| 1. |
- Ablikim, M., et al.
(författare)
-
Probing CP symmetry and weak phases with entangled double-strange baryons
- 2022
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 606:7912, s. 64-69
-
Tidskriftsartikel (refereegranskat)abstract
- Though immensely successful, the standard model of particle physics does not offer any explanation as to why our Universe contains so much more matter than antimatter. A key to a dynamically generated matter-antimatter asymmetry is the existence of processes that violate the combined charge conjugation and parity (CP) symmetry(1). As such, precision tests of CP symmetry may be used to search for physics beyond the standard model. However, hadrons decay through an interplay of strong and weak processes, quantified in terms of relative phases between the amplitudes. Although previous experiments constructed CP observables that depend on both strong and weak phases, we present an approach where sequential two-body decays of entangled multi-strange baryon-antibaryon pairs provide a separation between these phases. Our method, exploiting spin entanglement between the double-strange baryon and its antiparticle(2) (+), has enabled a direct determination of the weak-phase difference, (xi(P) - xi(S)) = (1.2 +/- 3.4 +/- 0.8) x 10(-2) rad. Furthermore, three independent CP observables can be constructed from our measured parameters. The precision in the estimated parameters for a given data sample size is several orders of magnitude greater than achieved with previous methods(3). Finally, we provide an independent measurement of the recently debated Lambda decay parameter alpha(Lambda) (refs. (4,5)). The Lambda(Lambda) over bar asymmetry is in agreement with and compatible in precision to the most precise previous measurement(4).
|
|
| 2. |
- Ahlgren, Sara, et al.
(författare)
-
Targeting of HER2-Expressing Tumors Using 111In-ABY-025, a Second-Generation Affibody Molecule with a Fundamentally Reengineered Scaffold
- 2010
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 51:7, s. 1131-1138
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of HER2 in breast carcinomas predicts response to trastuzumab therapy. Affibody molecules based on a non-immunoglobulin scaffold have demon-strated high potential for in vivo molecular imaging of HER2-expressing tumors. Re-engineering of the molecular scaffold has led to a second generation of optimized Affibody molecules, having a surface distinctly different from the parental protein domain from staphylococcal protein A. The new tracer showed further increased melting point, stability and overall hydrophilicity compared to the parental molecule, and was shown to be more amenable for chemical peptide synthesis. The goal of this study was to assess potential effects of this extensive re-engineering on HER2 targeting, using ABY-025, a DOTA conjugated variant of the novel tracer. Methods: 111In-ABY-025 was compared with previously evaluated parent HER2-binding Affibody tracers in vitro and in vivo. The in vivo behavior was further evaluated in mice bearing SKOV-3 xenografts, in rats and in cynomolgus macaques. Results: 111In-ABY-025 bound specifically to HER2 in vitro and in vivo. Direct comparison with the previous generation of HER2-binding tracers showed that ABY-025 retained excellent targeting properties. Rapid blood clearance was shown in mice, rats and macaques. A highly specific tumor uptake of 16.7 ± 2.5 %IA/g was seen at 4 h after injection. The tumor-to-blood ratio was 6.3 at 0.5 h, 88 at 4 h, and increased up to 3 days after injection. Gamma camera imaging of tumors was already possible 0.5 h after injection. Furthermore, repeated i.v. administration of ABY-025 did not induce antibody formation in rats. Conclusions: The biodistribution of 111In-ABY-025 was in remarkably good agreement with the parent tracers, despite profound re-engineering of the non-binding surface. The molecule displayed rapid blood clearance in all species investigated and excellent targeting capacity in tumor bearing mice, leading to high tumor-to-organ-ratios and high contrast imaging shortly after injection.
|
|
| 3. |
- Almquist, Joachim, et al.
