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Sökning: WFRF:(Kooi J.)

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  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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  • de Graauw, Th., et al. (författare)
  • The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
  • 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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  • Gupta, H., et al. (författare)
  • Detection of OH+ and H2O+ towards Orion KL
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L47-
  • Tidskriftsartikel (refereegranskat)abstract
    • We report observations of the reactive molecular ions OH+, H2O+, and H3O+ towards Orion KL with Herschel/HIFI. All three N = 1-0 fine-structure transitions of OH+ at 909, 971, and 1033 GHz and both fine-structure components of the doublet ortho-H2O+ 111-000 transition at 1115 and 1139 GHz were detected; an upper limit was obtained for H3O+. OH+ and H2O+ are observed purely in absorption, showing a narrow component at the source velocity of 9 km s-1, and a broad blueshifted absorption similar to that reported recently for HF and para-H218O, and attributed to the low velocity outflow of Orion KL. We estimate column densities of OH+ and H2O+ for the 9 km s-1 component of 9 ± 3 × 1012 cm-2 and 7 ± 2 × 1012 cm-2, and those in the outflow of 1.9 ± 0.7 × 1013 cm-2 and 1.0 ± 0.3 × 1013 cm-2. Upper limits of 2.4 × 1012 cm-2 and 8.7 × 1012 cm-2 were derived for the column densities of ortho and para-H3O+ from transitions near 985 and 1657 GHz. The column densities of the three ions are up to an order of magnitude lower than those obtained from recent observations of W31C and W49N. The comparatively low column densities may be explained by a higher gas density despite the assumption of a very high ionization rate.
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  • Lis, D. C., et al. (författare)
  • Herschel/HIFI measurements of the ortho/para ratio in water towards Sagittarius B2(M) and W31C
  • 2010
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L26 -
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Herschel/HIFI observations of the fundamental rotational transitions of ortho- and para-H216O and H218O in absorption towards Sagittarius B2(M) and W31C. The ortho/para ratio in water in the foreground clouds on the line of sight towards these bright continuum sources is generally consistent with the statistical high-temperature ratio of 3, within the observational uncertainties. However, somewhat unexpectedly, we derive a low ortho/para ratio of 2.35 +/- 0.35, corresponding to a spin temperature of similar to 27 K, towards Sagittarius B2(M) at velocities of the expanding molecular ring. Water molecules in this region appear to have formed with, or relaxed to, an ortho/para ratio close to the value corresponding to the local temperature of the gas and dust.
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  • Roelfsema, P. R., et al. (författare)
  • In-orbit performance of Herschel-HIFI
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: In this paper the calibration and in-orbit performance of the Heterodyne Instrument for the Far-Infrared (HIFI) is described.Methods: The calibration of HIFI is based on a combination of ground and in-flight tests. Dedicated ground tests to determine those instrument parameters that can only be measured accurately using controlled laboratory stimuli were carried out in the instrument level test (ILT) campaign. Special in-flight tests during the commissioning phase (CoP) and performance verification (PV) allowed the determination of the remaining instrument parameters. The various instrument observing modes, as specified in astronomical observation templates (AOTs), were validated in parallel during PV by observing selected celestial sources.Results: The initial calibration and in-orbit performance of HIFI has been established. A first estimate of the calibration budget is given. The overall in-flight instrument performance agrees with the original specification. Issues remain at only a few frequencies. 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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  • van Es, Michael A, et al. (författare)
  • Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
  • 2009
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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  • van Rheenen, W, et al. (författare)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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  • van Es, Michael A, et al. (författare)
  • Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
  • 2011
  • Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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  • Mooij, Wolf M., et al. (författare)
  • Serving many at once : How a database approach can create unity in dynamical ecosystem modelling
  • 2014
  • Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 61, s. 266-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Simulation modelling in ecology is a field that is becoming increasingly compartmentalized. Here we propose a Database Approach To Modelling (DATM) to create unity in dynamical ecosystem modelling with differential equations. In this approach the storage of ecological knowledge is independent of the language and platform in which the model will be run. To create an instance of the model, the information in the database is translated and augmented with the language and platform specifics. This process is automated so that a new instance can be created each time the database is updated. We describe the approach using the simple Lotka-Volterra model and the complex ecosystem model for shallow lakes PCLake, which we automatically implement in the frameworks OSIRIS, GRIND for MATLAB, ACSL, R, DUFLOW and DELWAQ. A clear advantage of working in a database is the overview it provides. The simplicity of the approach only adds to its elegance.
