| 1. |
- Ahlford, Annika, et al.
(författare)
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Dried reagents for multiplex genotyping by tag-array minisequencing to be used in microfluidic devices
- 2010
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 135:9, s. 2377-2385
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Tidskriftsartikel (refereegranskat)abstract
- We present an optimized procedure for freeze-drying and storing reagents for multiplex PCR followed by genotyping using a tag-array minisequencing assay with four color fluorescence detection which is suitable for microfluidic assay formats. A test panel was established for five cancer mutations in three codons (175, 248 and 273) of the tumor protein gene (TP53) and for 13 common single nucleotide polymorphisms (SNPs) in the TP53 gene. The activity of DNA polymerase was preserved for six months of storage after freeze-drying, and the half-life of activities of exonuclease I and shrimp alkaline phosphatase were estimated to 55 and 200 days, respectively. We conducted a systematic genotyping comparison using freeze-dried and liquid reagents. The accuracy of successful genotyping was 99.1% using freeze-dried reagents compared to liquid reagents. As a proof of concept, the genotyping protocol was carried out with freeze-dried reagents stored in reaction chambers fabricated by micromilling in a cyclic olefin copolymer substrate. The results reported in this study are a key step towards the development of an integrated microfluidic device for point-of-care DNA-based diagnostics.
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| 2. |
- Bellec, G., et al.
(författare)
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A social network integrated game experiment to relate tapping to speed perception and explore rhythm reproduction
- 2013
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Ingår i: Proceedings of the Sound and Music Computing Conference 2013. - 9783832534721 ; , s. 19-26
-
Konferensbidrag (refereegranskat)abstract
- During recent years, games with a purpose (GWAPs) have become increasingly popular for studying human behaviour [1–4]. However, no standardised method for web-based game experiments has been proposed so far. We present here our approach comprising an extended version of the CaSimIR social game framework [5] for data collection, mini-games for tempo and rhythm tapping, and an initial analysis of the data collected so far. The game presented here is part of the Spot The Odd Song Out game, which is freely available for use on Facebook and on the Web 1 .We present the GWAP method in some detail and a preliminary analysis of data collected. We relate the tapping data to perceptual ratings obtained in previous work. The results suggest that the tapped tempo data collected in a GWAP can be used to predict perceived speed. I toned down the above statement as I understand from the results section that our data are not as good as When averagingthe rhythmic performances of a group of 10 players in the second experiment, the tapping frequency shows a pattern that corresponds to the time signature of the music played. Our experience shows that more effort in design and during runtime is required than in a traditional experiment. Our experiment is still running and available on line.
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| 3. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 4. |
- Aranda-Guillén, Maribel, et al.
(författare)
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A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
- 2023
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Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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| 5. |
- Arnalds, Unnar B., et al.
(författare)
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A new look on the two-dimensional Ising model : thermal artificial spins
- 2016
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- We present a direct experimental investigation of the thermal ordering in an artificial analogue of an asymmetric two-dimensional Ising system composed of a rectangular array of nano-fabricated magnetostatically interacting islands. During fabrication and below a critical thickness of the magnetic material the islands are thermally fluctuating and thus the system is able to explore its phase space. Above the critical thickness the islands freeze-in resulting in an arrested thermalized state for the array. Determining the magnetic state we demonstrate a genuine artificial two-dimensional Ising system which can be analyzed in the context of nearest neighbor interactions.
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| 6. |
- Brantnell, Anders, 1983-, et al.
