| 1. |
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| 2. |
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| 3. |
- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
-
Journal article (peer-reviewed)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 4. |
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| 5. |
- Chu, Hencelyn, et al.
(author)
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Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae
- 2010
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In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 36:2, s. 145-150
-
Journal article (peer-reviewed)abstract
- Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis (serovar L2), Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50 microM towards C. trachomatis L2. Three INPs had a MIC <12.5 microM against N. gonorrhoeae. Inhibition was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection (P<0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.
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| 6. |
- de Jong, S, et al.
(author)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
-
Journal article (peer-reviewed)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 7. |
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| 8. |
- Forthal, Donald N, et al.
(author)
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In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds
- 2012
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In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 40:4, s. 354-360
-
Journal article (peer-reviewed)abstract
- Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. In this study, the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides were determined. Inhibitory activity was assessed using TZM-bl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Antiviral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the antibacterial activity of salicylidene acylhydrazides is reversible by Fe(2+), the ability of Fe(2+) and other cations to reverse the anti-HIV-1 activity of the compounds was determined. Real-time PCR was also employed to determine the stage affected in the HIV-1 replication cycle. Four compounds with 50% inhibitory concentrations against HIV-1 of 1-7μM were identified. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether the target for virus replication was TZM-bl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe(2+), but not other cations, reversed the anti-HIV-1 effect. Finally, the inhibitory effect of the compounds occurred at a post-integration step. In conclusion, salicylidene acylhydrazides were identified with in vitro anti-HIV-1 activity in the micromolar range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide.
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| 9. |
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| 10. |
- Hallander, Per, et al.
(author)
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An experimental study of mechanisms behind wrinkle development during forming of composite laminates
- 2013
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In: Composites. Part A, Applied science and manufacturing. - : Elsevier. - 1359-835X .- 1878-5840. ; 50, s. 54-64
-
Journal article (peer-reviewed)abstract
- A general problem when forming quasi-isotropic, multilayer unidirectional (UD) prepreg over a double curved geometry is out-of-plane wrinkling. The presented study aims to show the existence of compression in the laminate in a recess area that is globally under tension during forming. Further it aims to investigate the influence of compression on the out-of-plane wrinkle development.An experimental study is performed with pre-stacked UD prepreg on a forming tool with varying cross section. Investigated parameters include lay-up sequence, prepreg ply thickness, inter-ply friction and prepreg ply impregnation. Experimental evaluation is performed on the out-of-plane defect height, type, location and number. Further, measurements are performed on the outer-ply deformation in the z-direction and inside the formed component using Micro CT. The study show that compression is to some degree always developed during forming of a recess area but that the lay-up sequence has a dominant effect on the wrinkling development.
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| 11. |
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| 12. |
- Hughes, Joseph L, et al.
(author)
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Photoconversion of chlorophylls in higher-plant CP43 characterized by persistent spectral hole burning at 1.7 K.
- 2004
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In: Journal of Luminescence. - : Elsevier BV. - 0022-2313. ; 108:1-4, s. 131-136
-
Journal article (peer-reviewed)abstract
- The chorophyll-protein complex CP43 is a proximal-antenna subunit important for excitation energy transfers from peripheral light-harvesting antenna to the Photosystem II (PSII) reaction centre. We report persistent spectral hole burning at 1.7 K in the Qy(0,0) origin and Qy(1,0) vibrational satellite bands of chorophyll a (chl a) in CP43 isolated from higher plants. The isolated CP43 is known to possess two quasi-degenerate 'red' trap states. We find persistent hole burning in the primary trap exhibits a photoconversion property, with a photoproduct located well outside its inhomogeneous distribution. This photoconversion of trap chl a molecules also occurs with non-selective white light illumination. The contribution of the 'red' states to CP43 absorption is discussed.
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| 13. |
-
Hur är det i praktiken? : Lärare utforskar ämnet idrott och hälsa
- 2016
-
Editorial collection (other academic/artistic)abstract
- Vad ska elever lära sig i idrott och hälsa? Hur lägger man upp undervisning som stödjer alla elever i deras lärande? Hur kan lärare göra likvärdiga bedömningar av elevers kunskaper? Detta är några av de frågor som behandlas i denna bok. Boken sammanfattar den forskning som genomförts inom Forskarskolan i idrott och hälsas didaktik (FIHD). FIHD startade år 2011 som ett led i den statliga satsningen Lärarlyftet, där särskilda medel avsattes för genomförandet av forskarskolor för lärare och förskollärare. Deltagarna i FIHD är alla verksamma lärare i idrott och hälsa. I denna bok presenterar de översiktligt resultat och slutsatser från sina olika forskningsprojekt. Kapitlen behandlar aktuella teman som lärande, hälsa, etnicitet och genus samt betyg och bedömning i idrott och hälsa.Boken finns fritt tillgänglig på webben.Innehåll:Forskarskolan i idrott och hälsas didaktik: praktiknära idrottsdidaktikTräffar vi alltid rätt? Elevers lärande i idrott och hälsa / Andreas JacobssonElevers förståelse av hälsa i idrott och hälsa / Annika AhlbergÄr grönsaker alltid hälsosamt? / Magnus BrolinHitta lätt – så blir det rätt! / Kerstin NilssonDansspel som läromedel / Béatrice GibbsDokumentation i idrott och hälsa – en omöjlig ekvation? / Rickard HåkansonPassar jag in? Nyanlända ungas möte med idrott och hälsa / Åke HuitfeldtAtt göra tudelning – idrott och hälsa i åk 1 ur ett genusperspektiv / Inga OliynykBedömning för lärande (BFL) i ämnet idrott och hälsa / Björn TolgforsVad är ”kroppslig förmåga”? Om behovet av ett yrkesspråk i idrott och hälsa / Jenny KroonBetygsättning – ett (o)möjligt uppdrag? / Izabela Seger
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| 14. |
- Johansson, Morgan, et al.
