| 1. |
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| 2. |
- Ytreberg, Agnes, et al.
(författare)
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God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 3: Övervakningsprogram
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att fastställa övervakningsprogram.God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för elva temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. Utifrån de elva deskriptorerna har Sverige fastställt 13 övervakningsprogram. Sex program utgår ifrån olika biodiversitetsteman som berörs av en upp till tre deskriptorer, medan de övriga sju programmen utgår ifrån de deskriptorer som är mer inriktade mot belastning och miljöförändring.För varje program har ett antal underprogram föreslagits baserat på den nuvarande övervakningen och/eller planerad övervakning. Övervakning som ingår i programmen ska vara pågående och data ska vara tillgängliga. I programmen ingår nationell och regional miljöövervakning inklusive verksamhetsutövares recipientkontroll. Dessutom ingår annan typ av datainsamling som till exempel inventeringar av tumlare och uppgifter om omfattningen av mänskliga aktiviteter som orsakar belastning och miljöförändringar. Enligt havsmiljödirektivet ska övervakningen fånga upp tillstånd och miljöförändringar, belastning och omfattning av aktiviteterna som orsakar belastningen samt effekter av åtgärder. Eftersom nästa steg i havsförvaltningscykeln är att fastställa åtgärdsprogram kommer övervakning för att följa upp åtgärder att läggas till övervakningsprogrammen först under nästa förvaltningscykel.I beskrivningarna av programmen framgår hur den nuvarande övervakningen motsvarar de krav som ställs på dataunderlag genom havsmiljödirektivets bilaga III samt genom deskriptorer, kriterier, indikatorer och beslutade miljökvalitetsnormer. I dagens övervakning saknas bland annat tillräcklig övervakning för uppföljning av livsmiljöers tillstånd och utbredning. För marint avfall, buller och främmande arter saknas nationellt samordnad övervakning, men det görs regionala insatser och ett antal projekt har genomförts eller påbörjats för att öka kunskapen om hur övervakning bäst ska utformas. För de program som har pågående övervakning beskrivs utvecklingsbehoven för att förbättra underlaget för de återkommande tillståndsbedömningarna.Övervakningsprogrammet som fastställs under 2014 utgör således inte ett fast program för kunskapsinhämtning. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där utveckling av indikatorer och övervakning kommer att ske kontinuerligt.
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| 5. |
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| 6. |
- Ax, Anna, et al.
(författare)
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Synthesis of a small library of non-symmetric cyclic sulfamide HIV-1 protease inhibitors
- 2010
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 66:23, s. 4049-4056
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Tidskriftsartikel (refereegranskat)abstract
- A set of 11 non-symmetric cyclic sulfamide HIV-1 protease inhibitors were synthesized and evaluated. The use of a key microwave-assisted silver(I) oxide mediated selective mono N-benzylation reaction enabled fast and straightforward synthesis. The K-i values of the new inhibitors ranged between 0.28 mu M and >20 mu M.
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| 7. |
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| 8. |
- Di Gennaro, Antonio, et al.
(författare)
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Increased expression of leukotriene C-4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:49, s. 21093-21097
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Tidskriftsartikel (refereegranskat)abstract
- Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC4, LTD4, and LTE4 are important mediators of asthma, and LTB4 has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC4 synthase (LTC4S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme responsible for the biosynthesis of LTB4, are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC4S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB4. Furthermore, challenge of AAA wall tissue with exogenous LTD4 increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC4S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA.
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| 9. |
- Farnebo, Simon, et al.
(författare)
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Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
- 2010
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Ingår i: EUROPEAN SURGICAL RESEARCH. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 45:2, s. 105-112
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Tidskriftsartikel (refereegranskat)abstract
- Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.
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| 10. |
- Fytagoridis, Anders, et al.
(författare)
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Deep Brain Stimulation of the Caudal Zona Incerta : Tremor Control in Relation to the Location of Stimulation Fields
- 2016
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 94:6, s. 363-370
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Tidskriftsartikel (refereegranskat)abstract
- Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.
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| 11. |
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| 15. |
- Hultén, Johan, et al.
(författare)
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Cyclic HIV-1 protease inhibitors derived from mannitol : synthesis, inhibitory potencies, and computational predictions of binding affinities
- 1997
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 40:6, s. 885-897
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Tidskriftsartikel (refereegranskat)abstract
- Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.
