| 1. |
- Berglund, Kim, 1982-, et al.
(författare)
-
A novel reciprocating tribometer for friction and wear measurements with high contact pressure and large area contact configurations
- 2021
-
Ingår i: Lubricants. - : MDPI. - 2075-4442. ; 9:12
-
Tidskriftsartikel (refereegranskat)abstract
- There are many moving machine assemblies with conformal tribological contacts at very high contact pressures, e.g., sliding bearings, propeller shaft bearings and machine guideways. Furthermore, applications such as trunnion and guide vane bearing in Kaplan turbines have very low sliding speeds and oscillatory types of motion. Although there is a vast selection of tribology test rigs available, there is still a lack of test equipment to perform friction and wear tests under high contact pressure, reciprocatory sliding and large area contact. The aim of this work is thus to develop a novel reciprocating tribometer and test method that enables friction and wear tests under low-speed reciprocatory sliding with contact pressures up to 90 MPa in a flat-on-flat contact configuration. First, a thorough description of the test rig design is given. Secondly, the influence of contact pressure and stroke length on the tribological properties of a stainless steel and polymer composite material combination is studied. The significance of considering creep, friction during the stroke and contact temperature is specifically highlighted. The novel tribometer can be used to screen different bearing and shaft material combinations and to evaluate the friction and wear performance of self-lubricating bearings for the specific operating conditions found in Kaplan turbines.
|
|
| 2. |
|
|
| 3. |
- Bucin, Dragan, et al.
(författare)
-
Heart transplantation across the antibodies against HLA and ABO
- 2006
-
Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 19:3, s. 239-244
-
Tidskriftsartikel (refereegranskat)abstract
- We have intentionally performed heart transplantation in a 5-year-old child, despite the most unfavourable risk factors for patient survival; the presence of high level of antibodies against donor's human leucocyte antigen (HLA) class I/II and blood group antigens. Pretransplant treatment by mycophenolate mofetil, prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A immunoadsorption (IA) and plasma exchange reduced antibody titres against the donor's lymphocytes from 128 to 16 and against the donor's blood group antigen from 256 to 0. The patient was urgently transplanted with a heart from an ABO incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol was used. No hyperacute rejection was seen. Antibodies against the donor's HLA antigens remained at a low level despite three acute rejections. Rising anti-A(1) blood group antibodies preceded the second rejection and were reduced by two blood group-specific IAs and remained at a low level. The patient is doing well despite the persistence of donor-reactive antibodies.
|
|
| 4. |
- Fricke, Katrin, et al.
(författare)
-
Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome: 20 Years of National Data From Sweden
- 2022
-
Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation. METHODS AND RESULTS: This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob-LV: HR, 2.1; P=0.03). CONCLUSIONS: Glob-LV and AA-MS are independent morphological risk factors for adverse short-and long-term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome.
|
|
| 5. |
- Grabowski, Martin, et al.
(författare)
-
Influence of an enriched environment and cortical grafting on functional outcome in brain infarcts of adult rats
- 1995
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 133:1, s. 96-102
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to study if enriched housing conditions and fetal neocortical transplantation could enhance the functional outcome after focal brain ischemia in adult rats. The right middle cerebral artery (MCA) was ligated in 34 inbred, spontaneously hypertensive male rats, which were then randomly divided into three groups. Groups A and B were transferred to an enriched environment, i.e., a large cage with opportunities for various activities but not forcing the rats to do any particular tasks; group C was kept in standard laboratory cages. Three weeks after the MCA occlusion blocks of fetal neocortical tissue (Embryonic Day 17) were transplanted to the infarct cavity in groups B and C. Rats in group A (n = 11) and group B (n = 11) performed equally well and significantly better than rats in group C (n = 10) when placed on an inclined plane and when traversing a rotating pole 6 and 9 weeks after the MCA occlusion and in a leg placement test at 9, but not 6 and 12 weeks. Skilled forelimb function did not differ between the groups. Infarct size and thalamic atrophy did not differ between the groups and graft size was similar in group B and C. There was no correlation between infarct size and motor function in any of the tests in rats housed in an enriched environment. Since the environment can significantly alter functional outcome without reducing infarct size we suggest that more attention should be given to the role of the laboratory environment and to long term behavioral outcome in experimental stroke.
|
|
| 6. |
- Johansson, Jens
(författare)
-
Impact of Water-Level Variations on Slope Stability
- 2014
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Waterfront-soil slopes are exposed to water-level fluctuations originating from either natural sources, e.g. extreme weather and tides, or from human activities such as watercourse regulation for irrigation, freshwater provision, hydropower production etc. Slope failures and bank erosion is potentially getting trees and other vegetation released along with bank landslides. When floating debris is reaching hydropower stations, there will be immediate risks of adverse loading on constructions, and clogging of spillways; issues directly connected to as well energy production as dam safety.The stability of a soil slope is governed by slope geometries, stress conditions, and soil properties. External water loading, pore-pressure changes, and hydrodynamic impact from water flow are factors being either influencing, or completely governing the actual soil properties. As a part of this study, knowledge concerning water-level fluctuations has been reviewed; sources, geotechnical effects on slopes, and approaches used for modelling, have been focused. It has been found a predominance of research focused on coastal erosion, quantification of sediment production, bio-environmentallyissues connected to flooding, and effects on embankment dams subjected to rapid drawdown. Though, also water-level rise has been shown to significantly influence slope stability. There seems to be a need for further investigations concerning effects of rapidly increased water pressures, loss of negative pore pressures, retrogressive failure development, and long-term effects of recurring rise-drawdown cycling.Transient water flow within soil structures affects pore-pressure conditions, strength, and deformation behavior of the soil. This in turn does potentially lead to soil-materialmigration, i.e. erosion. This process is typically considered in the context of embankment dams. Despite the effects of transient water flow, the use of simple limitequilibrium methods for slope analysis is still widely spread. Though, improved accessibility of high computer capacity allows for more and more advanced analyses to be carried out. In addition, optimized designs and constructions are increasingly demanded, meaning less conservative design approaches being desired. This is not atleast linked to economic as environmental aspects. One non-conservative view ofslope-stability analysis regards consideration of negative pore pressures in unsaturated soils. In this study, three different approaches used for hydro-mechanical coupling in FEM-modelling of slope stability, were evaluated. A fictive slope consisting of a wellgraded postglacial till was exposed to a series of water-level fluctuation cycles. Modelling based on classical theories of dry/fully saturated soil conditions, was put against two more advanced approaches with unsaturated-soil behavior considered. In the classical modelling, computations of pore-pressures and deformations were run separately, whereas the advanced approaches did allow for computations of porepressures and deformation to be fully coupled. The evaluation was carried out by comparing results concerning stability, vertical displacements, pore pressures, flow, and model-parameter influence. It was found that the more advanced approaches used did capture variations of pore pressures and flow to a higher degree than did the classical, more simple approach. Classical modelling resulted in smaller vertical displacements and smoother porepressure and flow developments. Flow patterns, changes of soil density governed by suction fluctuations, and changes of hydraulic conductivity, are all factors governing as well water-transport (e.g. dissipation of excess pore pressures) as soil-material transport(e.g. susceptibility to internal erosion to be initiated and/or continued). Therefore, the results obtained underline the strengths of sophisticated modelling.