(author)
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Explosionslast och dynamisk strukturrespons i armerade betongkonstruktioner
- 2023
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In: Bygg och Teknik. - 0281-658X .- 2002-8350. ; 115:6
-
Journal article (pop. science, debate, etc.)abstract
- Med syfte att frigöra attraktiv markyta för ny bebyggelse finns det imånga svenska städer idag ett önskemål att förtäta den befintliga stadsmiljön. En sådan åtgärd kan dock resultera i minskade avstånd mellan byggnader och transportled, vilket kan medföra ökade krav med hänsyn till bland annat explosioner. För att skapa en optimal helhetslösning för sådana olycksscenarion behöver de tre delområdena riskhantering, explosionslast och strukturrespons samordnas på ett korrekt sätt. I dagens explosionshantering finns dock betydande brister bland både riskanalytiker och konstruktörer, något som ofta beror på otillräcklig kommunikation och kunskap.
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| 15. |
- Jones, Geraint H., et al.
(author)
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The Comet Interceptor Mission
- 2024
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In: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
-
Journal article (peer-reviewed)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 16. |
- Kadi, Nawar, 1970-, et al.
(author)
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The Effect of Warp Tension on the Colour of Jacquard Fabric
- 2017
-
In: IOP Conference Series: Materials Science and Engineering.
-
Conference paper (pop. science, debate, etc.)abstract
- The aims of this paper is to demonstrate the effect of warp tension on fabric colour for several types of weaves structures, and found a relationship between them. The image analyse technique used to determine the proportion of yarns colour appearance, the advantage of this techniques is the rapidity and reliability. The woven fabric samples are consisting of a polyester warp yarn with continuous filaments and density of 33 end/cm, a polypropylene weft yarn with a density of 24 pick/cm, and the warp tension ranged between 12-22 cN/tex. The experimental results demonstrated the effect of the warp tension on the colour of fabric, and this effect is related to several factors, where the large proportion of warp appearance leads to larger effect on fabric colour. The difference in the value of colour differences ΔEcmc is larger is in the range 16 to 20 cN/tex of warp tension. Using statistical methods, a mathematical model to calculate the amount of the colour difference ΔEcmc caused by the change in warp tension had been proposed.
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| 17. |
- Karageorgis, Anastassia, et al.
(author)
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A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
- 2018
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:5
-
Journal article (peer-reviewed)abstract
- Drug-induced liver injury (Dili) is a leading cause of acute liver failure and transplantation. Dili can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s -1 (n = 23) and 11.7 +/- 1.3 s -1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s -1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s -1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic. Conclusion: Rate constants of
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| 18. |
- Karnoub, Amer, et al.
(author)
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The Effect of Warp Tension on the Colour of Jacquard Fabric Made with Different Weaves Structures
- 2017
-
In: IOP Conference Series. - 1757-8981 .- 1757-899X. ; 254
-
Journal article (peer-reviewed)abstract
- The aims of this paper is to demonstrate the effect of warp tension on fabric colour for several types of weaves structures, and found a relationship between them. The image analyse technique used to determine the proportion of yarns colour appearance, the advantage of this techniques is the rapidity and reliability. The woven fabric samples are consisting of a polyester warp yarn with continuous filaments and density of 33 end/cm, a polypropylene weft yarn with a density of 24 pick/cm, and the warp tension ranged between 12-22 cN/tex. The experimental results demonstrated the effect of the warp tension on the colour of fabric, and this effect is related to several factors, where the large proportion of warp appearance leads to larger effect on fabric colour. The difference in the value of colour differences ΔEcmc is larger is in the range 16 to 20 cN/tex of warp tension. Using statistical methods, a mathematical model to calculate the amount of the colour difference ΔEcmc caused by the change in warp tension had been proposed.
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| 19. |
- Larsson, Håkan, et al.
(author)
-
Forskarskolan i idrott och hälsas didaktik : praktiknära idrottsdidaktik
- 2016
-
In: Hur är det i praktiken?. - Stockholm : Gymnastik- och idrottshögskolan, GIH. - 9789198086287 ; , s. 5-16
-
Book chapter (other academic/artistic)abstract
- Vad ska elever lära sig i idrott och hälsa? Hur lägger man upp undervisning som stödjer alla elever i deras lärande? Hur kan lärare göra likvärdiga bedömningar av elevers kunskaper? Detta är några av de frågor som behandlas i boken du nu håller i. Boken sammanfattar den forskning som genomförts inom Forskarskolan i idrott och hälsas didaktik (FIHD). FIHD startade år 2011 som ett led i den statliga satsningen Lärarlyftet, där särskilda medel avsattes för genomförandet av forskarskolor för lärare och förskollärare. Deltagarna i FIHD är alla verksamma lärare i idrott och hälsa. Detta har en central betydelse i sammanhanget. Skolämnet idrott och hälsa har funnits länge i den svenska skolan, men den vetenskapliga förankringen och utforskningen av ämnet har varit svag. Den forskning som existerat har inte i första hand genomförts av, eller på initiativ av, lärare i ämnet. Initiativen har istället kommit från annat håll, ofta från olika myndigheter. Forskningsresultaten har speglat myndigheternas intressen snarare än lärarnas. Därför är det ett stort nöje att i denna bok få möjlighet att presentera forskningsresultat som bygger på lärares frågor och där lärare har varit forskare. I detta inledande kapitel presenterar FIHD:s styrgrupp, bestående av medarbetare vid Gymnastik- och idrottshögskolan (GIH), Malmö högskola och Örebro universitet, bakgrunden till FIHD, den forskning som fanns till hands då lärarna påbörjade sina forskningsprojekt samt de ambitioner som varit förknippade med forskarskolan.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Mortensen, Jens Jorgen, et al.