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  • Notarnicola, A., et al. (författare)
  • Autoantibodies against a subunit of mitochondrial respiratory chain complex I in inclusion body myositis
  • 2023
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 574-574
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Autoantibodies are found in up to 80% of patients with idiopathic inflammatory myopathies (IIM) and are associated with distinct clinical phenotypes [1]. Autoantibodies targeting cytosolic 5´-nucleotidase 1A (anti-cN1A) are currently the only known serum biomarker for the subgroup inclusion body myositis (IBM) (2), although detected even in other autoimmune diseases.Objectives To identify new autoimmune targets in IIM by antigen bead array assay.Methods In a first cross-sectional exploratory study, 357 antigens representing 268 proteins were incubated with plasma samples from 219 IIM (108 Polymyositis (PM), 80 Dermatomyositis (DM) and 31 IBM) patients, 349 Systemic Lupus Erythematosus (SLE) patients and 306 population controls for screening of IgG reactivity by antigen bead array. All samples were identified in the local biobank of the Rheumatology clinic, Karolinska University Hospital. Interesting results obtained for the IBM subgroup were then validated in an independent larger cohort of 287 patients with IBM followed at nine European rheumatological or neurological centers. IBM serum samples were explored by antigen bead array and results validated by western blot. As controls, serum samples from 30 patients with PM and 30 with DM, HLA-matched with the IBM Swedish cohort, were included. Demographics, laboratory, clinical, and muscle biopsy data of the IBM cohort was retrieved.Results In the exploratory study IgG reactivity towards NADH dehydrogenase 1 α subcomplex 11 (NDUFA11), a subunit of the membrane-bound mitochondrial respiratory chain complex I, was discovered with higher frequency in the IBM (9,7%) than PM (2,8%) and DM samples (2,5%), although the difference was not statistically significant. Anti-NDUFA11 IgG was also found in 2,3% of SLE and 2,6% of population control samples. In the validation study anti-NDUFA11 autoantibodies were detected in 11/287 IBM patients (3,8%), 0/30 PM and 0/30 DM patients. Reactivity against NDUFA11 could be confirmed by western blot (Table 1, Figure 1). The eleven anti-NDUFA11 positive patients showed a trend of lower frequency of wheelchair/walker ever use and higher creatine kinase levels at time of IBM diagnosis compared to the anti-NDUFA11 negative group. Ragged red fibers were significantly more prevalent in anti-NDUFA11 positive than negative patients (p=0.04). Anti-cN1A autoantibodies were detected in 98/287 (34,1%) of IBM, 3/30 (10%) DM and 9/29 (31%) PM patients, p=0.03. Coexistence of anti NDUFA11 and anti-cN1A antibodies was observed in 3 IBM patients.Conclusion Our results reveal a new autoimmune target in the mitochondrial respiratory chain complex I that might be specifically associated with IBM. This is of particular interest as mitochondrial abnormalities are known histological findings in muscle biopsies of IBM patients.References [1]Galindo-Feria AS, Wang G, Lundberg IE. Autoantibodies: Pathogenic or epiphenomenon. Best Pract Res Clin Rheumatol. 2022;36(2):101767.[2]Herbert MK,et al. Disease specificity of autoantibodies to cytosolic 5’-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis. 2016;75(4):696-701.