|
|
| 7. |
- Johansson, Maria, et al.
(författare)
-
Factors Governing Human Fear of Brown Bear and Wolf
- 2012
-
Ingår i: Human Dimensions of Wildlife. - London : Taylor & Francis. - 1087-1209 .- 1533-158X. ; 17:1, s. 58-74
-
Tidskriftsartikel (refereegranskat)abstract
- This article analyzes people's subjectively experienced fear in areas with presence of brown bear or wolf. Departing from the Human-Environment Interaction Model (Küller, 1991), a hypothetical model of environmental and individual antecedents of fear was tested using structural equation modeling of survey data (n = 391). In the model of fear of brown bear, the main predictor was the appraisal of the species as dangerous/uncontrollable and unpredictable. In the model of fear of wolf, the greater experience with the species and a stronger appraisal of wolf as dangerous, uncontrollable, and unpredictable led to low social trust and this, together with the appraisal of wolf as dangerous/uncontrollable and unpredictable, increased the likelihood of fear. Efforts to reduce human fear of wolves should focus on building trust between the public and authorities, whereas efforts to reduce fear of brown bear should focus on the individual's appraisal of the species. © 2012 Copyright Taylor and Francis Group, LLC.
|
|
| 8. |
- Johansson, Maria, et al.
(författare)
-
Is Human Fear Affecting Public Willingness to Pay for the Management and Conservation of Large Carnivores?
- 2012
-
Ingår i: Society & Natural Resources. - : Informa UK Limited. - 0894-1920 .- 1521-0723. ; 25:6, s. 610-620
-
Tidskriftsartikel (refereegranskat)abstract
- From an interdisciplinary approach, this study aims at analyzing self-reported animal fear, specifically large carnivore fear, in relation to public willingness to pay to fulfill a governmental policy on large carnivore-induced costs. In a survey in Sweden involving more than 2,000 respondents, it was found that people whose animal fear was directed particularly toward large carnivores were less likely to be willing to pay these costs, or were likely to be willing to pay a lower amount of money. In the prediction of willingness to pay (WTP), the contribution of the fear variable was as equally important as previously addressed socioeconomic factors.
|
|
| 9. |
- Johansson, Maria, et al.
(författare)
-
Subjective experience of fear and the cognitive interpretation of large carnivores
- 2011
-
Ingår i: Human Dimensions of Wildlife. - : Informa UK Limited. - 1087-1209 .- 1533-158X. ; 16:1, s. 15-29
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes the psychological characteristics of fear of brown bear (Ursus arctos) and wolf (Canis lupus) using the Cognitive Vulnerability Model. Data were obtained from a survey of 154 stakeholders. Subjective experience of fear was primarily linked to the perceived danger or harm that the animal represents and the perceived uncontrollability of the person's own response when encountering an animal. Feelings of disgust and perceived unpredictability of the animals' movements were of less importance. To reduce fear of brown bear and wolf it might therefore be more effective to enable people to learn more about their own reactions rather than learning more about wolf or bear behavior. Stakeholders varied in terms of which perceptions were more strongly linked to the fear. In efficient management of large carnivores, the consequences for the cognitive vulnerability in different stakeholder groups should be considered.
|
|
| 10. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 11. |
- Larsson, Gerry, et al.
(författare)
-
A comprehensive system for leader evaluation and development
- 2003
-
Ingår i: Leadership & Organization Development Journal. - : Emerald. - 0143-7739 .- 1472-5347. ; 24:1, s. 16-25
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to describe the development of a theoretical model for leader evaluation and development, an instrument based on this model, and a strategy for large scale implementation in the Swedish armed forces. The model rests on an interactional person by situation paradigm. It emphasises “developmental leadership”, which is inspired by transformational and functionalistic leadership approaches. The developmental leadership questionnaire (DLQ) was operationalised from the model and refined through structural equation modelling. The model and the DLQ will be used for three purposes: yearly evaluation of all personnel in the Swedish armed forces; yearly planning dialogues between each employee and his or her nearest supervisor; and a tool for leadership training. The implementation strategy includes an initial course in developmental leadership for all colonels. This is followed by the selection and training of local trainers, who, in turn, initiate the comprehensive programme locally. The system should be fully implemented by 2005.
|
|
| 12. |
- Larsson, Gerry, et al.
(författare)
-
A Comprehensive system for leader evaluation and development
- 2002
-
Ingår i: The Leadership & Organization Development Journal. - 0143-7739. ; 24:1, s. 16-25
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to describe the development of a theoretical model for leader evaluation and development, an instrument based on this model, and a strategy for large scale implementation in the Swedish armed forces. The model rests on an interactional person by situation paradigm. It emphasises "developmental leadership", which is inspired by transformational and functionalistic leadership approaches. The developmental leadership questionnaire (DLQ) was operationalised from the model and refined through structural equation modelling. The model and the DLQ will be used for three purposes: yearly evaluation of all personnel in the Swedish armed forces; yearly planning dialogues between each employee and his or her nearest supervisor; and a tool for leadership training. The implementation strategy includes an initial course in developmental leadership for all colonels. This is followed by the selection and training of local trainers, who, in turn, initiate the comprehensive programme locally. The system should be fully implemented by 2005.
|
|
| 13. |
- Mattsson, Bengt, et al.