(author)
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GPAW: An open Python package for electronic structure calculations
- 2024
-
In: Journal of Chemical Physics. - 1089-7690 .- 0021-9606. ; 160:9
-
Journal article (peer-reviewed)abstract
- We review the GPAW open-source Python package for electronic structure calculations. GPAW is based on the projector-augmented wave method and can solve the self-consistent density functional theory (DFT) equations using three different wave-function representations, namely real-space grids, plane waves, and numerical atomic orbitals. The three representations are complementary and mutually independent and can be connected by transformations via the real-space grid. This multi-basis feature renders GPAW highly versatile and unique among similar codes. By virtue of its modular structure, the GPAW code constitutes an ideal platform for the implementation of new features and methodologies. Moreover, it is well integrated with the Atomic Simulation Environment (ASE), providing a flexible and dynamic user interface. In addition to ground-state DFT calculations, GPAW supports many-body GW band structures, optical excitations from the Bethe-Salpeter Equation, variational calculations of excited states in molecules and solids via direct optimization, and real-time propagation of the Kohn-Sham equations within time-dependent DFT. A range of more advanced methods to describe magnetic excitations and non-collinear magnetism in solids are also now available. In addition, GPAW can calculate non-linear optical tensors of solids, charged crystal point defects, and much more. Recently, support for graphics processing unit (GPU) acceleration has been achieved with minor modifications to the GPAW code thanks to the CuPy library. We end the review with an outlook, describing some future plans for GPAW.
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| 24. |
- Munn-Chernoff, M. A., et al.
(author)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
-
In: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
-
Journal article (peer-reviewed)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 25. |
- Peterson, Kristoffer, et al.
(author)
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Systematic Tuning of Fluoro-galectin-3 Interactions Provides Thiodigalactoside Derivatives with Single-Digit nM Affinity and High Selectivity
- 2018
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:3, s. 1164-1175
-
Journal article (peer-reviewed)abstract
- Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional affinities (Kd down to 1-2 nM) in symmetrically substituted thiodigalactosides as well as unsurpassed combination of high affinity (Kd 7.5 nM) and selectivity (46-fold) over galectin-1 for asymmetrical thiodigalactosides by carrying one trifluorphenyltriazole and one coumaryl moiety. Studies of the inhibitor-galectin complexes with isothermal titration calorimetry and X-ray crystallography revealed the importance of fluoro-amide interaction for affinity and for selectivity. Finally, the high affinity of the discovered inhibitors required two competitive titration assay tools to be developed: a new high affinity fluorescent probe for competitive fluorescent polarization and a competitive ligand optimal for analyzing high affinity galectin-3 inhibitors with competitive isothermal titration calorimetry.
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| 26. |
- Peterson, Mikael, et al.
(author)
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Construction of a Pre-Clinical High Resolution Tomographic Scintillation Camera System
- 2009
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In: 2009 IEEE Nuclear Science Symposium Conference Record, Vols 1-5. - 1082-3654. ; , s. 3670-3671
-
Conference paper (peer-reviewed)abstract
- We are constructing a High Resolution Tomographic Scintillation Camera System for small animal imaging. The system consists of a CsI(Tl) scintillator coupled to a military surplus image intensifier with a CCD camera focused on the output window. The system operates in photons counting mode and the spatial resolution is improved by centroid calculations for every photon interaction. The system can be mounted on an optical rail together with a pinhole collimator and a rotating table. A hot rod phantom was filled with Tl-201 or Tc-99m solute and imaged. The phantom rod diameters range from 1.1 to 1.6 mm. 64 projections were acquired (300 s/projection) with 1 mm pinhole insert. Data was reconstructed using an OSEM algorithm. Image data was corrected for decay, position non-linearities in image intensifier and the angular dependence of the pinhole. The reconstructed resolution is 13 mm (by visual inspection) for both Tc-99m and Tl-201. Higher spatial resolution is achievable with smaller pinhole diameters. Future work includes optimizing spatial resolution and sensitivity of a single system using analytical calculations, experiments and simulations. With the conclusions drawn from those calculations we plan to construct a multi-camera system.
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| 27. |
- Peterson, Mikael, et al.
(author)
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Monte Carlo-based quantitative pinhole SPECT reconstruction using a ray-tracing back-projector
- 2017
-
In: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1
-
Journal article (peer-reviewed)abstract
- Background: Monte Carlo simulations provide accurate models of nuclear medicine imaging systems as they can properly account for the full physics of photon transport. The accuracy of the model included in the maximum-likelihood–expectation-maximization (ML-EM) reconstruction limits the overall accuracy of the reconstruction results. In this paper, we present a Monte Carlo-based ML-EM reconstruction method for pinhole single-photon emission computed tomography (SPECT) that has been incorporated into the SIMIND Monte Carlo program. The Monte Carlo-based model, which accounts for all of the physical and geometrical characteristics of the camera system, is used in the forward-projection step of the reconstruction, while a simpler model based on ray-tracing is used for back-projection. The aim of this work was to investigate the quantitative accuracy of this combination of forward- and back-projectors in the clinical pinhole camera GE Discovery NM 530c. Results: The total activity was estimated in 99mTc-filled spheres with volumes between 0.5 and 16 mL. The total sphere activity was generally overestimated but remained within 10% of the reference activity defined by the phantom preparation. The recovered activity converged towards the reference activity as the number of iterations increased. Furthermore, the recovery of the activity concentrations within the physical boundaries of the spheres increased with increasing sphere volume. Additionally, the Monte Carlo-based reconstruction enabled recovery of the true activity concentration in the myocardium of a cardiac phantom mounted in a torso phantom regardless of whether the torso was empty or water-filled. A qualitative comparison to data reconstructed using the clinical reconstruction algorithm showed that the two methods performed similarly, although the images reconstructed using the clinical software were more uniform due to the incorporation of noise regularization and post-filtration in that reconstruction technique. Conclusions: We developed a Monte Carlo-based reconstruction method for pinhole SPECT and evaluated it using phantom measurements. The combination of a Monte Carlo-based forward-projector and a simplified analytical ray-tracing back-projector produced quantitative images of acceptable image quality. No explicit calibration is necessary in this method since the forward-projector model maintains a relationship between the number of counts and activity.
