| 1. |
- Bell, Brian, et al.
(författare)
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Sustainable Bridges – Past and Future. Reflections on a European Project 2003 – 2007
- 2023
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Ingår i: IABSE Congress 2023 New Delhi, Engineering for Sustainable Development. - : International Association for Bridge and Structural Engineering. ; , s. 690-698
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Konferensbidrag (refereegranskat)abstract
- Twenty years ago, in 2003, a European project was started to increase the sustainability of existing railway bridges. This paper summarises what was achieved and looks ahead. Nine Working Packages were organized: (1) Background material; (2) Guidance by stakeholders; (3) Condition Assessment and Inspection Guidelines; (4) Loads, Capacity and Resistance Guidelines; (5) Monitoring Guidelines; (6) Repair and Strengthening Guidelines; (7) Demonstration with Field testing of Bridges; (8) Demonstration on Monitoring on Bridges; and (9) Training and Dissemination.Some of the main results (from 4 Guidelines and 47 Background documents) are highlighted and some experiences, conclusions and thoughts about the future are given. Hidden strengths and weaknesses are discussed, analyses and codes for assessment can be improved, new monitoring and strengthening methods are available and life length can be prolonged.
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| 2. |
- Bernander, Stig, et al.
(författare)
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Downhill progressive landslides in long natural slopes: triggering agents and landslide phases modeled with a finite difference method
- 2016
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Ingår i: Canadian geotechnical journal (Print). - : Canadian Science Publishing. - 0008-3674 .- 1208-6010. ; 53:10, s. 1565-1582
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Tidskriftsartikel (refereegranskat)abstract
- A large landslide in Tuve (Gothenburg, Sweden 1977) initiated the development of a model for slope stability analysis taking the deformation-softening of soft sensitive clays into consideration. The model studies triggering agents and five phases in progressive slope failure are identified: (1) in-situ, (2) disturbance, (3) unstable ‘dynamic’, (4) transitory (or permanent) equilibrium, and (5) ‘global’ failure. The clay resistance in these phases may differ widely; mostly due to different rates of loading. Two time dependent failure criteria are defined: (i) the triggering load condition in the disturbance Phase (2), and (ii) the transitory equilibrium in Phase (4), indicating whether minor downhill displacements or a veritable landslide catastrophe will occur. The analysis explains why downhill landslides tend to spread over vast areas of almost horizontal ground further down-slope. The model has been applied to landslides in Scandinavia and Canada. Three case studies are briefly discussed. The model is a finite difference approach, where local downhill deformations caused by normal forces is maintained compatible with deviatory shear deformations above the potential (or the established) failure surface. Software and an easy-to-use spreadsheet are introduced as well as recent developments. See also Video Abstract.
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| 3. |
- Cesta, Carolyn E., et al.
(författare)
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A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization : influence on embryo quality and clinical pregnancy rate
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 97:3, s. 258-268
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWomen undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes.Material and methodsA prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. ResultsUltrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively.ConclusionsPerceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.
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| 4. |
- Dalenbäck, Jan-Olof, 1954, et al.
(författare)
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Ställ tekniska egenskapskrav och använd deklarationerna
- 2014
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Ingår i: Energi & Miljö. - 1101-0568. ; 2014:4, s. 40-41
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ta bort energikraven i BBR och ersätt dem med ändamålsenliga egenskaps¬krav. Gör sedan energideklarationerna värda namnet genom att inkludera hushålls- och verk¬sam¬hets¬el så att de kan användas för att följa upp energi¬användningen. I anslutning till Boverkets regeringsuppdrag (N2014/75/E) att definiera nya energihus¬håll¬ningskrav, finns det all anledning att diskutera om vi är på rätt väg med de krav på bygg¬naders energi¬prestanda som ställs i Boverkets Byggregler (BBR). Speciellt om dess uppfyllelse ska vara juridiskt bindande.
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| 5. |
- Eldh, Maria, 1980, et al.
(författare)
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MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
- 2014
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Ingår i: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
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| 6. |
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| 7. |
- Iliadou, Anastasia N., et al.
(författare)
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The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study
- 2019
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.Participants: Recruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.Findings to date: Self-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.Future plans: Through the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart
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| 8. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 9. |
- Karlsson, Fredrik, 1975-, et al.
(författare)
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Articulatory closure proficiency in Parkinson's disease patients following deep brain stimulation of the subthalamic nucleus and caudal zona incerta.
- 2014
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Ingår i: Journal of Speech, Language and Hearing Research. - 1092-4388 .- 1558-9102. ; 57, s. 1178-1190
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThe present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on Parkinson's disease patients' proficiency in achieving oral closure and release during plosive production. METHODS Nineteen patients were evaluated preoperatively and 12 months after DBS surgery. Nine patients were implanted in the STN, seven bilaterally and two unilaterally (left). Ten were bilaterally implanted in the cZi. Postoperative examinations were made off and on stimulation. All patients received simultaneous L-dopa treatment in all conditions. For a series of plosives extracted from a reading passage, absolute and relative measures of duration of frication and amplitude of plosive release were compared between conditions within each treatment group. RESULTS Relative duration of frication increased in voiceless plosives in the on stimulation condition in cZi patients. Similar trends were observed across the data set. Duration of pre-release frication and the release peak prominence increased in voiceless plosives on stimulation for both groups. CONCLUSIONS The increased release prominence suggests that patients achieved a stronger closure gesture due to DBS, but that the increased energy available resulted in increased frication.