(författare)
-
Model-Based Analysis Reveals a Sustained and Dose-Dependent Acceleration of Wound Healing by VEGF-A mRNA (AZD8601)
- 2020
-
Ingår i: CPT. - : WILEY. - 2163-8306. ; 9:7, s. 384-394
-
Tidskriftsartikel (refereegranskat)abstract
- Intradermal delivery of AZD8601, an mRNA designed to produce vascular endothelial growth factor A (VEGF-A), has previously been shown to accelerate cutaneous wound healing in a murine diabetic model. Here, we develop population pharmacokinetic and pharmacodynamic models aiming to quantify the effect of AZD8601 injections on the dynamics of wound healing. A dataset of 584 open wound area measurements from 131 mice was integrated from 3 independent studies encompassing different doses, dosing timepoints, and number of doses. Evaluation of several candidate models showed that wound healing acceleration is not likely driven directly by time-dependent VEGF-A concentration. Instead, we found that administration of AZD8601 induced a sustained acceleration of wound healing depending on the accumulated dose, with a dose producing 50% of the maximal effect of 92 mu g. Simulations with this model showed that a single dose of 200 mu g AZD8601 can reduce the time to reach 50% wound healing by up to 5 days.
|
|
| 4. |
- Brandner, Birgit D., et al.
(författare)
-
Solvent segregation and capillary evaporation at a superhydrophobic surface investigated by confocal Raman microscopy and force measurements
- 2011
-
Ingår i: SOFT MATTER. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:3, s. 1045-1052
-
Tidskriftsartikel (refereegranskat)abstract
- Wetting of water, a 1 : 1 water/ethanol mixture and an aqueous dodecylbenzene sulfonic acid surfactant solution on hydrophobic and superhydrophobic surfaces were studied using confocal Raman microscopy. The superhydrophobic surfaces were prepared by immersion of a glass substrate in a silica particle/fluoropolymer formulation followed by silanization. Preparation of hydrophobic surfaces was done in the same way with the exception that the silica particles were excluded from the formulation. The hydrophobic and superhydrophobic surfaces were characterized with respect to surface roughness using AFM, and by contact angle measurements using different liquids. Confocal Raman microscopy measurements in a 1 : 1 water/ethanol mixture showed an enrichment of ethanol close to the superhydrophobic surface, which could not be observed for the hydrophobic surface. Unexpectedly, the Raman spectrum of a pure water film in close proximity to the superhydrophobic surface displayed some differences compared to that of bulk water and indicated a stronger hydrogen-bonding close to the superhydrophobic surface. Evidence for capillary evaporation next to the superhydrophobic surface was also found, and this results in very long-range capillary attraction between one superhydrophobic surface and a hydrophobic colloidal probe as shown by AFM colloidal probe force measurements. Addition of a surfactant or ethanol suppresses capillary evaporation.
|
|
| 5. |
- Bridel, Claire, et al.
(författare)
-
Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
|
|
| 6. |
- Eldh, Sigrid, 1961-
(författare)
-
On Evaluating Test Techniques in an Industrial Setting
- 2007
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Testing is a costly and an important activity in the software industry today. The systems are becoming more complex and the amount of code is constantly increasing. The majority of systems need to rely on its testing to show that it works, is reliable, and performs according to user expectations and specifications.Testing is performed in a multitude of ways, using different test approaches. How testing is conducted becomes essential, when time is limited, since exhaustive testing is not an option in large complex systems, Therefore, the design of the individual test case – and what part and aspect of the system it exercises, is the main focus of testing. Not only do we need to create, and execute test cases efficiently, but we also want them to expose important faults in the system. This main topic of testing has long been a focus of practitioners in industry, and there exists over 70 test techniques that aim to describe how to design a test case. Unfortunately, despite the industrial needs, research on test techniques are seldom performed in large complex systems.The main purpose of this licentiate thesis is to create an environment and framework where it is possible to evaluate test techniques. Our overall goal is to investigate suitable test techniques for different levels, (e.g. component, integration and system level) and to provide guidelines to industry on what is effective, efficient and applicable to test, based on knowledge of failure-fault distribution in a particular domain. In this thesis, our research has been described through four papers that start from a broad overview