, and demonstrate 99.5% assignment fidelity for two-state readout and 96.9% for three-state readout–without using a quantum-limited amplifier.
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15.
  • Chiang, S. C. C., et al. (författare)
  • Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production
  • 2013
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:8, s. 1345-1356
  • Tidskriftsartikel (refereegranskat)abstract
    • Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8(+) T cells to enable the comparison of bona fide CTLs with NK cells. Analysis identified CD57(bright) expression as a reliable phenotype of granule marker-containing CTLs. We then compared CD3(+)CD8(+)CD57(bright) CTLs with NK cells. Healthy adult peripheral blood CD3(+)CD8(+)CD57(bright) CTLs expressed more granzyme B but less perforin than CD3(-)CD56(dim) NK cells. On stimulation, such CTLs degranulated more readily than other T-cell subsets, but had a propensity to degranulate that was similar to NK cells. Remarkably, the CTLs produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2 associated with familial hemophagocytic lymphohistiocytosis, CTL and NK cell degranulation were similarly impaired. Therefore, cytotoxic lymphocyte subsets have similar requirements for Munc13-4, syntaxin-11, and Munc18-2 in lytic granule exocytosis. The present results provide a detailed comparison of human CD3(+)CD8(+)CD57(bright) CTLs and NK cells and suggest that analysis of CD57(bright) CTL function may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagocytic lymphohistiocytosis.
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16.
  • Egenhoff, Sven, et al. (författare)
  • Sedimentology of the Lower Ordovician (upper Tremadocian) Bjørkasholmen Formation at Flagabro, southern Sweden
  • 2018
  • Ingår i: GFF. - : TAYLOR & FRANCIS LTD. - 1103-5897 .- 2000-0863. ; 140:1, s. 55-65
  • Tidskriftsartikel (refereegranskat)abstract
    • The Lower Ordovician Bjørkasholmen Formation at Flagabro, Scania, southern Sweden, consists of a 0.8m thick succession of carbonates with three siliciclastic mudstones, 5, 1 and 100mm thick, intercalated in the central part of the unit. Carbonate and siliciclastic mudstone beds show both normal and inverse grading. The carbonates are mud-rich and subdivided into a mudstone, a wackestone and a packstone facies. Grain types in the carbonates are mostly shells and shell fragments of brachiopods and trilobites. The carbonate rocks are strongly bioturbated seen as in roundish burrows filled with mud and a clear cement; additionally, bioturbation is reflected in the random orientation of shells. The siliciclastic mudstones are subdivided into two facies; one contains large amounts of shells and is in part grain-supported, the other is matrix-dominated and laminated to massive. The succession reflects sedimentation on a low-inclined shelf equivalent to a mid-ramp to basinal setting. Most mud- and wackestones (facies 3 and 4) represent fair-weather sedimentation, and the intercalated wacke- and packstones (facies 4 and 5) represent concentration of shell debris during high-energy storm. The siliciclastic mudstones in the central part of the succession reflect deposition in a basinal setting. The entire BjOrkasholmen Formation at Flagabro is equivalent to a lowstand of third (?) order without a well-developed internal cyclicity and is in that respect similar to the Bjørkasholmen Formation of oland, but different from the age-equivalent Norwegian sections.
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17.
  • Fan, B. X., et al. (författare)
  • Breakdown of the Cross-Kerr Scheme for Photon Counting
  • 2013
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 110:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We show, in the context of single-photon detection, that an atomic three-level model for a transmon in a transmission line does not support the predictions of the nonlinear polarizability model known as the cross-Kerr effect. We show that the induced displacement of a probe in the presence or absence of a single photon in the signal field, cannot be resolved above the quantum noise in the probe. This strongly suggests that cross-Kerr media are not suitable for photon counting or related single-photon applications. Our results are presented in the context of a transmon in a one-dimensional microwave waveguide, but the conclusions also apply to optical systems.
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18.