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| 28. |
- Peterson, Mikael
(author)
-
SPECT Imaging using Pinhole Collimation : System Design and Simulation Studies for Pre-Clinical and Clinical Imaging
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- The focus of this dissertation is the use of pinhole collimation in Nuclear Medicine. A pinhole is a single aperture in an opaque material that is placed between the detector and source of interest, and photons must pass through the hole to reach the detector. The choices of pinhole parameters, e.g. the pinhole material and size of the opening, are closely linked to the performance of the detector system.Pinhole-based single-photon emission computed tomography (SPECT) has primarily been used to investigate human diseases in small animals because of the superior resolution and efficiency achieved with this type of collimation. The SPECT methodology involves determination of the radiopharmaceutical distribution within an object. An essential step in this methodology is the image reconstruction, i.e., the transformation of the acquired two-dimensional (2D) data into a three-dimensional (3D) distribution.This dissertation describes the development of a SPECT system for small animal imaging called InSPECT. In Paper I, determination of the reconstructed resolution for a prototype setup with a video-based detector system is discussed, and in Paper II, construction of the InSPECT system with eight separate video detectors is described. A fusible metal, Rose’s metal, was used to cast the centre bore, in which platinum pinholes were mounted. The cast pieces could adequately shield the detectors and could be machined with a high precision. Thus, Rose’s metal, which is relatively inexpensive, could be employed for pinhole collimation but would lead to image characteristics that are less favourable than those achievable using gold or platinum pinholes. In Paper III, we present an evaluation of the performance of Rose’s metal pinholes and a comparison with other pinhole materials.Monte Carlo-based computer models can be utilised to simulate the image formation process and can enable expensive and time-consuming instrumentation changes to be evaluated prior to building prototypes. In Paper IV, we discuss the implementation of a cadmium zinc telluride (CZT) semiconductor detector model in the Monte Carlo program SIMIND. The accuracy of the model was confirmed by comparing its results to measurements. In Paper V, we address the use of the CZT model in an SIMIND-based maximum-likelihood–expectation-maximisation iterative reconstruction of the measured data. The images reconstructed using the computer model enabled the quantification of the total activity without requiring calibration of the detector count per unit second per unit activity. In Paper VI, we describe the simulation of a dedicated SPECT scanner that employs 19 semiconductor detector–pinhole units for myocardial perfusion imaging. Compared to conventional SPECT devices, this camera is more efficient, and the efficiency is often traded for a reduction in imaging times and patient doses. An alternative use of the efficiency is to use smaller pinhole which yields better spatial resolution in the projections. No increase in contrast-to-noise was seen for smaller pinholes since any increase in contrast was also accompanied by an equal increase in noise. Also, changes in transmurality affected the CNR to a greater extent than did changes in lesion extent.
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| 29. |
- Peterson, Mikael, et al.
(author)
-
Using Rose's metal alloy as a pinhole collimator material in preclinical small-animal imaging: A Monte Carlo evaluation.
- 2015
-
In: Medical Physics. - : Wiley. - 0094-2405. ; 42:4, s. 1698-1709
-
Journal article (peer-reviewed)abstract
- Pinhole collimation is the most common method of high-resolution preclinical single photon emission computed tomography imaging. The collimators are usually constructed from dense materials with high atomic numbers, such as gold and platinum, which are expensive and not always flexible in the fabrication step. In this work, the authors have investigated the properties of a fusible alloy called Rose's metal and its potential in pinhole preclinical imaging. When compared to current standard pinhole materials such as gold and platinum, Rose's metal has a lower density and a relatively low effective atomic number. However, it is inexpensive, has a low melting point, and does not contract when solidifying. Once cast, the piece can be machined with high precision. The aim of this study was to evaluate the imaging properties for Rose's metal and compare them with those of standard materials.
