| 1. |
- Dahlin, Andreas, 1980
(författare)
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Nanoplasmonic Biosensors compatible with Artificial Cell Membranes
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Within life science, there is currently an intense search for novel techniques that enable efficient and reliable analysis of biomolecular interactions. Such methods have future applications within medical diagnostics and drug development, as well as within proteomic research in general. Lately, several concepts have emerged that are based on monitoring molecular binding to surfaces via optical, mechanical or electrical signal transduction. In particular, the plasmons associated with metallic nanoparticles are of interest since they offer a convenient way to monitor biomolecular interactions, also in a miniaturized format, by optical spectroscopy.This thesis describes the development of a biosensor based on the optical properties of nanoscale apertures in continuous metal films. The fabrication and characterization of the nanostructure is described, as well as surface modification protocols based on thiol chemistry for material-specific functionalization. In addition, an experimental setup for spectroscopy is presented together with data analysis algorithms for minimizing noise.It is emphasized that, from an experimental sensing perspective, nanoholes and nanoparticles have essentially the same plasmonic properties. However, the nanoholes offer several advantages because of the fact that the structure is physically different. In particular, it is shown how various artificial cell membranes can be spontaneously formed inside nanoholes. This makes the sensor compatible with studies of processes related to biological membranes. In this context, membrane-bound proteins are of special interest since they constitute a third of our genome and represent the target of half of the most common medical drugs. Potential future applications of the artificial membranes on the plasmonic nanostructures are discussed, with focus on probing transport across the membrane.
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| 2. |
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| 3. |
- Björn, Niclas, et al.
(författare)
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Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia
- 2020
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Ingår i: The Pharmacogenomics Journal. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 20:2, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.
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| 4. |
- Chandolias, Konstantinos, et al.
(författare)
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Protective effect of a reverse membrane bioreactor against toluene and naphthalene in anaerobic digestion
- 2022
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Ingår i: Biotechnology and Applied Biochemistry. - : Wiley. - 1470-8744 .- 0885-4513. ; 69:3, s. 1267 -1274
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Tidskriftsartikel (refereegranskat)abstract
- Raw syngas contains tar contaminants including toluene and naphthalene, which inhibit its conversion to methane. Cell encasement in a hydrophilic reverse membrane bioreactor (RMBR) could protect the cells from hydrophobic contaminants. This study aimed to investigate the inhibition of toluene and naphthalene and the effect of using RMBR. In this work, toluene and naphthalene were added at concentrations of 0.5–1.0 and 0.1–0.2 g/L in batch operation. In continuous operation, concentration of 0–6.44 g/L for toluene and 0–1.28 g/L for naphthalene were studied. The results showed that no inhibition was observed in batch operation for toluene and naphthalene at concentrations up to 1 and 0.2 g/L, respectively. In continuous operation of free cell bioreactors (FCBRs), inhibition of toluene and naphthalene started at 2.05 and 0.63 g/L, respectively. When they were present simultaneously, inhibition of toluene and naphthalene occurred at concentrations of 3.14 and 0.63 g/L, respectively. In continuous RMBRs, no inhibition for toluene and less inhibition for naphthalene were observed, resulting in higher methane production from RMBR than that of FCBR. These results indicated that RMBR system gave a better protection effect against inhibitors compared with FCBR.
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| 5. |
- Singh, Shalini, et al.
(författare)
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Conformational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:46, s. 40094-40106
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Tidskriftsartikel (refereegranskat)abstract
- Successful use of microgels as delivery systems of antimicrobial peptides (AMPs) requires control of factors determining peptide loading and release to/from the microgels as well as of membrane interactions of both microgel particles and released peptides. Addressing these, we here investigate effects of microgel charge density and conformationally induced peptide amphiphilicity on AMP loading and release using detailed nuclear magnetic resonance (NMR) structural studies combined with ellipsometry, isothermal titration calorimetry, circular dichroism, and light scattering. In parallel, consequences of peptide loading and release for membrane interactions and antimicrobial effects were investigated. In doing so, poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate the cationic AMPs EFK17a (EFKRIVQRIKDFLRNLV) and its partially D-amino acid-substituted variant EFK17da (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV). Peptide incorporation was found to increase with increasing with microgel charge density and peptide amphiphilicity. After microgel incorporation, which appeared to occur preferentially in the microgel core, NMR showed EFK17a to form a helix with pronounced amphiphilicity, while EFK17da displayed a folded conformation, stabilized by a hydrophobic hub consisting of aromatic/aromatic and aliphatic/aromatic interactions, resulting in much lower amphiphilicity. Under wide ranges of peptide loading, the microgels displayed net negative z-potential. Such negatively charged microgels do not bind to, nor lyre, bacteria-mimicking membranes. Instead, membrane disruption in these systems is mediated largely by peptide release, which in turn is promoted at higher ionic strength and lower peptide amphiphilicity. Analogously, antimicrobial effects against Escherichia coli were found to be dictated by peptide release. Taken together, the findings show that peptide loading, packing, and release strongly affect the performance of microgels as AMP delivery systems, effects that can be tuned by (conformationally induced) peptide amphiphilicity and by microgel charge density.