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| 16. |
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| 17. |
- Hämäläinen, Markku D., et al.
(författare)
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Characterization of a set of HIV-1 protease inhibitors using binding kinetics data from a biosensor-based screen
- 2000
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Ingår i: Journal of Biomolecular Screening. - : Elsevier BV. - 1087-0571 .- 1552-454X. ; 5:5, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between 290 structurally diverse human immunodeficiency virus type 1 (HIV-1) protease inhibitors and the immobilized enzyme was analyzed with an optical biosensor, Although only a single concentration of inhibitor was used, information about the kinetics of the interaction could be obtained by extracting binding signals at discrete time points. The statistical correlation between the biosensor binding data, inhibition of enzyme activity (K-i), and viral replication (EC50) revealed that the association and dissociation rates for the interaction could be resolved and that they were characteristic for the compounds. The most potent inhibitors, with respect to K-i and EC50 values, including the clinically used drugs, all exhibited fast association and slow dissociation rates. Selective or partially selective binders for HIV-1 protease could be distinguished from compounds that showed a general protein-binding tendency by using three reference target proteins. This biosensor-based direct binding assay revealed a capacity to efficiently provide high-resolution information on the interaction kinetics and specificity of the interaction of a set of compounds with several targets simultaneously.
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| 18. |
- Lundin, Anders, et al.
(författare)
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Corticosteroids peroperatively diminishes damage to the C-fibers in microscopic lumbar disc surgery
- 2005
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 30:21, s. 2362-2368
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN:A subgroup analysis of patient outcomes from a double-blind randomized controlled study comparing corticosteroid versus saline in microscopic lumbar disc surgery.OBJECTIVES:To study if the use of corticosteroids combined with surgery alleviates the damage to the nerve fibers in lumbar disc herniation.SUMMARY OF BACKGROUND DATA:The use of quantitative sensory testing can detect damage to the myelinated A-delta fibers (cold sense) and the unmyelinated C-fibers (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery enhance the outcome after surgery in terms of less pain and more rapid rehabilitation.METHODS:Analyzing quantitative sensory testing before surgery and after 2 weeks and 2 years.RESULTS:In the corticosteroid group, we saw a statistically significant normalization for the warmth disturbance comparing with control group, which not was detected concerning the cold disturbance.CONCLUSIONS:The use of corticosteroids combined with surgery seems to protect some of the damage to the C-fibers in lumbar disc herniation.
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| 19. |
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| 24. |
- Orwelius, Lotti, 1956-, et al.
(författare)
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Pre-existing disease : the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial
- 2010
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life. Methods Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age ≥ 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for. Results Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible. Conclusions A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further supported by the small, long term increment in the health related quality of life after treatment in the ICU. The reliability of the conclusions is supported by the size of the study populations and the long follow-up period.
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| 25. |
- Samuelsson, Peter, et al.
(författare)
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Use of Physical Modelling to Study How to Increase the Production Capacity by Implementing a Novel Oblong AOD Converter
- 2017
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Ingår i: Ironmaking and Steelmaking: Processes, Products and Applications. - 0301-9233.