(författare)
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Barriers and facilitators to the implementation of additive manufacturing in cardiology : A qualitative study
- 2022
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Ingår i: Annals of 3D Printed Medicine. - : Elsevier. - 2666-9641. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Additive manufacturing (AM) is a fast-developing technology with possible applications in car-diology. Existing research has identified two general factors that can influence implementing AM in cardiol-ogy: economics and technology.Objective: In this study we aimed to identify barriers and facilitators to implementing AM in cardiology.Methods: We conducted a multiple case study of two Swedish cardiac surgery departments representingimplementers and non-implementers of AM. We interviewed key stakeholders (n=8) who had been or wereinvolved in implementing AM in cardiology or AM in general at the hospitals: cardiologists, physicians work-ing with AM but not specialized in cardiology such as radiologists, company representatives, and individualsinvolved in the 3D-printing facilities. A combination of an inductive and deductive approach was used to ana-lyze the interviews.Results: Several barriers and facilitators influenced implementing AM in cardiology. Most barriers (n=4) wererelated to innovation factors, whereas most facilitators (n=4) were related to healthcare professionals. No barriers and facilitators were related to patients.Conclusion: Our findings show that AM in cardiology is in its very early phases in both hospitals and mostlythe work of a few individuals. In the two hospitals studied, there were some unique differences in terms ofbarriers that could explain the low level of implementation. These barriers could be important to addresswhen supporting implementation of AM at hospitals where AM use is still low.
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| 7. |
- Bruserud, Oyvind, et al.
(författare)
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A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:8, s. 2975-2983
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Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. Objective: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016). Patients: All known Norwegian patients with APS1. Results: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceasedsiblingswithahighprobability of undisclosed APS1. All except three had interferon-omega) autoantibodies, and allhadorgan-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. Conclusions: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-omega) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center.
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| 8. |
- Chulapakorn, Thawatchart, 1988-, et al.
(författare)
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Si-nanoparticle synthesis using ion implantation and MeV ion irradiation
- 2015
-
Ingår i: Physica Status Solidi (C) Current Topics in Solid State Physics. - : Wiley-VCH Verlagsgesellschaft. - 1862-6351.
-
Tidskriftsartikel (refereegranskat)abstract
- A dielectric matrix with embedded Si-nanoparticles may show strong luminescence depending on nanoparticles size, surface properties, Si-excess concentration and matrix type. Ion implantation of Si ions with energies of a few tens to hundreds of keV in a SiO2 matrix followed by thermal annealing was identified as a powerful method to form such nanoparticles. The aim of the present work is to optimize the synthesis of Si-nanoparticles produced by ion implantation in SiO2 by employing MeV ion irradiation as an additional annealing process. The luminescence properties are measured by spectrally resolved photoluminescence including PL lifetime measurement, while X-ray reflectometry, atomic force microscopy and ion beam analysis are used to characterize the nanoparticle formation process. The results show that the samples implanted at 20%-Si excess atomic concentration display the highest luminescence and that irradiation of 36 MeV 127I ions affects the luminosity in terms of wavelength and intensity. It is also demonstrated that the nanoparticle luminescence lifetime decreases as a function of irradiation fluence.
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| 9. |
- Dave, Vivek Priy, et al.
(författare)
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MicroRNA amplification and detection technologies : opportunities and challenges for point of care diagnostics
- 2018
-
Ingår i: Laboratory Investigation. - : Nature Publishing Group. - 0023-6837 .- 1530-0307. ; 99:4, s. 452-469
-
Forskningsöversikt (refereegranskat)abstract
- The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling-based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.
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| 10. |
- Elias Wolff, Federico, et al.
(författare)
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How Levins’ dynamics emerges from a Ricker metapopulation model
- 2016
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Ingår i: Theoretical Ecology. - : Springer Science and Business Media LLC. - 1874-1738 .- 1874-1746. ; 9:2, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the dynamics of metapopulations close to extinction is of vital importance for management. Levins-like models, in which local patches are treated as either occupied or empty, have been used extensively to explore the extinction dynamics of metapopulations, but they ignore the important role of local population dynamics. In this paper, we consider a stochastic metapopulation model where local populations follow a stochastic, density-dependent dynamics (the Ricker model), and use this framework to investigate the behaviour of the metapopulation on the brink of extinction. We determine under which circumstances the metapopulation follows a time evolution consistent with Levins’ dynamics. We derive analytical expressions for the colonisation and extinction rates (c and e) in Levins-type models in terms of reproduction, survival and dispersal parameters of the local populations, providing an avenue to parameterising Levins-like models from the type of information on local demography that is available for a number of species. To facilitate applying our results, we provide a numerical algorithm for computing c and e.