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| 10. |
- Karlsson, Fredrik, 1975-, et al.
(författare)
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Control of phonatory onset and offset in Parkinson patients following deep brain stimulation of the subthalamic nucleus and caudal Zona Incerta
- 2012
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:7, s. 824-827
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Tidskriftsartikel (refereegranskat)abstract
- Laryngeal hypokinesia is a common symptom in Parkinson’s disease (PD) that affects quality of life. Deep brain stimulation (DBS) is well recognized as a complementary method for treatment of motor symptoms in PD but the outcomes on patients’ control over phonatory alternation have yet not been clearly elucidated. The present study examined the effect of subthalamic nucleus STN-DBS (n=8, aged 51-72 yrs; median=63 yrs) and caudal Zona incerta cZi-DBS (n=8,aged 49-71 yrs; median=61 yrs) on control of onset and offset of phonation in connected speech. The patients were evaluated in a preoperatively (Med ON, 1.5 times the ordinary Levodopa dose) and 12 months postoperatively (Med ON, ordinary Levodopa dose). The results provided evidence of a progressive reduction in the ability to manifest alternations between voicing and voiceless states in a reading task. Mean proportion produced with inappropriate voicing increased from 47.6% to 55.3% and from 62.9% to 68.6% of the total duration for the two groups of patients between Pre-op and Post-op, Stim OFF evaluations. The medial and final parts of the fricative were more affected than the initial part, indicating an increased voicing lead into the following vowel. We propose that this reduction in phonatory control is be due to either progression of the disease, an effect of reduced Levodopa dosage or a microlesional effect. Patients’ proficiency in alternating between voiced and voiceless states in connected speech remained unaffected by both STN-DBS and cZi-DBS.
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| 11. |
- Karlsson, Fredrik, 1975-, et al.
(författare)
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Pitch variability in patients with Parkinson’s disease : effects of deep brain stimulation of caudal zona incerta and subthalamic nucleus
- 2013
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Ingår i: Journal of Speech, Language and Hearing Research. - : American Speech-Language-Hearing Association. - 1092-4388 .- 1558-9102. ; 56:1, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- Objective The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of con- nected speech in patients with Parkinson’s disease (PD).Methods Sixteen patients were evaluated preoperatively and 12 months after DBS surgery. Eight pa- tients were implanted in the STN (aged 51-72 yrs; xC=63 yrs). Six received bilateral implanta- tion and two unilateral (left) implantation. Eight patients were bilaterally implanted in the cZi (aged 49-71 yrs; xC=60.8 yrs). Preoperative assessments were made after an L-Dopa challenge (approximately 1.5 times the ordinary dose). All postoperative examinations were made off and on stimulation, with a clinically optimized dose of L-dopa. Measurements of pitch range and var- iability were obtained from each utterance in a recorded read speech passage.Results Pitch range and coefficient of variation showed an increase in patients under STN-DBS. Patients under cZi-DBS showed no significant effects of treatment on investigated pitch properties.Conclusions STN-DBS was shown to increase pitch variation and range. The results provided no evidence of cZi-DBS having a beneficial effect on PD patients’ pitch variability.
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| 12. |
- Karlström, Per-Olof, et al.
(författare)
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Does ovarian stimulation regimen affect IVF outcome? : a two-centre, real-world retrospective study using predominantly cleavage-stage, single embryo transfer
- 2018
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Ingår i: Reproductive BioMedicine Online. - : ELSEVIER SCI LTD. - 1472-6483 .- 1472-6491. ; 36:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- In this study, ovarian stimulation using highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) for IVF were compared in two large assisted reproduction technique centres in Sweden. A total of 5902 women underwent 9631 oocyte retrievals leading to 8818 embryo transfers (7720 on day 2): single embryo transfers (74.2%); birth rate per embryo transfer (27.7%); multiple birth rate (5.0%); incidence of severe ovarian hyperstimulation syndrome (0.71%). Compared with ovarian stimulation with rFSH, women who received HP-HMG were older, had higher dosages of gonadotrophins administered, fewer oocytes retrieved and more embryos transferred. After multivariate analysis controlling for age and generalized estimating equation model, no differences were found in delivery outcomes per embryo transfers between HP-HMG and rFSH, independent of gonadotrophin releasing hormone analogue (GnRH) used. Logit curves for live birth rate suggested differences for various subgroups, most prominently for women with high oocyte yield or when high total doses were used. Differences were not significant, perhaps owing to skewed distributions of the FSH compounds versus age and other covariates. These 'real-life patients' had no differences in live birth rate between HP-HMG and rFSH overall or in subgroups of age, embryo score, ovarian sensitivity or use of GnRH analogue regimen.
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| 13. |
- Kraus, Stefan, et al.
(författare)
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Planet Formation Imager (PFI) : Science vision and key requirements
- 2016
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Ingår i: Optical and Infrared Interferometry and Imaging V. - : SPIE. - 9781510601932 ; 9907
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Konferensbidrag (refereegranskat)abstract
- The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.