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Tidskriftsartikel (refereegranskat)abstract
- There is no known example of an AOD converter with oblong cross sections in the literature. Changing the geometry of the converter vessel, from the traditional circular cross sections, to increase converter volume could potentially influence the performance of the converter and in particular the decarburisation rate. Due to physical limitations in an existing melt shop the only available way to increase the tapped weight and hence the productivity was to consider a modified converter cross section, namely an oblong cross section. A change in cross section could potentially influence the decarburisation performance and in the worst case counteract the intended increase in productivity. In order to study the feasibility of implementing an oblong converter, physical modelling was used to establish whether it would be suitable to change the AOD geometry from a circular cross section to a novel oblong cross section to increase the converter volume and thus the productivity. Specifically, the aim was to use physical modelling to study the fluid flow of the proposed converter configuration (geometry and number of tuyeres) and the potential influence on the decarburisation rate. Two water models linearly scaled down to a 1:4.6 dimension in comparison to a production converter were employed using water containing ???? and gas injected through six or eight tuyeres as fluids. In the model one tuyere was used for injection of ??2 gas, while air was injected through the remaining five or seven tuyeres. The reaction of ??2 and ???? (??2 + 2???? ⇄ ??&??3 + ?2?) was indirectly measured by detecting the pH value of the water in the model. The purpose of the model was to simulate the decarburisation part of the converter process as any prolongation of the decarburisation will defeat the purpose of increasing the productivity. The mixing time is considered to be a good indicator of the decarburisation as the kinetics will be diffusion controlled in the latter parts of the process. According to our experience, the thermodynamics of decarburisation will not be dependent on the converter shape. The following three converter figurations were studied: i) a circular converter with six tuyeres, ii) an oblong converter with six tuyeres, and iii) an oblong converter with eight tuyeres. The mixing time, defined as the time to reach 95% of the final ??2 concentration, can be used to evaluate the different converter configurations. The average ??2 concentrations based on several experiments, calculated based on pH measurements in the water, differed by less than 5% between the circular and oblong models after 165 s of injection of air and ??2. The results also showed that no difference in mixing time could be found when using 6 and 8 tuyeres, respectively in the oblong model. In fact, the ??2 concentrations in the oblong model differed by less than 2% after 165 s of injection of air and ??2 between six and eight tuyeres. Based on the findings, it has been observed that the influence of converter geometry on mixing time is small, it was concluded that decarburisation rate is likely to be the same irrespectively of converter geometry. Thus it is possible to construct an oblong converter to increase the productivity.
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| 26. |
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| 27. |
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| 28. |
- Wannberg, Johan, et al.
(författare)
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A New Structural Theme in C2-Symmetric HIV-1 Protease Inhibitors: ortho-Substituted P1/P1’ Side Chains
- 2006
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Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 14:15, s. 5303-5315
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Tidskriftsartikel (refereegranskat)abstract
- In this report, the rapid syntheses of 24 novel C2-symmetric HIV-1 protease inhibitors are described. Two ortho-iodobenzyloxy containing C-terminal duplicated inhibitors served as starting materials for microwave-enhanced palladium(0)-catalyzed carbon-carbon bond forming reactions (Suzuki, Sonogashira, Heck, and Negishi). Highly potent inhibitors equipped with ortho-functionalized P1/P1' side chains as the structural theme were identified. Computational efforts were applied to study the binding mode of this class of inhibitors and to establish structure-activity relationships. The overall orientation of the inhibitors in the active site was reproduced by docking which suggested three possible conformations of the P1/P1' groups of which two seem more plausible.
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| 29. |
- Zuccarello, Guido, et al.
(författare)
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HIV-1 protease inhibitors based on acyclic carbohydrates
- 1998
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 63:15, s. 4898-4906
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Tidskriftsartikel (refereegranskat)abstract
- A series of acyclic C2-symmetric HIV protease inhibitors readily accessible from D-mannitol have been developed. Several of the compounds synthesized showed significant in vitro activity against HIV-1 protease.
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| 30. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and Synthesis of BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold: Potent activities in a cellular assay
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In a preceding report from our group we disclosed the development of a novel HE transition state isostere with a difluorophenoxymethyl side chain in the P1 position and a methoxy group in the P1’ position furnishing highly potent inhibitors of BACE-1 (i.e. lead compound 1), which moreover exhibit very promising selectivity over cathepsin D. In a continuation of this work with the aim at improving on the cell-based activity and pharmacokinetic properties, we have further developed the SAR for the P1 side chain of inhibitor 1 whereby the P1 side chain oxygen has been substituted for an amine, a carbon or a bond. The chemistry developed for the previous HE inhibitor structure 1 has now been extended to readily accommodate the introduction of new P1 side chains into this new HE scaffold. These modifications have given rise to several highly potent inhibitors where the most potent displayed a BACE-1 Ki value of 0.2 nM and a cell-based Aβ40 IC50 value of 9 nM. Thus, regarding the enzyme inhibition in the cell assay a more than 600-fold improvement compared to compound 1 was achieved via minor structural alterations.
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| 31. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors
- 2010
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an L-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed K-i values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 mu M and 0.33 mu M respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M461, V82F, and 184V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.
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| 32. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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P2 '-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
- 2010
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:2, s. 542-554
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Tidskriftsartikel (refereegranskat)abstract
- Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.
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| 33. |
- Ahlsén, Göran, et al.