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| 11. |
- Eriksson, Anders, 1975, et al.
(författare)
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Metapopulation dynamics on the brink of extinction
- 2013
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Ingår i: Theoretical Population Biology. - : Elsevier BV. - 0040-5809. ; 83, s. 101-122
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Tidskriftsartikel (refereegranskat)abstract
- We analyse metapopulation dynamics in terms of an individual-based, stochastic model of a finite metapopulation. We suggest a new approach, using the number of patches in the population as a large parameter. This approach does not require that the number of individuals per patch is large, neither is it necessary to assume a time-scale separation between local population dynamics and migration. Our approach makes it possible to accurately describe the dynamics of metapopulations consisting of many small patches. We focus on metapopulations on the brink of extinction. We estimate the time to extinction and describe the most likely path to extinction. We find that the logarithm of the time to extinction is proportional to the product of two vectors, a vector characterising the distribution of patch population sizes in the quasi-steady state, and a vector–related to Fisher’s reproduction vector–that quantifies the sensitivity of the quasi-steady state distribution to demographic fluctuations. We compare our analytical results to stochastic simulations of the model, and discuss the range of validity of the analytical expressions. By identifying fast and slow degrees of freedom in the metapopulation dynamics, we show that the dynamics of large metapopulations close to extinction is approximately described by a deterministic equation originally proposed by Levins (1969). We were able to compute the rates in Levins’ equation in terms of the parameters of our stochastic, individual-based model. It turns out, however, that the interpretation of the dynamical variable depends strongly on the intrinsic growth rate and carrying capacity of the patches. Only when the local growth rate and the carrying capacity are large does the slow variable correspond to the number of patches, as envisaged by Levins. Last but not least, we discuss how our findings relate to other, widely used metapopulation models.
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| 12. |
- Eriksson, Anders, 1975, et al.
(författare)
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The emergence of the rescue effect from explicit within- and between-patch dynamics in a metapopulation
- 2014
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 281:1780
-
Tidskriftsartikel (refereegranskat)abstract
- Immigration can rescue local populations from extinction, helping to stabilise a metapopulation. Local population dynamics is important for determining the strength of this rescue effect, but the mechanistic link between local demographic parameters and the rescue effect at the metapopulation level has received very little attention by modellers. We develop an analytical framework that allows us to describe the emergence of the rescue effect from interacting local stochastic dynamics. We show this framework to be applicable to a wide range of spatial scales, providing a powerful and convenient alternative to individual‐based models for making predictions concerning the fate of metapopulations. We show that the rescue effect plays an important role in minimising the increase in local extinction probability associated with high demographic stochasticity, but its role is more limited in the case of high local environmental stochasticity of recruitment or survival. While most models postulate the rescue effect, our framework provides an explicit mechanistic link between local dynamics and the emergence of the rescue effect, and more generally the stability of the whole metapopulation.
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| 13. |
- Eriksson, Daniel, et al.
(författare)
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GWAS for autoimmune Addison’s disease identifies multiple risk loci and highlights AIRE in disease susceptibility
- 2021
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10-8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10-25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h2).
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| 14. |
- Falowska-Pietrzak, Olga, et al.
(författare)
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Investigation of the stray radiation origin and composition at the European XFEL undulators with gafchromic films measurements and Geant4 simulations
- 2023
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 1056
-
Tidskriftsartikel (refereegranskat)abstract
- At EuXFEL, a stray field of ionizing radiation is present near undulator magnets which eventually can lead to their demagnetization and decreased efficiency of the Self-Amplified Spontaneous Emission (SASE) process. In this work we investigate both the origin and composition of the radiation field at the undulator magnets with gafchromic film measurements and Geant4 Monte Carlo simulations. Both measurements and simulations suggest that the radiation field in the upstream undulator cells comes from high-energy electrons striking the beam pipe. In addition, horizontal dose distributions at the entrance of the undulator segments depend on where the electrons hit the beam pipe. Geant4 simulations show that the radiation fluence near magnets is dominated by photons, while charged secondary electrons and positrons contribute almost entirely to the ionizing dose absorbed by magnets.
