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Sökning: WFRF:(Mahler G.)

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  • Stinton, L. M., et al. (författare)
  • PR3-ANCA: A Promising Biomarker in Primary Sclerosing Cholangitis (PSC)
  • 2014
  • Ingår i: Plos One. - 1932-6203. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. Methods: A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. Results: When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. Conclusion: PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.
  • Bentow, C., et al. (författare)
  • International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies
  • 2016
  • Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 25:8, s. 864-872
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.
  • de La Vieuville, G., et al. (författare)
  • Faint end of the z similar to 3-7 luminosity function of Lyman-alpha emitters behind lensing clusters observed with MUSE
  • 2019
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 628
  • Tidskriftsartikel (refereegranskat)abstract
    • Contact. This paper presents the results obtained with the Multi-Unit Spectroscopic Explorer (MUSE) at the ESOVery Large Telescope on the faint end of the Lyman-alpha luminosity function (LF) based on deep observations of four lensing clusters. The goal of our project is to set strong constraints on the relative contribution of the Lyman-alpha emitter (LAE) population to cosmic reionization.Aims. The precise aim of the present study is to further constrain the abundance of LAEs by taking advantage of the magnification provided by lensing clusters to build a blindly selected sample of galaxies which is less biased than current blank field samples in redshift and luminosity. By construction, this sample of LAEs is complementary to those built from deep blank fields, whether observed by MUSE or by other facilities, and makes it possible to determine the shape of the LF at fainter levels, as well as its evolution with redshift.Methods. We selected a sample of 156 LAEs with redshifts between 2.9 <= z <= 6.7 and magnification-corrected luminosities in the range 39 less than or similar to log L-Ly alpha [erg s(-1)] less than or similar to 43. To properly take into account the individual differences in detection conditions between the LAEs when computing the LF, including lensing configurations, and spatial and spectral morphologies, the non-parametric 1/V-max method was adopted. The price to pay to benefit from magnification is a reduction of the effective volume of the survey, together with a more complex analysis procedure to properly determine the effective volume V-max for each galaxy. In this paper we present a complete procedure for the determination of the LF based on IFU detections in lensing clusters. This procedure, including some new methods for masking, effective volume integration and (individual) completeness determinations, has been fully automated when possible, and it can be easily generalized to the analysis of IFU observations in blank fields.Results. As a result of this analysis, the Lyman-alpha LF has been obtained in four different redshift bins: 2.9 < z < 6; 7, 2.9 < z < 4.0, 4 : 0 < z < 5.0; and 5 : 0 < z < 6.7 with constraints down to log L-Ly alpha = 40.5. From our data only, no significant evolution of LF mean slope can be found. When performing a Schechter analysis also including data from the literature to complete the present sample towards the brightest luminosities, a steep faint end slope was measured varying from alpha = -1.69(-0.08)(+0.08) to alpha = -1.87(-0 .12)(+0.12) between the lowest and the highest redshift bins.Conclusions. The contribution of the LAE population to the star formation rate density at z similar to 6 is less than or similar to 50% depending on the luminosity limit considered, which is of the same order as the Lyman-break galaxy (LBG) contribution. The evolution of the LAE contribution with redshift depends on the assumed escape fraction of Lyman-alpha photons, and appears to slightly increase with increasing redshift when this fraction is conservatively set to one. Depending on the intersection between the LAE/LBG populations, the contribution of the observed galaxies to the ionizing flux may suffice to keep the universe ionized at z similar to 6.
  • Drake, A. B., et al. (författare)
  • The MUSE Hubble Ultra Deep Field Survey VI. The faint-end of the Lyα luminosity function at 2.91
  • 2017
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 608
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the deepest study to date of the Ly alpha luminosity function in a blank field using blind integral field spectroscopy from MUSE. We constructed a sample of 604 Ly alpha emitters (LAEs) across the redshift range 2.91 < z < 6.64 using automatic detection software in the Hubble Ultra Deep Lield. The deep data cubes allowed us to calculate accurate total Ly alpha fluxes capturing low surface-brightness extended Ly alpha emission now known to be a generic property of high-redshift star-forming galaxies. We simulated realistic extended LAEs to fully characterise the selection function of our samples, and performed flux-recovery experiments to test and correct for bias in our determination of total Ly alpha fluxes. We find that an accurate completeness correction accounting for extended emission reveals a very steep faint-end slope of the luminosity function, alpha, down to luminosities of log(10) L erg s(-1) < 41.5, applying both the 1/V-max and maximum likelihood estimators. Splitting the sample into three broad redshift bins, we see the faint-end slope increasing from -2.03(-0.07)(+1.42) at z approximate to 3.44 to -2.86(-infinity)(+0.76) Z approximate to 76 at z approximate to 5.48, however no strong evolution is seen between the 68% confidence regions in L*-alpha parameter space. Using the Ly alpha line flux as a proxy for star formation activity, and integrating the observed luminosity functions, we find that LAEs' contribution to the cosmic star formation rate density rises with redshift until it is comparable to that from continuum-selected samples by z approximate to 6. This implies that LAEs may contribute more to the star-formation activity of the early Universe than previously thought, as any additional intergalactic medium (IGM) correction would act to further boost the Ly alpha luminosities. Linally, assuming fiducial values for the escape of Ly alpha and LyC radiation, and the dumpiness of the IGM, we integrated the maximum likelihood luminosity function at 5.00 < z < 6.64 and find we require only a small extrapolation beyond the data (<1 dex in luminosity) for LAEs alone to maintain an ionised IGM at z approximate to 6.
  • Gandla, M. L., et al. (författare)
  • Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees
  • 2021
  • Ingår i: Biotechnology for Biofuels. - : BioMed Central. - 1754-6834. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth. Results In this study, we report on transgenic hybrid aspen (Populus tremula x tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for Populus tremula x tremuloides vesicle-associated membrane protein (VAMP)-associated protein PttVAP27-17 that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20-44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26-50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control. Conclusions The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.
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