| 31. |
- Collins, Ruairi, et al.
(författare)
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Biochemical discrimination between selenium and sulfur 1 : a single residue provides selenium specificity to human selenocysteine lyase
- 2012
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Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1932-6203.
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Tidskriftsartikel (refereegranskat)abstract
- Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.
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| 32. |
- Creelman, Alastair, 1958-, et al.
(författare)
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Open courses as virtual mobility and the role of collaborative literacy in staff development
- 2016
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Ingår i: EDEN 2016 Annual Conference. Re-Imagining Learning Scenarios. - Budapest : European Distance and E-Learning Network, 2016. - 9786155511080
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Open Networked Learning (ONL) https://opennetworkedlearning.wordpress.com is an open online course that is offered both as an internal professional development course at the partner universities (Karolinska Institute, Lund University, Linnaeus University, KTH in Sweden and IIE Varsity College in South Africa) as well as being open to learners from all over the world. The course has been derived from an earlier model that has in turn led to several other online courses. The primary target group is university teachers, educational technologists and course designers but it also attracts educators from other educational sectors both public and private. Using an open collaborative learning environment learners investigate aspects of connected, collaborative learning with modules based around topics such as digital literacies, collaborative and flexible learning, teaching in open spaces and course design.
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| 33. |
- Deckner, Fanny, et al.
(författare)
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Sheet pile behavior during vibratory driving : numerical study based on a field test
- 2017
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Ingår i: Soil Dynamics and Earthquake Engineering. - 0267-7261 .- 1879-341X.
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Tidskriftsartikel (refereegranskat)abstract
- Vibrations due to sheet pile driving are a problem in many urban areas today. Increased knowledgeof the vibration transfer process from source to nearby objects is important in order to enableminimization of induced vibrations. The transfer of vibrations from sheet pile to soil is dependent onthe sheet pile behaviour during driving. This paper presents a 3D finite element study of thebehaviour of a vibratory driven sheet pile, complementing results from a full-scale field test. Thefinite element model accounts for strain dependent soil stiffness using an equivalent linear soilmodel. The conclusion is that the sheet pile bends considerably during driving with eccentricclamping. Furthermore, it is shown that the bending mode is similar irrespective of sheet pilepenetration depth.
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| 34. |
- Dewhurst, Richard, et al.
(författare)
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How task demands influence scanpath similarity in a sequential number-search task
- 2018
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Ingår i: Vision Research. - : Elsevier BV. - 1878-5646 .- 0042-6989. ; , s. 9-23
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Tidskriftsartikel (refereegranskat)abstract
- More and more researchers are considering the omnibus eye movement sequence—the scanpath—in their studies of visual and cognitive processing (e.g. Hayes, Petrov, & Sederberg, 2011; Madsen, Larson, Loschky, & Rebello, 2012; Ni et al., 2011; von der Malsburg & Vasishth, 2011). However, it remains unclear how recent methods for comparing scanpaths perform in experiments producing variable scanpaths, and whether these methods supplement more traditional analyses of individual oculomotor statistics. We address this problem for MultiMatch (Jarodzka et al., 2010; Dewhurst et al., 2012), evaluating its performance with a visual search-like task in which participants must fixate a series of target numbers in a prescribed order. This task should produce predictable sequences of fixations and thus provide a testing ground for scanpath measures. Task difficulty was manipulated by making the targets more or less visible through changes in font and the presence of distractors or visual noise. These changes in task demands led to slower search and more fixations. Importantly, they also resulted in a reduction in the between-subjects scanpath similarity, demonstrating that participants’ gaze patterns became more heterogenous in terms of saccade length and angle, and fixation position. This implies a divergent strategy or random component to eye-movement behaviour which increases as the task becomes more difficult. Interestingly, the duration of fixations along aligned vectors showed the opposite pattern, becoming more similar between observers in 2 of the 3 difficulty manipulations. This provides important information for vision scientists who may wish to use scanpath metrics to quantify variations in gaze across a spectrum of perceptual and cognitive tasks. © 2018 Elsevier Ltd
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| 35. |
- Dewhurst, Richard, et al.
(författare)
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It depends on how you look at it: Scanpath comparison in multiple dimensions with MultiMatch, a vector-based approach
- 2012
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Ingår i: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-3528.
