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| 2. |
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| 3. |
- Abe, K., et al.
(author)
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Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
- 2022
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In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
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Journal article (peer-reviewed)abstract
- We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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| 4. |
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| 5. |
- Birney, Ewan, et al.
(author)
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Prepublication data sharing
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
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Journal article (peer-reviewed)abstract
- Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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| 6. |
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| 7. |
- J L Sussman, M Harel, M L Raves, K Giles, R B G Ravelli, L G M Peng, G J Kleywegt, D M Quinn, H K Nair, and I Silman
(author)
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Studies on the 3-D structure of Torpedo Acetylcholinesterase
- 1996
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In: 1996 U.S. Army Medical Defense Bioscience Review. - : U.S. Army Medical Research Institute of Chemical Defense, Baltimore, MD. ; , s. 13-22
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Book chapter (peer-reviewed)
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| 8. |
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| 9. |
- Daniel, Ed, et al.
(author)
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IceBear : an intuitive and versatile web application for research-data tracking from crystallization experiment to PDB deposition
- 2021
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In: Acta Crystallographica Section D. - : International Union of Crystallography (IUCr). - 2059-7983. ; 77:2, s. 151-163
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Journal article (peer-reviewed)abstract
- The web-based IceBear software is a versatile tool to monitor the results of crystallization experiments and is designed to facilitate supervisor and student communications. It also records and tracks all relevant information from crystallization setup to PDB deposition in protein crystallography projects. Fully automated data collection is now possible at several synchrotrons, which means that the number of samples tested at the synchrotron is currently increasing rapidly. Therefore, the protein crystallography research communities at the University of Oulu, Weizmann Institute of Science and Diamond Light Source have joined forces to automate the uploading of sample metadata to the synchrotron. In IceBear, each crystal selected for data collection is given a unique sample name and a crystal page is generated. Subsequently, the metadata required for data collection are uploaded directly to the ISPyB synchrotron database by a shipment module, and for each sample a link to the relevant ISPyB page is stored. IceBear allows notes to be made for each sample during cryocooling treatment and during data collection, as well as in later steps of the structure determination. Protocols are also available to aid the recycling of pins, pucks and dewars when the dewar returns from the synchrotron. The IceBear database is organized around projects, and project members can easily access the crystallization and diffraction metadata for each sample, as well as any additional information that has been provided via the notes. The crystal page for each sample connects the crystallization, diffraction and structural information by providing links to the IceBear drop-viewer page and to the ISPyB data-collection page, as well as to the structure deposited in the Protein Data Bank.
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| 10. |
- Graslund, S, et al.
(author)
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Protein production and purification
- 2008
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In: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
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Journal article (peer-reviewed)
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| 11. |
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| 12. |
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| 13. |
- Domínguez, José L, et al.
(author)
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Effect of the Protonation State of the Titratable Residues on the Inhibitor Affinity to BACE-1
- 2010
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In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:34, s. 7255-7263
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Journal article (peer-reviewed)abstract
- BACE-1 is one of the aspartic proteases involved in the cleavage of beta amyloid peptide, an initial step in the formation of amyloid plaques whose toxicity induces neuron death in Alzheimer's disease patients. One of the central issues in the search of novel BACE-1 inhibitors is the optimum pH for the binding of inhibitors to the enzyme. It is known that the enzyme has optimal catalytic activity at acidic pH, while cell active inhibitors may bind optimally at higher pH. In this work we determine the effect of the pH on the affinities of a set of inhibitors, with a variety of chemical motifs, for the ectodomain region of BACE-1 by a surface plasmon resonance (SPR) biosensor based assay. In order to understand the molecular interactions that underlie the diverse optimum pH for the binding of the various inhibitors as observed experimentally, we have calculated the titration curves for a set of BACE-1 ligand complexes. The results indicate that the pK(a) values of the titratable residues of the protein depend on the nature of the ligand involved, in disagreement with previous work. The enzyme-inhibitor structures with the resulting protonation states at pH values 4.5 and 7.4 served as the starting point for the prediction of the pH-dependent binding ranking. Our calculations reproduced the entire affinity ranking observed upon pH increase and most of the binding trends among inhibitors, especially at low pH. Finally, our cell-based assays indicate a possible correlation between high inhibitor affinity at both acidic and neutral pH values, with optimal cell response, a result that may open new venues for the search of potent BACE-1 inhibitors that are active at the cellular level.