of typical industrial systems and arrive at a specific focus on how to set up a controlled experiment in an industrial environment. Our initial paper has stated the status of testing in industry, and aided in identifying specific issues as well as underlined the need for further research. We then made experiments with component test improvements, by simple utilization of known approaches (e.g. static analysis, code reviews and statement coverage). This resulted in a substantial cost-reduction and increased quality, and provided us better understanding of the difficulties in deploying known test techniques in reality, which are described in our second paper. These works lead us to our third paper, which describes the framework and process for evaluating test techniques. The first sub-process in this framework deals with how to prepare the experiment with a known set of faults. We aimed to investigate fault classifications to get a useful set of faults of different types to inject. In addition, we investigated real faults reported in an industrial system, performed controlled experiments, and the results were published in our fourth paper.The main contributions of this Licentiate thesis are the valuable insights in the context of evaluation of test techniques, specifically the problems of creating a useful experiment in an industrial setting, in addition to the survey of the state of practice of software testing in Industry. We want to better understand what needs to be done to create efficient evaluations of test techniques, and secondly what is the relation between faults/failures and test techniques. Though our experiments have not yet been able to create ‘the ultimate’ classification for such an aim, the results indicate the appropriateness of this approach. With these valuable insights, we believe that we will be able to direct our future research, to make better evaluations that have a larger potential to generalize and scale.
|
|
| 7. |
- Eldh, Sigrid, et al.
(författare)
-
Towards Fully Automated Test Management for Large Complex Systems
- 2010
-
Ingår i: ICST 2010 - 3rd International Conference on Software Testing, Verification and Validation. - Paris. ; , s. 412-420
-
Konferensbidrag (refereegranskat)abstract
- Development of large and complex software intensive systems with continuous builds typically generates large volumes of information with complex patterns and relations. Systematic and automated approaches are needed for efficient handling of such large quantities of data in a comprehensible way. In this paper we present an approach and tool enabling autonomous behavior in an automated test management tool to gain efficiency in concurrent software development and test. By capturing the required quality criteria in the test specifications and automating the test execution, test management can potentially be performed to a great extent without manual intervention. This work contributes towards a more autonomous behavior within a distributed remote test strategy based on metrics for decision making in automated testing. These metrics optimize management of fault corrections and retest, giving consideration to the impact of the identified weaknesses, such as fault-prone areas in software.
|
|
| 8. |
- Eriksson, Dennis, et al.
(författare)
-
Options to Reform the European Union Legislation on GMOs : Scope and Definitions
- 2020
-
Ingår i: Trends in Biotechnology. - : Elsevier BV. - 0167-7799 .- 1879-3096. ; 38:3, s. 231-234
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a threepart series, this article focuses on reform options related to the scope of the legislation and the GMO definition.
|
|
| 9. |
- Eriksson, Dennis, et al.
(författare)
-
Options to Reform the European Union Legislation on GMOs : Risk Governance
- 2020
-
Ingår i: Trends in Biotechnology. - : Elsevier BV. - 0167-7799 .- 1879-3096. ; 38:4, s. 349-351
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Here, we discuss options to reform the EU genetically modified organism (GMO) regulatory framework, to make risk assessment and decision-making more consistent with scientific principles, and to lay the groundwork for international coherence. We discussed the scope and definitions in a previous article and, thus, here we focus on the procedures for risk assessment and risk management.
|
|
| 10. |
- Forsman, Anna K, et al.
(författare)
-
Research priorities for public mental health in Europe: recommendations of the ROAMER project.
- 2015
-
Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 25:2, s. 249-254
-
Tidskriftsartikel (refereegranskat)abstract
- The ROAdmap for MEntal health Research in Europe project aimed to create an integrated European roadmap for mental health research. Leading mental health research experts across Europe have formulated consensus-based recommendations for future research within the public mental health field.
|
|
