| 1. |
- Olofsson, Anders, et al.
(författare)
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Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2
- 2009
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Ingår i: The FEBS Journal. - : Wiley InterScience. - 1742-464X .- 1742-4658. ; 276:15, s. 4051-4060
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-β peptide (Aβ). Divalent metal ions such as Cu2+ and Zn2+ are known to significantly affect the rate of aggregation and morphology of Aβ assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Aβ(1–40) and Aβ(1–42) in the presence or absence of either Cu2+ or Zn2+ using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Aβ aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1–Lys16. Our results suggest that Aβ in complex with either Cu2+ or Zn2+ can attain an aggregation-prone β-strand–turn–β-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.
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| 2. |
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| 3. |
- Backman, Ylva, et al.
(författare)
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Ethics in school : from moral development to children's conceptions of justice
- 2009
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Konferensbidrag (refereegranskat)abstract
- A main issue in Swedish school debate is the question of how to teach the student a common value system based on democracy and western humanism. The debate is rather intense, to say the least. Not only is the premise that there exists one value system that we share a target for critique, but there is also the question of what value education is or could be. There is, as well, quite a body of research on children's moral development, where many take as their departure the work of Kohlberg. However, there has been little or no attention on how the individual learner conceptualizes and makes meaning out of ethical issues. That is, descriptions of processes. In this paper we will present what we take to be urgent questions that need to be investigated against the background of prior research and practical work at Södra teatern in Stockholm, Sweden. For eight years in a row, Södra teatern has had as a main project to lead a practice on the subject of philosophy with children. Several groups of youths in the age of nine to eighteen have regularly met to discuss philosophical thoughts and problems, which in a democratic manner are settled for discussion by the participants. Today this philosophical practice has spread to the north of Sweden. In Backman's final exam within the teacher education she has explored the development of children's (7‐8 years old) ability to argue for different ethical positions, both verbally and in writing and painting. This practice has been inspired by the tradition at Södra teatern, but customized to fit a regular school class in Luleå, with very little experience of philosophical discussion. In the very short period of five weeks Backman has been able to see quite significant changes in the children's ability to argue for their ethical positions. The study was initiated by examining some argumentative abilities of the pupils, for instance the ability of expressing an argument for an ethical position in writing. In the final part of the study, the same ability was examined in very similar circumstances, and the augment of expressed arguments in writing was significant. Another consideration that was raised as a consequence of the study regards the pupil's conceptualizing of ethical issues. In some conversations about the notion of justice it became clear that children interpreted the term very differently. This is not very surprising but important to pay further attention to. As mentioned earlier, there has been very little attention on how individual children conceptualize ethical issues. In this paper we argue that more interest should be put on investigating these issues in more depth, and we will do this by an outlining of a research application.
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| 4. |
- Balaz, Martina, et al.
(författare)
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Protein-surface Interactions and Functional Geometry of Surface-adsorbed Myosin Motor Fragments
- 2009
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Ingår i: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 96:3 Suppl. 1, s. 495A-495A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biophysical studies with myosin motor fragments (heavy meromyosin; HMM and subfragment 1; S1) adsorbed to artificial surfaces, are important for elucidation of actomyosin function. In spite of the widespread use of such in vitro motility assays and single molecule studies, little is known about the adsorption geometry and effects of protein-surface interactions on the motor properties. Here, we investigate these factors with focus on HMM using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) spectroscopy based ATPase assays. In the latter, we monitored the turnover of Alexa-fluor647-ATP (Alexa-ATP) by surface adsorbed HMM. Studies were performed with HMM/S1 adsorbed to model hydrophilic (SiO2) or hydrophobic (trimethyl-chlorosilane [TMCS] - derivatized) surfaces. The results suggest that adsorption of HMM is weakened on SiO2 (but not on TMCS) at high (245 mM) compared to low (65 mM) ionic strengths. The changes in ionic strength were also associated with structural changes in the protein layer according to QCM-D studies. Moreover, the TIRF based ATPase assay suggested a larger fraction of HMM molecules with low catalytic activity on SiO2. These and other TIRF and QCM-D results, suggest that HMM preferentially adsorbs to negatively charged hydrophilic surfaces via the actin-binding region. In contrast, the majority of the HMM molecules seem to adsorb via their C-terminal tail on moderately hydrophobic surfaces. In the latter case the catalytic sites appear to be close to, but not immobilized on the surface. The results with HMM were compared to, and found consistent with, QCM-D and TIRF-data obtained with S1 motor fragments.