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  • Van Es, Michael A, et al. (författare)
  • Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis
  • 2009
  • Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 10:5-6, s. 441-447
  • Tidskriftsartikel (refereegranskat)abstract
    • A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe. Genotyping experiments were performed using Illumina Beadchips, Sequenom iPLEX assays and Taqman technology on large case-control series from The Netherlands, Belgium, Sweden and Ireland (total: 1883 sporadic ALS patients and 2063 controls). No significant association between sporadic ALS and the six previously reported associated SNPs in FGGY was observed: rs6700125 (p =0.56), rs6690993 (p =0.30), rs10493256 (p =0.68), rs6587852 (p =0.64), rs1470407 (p =0.28) and rs333662 (p =0.44). Screening of the additional candidate loci did not yield significant associations either, with the lowest p-value in joint analysis for rs7772593 (p =0.14). We concluded that common genetic variation in FGGY is not associated with susceptibility to sporadic ALS in genetically homogeneous populations from northern Europe.
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  • van Gerven, Luuk P. A., et al. (författare)
  • Advantages of concurrent use of multiple software frameworks in water quality modelling using a database approach
  • 2015
  • Ingår i: Fundamental and Applied Limnology. - : Schweizerbart. - 1863-9135. ; 186:1-2, s. 5-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Water quality modelling deals with multidisciplinary questions ranging from fundamental to applied. Addressing this broad range of questions requires multiple analysis techniques and therefore multiple frameworks. Through the recently developed database approach to modelling (DATM), it has become possible to run a model in multiple software frameworks without much overhead. Here we apply DATM to the ecosystem model for ditches PCDitch and its twin model for shallow lakes PCLake. Using DATM, we run these models in six frameworks (ACSL, DELWAQ, DUFLOW, GRIND for MATLAB, OSIRIS and R), and report on the possible model analyses with tools provided by each framework. We conclude that the dynamic link between frameworks and models resulting from DATM has the following main advantages: it allows one to use the framework one is familiar with for most model analyses and eases switching between frameworks for complementary model analyses, including the switch between a 0-D and 1-D to 3-D setting. Moreover, the strength of each framework - including runtime performance - can now be easily exploited. We envision that a community-based further development of the concept can contribute to the future development of water quality modelling, not only by addressing multidisciplinary questions but also by facilitating the exchange of models and process formulations within the community of water quality modellers.
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  • Baldi, A., et al. (författare)
  • Mg/Ti multilayers : Structural and hydrogen absorption properties
  • 2010
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 81:22, s. 224203-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mg-Ti alloys have uncommon optical and hydrogen absorbing properties, originating from a "spinodal-like" microstructure with a small degree of chemical short-range order in the atomic distribution. In the present study we artificially engineer short-range order by depositing Pd-capped Mg/Ti multilayers with different periodicities. Notwithstanding the large lattice mismatch between Mg and Ti, the as-deposited metallic multilayers show good structural coherence. On exposure to H-2 gas a two-step hydrogenation process occurs with the Ti layers forming the hydride before Mg. From in situ measurements of the bilayer thickness Lambda at different hydrogen pressures, we observe large out-of-plane expansions of Mg and Ti layers on hydrogenation, indicating strong plastic deformations in the films and a consequent shortening of the coherence length. On unloading at room temperature in air, hydrogen atoms remain trapped in the Ti layers due to kinetic constraints. Such loading/unloading sequence can be explained in terms of the different thermodynamic properties of hydrogen in Mg and Ti, as shown by diffusion calculations on a model multilayered systems. Absorption isotherms measured by hydrogenography can be interpreted as a result of the elastic clamping arising from strongly bonded Mg/Pd and broken Mg/Ti interfaces.