  • Forslund, E., et al. (författare)
  • Novel microchip-based tools facilitating live cell imaging and assessment of functional heterogeneity within NK cell populations
  • 2012
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 3:OCT, s. 300-
  • Tidskriftsartikel (refereegranskat)abstract
    • Each individual has a heterogeneous pool of NK cells consisting of cells that may be specialized towards specific functional responses such as secretion of cytokines or killing of tumor cells. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended periods of time. This paper presents a versatile microchip platform enabling long-term microscopic studies of individual NK cells interacting with target cells. Each microchip contains an array of microwells, optimized for medium or high-resolution time-lapse imaging of single or multiple NK and target cells, or for screening of thousands of isolated NK-target cell interactions. Individual NK cells confined with target cells in small microwells is a suitable setup for high-content screening and rapid assessment of heterogeneity within populations, while microwells of larger dimensions are appropriate for studies of NK cell migration and sequential interactions with multiple target cells. By combining the chip technology with ultrasonic manipulation, NK and target cells can be forced to interact and positioned with high spatial accuracy within individual microwells.This setup effectively and synchronously creates NK-target conjugates at hundreds of parallel positions in the microchip. Thus, this facilitates assessment of temporal aspects of NK-target cell interactions, e.g., conjugation, immune synapse formation, and cytotoxic events.The microchip platform presented here can be used to effectively address questions related to fundamental functions of NK cells that can lead to better understanding of how the behavior of individual cells add up to give a functional response at the population level.
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19.
  • Frisk Kockum, Anton, 1987, et al. (författare)
  • Designing frequency-dependent relaxation rates and Lamb shifts for a giant artificial atom
  • 2014
  • Ingår i: Physical Review A - Atomic, Molecular, and Optical Physics. - 2469-9926 .- 2469-9934. ; 90:1, s. 013837-
  • Tidskriftsartikel (refereegranskat)abstract
    • In traditional quantum optics, where the interaction between atoms and light at optical frequencies is studied, the atoms can be approximated as pointlike when compared to the wavelength of light. So far, this relation has also been true for artificial atoms made out of superconducting circuits or quantum dots, interacting with microwave radiation. However, recent and ongoing experiments using surface acoustic waves show that a single artificial atom can be coupled to a bosonic field at several points wavelengths apart. Here, we theoretically study this type of system. We find that the multiple coupling points give rise to a frequency dependence in the coupling strength between the atom and its environment and also in the Lamb shift of the atom. The frequency dependence is given by the discrete Fourier transform of the coupling-point coordinates and can therefore be designed. We discuss a number of possible applications for this phenomenon, including tunable coupling, single-atom lasing, and other effects that can be achieved by designing the relative coupling strengths of different transitions in a multilevel atom.
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20.
  • Frisk, Margot, et al. (författare)
  • Occupational therapy adaptation of the home environment in Sweden for people with asthma
  • 2002
  • Ingår i: Occupational Therapy International. - : Wiley. - 0966-7903 .- 1557-0703. ; 9:4, s. 294-311
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to evaluate changes of lung function, respiratory symptoms and indoor air quality after reducing allergens and indoor pollutants in the home environment of people with asthma (n = 21). A quasi-experimental pre-/post-test design with one group of participants was implemented. The interventions included removal of wall-to-wall carpets (n = 14) or improvement of indoor air exchange (n = 7). Participants' lung function, symptoms, medication and type-1 allergy were recorded before and after the intervention. The indoor environment was monitored at house calls by an occupational therapist using conventional physical, biological and chemical methods. There was an improvement of lung function evidenced by an increased mean Forced Expiratory Volume (FEV(1) %) and a reduction of airway obstruction (reversibility, % of baseline value), which indicate an improved asthmatic condition. Lung function assessed by vital capacity, bronchial hyper-responsiveness, mean of Peak Expiratory Flow, symptom score and medicine consumption did not change significantly. There was a tendency that the amount of airborne dust (p=0.06) was reduced in the indoor environment. Relative humidity, carbon dioxide, formaldehyde and house dust mite levels had decreased after the intervention, but not significantly. Asthma symptoms related to the home environment are probably caused by several factors. When people with asthma suffer from increased symptoms in the home, house calls should be performed routinely. Dust samples from beds and carpets for analysis of allergens give information about exposure, and environmental assessments should be performed before interventions. Occupational therapists can make a valuable contribution in evaluating the home environment and suggesting ergonomic adaptations for individuals with asthma.
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22.
