| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
- Fornara, Andrea, et al.
(author)
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Tailored Magnetic Nanoparticles for Direct and Sensitive Detection of Biomolecules in Biological Samples
- 2008
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 8:10, s. 3423-3428
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Journal article (peer-reviewed)abstract
- We developed nanoparticles with tailored magnetic properties for sensitive detection of biomolecules directly in biological samples in a single step. Thermally blocked nanoparticles obtained by thermal hydrolysis are mixed with sample solutions and the variation of the magnetic relaxation due to surface binding is used to detect the presence of biomolecules. The binding events significantly increase the hydrodynamic volume of nanoparticles, thus changing their Brownian relaxation frequency which is measured by a specifically developed AC-susceptometer.The system was tested for the presence of Brucella antibodies in serum samples from infected cows and the surface of the nanoparticles was functionalized with lipopolysaccarides (LPS) from Brucella abortus. The hydrodynamic volume of functionalized particles increased by 25-35% as a result of the binding of the antibodies, as measured by changes in the susceptibility in an alternating magnetic field. The method has shown high sensitivity, with detection limit of 7 nmol·L-1 in serum without any pre-treatment of the biological samples.The detection method is very sensitive, cost-efficient and versatile, giving a direct indication if the animal is infected or not, making it suitable for point-of care applications. The functionalization of tailored magnetic nanoparticles can be modified to suit numerous homogenous assays for a wide range of applications.
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| 3. |
- Grigoriev, Igor, 1984-
(author)
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Turbulence modeling of compressible flows with large density variation
- 2016
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Doctoral thesis (other academic/artistic)abstract
- In this study we highlight the influence of mean dilatation and mean density gradient on the Reynolds stress modeling of compressible, heat-releasing and supercritical turbulent flows.Firstly, the modeling of the rapid pressure-strain correlation has been extended to self-consistently account for the influence of mean dilatation.Secondly, an algebraic model for the turbulent density flux has been developed and coupled to the tensor equationfor Reynolds stress anisotropy via a 'local mean acceleration',a generalization of the buoyancy force.We applied the resulting differential Reynolds stress model (DRSM) and the corresponding explicit algebraic Reynolds stress model (EARSM) to homogeneously sheared and compressed or expanded two-dimensional mean flows. Both formulations have shown that our model preserves the realizability of the turbulence, meaning that the Reynolds stresses do not attain unphysical values, unlike earlier approaches. Comparison with rapid distortion theory (RDT) demonstrated that the DRSM captures the essentials of the transient behaviour of the diagonal anisotropies and gives good predictions of the turbulence kinetic energy.A general three-dimensional solution to the coupled EARSM has been formulated. In the case of turbulent flow in de Laval nozzle we investigated the influence of compressibility effects and demonstrated that the different calibrations lead to different turbulence regimes but with retained realizability. We calibrated our EARSM against a DNS of combustion in a wall-jet flow. Correct predictions of turbulent density fluxes have been achieved and essential features of the anisotropy behaviour have been captured.The proposed calibration keeps the model free of singularities for the cases studied. In addition, we have applied the EARSM to the investigation of supercritical carbon dioxide flow in an annulus. The model correctly captured mean enthalpy, temperature and density as well as the turbulence shear stress. Hence, we consider the model as a useful tool for the analysis of a wide range of compressible flows with large density variation.
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| 4. |
- Johansson, Linda, et al.
(author)
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Surface acoustic wave induced particle manipulation in a PDMS channel : principle concepts for continuous flow applications
- 2012
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In: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 14:2, s. 279-289
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Journal article (peer-reviewed)abstract
- A device for acoustic particle manipulation in the40 MHz range for continuous-flow operation in a 50 μm wide PDMS channel has been evaluated. Unidirectionalinterdigital transducers on a Y-cut Z-propagation lithiumniobate wafer were used to excite a surface acoustic wavethat generated an acoustic standing wave inside the microfluidicchannel. It was shown that particle alignment nodeswith different inter-node spacing could be obtained,depending on device design and driving frequency. Theobserved inter-node spacing differed from the standard halfwavelengthinter-node spacing generally employed in bulkacoustic transducer excited resonant systems. This effectand the related issue of acoustic node positions relative thechannel walls, which is fundamental for most continuousflow particle manipulation operations in channels, wasevaluated in measurements and simulations. Specificapplications of particle separation and alignment wherethese systems can offer benefits relative state-of the artdesigns were identified.
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| 5. |
- Johansson, Linda, et al.
(author)
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Surface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic channel
- 2012
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In: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 22:2, s. 025018-
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Journal article (peer-reviewed)abstract
- Surface acoustic wave (SAW) excitation of an acoustic field in a trapezoidal glass microfluidic channel for particle manipulation in continuous flow has been demonstrated. A unidirectional interdigital transducer (IDT) on a Y-cut Z-propagation lithium niobate (LiNbO3) substrate was used to excite a surface acoustic wave at approximately 35 MHz. An SU8 layer was used for adhesive bonding of the superstrate glass layer and the substrate piezoelectric layer. This work extends the use of SAWs for acoustic manipulation to also include glass channels in addition to prior work with mainly poly-di-methyl-siloxane channels. Efficient alignment of 1.9 mu m polystyrene particles to narrow nodal regions was successfully demonstrated. In addition, particle alignment with only one IDT active was realized. A finite element method simulation was used to visualize the acoustic field generated in the channel and the possibility of 2D alignment into small nodal regions was demonstrated.
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| 6. |
- Kilic, Nuzhet I., et al.
