| 1. |
- Morrison, Hilary G., et al.
(författare)
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Genomic minimalism in the early diverging intestinal parasite Giardia lamblia
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 317:5846, s. 1921-1926
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Tidskriftsartikel (refereegranskat)abstract
- The genome of the eukaryotic protist Giardia lamblia, an important human intestinal parasite, is compact in structure and content, contains few introns or mitochondrial relics, and has simplified machinery for DNA replication, transcription, RNA processing, and most metabolic pathways. Protein kinases comprise the single largest protein class and reflect Giardia's requirement for a complex signal transduction network for coordinating differentiation. Lateral gene transfer from bacterial and archaeal donors has shaped Giardia's genome, and previously unknown gene families, for example, cysteine-rich structural proteins, have been discovered. Unexpectedly, the genome shows little evidence of heterozygosity, supporting recent speculations that this organism is sexual. This genome sequence will not only be valuable for investigating the evolution of eukaryotes, but will also be applied to the search for new therapeutics for this parasite.
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| 2. |
- Ahuja, Dipali, et al.
(författare)
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Investigation of solid-liquid phase diagrams of the sulfamethazine-salicylic acid co-crystal
- 2019
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Ingår i: CrystEngComm. - : ROYAL SOC CHEMISTRY. - 1466-8033. ; 21:18, s. 2863-2874
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Tidskriftsartikel (refereegranskat)abstract
- The influence of temperature and solvent on the solid-liquid phase diagram of the 1 : 1 sulfamethazinesalicylic acid co-crystal has been investigated. Ternary phase diagrams of this co-crystal system have been constructed in three solvents: methanol, acetonitrile and a 7 : 3 (v/v) dimethylsulfoxide-methanol mixture, at three temperatures. The system exhibits congruent dissolution in acetonitrile and the co-crystal solubility has been determined by a gravimetric technique. The Gibbs energy of co-crystal formation from the respective solid components has been estimated from solubility data, together with the corresponding enthalpic and entropic component terms. The Gibbs energy of formation ranges from -5.7 to -7.7 kJ mol -1, with the stability increasing with temperature. In methanol and the DMSO-methanol mixture, the co-crystal dissolves incongruently. It is shown that the solubility ratio of the pure components cannot be used to predict with confidence whether the co-crystal will dissolve congruently or incongruently. The size of the region where the co-crystal is the only stable solid phase is inversely related to the pure component solubility ratio of salicylic acid and sulfamethazine.
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| 3. |
- Ahuja, Dipali, et al.
(författare)
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Solution and calorimetric thermodynamic study of a new 1:1 sulfamethazine-3-methylsalicylic acid co-crystal
- 2020
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033. ; 22:20, s. 3463-3473
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Tidskriftsartikel (refereegranskat)abstract
- A new 1:1 co-crystal of sulfamethazine (API, SMT) and 3-methylsalicylic acid (coformer, 3mSA) has been synthesized and its crystal structure solved by single crystal X-ray diffraction (XRD). The co-crystal has been thoroughly characterized by powder XRD, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The pure co-crystal could be synthesized by solvent drop grinding, cooling crystallization and slurry conversion co-crystallization. Ternary phase diagrams have been constructed in methanol and acetonitrile at 30 degrees C. The co-crystal exhibits incongruent dissolution in both solvents. The thermodynamics of co-crystal formation have been estimated from solubility data and calorimetric data, respectively, showing that formation of the SMT-3mSA co-crystal from its solid components is spontaneous and entropy-driven. The co-crystal formation is associated with a 5% increase in molecular volume. A relationship between the size of the region where the co-crystal is the most stable solid phase and the relative solubility of the co-crystal components has been uncovered. The co-crystal region becomes smaller as the solubility ratio increases.
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| 4. |
- Andersson, Peter, 1981-
(författare)
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Fast-Neutron Tomography using a Mobile Neutron Generator for Assessment of Steam-Water Distributions in Two-Phase Flows
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes the measurement technique of fast-neutron tomography for assessing spatial distributions of steam and water in two-phase flows. This so-called void distribution is of importance both for safe operation and for efficient use of the fuel in light water reactors, which compose the majority of the world’s commercial nuclear reactors. The technique is aimed for usage at thermal-hydraulic test loops, where heated two-phase flows are being investigated under reactor-relevant conditions.By deploying portable neutron generators in transmission tomography, the technique becomes applicable to stationary objects, such as thermal-hydraulic test loops. Fast neutrons have the advantage of high transmission through metallic structures while simultaneously being relatively sensitive to the water/void content. However, there are also challenges, such as the relatively low yield of commercially available fast-neutron generators, the tendency of fast neutrons to scatter in the interactions with materials and the relatively low efficiency encountered in fast-neutron detection.The thesis describes the design of a prototype instrument, FANTOM, which has been assembled and demonstrated. The main design parameters have been optimized to achieve maximal signal count rate in the detector elements, while simultaneously reaching an image unsharpness of ≤0.5 mm. Radiographic projections recorded with the assembled instrument are presented, and the performance parameters of FANTOM are deduced.Furthermore, tomographic reconstruction methods for axially symmetric objects, which is relevant for some test loops, have been developed and demonstrated on measured data from three test objects. The attenuation distribution was reconstructed with a radial resolution of 0.5 mm and an RMS error of 0.02 cm-1, based on data recorded using an effective measurement time of 3.5 hours per object. For a thermal-hydraulic test loop, this can give a useful indication of the flow mode, but further development is desired to improve the precision of the measurements.Instrument upgrades are foreseen by introducing a more powerful neutron generator and by adding detector elements, speeding up the data collection by several orders of magnitude and allowing for higher precision data. The requirements and performance of an instrument for assessment of arbitrary non-symmetric test loops is discussed, based on simulations.