(författare)
-
Neural grafting to experimental neocortical infarcts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments
- 1997
-
Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 28:6, s. 1225-1232
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The purpose of this study was to evaluate whether grafting of fetal neocortical tissue 1 week after focal brain ischemia improved behavioral outcome and reduced secondary thalamic atrophy. METHODS: One week after distal ligation of the right middle cerebral artery in spontaneously hypertensive male rats, blocks of fetal neocortex (embryonic day 17) were homografted to rats housed in standard or enriched environments. Control infarcted nongrafted rats were housed in the enriched environment. Behavioral outcome was repeatedly tested until the rats were killed 20 weeks after the ligation. Ten days earlier, a mixture of 2% Fluoro-Gold and 10% biotinylated dextran amine was injected into the transplants for retrograde and anterograde tracing of graft-host connections. RESULTS: Grafted and nongrafted rats with enriched housing performed significantly better than grafted rats with standard housing on a rotating pole and a prehensile traction test. Grafted "enriched" rats were moreover significantly better than grafted "standard" rats and nongrafted enriched rats in a rotation test and a postural and locomotor tail position test. In the latter test, nongrafted enriched rats performed significantly better than grafted standard rats. The lesion-induced atrophy in posterior thalamus with its major sensorimotor cortex relay nuclei was significantly reduced in grafted enriched rats compared with nongrafted enriched rats. Afferent and efferent graft-host connections were identified in both grafted groups. Graft volumes did not differ. CONCLUSIONS: Neural grafting enhanced functional outcome and reduced thalamic atrophy only when combined with housing in enriched environments.
|
|
| 14. |
|
|
| 15. |
- Olofsson, Cecilia Kjellberg, et al.
(författare)
-
A national study of the outcome after treatment of critical aortic stenosis in the neonate.
- 2020
-
Ingår i: Cardiology in the young. - 1467-1107. ; 30:9, s. 1321-1327
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes short-term and long-term outcome after treatment of critical valvular aortic stenosis in neonates in a national cohort, with surgical valvotomy as first choice intervention.All neonates in Sweden treated for critical aortic stenosis between 1994 and 2016 were included. Patient files were analysed and cross-checked against the Swedish National Population Registry as of December 2017, giving complete survival data. Diagnosis was confirmed by reviewing echo studies. Critical aortic stenosis was defined as valvular stenosis with duct-dependent systemic circulation or depressed left ventricular function. Primary outcome was all-cause mortality and secondary outcomes were reintervention and aortic valve replacement.Sixty-one patients were identified (50 boys, 11 girls). Primary treatment was surgical valvotomy in 52 neonates and balloon valvotomy in 6. Median age at initial treatment was 5 days (0-26), and median follow-up time was 10.8 years (0.14-22.6). There was no 30-day mortality but four late deaths. Freedom from reintervention was 66%, 61%, 54%, 49%, and 46% at 1, 5, 10, 15, and 20 years, respectively. Median time to reintervention was 3.4 months (4 days to 17.3 years). Valve replacement was performed in 23 patients (38%).Surgical valvotomy is a safe and reliable treatment in these critically ill neonates, with no 30-day mortality and long-term survival of 93% in this national study. At 10 years of age, reintervention was performed in 54% and at end of follow-up 38% had had an aortic valve replacement.
|
|
| 16. |
- Olofsson, Cecilia Kjellberg, et al.
(författare)
-
Outcomes in neonatal critical and non-critical aortic stenosis: A retrospective cohort study
- 2023
-
Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 108:5, s. 398-404
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare long-term survival, reinterventions and risk factors using strict definitions of neonatal critical and non-critical valvular aortic stenosis (VAS). Design: A nationwide retrospective study using data from patient files, echocardiograms and the Swedish National Population Registry. Setting and patients: All neonates in Sweden treated for isolated VAS 1994-2018. We applied the following criteria for critical aortic stenosis: valvular stenosis with duct-dependent systemic circulation or depressed left ventricular function (fractional shortening ≤27%). Indication for treatment of non-critical VAS was Doppler mean gradient >50 mm Hg. Main outcome measures: Short-term and long-term survival, aortic valve reinterventions need of valve replacements, risk factors for reintervention and event-free survival. Results: We identified 65 patients with critical VAS and 42 with non-critical VAS. The majority of the neonates were managed by surgical valvotomy. Median follow-up time was 13.5 years, with no patients lost to follow-up. There was no 30-day mortality. Long-term transplant-free survival was 91% in the critical stenosis group and 98% in the non-critical stenosis group (p=0.134). Event-free survival was 40% versus 67% (p=0.002) in the respective groups. Median time from the initial treatment to reintervention was 3.6 months versus 3.9 years, respectively (p=0.008). Conclusions: Critical VAS patients had significantly higher need for reintervention during the first year of life, lower event-free survival and lower freedom from aortic valve replacement at age ≥18 years, compared with neonates with non-critical stenosis.
|
|
| 17. |
- Pätzold, Jens, et al.
(författare)
-
Exclusive measurements of the pp --> pp pi+pi- reaction
- 2002
-
Ingår i: Proc. 9th Int. Symp. on Meson-Nucleon Physics and the Structure of the Nucleon, MENU 2001, Washington D.C., USA, 2001., piN Newsletter. ; , s. 370-
-
Konferensbidrag (refereegranskat)
|
|
| 18. |
|
|
| 19. |
- Sorensen, Jens Christian, et al.