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| 30. |
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| 31. |
- Peterson, Viktor
(author)
-
Assessment of shear and energy‐absorption capacity of reinforced concrete elements under impulsive loads
- 2023
-
Licentiate thesis (other academic/artistic)abstract
- Impulsive loads have been observed to cause brittle shear failure in reinforced concrete elements designed for ductile failure modes under static loads. Brittle failure modes exhibit poorer energy absorption capabilities compared to ductile flexural failure modes due to their limited deformation capacity, leading to premature failure. The discrepancy between the responses under static and extreme dynamic loads arises from inertia and wave propagation effects, which tend to increase as the load duration decreases relative to the fundamental period of the element. This thesis investigated the occurrence of shear failures in reinforced concrete elements subjected to impulsive loads, both experimentally and numerically, and evaluated to what extent current analysis methods for impulse-loaded structures can predict shear failure. Furthermore, the study examined the influence of crucial parameters on the energy absorption capacity during flexural failure modes when shear failure was inhibited. The results demonstrated that shear-plug damage, prevalent during impact loads, may lead to premature shear failure during sequential impact testing. This occurred for a statically flexure-critical beam with a significantly larger static flexural-shear capacity relative to its flexural capacity. Similar conclusions applied to the residual static capacity after an initial impact introduced shear-plug damage. These findings indicate potentially severe consequences of shear-plug damage, which should be considered when assessing structures damaged by impact loads. The energy absorption capacity of reinforced concrete elements is closely related to the plastic work capacity of the reinforcement. The experimental study showed how the plastic work capacity varied with reinforcement properties, concrete properties, and impact velocity using static and dynamic four-point flexural tests. The results revealed that the reinforcement type, specifically whether the steel is mild or stiff, governs the strain distribution during static and low-velocity impact testing. Generally, stiff steels result in strain localization before rupturing, indicating a lower plastic work capacity. Factors such as stress and strain capacity also proved significant. However, as the impact velocity increased, wave propagation effects governed strain distribution rather than reinforcement type. Numerical studies comparing results with outcomes using proposed design methods indicated agreement for support reactions used to verify the shear capacity in the later stages of the response. However, this agreement decreased in the initial stages of the response. This may be because the dynamic equilibrium method only considers a global response, while the local response due to wave propagation is influential in the initial stages of the response. Today, resources such as Biggs [8] and the Swedish Fortifications Agency [86] recommend using two stages of the response to determine the internal forces; an elastic global response and a later elastoplastic global response. From the observations in the papers, it is suggested to add a third initial stage of the response considering wave propagation effects. However, it is deemed that this response stage only has a significant effect for high-intensity blast loads with short rise times relative to the shear wave velocity.
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| 32. |
- Peterson, Viktor, et al.
(author)
-
Numerical simulations of shear reinforced RC beams subjected to blast loads
- 2022
-
In: <em>fib Symposium</em>. - : fib. The International Federation for Structural Concrete.
-
Conference paper (peer-reviewed)abstract
- The numerical simulations presented in the present paper were on beam models geometrically identical to the beams previously tested in a shock tunnel but now provided with increased shear reinforcement consisting of vertical stirrups. The tested beam failed in brittle flexural shear during the blast loading in the tunnel. The results from the numerical investigation showed that brittle shear failures of beams subjected to blast loads may be prevented by dense shear reinforcement. The guideline for impulse loaded structure showed to underestimate the dynamic shear capacity as it is not dependent on the actual transverse reinforcement amount. This is however considered in the model used for determining the static shear capacity, meaning that further work developing a similar model fit to impulse loading is advised. To realize this development a new test series is proposed.
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| 33. |
- Peterson, Viktor, et al.
(author)
-
On the Residual Static and Impact Capacity of Shear-Reinforced Concrete Beams Subjected to an Initial Impact
- 2022
-
In: Applied Sciences. - : MDPI. - 2076-3417. ; 12:22, s. 11377-
-
Journal article (peer-reviewed)abstract
- Impact loads in previous research showed to induce brittle responses of statically flexure-critical reinforced concrete (RC) beams designed for ductility. The impact load may produce flexural shear damage modes similar to that observed during quasi-static loads and local shear damage under the impact zone. The occurrence of shear damage modes during impact tests has been investigated extensively, but their effect on the residual quasi-static and dynamic capacity is not fully understood. For this aim, an initial high-velocity impact test initiated severe shear damage to RC beams. The beams were then tested quasi-statically and by sequential impact testing using the same setup as the initial tests. The results indicate a flexure-dominated response during sequential impact tests for beams containing extreme shear reinforcement amounts, favouring the energy-absorption capacity. Significant shear and flexural damage occurred for beams with less shear reinforcement, indicating a hybrid response that varied throughout the tests. The tests for the residual quasi-static capacity indicated severe consequences from initial local shear damage on the capacity, as shown by the brittle response of the beam with the most shear reinforcement. However, wide initial flexural cracks instead showed a favourable effect, as there was an indication of transfer from brittle to ductile failure. For beams showing both global and local shear damage, it was concluded that global shear damage modes were critical for the residual static and dynamic shear capacity.
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| 34. |
- Peterson, Viktor, et al.
(author)
-
The effect of explosions in road tunnels on critical structural elements
- 2023
-
In: Expanding Underground - Knowledge and Passion to Make a Positive Impact on the World. - : CRC Press/Balkema. ; , s. 3263-3271
-
Conference paper (peer-reviewed)abstract
- In the present paper, the walls of a concrete frame used for over-decking in a road tunnel were first designed using the relevant design provisions. The response of the wall was then analysed using non-linear finite element analysis, and the results of the finite element analysis were compared to what was predicted using the design guidelines. Additionally, simulations of the blast load resulting from gas leakage during transportation were conducted as a separate study. The results from two vapour clouds containing gases of hydrogen and propane were compared.
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| 35. |
- Peterson Årsköld, Sindra, et al.
(author)
-
Low-temperature spectroscopy of fully active cores. Comparison with CP43, CP47
- 2004
-
In: Journal of Luminescence. - : Elsevier BV. - 0022-2313. ; 108:1-4, s. 97-100
-
Journal article (peer-reviewed)abstract
- Comparisons of absorption spectra of photosystem II (PSII) core complexes with those of isolated CP43, CP47 and D1/D2/cyt b559 complexes show broadenings and shifts upon disassembly of the PSII core material. Spectra of PSII cores isolated from plants and cyanobacteria reveal marked changes in energies and intensities of the sharp features associated with P680. Low-temperature, illumination-induced electrochromic shifts in PSII cores allow identification of an excitation localized on pheopytin-a (pheo a) in D1. A weak interaction between an exciton component of P680 and the D1 pheo a, both located near 684 nm, is suggested. MCD spectra of 5- and 6-chlorophyll a D1/D2/cytochrome b559 preparations provide links to photoactive pigments in intact PSII cores.
