| 1. |
- 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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| 2. |
- 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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| 3. |
- Hamrin Senorski, Eric, 1989, et al.
(författare)
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“I never made it to the pros…” Return to sport and becoming an elite athlete after pediatric and adolescent anterior cruciate ligament injury - Current evidence and future directions
- 2018
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:4, s. 1011-1018
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Tidskriftsartikel (refereegranskat)abstract
- The management of anterior cruciate ligament (ACL) injuries in the skeletally immature and adolescent patient remains an area of controversy in sports medicine. This study, therefore, summarizes and discusses the current evidence related to treating pediatric and adolescent patients who sustain an ACL injury. The current literature identifies a trend towards ACL reconstruction as the preferred treatment option for ACL injuries in the young, largely justified by the risk of further structural damage to the knee joint. Worryingly, a second ACL injury is all too common in the younger population, where almost one in every three to four young patients who sustain an ACL injury and return to high-risk pivoting sport will go on to sustain another ACL injury. The clinical experience of these patients emphasizes the rarity of an athlete who makes it to elite level after a pediatric or adolescent ACL injury, with or without reconstruction. If these patients are unable to make it to an elite level of sport, treatment should possibly be modified to take account of the risks associated with returning to pivoting and strenuous sport. The surveillance of young athletes may be beneficial when it comes to reducing injuries. Further research is crucial to better understand specific risk factors in the young and to establish independent structures to allow for unbiased decision-making for a safe return to sport after ACL injury. Level of evidence V.
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| 4. |
- Johansson, Johas, et al.
(författare)
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Tekniska Infrastruktures sårbarhet
- 2010
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Ingår i: FRIVA - risk, sårbarhet och förmåga. - 9789163376917 ; , s. 111-128
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 6. |
- Moore, Karen, et al.
(författare)
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Effects of Warmer World Scenarios on Hydrologic Inputs to Lake Mälaren, Sweden and Implications for Nutrient Loads
- 2008
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Ingår i: Hydrobiologia. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 599, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- A simple, rapid, and flexible modelling approach was applied to explore the impacts of climate change on hydrologic inputs and consequent implications for nutrient loading to Lake Malaren, Sweden using a loading function model (GWLF). The first step in the process was to adapt the model for use in a large and complex Swedish catchment. We focused on the Galten basin with four rivers draining into the western region of Malaren. The catchment model was calibrated and tested using long-term historical data for river discharge and dissolved nutrients (N, P). Then multiple regional climate model simulation results were downscaled to the local catchment level, and used to simulate possible hydrological and nutrient loading responses to warmer world scenarios. Climate change projections for the rivers of Galten basin show profound changes in the timing of discharge and nutrient delivery due to increased winter precipitation and earlier snow melt. Impacts on total annual discharge and load are minimal, but the alteration in river flow regime and the timing of nutrient delivery for future climate scenarios is strikingly different from historical conditions.
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| 7. |
- Nilsson, Magnus, et al.
(författare)
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Discovery of 4 '-azido-2 '-deoxy-2 '-C-methyl cytidine and prodrugs thereof : A potent inhibitor of Hepatitis C virus replication
- 2012
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 22:9, s. 3265-3268
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Tidskriftsartikel (refereegranskat)abstract
- 4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 value of 1.2 mu M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof. (C) 2012 Elsevier Ltd. All rights reserved.
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| 8. |
- Nilsson, Magnus, et al.
(författare)
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Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease : Exploration of P2 quinazoline substituents
- 2010
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 20:14, s. 4004-4011
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Tidskriftsartikel (refereegranskat)abstract
- Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. (C) 2010 Elsevier Ltd. All rights reserved.
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| 9. |
- Rydberg, Lennart, 1944, et al.
(författare)
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In vitro assessment of a new ABO immunosorbent with synthetic carbohydrates attached to sepharose.
- 2005
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 0934-0874. ; 17:11, s. 666-72
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation across the ABO barrier is sometimes done in cases of emergency, such as acute liver failure, but is also carried out in elective cases, e.g. kidneys from living donors. Reducing the recipient anti-A/B antibody titres is often necessary in ABO-incompatible kidney transplantation. This is usually done by the use of techniques such as plasmapheresis and protein A- or sepharose-linked anti-human Ig immunoadsorption. A new ABO immunosorbent with synthetic A- or B-trisaccharide carbohydrate epitopes linked to a sepharose matrix has been tested. Columns made of this material have been tested in vitro with plasma from A- and B-individuals, assessed for antibody reduction capacity, flow characteristics, biocompatibility, and unspecific protein adsorption. The columns have a high capacity for ABO antibody removal, reducing titres by three to seven steps in one passage. We noted a high biocompatibility, with no unspecific protein adsorption, no activation of coagulation factors, and a low activation of complement, no immune complex formation and no cytotoxicity towards cultured mammalian L929 cells.
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| 10. |
- Samuelsson, Eva, et al.
(författare)
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Determinants of urinary incontinence in a population of young and middle-aged women
- 2000
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 79:3, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Background. Urinary incontinence and genital prolapse are prevalent conditions in the female population. The aim of this study was to study possible determinants of female urinary incontinence in a population-based sample of young and middle-aged women. Methods. Of 641 eligible women aged 20-59 years in a primary health care district, 487 (76%) responded to a questionnaire and accepted an invitation to a gynecological examination. The examination included digital assessment of the pelvic floor muscle strength (PFMS). Genital prolapse presence (cystocele, rectocele, uterine prolapse or absence of the urethrovesical crease) was graded in relation to the vaginal introitus. Results. The prevalence of urinary incontinence was 28%, 3.5% having daily leakage. Stress urinary incontinence was the dominant type. The odds ratio (OR) of having incontinence increased From 1 to 3.5 with increasing age and From 1 to 2.7 with increasing parity. The OR also increased with decreasing PFMS; from 1 in the group with the best PI;MS to 3.4 in the group unable to contract their pelvic musculature. In addition. women with cystocele and/or absence of the urethrovesical crease had a 2.5-fold increased OR of incontinence (95% CI 1.5-4.2), smoking increased the OR 1.9 times (95% CI 1.1-3.2) and estrogen replacement therapy (ERT) increased the OR 2.9 times (95% CI 1.4-5.9). There were no significant correlations with the presence of chronic disease, episiotomy or the birth weights of children but small non-significant correlations with performed hysterectomy and the woman's weight. Conclusions. Urinary incontinence is a frequent symptom in the female general population and related to age, pelvic floor muscle strength, genital prolapse, smoking, parity and estrogen replacement therapy.
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