(författare)
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Resistance profiles of cyclic and linear inhibitors of HIV-1 protease
- 2002
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Ingår i: Antiviral Chemistry & Chemotherapy. - 0956-3202 .- 2040-2066. ; 13:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to anti-HIV protease drugs is a major problem in the design of AIDS drugs with long-term efficacy. To identify structural features associated with a certain resistance profile, the inhibitory properties of a series of symmetric and asymmetric cyclic sulfamide, cyclic urea and linear transition-state analogue inhibitors of HIV-1 protease were investigated using wild-type and mutant enzyme. To allow a detailed structure-inhibition analysis, enzyme with single, double, triple and quadruple combinations of G48V, V82A, 184V and L90M substitutions was used. Kinetic analysis of the mutants revealed that catalytic efficiency was 1-30% of that for the wild-type enzyme, a consequence of reduced kcat in all cases and an increased KM for all mutants except for the G48V enzyme. The overall structure-inhibitory profiles of the cyclic compounds were similar, and the inhibition of the V82A, 184V and G48V/L90M mutants were less efficient than of the wild-type enzyme. The greatest increase in Ki was generally observed for the 184V mutant and least for the G48V/L90M mutant, and additional combinations of mutations did not result in improved inhibition profiles for the cyclic compounds. An extended analysis of additional mutants, and including a set of linear compounds, showed that the profile was unique for each compound, and did not reveal any general structural features associated with a certain inhibition profile. The effects of structural modifications in the inhibitors, or of mutations, were not additive and they differed depending on their context. The results demonstrate the difficulties in predicting resistance, even for closely related compounds, and designing compounds with improved resistance profiles.
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| 34. |
- Albinsson, Anders
(författare)
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”De va svinhögt typ 250 kilo” : Förskolebarns mätande av längd, volym och tid i legoleken
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of the dissertation is to study, describe and analyses which comparative measurement activities preschool children construct and use, and how they solve problems and communicate when they use the comparative measurement activities whilst playing with Lego (“the Lego play”). The measurement activities chosen are length/height, quantity and time.The empirical material is based on data from two preschool classes with children aged 2 – 5 year, It was collected through participant observation (video captures) of the children’s Lego play. The theoretical starting points in this study are grounded in childhood sociology and the sociocultural perspective. The study assumes the childhood sociology perspective by viewing the children as competent and active in creating meaning as well as controlling and influencing their own and others’ social environment. The sociocultural perspective gives prominence to development and learning, and its related tools and concepts are used to analyses the results of the study. That is, the Lego play is studied in a social context from the child’s perspective, and the sociocultural perspective describes and analyses the child’s use of mathematics and the acquisition of knowledge in the Lego play in a sociocultural context.The results show that children measuring length/height and quantity explored a store of measurement tools in order to make comparisons, and adapted these to the context in question. These were own body, other body, artefacts, numbers and counting. The measurements were used individually and with others, and the solving of the own or shared problems constituted a large share of the time spent constructing models during Lego play. By contrast, the time concept was used mainly as a tool when the children played with their finished Lego models. Thus, a time perspective was added to the child’s finished model, which inspired thoughts and reflections about time used in the Lego play. The children used the time concepts of the present, the past and the future, and also considered the concept of velocity in the context of the timescale. The children’s communication had a large impact on the Lego play, and they expressed their ideas verbally, physically and through action. The children’s use of mathematics was prominent and meaningful during the Lego play.
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| 35. |
- Albinsson, Anders, 1958-, et al.
(författare)
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Förskolebarn använder mätning i legoleken
- 2016
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Ingår i: Venue. - Linköping : Linköpings universitet. - 2001-788X.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- I legoleken använder förskolebarn mätning på många olika sätt. De växlar mellan olika mätredskap och måttenheter, beroende på kontext och önskat mätresultat. Genom mätningar löser barnen problem i legoleken. Mätresultatet kommuniceras genom att visa, förklara och argumentera med matematiska begrepp.
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| 36. |
- Almgren, Torbjörn, 1959, et al.
(författare)
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Diabetes in treated hypertension is common and carries a high cardiovascular risk: results from a 28-year follow-up.
