| 1. |
- Aaldering, L. J., et al.
(författare)
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Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule
- 2017
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Ingår i: ChemBioChem. - : Wiley-VCH Verlag. - 1439-4227 .- 1439-7633. ; 18:8, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties.
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| 2. |
- Andersson, Måns, et al.
(författare)
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Breaking Down the Parallel Performance of GROMACS, a High-Performance Molecular Dynamics Software
- 2023
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Ingår i: PPAM 2022. Lecture Notes in Computer Science, vol 13826.. - : Springer Nature. ; , s. 333-345
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Konferensbidrag (refereegranskat)abstract
- GROMACS is one of the most widely used HPC software packages using the Molecular Dynamics (MD) simulation technique. In this work, we quantify GROMACS parallel performance using different configurations, HPC systems, and FFT libraries (FFTW, Intel MKL FFT, and FFT PACK). We break down the cost of each GROMACS computational phase and identify non-scalable stages, such as MPI communication during the 3D FFT computation when using a large number of processes. We show that the Particle-Mesh Ewald phase and the 3D FFT calculation significantly impact the GROMACS performance. Finally, we discuss performance opportunities with a particular interest in developing GROMACS for the FFT calculations.
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| 3. |
- Arrhenius, Karine, et al.
(författare)
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Suitability of vessels and adsorbents for the short-term storage of biogas/biomethane for the determination of impurities – Siloxanes, sulfur compounds, halogenated hydrocarbons, BTEX
- 2017
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Ingår i: Biomass and Bioenergy. - : Elsevier BV. - 0961-9534 .- 1873-2909. ; 105, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Biogas is a renewable energy source with many different production pathways and various excellent opportunities to use, for example as vehicle fuel (biomethane). Reliable analytical methodologies for assessing the quality of the gas are critical to ensure that the gas can technically and safely be used. An essential part of any procedure aiming to determine the quality is the sampling and the transfer to the laboratory. One of the greatest challenges is then to ensure that the composition of the sample collected does not change between the time of sampling and the analysis. The choice of the sampling vessel to be used must be made only after fully assessing its short-term stability. In this paper, the results from short-term stability studies in different vessels (cylinders, bags and sorbents) are presented for siloxanes, BTEX, halogenated hydrocarbons and sulfur compounds. Storage of dry gas at high pressure (> 6 MPa) appears to be a good alternative however it is currently challenging to find an optimal treatment of the cylinders for all species to be assessed in biogas/biomethane. At lower pressure, adsorption effects on the inner surface of the cylinders have been observed. The use of bags and sorbent tubes also shows limitation. No existing sorbent tubes are sufficiently universal as to trap all possible impurities and high boiling compounds may adsorbed on the inner surface of the bags walls. Moreover, the presence of water when storing biogas most certainly impacts the storage stability of compounds in most vessels. Using at least two sampling methods for a given compound and comparing results will allow taking into account the eventual effects of water vapour, and adsorption on the inner surface of the vessels.
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| 4. |
- Arul Murugan, N., et al.
(författare)
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Unusual binding-site-specific photophysical properties of a benzothiazole-based optical probe in amyloid beta fibrils
- 2018
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : The Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 20:31, s. 20334-20339
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Tidskriftsartikel (refereegranskat)abstract
- Optical imaging of amyloid fibrils serves as a cost-effective route for the diagnosis of Alzheimer-like conformational diseases. However{,} the challenge here is to optimize the binding affinity and photophysical properties of the optical imaging agents in a way specific to certain types of amyloids. In a few occasions it is shown that novel optical imaging agents can be designed to bind to a particular type of amyloid fibril with larger binding affinity and specificity. There is also a recent report on photoluminescent polythiophenes which display photophysical properties that can be used to distinguish the variants or subtypes of amyloids (J. Rasmussen et al.{,} Proc. Natl. Acad. Sci. U. S. A.{,} 2017{,} 114(49){,} 13018–13023). Based on a multiscale modeling approach{,} here{,} we report on the complementary aspect that the photophysical properties of a benzothiazole based optical probe (referred to as BTA-3) can be specific to the binding sites in the same amyloid fibrils and we attribute this to its varying electronic structure in different sites. As reported experimentally from competitive binding assay studies for many amyloid staining molecules and tracers{,} we also show multiple binding sites in amyloid fibrils for this probe. In particular{,} BTA-3 displayed a red-shift in its low-frequency absorption band only in site-4{,} a surface site of amyloid fibrils when compared to the spectra in water solvent. In the remaining sites{,} it exhibited a less significant blue shift for the same absorption band.
