1. |
- Olsson, A., et al.
(författare)
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Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia
- 2007
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 97:6, s. 769-777
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Tidskriftsartikel (refereegranskat)abstract
- B-cell chronic lymphocytic leukaemia (B-CLL) is characterised by the progressive accumulation of monoclonal CD5+ B cells. In a previous study, we have analysed the expression profile of apoptosis-regulating genes using a cDNA-based microarray and found overexpression of the antiapoptotic bcl-2 family member, bfl-1, in B-CLL cells with an apoptosis-resistant phenotype. In this study, bfl-1 mRNA levels have been determined by competitive PCR in an extended population of B-CLL patients to characterise its role in disease progression and development of chemoresistance. bfl-1 levels were significantly higher in patients with no response (NR) to last chemotherapy than in patients responding (partial response (PR)) to last chemotherapy (P<0.05) and in patients who had not required treatment (P<0.05). We found no correlation between bfl-1 mRNA levels and disease progression, IGHV mutational status or other clinical parameters. In addition, bfl-1 mRNA levels were inversely correlated with apoptotic response to in vitro fludarabine treatment of B-CLL cells. Specific downregulation of bfl-1 using siRNA induced apoptosis in resistant cells. Our data suggest that bfl-1 contributes to chemoresistance and might be a therapeutic target in B-CLL.
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2. |
- El-Tawil, Asmaa A., et al.
(författare)
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Devolatilization Kinetics of Different Types of Bio-Coals Using Thermogravimetric Analysis
- 2019
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The interest of the steel industry in utilizing bio-coal (pre-treated biomass) as CO2-neutral carbon in iron-making is increasing due to the need to reduce fossil CO2 emission. In order to select a suitable bio-coal to be contained in agglomerates with iron oxide, the current study aims at investigating the thermal devolatilization of different bio-coals. A thermogravimetric analyzer (TGA) equipped with a quadrupole mass spectrometer (QMS) was used to monitor the weight loss and off-gases during non-isothermal tests with bio-coals having different contents of volatile matter. The samples were heated in an inert atmosphere to 1200 °C at three different heating rates: 5, 10, and 15 °C/min. H2, CO, and hydrocarbons that may contribute to the reduction of iron oxide if contained in the self-reducing composite were detected by QMS. To explore the devolatilization behavior for different materials, the thermogravimetric data were evaluated by using the Kissinger– Akahira–Sonuse (KAS) iso-conversional model. The activation energy was determined as a function of the conversion degree. Bio-coals with both low and high volatile content could produce reducing gases that can contribute to the reduction of iron oxide in bio-agglomerates and hot metal quality in the sustained blast furnace process. However, bio-coals containing significant amounts of CaO and K2O enhanced the devolatilization and released the volatiles at lower temperature.
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3. |
- El-Tawil, Asmaa A., et al.
(författare)
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Self-Reduction Behavior of Bio-Coal Containing Iron Ore Composites
- 2020
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The utilization of CO2 neutral carbon instead of fossil carbon is one way to mitigate CO2 emissions in the steel industry. Using reactive reducing agent, e.g., bio-coal (pre-treated biomass) in iron ore composites for the blast furnace can also enhance the self-reduction. The current study aims at investigating the self-reduction behavior of bio-coal containing iron ore composites under inert conditions and simulated blast furnace thermal profile. Composites with and without 10% bio-coal and sufficient amount of coke breeze to keep the C/O molar ratio equal to one were mixed and Portland cement was used as a binder. The self-reduction of composites was investigated by thermogravimetric analyses under inert atmosphere. To explore the reduction progress in each type of composite vertical tube furnace tests were conducted in nitrogen atmosphere up to temperatures selected based on thermogravimetric results. Bio-coal properties as fixed carbon, volatile matter content and ash composition influence the reduction of iron oxide. The reduction of the bio-coal containing composites begins at about 500 °C, a lower temperature compared to that for the composite with coke as only carbon source. The hematite was successfully reduced to metallic iron at 850 °C by using bio-coal, whereas with coke as a reducing agent temperature up to 1100 °C was required.
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4. |
- Holmner, Åsa, et al.
(författare)
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Blood group antigen recognition by Escherichia coli heat-labile enterotoxin
- 2007
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Ingår i: Journal of Molecular Biology. - London : Elsevier BV. - 0022-2836 .- 1089-8638. ; 371:3, s. 754-764
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Tidskriftsartikel (refereegranskat)abstract
- In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 angstrom crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAc alpha 3(Fuc alpha-2)Gal beta 4(Fuc alpha-3)Glc beta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.
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5. |
- Holmner, Åsa, et al.
(författare)
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Crystal Structures Exploring the Origins of the Broader Specificity of Escherichia coli Heat-Labile Enterotoxin Compared to Cholera Toxin.
- 2011
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Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 406:3, s. 387-402
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Tidskriftsartikel (refereegranskat)abstract
- Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are structurally and functionally related and share the same primary receptor, the GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit distinct ligand specificities, with LT being more promiscuous than CT. Here, we have attempted to rationalize the broader binding specificity of LT and the subtle differences between the binding characteristics of LTs from human and porcine origins (mediated by their B subunit pentamers, hLTB and pLTB, respectively). The analysis is based on two crystal structures of pLTB in complexes with the pentasaccharide of its primary ligand, GM1, and with neolactotetraose, the carbohydrate determinant of a typical secondary ligand of LTs, respectively. Important molecular determinants underlying the different binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18 and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by positioning Lys91, Glu51 and the adjacent loop region (50-61) containing Ile58 for ligand binding. Glu7 and Ala1 may also play an important role. Many of these residues are closely connected with a recently identified second binding site, and there appears to be cross-talk between the two binding sites. Binding to N-acetyllactosamine-terminated receptors is further augmented by Arg13 (present in pLT and some hLT variants), as previously predicted.
