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Sökning: WFRF:(Sandberg Lars)

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  • Lindskog, Bengt I., et al. (författare)
  • Medicinsk terminologi
  • 2004
  • Bok (övrigt vetenskapligt/konstnärligt)
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6.
  • Mikulskis, Paulius, et al. (författare)
  • Binding affinities in the SAMPL3 trypsin and host-guest blind tests estimated with the MM/PBSA and LIE methods.
  • 2012
  • Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 1573-4951 .- 0920-654X. ; 26:5, s. 527-541
  • Tidskriftsartikel (refereegranskat)abstract
    • We have estimated affinities for the binding of 34 ligands to trypsin and nine guest molecules to three different hosts in the SAMPL3 blind challenge, using the MM/PBSA, MM/GBSA, LIE, continuum LIE, and Glide score methods. For the trypsin challenge, none of the methods were able to accurately predict the experimental results. For the MM/GB(PB)SA and LIE methods, the rankings were essentially random and the mean absolute deviations were much worse than a null hypothesis giving the same affinity to all ligand. Glide scoring gave a Kendall's τ index better than random, but the ranking is still only mediocre, τ = 0.2. However, the range of affinities is small and most of the pairs of ligands have an experimental affinity difference that is not statistically significant. Removing those pairs improves the ranking metric to 0.4-1.0 for all methods except CLIE. Half of the trypsin ligands were non-binders according to the binding assay. The LIE methods could not separate the inactive ligands from the active ones better than a random guess, whereas MM/GBSA and MM/PBSA were slightly better than random (area under the receiver-operating-characteristic curve, AUC = 0.65-0.68), and Glide scoring was even better (AUC = 0.79). For the first host, MM/GBSA and MM/PBSA reproduce the experimental ranking fairly good, with τ = 0.6 and 0.5, respectively, whereas the Glide scoring was considerably worse, with a τ = 0.4, highlighting that the success of the methods is system-dependent.
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7.
  • Popova, Gergana, et al. (författare)
  • Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability
  • 2020
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:8, s. 3915-3934
  • Tidskriftsartikel (refereegranskat)abstract
    • Human dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, is a target for the treatment of rheumatoid arthritis and multiple sclerosis and is re-emerging as an attractive target for cancer therapy. Here we describe the optimization of recently identified tetrahydroindazoles (HZ) as DHODH inhibitors. Several of the HZ analogues synthesized in this study are highly potent inhibitors of DHODH in an enzymatic assay, while also inhibiting cancer cell growth and viability and activating p53-dependent transcription factor activity in a reporter cell assay. Furthermore, we demonstrate the specificity of the compounds toward the de novo pyrimidine synthesis pathway through supplementation with an excess of uridine. We also show that induction of the DNA damage marker gamma-H2AX after DHODH inhibition is preventable by cotreatment with the pancaspase inhibitor Z-VAD-FMK. Additional solubility and in vitro m etabolic stability profiling revealed compound 51 as a favorable candidate for preclinical efficacy studies.
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8.
  • Sandberg, Maria, et al. (författare)
  • Recent infections are associated with decreased risk of rheumatoid arthritis: a population-based case-control study.
  • 2014
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:5, s. 904-907
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Do recent infections affect the risk of rheumatoid arthritis (RA)? Methods We used the population-based case-control study EIRA (N= 6401) on incident RA and healthy controls, matched for sex, age, calendar period and area of residence. Gastroenteritis, urinary tract infection, genital infection, prostatitis, sinusitis, tonsillitis and pneumonia during the 2 years before inclusion in the study were investigated. Conditional logistic regression was used to calculate OR, adjusting for smoking and socioeconomic status. Results Infections in the gastrointestinal and urogenital tract before clinical onset were associated with a lowered risk of RA: gastroenteritis (OR= 0.71 (95% CI 0.63 to 0.80)), urinary tract infections (OR= 0.78 (95% CI 0.68 to 0.90)) and genital infections (OR= 0.80 (95% CI 0.64 to 1.00)), while a non-significant association of similar magnitude was observed for the less common prostatitis (OR= 0.64 (95% CI 0.38 to 1.08)). In contrast, no associations were observed for sinusitis, tonsillitis or pneumonia. Conclusions Gastrointestinal and urogenital infections, but not respiratory infections, are associated with a significantly lowered risk of RA. The results indicate that infections in general do not affect the risk for RA, but that certain infections, hypothetically associated with changes in the gut microbiome, could diminish the risk.
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  • Ahlström, Johan, et al. (författare)
  • Galvanic corrosion properties of steel in water saturated concrete
  • 2015
  • Ingår i: Materials and corrosion - Werkstoffe und Korrosion. - : Wiley. - 0947-5117 .- 1521-4176. ; 66:1, s. 67-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Aluminum-based sacrificial anodes were installed to reinforced concrete to stop ongoing corrosion in cooling water tunnels in a Swedish nuclear power plant. The steel rebars were also unintentionally connected to stainless steel water pumps. Therefore, the consumption rate of the sacrificial anodes was higher than predicted. An experimental and a field study were performed to assess if the steel rebar suffer from galvanic corrosion and if the stainless steel pumps are responsible alone for the high consumption rate. It was found from the experimental study that there is an increased risk of galvanic corrosion for steel rebar when the corrosion potential is raised to -200mV (SCE) for samples with 1% CL- by mass of cement and -500mV (SCE) for samples with 2% Cl- by mass of cement. The experimental results were compared with the corrosion potential measured in the cooling water tunnel where sacri ficial anodes were in use and not mounted at all. The cooling water tunnel without sacrificial anodes had generally more anodic corrosion potentials compared to the tunnel with anodes. The tunnel with anodes had also more anodic potentials closer to the stainless steel pumps than further away which means that the rebar is affected by the stainless steel pumps. However, the measured corrosion potentials in the tunnels were not as anodic as the potentials needed for high galvanic current measured in the experimental study.
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10.
  • Ahmad, I., et al. (författare)
  • Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy
  • 2022
  • Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 76:2, s. 96-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. Aim This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. Materials and methods From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery angstrom sberg Depression Rating Scale between the Q-ECT and the patient record. Results A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. Conclusions We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.
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