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| 5. |
- Andersson, Peter, 1981-
(författare)
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Optimization of Equipment for Tomographic Measurements of Void Distributions using Fast Neutrons
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This licentiate thesis describes a novel nondestructive measuring technique for determiningspatial distributions of two-phase water flows. In Boiling Water Reactors, which compose themajority of the world's commercial nuclear reactors, this so called void distribution is of importance for safe operation.The presented measurement technique relies on fast neutron transmission tomography using portable neutron generators. Varying hardware options for such an instrument based on this technique and a prototype instrument, which is under construction, are described. The main design parameters are detailed and motivated from a performance point of view. A Paretomultiple objective optimization of the count rate and image unsharpness is presented. The resulting instrument design comprises an array of plastic scintillators for neutron detection. Such detector elements allow for spectroscopic data acquisition and subsequent reduction of background events at low energy by means of introducing an energy threshold in the analysis.The thesis includes two papers: In paper I, the recoil proton energy deposition distribution resulting from the interaction of the incoming neutrons is investigated for thin plastic scintillator elements. It is shown that the recoil proton losses have a large effect on the pulse height distribution and the intrinsic neutron detection efficiency is calculated for varying energy thresholds.In paper II the performance of the planned FANTOM device is investigated using the particle transport code MCNP5. An axially symmetric phantom void distribution is modeled and there construction is compared with the correct solution. According to the solutions, the phantom model can be reconstructed with 10 equal size ring-shaped picture elements, with a precision of better than 5 void percent units using a deuterium-tritium neutron generator with a yield of 3 · 107 neutrons per second and a measurement time of 13 h. However, it should be noted that commercial neutron generators with a factor of 103 higher yields exist and that the measurement time could decrease to less than a minute if such a neutron generator would beutilized.
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| 6. |
- Ansell, Brendan R. E., et al.
(författare)
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Drug resistance in Giardia duodenalis
- 2015
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Ingår i: Biotechnology Advances. - : Elsevier BV. - 0734-9750 .- 1873-1899. ; 33:6, s. 888-901
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Forskningsöversikt (refereegranskat)abstract
- Giardia duodenalis is a microaerophilic parasite of the human gastrointestinal tract and a major contributor to diarrheal and post-infectious chronic gastrointestinal disease world-wide. Treatment of G. duodenalis infection currently relies on a small number of drug classes. Nitroheterocyclics, in particular metronidazole, have represented the front line treatment for the last 40 years. Nitroheterocyclic-resistant G. duodenalis have been isolated from patients and created in vitro, prompting considerable research into the biomolecular mechanisms of resistance. These compounds are redox-active and are believed to damage proteins and DNA after being activated by oxidoreductase enzymes in metabolically active cells. In this review, we explore the molecular phenotypes of nitroheterocyclic-resistant G. duodenalis described to date in the context of the protisfs unusual glycolytic and antioxidant systems. We propose that resistance mechanisms are likely to extend well beyond currently described resistance-associated enzymes (i.e., pyruvate ferredoxin oxidoreductases and nitroreductases), to include NAD(P)H- and flavin-generating pathways, and possibly redox-sensitive epigenetic regulation. Mechanisms that allow G. duodenalis to tolerate oxidative stress may lead to resistance against both oxygen and nitroheterocyclics, with implications for clinical control. The present review highlights the potential for systems biology tools and advanced bioinformatics to further investigate the multifaceted mechanisms of nitroheterocyclic resistance in this important pathogen.
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| 7. |
- Ashour, Radwa, et al.