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| 14. |
- Kulneff, Linda, et al.
(författare)
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Deep brain stimulation : effects on swallowing function in Parkinson's disease
- 2013
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Ingår i: Acta Neurologica Scandinavica. - Hoboken : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 127:5, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In patients with Parkinson’s disease (PD), deep brainstimulation of the subthalamic nucleus (STN DBS) is well recognizedin improving limb function, but the outcome on swallowing functionhas rarely been studied. The aim of this work was to evaluate theeffect of STN DBS on pharyngeal swallowing function in patientswith PD using self-estimation and fiberoptic endoscopic evaluation ofswallowing.Methods: Eleven patients (aged 41–72, median 61 years)were evaluated preoperatively and at 6 and 12 months after STN DBSsurgery. All patients were evaluated with self-estimation on a visualanalogue scale, and eight of them with a fiberoptic endoscopicexamination with a predefined swallowing protocol includingRosenbek’s Penetration-Aspiration Scale, Secretion Severity Scale,preswallow spillage, pharyngeal residue, and pharyngeal clearance.Results: The self-assessments of swallowing function revealed asubjective improvement with STN DBS stimulation, whereas the datafrom the swallowing protocol did not show any significant effect ofthe STN DBS treatment itself. The prevalence of aspiration was notaffected by the surgery.Conclusions: The results show thatswallowing function was not negatively affected by STN DBS and therisk of aspiration did not increase. Self-estimation of swallowingfunction showed a subjective improvement due to stimulation.
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| 15. |
- Lind, Tekla, et al.
(författare)
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Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy : results of a multicentre cohort study
- 2018
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 33:2, s. 238-247
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Tidskriftsartikel (refereegranskat)abstract
- Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linn, Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linkoping University Hospital (D) and A-rebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. MAIN RESULTS AND THE ROLE OF CHANCE: The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P =< 0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i. e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. WIDER IMPLICATIONS OF THE FINDINGS: To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.
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| 16. |
- Lindén, Daniel, 1971, et al.
(författare)
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Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48.
- 2002
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 277:25, s. 23044-53
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Tidskriftsartikel (refereegranskat)abstract
- The peroxisome proliferator-activated receptor (PPAR) alpha agonist WY 14,643 increased the secretion of apolipoprotein (apo) B-100, but not that of apoB-48, and decreased triglyceride biosynthesis and secretion from primary rat hepatocytes. These effects resulted in decreased secretion of apoB-100-very low density lipoprotein (VLDL) and an increased secretion of apoB-100 on low density lipoproteins/intermediate density lipoproteins. ApoB-48-VLDL was also replaced by more dense particles. The proteasomal inhibitor lactacystin did not influence the recovery of apoB-100 or apoB-48 in primary rat hepatocytes, indicating that co-translational (proteasomal) degradation is of less importance in these cells. Treatment with WY 14,643 made the recovery of apoB-100 sensitive to lactacystin, most likely reflecting the decreased biosynthesis of triglycerides. The PPAR alpha agonist induced a significant increase in the accumulation of pulse-labeled apoB-100 even after a short pulse (2-5 min). There was also an increase in apoB-100 nascent polypeptides, indicating that the co-translational degradation of apoB-100 was inhibited. However, a minor influence on an early posttranslation degradation cannot be excluded. This decreased co-translational degradation of apoB-100 explained the increased secretion of the protein. The levels of apoB-48 remained unchanged during these pulse-chase experiments, and albumin production was not affected, indicating a specific effect of PPAR alpha agonists on the co-translational degradation of apoB-100. These findings explain the difference in the rate of secretion of the two apoB proteins seen after PPAR alpha activation. PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP). Increased expression of LFABP by transfection of McA-RH7777 cells increased the secretion of apoB-100, decreased triglyceride biosynthesis and secretion, and increased PPAR alpha mRNA levels. These findings suggest that PPAR alpha and LFABP could interact to amplify the effect of endogenous PPAR alpha agonists on the assembly of VLDL.
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| 17. |
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| 18. |
- Louise, Johansson, et al.
(författare)
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Word-level intelligibility after caudal zona incerta stimulation for Parkinson’s disease
- 2014
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 130:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objectives – To investigate the effect of caudal zona incerta-deep brain stimulation (cZi-DBS) on word-level speech intelligibility in patients with Parkinson’s disease, under both an optimal listening condition and a simulated more naturalistic listening condition.Materials and methods – Spoken single words were extracted from read samples collected from 10 bilaterally implanted patients with PD pre- and post-cZi-DBS. Intelligibility was assessed through a transcription task performed by 32 naive listeners under two listening conditions: (i) with low-amplitude conversational speech added as background and (ii) with no added background noise. The listeners′ responses were scored in terms of agreement with the intended words.Results – Post-operatively, the total intelligibility score was significantly lower when cZi stimulation was switched on compared with off, for both listening conditions (with and without added background noise). Intelligibility was also significantly lower on stimulation compared with preoperative recordings, but only when assessed in the listening condition without background noise. The listening condition with added background noise resulted in significantly lower intelligibility scores compared with the no added noise condition for all stimulation conditions.Conclusions – The results of this study indicate that cZi-DBS in patients with PD can be detrimental to word-level speech intelligibility.
