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- Baldassarre, Maurizio, et al.
(författare)
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Pushing the detection limit of infrared spectroscopy for structural analysis of dilute protein samples.
- 2014
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Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 139:21, s. 5393-5399
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Tidskriftsartikel (refereegranskat)abstract
- Fourier-transform infrared spectroscopy is a powerful and versatile tool to investigate the structure and dynamics of proteins in solution. The intrinsically low extinction coefficient of the amide I mode, the main structure-related oscillator, together with the high infrared absorptivity of aqueous media, requires that proteins are studied at high concentrations (>10 mg L(-1)). This may represent a challenge in the study of aggregation-prone proteins and peptides, and questions the significance of structural data obtained for proteins physiologically existing at much lower concentrations. Here we describe the development of a simple experimental approach that increases the detection limit of protein structure analysis by infrared spectroscopy. Our approach relies on custom-made filters to isolate the amide I region (1700-1600 cm(-1)) from irrelevant spectral regions. The sensitivity of the instrument is then increased by background attenuation, an approach consisting in the use of a neutral density filter, such as a non-scattering metal grid, to attentuate the intensity of the background spectrum. When the filters and grid are combined, a 2.4-fold improvement in the noise level can be obtained. We have successfully tested this approach using a highly diluted solution of pyruvate kinase in deuterated medium (0.2% w/v), and found that it provides spectra of a quality comparable to those recorded with a 10-fold higher protein concentration.
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- Grönwall, Caroline, et al.
(författare)
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Selection and characterization of Affibody ligands binding to Alzheimer amyloid beta peptides
- 2007
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 128:1, s. 162-183
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Tidskriftsartikel (refereegranskat)abstract
- Affibody (Affibody) ligands specific for human amyloid beta (Abeta) peptides (40 or 42 amino acid residues in size), involved in the progress of Alzheimer's disease, were selected by phage display technology from a combinatorial protein library based on the 58-amino acid residue staphylococcal protein A-derived Z domain. Post-selection screening of 384 randomly picked clones, out of which 192 clones were subjected to DNA sequencing and clustering, resulted in the identification of 16 Affibody variants that were produced and affinity purified for ranking of their binding properties. The two most promising Affibody variants were shown to selectively and efficiently bind to Abeta peptides, but not to the control proteins. These two Affibody ligands were in dimeric form (to gain avidity effects) coupled to affinity resins for evaluation as affinity devices for capture of Abeta peptides from human plasma and serum. It was found that both ligands could efficiently capture Abeta that were spiked (100 microgml(-1)) to plasma and serum samples. A ligand multimerization problem that would yield suboptimal affinity resins, caused by a cysteine residue present at the binding surface of the Affibody ligands, could be circumvented by the generation of second-generation Affibody ligands (having cysteine to serine substitutions). In an epitope mapping effort, the preferred binding site of selected Affibody ligands was mapped to amino acids 30-36 of Abeta, which fortunately would indicate that the Affibody molecules should not bind the amyloid precursor protein (APP). In addition, a significant effort was made to analyze which form of Abeta (monomer, dimer or higher aggregates) that was most efficiently captured by the selected Affibody ligand. By using Western blotting and a dot blot assay in combination with size exclusion chromatography, it could be concluded that selected Affibody ligands predominantly bound a non-aggregated form of analyzed Abeta peptide, which we speculate to be dimeric Abeta. In conclusion, we have successfully selected Affibody ligands that efficiently capture Abeta peptides from human plasma and serum. The potential therapeutic use of these optimized ligands for extracorporeal capture of Abeta peptides in order to slow down or reduce amyloid plaque formation, is discussed.
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- Mattsson, Lars
(författare)
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On the grain-sized distribution of turbulent dust growth
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 499:4, s. 6035-6043
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Tidskriftsartikel (refereegranskat)abstract
- It has recently been shown that turbulence in the interstellar medium can significantly accelerate the growth of dust grains by accretion of molecules, but the turbulent gas density distribution also plays a crucial role in shaping the grain-sized distribution (GSD). The growth velocity, i.e. the rate of change of the mean grain radius, is proportional to the local gas density if the growth species (molecules) are well mixed in the gas. As a consequence, grain growth happens at vastly different rates in different locations, since the gas density distribution of the interstellar medium (ISM) shows a considerable variance. Here, it is shown that GSD rapidly becomes a reflection of the gas density distribution, irrespective of the shape of the initial GSD. This result is obtained by modelling ISM turbulence as a Markov process, which in the special case of an Ornstein-Uhlenbeck process leads to a lognormal gas density distribution, consistent with numerical simulations of isothermal compressible turbulence. This yields an approximately lognormal GSD; the sizes of dust grains in cold ISM clouds may thus not follow the commonly adopted power-law GSD with index -3.5 but corroborate the use of a lognormal GSD for large grains, suggested by several studies. It is also concluded that the very wide range of gas densities obtained in the high Mach-number turbulence of molecular clouds must allow formation of a tail of very large grains reaching radii of several microns.
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- Narayanan, Aditya, 1988, et al.