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Tidskriftsartikel (refereegranskat)abstract
- Eye movement sequences---or scanpaths---vary depending on stimulus characteristics and task (Foulsham \& Underwood, 2008; Land, Mennie, \& Rusted, 1999). Common methods for comparing scanpaths, however, are limited in their ability to capture both the spatial and temporal properties of which a scanpath consists. Here we validate a new method for scanpath comparison based on geometric vectors, which compares scanpaths over multiple dimensions retaining positional and sequential information (Jarodzka, Holmqvist, \& Nyström, 2010). `MultiMatch' was tested in two experiments and pitted against ScanMatch (Cristino, Mathôt, Theeuwes, \& Gilchrist, 2010), the most comprehensive adaptation of the popular Levenshtein method. Experiment 1 used synthetic data, demonstrating the greater sensitivity of MultiMatch to variations in spatial position. In experiment 2 real eye movement recordings were taken from participants viewing sequences of dots, designed to elicit scanpath pairs with commonalities known to be problematic for algorithms (for example, when one scanpath is shifted in locus, or fixations fall either side of an AOI boundary). Results illustrate the advantages of a multidimensional approach, revealing how two scanpath differ. For instance, if one scanpath is the reverse copy of another the difference is in direction but not the position of fixations; or if a scanpath is scaled down, the difference is in the length of saccadic vectors but not overall shape. As well as having enormous potential for any task in which consistency in eye movements is important (e.g. learning), MultiMatch is particularly relevant for "eye movements to nothing" in mental imagery research and embodiment of cognition, where satisfactory scanpath comparison algorithms are lacking.
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| 36. |
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| 37. |
- Dods, Robert, 1989, et al.
(författare)
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From Macrocrystals to Microcrystals: A Strategy for Membrane Protein Serial Crystallography.
- 2017
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Ingår i: Structure. - : Elsevier BV. - 1878-4186 .- 0969-2126. ; 25:9, s. 1461-1468
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Tidskriftsartikel (refereegranskat)abstract
- Serial protein crystallography was developed at X-ray free-electron lasers (XFELs) and is now also being applied at storage ring facilities. Robust strategies for the growth and optimization of microcrystals are needed to advance the field. Here we illustrate a generic strategy for recovering high-density homogeneous samples of microcrystals starting from conditions known to yield large (macro) crystals of the photosynthetic reaction center of Blastochloris viridis (RCvir). We first crushed these crystals prior to multiple rounds of microseeding. Each cycle of microseeding facilitated improvements in the RCvir serial femtosecond crystallography (SFX) structure from 3.3-Å to 2.4-Å resolution. This approach may allow known crystallization conditions for other proteins to be adapted to exploit novel scientific opportunities created by serial crystallography.
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| 38. |
- Dods, Robert, 1989, et al.
(författare)
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Ultrafast structural changes within a photosynthetic reaction centre.
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7841, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography1 using an X-ray free-electron laser2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions.
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| 39. |
- Ebenhag, Sven-Christian, 1976, et al.
(författare)
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Time transfer using an asynchronous computer network: Results from three weeks of measurements
- 2007
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Ingår i: European Frequency and Time Forum, 29/5 - 1/6, Geneva, CH.
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Konferensbidrag (refereegranskat)abstract
- We have performed a time transfer experimentbetween two atomic clocks, over a distance of approximately 75km using an 10 Gbit/s asynchronous fiber-optic computernetwork. The time transfer was accomplished through passivelistening on existing data traffic and a pilot sequence in the SDHbit stream. In order to assess the fiber-link clock comparison, wesimultaneously compared the clocks using a GPS carrier phaselink. The standard deviation of the difference between the twotime transfer links over the three-week time period was 243 ps.
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| 40. |
- Egstrup, Kenneth, et al.
(författare)
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QT Response after a Test Dose and during Maintenance Therapy with AZD1305 in Patients with Atrial Fibrillation: A Double-Blind, Randomized, Placebo-Controlled Trial.
- 2011
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Ingår i: American journal of cardiovascular drugs : drugs, devices, and other interventions. - : Springer Science and Business Media LLC. - 1179-187X. ; 11:3, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance treatment with AZD1305. Methods: This was a randomized, double-blind, parallel-group, placebo-controlled trial carried out at multiple hospital cardiac facilities in Denmark, Norway, Poland, Slovakia, and Sweden. Patients with documented atrial fibrillation (AF) but currently in stable sinus rhythm for ≥2 hours and ≤90 days were eligible for inclusion. Patients were randomized in a 1 : 1 : 1 ratio to receive AZD1305 extended-release or matching placebo tablets as follows: group A - test dose 250 mg, evening dose 125 mg on day 1, maintenance dose 125 mg twice daily; group B - test dose 500 mg, placebo evening dose, maintenance dose 125 mg twice daily; placebo group - placebo test and maintenance dose. Maintenance dosing was for 9 days. QTcF >550 ms at any time during the in-patient phase or >500 ms after discharge (day 4) were predefined study drug discontinuation criteria. The main outcome measure was the relationship between QTcF following the test dose and during maintenance treatment. Results: Sixty-five patients were randomized (n = 21, 22, and 22 in group A, group B, and the placebo group, respectively). AZD1305 dose-dependently increased QTcF. There was a positive, linear correlation between the change in QTcF during the first 6 hours after the test dose and during the maintenance phase. Three patients, all from group B, discontinued treatment on day 1 due to QTcF >550 ms. All other patients completed the study without events related to QT prolongation. There was a trend for reduced AF recurrence with AZD1305 compared with placebo. Conclusion: In this exploratory study a test dose predicted the QT response during maintenance treatment with AZD1305 and may thus be employed in further studies. [ClinicalTrials.gov Identifier: NCT00643448].
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