- 2007
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Ingår i: Journal of hypertension. - 0263-6352. ; 25:6, s. 1311-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to analyse predictive factors for development of type 2 diabetes during life-long therapy for hypertension and the alleged additional cardiovascular risk this constitutes. METHODS: The study group (n = 754) comprised the hypertensive subgroup of a randomized population sample of 7500 men, aged 47-54 years, screened for cardiovascular risk factors and followed for 25-28 years. The patients were treated with thiazide diuretics and beta-adrenergic blocking drugs with the addition of hydralazin during the first decade. Calcium antagonists were substituted for hydralazin and, if needed, angiotensin-converting enzyme inhibitors were added when these drugs became available. RESULTS: A total of 148 (20.4%) treated hypertensive patients developed diabetes during 25 years, and in multivariate Cox regression analysis body mass index, serum triglycerides and treatment with beta-blockers were positively related with this complication. New-onset diabetes implied a significantly increased risk for stroke [hazard ratio (HR): 1.67; 95% confidence interval (95% CI): 1.1-2.6; P < 0.05], myocardial infarction (OR: 1.66; 95% CI: 1.1-2.5; P < 0.05) and mortality (OR: 1.42; 95% CI: 1.1-1.9; P < 0.05). The greatest risk for stroke was new-onset diabetes, followed by smoking (OR: 1.46; 95% CI: 1-2.2; P = 0.07) and the greatest risk for myocardial infarction was new-onset diabetes, followed by smoking (HR: 1.64; 95% CI: 1.1-2.4; P < 0.01). The greatest risk for mortality was smoking (HR: 1.73; 95% CI: 1.3-2.2; P < 0.005). Achieved systolic and diastolic blood pressure were not predictive of cardiovascular complications or death. The mean observation time from onset of diabetes mellitus to a first stroke was 9.1 years and to a first myocardial infarction 9.3 years. CONCLUSION: Diabetes in treated hypertensive patients is alarmingly common and carries a high risk for cardiovascular complications and mortality.
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| 37. |
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| 38. |
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| 39. |
- Alterman, Mathias, et al.
(författare)
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P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 13:2, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.
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| 40. |
- Ayesa, Susana, et al.
(författare)
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Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S : Effect of sulfonamides P3 substituents on potency and selectivity.
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 17:3, s. 1307-1324
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Tidskriftsartikel (refereegranskat)abstract
- Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure–activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity profile and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K.
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| 41. |
- Beraki, Åsa, et al.
(författare)
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Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes : results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)
- 2014
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Ingår i: Diabetes Research and Clinical Practice. - Clare, Ireland : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.Methods: Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.Results: Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% +/- 1.5 (72 +/- 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% +/- 1.0 (60 +/- 11 mmol/mol)) (p < 0.001). An inverse dose-response association was found between PA and HbA1c (beta: -0.30, 95%CI: -0.34 to -0.26, p < 0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (beta: -0.21, 95% CI: -0.25 to -0.18, p < 0.001) when adjusted for possible confounding factors.Conclusions: Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.
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| 42. |
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| 43. |
- Bergquist, Maria, et al.
(författare)
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TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Adult patients admitted to the ICU with an arterial catheter were included. Clinical data and blood samples were prospectively recorded daily. Diagnoses were set retrospectively. Descriptive statistics and logistic regression models were used. NGAL, TNFR1 and TNFR2 were higher in sepsis patients compared to other diagnoses, as well as in non-survivors compared to survivors. In addition, these biomarkers increased with increasing stages of acute kidney injury. TNFR1 and TNFR2 performed similarly to NGAL and CRP in identifying sepsis patients, but they performed better than CRP in predicting 30-day mortality in this ICU cohort. Thus, TNFR1 and TNFR2 may be particularly useful in identifying high risk sepsis patients and facilitate relevant health care actions in this group of sepsis patients.
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| 44. |
- Berntson, Lillemor, 1957-, et al.
(författare)
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Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis : a cross-sectional study
- 2024
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Ingår i: Pediatric Rheumatology. - : Springer Nature. - 1546-0096. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity.Methods: EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm).Results: Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group.Conclusion: The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.
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| 45. |
- Birgegård, Gunnar, 1944-, et al.
(författare)
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Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group
- 2019
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Ingår i: European Journal of Haematology. - : Munksgaard Forlag. - 0902-4441 .- 1600-0609. ; 102:3, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia.METHODS: A cross-sectional study of 80 MF and 23 ET patients was performed.RESULTS: About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation <20 and normal or elevated S-ferritin (<500 µg/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion-dependent patients, 50.6 vs 24.4 µg/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL-2, IL-6 and TNF-α, (P < 0.01-0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table ). Tsat correlated negatively with CRP (P < 0.001). Symptom burden was heavier in MF patients with FID, and MPN-SAF quality of life scores correlated with IL-6 and CRP.CONCLUSIONS: The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID.