(författare)
-
Fetal neocortical tissue blocks implanted in brain infarcts of adult rats interconnect with the host brain
- 1996
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 138:2, s. 227-235
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to study if the connectivity of fetal neocortical tissue blocks placed in ischemic brain infarcts of adult rats would be enhanced in rats housed in an enriched environment. We also investigated whether the enriched housing conditions could enhance the postischemic and postgrafting functional outcome, in terms of motor behavior. This part of the study has been published recently. The middle cerebral artery was ligated on the right side in 37 inbred, adult male spontaneously hypertensive rats. The rats were placed at random either in an enriched environment (groups A and B) or in standard laboratory cages (group C). Three weeks after the artery occlusion, blocks of fetal sensorimotor cortex (embryonic day 17) were transplanted into the infarct cavity of rats from groups B and C. After 9 weeks all transplanted rats received an injection, into the graft, of a mixture containing the two tracers Fluoro-Gold and biotinylated Dextran amine. The transplants revealed a structured morphology with whorls and bands of cells reminiscent of normal neocortex. Tracing of efferent transplant to host fibers with biotinylated Dextran amine showed pronounced intrinsic transplant projections, as well as fibers, although significantly fewer, to the host ipsilateral sensorimotor cortex, striatum, and thalamus. Host to transplant projections were revealed by Fluoro-Gold-labeled cells found in the ipsilateral host sensorimotor cortex, the basal nucleus of Meynert, the thalamic ventrobasal, ventrolateral and posterior nuclei, and in the dorsal raphe nuclei. We conclude that fetal frontal neocortical block grafts placed in brain infarcts of adult rats develop a morphology reminiscent of normal neocortex and that both afferent and efferent neural connections, although sparse, are established with the host brain, whether the rats are reared under enriched housing conditions or not.
|
|
| 20. |
- Tran, Phan-Kiet, et al.
(författare)
-
Smart placement of a mediastinal drain in a neonate who requires a postoperative open sternum.
- 2014
-
Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 97:6, s. 2217-2218
-
Tidskriftsartikel (refereegranskat)abstract
- Crowding of the mediastinum after complex cardiac repair procedures in neonates and young children is a frequent problem. To create space, the sternal wound is kept open, commonly with a plastic stent, for later closure. Despite this maneuver, space is still an issue, and appropriate placement of the mediastinal drain can become a challenge. In this article we describe a simple and effective way to eliminate the problem. Holes are made in the sternal stent, and the drain is pulled through these holes. The drain is elevated away from the heart surface and does not contribute to the crowding.
|
|
| 21. |
- Winberg, Johanna, et al.
(författare)
-
No evidence for mosaic pathogenic copy number variations in cardiac tissue from patients with congenital heart malformations.
- 2015
-
Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 58:3, s. 129-133
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if pathogenic copy number variations (CNVs) are present in mosaic form in patients with congenital heart malformations. We have collected cardiac tissue and blood samples from 23 patients with congenital heart malformations that underwent cardiac surgery and screened for mosaic gene dose alterations restricted to cardiac tissue using array comparative genomic hybridization (array CGH). We did not find evidence of CNVs in mosaic form after array CGH analysis. Pathogenic CNVs that were present in both cardiac tissue and blood were detected in 2/23 patients (9%), and in addition we found several constitutional CNVs of unclear clinical significance. This is the first study investigating mosaicism for CNVs in heart tissue compared to peripheral blood and the results do not indicate that pathogenic mosaic copy number changes are common in patients with heart malformations. Importantly, in line with previous studies, our results show that constitutional pathogenic CNVs are important factors contributing to congenital heart malformations.
|
|
| 22. |
- Abghari, Shahrooz, et al.
(författare)
-
District Heating Substation Behaviour Modelling for Annotating the Performance
- 2020
-
Ingår i: Communications in Computer and Information Science. - Cham : Springer. - 9783030438869 ; , s. 3-11
-
Konferensbidrag (refereegranskat)abstract
- In this ongoing study, we propose a higher order data mining approach for modelling district heating (DH) substations’ behaviour and linking operational behaviour representative profiles with different performance indicators. We initially create substation’s operational behaviour models by extracting weekly patterns and clustering them into groups of similar patterns. The built models are further analyzed and integrated into an overall substation model by applying consensus clustering. The different operational behaviour profiles represented by the exemplars of the consensus clustering model are then linked to performance indicators. The labelled behaviour profiles are deployed over the whole heating season to derive diverse insights about the substation’s performance. The results show that the proposed method can be used for modelling, analyzing and understanding the deviating and sub-optimal DH substation’s behaviours. © 2020, Springer Nature Switzerland AG.
|
|
| 23. |
- Abugabbara, Marwan, et al.
(författare)
-
How to develop fifth-generation district heating and cooling in Sweden? : Application review and best practices proposed by middle agents
- 2023
-
Ingår i: Energy Reports. - : Elsevier Ltd. - 2352-4847. ; 9, s. 4971-4983
-
Tidskriftsartikel (refereegranskat)abstract
- Sweden has an ambitious plan to fully decarbonise district heating by 2030 and to contribute with negative emissions of greenhouse gases in 2050. The vagaries of the energy market associated with climate, political, and social changes entail cross-sectoral integration that can fulfill these national targets. Fifth-generation district heating and cooling (5GDHC) is a relatively new concept of district energy systems that features a simultaneous supply of heating and cooling using power-to-heat technologies. This paper presents best practices for developing 5GDHC systems in Sweden to reach a consensus view on these systems among all stakeholders. A mixed-method combining best practice and roadmapping workshops has been used to disseminate mixed knowledge and experience from middle agents representing industry professionals and practitioners. Four successful implementations of 5GDHC systems are demonstrated and the important learned lessons are shared. The best practices are outlined for system planning, system modeling and simulation, prevailing business models for energy communities, and system monitoring. A roadmap from the middle agents’ point of view is composed and can be utilised to establish industry standards and common regulatory frameworks. © 2023 The Author(s)
|
|
| 24. |
- Ahlström, Love, et al.