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| 36. |
- Pretorius, P. Hendrik, et al.
(author)
-
Monte Carlo Simulations of the GE Discovery Alcyone CZT SPECT Systems
- 2015
-
In: IEEE Transactions on Nuclear Science. - 0018-9499. ; 62:3, s. 832-839
-
Journal article (peer-reviewed)abstract
- Compact SPECT systems with cadmium zinc telluride (CZT) solid-state detectors with improved energy resolution and shorter acquisition times have recently been introduced. These systems have, however, different energy characteristics compared to NaI(Tl) crystal-based cameras; therefore, a need exists to develop new simulation models for these cameras. We modeled the charge transport within the CZT detectors for a GE Discovery 530c/570c SPECT system with multiple pinhole collimators employing the SIMIND Monte Carlo program and validated simulations against measurements. The incomplete charge collection between the anode and cathode in the pixilated CZT was modeled with the Hecht equation. The simulation also included charge-sharing effects across pixels due to physical interactions and charge diffusion. To validate our CZT-model, Tc-99m and I-123 point sources and a Tl-201 line source were acquired and measured. Measured energy spectra were compared with simulated energy spectra. The Monte Carlo simulated energy spectra agreed well with the experimental measurements within the photopeak, overestimated the k-edge x-ray escape peaks of cadmium and telluride, and slightly underestimated the remainder of the tail. Comparisons of system sensitivity and spatial resolution were also conducted for an array of point source locations with results showing excellent agreement. Lastly, to demonstrate a clinically realistic case, a simulation of an anthropomorphic phantom with a cardiac insert and an inferior defect was performed. Simulated projections were processed using the GE Xeleris software confirming the accuracy of the SIMIND geometry. We conclude that it is feasible to simulate the GE Discovery 530c/570c SPECT system using the SIMIND code.
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| 37. |
- Rosentau, A., et al.
(author)
-
A Holocene relative sea-level database for the Baltic Sea
- 2021
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 266
-
Journal article (peer-reviewed)abstract
- We present a compilation and analysis of 1099 Holocene relative shore-level (RSL) indicators located around the Baltic Sea including 867 relative sea-level data points and 232 data points from the Ancylus Lake and the following transitional phase. The spatial distribution covers the Baltic Sea and near-coastal areas fairly well, but some gaps remain mainly in Sweden. RSL data follow the standardized HOLSEA format and, thus, are ready for spatially comprehensive applications in, e.g., glacial isostatic adjustment (GIA) modelling. We apply a SQL database system to store the nationally provided data sets in their individual form and to map the different input into the HOLSEA format as the information content of the individual data sets from the Baltic Sea area differs. About 80% of the RSL data is related to the last marine stage in Baltic Sea history after 8.5 ka BP (thousand years before present). These samples are grouped according to their dominant RSL tendencies into three clusters: regions with negative, positive and complex (transitional) RSL tendencies. Overall, regions with isostatic uplift driven negative tendencies dominate and show regression in the Baltic Sea basin during the last marine stage. Shifts from positive to negative tendencies in RSL data from transitional regions show a mid-Holocene highstand around 7.5-6.5 ka BP which is consistent with the end of the final melting of the Laurentide Ice Sheet. Comparisons of RSL data with GIA predictions including global ICE-5G and ICE-6G_C ice histories show good fit with RSL data from the regions with negative tendencies, whereas in the transitional areas in the eastern Baltic, predictions for the mid-Holocene clearly overestimate the RSL and fail to recover the midHolocene RSL highstand derived from the proxy reconstructions. These results motivate improvements of ice-sheet and Earth-structure models and show the potential and benefits of the new compilation for future studies. (C) 2021 The Authors. Published by Elsevier Ltd.
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| 38. |
- Siikanen, Jonathan, et al.
(author)
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A Peristaltic Pump Driven Zr-89 Separation Module
- 2012
-
In: 14th International Workshop on Targetry and Target Chemistry. - : AIP. - 1551-7616 .- 0094-243X. ; 1509, s. 206-210
-
Conference paper (peer-reviewed)abstract
- To facilitate the separation of Zr-89 produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced Zr-89 - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated Zr-89 activity was investigated for labeling of the HER2-binding monoclonal antibody fragment, trastuzumab-Fab.
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| 39. |
- Slepenkin, Anatoly, et al.
(author)
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Protection of mice from a chlamydia trachomatis vaginal infection using a salicylidene acylhydrazide, a potential Mmcrobicide
- 2011
-
In: Journal of Infectious Diseases. - Chicago : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 204:9, s. 1314-1320
-
Journal article (peer-reviewed)abstract
- The salicylidene acylhydrazide INP0341 inhibits growth of Chlamydia in HeLa cells, has negligible cell toxicity, and does not inhibit the growth of lactobacilli. The antichlamydial activity of INP0341 was retained when tested in vaginal and semen simulants. Vaginal tissue from INP0341-treated mice appeared similar to control sham-treated mice. To determine whether INP0341 can protect mice from a vaginal challenge, C3H/HeJ mice were either sham or INP0341 treated intravaginally pre- and postinoculation with 5 × 10(2) inclusion-forming units (IFUs) of Chlamydia trachomatis serovar D. Vaginal cultures taken over a month-long period showed a significant difference in the number of control mice that were culture positive versus the number in the INP0341-treated group, 100% (25/25) and 31% (8/26), respectively (P < .05). The quantity of IFUs shed and antibody titers to Chlamydia were significantly higher for the control group (P < .05). In summary, INP0341 is a promising compound to be considered for formulation as a vaginal microbicide.
