| 1. |
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| 2. |
- Nilsson, Erik, 1983-, et al.
(författare)
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Evaluating humidity and sea salt disturbances on CO2 flux measurements
- 2018
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Ingår i: Journal of Atmospheric and Oceanic Technology. - 0739-0572 .- 1520-0426. ; 35, s. 859-875
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Tidskriftsartikel (refereegranskat)abstract
- Global oceans are an important sink of atmospheric carbon dioxide (CO2). Therefore, understanding the air-sea flux of CO2 is a vital part in describing the global carbon balance. Eddy covariance (EC) measurements are often used to study CO2 fluxes from both land and ocean. CO2 are usually measured with infrared absorption sensors, which at the same time measure water vapor. Studies have shown that presence of water vapor fluctuations in the sampling air potentially result in erroneous CO2 flux measurements due to cross-sensitivity of the sensor. Here we compare measured CO2 fluxes from both enclosed path Li-Cor 7200 sensors and open-path Li-Cor 7500 instruments from an inland measurement site and a marine site. We also introduce new quality control criteria based upon a Relative Signal Strength Indicator (RSSI). The sampling gas in one of the Li-Cor 7200 instruments was dried by means of a multi-tube diffusion dryer so that the water vapor fluxes were close to zero. With this setup we investigated the effect that cross-sensitivity of the CO2 signal to water vapor can have on the CO2 fluxes. The dryer had no significant effect on the CO2 fluxes. We tested the hypothesis that the cross-sensitivity effect is caused by hygroscopic particles such as sea salt by spraying a saline solution on the windows of the Li-Cor 7200 instruments during the inland field test. Our results confirm earlier findings that sea salt contamination can affect CO2 fluxes significantly and confirm earlier findings, that drying the sampling air for the gas analyzer is an effective method to reduce this signal contamination.
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| 3. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 4. |
- Agholme, Lotta, et al.
(författare)
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Low-dose γ-secretase inhibition increases secretion of Aβ peptides and intracellular oligomeric Aβ.
- 2017
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 85, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibitors have been considered promising drug candidates against Alzheimer's disease (AD) due to their ability to reduce amyloid-β (Aβ) production. However, clinical trials have been halted due to lack of clinical efficacy and/or side effects. Recent in vitro studies suggest that low doses of γ-secretase inhibitors may instead increase Aβ production. Using a stem cell-derived human model of cortical neurons and low doses of the γ-secretase inhibitor DAPT, the effects on a variety of Aβ peptides were studied using mass spectrometry. One major focus was to develop a novel method for specific detection of oligomeric Aβ (oAβ), and this was used to study the effects of low-dose γ-secretase inhibitor treatment on intracellular oAβ accumulation. Low-dose treatment (2 and 20nM) with DAPT increased the secretion of several Aβ peptides, especially Aβx-42. Furthermore, using the novel method for oAβ detection, we found that 2nM DAPT treatment of cortical neurons resulted in increased oAβ accumulation. Thus, low dose-treatment with DAPT causes both increased production of long, aggregation-prone Aβ peptides and accumulation of intracellular Aβ oligomers, both believed to contribute to AD pathology.
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| 5. |
- Bárcena-Uribarri, Iván, et al.
(författare)
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P66 porins are present in both Lyme disease and relapsing fever spirochetes : a comparison of the biophysical properties of P66 porins from six Borrelia species
- 2010
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier. - 0005-2736 .- 1879-2642. ; 1798:6, s. 1197-1203
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Tidskriftsartikel (refereegranskat)abstract
- The genus Borrelia is the cause of the two human diseases: Lyme disease (LD) and relapsing fever (RF). BothLD and RF Borrelia species are obligate parasites and are dependent on nutrients provided by their hosts. Thefirst step of nutrient uptake across the outer membrane of these Gram-negative bacteria is accomplished bywater-filled channels, so-called porins. The knowledge of the porin composition in the outer membranes ofthe different pathogenic Borrelia species is limited. Only one porin has been described in relapsing feverspirochetes to date, whereas four porins are known to be present in Lyme disease agents. From these, theBorrelia burgdorferi outer membrane channel P66 is known to act as an adhesin and was well studied as aporin. To investigate if P66 porins are expressed and similarly capable of pore formation in other Borreliacausing Lyme disease or relapsing fever three LD species (B. burgdorferi, B. afzelii, B. garinii) and three RFspecies (B. duttonii, B. recurrentis and B. hermsii) were investigated for outer membrane proteins homologousto P66. A search in current published RF genomes, comprising the ones of B. duttonii, B. recurrentis and B.hermsii, indicated that they all contained P66 homologues. The P66 homologues of the six Borrelia specieswere purified to homogeneity and their pore-forming abilities as well as the biophysical properties of thepores were analyzed using the black lipid bilayer assay.