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6. |
- Karlsson, Lennart, et al.
(författare)
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Design of die and its effect on wear in cup forming
- 1995
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Ingår i: Simulation of materials processing. - Rotterdam : Balkema Publishers, A.A. / Taylor & Francis The Netherlands. - 9054105534 ; , s. 587-591
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Konferensbidrag (refereegranskat)
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7. |
- Krengel, Ute, 1964, et al.
(författare)
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Preliminary X-ray crystallographic analysis of the secreted chorismate mutase from Mycobacterium tuberculosis: A tricky crystallization problem solved
- 2006
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Ingår i: Acta Crystallographica Section F: Structural Biology and Crystallization Communications. - 1744-3091. ; 62:5, s. 441-445
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Tidskriftsartikel (refereegranskat)abstract
- Chorismate mutase catalyzes the conversion of chorismate to prephenate in the biosynthesis of the aromatic amino acids tyrosine and phenylalanine in bacteria, fungi and plants. Here, the crystallization of the unusual secreted chorismate mutase from Mycobacterium tuberculosis (encoded by Rv1885c), a 37.2 kDa dimeric protein belonging to the AroQγ subclass of mutases, is reported. Crystal optimization was non-trivial and is discussed in detail. To obtain crystals of sufficient quality, it was critical to initiate crystallization at higher precipitant concentration and then transfer the drops to lower precipitant concentrations within 5-15 min, in an adaptation of a previously described technique [Saridakis & Chayen (2000), Protein Sci. 9, 755-757]. As a result of the optimization, diffraction improved from 3.5 to 1.3 Å resolution. The crystals belong to space group P21, with unit-cell parameters a = 42.6, b = 72.6, c = 62.0 Å., β = 104.5°. The asymmetric unit contains one biological dimer, with 167 amino acids per protomer. A soak with a transition-state analogue is also described.
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8. |
- Oswald, Christine, et al.
(författare)
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Crystallization and preliminary crystallographic analysis of the NAD(H)-binding domain of Escherichia coli transhydrogenase
- 2004
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Ingår i: Acta Crystallographica Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; 60:4, s. 743-745
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Tidskriftsartikel (refereegranskat)abstract
- Transhydrogenase is a proton-pumping membrane protein that is required for the cellular regeneration of NADPH. The NAD(H)-binding domain (domain I) of transhydrogenase from Escherichia coli was crystallized using the hanging-drop vapour-diffusion technique at room temperature. The crystals, which were grown from PEG 4000 and ammonium acetate in citrate buffer, belong to the triclinic space group P1, with unit-cell parameters a = 38.8, b = 66.8, c = 76.4 Å, α = 67.5, β = 80.8, γ = 81.5°. X-ray diffraction data were collected to 1.9 Å resolution using synchrotron radiation. The crystals contain one dimer of transhydrogenase domain I per asymmetric unit. © 2004 International Union of Crystallography. Printed in Denmark - all rights reserved.
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9. |
- Åström, E., et al.
(författare)
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Precision measurements of linear scattering density using muon tomography
- 2016
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing. - 1748-0221. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that muon tomography can be used to precisely measure the properties of various materials. The materials which have been considered have been extracted from an experimental blast furnace, including carbon (coke) and iron oxides, for which measurements of the linear scattering density relative to the mass density have been performed with an absolute precision of 10%. We report the procedures that are used in order to obtain such precision, and a discussion is presented to address the expected performance of the technique when applied to heavier materials. The results we obtain do not depend on the specific type of material considered and therefore they can be extended to any application.
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10. |
- Ökvist, Lena Sundqvist., et al.
(författare)
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Injection of alternative carbon containing materials into the blast furnace
- 2012
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Ingår i: TMS Annual Meeting. - 9781118291160 ; , s. 161-169
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Konferensbidrag (refereegranskat)abstract
- Residual materials from the integrated steel plant itself or other sources often contain valuable compounds of e.g. C and Fe. Dust and sludge have to be agglomerated to be able to recycle to the blast furnace (BF) via top-charging. By injection of the materials, preparation methods in terms of e.g. drying and/or screening only, can be used. Alternative carbon materials (ACM) in terms of BF dust and sludge have been successfully injected up to levels of 60 kg/tHM in the LKAB Experimental Blast Furnace (LKAB EBF®). Efficiency in recovery of valuable compounds as well as the behavior of undesired elements have been evaluated and are discussed.
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11. |
- Ökvist, M., et al.
(författare)
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1.6 Å crystal structure of the secreted chorismate mutase from Mycobacterium tuberculosis: Novel fold topology revealed
- 2006
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 357:5, s. 1483-1499
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Tidskriftsartikel (refereegranskat)abstract
- The presence of exported chorismate mutases produced by certain organisms such as Mycobacterium tuberculosis has been shown to correlate with their pathogenicity. As such, these proteins comprise a new group of promising selective drug targets. Here, we report the high-resolution crystal structure of the secreted dimeric chorismate mutase from M. tuberculosis (*MtCM; encoded by Rv1885c), which represents the first 3D-structure of a member of this chorismate mutase family, termed the AroQγ subclass. Structures are presented both for the unliganded enzyme and for a complex with a transition state analog. The protomer fold resembles the structurally characterized (dimeric) Escherichia coli chorismate mutase domain, but exhibits a new topology, with helix H4 of*MtCM carrying the catalytic site residue missing in the shortened helix H1. Furthermore, the structure of each*MtCM protomer is significantly more compact and only harbors one active site pocket, which is formed entirely by one polypeptide chain. Apart from the structural model, we present evidence as to how the substrate may enter the active site.
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