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- Pulkkinen, Karoliina, et al.
(author)
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The value of values in climate science
- 2022
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In: Nature Climate Change. - : Springer Nature. - 1758-678X .- 1758-6798. ; 12:1, s. 4-6
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Journal article (peer-reviewed)
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- Svanberg, Sune, et al.
(author)
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Applications of terawatt lasers
- 1994
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In: LASER SPECTROSCOPY - XITH INTERNATIONAL CONFERENCE. - : AIP. - 1551-7616 .- 0094-243X. - 1563962624 ; :290, s. 264-269
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Conference paper (peer-reviewed)
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| 11. |
- Carlsson, Per-Ola, et al.
(author)
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Umbilical cord-derived mesenchymal stromal cells preserve endogenous insulin production in type 1 diabetes : a Phase I/II randomised double-blind placebo-controlled trial
- 2023
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:8, s. 1431-1441
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Journal article (peer-reviewed)abstract
- Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes.Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden.Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas those in ProTrans-treated individuals declined by only 10% (p<0.05). Similarly, insulin requirements increased in placebo-treated individuals by a median of 10 U/day, whereas insulin needs of ProTrans-treated individuals did not change over the follow-up period of 12 months (p<0.05).Conclusions/interpretation This study suggests that allogeneic Wharton's jelly-derived MSCs (ProTrans) is a safe treatment for recent-onset type 1 diabetes, with the potential to preserve beta cell function.
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- Gantelius, Jesper, et al.
(author)
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Improved sensitivity on an allergen lateral flow microarray by means of dendritic amplification
- 2009
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In: Proceedings of Conference, MicroTAS 2009 - The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. - 9780979806421 ; , s. 1136-1137
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Conference paper (peer-reviewed)abstract
- Recently, paper-based substrates have been proposed as an alternative to commonly used activated glass slides for microarray patterning[1], used in conjunction with capillary driven lateral flow of sample and detection reagents through the membrane. While fluorescent detection reagents may be employed to achieve high sensitivity, gold nanoparticles can also be used to allow readout by means of common table top scanners or digital cameras. Here, we demonstrate first results from employing a dendritic, or layer-by-layer, amplification approach for a high-density lateral flow allergen protein microarray, indicating that substantially increased sensitivity can be achieved with very modest increase of assay handling and time requirements.
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| 14. |
- Hammond, Maria, et al.
(author)
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Picodroplet partitioned whole genome amplification of low biomass samples preserves genomic diversity for metagenomic analysis
- 2016
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In: Microbiome. - : BioMed Central. - 2049-2618. ; 4
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Journal article (peer-reviewed)abstract
- Background: Whole genome amplification (WGA) is a challenging, key step in metagenomic studies of samples containing minute amounts of DNA, such as samples from low biomass environments. It is well known that multiple displacement amplification (MDA), the most commonly used WGA method for microbial samples, skews the genomic representation in the sample. We have combined MDA with droplet microfluidics to perform the reaction in a homogeneous emulsion. Each droplet in this emulsion can be considered an individual reaction chamber, allowing partitioning of the MDA reaction into millions of parallel reactions with only one or very few template molecules per droplet. Results: As a proof-of-concept, we amplified genomic DNA from a synthetic metagenome by MDA either in one bulk reaction or in emulsion and found that after sequencing, the species distribution was better preserved and the coverage depth was more evenly distributed across the genomes when the MDA reaction had been performed in emulsion. Conclusions: Partitioning MDA reactions into millions of reactions by droplet microfluidics is a straightforward way to improve the uniformity of MDA reactions for amplifying complex samples with limited amounts of DNA.
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| 15. |
- Herrlin, K, et al.