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| 5. |
- Barfod, Anders, et al.
(författare)
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In vitro selection of RNA aptamers against a conserved region of the Plasmodium falciparum erythrocyte membrane protein 1.
- 2009
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Ingår i: Parasitology Reseach. - : Springer Science and Business Media LLC. - 1432-1955 .- 0932-0113. ; Aug 20, s. 1557-1566
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Tidskriftsartikel (refereegranskat)abstract
- The var-gene encoding Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is known to play a major role in the pathogenicity of the P. falciparum parasite. The protein enables the parasite to adhere to the endothelial linings of small blood vessels (cytoadherence) as well as to non-infected erythrocytes (rosetting), thus preventing clearance from the bloodstream. The development and spread of resistance towards most anti-malarial drugs used for treatment and prevention of the most severe form of malaria truly emphasise the importance of a continuous research and development of new drugs. In this study we use Systematic Evolution of Ligands by EXponential enrichment (SELEX) methodology to isolate high-affinity ligands (aptamers). To validate the results from the SELEX in vitro selection, different aptamers have been selected against PfEMP1 in a live cell assay of P. falciparum strain FCR3S1.2, a highly rosetting strain. We have been able to show the rosette disrupting capacity of these SELEX-aptamers at concentrations of 33 nM and with 100% disruption at 387 nM. The described results show that RNA aptamers are promising candidates for adjunct therapy in severe malaria.
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| 6. |
- Bivall Persson, Petter, 1979-, et al.
(författare)
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Improved Feature Detection over Large Force Ranges Using History Dependent Transfer Functions
- 2009
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Ingår i: Third Joint Eurohaptics Conference and Symposium on Haptic Interfaces for Virtual Environments and Teleoperator Systems, WorldHaptics 2009. - : IEEE. - 9781424438587 ; , s. 476-481
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Konferensbidrag (refereegranskat)abstract
- In this paper we present a history dependent transfer function (HDTF) as a possible approach to enable improved haptic feature detection in high dynamic range (HDR) volume data. The HDTF is a multi-dimensional transfer function that uses the recent force history as a selection criterion to switch between transfer functions, thereby adapting to the explored force range. The HDTF has been evaluated using artificial test data and in a realistic application example, with the HDTF applied to haptic protein-ligand docking. Biochemistry experts performed docking tests, and expressed that the HDTF delivers the expected feedback across a large force magnitude range, conveying both weak attractive and strong repulsive protein-ligand interaction forces. Feature detection tests have been performed with positive results, indicating that the HDTF improves the ability of feature detection in HDR volume data as compared to a static transfer function covering the same range.
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| 7. |
- Brismar, Torkel, et al.
(författare)
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Liver Vessel Enhancement by Gd-BOPTA and Gc-EOB-DTPA – a Comparison in Healthy Volunteers.