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| 46. |
- Björkblad, Anders, 1963-
(författare)
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Fatigue Assessment of Cast Components : Influence of Cast Defects
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is on the fatigue assessment of cast components with special attention to defects. The primary material in view is nodular cast iron, but also cast steel is considered. However, the fatigue behaviour is in principle valid for general use on other cast metals.The first two papers is about general cast material behaviour in fatigue loading. The materials considered are a high strength alloyed cast steel and a medium strength nodular cast iron. It is concluded that cast defects is the main fatigue initiation cause and it is only in exception that the fatigue life is not ruled by fracture mechanics. The third paper is a fracture mechanics evaluation of a nodular iron cast sleeve. The analysis of the component is based on crack initiation from cast defects and low-cycle fatigue. Fracture mechanics material parameters for Paris law, c and m, are extracted for the materials considered. In paper D design quality rules for nodular cast iron based on the Swedish standard SS 11 40 60 is presented. The quality rules regard cast defects in fatigue assessments and facilitate defect-based component design. In paper E, a finite element tool that is capable to predict and calculate 3D crack propagation for embedded cracks and defects is presented. The tool is an add-on for ANSYS finite element program. In paper F, closure equations for nodular cast iron are proposed in parallel to refined fracture mechanics material data. The paper includes crack propagation at different load ratios and in different microstructures.Summarized, the thesis composes a further development of the fatigue assessment of cast components. The central role of defects in fatigue is clarified and tools are provided for fracture mechanics evaluations of defects as well as for defect based design. The quality rules are also fit for application in manufacturing and for acceptance tests, hence covering the span from design to complete product.
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| 47. |
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| 48. |
- Björklund, Catarina, 1981-, et al.
(författare)
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Design and synthesis of potent and selective BACE-1 inhibitors
- 2010
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 53:4, s. 1458-1464
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Tidskriftsartikel (refereegranskat)abstract
- Several highly potent BACE-1 protease inhibitors have been developed from an inhibitor series containing a novel hydroxyethylene (HE) core structure displaying aryloxymethyl or benzyloxymethyl P1 side chains and a methoxy P1’ side chain. The target molecules were readily synthesized from chiral carbohydrate starting materials, furnishing the inhibitor compounds in good overall yields. The inhibitors show both high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnish a BACE-1 IC50 value of 0.32 nM and displays > 3000 fold selectivity over cathepsin D.
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| 49. |
- Björklund, Catarina, 1981-, et al.
(författare)
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Discovery of Potent BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold : Exploration of P1’ Alkoxy Residues and an Aminoethylene (AE) Central Core
- 2010
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd.. - 0968-0896 .- 1464-3391. ; 18:4, s. 1711-1723
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Tidskriftsartikel (refereegranskat)abstract
- In a preceding study we have described the development of a new hydroxyethylene (HE) core motif displaying P1 aryloxymethyl and P1’ methoxy substituents delivering potent BACE-1 inhibitors. In a continuation of this work we have now explored the SAR of the S1’ pocket by introducing a set of P1’ alkoxy groups and evaluated them as BACE-1 inhibitors. Previously the P1 and P1’ positions of the classical HE template have been relatively little explored due to the complexity of the chemical routes involved in modifications at these positions. However, the chemistries developed for the current HE template renders substituents in both the P1 and P1’ positions readily available for SAR exploration. The BACE-1 inhibitors prepared displayed IC50 values in the range of 4-45 nM, where the most potent compounds featured small P1’ groups. The cathepsin D selectivity which was high for the smallest P1’ sustituents (P1’=ethoxy, fold selectively >600) dropped for larger groups (P1’=benzyloxy, fold selectivity of 1.6). We have also confirmed the importance of both the hydroxyl group and its stereochemistry preference for this HE transition state isostere by preparing both the deoxygenated analogue and by inverting the configuration of the hydroxyl group to the R-configuration, which as expected resulted in large activity drops. Finally substituting the hydroxyl group by an amino group having the same configuration (S), which previously have been described to deliver potent BACE-1 inhibitors with advantageous properties, surprisingly resulted in a large drop in the inhibitory activity.
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| 50. |
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