| 1. |
- Mårtensson, Ulrika, et al.
(författare)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 2. |
- Nilsson, Christian, et al.
(författare)
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Nanoparticle-based continuous full filling capillary electrochromatography/electrospray ionization-mass spectrometry for separation of neutral compounds
- 2006
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 78:17, s. 6088-6095
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Tidskriftsartikel (refereegranskat)abstract
- Highly efficient reversed-phase capillary electrochromatography (CEC) separations (plate numbers up to 700 000/m), with electrospray ionization mass spectrometry detection were achieved utilizing novel dextran-coated polymer nanoparticles as a pseudostationary phase. A continuous full filling (CFF) technique in which nanoparticles are continuously introduced into the capillary was employed for separation of neutral analytes (dialkyl phthalates), utilizing an orthogonal electrospray interface to prevent nanoparticles from entering the mass spectrometer. CFF-CEC benefits from that an entirely fresh column is employed for every analysis, avoiding carryover effects associated with stationary-phase contamination. The highly efficient separations obtained were accomplished by optimizing the organic modifier concentration in the electrolyte and by using a high nanoparticle concentration (5 mg/mL), to improve interparticle mass transfer and gain sufficient retention. Nanoparticles, with an average diameter of 600 nm, were prepared by polymerization of methacrylic acid and trimethylolpropane trimethacrylate, which in turn were coated with dextran. These nanoparticles formed stable suspensions in electrolytes having broad ranges of polarities, enabling straightforward optimization of the reversed-phase conditions.
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| 3. |
- Almefelt, Lars, 1968, et al.
(författare)
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Requirements management in practice: findings from an empirical study in the automotive industry
- 2006
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Ingår i: Research in Engineering Design. ; 17:3, s. 113-134
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an empirical study carried out in the automotive industry, with the aim to bring forward new experiences and knowledge on management of requirements in practice. Adopting a qualitative systems approach, and using multiple information sources, the requirements management process during the development of a passenger car cockpit has been mapped out. More specifically, the intention has been to identify and describe progress, changes, deviations, and compromises regarding the requirements and their fulfilment linked to the different phases of the product development. The logical reconstruction of the requirements management process is complemented with broad descriptions of associated phenomena, such as important events, organisational structures, competences, and attitudes. Findings are presented, analysed and discussed considering also factors underlying observed phenomena. Accompanying the empirical findings, the paper concludes with recommendations for constructive and efficient requirements management in practice.
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| 4. |
- Andersson, Anna, et al.
(författare)
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Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
- 2005
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
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| 5. |
- Arlos, Patrik, et al.
(författare)
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A Distributed Passive Measurement Infrastructure
- 2005
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Konferensbidrag (refereegranskat)abstract
- In this paper we describe a distributed passive measurement infrastructure. Its goals are to reduce the cost and configuration effort per measurement. The infrastructure is scalable with regards to link speeds and measurement locations. A prototype is currently deployed at our university and a demo is online at http://inga.its.bth.se/projects/dpmi. The infrastructure differentiates between measurements and the analysis of measurements, this way the actual measurement equipment can focus on the practical issues of packet measurements. By using a modular approach the infrastructure can handle many different capturing devices. The infrastructure can also deal with the security and privacy aspects that might arise during measurements.
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| 6. |
- Artacho Ruiz, Josep, et al.
(författare)
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The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue: New chiral cleft compounds
- 2006
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 12:10, s. 2692-2701
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue are described. The diastereomers are unambiguously assigned as syn-anti 1a, anti-anti 1b, and syn-syn 1c isomers, by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris-Troger's base analogue have been synthesized. Molecules 1a and 1c are new cleft compounds and analysis of compound 1a in the solid state shows inclusion of one molecule of CH2Cl2 in the larger aromatic cleft, whereas in isomer 1c disordered solvent molecules are trapped in the extended aromatic cleft. Furthermore, in the solid state, isomer 1c forms infinite open channels along one of the crystallographic axes and perpendicular to this axis there are infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1a-c is resistant to inversion at the stereogenic nitrogen atoms under strongly and weakly acidic conditions in the range from room temperature (RT) to 95 degrees C. This observed configurational stability at the stereogenic nitrogens of 1a-c is unique for analogues of Troger's base in general to date. Finally, the ratio of cleft compounds 1a and 1c significantly increased relative to cavity compound 1b when ammonium chloride was used as an additive in the Troger's base condensation to 1a-c suggesting a templating effect of the ammonium ion.
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| 7. |
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| 8. |
- Cenci Nilsson, Angela, et al.