(author)
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Contrast-enhanced radiography by differential absorption, using a laser-produced X-ray source
- 1997
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In: Investigative Radiology. - 0020-9996. ; 32:5, s. 306-310
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES. The authors evaluate the feasibility of differential imaging of contrast media, with division of individual pixel values obtained from digital images generated by characteristic radiation from a laser-produced plasma, bridging the K-absorption edge of the contrast agent. METHODS. Laser pulses from an ultrashort-pulse terawatt laser system were focused onto gadolinium and tantalum targets, creating a plasma from which characteristic radiation and Bremsstrahlung was emitted. The elements of the target were selected so the characteristic emission lines of one of the elements were below the K edge of the contrast agent and the emission lines of the other element above. A phantom with gadolinium and other elements in various concentrations was examined. One radiographic exposure was made using a gadolinium target source and a subsequent exposure using a tantalum source. Both images were recorded digitally and the transmission ratios calculated by division of the individual pixel values. RESULTS. When viewed separately, the two images of the test phantom appeared similar. In the differential image, only the gadolinium solutions were bright, reflecting a difference in attenuation between the two exposures. CONCLUSIONS. Element-specific radiographs can be obtained by differential imaging. When fully explored, the technique may allow for contrast-enhanced radiography with increased sensitivity and decreased contrast dose.
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| 16. |
- Herrlin, K, et al.
(author)
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Generation of X-rays For Medical Imaging By High-power Lasers - Preliminary-results
- 1993
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In: Radiology. - 1527-1315. ; 189:1, s. 65-68
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Journal article (peer-reviewed)abstract
- PURPOSE: To evaluate the use of x-ray imaging performed with a high-power laser system in biologic and medical studies. MATERIALS AND METHODS: A compact terawatt laser system based on chirped pulse amplification in titanium-doped sapphire was used. X rays were generated by irradiating a high-atomic-number target (tantalum). RESULTS: When photons with an energy below 10 keV were removed with use of 3 mm of aluminum, the half-value layer in aluminum for the remaining x rays was approximately 10 mm. The x-ray source allowed performance of biologic magnification radiography. Star-pattern tests indicated an equivalent focal spot size of less than 60 mum. Exposures of a single pulse could be obtained. The duration of a single x-ray pulse was estimated to be of the order of picoseconds. CONCLUSION. With use of subpicosecond laser pulses, x-ray generation can occur with a smaller equivalent focal spot size than with conventional x-ray sources.
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| 25. |
- Lee, Hyun Ju, et al.
(author)
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Intricate role of water in proton transport through cytochrome c oxidase
- 2010
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 132:45, s. 16225-16239
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Journal article (peer-reviewed)abstract
- Cytochrome c oxidase (CytcO), the final electron acceptor in the respiratory chain, catalyzes the reduction of O2 to H2O while simultaneously pumping protons across the inner mitochondrial or bacterial membrane to maintain a transmembrane electrochemical gradient that drives, for example, ATP synthesis. In this work mutations that were predicted to alter proton translocation and enzyme activity in preliminary computational studies are characterized with extensive experimental and computational analysis. The mutations were introduced in the D pathway, one of two proton-uptake pathways, in CytcO from Rhodobacter sphaeroides. Serine residues 200 and 201, which are hydrogen-bonded to crystallographically resolved water molecules halfway up the D pathway, were replaced by more bulky hydrophobic residues (Ser200Ile, Ser200Val/Ser201Val, and Ser200Val/Ser201Tyr) to query the effects of changing the local structure on enzyme activity as well as proton uptake, release, and intermediate transitions. In addition, the effects of these mutations on internal proton transfer were investigated by blocking proton uptake at the pathway entrance (Asp132Asn replacement in addition to the above-mentioned mutations). Even though the overall activities of all mutant CytcO's were lowered, both the Ser200Ile and Ser200Val/Ser201Val variants maintained the ability to pump protons. The lowered activities were shown to be due to slowed oxidation kinetics during the PR → F and F → O transitions (PR is the "peroxy" intermediate formed at the catalytic site upon reaction of the four-electron-reduced CytcO with O2, F is the oxoferryl intermediate, and O is the fully oxidized CytcO). Furthermore, the PR → F transition is shown to be essentially pH independent up to pH 12 (i.e., the apparent pKa of Glu286 is increased from 9.4 by at least 3 pKa units) in the Ser200Val/Ser201Val mutant. Explicit simulations of proton transport in the mutated enzymes revealed that the solvation dynamics can cause intriguing energetic consequences and hence provide mechanistic insights that would never be detected in static structures or simulations of the system with fixed protonation states (i.e., lacking explicit proton transport). The results are discussed in terms of the proton-pumping mechanism of CytcO.