  • Frisk, Per, et al. (författare)
  • A longitudinal study of pulmonary function after stem cell transplantation, from childhood to young adulthood
  • 2012
  • Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 58:5, s. 775-779
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Impairment of pulmonary function after stem cell transplantation (SCT) in childhood has been reported before. However, long-term longitudinal studies are scarce. Procedure. We measured lung volumes and performed dynamic spirometry serially in 18 patients after SCT. At the last investigation, a median of 18.2 years after SCT, the patients were compared with 18 matched controls. The diffusing capacity (DLCO) was only compared cross-sectionally. Results. There was a significant increase in the prevalence of restrictive lung disease (RLD, total lung capacity <80% of that predicted) from 7% (1/14) before SCT to 28% (5/18) 5 years after SCT, and 61% (11/18) a median of 18.2 years after SCT (P = 0.002). In comparison, none of the controls had RLD (61% vs. 0%, P = 0.001). Before SCT, no patient had obstructive lung disease (OLD, forced expiratory volume in 1 sec/vital capacity < 70). OLD was found in one of 18 patients (6%) 5 years after SCT but in none of the patients a median of 18.2 years after SCT. Three of the controls had OLD (P = 0.25). Eleven patients had diffusion impairment (DLCO < 80% of that predicted), as opposed to none of the controls (P = 0.001). The DLCO corrected for alveolar volume was decreased in only two patients. Conclusion. We documented an increase in the prevalence of RLD, but not of OLD, after SCT. At the last investigation, only two patients had diffusion impairment after correction for alveolar volume.
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23.
  • Frisk, Per, 1966-, et al. (författare)
  • Decreased bone mineral density in young adults treated with SCT in childhood : the role of 25-hydroxyvitamin D
  • 2012
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 47:5, s. 657-662
  • Tidskriftsartikel (refereegranskat)abstract
    • We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <−1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.
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24.
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25.
  • Frisk, Per, et al. (författare)
  • Glomerular and tubular function in young adults treated with stem-cell transplantation in childhood
  • 2010
  • Ingår i: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 25:7, s. 1337-1342
  • Tidskriftsartikel (refereegranskat)abstract
    • We evaluated renal function at a median follow-up of 18 (range 10.3-22.1) years after total body irradiation in 18 patients treated with stem-cell transplantation (SCT) (autologous SCT in 15 and allogeneic SCT in three) for hematologic malignancies and compared them with 18 healthy controls. No patient had chronic graft-versus-host disease. We found no difference in glomerular filtration rate estimated from cystatin C (105 vs 111 ml/min/1.73 m(2), p = 0.28). Patients had higher albumin excretion (0.8 vs 0.4 mg/mmol, p = 0.001), but no patient had overt albuminuria (>200 mg/L). Patients had higher diastolic blood pressure (74 vs 67 mmHg, p = 0.003). Two patients (11%) had hypertension. Patients had lower tubular reabsorption of phosphate (0.78 vs 0.91 mmol/L, p = 0.014) and higher excretion of alpha-1-microglobulin (AMG/urine creatinine, 0.4 vs 0.25 mg/mmol, p = 0.038), which correlated with time after SCT (r = 0.6, p = 0.01). We found no difference in fractional excretion (FE) of other electrolytes, amino acid excretion, or urine osmolality. We conclude that renal function was relatively well preserved at a median follow-up of 18 years after childhood SCT. The higher albumin excretion in our patients is of concern, as is the association between excretion of AMG and time after SCT, suggesting that both glomerular and tubular function may deteriorate further.
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26.
  • Frisk, Per, et al. (författare)
  • Glucose metabolism and body composition in young adults treated with TBI during childhood
  • 2011
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 46:10, s. 1303-1308
  • Tidskriftsartikel (refereegranskat)abstract
    • After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.
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27.