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| 6. |
- Bárcena-Uribarri, Iván, et al.
(författare)
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Study of the protein complex, pore diameter, and pore-forming activity of the Borrelia burgdorferi P13 porin
- 2014
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 289:27, s. 18614-18624
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Tidskriftsartikel (refereegranskat)abstract
- P13 is one of the major outer membrane proteins of Borrelia burgdorferi. Previous studies described P13 as a porin. In the present study some structure and function aspects of P13 were studied. P13 showed according to lipid bilayer studies a channel-forming activity of 0.6 nanosiemens in 1 M KCl. Single channel and selectivity measurements demonstrated that P13 had no preference for either cations or anions and showed no voltage-gating up to +/-100 mV. Blue native polyacrylamide gel electrophoresis was used to isolate and characterize the P13 protein complex in its native state. The complex had a high molecular mass of about 300 kDa and was only composed of P13 monomers. The channel size was investigated using non-electrolytes revealing an apparent diameter of about 1.4 nm with a 400-Da molecular mass cut-off. Multichannel titrations with different substrates reinforced the idea that P13 forms a general diffusion channel. The identity of P13 within the complex was confirmed by second dimension SDS-PAGE, Western blotting, mass spectrometry, and the use of a p13 deletion mutant strain. The results suggested that P13 is the protein responsible for the 0.6-nanosiemens pore-forming activity in the outer membrane of B. burgdorferi.
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| 7. |
- Barcena-Uribarri, Ivan, et al.
(författare)
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Use of Nonelectrolytes Reveals the Channel Size and Oligomeric Constitution of the Borrelia burgdorferi P66 Porin
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:11, s. e78272-
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Tidskriftsartikel (refereegranskat)abstract
- In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs) with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be <= 1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.
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| 8. |
- Bárcena-Uribarri, Iván, et al.
(författare)
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Use of nonelectrolytes reveals the channel size and oligomeric constitution of the Borrelia burgdorferi P66 porin
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The outer membrane protein P66 of the Lyme disease spirochete Borrelia burgdorferi is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl. We studied in a non-theoretical manner the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. Furthermore, we calculated the filling of the channel with these nonelectrolytes and the results revealed that nonelectrolytes with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. Thus, the diameter of the P66 entrance was determined to be ≤ 1.9 nm with a constriction site diameter of about 0.7 nm. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% after addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose in the low millimolar range. Interestingly, the analysis of the power density spectra of P66 after blockage with nonelectrolytes revealed no chemical interaction responsible for channel block. The blockage of one P66 single-channel conductance unit of 11 nS occurred by seven subconducting states, thus indicating a heptameric organization of the P66 oligomer. This organization of P66 as a heptamer was confirmed by Blue Native PAGE and immunoblot analysis, which demonstrated that P66 forms a complex with a mass of approximately 460 kDa.
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| 9. |
- Bergström, Anders, 1965-, et al.
(författare)
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KI Arkitektur och kunskapsmiljö : Tävlingen/Etableringen/Förnyelsen
- 2010. - 1
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Universitet och högskolor förknippas liksom många andra institutioner och verksamheter i vårt samhälle i så hög grad med sina byggnader att verksamheter och byggnader kan vara svåra att skilja från varandra. Det vi kan ana är att människor alltid använt byggandet för att etablera och upprätthålla både samhälleliga funktioner och mer vardagliga seder och bruk. Aktiviteter som lyckas etablera sig i byggd form blir en naturlig och stödjande del av vår fysiska verklighet, medan aktiviteter som inte blir manifesterade kan få svårare att överleva. I vår samtid, som präglas av en ständigt pågående förändring, kan etablerade lösningar också stå i vägen för ny utveckling och hindra oss från att se hur bebyggelsen skulle kunna utformas på ett annorlunda sätt. Mot denna bakgrund utgör KI – Karolinska Institutet – ett intressant exempel på samspelet mellan medvetet utformad bebyggelse och kvalificerad verksamhet. Karolinska Institutet är sedan lång tid tillbaka en av landets mest kreativa kunskapsmiljöer. Institutets bebyggelse har tillkommit under en längre tidsperiod och karakteriseras av höga ambitioner, där olika idéer om kunskapsproduktionens villkor har styrt såväl den övergripande planeringen som de enskilda byggnadernas utformning. Genom att tydliggöra dessa idéer och samtidigt undersöka hur det byggda resultatet fungerar, hoppas vi kunna bidra inte bara till en förståelse för Karolinska Institutets utveckling utan också till en mer generell kunskap om relationen mellan arkitektur och kunskapsmiljö.
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| 10. |
- Bergström, Christel A. S., et al.
(författare)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Tidskriftsartikel (refereegranskat)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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