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| 5. |
- Ashaduzzaman, Md., et al.
(författare)
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On/off-switchable LSPR nano-immunoassay for troponin-T
- 2017
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Regeneration of immunosensors is a longstanding challenge. We have developed a re-usable troponin-T (TnT) immunoassay based on localised surface plasmon resonance (LSPR) at gold nanorods (GNR). Thermosensitive poly(N-isopropylacrylamide) (PNIPAAM) was functionalised with anti-TnT to control the affinity interaction with TnT. The LSPR was extremely sensitive to the dielectric constant of the surrounding medium as modulated by antigen binding after 20 min incubation at 37 degrees C. Computational modelling incorporating molecular docking, molecular dynamics and free energy calculations was used to elucidate the interactions between the various subsystems namely, IgG-antibody (c. f., anti-TnT), PNIPAAM and/or TnT. This study demonstrates a remarkable temperature dependent immuno-interaction due to changes in the PNIPAAM secondary structures, i.e., globular and coil, at above or below the lower critical solution temperature (LCST). A series of concentrations of TnT were measured by correlating the lambda(LSPR) shift with relative changes in extinction intensity at the distinct plasmonic maximum (i. e., 832 nm). The magnitude of the red shift in lambda(LSPR) was nearly linear with increasing concentration of TnT, over the range 7.6 x 10(-15) to 9.1 x 10(-4) g/mL. The LSPR based nano-immunoassay could be simply regenerated by switching the polymer conformation and creating a gradient of microenvironments between the two states with a modest change in temperature.
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| 6. |
- Ashaduzzaman, M., et al.
(författare)
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Studies on an on/off-switchable immunosensor for troponin T
- 2015
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 73
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Tidskriftsartikel (refereegranskat)abstract
- Regeneration is a key goal in the design of immunosensors. In this study, we report the temperature-regulated interaction of N-isopropylacrylamide (PNIPAAm) functionalised cardiac troponin T (cTnT) with anti-cTnT. Covalently bonded PNIPAAm on an anti-cTnT bioelectrode showed on/off-switchability, regeneration capacity and temperature triggered sensitivity for cTnT. Above the lower critical solution temperature (LCST), PNIPAAm provides a liphophilic microenvironment with specific volume reduction at the bioelectrode surface, making available binding space for cTnT, and facilitating analyte recognition. Computational studies provide details about the structural changes occurring at the electrode above and below the LCST. Furthermore, free energies associated with the binding of cTnT with PNIPAAm at 25 (δGcoil=-6.0Kcal/mole) and 37°C (δGglobular=-41.0kcal/mole) were calculated to elucidate the interaction and stability of the antigen-antibody complex. The responsiveness of such assemblies opens the way for miniaturised, smart immuno-technologies with 'built-in' programmable interactions of antigen-antibody upon receiving stimuli.
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| 7. |
- Awasthi, Saurabh, et al.
(författare)
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Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin
- 2015
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 12:9, s. 3312-3322
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Tidskriftsartikel (refereegranskat)abstract
- The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.
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| 8. |
- Bacquart, Thomas, et al.