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| 40. |
- Slepenkin, Anatoly, et al.
(author)
-
Reversal of the Antichlamydial Activity of Putative Type III Secretion Inhibitors by Iron
- 2007
-
In: Infection and Immunity. ; 75:7, s. 3478-89
-
Journal article (peer-reviewed)abstract
- INPs, which are chemically synthesized compounds belonging to a class of acylated hydrazones of salicylaldehydes, can inhibit the growth of Chlamydiaceae. Evidence has been presented that in Yersinia and Chlamydia INPs may affect the type III secretion (T3S) system. In the present study 25 INPs were screened for antichlamydial activity at a concentration of 50 µM, and 14 were able to completely inhibit the growth of Chlamydia trachomatis serovar D in McCoy and HeLa 229 cells. The antichlamydial activities of two of these INPs, INPs 0341 and 0400, were further characterized due to their low cytotoxicity. These compounds were found to inhibit C. trachomatis in a dose-dependent manner; were not toxic to elementary bodies; were cidal at a concentration of 20 µM; inhibited all Chlamydiaceae tested; and could inhibit the development of C. trachomatis as determined by the yield of progeny when they were added up to 24 h postinfection. INP 0341 was able to affect the expression of several T3S genes. Compared to the expression in control cultures, lcrH-1, copB, and incA, all middle- to late-expressed T3S genes, were not expressed in the INP 0341-treated cultures 24 to 36 h postinfection. Iron, supplied as ferrous sulfate, as ferric chloride, or as holo-transferrin, was able to negate the antichlamydial properties of the INPs. In contrast, apo-transferrin and other divalent metal ions tested were not able to reverse the inhibitory effect of the INPs. In conclusion, the potent antichlamydial activity of INPs is directly or indirectly linked with iron, and this inhibition of Chlamydia has an effect on the T3S system of this intracellular pathogen.
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| 41. |
- Strand, Niklas, 1981-, et al.
(author)
-
Report on simulator test results and driver acceptance of PROSPECT functions
- 2019
-
Reports (other academic/artistic)abstract
- The process of developing new automotive systems includes various testing cycles to assure a save operation in traffic. Physical system testing on test tracks is very important for this purpose, but rather expensive and might only become possible in later stages of the development process. Using a virtual simulation environment offers a safe possibility of testing new systems in early stages of development. Aditionally, driver-in-the-loop tests at test track and in a virtual simulator make it possible to evaluate driver reaction and potential acceptance by the future users of those systems. Within PROSPECT the new functions are investigated under various aspects in several simulator studies and test track studies.This deliverable D7.3 gives detailed information of conduction and results of the each study. Three studies focus exclusively on the for Vulnerable Road Users (VRUs) specifically dangerous urban intersection scenarios. The first of those studies examines the driver behaviour in a turning situation when a byciclist might be crossing. The second study, which provides an initial step in this line of research, analyzed the acceptance of issued forward collision warning times. In the third study acceptance of an intersection assist autonomous emergency braking systems was tested regarding the acceptance of potential buyers.Two studies focused on longitudinal scenarios. Both studies followed the same design, but one was conducted on a test track and the other one in a simulator. The main objective was to investigate drivers reactions to FCW warnings and Active Steering interventions in critical VRU scenarios in case of a distraction of the driver.
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| 42. |
- Söderholm, Johan D, 1958-, et al.
(author)
-
Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of crohn's disease
- 2002
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 50:3, s. 307-313
-
Journal article (peer-reviewed)abstract
- Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=l 2) were studied, and ileal specimens from colon cancer patients (n=l 3) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability - that is, increased permeation of 51Cr-EDTA and decreased electrical resistance - which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.
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| 43. |
- Thompson, Paul M., et al.
(author)
-
The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
-
In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
-
Journal article (peer-reviewed)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 44. |
- Tsapogas, Panagiotis, et al.
(author)
-
RNA analysis of B cell lines arrested at defined stages of differentiation allows for an approximation of gene expression patterns during B cell development
- 2003
-
In: Journal of Leukocyte Biology. - : Society for Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 74:1, s. 102-110
-
Journal article (peer-reviewed)abstract
- The development of a mature B lymphocyte from a bone marrow stem cell is a highly ordered process involving stages with defined features and gene expression patterns. To obtain a deeper understanding of the molecular genetics of this process, we have performed RNA expression analysis of a set of mouse B lineage cell fines representing defined stages of B cell development using Affymetrix(TM) microarrays. The cells were grouped based on their previously defined phenotypic features, and a gene expression pattern for each group of cell. lines was established. The data indicated that the cell lines representing a defined stage generally presented a high similarity in overall expression profiles. Numerous genes could be identified as expressed with a restricted pattern using dCHIP-based, quantitative comparisons or presence/absence-based, probabilistic state analysis. These experiments provide a model for gene expression during B cell development, and the correctly identified expression patterns of a number of control genes suggest that a series of cell fines can be useful tools in the elucidation of the molecular genetics of a complex differentiation process.
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| 45. |
- Ur-Rehman, Tofeeq, et al.
