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| 2. |
- Ericsson, Hans, et al.
(författare)
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The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food
- 2012
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:3, s. 436-444
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). less thanbrgreater than less thanbrgreater thanMethods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n = 8). In Part B, patients (n = 8) received placebo and a total dose of AZD6370 180 mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. less thanbrgreater than less thanbrgreater thanResults: AZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (p andlt; 0.001 at 60 and 180 mg doses). Insulin secretion increased with dose, but absolute increases were relatively small in the fasted versus fed state (0-4 h). Dosing AZD6370 twice or four-times over 1 day gave a smoother 24-h glucose profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well tolerated. less thanbrgreater than less thanbrgreater thanConclusions: AZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM.
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| 3. |
- Mu, Yabing, et al.
(författare)
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TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer
- 2011
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Ingår i: Nature Communications. - London : Macmillan Publishers Limited. - 2041-1723. ; 2:330
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor β (TGFβ) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGFβ binding to type II and type I serine/threonine kinase receptors (TβRII and TβRI) causes activation of different intracellular signaling pathways. TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Here we show that TGFβ, via TRAF6, causes Lys63-linked polyubiquitination of TβRI, promoting cleavage of TβRI by TNF-alpha converting enzyme (TACE), in a PKCζ-dependent manner. The liberated intracellular domain (ICD) of TβRI associates with the transcriptional regulator p300 to activate genes involved in tumour cell invasiveness, such as Snail and MMP2. Moreover, TGFβ-induced invasion of cancer cells is TACE- and PKCζ- dependent and the TβRI ICD is localized in the nuclei of different kinds of tumour cells in tissue sections. Thus, our data reveal a specific role for TβRI in TGFβ mediated tumour invasion.
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| 5. |
- Spante, Maria, 1967-, et al.
(författare)
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Unlock the rigidity and design for flexibility
- 2010
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Ingår i: US-China Education Review. - : David Publishing Company. - 1548-6613. ; 7:11, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports findings from a project implementing the VL (virtual labs) site featuringflash-based animations developed at Stanford University. The main conclusion in this paper stresses the need todesign for flexibility and adaptability of interactive media to better suit the specific situation teachers encounter intheir everyday work, in order to allow them to build their own audiovisual presentation kits based on variousavailable resources. Ambitious but rigid visualization products might otherwise end up not being used at all.
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| 6. |
- Andersson Sundén, Erik, et al.
(författare)
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Evaluation of neutron spectrometer techniques for ITER using synthetic data
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 701, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- A neutron spectrometer at ITER is expected to provide estimates of plasma parameters such as ion temperature, Ti, fuel ion ratio, nt/nd, and Qthermal/Qtot, with 10-20% precision at a time resolution, Δt, of at least 100 ms. The present paper describes a method for evaluating different neutron spectroscopy techniques based on their instrumental response functions and synthetic measurement data. We include five different neutron spectrometric techniques with realistic response functions, based on simulations and measurements where available. The techniques are magnetic proton recoil, thin-foil proton recoil, gamma discriminating organic scintillator, diamond and time-of-flight. The reference position and line of sight of a high resolution neutron spectrometer on ITER are used in the study. ITER plasma conditions are simulated for realistic operating scenarios. The ITER conditions evaluated are beam and radio frequency heated and thermal deuterium-tritium plasmas. Results are given for each technique in terms of the estimated time resolution at which the parameter determination can be made within the required precision (here 10% for Ti and the relative intensities of NB and RF emission components). It is shown that under the assumptions made, the thin-foil techniques out-perform the other spectroscopy techniques in practically all measurement situations. For thermal conditions, the range of achieved Δt in the determination of Ti varies in time scales from ms (for the magnetic and thin-foil proton recoil) to s (for gamma discriminating organic scintillator).
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| 7. |
- Andersson Sundén, Erik, et al.
(författare)
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Instrumentation for neutron emission spectrometry in use at JET
- 2010
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 623:2, s. 681-685
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Tidskriftsartikel (refereegranskat)abstract
- The present contribution discusses two neutron spectrometers: the time-of-flight spectrometer (TOFOR) and the magnetic proton recoil spectrometer (MPRu). TOFOR uses fast plastic scintillators equipped with digital time-stamping electronics to register the time of each eligible scintillation event. The time trace for each detector is acquired practically dead-time free. The detectors of the MPRu are of phoswich type and each detector is connected to a digital transient recorder card that stores the full waveform for an event. By using phoswich detectors, pulse-shape discrimination techniques can be applied offline to distinguish signal events from background. A future upgrade of TOFOR could be digital “hybrid” cards, which store correlated time and waveform information. This information can be used to decrease the background level in the ttof spectrum, thereby increasing the operating range.