- 2009
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Ingår i: Acta Radiologica. - : Informa Healthcare. - 0284-1851 .- 1600-0455. ; 50:7, s. 709-715
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Tidskriftsartikel (refereegranskat)abstract
- Background: A thorough understanding of magnetic resonance (MR) contrast media dynamics makes it possible to choose the optimal contrast media for each investigation. Differences in visualizing hepatobiliary function between Gd-BOPTA and Gd-EOB-DTPA have previously been demonstrated, but less has been published regarding differences in liver vessel visualization.Purpose: To compare the liver vessel and liver parenchymal enhancement dynamics of Gd-BOPTA (MultiHance®) and Gd-EOB-DTPA (Primovist®). Material and Methods: The signal intensity of the liver parenchyma, the common hepatic artery, the middle hepatic vein, and a segmental branch of the right portal vein, was obtained in 10 healthy volunteers before contrast media administration, during arterial and portal venous phases, and 10, 20, 30, 40 and 130 minutes after intravenous contrast medium injection, but due to scanner limitations not during the hepatic venous phase. Results: Maximum enhancement of liver parenchyma was observed from the portal venous phase until 130 minutes after Gd-BOPTA administration and from 10 minutes to 40 minutes after Gd-EOB-DTPA. There was no difference in maximum enhancement of liver parenchyma between the two contrast media. When using Gd-BOPTA, the vascular contrast enhancement was still apparent 40 minutes after injection, but had vanished 10 minutes after Gd-EOB-DTPA injection. The maximum difference in signal intensity between the vessels and the liver parenchyma was significantly greater with Gd-BOPTA than with Gd-EOB-DTPA (p<0.0001). Conclusion: At the dosage used in this study Gd-BOPTA yields higher maximum enhancement of the hepatic artery, portal vein and middle hepatic vein during the arterial and the portal venous phase and during the delayed phases than Gd-EOB-DTPA does, whereas there is no difference in liver parenchymal enhancement between the two contrast agents.
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| 8. |
- Bryngelsson, David, 1981, et al.
(författare)
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The effect of food-price movements on African households - An investigation of food production and consumption patterns in four African countries
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The recent spike in world food prices has intensified the debate regarding the impact of food prices on poverty. In this paper we aim to assess households’ vulnerability to food-price increases in four countries in Sub-Saharan Africa. Using household data from the World Bank’s Living Standard Measurement Surveys in Ghana (2005–2006), Kagera region, Tanzania (2004), Malawi (2004–2005) and South Africa (1993) we analyze food production and consumption patterns in rural and urban populations. We use two established indicators of sensitivity to food price changes—one measuring the share of income spent on food, the other measuring net sales of food compared to total expenditures. We find that the shares of the populations spending more than half of their income on food ranges from 62–81% in rural areas and from 26–67% in urban areas. Further we find that in all regions studied, most households (74–99%) in rural areas are net buyers of food and stand to lose in the short term from higher food prices. As expected, for urban households this is true to an even higher extent. In contrast to earlier studies we look at all food items and not just one or a few staple foods, giving a better understanding of vulnerability to general food price changes. We find that the exclusion of non-staple foods has a significant impact on theresults.
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| 9. |
- Carroll, David C., et al.
(författare)
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Dynamic control and enhancement of laser-accelerated protons using multiple laser pulses
- 2009
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Ingår i: Comptes Rendus. Physique. - : Elsevier BV. - 1631-0705. ; 10:2-3, s. 188-196
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Tidskriftsartikel (refereegranskat)abstract
- The use of schemes involving multiple laser pulses to enhance and control the properties of beams of protons accelerated in ultra-intense laser irradiation of planar foil targets is discussed. Specifically, the schemes include the use of a second laser pulse to produce and control preplasma expansion of the target to enhance energy coupling to the proton beam; the use of a second laser pulse to drive shock deformation of the target to change the direction of the proton beam; and a scheme involving dual high intensity laser pulses to change the properties of the sheath field, with the aim of modifying the proton energy spectrum. An overview of our recent experimental and theoretical results is given. The overall aim of this work is to determine the extent to which the properties of the sheath-accelerated proton beam can be optically controlled, to enable beam delivery at high repetition rates. To cite this article: D.C. Carroll et al., C. R. Physique 10 (2009). (C) 2009 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
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| 10. |
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