(författare)
-
Preoperative Coronary Anatomy Assessment with Echocardiography and Morbidity After Arterial Switch Operation of Transposition of the Great Arteries
- 2018
-
Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 39:8, s. 1620-1626
-
Tidskriftsartikel (refereegranskat)abstract
- In transposition of the great arteries (TGA), certain coronary patterns have been associated with major adverse events early after the arterial switch operation (ASO). We sought to determine the impact of preoperative echocardiographic (ECHO) diagnosis on the intra and postoperative morbidity. All patients with TGA born between June 2001 and June 2017 and who underwent ASO were reviewed. Data on presumed coronary anatomy (CA) preoperatively were obtained from the preoperative ECHO report. Intraoperative CA was categorized according to Yacoub classification. Major postoperative morbidity included at least one of the following: delayed sternal closure (DSC), prolonged (> 72 h) mechanical ventilation, reintubation, peritoneal dialysis (PD), ECMO, reoperation, and readmission within 30 days after surgery. 240 patients with median age of 5 days (range 1–614) and mean weight at surgery was 3.6 kg (1.8–8.4) were included. Preoperative ECHO assessment of CA was available in 228 patients. Intraoperatively, 181 patients (75%) were found to have type A, 25 patients had type B or C or intramural (B–C–IM; 10%), and 34 patients had type D or E (D–E; 14%). Patients with types B, C, and intramural coronary (B–C–IM) had increased risk for delayed sternum closure (9/25 vs. 20/181 in type A and 8/34 in type D–E; p = 0.04), peritoneal dialysis (4/25 vs. 8/181 and 1/34; p = 0.04), and ECMO (2/25 vs. 1/131 and 1/34; p = 0.02). Within the B–C–IM group, preoperative ECHO raised suspicion of type A in 13 patients (i.e., incorrect diagnosis, ID; 52%), whereas non-A CA was suspected in 12 patients (i.e., correct diagnosis, CD; 48%). With the exception of reoperation, which was seen only in the ID subgroup (4/12 vs. 0/10 in the CD subgroup; p = 0.04), the intraoperative (cardiopulmonary bypass time and cross-clamp time) and postoperative morbidity indices were comparable in both ID and CD subgroups (p > 0.1). Although there is a significant risk for early postoperative morbidity in TGA patients with single, interarterial, and intramural CA, there seems to be relatively limited influence of preoperative ECHO assessment of coronary anatomy on this morbidity burden.
|
|
| 25. |
- Ahlström, Love, et al.
(författare)
-
Surgical Age and Morbidity After Arterial Switch for Transposition of the Great Arteries
- 2019
-
Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 108:4, s. 1242-1247
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Transposition of the great arteries (TGA) is a complex congenital heart disease that requires early diagnosis as well as advanced surgical repair and postoperative support. We sought herein to study the impact of surgical timing on early postoperative morbidity.Methods: We reviewed all patients with TGA corrected at our institution via arterial switch operation (ASO) between June 2001 and June 2016. Major postoperative morbidity (MPM) and death within 30 days after ASO were documented. Patients with double outlet right ventricle, chromosome abnormalities and non-cardiac diseases were excluded. MPM was defined as presence of at least 1 of the following: delayed sternum closure, reoperation, prolonged mechanical ventilation, noninvasive ventilation after extubation, peritoneal dialysis, ECMO and readmission. Results: 241 patients were included, with medians for birth weight, gestational week and age at surgery of 3.5 kg, 39 weeks, and 5 days, respectively. MPM was encountered in 32.3% of patients. Prematurity (p=0.001) and need for aortic arch repair at the time of ASO (p=0.04) were associated with significant increase in MPM. Non-A coronary anatomy, associated ventricular septal defect requiring surgical closure and fetal diagnosis of TGA had no significant impact on MPM (p=0.35, 0.08 and 0.21, respectively). There was no significant difference in MPM between the surgical groups (p=0.49).Conclusions: Early complications after ASO do occur and are mostly associated with prematurity and need for aortic arch repair. Timing of surgical repair does not seem to influence the rate of these complications.
|
|
| 26. |
- Alenius Dahlqvist, Jenny, 1972-, et al.
(författare)
-
Pacemaker treatment after Fontan surgery-A Swedish national study
- 2019
-
Ingår i: Congenital Heart Disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-079X .- 1747-0803. ; 14:4, s. 582-589
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveFontan surgery is performed in children with univentricular heart defects. Previous data regarding permanent pacemaker implantation frequency and indications in Fontan patients are limited and conflicting. We examined the prevalence of and risk factors for pacemaker treatment in a consecutive national cohort of patients after Fontan surgery in Sweden. MethodsWe retrospectively reviewed all Swedish patients who underwent Fontan surgery from 1982 to 2017 (n=599). ResultsAfter a mean follow-up of 12.2years, 13% (78/599) of the patients with Fontan circulation had received pacemakers. Patients operated with the extracardiac conduit (EC) type of total cavopulmonary connection had a significantly lower prevalence of pacemaker implantation (6%) than patients with lateral tunnel (LT; 17%). Mortality did not differ between patients with (8%) and without pacemaker (5%). The most common pacemaker indication was sinus node dysfunction (SND) (64%). Pacemaker implantation due to SND was less common among patients with EC. Pacemaker implantation was significantly more common in patients with mitral atresia (MA; 44%), double outlet right ventricle (DORV; 24%) and double inlet left ventricle (DILV; 20%). In contrast, patients with pulmonary atresia with intact ventricular septum and hypoplastic left heart syndrome were significantly less likely to receive a pacemaker (3% and 6%, respectively). ConclusionsThirteen percent of Fontan patients received a permanent pacemaker, most frequently due to SND. EC was associated with a significantly lower prevalence of pacemaker than LT. Permanent pacemaker was more common in patients with MA, DORV, and DILV.
|
|
| 27. |
- Algander, Per, 1981-
(författare)
-
Harm, Benefit, and Non-Identity
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis in an invistigation into the concept of "harm" and its moral relevance. A common view is that an analysis of harm should include a counterfactual condition: an act harms a person iff it makes that person worse off. A common objection to the moral relevance of harm, thus understood, is the non-identity problem.This thesis criticises the counterfactual condition, argues for an alternative analysis and that harm plays two important normative roles.The main ground for rejecting the counterfactual condition is that it has unacceptable consequences in cases of overdetermination and pre-emption. Several modifications to the condition are considered but all fail to solve this problem.According to the alternative analysis to do harm is to perform an act which (1) is responsible for the obtaining of a state of affairs which (2) makes a person’s life go worse. It is argued that (1) should be understood in terms of counterfactual dependence. This claim is defended against counterexamples based on redundant causation. An analysis of (2) is also provided using the notion of a well-being function. It is argued that by introducing this notion it is possible to analyse contributive value without making use of counterfactual comparisons and to solve the non-identity problem.Regarding the normative importance of harm, a popular intuition is that there is an asymmetry in our obligations to future people: that a person would have a life worth living were she to exist is not a reason in favour of creating that person while that a person would have a life not worth living is a reason against creating that person. It is argued that the asymmetry can be classified as a moral option grounded in autonomy. Central to this defence is the suggestion that harm is relevant to understanding autonomy. Autonomy involves partly the freedom to pursue one’s own aims as long as one does no harm.
|
|
| 28. |
- Alkema, W. B. L., et al.