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| 15. |
- Fischer, Hubertus, et al.
(författare)
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Palaeoclimate constraints on the impact of 2 °C anthropogenic warming and beyond
- 2018
-
Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 11:7, s. 474-485
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 3.5 million years, there have been several intervals when climate conditions were warmer than during the pre-industrial Holocene. Although past intervals of warming were forced differently than future anthropogenic change, such periods can provide insights into potential future climate impacts and ecosystem feedbacks, especially over centennial-to-millennial timescales that are often not covered by climate model simulations. Our observation-based synthesis of the understanding of past intervals with temperatures within the range of projected future warming suggests that there is a low risk of runaway greenhouse gas feedbacks for global warming of no more than 2 °C. However, substantial regional environmental impacts can occur. A global average warming of 1–2 °C with strong polar amplification has, in the past, been accompanied by significant shifts in climate zones and the spatial distribution of land and ocean ecosystems. Sustained warming at this level has also led to substantial reductions of the Greenland and Antarctic ice sheets, with sea-level increases of at least several metres on millennial timescales. Comparison of palaeo observations with climate model results suggests that, due to the lack of certain feedback processes, model-based climate projections may underestimate long-term warming in response to future radiative forcing by as much as a factor of two, and thus may also underestimate centennial-to-millennial-scale sea-level rise.
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| 16. |
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| 17. |
- Holzapfel, Damian M., et al.
(författare)
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Enhanced thermal stability of (Ti,Al)N coatings by oxygen incorporation
- 2021
-
Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Thermal stability of protective coatings is one of the performance-defining properties for advanced cutting and forming applications as well as for energy conversion. To investigate the effect of oxygen incorporation on the high-temperature behavior of (Ti,Al)N, metastable cubic (Ti,Al)N and (Ti,Al)(OxN1-x) coatings are synthesized using reactive arc evaporation. X-ray diffraction of (Ti,Al)N and (Ti,Al)(OxN1-x) coatings reveals that spinodal decomposition is initiated at approximately 800 degrees C, while the subsequent formation of wurtzite solid solution is clearly delayed from 1000 degrees C to 1300 degrees C for (Ti,Al)(OxN1-x) compared to (Ti,Al)N. This thermal stability enhancement can be rationalized based on calculated vacancy formation energies in combination with spatially-resolved composition analysis and calorimetric data: Energy dispersive X-ray spectroscopy and atom probe tomography data indicate a lower O solubility in wurtzite solid solution compared to cubic (Ti,Al)(O,N). Hence, it is evident that for the growth of the wurtzite, AlN-rich phase in (Ti,Al)N, only mobility of Ti and Al is required, while for (Ti,Al)(O,N), in addition to mobile metal atoms, also non-metal mobility is required. Prerequisite for mobility on the non-metal sublattice is the formation of non-metal vacancies which require larger temperatures than for the metal sublattice due to significantly larger magnitudes of formation energies for the non-metal vacancies compared to the metal vacancies. This notion is consistent with calorimetry data which indicate that the combined energy necessary to form and grow the wurtzite phase is larger by a factor of approximately two in (Ti,Al)(O,N) than in (Ti,Al)N, causing the here reported thermal stability increase. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 18. |
- Ohlander, Anna
(författare)
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Foil-based Lab-on-Chip technologies for advanced Point-of-Care molecular diagnostics
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infectious diseases pose a serious threat to global health. Molecular diagnostics provide solutions for effective control and prevention of infections, however suffers from expensive laboratory equipment, and infrastructure to be fully implemented at point of care (POC), especially at low-resource settings. Lab-on-a-chip that aims to integrate complex biochemical analyses into automated systems is promising for POC analysis. A major challenge is the integration of a complete molecular diagnostic assay, generally translating into complex microfluidics, with the requirement of low fabrication cost. This thesis explores the use of flexible electronics, plastic foils and roll-to-roll manufacturing to enable low-cost microfluidic systems, for molecular diagnostic assays especially targeted towards infectious diseases. Many biochemical assays rely on heat; hence a first aspect in this thesis is the integration of a microheater into microfluidics. In a first project a system for