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| 19. |
- Lundgren, Sofie, et al.
(författare)
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Deep brain stimulation of caudal zona incerta and subthalamic nucleus in patients with Parkinson’s disease : effects on voice intensity
- 2011
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Ingår i: Parkinson's Disease. - : Hindawi Publishing Corporation. - 2090-8083 .- 2042-0080. ; 2011, s. 658956-
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Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson’s disease (PD) affects speech in small, inconsistent ways. However, voice intensity generally increases. Recently the caudal zona inserta (cZi) has been investigated as an alternate target in DBS treatment of PD. The effects of cZi-DBS on voice intensity have not yet been investigated. The aim of this study was to compare the voice intensity effects of cZi-DBS and STN-DBS in PD patients. Voice intensity during reading and intensity decay during rapid syllable repetition were measured for eight STN-DBS and eight cZi-DBS patients in a pre-surgical baseline and then on- and off-stimulation 12 months after surgery. Voice intensity on-stimulation was larger than off-stimulation for the STN-DBS patients, but smaller for the cZi-DBS patients. There were no significant changes in intensity decay. The results suggest that cZi and STN are involved differently in neuromuscular control of the speech respiratory subsystem.
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| 20. |
- Nord, Helena, et al.
(författare)
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Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array
- 2009
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 11:6, s. 803-818
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.
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| 21. |
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| 22. |
- Olofsson, Ingvar, 1943, et al.
(författare)
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Sustainable Bridges: Tillämpning av erfarenheter från ett EU-projekt, slutrapport
- 2008
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the project was to systematically collect and analyse knowledge about the weaknesses and identified problems of the present European stock of railway bridges. The intention was to further analyse, develop and use this knowledge as a basis for improved design and construction methods of new bridges in Sweden, railway bridges as well asroad bridges.Basic background data is collected within the European project “Sustainable Bridges”, funded by the European Commission within its sixth framework programme, where the project members are actively participating in areas of strategic importance. Background data regarding the Swedish bridges is collected also through the recently launched Swedish bridge management system BaTMan, which is developed, owned and managed by the Swedish Road Administration and The Swedish Railway Authorities. The system is not a final system and some suggestions for improvement are presented.The results of the present project (enhanced methods for design and construction, improved detailing, proposals for amendments to standards etc) may be directly applied by contractors and design consultants and will be beneficial to the end users of the products, i.e. the owners of the bridges. The activities within “Sustainable Bridges” were started 1st of December 2003, with a superficial identification of “lack of knowledge”, as defined by the European railwayowners. A mapping of the European bridge demography was carried out and reported together with a specification of the most frequent problems of the existing bridges. Development work for enhanced assessment methods and improved methods for inspection and monitoring of the bridges followed. In the final phases of “Sustainable Bridges” the activities were concentrated on the identified problem areas and the degree of detailing was at the same time increased.The identified problem areas, as specified by the European railway owners, appear to be very similar to the needs of the Swedish bridge owners in spite of the fact that the studied bridges are geographically distributed over all Europe and its major climate zones. The same conclusion is valid for the defined improvement areas. The results achieved within “Sustainable Bridges” are therefore highly relevant for further development and application also to Swedish bridges and to the design and construction of new Swedish bridges.
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| 23. |
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| 24. |
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| 25. |
- Roy, Alan, et al.
(författare)
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VLBI at APEX: First Fringes
- 2012
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Ingår i: Proceedings of Science. - 1824-8039. ; 2012-October
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Konferensbidrag (refereegranskat)
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| 26. |
- Rönnberg, Sarah, et al.
(författare)
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On waveform distortion in the frequency range of 2 kHz–150 kHz—Review and research challenges
- 2017
-
Ingår i: Electric Power Systems Research. - : Elsevier BV. - 0378-7796 .- 1873-2046. ; 150, s. 1-10
-
Forskningsöversikt (refereegranskat)abstract
- The frequency range between 2 and 150 kHz has recently gained significant attention, triggered by standardization needs and increased emission in this wide frequency range. This paper gives an overview of the state-of-the-art concerning these so-called supraharmonics, and noticeably indicates the research challenges associated with waveform distortion in this frequency range, with emphasis on the following aspects: emission; propagation; interference; measurements; standardization; modelling and simulation.
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| 27. |
- Schumacher, Sebastian, et al.