(författare)
-
MSCAN : identification of functional clusters of transcription factor binding sites
- 2004
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 32, s. W195-W198
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of functional transcription factor binding sites in genomic sequences is notoriously difficult. The critical problem is the low specificity of predictions, which directly reflects the low target specificity of DNA binding proteins. To overcome the noise produced in predictions of individual binding sites, a new generation of algorithms achieves better predictive specificity by focusing on locally dense clusters of binding sites. MSCAN is a leading method for binding site cluster detection that determines the significance of observed sites while correcting for local compositional bias of sequences. The algorithm is highly flexible, applying any set of input binding models to the analysis of a user-specified sequence. From the user's perspective, a key feature of the system is that no reference data sets of regulatory sequences from co-regulated genes are required to train the algorithm. The output from MSCAN consists of an ordered list of sequence segments that contain potential regulatory modules. We have chosen the features in MSCAN such that sequence and matrix retrieval is highly facilitated, resulting in a web server that is intuitive to use. MSCAN is available at http://mscan.cgb.ki.se/cgi-bin/MSCAN.
|
|
| 29. |
|
|
| 30. |
- Allwood, Jens, 1947, et al.
(författare)
-
On the need for an ethical understanding of health-care accountability
- 2015
-
Ingår i: Journal of Organisational Transformation and Social Change. - 1477-9633. ; 12:2, s. 121-137
-
Tidskriftsartikel (refereegranskat)abstract
- In Sweden, as in many other Western countries, public health care is challenged by increasing demands for care and continuing budget deficits. Person-centred care (PCC) has been introduced as a new strategy to ameliorate the perceived fragmentation in care and is expected to decrease treatment time, reduce the need for return visits, as well as increase patient satisfaction. However, the changing clinical practices necessary for the PCC approach are assumed to require new accountability practices. This article is primarily an attempt to provide a conceptual analysis of ethical accountability, i.e. a type of accountability that takes into account the human relational responsibility, partial incoherence, and power of reflection. On the grounds of this characterisation, the article aims to provide a basis, among other things, for a discussion of the possibilities of identifying and empirically studying the multimodal expressions in communication that are relevant for this type of accountability. After an initial discussion of the debate on the limits of viewing accountability as transparency, we then turn to our methodological approach and introduce a conceptual analysis of accountability. Next, we discuss some additional features of accountability. Finally, we discuss the possibilities of empirically studying the institutionalisation of ethically informed accountability within person-centred health care.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Andersen, Michael Styrk, et al.
(författare)
-
Aerodynamic stability of long span suspension bridges with low torsional natural frequencies
- 2016
-
Ingår i: Engineering structures. - : Elsevier. - 0141-0296 .- 1873-7323. ; 120, s. 82-91
-
Tidskriftsartikel (refereegranskat)abstract
- Classical flutter of suspended bridge decks can be avoided if the torsional frequencies are lower than the vertical. Wind tunnel tests of single boxes and twin box section models with torsional natural frequencies above and below the vertical frequency has been conducted. Flutter was avoided in all tests where the torsional frequency was lower than the vertical. But too low torsional stiffness caused large static displacements of the girder at medium–high wind speeds and steady state oscillations driven by a combination of torsional divergence and stalling behavior at the critical wind seed. In order to design aerodynamically stable suspension bridges with low torsional natural frequencies it is suggested to increase the mass moment of inertia and provide adequate torsional stiffness by the main cables spacing.
|
|
| 34. |
|
|
| 35. |
- Andersson, Anna, et al.
(författare)
-
Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
- 2005
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050
-
Tidskriftsartikel (refereegranskat)abstract
- Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
|
|
| 36. |
|
|
| 37. |
- Andersson, Jens, et al.
(författare)
-
Interactions between predator- and diet-induced phenotypic changes in body shape of crucian carp
- 2006
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 273:1585, s. 431-437
-
Tidskriftsartikel (refereegranskat)abstract
- Predator cues and diet, when studied separately, have been shown to affect body shape of organisms. Previous studies show that the morphological responses to predator absence/presence and diet may be similar, and hence could confound the interpretation of the causes of morphological differences found between groups of individuals. In this study, we simultaneously examined the effect of these two factors on body shape and performance in crucian carp in a laboratory experiment. Crucian carp (Carassius carassius) developed a shallow body shape when feeding on zooplankton prey and a deep body shape when feeding on benthic chironomids. In addition, the presence of chemical cues from a pike predator affected body shape, where a shallow body shape was developed in the absence of pike and a deep body shape was developed in the presence of pike. Foraging activity was low in the presence of pike cues and when chironomids were given as prey. Our results thereby suggest that the change in body shape could be indirectly mediated through differences in foraging activity. Finally, the induced body shape changes affected the foraging efficiency, where crucians raised on a zooplankton diet or in the absence of pike cues had a higher foraging success on zooplankton compared to crucian raised on a chironomid diet or in the presence of pike. These results suggest that body changes in response to predators can be associated with a cost, in terms of competition for resources.
|
|
| 38. |
- Andersson, Kent, 1967-, et al.