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| 42. |
- Svahn, Carina, et al.
(author)
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Photosynthetic activity in marine and brackish water strains of Fucus vesiculosus and Fucus radicans (Phaeophyceae) at different light qualities
- 2012
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In: Photochemistry and Photobiology. - : Wiley. - 0031-8655 .- 1751-1097. ; 88:6, s. 1455-1460
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Journal article (peer-reviewed)abstract
- This study investigates the effects of different light qualities on the photosynthetic capacity of the brown algae Fucus vesiculosus, from the Norwegian Sea, and Fucus radicans and F. vesiculosus, from the Bothnian Sea. The electron transport rates (ETR) obtained for F. vesiculosus from the Norwegian Sea showed significantly higher levels of light saturation compared with both species of algae from the Bothnian Sea. The maximum of ETR values for the Norwegian Sea strain showed no significant changes due to varying light quality compared with the initial values. For F. vesiculosus, from the Bothnian Sea, treatment with blue light showed an effect after 1 week of 30 and 90 μmol photons m -2 s -1 (P < 0.01), and for F. radicans from the Bothnian Sea, at the irradiance of 90 μmol photons m -2 s -1 and 1 week (P < 0.01). After 1 week in the Bothnian Sea species and after 2 weeks in F. vesiculosus from the Norwegian Sea, the photosynthetic efficiency (α) was significantly higher regardless of light quality and irradiance compared with the initial values. Variation in light quality and irradiance had minor effects on the F v:F m values of the three algal strains studied. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
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| 43. |
- Svahn, Fedrik, et al.
(author)
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A novel method for producing electron transparent thin films of inat interfaces between cells and biomaterials
- 2008
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In: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 19:1, s. 467-470
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Journal article (peer-reviewed)abstract
- Transmission electron microscopy (TEM) investigations of intact interfaces of cells and brittle biomaterials have proven difficult using common TEM preparation techniques. This paper describes a technique to fabricate thin sections for TEM investigation of intact interfaces between human monocytes and sintered hydroxylapatite by the use of focused ion beam (FIB) microscopy. The interfaces were examined using energy filtered TEM.
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| 46. |
- Svahn, Mathias G
(author)
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DNA analogs for the purpose of gene therapy
- 2007
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Doctoral thesis (other academic/artistic)abstract
- This thesis describes DNA analogs and their potential use for gene therapeutic purposes, primarily by sequence specific strand-invasion of double-stranded DNA. Gene therapy is classically thought of as restoration of a defect gene. Correction of dysfunctional genes is not feasible with today's technology, instead a new therapeutic gene is introduced. Nature's own gene delivery system, the virus, has gained its potency through evolution. Viruses can be modified, to instead of delivering its genome, be exploited as a vector to convey a therapeutic gene. Biotechnologically engineered viruses are expensive to produce, involving extensive monitoring for recombinant competent viruses, and if to become readministrated, the isotype has to be changed in order to prevent a specific immune response. Furthermore, humans have also developed defense mechanisms to prevent pathogens as viruses to fulfill their purpose. Non-viral gene delivery techniques are being developed to avoid viral associated complications. Bioplex (biological complex) is based on attachment of biologically active molecules, called functional entities (FE), on double-stranded DNA. Gene delivery is a complex process where FEs of different sources and origins are anticipated to guide the genetic material through the body, taken up by the correct cell-type and gain entrance to the nuclei. The FEs are anchored to DNA at specific positions by DNA analogs with superior binding affinity. Analogs presented here are peptide nucleic acid (PNA) and locked nucleic acid (LNA). Paper I addresses the assembly of the Bioplex. Instead of having a FE directly conjugated to the anchor, multiple molecules could be added to each anchor by selfassembling of singlestranded oligonucleotides, presenting exponentially growing number of anchoring sites without compromising the structure of the DNA. There are circumstances when it is advantageous to detach the FE from the cargo. Paper II presents a possible strategy by insertion of an amino acid recognition sequence for the endosomal protease, cathepsin L. In this way, the FE is released when the pH drops and the enzyme is activated. The FE could be carbohydrates or peptides of endogenous or viral origin, or synthetic. Furthermore, combinations of FEs are needed for optimal effect. Literature offers many alternatives and to try all of them in combinations is manually undoable, even for small ligand libraries. Paper III utilizes robots for transfection and analyzation. Ligands in combinations of two are screened for combinatorial effect on cellular association of 6 different human cell-lines. Even though only 22 ligands are included, it equals 484 unique combinations, resulting in 10 000 transfections. The field of oligonucleotide mediated gene therapy was founded with the discovery of antisense in the early 1970s. Paper IV is a study aiming to optimize our own oligonucleotide based construct called Zorro LNA. It inhibits transcription by directly blocking the polymerase machinery sterically by stably hybridizing to both strands of the helical DNA. Zorro has two arms of LNA oligonucleotides, each hybridizing to one strand of the DNA strands. They are interconnected by base paring, creating a Zlike structure within the double-stranded DNA.