(author)
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Two-Photon Polymerization Printing with High Metal Nanoparticle Loading
- 2023
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In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:42, s. 49794-49804
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Journal article (peer-reviewed)abstract
- Two-photon polymerization (2PP) is an efficient technique to achieve high-resolution, three-dimensional (3D)-printed complex structures. However, it is restricted to photocurable monomer combinations, thus presenting constraints when aiming at attaining functionally active resist formulations and structures. In this context, metal nanoparticle (NP) integration as an additive can enable functionality and pave the way to more dedicated applications. Challenges lay on the maximum NP concentrations that can be incorporated into photocurable resist formulations due to the laser-triggered interactions, which primarily originate from laser scattering and absorption, as well as the limited dispersibility threshold. In this study, we propose an approach to address these two constraints by integrating metallic Rh NPs formed ex situ, purposely designed for this scope. The absence of surface plasmon resonance (SPR) within the visible and near-infrared spectra, coupled with the limited absorption value measured at the laser operating wavelength (780 nm), significantly limits the laser-induced interactions. Moreover, the dispersibility threshold is increased by engineering the NP surface to be compatible with the photocurable resin, permitting us to achieve concentrations of up to 2 wt %, which, to our knowledge, is significantly higher than the previously reported limit (or threshold) for embedded metal NPs. Another distinctive advantage of employing Rh NPs is their role as promising contrast agents for X-ray fluorescence (XRF) bioimaging. We demonstrated the presence of Rh NPs within the whole 2PP-printed structure and emphasized the potential use of NP-loaded 3D-printed nanostructures for medical devices.
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| 7. |
- Kronqvist, Nina, et al.
(author)
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Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation
- 2014
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 5:1, s. 3254-
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Journal article (peer-reviewed)abstract
- The mechanisms controlling the conversion of spider silk proteins into insoluble fibres, which happens in a fraction of a second and in a defined region of the silk glands, are still unresolved. The N-terminal domain changes conformation and forms a homodimer when pH is lowered from 7 to 6; however, the molecular details still remain to be determined. Here we investigate site-directed mutants of the N-terminal domain from Euprosthenops australis major ampullate spidroin 1 and find that the charged residues D40, R60 and K65 mediate intersubunit electrostatic interactions. Protonation of E79 and E119 is required for structural conversions of the subunits into a dimer conformation, and subsequent protonation of E84 around pH 5.7 leads to the formation of a fully stable dimer. These residues are highly conserved, indicating that the now proposed three-step mechanism prevents premature aggregation of spidroins and enables fast formation of spider silk fibres in general.
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| 8. |
- Landreh, M., et al.
(author)
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A pH-dependent dimer lock in spider silk protein
- 2010
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In: Journal of Molecular Biology. - : Academic Press. - 0022-2836 .- 1089-8638. ; 404:2, s. 328-336
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Journal article (peer-reviewed)abstract
- Spider dragline silk, one of the strongest polymers in nature, is composed of proteins termed major ampullate spidroin (MaSp) 1 and MaSp2. The N-terminal (NT) domain of MaSp1 produced by the nursery web spider Euprosthenops australis acts as a pH-sensitive relay, mediating spidroin assembly at around pH 6.3. Using amide hydrogen/deuterium exchange combined with mass spectrometry (MS), we detected pH-dependent changes in deuterium incorporation into the core of the NT domain, indicating global structural stabilization at low pH. The stabilizing effects were diminished or abolished at high ionic strength, or when the surface-exposed residues Asp40 and Glu84 had been exchanged with the corresponding amides. Nondenaturing electrospray ionization MS revealed the presence of dimers in the gas phase at pH values below--but not above--6.4, indicating a tight electrostatic association that is dependent on Asp40 and Glu84 at low pH. Results from analytical ultracentrifugation support these findings. Together, the data suggest a mechanism whereby lowering the pH to <6.4 results in structural changes and alteration of charge-mediated interactions between subunits, thereby locking the spidroin NT dimer into a tight entity important for aggregation and silk formation.
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| 9. |
- Vasicek, Jakub, et al.
(author)
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Finding haplotypic signatures in proteins
- 2023
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 12
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Journal article (peer-reviewed)abstract
- Background: The nonrandom distribution of alleles of common genomic variants produces haplotypes, which are fundamental in medical and population genetic studies. Consequently, protein-coding genes with different co-occurring sets of alleles can encode different amino acid sequences: protein haplotypes. These protein haplotypes are present in biological samples and detectable by mass spectrometry, but they are not accounted for in proteomic searches. Consequently, the impact of haplotypic variation on the results of proteomic searches and the discoverability of peptides specific to haplotypes remain unknown. Findings: Here, we study how common genetic haplotypes influence the proteomic search space and investigate the possibility to match peptides containing multiple amino acid substitutions to a publicly available data set of mass spectra. We found that for 12.42% of the discoverable amino acid substitutions encoded by common haplotypes, 2 or more substitutions may co-occur in the same peptide after tryptic digestion of the protein haplotypes. We identified 352 spectra that matched to such multivariant peptides, and out of the 4,582 amino acid substitutions identified, 6.37% were covered by multivariant peptides. However, the evaluation of the reliability of these matches remains challenging, suggesting that refined error rate estimation procedures are needed for such complex proteomic searches. Conclusions: As these procedures become available and the ability to analyze protein haplotypes increases, we anticipate that proteomics will provide new information on the consequences of common variation, across tissues and time.
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| 10. |
- Yang, Zhijian, et al.
(author)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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In: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Journal article (peer-reviewed)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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