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| 14. |
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| 15. |
- Agwuele, Augustine, et al.
(author)
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The Effect of Speaking Rate on Consonant Vowel Coarticulation
- 2008
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In: Phonetica. - : Walter de Gruyter GmbH. - 1423-0321 .- 0031-8388. ; 65:4, s. 194-209
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Journal article (peer-reviewed)abstract
- In 2007 Lindblom et al. introduced a methodological tool to disentangle consonant-vowel (CV) coarticulation attributable to emphatic stress apart from the vowel expansion effects known to accompany the prosodic overlay. After empirically accounting for the altered vowel positions, they reported small but consistent increases in F2 transition onsets in emphatically produced CVs that could not be attributed to vowel context influences, and that differed across stop place. At issue is whether the findings of these authors can be replicated, but in the opposite direction, for CVs produced at fast speaking rates. A modified locus equation regression metric was similarly used to account for rate-induced vowel reduction effects in predicting frequencies of F2 transition onsets in rapid speech. Six American-English speakers produced [V1.CV2] sequences embedded in a carrier sentence, at three speaking tempos: normal, fast, and fastest. Significant differences were found between ‘predicted’ and ‘observed’ F2 onsets across stops, with alveolars and velars showing greater decreases in F2 onsets during more rapid speech than labials. The complementary findings are discussed relative to a unified view of anticipatory coarticulation in CV production across a continuum of hyperarticulated spectral expansion to hypoarticulated spectral reduction.
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| 16. |
- Aricescu, A R, et al.
(author)
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Eukaryotic expression: developments for structural proteomics.
- 2006
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In: Acta Crystallographica Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; 62, s. 1114-1124
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Journal article (peer-reviewed)abstract
- The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for co-expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.
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| 17. |
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| 18. |
- Dominguez, Jose L., et al.
(author)
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Experimental and 'in silico' analysis of the effect of pH on HIV-1 protease inhibitor affinity : Implications for the charge state of the protein ionogenic groups
- 2012
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 20:15, s. 4838-4847
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Journal article (peer-reviewed)abstract
- The pH dependence of the HIV-1 protease inhibitor affinity was studied by determining the interaction kinetics of a series of inhibitors at three pH values by surface plasmon resonance (SPR) biosensor analysis. The results were rationalized by molecular mechanics based protocols that have as a starting point the structures of the HIV-1 protease inhibitor complexes differing in the protonation states as predicted by our calculations. The SPR experiments indicate a variety of binding affinity pH dependencies which are rather well reproduced by our simulations. Moreover, our calculations are able to pinpoint the possible changes in the charged state of the protein binding site and of the inhibitor that underlie the observed effects of the pH on binding affinity. The combination of SPR and molecular mechanics calculations has afforded novel insights into the pH dependence of inhibitor interactions with their target. This work raises the possibility of designing inhibitors with different pH binding affinity profiles to the ones described here.
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| 19. |
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| 20. |
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| 21. |
- Grodin, Erica N., et al.
(author)
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Neural Correlates of Compulsive Alcohol Seeking in Heavy Drinkers
- 2018
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In: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 3:12, s. 1022-1031
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Journal article (peer-reviewed)abstract
- Compulsive alcohol use, the tendency to continue alcohol seeking and taking despite negative consequences, is a hallmark of alcohol use disorder. Preclinical rodent studies have suggested a role for the medial prefrontal cortex, anterior insula, and nucleus accumbens in compulsive alcohol seeking. It is presently unknown whether these findings translate to humans. We used a novel functional magnetic resonance imaging paradigm and tested the hypothesis that heavy drinkers would compulsively seek alcohol despite the risk of an aversive consequence, and that this behavior would be associated with the activity of frontostriatal circuitry.