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| 47. |
- Svahn, Mathias G., et al.
(author)
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Self-assembling supramolecular complexes by single-stranded extension from plasmid DNA
- 2007
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In: Oligonucleotides. - : Mary Ann Liebert Inc. - 1545-4576 .- 1557-8526. ; 17:1, s. 80-94
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Journal article (peer-reviewed)abstract
- Self-assembling supramolecular complexes are of great interest for bottom-up research like nanotechnology. DNA is an inexpensive building block with sequence-specific self-assembling capabilities through Watson-Crick and/or Hoogsteen base pairing and could be used for applications in surface chemistry, material science, nanomechanics, nanoelectronics, nanorobotics, and of course in biology. The starting point is usually single-stranded DNA, which is rather easily accessible for base pairing and duplex formation. When long stretches of double-stranded DNA are desirable, serving either as genetic codes or electrical wires, bacterial expansion of plasmids is an inexpensive approach with scale-up properties. Here, we present a method for using double-stranded DNA of any sequence for generating simple structures, such as junctions and DNA lattices. It is known that supercoiled plasmids are strand-invaded by certain DNA analogs. Here we add to the complexity by using Selfassembling UNiversal (SUN) anchors formed by DNA analog oligonucleotides, synthesized with an extension, a sticky-end that can be used for further base pairing with single-stranded DNA. We show here how the same set of SUN anchors can be utilized for gene therapy, plasmid purification, junction for lattices, and plasmid dimerization through Watson-Crick base pairing. Using atomic force microscopy, it has been possible to characterize and quantify individual components of such supra-molecular complexes.
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| 49. |
- Svahn, Stefan, 1977-, et al.
(author)
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Antimicrobial activity of filamentous fungi isolated from highly antibiotic-contaminated river sediment
- 2012
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In: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 2, s. 11591-
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Journal article (peer-reviewed)abstract
- Background:Filamentous fungi are well known for their production of substances with antimicrobial activities, several of which have formed the basis for the development of new clinically important antimicrobial agents. Recently, environments polluted with extraordinarily high levels of antibiotics have been documented, leading to strong selection pressure on local sentinel bacterial communities. In such microbial ecosystems, where multidrug-resistant bacteria are likely to thrive, it is possible that certain fungal antibiotics have become less efficient, thus encouraging alternative strategies for fungi to compete with bacteria.Methods:In this study, sediment of a highly antibiotic-contaminated Indian river was sampled in order to investigate the presence of cultivable filamentous fungi and their ability to produce substances with antimicrobial activity.Results:Sixty one strains of filamentous fungi, predominantly various Aspergillus spp. were identified. The majority of the Aspergillus strains displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus faecalis and Candida albicans. Bioassay-guided isolation of the secondary metabolites of A. fumigatus led to the identification of gliotoxin.Conclusion:This study demonstrated proof of principle of using bioassay-guided isolation for finding bioactive molecules
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