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Sökning: WFRF:(Schuhmann M)

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  • Bowden, John A., et al. (författare)
  • Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
  • 2017
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
  • Tidskriftsartikel (refereegranskat)abstract
    • As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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  • Heyckendorf, J, et al. (författare)
  • Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
  • 2021
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 58:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.MethodsAdult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.Results50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
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  • Northcott, Paul A, et al. (författare)
  • Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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  • Gazaryan, I G, et al. (författare)
  • Tobacco peroxidase as a new reagent for amperometric biosensors
  • 2005
  • Ingår i: Journal of Analytical Chemistry. - : Springer Science and Business Media LLC. - 1608-3199 .- 1061-9348. ; 60:6, s. 558-566
  • Tidskriftsartikel (refereegranskat)abstract
    • The results of testing a new enzyme, anionic tobacco peroxidase (TOP), in various amperometric biosensors are summarized. The biochemical and electrochemical properties of the enzyme are briefly characterized. As compared to the commonly used cationic peroxidase from horseradish roots, TOP exhibits a wider optimum stability pH range, higher stability to inactivation with hydrogen peroxide, and higher efficiency in direct electron-transfer processes. The enzyme immobilized by adsorption on graphite is effective in determining aminophenols and aromatic diamines under flow conditions with a detection limit of 10 nM. Upon immobilization on graphite by incorporation into a get of a redox-active polymer (crosslinked polyvinylimidazole with osmium 4,4'-dimethylbipyridinium chloride), TOP exhibited sensitivity and stability comparable to those of horseradish peroxidase and a wider linearity range. Upon immobilization on a self-assembled thiol monolayer at a gold electrode, TOP was much superior to horseradish peroxidase in the sensitivity of determining hydrogen peroxide, regardless of the charge of the monolayer. Prospects for the further use of the native enzyme and its genetically engineered unglycosylated form are considered.
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  • Heyckendorf, J, et al. (författare)
  • Treatment responses in multidrug-resistant tuberculosis in Germany
  • 2018
  • Ingår i: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1815-7920. ; 22:4, s. 399-
  • Tidskriftsartikel (refereegranskat)
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  • Alpeeva, IS, et al. (författare)
  • Bi-enzyme alcohol biosensors based on genetically engineered alcohol oxidase and different peroxidases
  • 2005
  • Ingår i: Microchimica Acta. - : Springer Science and Business Media LLC. - 1436-5073 .- 0026-3672. ; 152:1-2, s. 21-27
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the development of a bi-layer bi-enzyme biosensor architecture using different peroxidases and alcohol oxidase from Hansenula polymorpha C-105 as biological recognition elements. The sensor architecture comprises a first layer containing either horseradish peroxidase or royal palm tree peroxidase crosslinked with an Osmium complex-modified redox hydrogel. On top, a second layer was formed by electrochemically induced precipitation of a cathodic electrodeposition paint simultaneously entrapping alcohol oxidase isolated from a genetically modified strain of Hansenula polymorpha C-105. The sensor architecture was optimized with respect to effective electron transfer and stability of the enzyme. The main characteristics of the biosensors are an apparent maximal current I-max(app) of 572-940 nA, an apparent Michaelis constant K-M(app) of 9.5 mM, a sensitivity of 60-98 nA mM(-1) and an improved operational stability represented by a deactivation constant of 1.5-2.0 x 10(-4) min(-1).