(author)
-
Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion
- 2012
-
In: The Journal of antibiotics. - : Springer Science and Business Media LLC. - 0021-8820 .- 1881-1469. ; 65, s. 397-404
-
Journal article (peer-reviewed)abstract
- Salicylidene acylhydrazides belong to a class of compounds shown to inhibit bacterial type III secretion (T3S) in pathogenic Gram-negative bacteria. This class of compounds also inhibits growth and replication of Chlamydiae, strict intracellular bacteria that possess a T3S system. In this study a library of 58 salicylidene acylhydrazides was screened to identify inhibitors of Chlamydia growth. Compounds inhibiting growth of both Chlamydia trachomatis and Chlamydophila pneumoniae were tested for cell toxicity and seven compounds were selected for preliminary pharmacokinetic analysis in mice using cassette dosing. Two compounds, ME0177 and ME0192, were further investigated by individual pharmacokinetic analysis. Compound ME0177 had a relatively high peak plasma concentration (C(max)) and area under curve and therefore may be considered for systemic treatment of Chlamydia infections. The other compound, ME0192, had poor pharmacokinetic properties but the highest anti-chlamydial activity in vitro and therefore was tested for topical treatment in a mouse vaginal infection model. ME0192 administered vaginally significantly reduced the infectious burden of C. trachomatis and the number of infected mice.Journal of Antibiotics advance online publication, 6 June 2012; doi:10.1038/ja.2012.43.
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| 46. |
- Wallerstein, Johan, et al.
(author)
-
Entropy-Entropy Compensation between the Protein, Ligand, and Solvent Degrees of Freedom Fine-Tunes Affinity in Ligand Binding to Galectin-3C
- 2021
-
In: Jacs Au. - : American Chemical Society (ACS). - 2691-3704. ; 1:4, s. 484-500
-
Journal article (peer-reviewed)abstract
- Molecular recognition is fundamental to biological signaling. A central question is how individual interactions between molecular moieties affect the thermodynamics of ligand binding to proteins and how these effects might propagate beyond the immediate neighborhood of the binding site. Here, we investigate this question by introducing minor changes in ligand structure and characterizing the effects of these on ligand affinity to the carbohydrate recognition domain of galectin-3, using a combination of isothermal titration calorimetry, X-ray crystallography, NMR relaxation, and computational approaches including molecular dynamics (MD) simulations and grid inhomogeneous solvation theory (GIST). We studied a congeneric series of ligands with a fluorophenyl-triazole moiety, where the fluorine substituent varies between the ortho, meta, and para positions (denoted O, M, and P). The M and P ligands have similar affinities, whereas the O ligand has 3-fold lower affinity, reflecting differences in binding enthalpy and entropy. The results reveal surprising differences in conformational and solvation entropy among the three complexes. NMR backbone order parameters show that the O-bound protein has reduced conformational entropy compared to the M and P complexes. By contrast, the bound ligand is more flexible in the O complex, as determined by F-19 NMR relaxation, ensemble-refined X-ray diffraction data, and MD simulations. Furthermore, GIST calculations indicate that the O-bound complex has less unfavorable solvation entropy compared to the other two complexes. Thus, the results indicate compensatory effects from ligand conformational entropy and water entropy, on the one hand, and protein conformational entropy, on the other hand. Taken together, these different contributions amount to entropy-entropy compensation among the system components involved in ligand binding to a target protein.
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| 47. |
- Wennerstrand, Patricia, 1982-
(author)
-
Biophysical Characterization of Thiopurine S-Methyltransferase : A Key enzyme in the Effects of Thiopurine Drugs
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- In the treatment of leukemia and inflammatory bowel disease, thiopurines are commonly used drugs. Thiopurine S-methyltransferase (TPMT) is one of the drug metabolizing enzymes responsible of counteracting the formation of TGNs that will be incorporated into the DNA and RNA synthesis and thus induce apoptosis. TPMT is a polymorphic enzyme and to date about 30 different sequence variants have been identified. Individuals who are to be treated with thiopurines are genotyped and/ or phenotyped at the time of diagnosis in order to individualize the treatment, with thiopurine dosage adjusted to the TPMT activity. In the treatment of acute lymphoblastic leukemia (ALL) high-dose methotrexate (MTX) is administered intravenously during the consolidation phase of the therapy and used in lower doses in the other phases of the ALL therapy. In blood samples from 53 children with ALL, we found decreased TPMT enzyme activity after 66 hours infusion of high-dose MTX. TPMT was recombinantly expressed, and the potential binding of MTX to TPMT was investigated by a fluorescence method. This showed that MTX bound to TPMT at relevant plasma concentrations observed in patient samples. At the time of leukemia diagnosis, TPMT activity was not correlated with the genotype for TPMT wild-types, which demonstrates the importance of using genotyping as a golden standard for determination of TPMT status in individuals with haematological malignancies. The low enzyme activity of TPMT*2 and TPMT*5 protein was evaluated by expressing these sequence variants in Escherichia coli (E.coli), and then characterizing them biophysically. Our results showed that TPMT*2 and TPMT*5 in the native state did not bind the extrinsic probe anilinonaphthalene sulfonate (ANS), which shows that the three-dimensional structure is already affected and restructured in that state. Based on these findings, we concluded that ANS can be used to probe the status of the active site. In another study we investigated the characteristics of TPMT*6 and TPMT*8 and found that the cofactor, S-adenosylmethionine (SAM) had a stabilizing effect on those sequence variants and on TPMT wild-type. Analysis of the structure of the TPMT protein by nuclear magnetic resonance (NMR) spectroscopy, enabled partial assignment of the backbone residue, of 64% of the TPMT sequence. Forty residues in TPMT exhibited millisecond dynamics but only 15 of those residues could be assigned, which emphasizes the difficulties involved in determining the three-dimensional structure of TPMT by NMR spectroscopy. In conclusion the present studies contribute to the understanding of the molecular characteristics of TPMT.
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