SNP-genotyping is presented using solid phase melting curve analysis to discriminate mutations at a single base resolution. Starting with a glass based concept (paper I) which is further developed to a foil based system (paper II), detection of the polymorphism in the neuropeptide Y associated with increased risk of type II diabetes is demonstrated as a proof of principle. Further development and optimization of the microheater concept has enabled roll-to-roll manufacturing compatibility and multiplexing of targets (paper III). A bacterial sub-typing and multiresistance detection in clinical Staphylococcus Aureus samples is demonstrated for applications in infectious diseases diagnostics. Finally, the microheater concept is further developed to enable μPCR (paper IV). Detection of genomic HIV-1 is demonstrated and a portable detection setup based on an LED light source and low cost CMOS camera for detection was developed. A second aspect of this thesis is integration of light sources and optical detection (paper V-VI). A multilayer system integrating an electroluminescent light source, reactive sensor dyes and organic semiconductor transistor for detection is demonstrated. The system could be used for amine detection in gases (paper V). System was made further roll-to-roll compatible. The system uses an external LED light source and a photodetector processed in only one screen printing- and one dispensing step (paper VI). As a proof of principle, absorbance based DNA hybridization was detected. Collectively, roll-to-roll manufacturing compatible “lab on foil” systems have the potential to improve our ability to diagnose at POC especially at resource-limited settings.
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| 19. |
- Schroeder, Fritz H., et al.
(författare)
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Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart after Radical Therapy for Prostate Cancer Study
- 2009
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Ingår i: BJU International. - 1464-4096. ; 103:5, s. 590-596
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Tidskriftsartikel (refereegranskat)abstract
- To describe the Avodart after Radical Therapy for prostate cancer Study (ARTS), investigating the use of dutasteride (a dual 5 alpha-reductase inhibitor that suppresses intraprostatic dihydrotestosterone, reduces tumour volume and improves other markers of tumour regression in prostate cancer) to prevent or delay disease progression in patients with biochemical recurrence after therapy with curative intent. An increasing serum prostate-specific antigen (PSA) level after radical prostatectomy (RP) or radiotherapy (RT) is indicative of recurrent prostate cancer and typically pre-dates clinically detectable metastatic disease by several years. ARTS is an ongoing European multicentre trial in which patients are stratified by previous therapy (RP with or without salvage RT vs primary RT) and randomized to double-blind treatment with dutasteride 0.5 mg or placebo once daily for 2 years. Eligible patients will have a PSA doubling time (DT) of 3-24 months. Biochemical recurrence is defined as three increases in PSA level from the nadir, with each increase >= 4 weeks apart and each PSA level >= 0.2 ng/mL, and a final PSA level of >= 0.4 ng/mL (after RP) or >= 2 ng/mL (after primary RT). Study endpoints include time to PSA doubling, time to disease progression, treatment response (PSA decrease or an increase of <= 15% from baseline), changes in PSA and PSADT, and changes in anxiety (Memorial Anxiety Scale for Prostate Cancer). ARTS will be the first study to evaluate the effects of dutasteride on PSADT, disease progression and treatment response in patients with biochemical failure after RP or RT, and should help to elucidate the potential role of dual 5 alpha-reductase inhibition in prostate cancer.
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| 20. |
- Spegel, Christer, et al.
(författare)
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On-chip determination of dopamine exocytosis using mercaptopropionic acid modified microelectrodes
- 2007
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Ingår i: Electroanalysis. - : Wiley. - 1040-0397 .- 1521-4109. ; 19:2-3, s. 263-271
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Tidskriftsartikel (refereegranskat)abstract
- Gold and platinum, which often are used for thin film metallization, are not suitable for the measurement of dopamine (DA), since the oxidation product of DA forms a non-conducting polymer on the electrode surface. In this work several thiols were screened for their ability to prevent this polymerization. It was found that mercaptopropionic acid (MPA) decreased the rate of DA polymerization. MPA, possessing a weak acidic functionality, had the greatest effect on the DA electrochemistry by decreasing electrode passivation, as well as improving reversibility and sensitivity. Modifications of microchip electrodes with MPA did not only improve DA electrochemistry but also significantly increased the storage stability of the transducers. The microchips were ultimately used to detect K+ stimulated quantal release of DA from PC12 cells.