  • Frisk, Per, 1966- (författare)
  • Late Effects After Autologous Bone Marrow Transplantation in Childhood
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Fifty children with hematologic malignancies have been treated with autologous BMT in Uppsala. The aim was to describe late effects in this group with special reference to cataracts, reduced final height, and to hepatic, renal, and pulmonary late effects. Cataracts: All patients who received TBI in their conditioning developed posterior subcapsular cataract after BMT. A few patients with visual impairment affecting daily life needed cataract surgery, whereas the visual acuity was well preserved in most of the other patients.Final height: There was a decrease in final height relative both to height at BMT and to target height. This decrease was significant both in those who had received TBI only and in those who had been given cranial irradiation. Cranial irradiation, young age at BMT, and short duration of GH treatment were predictors of height loss. Hepatic function: Hepatic function was well preserved over a period of 10 years after BMT. TBI did not appear to be a risk factor for hepatic impairment. Renal function: Six months after BMT there was a decrease in renal function in patients who had received TBI. It then recovered, albeit incompletely, and stabilized. After the first year there was little change over a period of 10 years after BMT. TBI appeared to be the most important risk factor for the development of chronic renal impairment in a number of patients. Nephrotoxic antibiotics may have contributed.Pulmonary function: Six months after BMT there was a decrease in pulmonary function in those who received TBI. It then recovered and stabilized at the pretransplant level. After the first year there was little change over a period of 10 years after BMT. TBI appeared to be the most important risk factor for restrictive pulmonary disease in a number of patients whereas chemotherapy might also have been of importance for impaired gas exchange.
  •  
28.
  • Frisk, Per, et al. (författare)
  • Normal long-term parathyroid function after autologous bone marrow transplantation in children
  • 2007
  • Ingår i: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 11:2, s. 205-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Parathyroid function was recently reported to be affected in more than one-third of pediatric BMT patients conditioned without irradiation. Our aim was to describe parathyroid function in children with malignant hematological disease after autologous BMT with and without TBI. PTH, albumin-corrected serum calcium, and serum phosphate were analyzed in 35 children followed for six months to nine yr after BMT. Twelve patients were conditioned with chemotherapy alone, and 23 patients received TBI as well. In the TBI group, 11 patients had previously received additional CRT. We found normal levels of PTH in children post-BMT, with the exception of four patients (11%) who showed transient PTH elevation during the first year of follow-up, There was no difference between those who had received irradiation and those who had not. Serum calcium was unchanged after BMT. An age-corrected quotient of serum phosphate decreased slightly. Renal function which was normal before BMT decreased slightly in both groups after BMT, but was within the normal range. Parathyroid function was found to be normal during the time frame of this study, irrespective of whether irradiation had been given.
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29.
  •  
30.
  • Frisk, Per, et al. (författare)
  • Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia
  • 2004
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 33:2, s. 205-210
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe pubertal development and growth in 17 children who underwent bone marrow transplantation (BMT), including total body irradiation (TBI) for ALL. Seven children also received cranial irradiation (CI) and five boys testicular irradiation. All underwent transplantation before (n=15) or at the beginning of (n=2) puberty and reached a final height (FH). Puberty started spontaneously in all boys not given testicular irradiation. All boys who received testicular irradiation developed hypergonadotrophic hypogonadism. Puberty started spontaneously in two girls and was induced with increasing doses of ethinylestradiol in two girls. In two girls, a low dose of ethinylestradiol was given until menarche. In one girl with early onset of puberty and short stature, puberty was blocked with a GnRH analogue. The standard deviation score for height decreased significantly from BMT to FH, both in the children who received TBI only (-1.1, P=0.005) as well as in those given additional CI (-1.7, P=0.027). Most of the loss occurred during puberty. In all, 10 children received growth hormone (GH) treatment. CI, young age at BMT, and short duration of GH treatment were predictors of height loss after BMT. Although limited by the small and heterogeneous sample, our study supports the use of early GH treatment in children with decelerating growth rate and low GH levels.
  •  
31.
  • Frisk, Per, et al. (författare)
  • Pulmonary function after autologous bone marrow transplantation in children : a long-term prospective study
  • 2004
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 33, s. 645-650
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed serial pulmonary function tests (PFTs) consisting of spirometry and diffusing capacity in 26 children after BMT. The median follow-up was 10 years. The influence of total body irradiation (TBI) on long-term pulmonary function was of particular interest. In the 20 children who had received TBI, after an initial decrease the PFTs showed recovery, but the mean lung volumes were still significantly decreased 5 years after BMT at 10% below baseline. The proportions of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%, respectively. Only one child was diagnosed with obstructive impairment. The proportions of children with isolated diffusing impairment at 5 and 10 years were 7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy only and showed isolated diffusing impairment as the only long-term sequela in 4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change in PFTs 1–10 years after BMT. TBI was associated with persistently decreased lung volumes in a proportion of patients, whereas chemotherapy also might have been of importance for the development of impaired gas exchange.
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32.