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| 8. |
- Barlow, Lotti, et al.
(författare)
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Nationellt fackspråk för vård och omsorg : Slutrapport
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- SammanfattningEtt tillgängligt och använt nationellt fackspråk ska bidra till en god och säker vård och omsorg. Det ska även medverka till att kvaliteten och resultaten på området ska kunna följas upp och jämföras på ett mer effektivt sätt. Slutrapporten presenterar resultatet av projektet Nationellt fackspråk för vård och omsorg samt förslag till förvaltning och utveckling.ResultatetResultatet innefattar bland annat att det internationella begreppssystemet Snomed CT är översatt till svenska och att det är förberett för förvaltning och distribution. Socialstyrelsen har även tagit fram och testat metoder för förvaltning och utveckling av det nationella fackspråket i sin helhet. Därtill har representanter för målgrupperna informerats och fått kunskap.Rapporten innehåller en utförlig beskrivning av det nationella fackspråkets sammantagna innehåll: Socialstyrelsens termbank, klassifikationer och kodverk, den svenska versionen av Snomed CT, metoder för utveckling och förvaltning samt regler för användning.Förvaltning, införande och resursbehovI rapporten finns förslag till hur hela det nationella fackspråket kan tas omhand av Socialstyrelsen och hur det kan införas i vården och omsorgen. Projektets övergång till en långsiktigt hållbar organisation kräver resurser. Därför redogör rapporten för det förväntade resursbehovet för förvaltning och utveckling. Bland annat föreslås en treårig utbildningsinsats samt stimulansbidrag för införande.Krav på styrning, samordning och förtydligat ansvarRapporten betonar behovet av en samlad och medveten styrning av utvecklingen inom området. Socialstyrelsen vill ha en samordnande roll i utvecklingen och förvaltningen av det nationella fackspråket. Myndigheten föreslås få det initiala ansvaret för att utbilda användare och att driva frågor om det nationella fackspråket.Vidare vill Socialstyrelsen få ett uttalat mandat att samordna de nationella aktiviteter som drivs med koppling till Snomed CT. Rapporten pekar ut några särskilt prioriterade områden som myndigheten borde få i uppdrag att arbeta vidare inom.Kunskapsstyrning och normgivningEn viktig slutsats i rapporten är att användningen av det nationella fackspråket behöver regleras för att målet om ökad säkerhet för klienter och patienter ska kunna uppnås. I dagsläget bedöms föreskrifter vara den metod som bäst kan garantera ett brett genomförande.Målgrupper för slutrapportenSlutrapporten riktar sig till beslutsfattare i kommuner och landsting, vård- och omsorgspersonal med särskilt intresse eller ansvar för dokumentationsfrågor och professionella organisationer. Den riktar sig också till terminologiansvariga i kommuner och landsting, IT-direktörer, IT-leverantörer samt aktörer inom den nationella strategin för eHälsa.
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| 9. |
- Bennermo, Marie, et al.
(författare)
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Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction : a case-control study
- 2011
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 31:2, s. 259-264
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.
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| 10. |
- Darmanis, Spyros, et al.
(författare)
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Sensitive plasma protein analysis by microparticle-based proximity ligation assays
- 2010
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 9:2, s. 327-335
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Tidskriftsartikel (refereegranskat)abstract
- Detection of proteins released in the bloodstream from tissues damaged by disease can promote early detection of pathological conditions, differential diagnostics, and follow-up of therapy. Despite these prospects and a plethora of candidate biomarkers, efforts in recent years to establish new protein diagnostic assays have met with limited success. One important limiting factor has been the challenge of detecting proteins present at trace levels in complex bodily fluids. To achieve robust, sensitive, and specific detection, we have developed a microparticle-based solid-phase proximity ligation assay, dependent on simultaneous recognition of target proteins by three antibody molecules for added specificity. After capture on a microparticle, solid-phase pairs of proximity probes are added followed by washes, enabling detection and identification of rare protein molecules in blood while consuming small amounts of sample. We demonstrate that single polyclonal antibody preparations raised against target proteins of interest can be readily used to establish assays where detection depends on target recognition by three individual antibody molecules, recognizing separate epitopes. The assay was compared with state-of-the-art sandwich ELISAs for detection of vascular endothelial growth factor, interleukin-8 and interleukin-6, and it was found to be superior both with regard to dynamic range and minimal numbers of molecules detected. Furthermore, the assays exhibited excellent performance in undiluted plasma and serum as well as in whole blood, producing comparable results for nine different antigens. We thus show that solid-phase proximity ligation assay is suitable for validation of a variety of protein biomarkers over broad dynamic ranges in clinical samples.
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