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| 22. |
- Harel, M, et al.
(author)
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Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target.
- 1995
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In: Structure. - 0969-2126. ; 3:12, s. 1355-66
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Journal article (peer-reviewed)abstract
- BACKGROUND: Fasciculin (FAS), a 61-residue polypeptide purified from mamba venom, is a three-fingered toxin which is a powerful reversible inhibitor of acetylcholinesterase (AChE). Solution of the three-dimensional structure of the AChE/FAS complex would provide the first structure of a three-fingered toxin complexed with its target. RESULTS: The structure of a complex between Torpedo californica AChE and fasciculin-II (FAS-II), from the venom of the green mamba (Dendroaspis angusticeps) was solved by molecular replacement techniques, and refined at 3.0 A resolution to an R-factor of 0.231. The structure reveals a stoichiometric complex with one FAS molecule bound to each AChE subunit. The AChE and FAS conformations in the complex are very similar to those in their isolated structures. FAS is bound at the 'peripheral' anionic site of AChE, sealing the narrow gorge leading to the active site, with the dipole moments of the two molecules roughly aligned. The high affinity of FAS for AChE is due to a remarkable surface complementarity, involving a large contact area (approximately 2000 A2) and many residues either unique to FAS or rare in other three-fingered toxins. The first loop, or finger, of FAS reaches down the outer surface of the thin aspect of the gorge. The second loop inserts into the gorge, with an unusual stacking interaction between Met33 in FAS and Trp279 in AChE. The third loop points away from the gorge, but the C-terminal residue makes contact with the enzyme. CONCLUSIONS: Two conserved aromatic residues in the AChE peripheral anionic site make important contacts with FAS. The absence of these residues from chicken and insect AChEs and from butyrylcholinesterase explains the very large reduction in the affinity of these enzymes for FAS. Several basic residues in FAS make important contacts with AChE. The complementarity between FAS and AChE is unusual, inasmuch as it involves a number of charged residues, but lacks any intermolecular salt linkages.
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| 23. |
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| 24. |
- Lindblom, Bjorn, et al.
(author)
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A Duration-Dependent Account of Coarticulation for Hyper- and Hypoarticulation
- 2009
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In: Phonetica. - : Walter de Gruyter GmbH. - 0031-8388 .- 1423-0321. ; 66:3, s. 188-195
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Journal article (peer-reviewed)abstract
- Previous studies investigating anticipatory coarticulation in emphatically stressed CV sequences and during fast speaking rates reported that three factors contributed to the overall extent of the documented coarticulation. These factors were: (1) vowel identity, (2) vowel space expansion (emphasis) or reduction (fast rate), and a hypothesized (3) 'deeper' and 'shallower' stop closure contact in emphatic and faster speech, respectively. The objective of the current research was to conceptually and quantitatively unify these two studies. This was accomplished by showing that the opposite changes to frequency onsets of F2 transitions due to emphatic and rapid speech systematically vary as a function of the durational changes in the stop closure interval. Specifically, the decrease in coarticulation in emphatic speech is characterized by increases in F2 onsets and longer stop closures (relative to a normal baseline); the increase in coarticulation due to rapid speech shows concomitant decreases in F2 onsets coinciding with shorter stop closure intervals. Vocal tract area function simulations corresponding to emphatic and reduced speech implicitly support 'deeper' and 'shallower' closure contacts as a third factor contributing to the overall extent of anticipatory CV coarticulation.
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| 25. |
- Lindblom, Björn, et al.
(author)
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Coarticulation as incomplete interpolation
- 2010
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In: Proceedings from Fonetik 2010. Lund, June 2-4, 2010. - Lund, Sweden : Lund University. ; , s. 57-62
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Conference paper (other academic/artistic)
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