(författare)
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Dyskinesias and neural grafting in Parkinson's disease
- 2006
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Ingår i: Restorative Therapies in Parkinson's Disease. - : Springer US. - 9780387299846 - 9780387328232 ; , s. 184-224
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Bokkapitel (populärvet., debatt m.m.)abstract
- In the past 20 years, intracerebral transplantation of embryonic ventral mesencephalic (VM) tissue has been looked upon as a particularly promising approach for the treatment of Parkinson's disease (PD). Among the many possible treatment options for the future, transplantation bore the promise of a truly curative approach: endogeneous, degenerating dopamine (DA) neurons would be substituted for by healthy DA-producing cells, restoring the damaged nigrostriatal circuit once and for all (Nikkhah and Brandis, 1995; Barker, 2000; Fricker-Gates et al., 2001). Hopes were fostered by the encouraging results produced by intrastriatal VM transplants both in animal models of PD (Bj?rklund, 1992; Bj?rklund and Stenevi, 1979; Herman and Abrous, 1994; Perlow et al., 1979) and in early openlabel clinical trials (Lindvall, 1994; Lindvall and Hagell, 2000 and Chapter 5). The latter showed that embryonic VM tissue can engraft in the parkinsonian striatum and provide a local source of DA storage and release. In a majority of transplanted patients the grafts were found to ameliorate many of the symptoms of PD and to reduce the need for L-DOPA pharmacotherapy (Lindvall and Hagell, 2000). In addition to their immediate implications for PD, these results also suggested that neural cell replacement could develop into a radically new treatment approach for a wide range of neurological disorders (Gage et al., 1988; Lindvall and Bj?rklund, 1992; Aichner et al., 2002; Turner and Shetty, 2003; Grisolia, 2002; Peschansky and Dunnett, 2002; Studer et al., 1998). This early enthusiasm was dampened by alarming reports from the first NIH-sponsored clinical trial of neural transplantation, where a subgroup of patients had manifested a severe and persistent form of dyskinesia at late postoperative periods (Freed et al., 2001; Greene et al., 1999; Kolata, 2001 and Chapter 6). Other reports were soon to follow indicating that dyskinesias indeed can develop as a complication of intrastriatal VM grafting (Hagell et al., 2002; Ma et al., 2002; Olanow et al., 2003). These dyskinesias are a puzzling phenomenon that had not been foreseen by experimental studies of VM transplantation in animal models. This phenomenon does not presently lend itself to any simple explanation. In fact, current pathophysiological models are inadequate to explain the emergence of dyskinesia after interventions that can provide a source of continuous DA release in the striatum. Yet, understanding this issue appears essential in order to be able to plan further application of cell-replacement therapy in PD. In this chapter, we shall first provide a general review of the clinical spectrum and pathophysiology of the dyskinesias that complicate the treatment of PD. We shall then discuss the effects of VM grafts on L-DOPA-induced dyskinesias that are present prior to transplantation surgery. Thereafter, we will specifically address the issue of graft-induced dyskinesia, viz., an apparently novel clinical entity that is caused by the intrastriatal grafts themselves. Finally, we shall provide a speculative review of possible mechanisms underlying the development of dyskinesia following intrastriatal VM transplantation.
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| 9. |
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| 10. |
- Ek, Patrik, 1980-
(författare)
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Mass Spectrometry with Electrospray Ionization from an Adjustable Gap
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis the fabrication and analytical evaluation of two new electrospray emitters utilized for mass spectrometry analysis is presented. The emitters are based on a new concept, where the spray orifice can be varied in size. The thesis is based on two papers. All present-day nanoelectrospray emitters have fixed dimensions. The range of the applicable flow rate for such an emitter is therefore rather limited and exchange of emitters may be necessary from one experiment to another. Optimization of the signal of the analyte ions is also limited to adjustments of the applied voltage or the distance between the emitter and the mass spectrometer inlet. Furthermore, clogging can occur in emitters with fixed dimensions of narrow orifice sizes. In this thesis, electrospray emitters with a variable size of the spray orifice are proposed. An open gap between two thin substrates is filled with sample solution via a liquid bridge from a capillary. Electrospray is generated at the end point of the gap, which can be varied in width. In Paper I, electrospray emitters fabricated in polyethylene terephthalate have been evaluated. Triangular tips are manually cut from the polymer film. The tips are mounted to form a gap between the edges of the tips. The gap wall surfaces are subjected to a hydrophilic surface treatment to increase the wetting of the gap walls. In Paper II, silicon electrospray chips with high precision are fabricated and evaluated. A thin beam, elevated from the bulk silicon chip is fabricated by means of deep reactive ion etching. The top surfaces of the beams of two chips act as a sample conduit when mounted in the electrospray setup. An anisotropic etching step with KOH of the intersecting <100> crystal planes results in a very sharp spray point. The emitters were given a hydrophobic surface treatment except for the hydrophilic gap walls. For both emitter designs, the gap width has been adjusted during the experiments without any interruption of the electrospray. For a continuously applied peptide mixture, a shift towards higher charge states and increased signal to noise ratios could be observed when decreasing the gap width. The limit of detection has been investigated and the silicon chips have been interfaced with capillary electrophoresis.
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