(författare)
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Hydrogen fuel quality from two main production processes : Steam methane reforming and proton exchange membrane water electrolysis
- 2019
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Ingår i: Journal of Power Sources. - : Elsevier B.V.. - 0378-7753 .- 1873-2755. ; 444
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Tidskriftsartikel (refereegranskat)abstract
- The absence of contaminants in the hydrogen delivered at the hydrogen refuelling station is critical to ensure the length life of FCEV. Hydrogen quality has to be ensured according to the two international standards ISO 14687–2:2012 and ISO/DIS 19880-8. Amount fraction of contaminants from the two hydrogen production processes steam methane reforming and PEM water electrolyser is not clearly documented. Twenty five different hydrogen samples were taken and analysed for all contaminants listed in ISO 14687-2. The first results of hydrogen quality from production processes: PEM water electrolysis with TSA and SMR with PSA are presented. The results on more than 16 different plants or occasions demonstrated that in all cases the 13 compounds listed in ISO 14687 were below the threshold of the international standards. Several contaminated hydrogen samples demonstrated the needs for validated and standardised sampling system and procedure. The results validated the probability of contaminants presence proposed in ISO/DIS 19880-8. It will support the implementation of ISO/DIS 19880-8 and the development of hydrogen quality control monitoring plan. It is recommended to extend the study to other production method (i.e. alkaline electrolysis), the HRS supply chain (i.e. compressor) to support the technology growth.
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| 9. |
- Bacquart, Thomas, et al.
(författare)
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METROLOGY FOR HYDROGEN VEHICLE 2 : ACHIEVEMENTS AND PROGRESSES
- 2022
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Ingår i: Proceedings of WHEC 2022 - 23rd World Hydrogen Energy Conference. - : International Association for Hydrogen Energy, IAHE. - 9786250008430 ; , s. 1223-1225
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Konferensbidrag (refereegranskat)abstract
- Hydrogen fuel cells are an alternative power supply for electric drive trains and could represent 32 % of fuel demand by 2050. To deploy fuel cell electrical vehicles, there is current regulatory barriers (ISO 14687, OIML recommendations) that requires accurate measurements. The European funded project MetroHyVe has provided solutions and improvements in the four measurements challenges (flow metering, quality control, quality assurance and sampling). New challenges arised due to increase of hydrogen economy, therefore a new European project MetroHyVe 2 started in 2020 and its objectives will provide perspectives for the hydrogen economy to solve all regulatory barriers (ISO 14687, ISO 19880-8, ISO 19880-1, ISO 21087, OIML R139-1) and new measurement challenges (flow metering, quality control, sampling and fuel cell stack testing). The presentation will provide a comprehensive overview of the project achievements. The achievements around primary standard for flow metering (light and heavy duty), worldwide inter-laboratory comparison for hydrogen fuel quality, hydrogen sampling intercomparison and fuel cell stack testing recommendations will be highlighted.
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| 10. |
- Balamurugan, Kanagasabai, et al.
(författare)
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Effect of Alzheimer Familial Chromosomal Mutations on the Amyloid Fibril Interaction with Different PET Tracers : Insight from Molecular Modeling Studies
- 2017
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 8:12, s. 2655-2666
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide, it poses a great challenge for the society and health care. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the fi region of the amyloid precursor protein, which is referred to as autosomal dominant AD (ADAD). These mutations may cause changes in the secondary structure of the amyloid fi fibrils and may alter the fibrillization rate leading to changes in the disease development and could also affect the binding to tracers used in diagnosis. In particular, from some recent clinical studies using PET tracers for detection of fibrillar amyloids, it is evident that in ADAD patients with Arctic mutation no amyloid plaque binding can be detected with the "C Pittsburgh Compound B (C-11-PIB). However, for in vitro conditions, significant binding of H-3-PIB has been reported for the amyloid fibrils carrying the Arctic mutation. The aim of the present study is to investigate if there is any mutation specific binding of commonly used amyloid tracers, namely, florbetaben, florbetapir, FPIB, AZD4694, and AZD2184, by means of molecular modeling techniques. Other than Arctic, ADAD mutations, such as the Dutch, Italian, Iowa, and Flemish mutations, are considered in this study. We report that all tracers except florbetapir show reduced binding affinity toward amyloid beta fibrils with the Arctic mutation when compared to the native type. Moreover, florbetapir is the only tracer that binds to all mutants with increased affinity when compared to the native fibril. The results obtained from these studies could increase the understanding of the structural changes caused by mutation and concomitant changes in the interaction pattern of the PET tracers with the mutated variants, which in turn can be useful in selecting the appropriate tracers for the purpose of diagnosis as well as for designing new tracers with desirable properties.
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