(författare)
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Zonal Distribution of Circumpolar Deep Water Transformation Rates and Its Relation to Heat Content on Antarctic Shelves
- 2023
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Ingår i: Journal of Geophysical Research-Oceans. - 2169-9275. ; 128:6
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Tidskriftsartikel (refereegranskat)abstract
- We analyze 15-year of observational data and a 5-year Southern Ocean model simulation to quantify the transformation rates of Circumpolar Deep Water (CDW) and the associated heat loss to the surface. This study finds that over the continental shelves of East Antarctica and the Weddell and Ross Seas, surface buoyancy fluxes transform similar to 4.4 Sv of surface waters into CDW, providing a path for CDW to lose heat to the surface. In addition, similar to 6.6 Sv of CDW are mixed with surface waters in the Weddell and Ross subpolar gyres. In contrast, enhanced stratification inhibits the outcropping of CDW isopycnals, reducing their transformation rates by a factor of similar to 8 over the continental shelf and by a factor of similar to 3 over the deeper ocean in the Amundsen and Bellingshausen Seas. The CDW retains its offshore warm properties as it intrudes over the continental shelves, resulting in elevated bottom temperatures there. This analysis demonstrates the importance of processes in subpolar gyres to erode CDW and to facilitate further transformation on the continental shelves, significantly reducing the heat able to access ice shelf fronts. This sheltering effect is strongest in the western Weddell Sea and tends to diminish toward the east, which helps explain the large zonal differences in continental-shelf bottom temperatures and the melt rates of Antarctic ice shelves. Plain Language Summary The continental slope around Antarctica acts as a barrier to deep and warmer offshore waters that can bring heat to the glaciers along the coastline, enhancing their melt rate and contributing to global sea level rise. Around the Antarctic continent these offshore waters, the so-called Circumpolar Deep Waters, differ in their ability to cross this barrier while retaining their heat, explaining to a large extent why West Antarctic glaciers melt much faster than other Antarctic ice sheets. We study the properties of the warm waters over the continental shelf and offshore regions and contrast them across regions. We show that in East Antarctica, the Ross Sea, and the Weddell Sea, deep warm waters are brought to the surface where they lose heat and mix with surface waters. However, in the Amundsen and Bellingshausen Seas, the warm water is insulated from the surface by land run-off of fresher and lighter waters that occupy the surface. These results highlight the importance of the subpolar gyres in sheltering Antarctic glaciers.
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- Nurmi, J, et al.
(författare)
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The SoC-mobinet model in system-on-chip education
- 2005
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Ingår i: 2005 IEEE International Conference on Microelectronic Systems Education, Proceedings. - LOS ALAMITOS, CA : IEEE COMPUTER SOC. - 0769523749 ; , s. 71-72
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Konferensbidrag (refereegranskat)abstract
- This paper describes the model of developing SoC curricula jointly by industry and academia, where joint effort research results are turned into course contents for SoC-curricula and industry training activities.
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- Reza Felix, Mariana, et al.
(författare)
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Bone Scan Index and Progression-free Survival Data for Progressive Metastatic Castration-resistant Prostate Cancer Patients Who Received ODM-201 in the ARADES Multicentre Study
- 2016
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 2:5, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- Background ODM-201, a new-generation androgen receptor inhibitor, has shown clinical efficacy in prostate cancer (PCa). Quantitative methods are needed to accurately assess changes in bone as a measurement of treatment response. The Bone Scan Index (BSI) reflects the percentage of skeletal mass a given tumour affects. Objective To evaluate the predictive value of the BSI in metastatic castration-resistant PCa (mCRPC) patients undergoing treatment with ODM-201. Design, setting, and participants From a total of 134 mCRPC patients who participated in the Activity and Safety of ODM-201 in Patients with Progressive Metastatic Castration-resistant Prostate Cancer clinical trial and received ODM-201, we retrospectively selected all those patients who had bone scan image data of sufficient quality to allow for both baseline and 12-wk follow-up BSI-assessments (n = 47). We used the automated EXINI bone BSI software (EXINI Diagnostics AB, Lund, Sweden) to obtain BSI data. Outcome measurements and statistical analysis We used the Cox proportional hazards model and Kaplan-Meier estimates to investigate the association among BSI, traditional clinical parameters, disease progression, and radiographic progression-free survival (rPFS). Results and limitations In the BSI assessments, at follow-up, patients who had a decrease or at most a 20% increase from BSI baseline had a significantly longer time to progression in bone (median not reached vs 23 wk, hazard ratio [HR]: 0.20; 95% confidence interval [CI], 0.07–0.58; p = 0.003) and rPFS (median: 50 wk vs 14 wk; HR: 0.35; 95% CI, 0.17–0.74; p = 0.006) than those who had a BSI increase >20% during treatment. Conclusions The on-treatment change in BSI was significantly associated with rPFS in mCRPC patients, and an increase >20% in BSI predicted reduced rPFS. BSI for quantification of bone metastases may be a valuable complementary method for evaluation of treatment response in mCRPC patients. Patient summary An increase in Bone Scan Index (BSI) was associated with shorter time to disease progression in patients treated with ODM-201. BSI may be a valuable method of complementing treatment response evaluation in patients with advanced prostate cancer.
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