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33.
  • Frisk, Per, et al. (författare)
  • Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood
  • 2012
  • Ingår i: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 16:4, s. 385-391
  • Tidskriftsartikel (refereegranskat)abstract
    • We measured risk factors for CVD in 18 patients at a median of 18.2 yr after SCT and in sex and age-matched controls. Three patients (17%), but none of the controls, met the criteria for the MetS (p = 0.25). In the patients, we found higher levels of triglycerides (0.94 vs. 0.62 mm, p = 0.019), total cholesterol (5.1 vs. 4.0 mm, p = 0.017), LDL (3.4 vs. 2.6 mm, p = 0.019), apolipoprotein B (1.04 vs. 0.74 g/L, p = 0.004), apolipoprotein B/A1 ratio (0.7 vs. 0.5, p = 0.026), and lower levels of adiponectin (4.9 vs. 7.5 mg/L, p = 0.008) than in the controls. The patients had a lower GHmax (9 vs. 20.7 mU/L, p = 0.002). GHmax was significantly correlated inversely with triglycerides (r = -0.64, p = 0.008), total cholesterol (r = -0.61, p = 0.011), apolipoprotein B (r = -0.60, p = 0.014), and apolipoprotein B/A1 ratio (r = -0.66, p = 0.005). We recorded a significantly thicker carotid intima layer among the patients than among matched controls (0.15 vs. 0.13 mm, p = 0.034). The level of adiponectin correlated inversely with carotid intima thickness (r = -0.55, p = 0.023). After SCT in childhood, long-term survivors may be at risk of developing premature CVD.
  •  
34.
  • Frisk, Peter, et al. (författare)
  • Sequential trace element changes in serum and blood during a common viral infection in mice
  • 2007
  • Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 21:1, s. 29-36
  • Tidskriftsartikel (refereegranskat)abstract
    • When trace elements are used as diagnostic tools during disease, it is important to know whether the balance is changed in free or bound elements. Although acute infections are associated with changed trace element balance in serum/plasma, it is not known whether changes occur concomitantly in serum and blood. In the present study the human coxsackievirus B3 (CB3), here adapted to Balb/c mice, was used to study whether infection alters the normal physiological trace element balance in blood and serum. Virus was quantitatively measured in two target organs (pancreas and liver) of this infection by reverse transcription polymerase chain reaction (RT-PCR), showing high concentrations of virus proving ongoing infection. Concentrations of 14 elements were measured in whole blood and serum using inductively coupled plasma mass spectrometry (ICP-MS) on days 3, 6 and 9 of the infection. Free and total thyroxine were measured in serum to prove metabolic changes associated with the infection. The thyroxine decreased, while iron and the Cu/Zn ratio in serum increased as a response to the infection. No clear changes in these elements were observed in blood. Cd and Hg tended to decrease in serum but to increase in blood, indicating accumulation in blood cells. Moreover, Al showed a similar decreasing trend in both serum and blood. A correlation between serum and blood levels was observed at different time points of the disease for 9 of the elements. However, As was the only element indicating correlations between serum and blood during the entire course of the disease.
  •  
35.
  • Frisk, Per, et al. (författare)
  • Skin infection caused by Mycobacterium szulgai after allogenic bone marrow transplantation
  • 2003
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 31:6, s. 511-513
  • Tidskriftsartikel (refereegranskat)abstract
    • Infections are responsible for a large part of the morbidity and mortality after BMT because of the sustained impairment of host defenses. We report a case of cutaneous infection caused by Mycobacterium szulgai in a boy who underwent BMT with marrow from a matched unrelated donor.
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36.
  •  
37.
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38.
  • Frisk, Thomas, et al. (författare)
  • An integrated QCM-based narcotics sensing microsystem
  • 2008
  • Ingår i: Lab on a Chip. - : RSC Publishing. - 1473-0197 .- 1473-0189. ; 8:10, s. 1648-1657
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the design, fabrication and successful testing of a 14 x 14 x 4 mm(3) integrated electronic narcotics sensing system which consists of only four parts. The microsystem absorbs airborne narcotics molecules and performs a liquid assay using an integrated quartz crystal microbalance (QCM). A vertically conductive double-sided adhesive foil (VCAF) was used and studied as a novel material for LOC and MEMS applications and provides easy assembly, electrical contacting and liquid containment. The system was tested for measuring cocaine and ecstasy, with successful detection of amounts as small as 100 ng and 200 ng, respectively These levels are of interest in security activities in customs, prisons and by the police.