(författare)
-
Communication Strategies
- 2010
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The goal of InPro is to transform the early design phase (ED) in construction by the developmentof an open information environment (OIE) for knowledge-based collaborative processes throughout the lifecycle of a building (LC), assuming the ED phase the cooperationfrom its start to its end of many actors with a common goal.The aim of Work Package 1 is to analyse thoroughly the traditional ways of working andtheir cultural, technical and economic reasons. This way we gather clues and means tochange attitudes and raise the stakeholder’s awareness for a need of change. The RTD work results in new customer-centred business concepts and key performance indicatorsthat allow companies and managers to monitor development and change.The aim of D11 “Communication strategies” (T1.4 "Strategies for take-up”) is to developstrategies for the quick take-up of an open and collaborative information environmentwith its model-based processes throughout the European construction sector. Main focusof this task is to influence the human behaviour and bias all stakeholders in a positiveway towards model-based working. This includes the development of use cases for winwin situations for distributed business processes and building project realisation in cooperation.This is developed into the “To-Be"-scenario for model-based working, includingjob descriptions, overview of technical infrastructure, and strategies for implementationand training.This deliverable is concerned with identifying what and which roles are those that need tobe changed or motivated to support the change in order to move towards a more desirablestate and improve organisational effectiveness. The first part of this document describesconcepts for the take-up necessary strategies, examining change. Change shouldhappen in three levels: project, company and industry level. Roles and responsibilitiesare described as they are in the present (the so called “As-Is” situation) as well as in thefuture InPro environment (the so called “To-Be” situation). The second part presents theresults which stakeholder can be an initiator or a driver of the change from demonstrationsof KPs and from the viewpoint of client. At the end of the second part, strategies toimplement in a short-term are determined.The findings of D11 “Communication strategies” consist of:Changes need to be implemented starting at project level and continued byspreading to company and industry levelMain changes required at project level: technology, staff and training, a commitmentamong project team members to collaboration Main changes required at company level: staffing needs, project organisationand company wide information use contained in the building model Main changes required at industry level: establishment of European boundaryconditions to an Open Information Environment (OIE) work The main affected roles are: client, project manager, architect and contractor New roles are: model manager and main actor Main beneficiaries of change from KPs demonstrations and several studies viewpoint input are: client, designers and contractorsMain initiators of change from client viewpoint input are: client and designers Main drivers of change from KPs demonstrations and client viewpoint input are: client, managers and consultants
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| 28. |
- Sundstedt, Stina, 1988-, et al.
(författare)
-
Swallowing function in Parkinson’s patients following Zona Incerta deep brain stimulation
- 2012
-
Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 126:5, s. 350-356
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The purpose of the present study was to examine if there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson’s patients (PD). There are no former reports on swallowing and cZI DBS.Methods Eight patients (aged 49 to 71 years; median 62) were evaluated pre- and postoperatively, at six and 12 months after DBS surgery. Evaluation tools were Fiberoptic Endoscopic Evaluation of Swallowing examinations and patients’ self-assessments of the swallowing function including a visual analogue scale and quality of life related questions. The swallowing protocol included Rosenbeck’s Penetration-Aspiration Scale, Secretion Severity Scale and parameters for pre-swallow spillage, pharyngeal residue and pharyngeal clearance.Results There was no clear-cut effect of neurostimulation postoperatively at six and 12 months on any of the swallowing parameters except for pre-swallow spillage which was slightly worsened in the stimulation on condition 12m postoperatively. The answers to the self assessment questions did not vary significantly.Conclusions The effect of the stimulation on swallowing function varied among individuals but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.
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| 29. |
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| 30. |
- Tobi, Elmar W., et al.
(författare)
-
DNA methylation differences at birth after conception through ART
- 2021
-
Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 36:1, s. 248-259
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI?SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI.WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed.STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes.PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests.MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, P-FDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences.LIMITATIONS, REASONS FOR CAUTION: We measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study.WIDER IMPLICATIONS OF THE FINDINGS: We find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI.
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| 31. |
- Wagner, J., et al.
(författare)
-
First 230? : GHz VLBI fringes on 3C 279 using the APEX Telescope (Research Note)
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 581
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We report about a 230? GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). Methods. We installed VLBI equipment and measured the APEX station position to 1? cm accuracy (1σ). We then observed 3C 279 on 2012 May 7 in a 5? h 230? GHz VLBI track with baseline lengths of 2800? Mλ to 7200? Mλ and a finest fringe spacing of 28.6? μas. Results. Fringes were detected on all baselines with signal-to-noise ratios of 12 to 55 in 420? s. The correlated flux density on the longest baseline was ∼0.3? Jy beam-1, out of a total flux density of 19.8? Jy. Visibility data suggest an emission region ≤ 38? μas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 1010? K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ∼ 38? μas. Conclusions. With APEX the angular resolution of 230? GHz VLBI improves to 28.6? μas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40? μas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.
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| 32. |
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| 33. |
- Adamiak, Beata, et al.
(författare)
-
Human antibodies to herpes simplex virus type 1 glycoprotein C are neutralizing and target the heparan sulfate-binding domain
- 2010
-
Ingår i: Virology. - : Elsevier BV. - 0042-6822. ; 400:2, s. 197-206
-
Tidskriftsartikel (refereegranskat)abstract
- Human antibodies specific for glycoprotein C (gC1) of herpes simplex virus type 1 (HSV-1) neutralized the virus infectivity and efficiently inhibited attachment of HSV-1 to human HaCaT keratinocytes and to murine mutant L cells expressing either heparan sulfate or chondroitin sulfate at the cell surface. Similar activities were observed with anti-gC1 monoclonal antibody B1C1. In addition to HaCaT and L cells, B1C1 antibody neutralized HSV-1 infectivity in simian GMK AH1 cells mildly pre-treated with heparinase III. Human anti-gC1 antibodies efficiently competed with the binding of gC1 to B1C1 antibody whose epitope overlaps a part of the attachment domain of gC1. Human anti-gC1 and B1C1 antibodies extended survival time of mice experimentally infected with HSV-1. We conclude that in HaCaT cells and in cell systems showing restricted expression of glycosaminoglycans, human and some monoclonal anti-gC1 antibodies can target the cell-binding domain of this protein and neutralize viral infectivity.