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  • Gaspar, S., et al. (författare)
  • A method for the design and study of enzyme microstructures formed by means of a flow-through microdispenser
  • 2001
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 73:17, s. 4254-4261
  • Tidskriftsartikel (refereegranskat)abstract
    • Micrometer-sized enzyme grids were fabricated on gold surfaces using a novel method based on a flow-through microdispenser. The method involves dispensing very small droplets of enzyme solution (similar to 100 pL) during the concomitant relative movement of a gold substrate with respect to the nozzle of a microdispenser, resulting in enzyme patterns with a line width of similar to 100 mum. Different immobilization methods have been evaluated, yielding either enzyme monolayers using functionalized self-assembled thiol monolayers for covalent binding of the enzyme or enzyme multilayers by cross-linking or entrapping the enzymes in a polymer film. The latter immobilization techniques allow the formation of coupled multienzyme structures. On the basis of this feature, coupled bienzyme (glucose oxidase and catalase) or three-enzyme (alpha -glucosidase, mutarotase, and glucose oxidase) microstructures consisting of line patterns of one enzyme intersecting with the patterned lines of the other enzyme(s) were fabricated. By means of scanning electrochemical microscopy (SECM) operated in the generator-collector mode, the enzyme microstructures and their integrity were visualized using the localized detection of enzymatically produced/consumed H2O2. A calibration curve for glucose could be obtained by subsequent SECM line scans over a glucose oxidase microstructure for increasing glucose concentrations, demonstrating the possibility of obtaining localized quantitative data from the prepared microstructures. Possible applications of these enzyme microstructures for multianalyte detection and interference elimination and for screening of different biosensor configurations are highlighted.
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  • Hopp, Sarah, et al. (författare)
  • Targeting Coagulation Factor XII as a Novel Therapeutic Option in Brain Trauma
  • 2016
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 79:6, s. 970-982
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury.Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury.Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage.Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.
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  • Mosbach, M., et al. (författare)
  • A miniaturised electrochemical affinity assay based on a wall-free sample droplet and micro-dispensing of the redox-labelled binding partner
  • 2001
  • Ingår i: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 16:9-12, s. 611-620
  • Tidskriftsartikel (refereegranskat)abstract
    • An affinity-assay was developed that is based on the modulation of the diffusion coefficient of a redox-labelled hapten upon complementary recognition of the analyte leading to an increase of molecular weight and hence to a decrease of the diffusion coefficient. The slower diffusion is monitored by means of cyclic voltammetry. In order to demonstrate the feasibility of this assay format, recognition of biotin by streptavidin has been chosen as a model system. Labelling of biotin was achieved by covalent binding of a ferrocene derivative to the biotin unit. To reduce the consumption of expensive compounds and to allow automatisation of the assay a novel miniaturised set-up was developed based on a wall-free sample droplet which forms the electrochemical cell with typical volumes of up to 10 mul. This droplet is dispensed by means of a step-motor driven syringe pump through a specially designed electrode holder spanning the gap between a micro-working electrode and a macroscopic counter electrode. By means of a piezo-driven micro-dispenser a predefined number of nano-droplets (100 pl volume each) containing the redox-labelled hapten are shot into the sample droplet. By this, any physical contact and hence any cross-contamination between the sample and the reagent solution could be avoided. Signal amplification can be achieved by redox recycling between the micro-electrode and the perpendicular positioned macroscopic counter electrode. (C) 2001 Elsevier Science B.V. All rights reserved.
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  • Mosbach, M., et al. (författare)
  • Determination of diffusion coefficients of electroactive species in time-of-flight experiments using a microdispenser and microelectrodes
  • 2001
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 73:11, s. 2468-2475
  • Tidskriftsartikel (refereegranskat)abstract
    • Two novel methods for the determination of diffusion coefficients of redox species combining the special properties of microdispensing devices and microelectrodes are presented Both are based on the local application of tiny volumes of the redox-active species by means of a dispenser nozzle at a defined distance from the surface of a microelectrode. The microelectrode, which is inserted through the bottom into an electrochemical cell, is held at a constant potential sufficient to oxidize or reduce the electro-active species under diffusional control. The dispenser, which is filled with the electro-active species, can be positioned by means of micrometer screws over the microelectrode, After dispensing a defined number of droplets near the microelectrode surface, the current through the microelectrode is recorded, usually yielding a peak-shaped curve having a defined time delay between the shooting of the droplets and the maximum current, The time that is necessary to attain maximum current, together with the known distance between two dispensing points, can be used to determine the diffusion coefficient of the electroactive species without knowledge of any system parameters, such as concentration of the redox species, diameter of the electroactive surface or number of transferred electrons. A similar method for the determination of diffusion coefficient of redox species involves a second redox species for calibration purposes. A mixture of both species is shot close to the microelectrode surface. Due to the different formal potentials of the redox species that are used, they can be distinguished in sequential experiments by variation of the potentials that are applied to the microelectrode, and it is thus possible to determine the individual transit times of the redox species independently. The difference in the transit times, together with the known diffusion coefficient of one of the redox species, can be used to calculate the unknown diffusion coefficient of the second one.