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39.
  • Frisk, U., et al. (författare)
  • The Odin satellite - I. Radiometer design and test
  • 2003
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 402:3, s. L27-L34
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sub-millimetre and Millimetre Radiometer (SMR) is the main instrument on the Swedish, Canadian, Finnish and French spacecraft Odin. It consists of a 1.1 metre diameter telescope with four tuneable heterodyne receivers covering the ranges 486-504 GHz and 541-581 GHz, and one fixed at 118.75 GHz together with backends that provide spectral resolution from 150 kHz to 1 MHz. This Letter describes the Odin radiometer, its operation and performance with the data processing and calibration described in Paper II.
  •  
40.
  • Genberg, Margareta, et al. (författare)
  • Cardiac Function After Hematopoietic Cell Transplantation : An Echocardiographic Cross-Sectional Study in Young Adults Treated in Childhood
  • 2015
  • Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 62:1, s. 143-147
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHematopoietic cell transplantation (HCT) including preparative regimens with chemotherapy and total body irradiation (TBI) is an accepted treatment for many malignant disorders but may have side-effects for several organs, including the cardiovascular system. The aim of this study was to study very long-term consequences on cardiac function after childhood HCT. ProcedureCardiac function was evaluated using echocardiography and levels of NT-proBNP and growth hormone (GHmax) in 18 patients, at a median of 18 years after HCT including TBI, and in 18 matched controls. ResultsPatients after HCT had cardiac dimensions, volumes, and left ventricular ejection fractions within normal range after correction for body size. However, compared with the control group, patients after HCT had significantly lower E/A ratio, as a measure of left ventricular diastolic function, significantly lower fractional shortening and mitral annular plane systolic excursion, as measures of left ventricular systolic function, significantly lower tricuspid annular plane systolic excursion, as a measure of right ventricular function, and significantly higher NT-proBNP, as a measure of total cardiac function. Also, pulmonary flow acceleration time was shorter in the group after HCT, indicating possible pulmonary involvement. Heart rate was significantly higher and GHmax significantly lower in patients after HCT. ConclusionsAlmost two decades after HCT, including preparative regimens with TBI, cardiac function in patients was found to be within normal range. However, when compared with a healthy control group, patients after HCT showed lower systolic and diastolic left ventricular function as well as lower right ventricular function. Pediatr Blood Cancer 2015;62:143-147.
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41.
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42.
  • Guldevall, Karolin, 1981-, et al. (författare)
  • Microchip screening platform for assessment of cytotoxic effector cells
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Here we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) or T cells within larger populations. Human primary NK cells or human Epstein-Barr virus (EBV)- specific T cells were distributed across a silicon-glass microchip containing 32 400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis the numbers of effector and live or dead target cells in each well could be assessed at different time-points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (≈75%) were non-cytotoxic to the leukemia cell line K562, some NK cells were able to kill several (≥3) target cells within the 12 hours long experiment. We demonstrate that this assay can be used to enumerate and characterize cytotoxic cells, something that could find clinical applications, e.g. in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.
  •  
43.
  • Guldevall, Karolin, et al. (författare)
  • Microchip screening Platform for single cell assessment of NK cell cytotoxicity
  • 2016
  • Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) cells within larger populations. Human primary NK cells were distributed across a silicon-glass microchip containing 32,400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis, the numbers of NK and live or dead target cells in each well could be assessed at different time points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (approximate to 75%) were non-cytotoxic against the leukemia cell line K562, some NK cells were able to kill several (>= 3) target cells within the 12-h long experiment. In addition, the screening approach was adapted to increase the chance to find and evaluate serial killing NK cells. Even if the cytotoxic potential varied between donors, it was evident that a small fraction of highly cytotoxic NK cells were responsible for a substantial portion of the killing. We demonstrate multiple assays where our platform can be used to enumerate and characterize cytotoxic cells, such as NK or T cells. This approach could find use in clinical applications, e.g., in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.
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44.
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45.