(författare)
-
Introduktion till Operationsanalys : En antologi med essäer av studerande i militärteknik 2011
- 2012
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- I ämnesplanen definieras militärteknik som ”den vetenskap som beskriver och förklarar hur tekniken inverkar på militär verksamhet på alla nivåer, strategisk, operativ och taktisk, samt hur officersprofessionen påverkar och påverkas av tekniken.”[1] En militärteknikers uppgift brukar, utgående från definitionen, uttryckas som att beskriva och förklara den militära nyttan med tekniken. För att kunna göra detta behövs verktyg. Och många av dem kommer från den vetenskapliga disciplinen Operationsanalys.Syftet med den här antologin är att introducera studerande i militärteknik på Försvarshögskolan till två av de mest refererade boktitlarna i operationsanalys – Methods for conducting military operational analysis editerad av Andrew G. Loerch och Larry B. Rainey samt Military Operations Research, quantitative decision making av N.K. Jaiswal.Kapitlen utgörs av essäer skrivna av studerande på den högre stabsofficersutbildningen med teknisk inriktning, som examinationsuppgift i en fördjupningskurs. Essäerna är till del referat av kapitel i de två böckerna ovan, men kryddade med exempel satta i svenskt sammanhang och med de studerandes egen värdering av metodernas användbarhet.[1]Försvarshögskolan, Ämnesplan militärteknik, 2007.
|
|
| 39. |
- Asenjo, Felipe A., et al.
(författare)
-
Semi-relativistic effects in spin-1/2 quantum plasmas
- 2012
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 14, s. 073042-
-
Tidskriftsartikel (refereegranskat)abstract
- Emerging possibilities for creating and studying novel plasma regimes, e. g. relativistic plasmas and dense systems, in a controlled laboratory environment also require new modeling tools for such systems. This motivates theoretical studies of the kinetic theory governing the dynamics of plasmas for which both relativistic and quantum effects occur simultaneously. Here, we investigate relativistic corrections to the Pauli Hamiltonian in the context of a scalar kinetic theory for spin-1/2 quantum plasmas. In particular, we formulate a quantum kinetic theory for the collective motion of electrons that takes into account effects such as spin-orbit coupling and Zitterbewegung. We discuss the implications and possible applications of our findings.
|
|
| 40. |
- Avdikos, Vasileios, et al.
(författare)
-
Outcomes following surgical repair of absent pulmonary valve syndrome : 30 years of experience from a Swedish tertiary referral centre
- 2022
-
Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 35:2
-
Tidskriftsartikel (refereegranskat)abstract
- Surgical approach with reduction pulmonary artery plasty and valved conduit in patients with respiratory compromise prior to repair is associated with excellent long-term survival at the cost of a higher reintervention rate. OBJECTIVES: Absent pulmonary valve syndrome is a rare congenital heart defect with pulmonary artery dilatation and secondary airway compression. Although preoperative respiratory support and early surgical repair with pulmonary arterioplasty are often required in patients with airway compromise, the need for extensive plasty in these patients and for plasty in general in those with no or mild respiratory issues remains debatable. METHODS: We performed a retrospective survey of patients with this diagnosis and repair from 1988 to 2018. RESULTS: Twenty patients were identified. The median age and weight at repair were 0.8 (0.1-2.4) years and 7.0 (2.5-13.8) kg and included a valved conduit in 17 (85%) patients and a transannular patch in 3 patients. Five (29%) patients were ventilator-dependent prior to repair at the age of 0.3 (0.1-0.4) years. Pulmonary arterioplasty was performed in 7 patients (35%), including all 5 with ventilator dependency and 2 with respiratory symptoms due to recurrent infections. Two patients (10%) with preoperative ventilator dependency underwent extensive intrahilar arterioplasty. Preoperative ventilator dependency was associated with earlier repair and reinterventions (P < 0.05). There were 3 late deaths among cases with repair after 2000 (n = 14), none with preoperative ventilator dependency. CONCLUSIONS: The long-term outcomes of patients with this rare defect are good, comparable to those of other previous studies. Reduction pulmonary arterioplasty, which in this study was used only in patients with respiratory distress and ventilator dependency, is associated with excellent survival. Reinterventions are common in these patients.
|
|
| 41. |
- Azhar, Salman, et al.
(författare)
-
Novel ABCA1 peptide agonists with antidiabetic action
- 2019
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 480, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice. CS6253 increased insulin secretion both under basal conditions and in response to high glucose stimulation in pancreatic INS-1 β-cells rendered leptin receptor deficient with specific siRNA. Additional in vitro cell studies suggest that the CS6253 agonist attenuates hepatic gluconeogenesis and glucose transport. It also potentiates insulin-stimulated glucose uptake and utilization. These observed anti-diabetic actions suggest additional benefits of the CS6253 and T6991-2 ABCA1 peptide agonists for cardiovascular disease beyond their direct anti-atherosclerosis properties previously described.
|
|
| 42. |
- Baresel, Christian, et al.
(författare)
-
Functionalized magnetic particles for water treatment
- 2019
-
Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 5:8
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we have taken the concept of water treatment by functionalized magnetic particles one step forward by integrating the technology into a complete proof of concept, which included the preparation of surface modified beads, their use as highly selective absorbents for heavy metals ions (Zinc, Nickel), and their performance in terms of magnetic separation. The separation characteristics were studied both through experiments and by simulations. The data gathered from these experimental works enabled the elaboration of various scenarios for Life Cycle Analysis (LCA). The LCA showed that the environmental impact of the system is highly dependent on the recovery rate of the magnetic particles. The absolute impact on climate change varied significantly among the scenarios studied and the recovery rates. The results support the hypothesis that chelation specificity, magnetic separation and bead recovery should be optimized to specific targets and applications.
|
|
| 43. |
- Begnini, Fabio, et al.
(författare)
-
Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction
- 2022
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:4, s. 3473-3517
-
Tidskriftsartikel (refereegranskat)abstract
- Upregulation of the transcription factor Nrf2 by inhibition of the interaction with its negative regulator Keap1 constitutes an opportunity for the treatment of disease caused by oxidative stress. We report a structurally unique series of nanomolar Keap1 inhibitors obtained from a natural product-derived macrocyclic lead. Initial exploration of the structure-derived macrocyclic lead. Initial exploration of the structure-activity relationship of the lead, followed by structure-guided optimization, resulted in a 100-fold improvement in inhibitory potency. The macrocyclic core of the nanomolar inhibitors positions three pharmacophore units for productive interactions with key residues of Keap1, including R415, R483, and Y572. Ligand optimization resulted in the displacement of a coordinated water molecule from the Keap1 binding site and a significantly altered thermodynamic profile. In addition, minor reorganizations of R415 and R483 were accompanied by major differences in affinity between ligands. This study therefore indicates the importance of accounting both for the hydration and flexibility of the Keap1 binding site when designing high-affinity ligands.
|
|
| 44. |
- Begnini, Fabio, et al.