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  • Mosbach, M, et al. (författare)
  • Picodroplet-deposition of enzymes on functionalized self-assembled monolayers as a basis for miniaturized multi-sensor structures
  • 2001
  • Ingår i: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 16:9-12, s. 827-837
  • Tidskriftsartikel (refereegranskat)abstract
    • We are reporting on a novel approach for structured immobilisation of enzymes on gold surfaces modified with monolayers of functionalised alkylthiols. The formation of enzyme spots is achieved by shooting very small volumes of an appropriate enzyme solution (down to 100 pl) onto a thiol-monolayer modified gold surface using a micro-dispenser. Formation of enzyme patterns is obtained by moving the micro-dispenser relative to the modified gold surface using a micro-positioning device. Enzyme spots with typical lateral dimensions of 100 ml are obtained, but also, more complex structures, e.g. lines or meander structures, can be achieved by multiple droplets dispensed during the concomitant movement of the micro-dispenser. The first enzyme layer on top of the functionalised thiol-monolayer is subsequently covalently immobilised using either carbodiimide activation of carboxilic headgroups at the enzyme or via already introduced activated ester functions at the monolayer. Immobilised enzyme activities of glucose oxidase and lactate oxidase patterns have been characterised by means of scanning electrochemical microscopy. The product of the enzyme-catalysed reaction, H2O2, is detected with an micro-electrode in the presence of either or both substrates, glucose and lactate, leading to a visualisation of the corresponding enzyme pattern and the lateral enzymatic activity. (C) 2001 Elsevier Science B.V. All rights reserved.
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  • Munteanu, Florentina, et al. (författare)
  • Fast-scan cyclic voltammetry and scanning electrochemical microscopy studies of the pH-dependent dissolution of 2-electron mediators immobilized on zirconium phosphate containing carbon pastes
  • 2002
  • Ingår i: Electroanalysis. - 1040-0397. ; 14:21, s. 1479-1487
  • Tidskriftsartikel (refereegranskat)abstract
    • A detailed study is presented on the leaking of two different 2-electron-transfer redox mediators from zirconium phosphate-modified carbon-paste electrodes. Two redox mediators commonly used in bioelectrochemistry, viz. methylene green and riboflavin, were adsorbed on zirconium phosphate and further integrated into carbon paste. Fast scan cyclic voltammetry and scanning electrochemical microscopy were used to characterize the leakage of these redox mediators at different pH conditions. It could be shown that an exposure to acidic pH-values significantly increased the rate of their leakage from the mediator-zirconium phosphate-modified carbon paste, whereas a tight adsorption was observed at neutral pH.
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  • Niculescu, M, et al. (författare)
  • Quinohemoprotein alcohol dehydrogenase-based reagentless amperometric biosensor for ethanol monitoring during wine fermentation
  • 2002
  • Ingår i: Analytica Chimica Acta. - 1873-4324. ; 463:1, s. 39-51
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the development and optimization of an amperometric biosensor for monitoring ethanol in beverages. The biosensor is constructed by cross-linking a quinoprotein alcohol dehydrogenase (QH-ADH) to an Os-complex-modified poly(vinylimidazole) redox polymer using poly(ethylene glycol) diglycidyl ether. The optimum biosensor configuration was evaluated by changing the ratio between enzyme, redox polymer, and cross-linker using conventional graphite rods as basis electrodes. The optimized sensor showed a sensitivity of 0.336+/-0.025 A M-1 cm(2) for ethanol and a detection limit (calculated as three times the signal-to-noise ratio) of 1 muM. This biosensor configuration was further evaluated in a conventional flow-injection system and the applicability for the determination of ethanol in diverse wine samples could be successfully demonstrated. Adaptation of this sensor configuration to screen-printed (SP) electrodes allowed their integration into an automated sequential-injection analyzer and the successful on-line monitoring of ethanol during wine fermentation processes.