(författare)
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DTPA-Functionalized Silica Nano- and Microparticles for Adsorption and Chromatographic Separation of Rare Earth Elements
- 2018
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Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 6:5, s. 6889-6900
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Tidskriftsartikel (refereegranskat)abstract
- Silica nanoparticles and porous microparticles have been successfully functionalized with a monolayer of DTPA-derived ligands. The ligand grafting is chemically robust and does not appreciably influence the morphology or the structure of the material. The produced particles exhibit quick kinetics and high capacity for REE adsorption. The feasibility of using the DTPA-functionalized microparticles for chromatographic separation of rare earth elements has been investigated for different sample concentrations, elution modes, eluent concentrations, eluent flow rates, and column temperatures. Good separation of the La(III), Ce(III), Pr(III), Nd(III), and Dy(III) ions was achieved using HNO3 as eluent using a linear concentration gradient from 0 to 0.15 M over 55 min. The long-term performance of the functionalized column has been verified, with very little deterioration recorded over more than 50 experiments. The results of this study demonstrate the potential for using DTPA-functionalized silica particles in a chromatographic process for separating these valuable elements from waste sources, as an environmentally preferable alternative to standard solvent-intensive processes.
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| 8. |
- Bertilson, Michael, et al.
(författare)
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Laboratory Soft X-Ray Cryo Tomography
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- X-rays allow quantitative high-spatial-resolution three-dimensional (3D) imaging of intact unstained cells. Such 3D imaging is provided by soft x-ray lens-based methods (water-window cryo tomography) and hard x-ray lens-less methods (coherent diffraction imaging) are emerging. However, both methods rely on high-brightness synchrotron-radiation sources, which limit the accessibility of a wider scientific community. Here we show 3D water-window cryo tomography with a laboratory-source-based microscope arrangement. The system relies on a λ=2.48-nm liquid-jet laser-plasma source, normal- incidence multilayer condenser optics, 30-nm zone-plate optics, and a cryo sample chamber. We demonstrate imaging of intact unstained yeast, protozoan parasites and mammalian cells. 3D images show noise-limited features close to ~100 nm and intra-cellular structure is classified based on the local absorption coefficient. A comprehensive theoretical model of the tomographic imaging system allows optimization of system parameters and a quantitative estimate of the 3D imaging accuracy. The model includes issues such as non-geometric projections of the thick samples and stray light, and is applicable to laboratory as well as synchrotron-based x-ray microscopes. The model shows that laboratory x-ray cryo tomography will allow quantitative 3D imaging with ~30-nm (half-period) resolution over a full 5 µm object.
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| 9. |
- Birkeland, Shanda R., et al.
(författare)
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Transcriptome analyses of the Giardia lamblia life cycle
- 2010
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier BV. - 0166-6851 .- 1872-9428. ; 174:1, s. 62-65
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Tidskriftsartikel (refereegranskat)abstract
- We quantified mRNA abundance from 10 stages in the Giardia lamblia life cycle in vitro using Serial Analysis of Gene Expression (SAGE). 163 abundant transcripts were expressed constitutively. 71 transcripts were upregulated specifically during excystation and 42 during encystation. Nonetheless, the transcriptomes of cysts and trophozoites showed major differences. SAGE detected co-expressed clusters of 284 transcripts differentially expressed in cysts and excyzoites and 287 transcripts in vegetative trophozoites and encysting cells. All clusters included known genes and pathways as well as proteins unique to Giardia or diplomonads. SAGE analysis of the Giardia life cycle identified a number of kinases, phosphatases, and DNA replication proteins involved in excystation and encystation, which could be important for examining the roles of cell signaling in giardial differentiation. Overall, these data pave the way for directed gene discovery and a better understanding of the biology of G. lamblia.
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| 10. |
- Cheuk, Dominic, et al.
(författare)
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Investigation into solid and solution properties of quinizarin
- 2015
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Ingår i: CrystEngComm. - : Royal Society of Chemistry. - 1466-8033. ; 17:21, s. 3985-3997
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphism, crystal shape and solubility of 1,4-dihydroxyanthraquinone (quinizarin) have been investigated in acetic acid, acetone, acetonitrile, n-butanol and toluene. The solubility of FI and FII from 20 degrees C to 45 degrees C has been determined by a gravimetric method. By slow evaporation, pure FI was obtained from n-butanol and toluene, pure FII was obtained from acetone, while either a mixture of the two forms or pure FI was obtained from acetic acid and acetonitrile. Slurry conversion experiments have established an enantiotropic relationship between the two polymorphs and that the commercially available FI is actually a metastable polymorph of quinizarin under ambient conditions. However, in the absence of FII, FI is kinetically stable for many days over the temperature range and in the solvents investigated. FI and FII have been characterized by infrared spectroscopy (IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission and ordinary powder X-ray diffraction (PXRD) at different temperatures. The crystal structure of FII has been determined by single-crystal XRD. DSC and high-temperature PXRD have shown that both FI and FII will transform into a not previously reported hightemperature form (FIII) around 185 degrees C before this form melts at 200-202 degrees C. By indexing FIII PXRD data, a triclinic P (1) over bar cell was assigned to FIII. The solubility of quinizarin FI and FII in the pure organic solvents used in the present work is below 2.5% by weight and decreases in the order: toluene, acetone, acetic acid, acetonitrile and n-butanol. The crystal shapes obtained in different solvents range from thin rods to flat plates or very flat leaves, with no clear principal difference observed between FI and FII.
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