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| 21. |
- Strong, K., et al.
(författare)
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Validation of ACE-FTS N2O measurements
- 2008
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8, s. 4759-4786
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Tidskriftsartikel (refereegranskat)abstract
- The Atmospheric Chemistry Experiment (ACE), also known as SCISAT, was launched on 12 August 2003, carrying two instruments that measure vertical profiles of atmospheric constituents using the solar occultation technique. One of these instruments, the ACE Fourier Transform Spectrometer (ACE-FTS), is measuring volume mixing ratio (VMR) profiles of nitrous oxide (N2O) from the upper troposphere to the lower mesosphere at a vertical resolution of about 3–4 km. In this study, the quality of the ACE-FTS version 2.2 N2O data is assessed through comparisons with coincident measurements made by other satellite, balloon-borne, aircraft, and ground-based instruments. These consist of vertical profile comparisons with the SMR, MLS, and MIPAS satellite instruments, multiple aircraft flights of ASUR, and single balloon flights of SPIRALE and FIRS-2, and partial column comparisons with a network of ground-based Fourier Transform InfraRed spectrometers (FTIRs). Between 6 and 30 km, the mean absolute differences for the satellite comparisons lie between −42 ppbv and +17 ppbv, with most within ±20 ppbv. This corresponds to relative deviations from the mean that are within ±15%, except for comparisons with MIPAS near 30 km, for which they are as large as 22.5%. Between 18 and 30 km, the mean absolute differences for the satellite comparisons are generally within ±10 ppbv. From 30 to 60 km, the mean absolute differences are within ±4 ppbv, and are mostly between −2 and +1 ppbv. Given the small N2O VMR in this region, the relative deviations from the mean are therefore large at these altitudes, with most suggesting a negative bias in the ACE-FTS data between 30 and 50 km. In the comparisons with the FTIRs, the mean relative differences between the ACE-FTS and FTIR partial columns (which cover a mean altitude range of 14 to 27 km) are within ±5.6% for eleven of the twelve contributing stations. This mean relative difference is negative at ten stations, suggesting a small negative bias in the ACE-FTS partial columns over the altitude regions compared. Excellent correlation (R=0.964) is observed between the ACE-FTS and FTIR partial columns, with a slope of 1.01 and an intercept of −0.20 on the line fitted to the data.
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| 22. |
- Wolff, D., et al.
(författare)
-
Creating audio based experiments as social Web games with the CASimIR framework
- 2014
-
Ingår i: Proceedings of the AES International Conference. - 9781632662842 ; , s. 288-297
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Konferensbidrag (refereegranskat)abstract
- This article presents the CASimIR framework for online experiments, its use for creating a music audio game, and initial results and analyses of the collected data. Gathering user data is essential to understand the semantics of music audio and CASimIR is a new open framework for creating games with a purpose and surveys to collect user data in the Web and social networks. Its design facilitates collaborative data annotation in dynamic environments by providing modules for managing media and annotation data, as well as functionality for creating and running online real-time multi-player games. Technical benefits of the extensible framework as well as its cost effectiveness are discussed. As a case-study, we present its use in Spot The Odd Song Out, a multi-player game for collecting annotations on musical similarity and rhythm and we analyse the quantity and quality of data obtained to date with this game. The results and lessons for future data collection projects in the context of shared and linked data are discussed.
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| 23. |
- Wolff, Johannes M., et al.
(författare)
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Is intermittent androgen-deprivation therapy beneficial for patients with advanced prostate cancer?
- 2014
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Ingår i: BJU International. - : Wiley. - 1464-4096. ; 114:4, s. 476-483
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Forskningsöversikt (refereegranskat)abstract
- Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short-and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT.
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| 24. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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