  • Gustafsson, Martin, 1979, et al. (författare)
  • Propagating phonons coupled to an artificial atom
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6206, s. 207-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum information can be stored in micromechanical resonators, encoded as quanta of vibration known as phonons. The vibrational motion is then restricted to the stationary eigenmodes of the resonator, which thus serves as local storage for phonons. In contrast, we couple propagating phonons to an artificial atom in the quantum regime and reproduce findings from quantum optics with sound taking over the role of light. Our results highlight the similarities between phonons and photons but also point to new opportunities arising from the unique features of quantum mechanical sound. The low propagation speed of phonons should enable new dynamic schemes for processing quantum information, and the short wavelength allows regimes of atomic physics to be explored that cannot be reached in photonic systems.
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46.
  • Hassan, Jasmin, et al. (författare)
  • Reference standards for follicular density in ovarian cortex from birth to sexual maturity
  • 2023
  • Ingår i: Reproductive BioMedicine Online. - : Elsevier. - 1472-6483 .- 1472-6491. ; 47:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Research question: Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation?Design: Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean +/- SD 11 +/- 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values.Results: No difference was observed between Z-scores in samples from untreated patients (0.3 +/- 3.5, n = 30) and patients treated with (0.5 +/- 2.9, n = 48) and without (0.1 +/- 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 +/- 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 +/- 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 +/- 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 +/- 4.2 versus 10.7 +/- 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009).Conclusion: Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
  •  
47.
  • Hjalmarson, Åke, et al. (författare)
  • Recent astronomy highlights from the Odin satellite
  • 2005
  • Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 36, s. 1031-1047
  • Tidskriftsartikel (refereegranskat)abstract
    • Astronomy highlights, mainly from the third year of Odin observations time shared 50/50% with aeronomy are presented: the very low O2 abundance limits achieved, the highly pressure broadened absorption lines of H2O, H218O, and CO (5 → 4) in the atmosphere of Mars, the high precision H2O and H218O observations of comets, the detections of NH3 and H2O around the C-rich star IRC+10216 (CW Leo) and of H2O around the O-rich star W Hya, NH3 and H2O observations of infall/outflow interactions, observations of H2O, H218O, H217O as well as NH3 and 15NH3 in multiple absorptions towards Sgr B2, and in emission towards Orion KL, the H2O detection of several new outflows in the DR21 W75S region. We also discuss the results of deconvolution of high S/N H2O, CO and 13CO (5 → 4) maps of the Orion KL region to 40″ resolution (the beam size of the Herschel telescope) and the first results from our ongoing “spectral scan” of Orion KL in bands around 555 and 570 GHz. Finally, a search for primordial molecules is presented.
  •  
48.
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49.
  • Hoi, Io Chun, 1984, et al. (författare)
  • Giant Cross–Kerr Effect for Propagating Microwaves Induced by an Artificial Atom
  • 2013
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 111:5, s. article nr. 053601-
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate the effective interaction between two microwave fields, mediated by a transmon-type superconducting artificial atom which is strongly coupled to a coplanar transmission line. The interaction between the fields and atom produces an effective cross–Kerr coupling. We demonstrate average cross–Kerr phase shifts of up to 20 degrees per photon with both coherent microwave fields at the single-photon level. Our results provide an important step toward quantum applications with propagating microwave photons.
  •  
50.
  • Hoi, Io Chun, 1984, et al. (författare)
  • Probing the quantum vacuum with an artificial atom in front of a mirror
  • 2015
  • Ingår i: Nature Physics. - 1745-2481 .- 1745-2473. ; 11:12, s. 1045-1049
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum fluctuations of the vacuum are both a surprising and fundamental phenomenon of nature. Understood as virtual photons, they still have a very real impact, for instance, in the Casimir effects and the lifetimes of atoms. Engineering vacuum fluctuations is therefore becoming increasingly important to emerging technologies. Here, we shape vacuum fluctuations using a superconducting circuit analogue of a mirror, creating regions in space where they are suppressed. Moving an artificial atom through these regions and measuring the spontaneous emission lifetime of the atom provides us with the spectral density of the vacuum fluctuations. Using the paradigm of waveguide quantum electrodynamics, we significantly improve over previous studies of the interaction of an atom with its mirror image, observing a spectral density as low as 0.02 quanta, a factor of 50 below the mirrorless result. This demonstrates that we can hide the atom from the vacuum, even though it is exposed in free space.
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