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| 34. |
- Adiels, Martin, 1976, et al.
(författare)
-
A brief review of lipoprotein metabolism
- 2009
-
Ingår i: Evidence-Based Management of Lipid Disorders. - : Tfm Publishing. - 1903378710
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 35. |
- Adiels, Martin, 1976, et al.
(författare)
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A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions
- 2005
-
Ingår i: J Lipid Res. - 0022-2275 .- 1539-7262. ; 46:1, s. 58-67
-
Tidskriftsartikel (refereegranskat)abstract
- The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.
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| 36. |
- Adiels, Martin, 1976, et al.
(författare)
-
Acute suppression of VLDL(1) secretion rate by insulin is associated with hepatic fat content and insulin resistance
- 2007
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:11, s. 2356-2365
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.
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| 37. |
- Adiels, Martin, 1976, et al.
(författare)
-
Diabetic dyslipidaemia
- 2006
-
Ingår i: Curr Opin Lipidol. - 0957-9672 .- 1473-6535. ; 17:3, s. 238-46
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Diabetic dyslipidaemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The increase of large type 1 very low density lipoprotein particles in type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense low-density lipoprotein and small dense high-density lipoprotein particles. Thus, it is of great importance to elucidate the mechanisms behind the overproduction of large very low density lipoprotein particles in diabetic dyslipidaemia. This review discusses the pathophysiology of very low density lipoprotein metabolism in type 2 diabetes and recent concepts of lipid management of diabetic dyslipidaemia. RECENT FINDINGS: Results indicate that triglyceride and apolipoprotein B production in types 1 and 2 very low density lipoprotein are significantly correlated, suggesting a coupling of the two processes governing the metabolism of these lipoprotein subpopulations. Insulin resistance, hyperglycaemia, and liver fat were associated with excess hepatic production of type 1 but not type 2 very low density lipoprotein particles. These data provide support for the independent regulation of types 1 and 2 very low density lipoprotein apolipoprotein B production. SUMMARY: Recent data suggest that the assembly of very low density lipoprotein is fundamentally altered in type 2 diabetes, explaining the overproduction of large type 1 very low density lipoprotein as well as the inability of insulin to suppress production of type 1 very low density lipoprotein in type 2 diabetes. Future discoveries hopefully will delineate the regulatory steps to allow more targeted treatment of diabetic dyslipidaemia.
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| 38. |
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| 39. |
- Adiels, Martin, 1976, et al.
(författare)
-
Overproduction of large VLDL particles is driven by increased liver fat content in man
- 2006
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:4, s. 755-65
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. METHODS: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
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| 40. |
- Adiels, Martin, 1976, et al.
(författare)
-
Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.
- 2008
-
Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636 .- 1079-5642. ; 28:7, s. 1225-36
-
Forskningsöversikt (refereegranskat)abstract
- Insulin resistance is a key feature of the metabolic syndrome and often progresses to type 2 diabetes. Both insulin resistance and type 2 diabetes are characterized by dyslipidemia, which is an important and common risk factor for cardiovascular disease. Diabetic dyslipidemia is a cluster of potentially atherogenic lipid and lipoprotein abnormalities that are metabolically interrelated. Recent evidence suggests that a fundamental defect is an overproduction of large very low-density lipoprotein (VLDL) particles, which initiates a sequence of lipoprotein changes, resulting in higher levels of remnant particles, smaller LDL, and lower levels of high-density liporotein (HDL) cholesterol. These atherogenic lipid abnormalities precede the diagnosis of type 2 diabetes by several years, and it is thus important to elucidate the mechanisms involved in the overproduction of large VLDL particles. Here, we review the pathophysiology of VLDL biosynthesis and metabolism in the metabolic syndrome. We also review recent research investigating the relation between hepatic accumulation of lipids and insulin resistance, and sources of fatty acids for liver fat and VLDL biosynthesis. Finally, we briefly discuss current treatments for lipid management of dyslipidemia and potential future therapeutic targets.
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| 41. |
- Adiels, Martin, 1976, et al.
(författare)
-
Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia
- 2005
-
Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636 .- 1079-5642. ; 25:8, s. 1697-703
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS AND RESULTS: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by diabetes per se. The production rates of VLDL1 apoB and TG were closely related, as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized particles was very similar in the 2 groups. Plasma glucose, insulin, and free fatty acids together explained 55% of the variation in VLDL1 TG production rate. CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic production of VLDL1 particles similar in size and composition to those in nondiabetic subjects. We propose that hyperglycemia is the driving force that aggravates overproduction of VLDL1 in DM2.
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| 42. |
- Adiels, Martin, 1976, et al.
(författare)
-
Postprandial accumulation of chylomicrons and chylomicron remnants is determined by the clearance capacity.