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| 6. |
- Svenson, Johan
(författare)
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På jakt efter nya läkemedel i Ishavet
- 2016
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Ingår i: Naturvetare. - : Naturvetarna. - 2000-2424. ; 6, s. 24-28
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ungefär en tredjedel av alla läkemedel har sin källa i naturen. Forskaren Johan Svenson skriver själv om sin expedition i Arktis, där forskarna samlar in alger och andra organismer i sökandet efter nya molekyler, som till exempel kan bli ny antibiotika.
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| 7. |
- Larsson, Mikael, 1982
(författare)
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Heterogeneities in polymer gels: Effects on swelling and mechanical properties
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polymeric hydrogels is a class of scientifically interesting materials that are being extensively studied. They are found in numerous applications within; drug delivery, hygiene products, food industry, analytical chemistry, etc. In addition, polymeric hydrogels have promising future applications as; cell scaffolds, implants, sensors, etc.One of the critical parameters for the performance of hydrogels in different applications is their structure. One such structural feature is the heterogeneity of the material, where the term heterogeneity applies to many different types of structural variations.The aim of this thesis was to investigate how different kinds of heterogeneities can be introduced into hydrogels, and how the presence of the different heterogeneities can be related to swelling and mechanical properties of such materials. The materials investigated were; polyacrylic acid neutralized with calcium hydroxide, polysodium acrylate superabsorbents with microfibrillated cellulose utilized as a filler and hydroxypropyl methylcellulose with heterogeneous distribution of the substituents.It was found that the presence of calcium ions during the synthesis of crosslinked polyacrylic acid introduces heterogeneities, both in network structure and in the form of phase separation, with dramatic impact on gel properties. Microfibrillated cellulose was found to even in small amounts cause significant changes to the swelling and shear modulus of crosslinked polysodium acrylate superabsorbents. The effect of the microfibrillated cellulose was similar as if an equivalent mass of covalent crosslinker had been used, but with improved resistance to fracture. For hydroxypropyl methylcellulose it was found that a heterogeneous distribution of the substituents causes increased interactions within the material, as determined from the glass transition temperature. Those increased interactions are coherent with earlier reports on solution behaviour for heterogeneously substituted hydroxypropyl methylcellulose.Hopefully the results presented in this thesis can contribute to the field of gel science, and in particular to the design of new multi-component soft materials.
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| 8. |
- Ragno, Rino, et al.
(författare)
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Structure-based modeling and target-selectivity prediction
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The present invention provides, inter alia, methods, models, and systems for selecting an effector having specificity for a target molecule. The methods and systems of the present invention involve several steps, including compiling a database containing structural data for a library of molecules and a population of ligands and activity data, establishing structure-based equivalence of sequence elements in the library of molecules, determining likely spatial orientations of population ligands in library molecules, calculating interaction energies for each ligand-molecule pair, generating statistical models that are predictive of sequence elements likely to contribute to a differential effect of ligands on molecules, selecting an effector that is likely to have a desired specificity for the target molecule, experimentally determining activity data for effector-library molecule pairs, and at least once repeating the steps listed above wherein the effector is a member of the population of ligands.
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| 9. |
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| 10. |
- Reza Seidi Goldar, Mohammad, et al.
(författare)
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Concept analysis of a frequency-sweeping delta/sigma beam-switching radar using machine learning
- 2021
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Ingår i: 2021 18Th European Radar Conference (EURAD). - : IEEE. ; , s. 145-148
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Konferensbidrag (refereegranskat)abstract
- this paper investigates a novel radar concept that is based on a minimalistic, small-aperture antenna array but features intelligent beam-shape switching and artificial-intelligence signal processing. In contrast to conventional phased-arrays, size, cost, and hardware complexity are drastically reduced by the proposed dual-antenna array which can create a broad and a frequency-scanning notched beam shape. The angular-resolution and target discrimination performance of the proposed radar concept have been validated by radar simulations for single and multiple target scenarios. For the signal processing, two convolutional neural networks (CNN) and a multilayer perceptron model are benchmarked against each other. A further CNN is implemented for estimating the number of targets, which can be used to pre-select the type of network determining range and cross-range of multiple targets. This paper shows that a small antenna aperture frontend in combination with beam-shape switching and artificial-intelligence signal processing methods is a suitable hardware-efficient radar concept for accurate multi-target location.
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