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  • Kenna, Kevin P., et al. (författare)
  • NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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  • Teyssier, D., et al. (författare)
  • Herschel/HIFI In-flight commissioning and performance
  • 2010
  • Ingår i: 21st International Symposium on Space Terahertz Technology 2010, ISSTT 2010; Oxford; United Kingdom; 23 March 2010 through 25 March 2010. - 9781617823626 ; , s. 23-28
  • Konferensbidrag (refereegranskat)abstract
    • The Herschel Space Observatory was successfully launched on the 14th of May, 2009, lifting into space the Heterodyne Instrument for the Far-Infrared (HIFI). After the standard early orbit operations on the Space-craft, the instrument was switched on for the first time on the 24th of May, kicking off an instrument Commissioning period of more than a month and a half. We present here the outcome of this Commissioning campaign, including the measured in-flight performance of the instrument. Among the challenges encountered during this period was the need to optimize the stability of the signal provided by the Local Oscillator (LO) chains in some of the frequency bands, in particular that covering the singly Ionized Carbon (C+) line at the upper edge of the HIFI range, and one of the backbones of the science program of the instrument. The same concept also allowed significant improvements in the upper end of the 3b LO chain. Another noticeable achievement was the very good co-alignment measured between the mixer beams in the respective H and V polarizations offered by HIFI, allowing for more than a simple build-in redundancy, as the observing efficiency will really benefits from the combination of the two mixers.
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23.
  • van Rheenen, Wouter, et al. (författare)
  • Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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24.
  • Best, Myron G., et al. (författare)
  • Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
  • 2017
  • Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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25.
  • Saba, Luca, et al. (författare)
  • Carotid plaque-RADS : a novel stroke risk classification system
  • 2024
  • Ingår i: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591. ; 17:1, s. 62-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features.Objectives: The aim of this document is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque–Reporting and Data System (RADS) score.Methods: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports.Results: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of “stenosis.” The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories.Conclusions: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.
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26.
  • van Rheenen, Wouter, et al. (författare)
  • H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis
  • 2013
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:5, s. 1517.e5-1517.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival. (C) 2013 Elsevier Inc. All rights reserved.
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27.
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28.
  • Dweck, MR, et al. (författare)
  • Contemporary rationale for non-invasive imaging of adverse coronary plaque features to identify the vulnerable patient: a Position Paper from the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology and the European Association of Cardiovascular Imaging
  • 2020
  • Ingår i: European heart journal. Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 21:11, s. 1177-1183
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment.
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29.
  • Kooi, J., et al. (författare)
  • HIFI stability as measured during ILT phase
  • 2008
  • Ingår i: 19th International Symposium on Space Terahertz Technology, ISSTT 2008; Groningen; Netherlands; 28 April 2008 through 30 April 2008. ; , s. 92-102
  • Konferensbidrag (refereegranskat)abstract
    • We present here the stability results of the high frequency heterodyne instrument (HIFI), to be flown on the Herschel space observatory. The measurements were taken as part of the instrument level tests (ILT) in the spring of 2007. Herschel is ESA's fourth cornerstone mission in the Horizon 2000+ program, and aims at observations in the Far-InfraRed and sub-millimeter wavelength region. HIFI itself is one of three instruments onboard Herschel. The other two being PACS, the photodetector array camera and spectrometer, and SPIRE, the spectral and photometric imaging receiver.
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30.
  • Krishnan, Gopi, et al. (författare)
  • Strategies to initiate and control the nucleation behavior of bimetallic nanoparticles
  • 2017
  • Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 9:24, s. 8149-8156
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work we report strategies to nucleate bimetallic nanoparticles (NPs) made by gas phase synthesis of elements showing difficulty in homogeneous nucleation. It is shown that the nucleation assisted problem of bimetallic NP synthesis can be solved via the following pathways: (i) selecting an element which can itself nucleate and act as a nucleation center for the synthesis of bimetallic NPs; (ii) introducing H-2 or CH4 as an impurity/trace gas to initiate nucleation during the synthesis of bimetallic NPs. The latter can solve the problem if none of the elements in a bimetallic NP can initiate nucleation. We illustrate the above mentioned strategies for the case of Mg based bimetallic NPs, which are interesting as hydrogen storage materials and exhibit both nucleation and oxidation issues even under ultra-high vacuum conditions. In particular, it is shown that adding H2 in small proportions favors the formation of a solid solution/alloy structure even in the case of immiscible Mg and Ti, where normally phase separation occurs during synthesis. In addition, we illustrate the possibility of improving the nucleation rate, and controlling the structure and size distribution of bimetallic NPs using H-2/CH4 as a reactive/nucleating gas. This is shown to be associated with the dimer bond energies of the various formed species and the vapor pressures of the metals, which are key factors for NP nucleation.