- 2012
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 222:1, s. 222-8
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To better understand the postprandial clearance of triglyceride-rich lipoproteins (TRLs) and its relation to the fasting kinetics of TRLs. Methods Two studies were performed on 30 male subjects: a fasting kinetic study to determine the fasting secretion and clearance rates of apolipoprotein B (apoB) 100 and triglycerides in the very low-density lipoprotein 1 and 2 (VLDL1 and VLDL2) fractions; and a postprandial study to determine the postprandial accumulation of apoB48, apoB100 and triglycerides in the chylomicron, VLDL1 and VLDL2 fractions. Results from these two studies were combined to characterize the postprandial clearance of TRLs in a physiologically relevant setting. Results Our results show that postprandial accumulation of the apoB48-carrying chylomicrons can be predicted from the clearance capacity of the lipolytic pathway, determined in the fasting state. Furthermore, we show that chylomicrons and VLDL1 particles are not cleared equally by the lipoprotein lipase pathway, and that chylomicrons seem to be the preferred substrate. Subjects with a rapid fasting lipid metabolism accumulate lower levels of postprandial triglycerides with less accumulation of apoB100 in the VLDL1 fraction and a faster transfer of apoB100 into the VLDL2 fraction. In contrast, fasting VLDL1 secretion does not predict postprandial triglyceride accumulation. Conclusions Non-fasting triglyceride levels have recently been identified as a major predictor of future cardiovascular events. Here we show that the capacity of the lipolytic pathway is a common determinant of both the fasting and non-fasting triglyceride levels and may thus play an important role in the development of dyslipemia and atherosclerosis.
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| 43. |
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| 44. |
- Alkner, Sara, et al.
(författare)
-
Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
-
Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 197
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.
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| 45. |
- Améen, Caroline, 1975, et al.
(författare)
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Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver
- 2005
-
Ingår i: J Biol Chem. ; 280:2, s. 1224-9
-
Tidskriftsartikel (refereegranskat)abstract
- Microsomal triglyceride transfer protein (MTP) is rate-limiting in the assembly and secretion of lipoproteins containing apolipoprotein (apo) B. Previously we demonstrated that Wy 14,643 (Wy), a peroxisome proliferator-activated receptor (PPAR) alpha agonist, increases apoB-100 secretion despite decreased triglyceride synthesis. In this study, we sought to determine whether PPARalpha activation increases MTP expression and activity. Treatment with Wy increased hepatic MTP expression and activity in rats and mice and increased MTP expression in primary cultures of rat and mouse hepatocytes. Addition of actinomycin D blocked this increase and the MTP promoter (-136 to +67) containing a conserved DR1 element was activated by Wy, showing that PPARalpha activates transcription of the gene. Wy did not affect MTP expression in the intestine or in cultured hepatocytes from PPARalpha-null mice. A retinoid X receptor agonist (9-cis-retinoic acid), but not a PPARgamma agonist (rosiglitazone), increased MTP mRNA expression in cultured hepatocytes from both wild type and PPARalpha-null mice. In rat hepatocytes incubated with Wy, MTP mRNA levels increased between 6 and 24 h, and MTP protein expression and apoB-100 secretion increased between 24 and 72 h. In conclusion, PPARalpha activation stimulates hepatic MTP expression via increased transcription of the Mtp gene. This effect is paralleled by a change in apoB-100 secretion, indicating that the effect of Wy on apoB-100 secretion is mediated by increased expression of MTP.
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| 46. |
- Andersson, Jonny K, 1972, et al.
(författare)
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Cost description of clinical examination and MRI in wrist ligament injuries
- 2018
-
Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 52:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The total number and cost of wrist MRIs in the catchment area of the Vastra Gotaland Region in Sweden (population 1 723 000) during 1 year was analysed, together with the number and content of referrals. Methods: Six radiology departments reported the numbers and rate of all MRI investigations intended to diagnose wrist ligament injuries (n=411) and other injuries to the wrist. Results: The additional cost of the difference between MRIs and a clinical examination by a hand surgeon, plus indirect costs for patients with suspected wrist ligament injuries, was calculated as 957 000 euros. Conclusions: It is recommended that MRI should only be used in patients in whom there are clinical difficulties in terms of diagnosing wrist ligament injuries. It is suggested that patients with suspected wrist ligament injuries should be referred directly to an experienced hand surgeon, capable of performing a standardised wrist examination and, when needed, diagnostic arthroscopy and final treatment. The proposed algorithm for the diagnosis and treatment of suspected wrist ligament injuries presented in the present study could save time for the patient and for the radiology departments, as well as reducing costs. The ability to implement the early and appropriate treatment of acute ligament injuries could be improved at the same time.
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| 47. |
- Andersson, Linda, 1973, et al.