(författare)
-
Structure-based optimization of a macrocyclic inhibitor of the Keap1-Nrf2 protein-protein interaction
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Activation of the transcription factor Nrf2 by inhibition of the interaction with its negative regulator Keap1 constitutes a potential opportunity for the treatment of oxidative stress related disease. Although highly potent inhibitors of the Keap1–Nrf2 protein-protein interaction (PPI) have been reported, these compounds are based on a few reoccurring scaffolds. Here, we report a novel, structurally unique series of double-digit nM Keap1 inhibitors obtained by optimization of a natural product-derived macrocyclic lead. Exploration of the structure-activity relationship, followed by structure-based design led to a 100-fold improvement in inhibitory potency compared to the starting point. The macrocyclic core positions the pharmacophores of the inhibitors suitably for productive interactions with key residues of Keap1, including R415 and R483; both of which contribute to the highly polar nature of the binding site for Nrf2. In addition, we discovered that minor, ligand-induced reorganizations of these two arginine residues are accompanied by major differences in binding affinity between compounds in the series.
|
|
| 45. |
- Bender, P., et al.
(författare)
-
Structural and magnetic properties of multi-core nanoparticles analysed using a generalised numerical inversion method
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- The structural and magnetic properties of magnetic multi-core particles were determined by numerical inversion of small angle scattering and isothermal magnetisation data. The investigated particles consist of iron oxide nanoparticle cores (9 nm) embedded in poly(styrene) spheres (160 nm). A thorough physical characterisation of the particles included transmission electron microscopy, X-ray diffraction and asymmetrical flow field-flow fractionation. Their structure was ultimately disclosed by an indirect Fourier transform of static light scattering, small angle X-ray scattering and small angle neutron scattering data of the colloidal dispersion. The extracted pair distance distribution functions clearly indicated that the cores were mostly accumulated in the outer surface layers of the poly(styrene) spheres. To investigate the magnetic properties, the isothermal magnetisation curves of the multicore particles (immobilised and dispersed in water) were analysed. The study stands out by applying the same numerical approach to extract the apparent moment distributions of the particles as for the indirect Fourier transform. It could be shown that the main peak of the apparent moment distributions correlated to the expected intrinsic moment distribution of the cores. Additional peaks were observed which signaled deviations of the isothermal magnetisation behavior from the non-interacting case, indicating weak dipolar interactions.
|
|
| 46. |
|
|
| 47. |
- Bengtsson, Ylva, et al.
(författare)
-
Ulriksdals slott under 350 år
- 1995
-
Rapport (populärvet., debatt m.m.)abstract
- Studierna har utgått från Ulriksdals slott, uppfört av Jacob De la Gardie för 350 år sedan. Som kungligt slott har Ulriksdal genomgått ombyggnader under 1600 - och 1700-talet, men präglas idag mest av Karl XVs omfattande omdaning på 1850-talet och Gustav VI Adolfs lika genomgripande förändringar på 1920-talet.Slottet har bjudit på rika studiemöjligheter av stilideal, planlösning, interiörgestaltning, snickerikultur och stormtekniska system från hela 350-årsperioden. Genom noggranna uppmätningar och inventeringar på plats kopplade till arkivstudier har slottets komplicerade förändringshistoria kunnat analyseras,
|
|
| 48. |
|
|
| 49. |
- Berling, Clas, et al.
(författare)
-
Deploying Goals and Measuring Efficiency in an Academic Organisation. A Pilot Study
- 2000
-
Ingår i: Proceedings of the 3rd International Conference on Building People and Organizational Excellence. ; , s. 342-346
-
Konferensbidrag (refereegranskat)abstract
- In many organizations it is considered of vital importance to translate its vision and strategy into objectives, to determine the best means of achieving these and to review the results – with participation from all members, from management to shop floor. The objective of this study was to make a first test of a method that could be applied for verbalizing and communicating a common vision and identify critical objectives concentrating on nonfinancial measures in an academic research organization. Being a rather heterogeneous multidisciplinary centre the focus was on critical issues, which could promote organizational alignment. Three different systems that could be applicable were identified: Balanced Scorecard, hoshin kanri and ProMES. A design team was formed to formulate objectives and measurements. They found that it was a far from easy task to identify relevant objectives for the organization and especially to establish their different importance. The discussions led to a more common view and agreement about issues that had to be given more attention.
|
|
| 50. |
- Birch, Jens, et al.
(författare)
-
Recent advances in ion-assisted growth of Cr/Sc multilayer X-ray mirrors for the water window
- 2002
-
Ingår i: Vacuum. - 0042-207X .- 1879-2715. ; 68:3, s. 275-282
-
Tidskriftsartikel (refereegranskat)abstract
- Cr/Sc multilayer X-ray mirrors intended for normal incidence reflection in the water window wavelength range, lambda=[2.4-4.4 nm], have been grown by ion-assisted sputter deposition and characterized using soft and hard X-ray reflectivity. By extracting low-energy ions, with energies, E-ion, ranging from 9 to 113 eV and with ion-to-metal flux ratios, Phi, between 0.76 and 23.1, from the sputtering plasma to the growing film, the nano-structure of the multilayer interfaces could be modified. A significantly increased soft X-ray reflectivity, using lambda = 3.374 nm, for Cr/Sc multilayers with layer thicknesses in the range 0.4-2.8 nm, was obtained when high ion-to-metal flux ratios, Phi(Cr) = 7.1 and Phi(Sc) = 23.1, and low energy ions, E-ion = 9eV, were used. An experimental reflectivity of 5.5% was obtained at 76degrees for a multilayer with 400 bi-layers. Simulations of the reflectivity data showed that the interface widths are < 0.425 nm. It could be concluded that roughness of low spatial frequency is reduced at lower ion energies than the high spatial frequency which was eliminated at the expense of intermixing at the interfaces at higher ion energies. The predicted performance of normal incidence multilayer mirrors grown at optimum conditions and designed for lambda = 3.374 and 3.115 nm indicates possible reflectivities of 6.5% and 14%, respectively.
|
|