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  • van Beest, Floris M, et al. (författare)
  • Classifying grey seal behaviour in relation to environmental variability and commercial fishing activity -a multivariate hidden Markov model
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Classifying movement behaviour of marine predators in relation to anthropogenic activity and environmental conditions is important to guide marine conservation. We studied the relationship between grey seal (Halichoerus grypus) behaviour and environmental variability in the southwestern Baltic Sea where seal-fishery conflicts are increasing. We used multiple environmental covariates and proximity to active fishing nets within a multivariate hidden Markov model (HMM) to quantify changes in movement behaviour of grey seals while at sea. Dive depth, dive duration, surface duration, horizontal displacement, and turning angle were used to identify travelling, resting and foraging states. The likelihood of seals foraging increased in deeper, colder, more saline waters, which are sites with increased primary productivity and possibly prey densities. Proximity to active fishing net also had a pronounced effect on state occupancy. The probability of seals foraging was highest <5 km from active fishing nets (51%) and decreased as distance to nets increased. However, seals used sites <5 km from active fishing nets only 3% of their time at sea highlighting an important temporal dimension in seal-fishery interactions. By coupling high-resolution oceanographic, fisheries, and grey seal movement data, our study provides a scientific basis for designing management strategies that satisfy ecological and socioeconomic demands on marine ecosystems.
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  • Xie, Kunpeng, 1985, et al. (författare)
  • Co3O4–MnO2–CNT Hybrids Synthesized by HNO3 Vapor Oxidation of Catalytically Grown CNTs as OER Electrocatalysts
  • 2015
  • Ingår i: ChemCatChem. - : Wiley. - 1867-3899 .- 1867-3880. ; 7:18, s. 3027-3035
  • Tidskriftsartikel (refereegranskat)abstract
    • An efficient two-step gas-phase method was developed for the synthesis of Co3O4–MnO2–CNT hybrids used as electrocatalysts in the oxygen evolution reaction (OER). Spinel Co–Mn oxide was used for the catalytic growth of multiwalled carbon nanotubes (CNTs) and the amount of metal species remaining in the CNTs was adjusted by varying the growth time. Gas-phase treatment in HNO3 vapor at 200 °C was performed to 1) open the CNTs, 2) oxidize encapsulated Co nanoparticles to Co3O4 as well as MnO nanoparticles to MnO2, and 3) to create oxygen functional groups on carbon. The hybrid demonstrated excellent OER activity and stability up to 37.5 h under alkaline conditions, with longer exposure to HNO3 vapor up to 72 h beneficial for improved electrocatalytic properties. The excellent OER performance can be assigned to the high oxidation states of the oxide nanoparticles, the strong electrical coupling between these oxides and the CNTs as well as favorable surface properties rendering the hybrids a promising alternative to noble metal based OER catalysts.
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25.
  • Xie, Kunpeng, 1985, et al. (författare)
  • Promoting effect of nitrogen doping on carbon nanotube-supported RuO2 applied in the electrocatalytic oxygen evolution reaction
  • 2016
  • Ingår i: Journal of Energy Chemistry. - : Elsevier BV. - 2095-4956. ; 25:2, s. 282-288
  • Tidskriftsartikel (refereegranskat)abstract
    • RuO2 nanoparticles supported on multi-walled carbon nanotubes (CNTs) functionalized with oxygen (OCNTs) and nitrogen (NCNTs) were employed for the oxygen evolution reaction (OER) in 0.1 M KOH. The catalysts were synthesized by metal-organic chemical vapor deposition using ruthenium carbonyl (Ru3(CO)12) as Ru precursor. The obtained RuO2/OCNT and RuO2/NCNT composites were characterized using TEM, H2-TPR, XRD and XPS in order probe structure-activity correlations, particularly, the effect of the different surface functional groups on the electrochemical OER performance. The electrocatalytic activity and stability of the catalysts with mean RuO2 particle sizes of 13-14 nm was evaluated by linear sweep voltammetry, cyclic voltammetry, and chronopotentiometry, showing that the generation of nitrogen-containing functional groups on CNTs was beneficial for both OER activity and stability. In the presence of RuO2, carbon corrosion was found to be significantly less severe.
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