(författare)
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PLD1 and ERK2 regulate cytosolic lipid droplet formation
- 2006
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Ingår i: J Cell Sci. ; 119:Pt 11, s. 2246-57
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Tidskriftsartikel (refereegranskat)abstract
- We have previously uncovered roles for phospholipase D (PLD) and an unknown cytosolic protein in the formation of cytosolic lipid droplets using a cell-free system. In this report, PLD1 has been identified as the relevant isoform, and extracellular signal-regulated kinase 2 (ERK2) as the cytosolic protein. Increased expression of PLD1 increased lipid droplet formation whereas knockdown of PLD1 using siRNA was inhibitory. A role for ERK2 in basal lipid droplet formation was revealed by overexpression or microinjection, and ablation by siRNA knockdown or pharmacological inhibition. Similar manipulations of other Map kinases such as ERK1, JNK1 or JNK2 and p38alpha or p38beta were without effect. Insulin stimulated the formation of lipid droplets and this stimulation was inhibited by knockdown of PLD1 (by siRNA) and by inhibition or knockdown (by siRNA) of ERK2. Inhibition of ERK2 eliminated the effect of PLD1 on lipid droplet formation without affecting PLD1 activity, suggesting that PLD1 functions upstream of ERK2. ERK2 increased the phosphorylation of dynein which increased the amount of the protein on ADRP-containing lipid droplets. Microinjection of antibodies to dynein strongly inhibited the formation of lipid droplets, demonstrating that dynein has a central role in this formation. Thus dynein is a possible target for ERK2.
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| 48. |
- Andersson, Staffan, 1952-, et al.
(författare)
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Building performance based on measured data
- 2011
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Ingår i: World Renewable Energy Congress – Sweden, 8–13 May, 2011, Linköping, Sweden. - Linköping : Linköping University Electronic Press. - 9789173930703 ; , s. 899-906
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Konferensbidrag (refereegranskat)abstract
- With increasing liability for builders, the need for evaluation methods that focuses on the building’s performance and thus excludes the impact from residents’ behavior increases. This is not only of interest for new buildings but also when retrofitting existing buildings in order to reduce energy end-use. The investigation in this paper is based on extensive measurements on two fairly representative type of buildings, a single family building in Ekerö, Stockholm built 2000 and two apartment buildings in Umeå (1964) in order to extract key energy performance parameters such as the building’s heat loss coefficient, heat transfer via the ground and heat gained from the sun and used electricity. With access to pre-processed daily data from a 2-month periods, located close to the winter solstice, a robust estimate of the heat loss coefficient was obtained based on a regression analysis. For the single family building the variation was within 1% and for the two heavier apartment buildings an average variation of 2%, with a maximum of 4%, between different analyzed periods close to the winter solstice. The gained heating from the used electricity in terms of a gain factor could not be unambiguously extracted and therefore could only a range for the heat transfer via ground be estimated. The estimated range for the transfer via ground for the two apartment buildings were in very good agreement with those calculated according to EN ISO 13 370 and corresponded to almost 10% of the heating demand at the design temperature. For the single family building with an insulated slab and parts of the walls below ground level, the calculations gave slightly higher transfer than what was obtained from the regression analysis. For the estimated gained solar radiation no comparison has been possible to make, but the estimated gain exhibited an expected correlation with the global solar radiation data that was available for the two apartment buildings.
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| 49. |
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| 50. |
- Anistratov, Pavel, 1990-
(författare)
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Autonomous Avoidance Maneuvers for Vehicles using Optimization
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To allow future autonomous passenger vehicles to be used in the same driving situations and conditions as ordinary vehicles are used by human drivers today, the control systems must be able to perform automated emergency maneuvers. In such maneuvers, vehicle dynamics, tire–road interaction, and limits on what the vehicle is capable of performing are key factors to consider. After detecting a static or moving obstacle, an avoidance maneuver or a sequence of lane changes are common ways to mitigate the critical situation. For that purpose, motion planning is important and is a primary task for autonomous-vehicle control subsystems. Optimization-based methods and algorithms for such control subsystems are the main focus of this thesis.Vehicle-dynamics models and road obstacles are included as constraints to be fulfilled in an optimization problem when finding an optimal control input, while the available freedom in actuation is utilized by defining the optimization criterion. For the criterion design, a new proposal is to use a lane-deviation penalty, which is shown to result in well-behaved maneuvers and, in comparison to minimum-time and other lateral-penalty objective functions, decreases the time that the vehicle spends in the opposite lane.It is observed that the final phase of a double lane-change maneuver, also called the recovery phase, benefits from a dedicated treatment. This is done in several steps with different criteria depending on the phase of the maneuver. A theoretical redundancy analysis of wheel-torque distribution, which is derived independently of the optimization criterion, complements and motivates the suggested approach.With a view that a complete maneuver is a sequence of two or more sub-maneuvers, a decomposition approach resulting in maneuver segments is proposed. The maneuver segments are shown to be possible to determine with coordinated parallel computations with close to optimal results. Suitable initialization of segmented optimizations benefits the solution process, and different initialization approaches are investigated. One approach is built upon combining dynamically feasible motion candidates, where vehicle and tire forces are important to consider. Such candidates allow addressing more complicated situations and are computed under dynamic constraints in the presence of body and wheel slip. To allow a quick reaction of the vehicle control system to moving obstacles and other sudden changes in the conditions, a feedback controller capable of replanning in a receding-horizon fashion is developed. It employs a coupling between motion planning using a friction-limited particle model and a novel low-level controller following the acceleration-vector reference of the computed plan. The controller is shown to have real-time performance.
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