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31.
  • Kuiper, Jan J., et al. (författare)
  • Bridging Theories for Ecosystem Stability Through Structural Sensitivity Analysis of Ecological Models in Equilibrium
  • 2022
  • Ingår i: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 70:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Ecologists are challenged by the need to bridge and synthesize different approaches and theories to obtain a coherent understanding of ecosystems in a changing world. Both food web theory and regime shift theory shine light on mechanisms that confer stability to ecosystems, but from different angles. Empirical food web models are developed to analyze how equilibria in real multi-trophic ecosystems are shaped by species interactions, and often include linear functional response terms for simple estimation of interaction strengths from observations. Models of regime shifts focus on qualitative changes of equilibrium points in a slowly changing environment, and typically include non-linear functional response terms. Currently, it is unclear how the stability of an empirical food web model, expressed as the rate of system recovery after a small perturbation, relates to the vulnerability of the ecosystem to collapse. Here, we conduct structural sensitivity analyses of classical consumer-resource models in equilibrium along an environmental gradient. Specifically, we change non-proportional interaction terms into proportional ones, while maintaining the equilibrium biomass densities and material flux rates, to analyze how alternative model formulations shape the stability properties of the equilibria. The results reveal no consistent relationship between the stability of the original models and the proportionalized versions, even though they describe the same biomass values and material flows. We use these findings to critically discuss whether stability analysis of observed equilibria by empirical food web models can provide insight into regime shift dynamics, and highlight the challenge of bridging alternative modelling approaches in ecology and beyond.
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32.
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33.
  • Naumann, Marcel, et al. (författare)
  • Phenotypes and malignancy risk of different FUS mutations in genetic amyotrophic lateral sclerosis
  • 2019
  • Ingår i: Annals of Clinical and Translational Neurology. - : John Wiley & Sons. - 2328-9503. ; 6:12, s. 2384-2394
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Mutations in Fused in Sarcoma (FUS or TLS) are the fourth most prevalent in Western European familial amyotrophic lateral sclerosis (ALS) populations and have been associated with causing both early and very late disease onset. FUS aggregation, DNA repair deficiency, and genomic instability are contributors to the pathophysiology of FUS-ALS, but their clinical significance per se and their influence on the clinical variability have yet to be sufficiently investigated. The aim of this study was to analyze genotype-phenotype correlations and malignancy rates in a newly compiled FUS-ALS cohort.Methods: We cross-sectionally reviewed FUS-ALS patient histories in a multicenter cohort with 36 novel cases and did a meta-analysis of published FUS-ALS cases reporting the largest genotype-phenotype correlation of FUS-ALS.Results: The age of onset (median 39 years, range 11-80) was positively correlated with the disease duration. C-terminal domain mutations were found in 90%. Among all, P525L and truncating/ frameshift mutations most frequently caused juvenile onset, rapid disease progression, and atypical ALS often associated with negative family history while the R521 mutation site was associated with late disease onset and pure spinal phenotype. Malignancies were found in one of 40 patients.Interpretation: We report the largest genotype-phenotype correlation of FUS-ALS, which enables a careful prediction of the clinical course in newly diagnosed patients. In this cohort, FUS-ALS patients did not have an increased risk for malignant diseases.
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34.
  • Tang, Yulung, et al. (författare)
  • Cryogenic W-band LNA for ALMA band 2+3 with average noise temperature of 24 K
  • 2017
  • Ingår i: IEEE MTT-S International Microwave Symposium Digest. - 0149-645X. - 9781509063604 ; , s. 176-179
  • Konferensbidrag (refereegranskat)abstract
    • A cryogenic low noise amplifier that operates across the E and W-bands, from 65 GHz to 116 GHz, has been developed using 0.1-?m InP HEMT technology. Such wideband performance makes this work suitable for the ALMA telescope where two of its bands, 67-90 GHz of Band 2 and 85-116 GHz of Band 3, can be combined into one. At an ambient temperature of 5.5 K, this W-band LNA demonstrates an average noise temperature of 24.7 K with more than 21 dB gain and +/-3.0 dB gain flatness from 65 GHz to 116 GHz. To the best knowledge of the authors, this combination of bandwidth, gain flatness and noise temperature has not been demonstrated before.
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35.
  • van der Kooi, Casper J., et al. (författare)
  • Achromatic Cues Are Important for Flower Visibility to Hawkmoths and Other Insects
  • 2022
  • Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies on animal colour vision typically focus on the chromatic aspect of colour, which is related to the spectral distribution, and disregard the achromatic aspect, which is related to the intensity (“brightness”) of a stimulus. Although the chromatic component of vision is often most reliable for object recognition because it is fairly context independent, the achromatic component may provide a reliable signal under specific conditions, for example at night when light intensity is low. Here we make a case for the importance of achromatic cues in plant-pollinator signalling, based on experimental data on naïve Deilephila elpenor and Macroglossum stellatarum hawkmoths, optical modelling and synthesising published experiments on bees, flies, butterflies and moths. Our experiments show that in ecologically relevant light levels hawkmoths express a strong preference for brighter stimuli. Published experiments suggest that for flower-visiting bees, butterflies, moths and flies, achromatic cues may be more important for object detection than often considered. Our optical modelling enabled disentangling the contribution of pigments and scattering structures to the flower’s achromatic contrast, and illustrates how flower anatomy and background are important mediating factors. We discuss our findings in the context of the often-assumed dichotomy between detection and discrimination, chromatic versus achromatic vision, and the evolution of floral visual signals.
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36.
  • Van Der Kooi, Casper J., et al. (författare)
  • Evolution of Insect Color Vision : From Spectral Sensitivity to Visual Ecology
  • 2021
  • Ingår i: Annual Review of Entomology. - : Annual Reviews. - 0066-4170 .- 1545-4487. ; 66, s. 435-461
  • Forskningsöversikt (refereegranskat)abstract
    • Color vision is widespread among insects but varies among species, depending on the spectral sensitivities and interplay of the participating photoreceptors. The spectral sensitivity of a photoreceptor is principally determined by the absorption spectrum of the expressed visual pigment, but it can be modified by various optical and electrophysiological factors. For example, screening and filtering pigments, rhabdom waveguide properties, retinal structure, and neural processing all influence the perceived color signal. We review the diversity in compound eye structure, visual pigments, photoreceptor physiology, and visual ecology of insects. Based on an overview of the current information about the spectral sensitivities of insect photoreceptors, covering 221 species in 13 insect orders, we discuss the evolution of color vision and highlight present knowledge gaps and promising future research directions in the field.
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37.
  • Van Der Kooi, Casper J., et al. (författare)
  • Mutualisms and (A)symmetry in Plant–Pollinator Interactions
  • 2021
  • Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 31:2, s. R91-R99
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of flowering plants relies on animal pollinators for sexual reproduction and many animal pollinators rely on floral resources. However, interests of plants and pollinators are often not the same, resulting in an asymmetric relationship that ranges from mutualistic to parasitic interactions. Our understanding of the processes that underlie this asymmetry remains fragmentary. In this Review, we bring together evidence from evolutionary biology, plant chemistry, biomechanics, sensory ecology and behaviour to illustrate that the degree of symmetry often depends on the perspective taken. We also highlight variation in (a)symmetry within and between plant and pollinator species as well as between geographic locations. Through taking different perspectives from the plant and pollinator sides we provide new ground for studies on the maintenance and evolution of animal pollination and on the (a)symmetry in plant-pollinator interactions.
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