| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Waeijen-Smit, Kiki, et al.
(author)
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Global mortality and readmission rates following COPD exacerbation-related hospitalisation : a meta-analysis of 65 945 individual patients
- 2024
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In: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:1
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Journal article (peer-reviewed)abstract
- Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations < 12 months prior to the index event. Conclusions This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.
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| 3. |
- Belz, Gabrielle T, et al.
(author)
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The CD8alpha+ dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens.
- 2002
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In: Journal of Experimental Medicine. - : The Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 196:8, s. 1099-1104
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Journal article (peer-reviewed)abstract
- We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow-derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8alpha(+) dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced beta-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c(+)CD8alpha(+) cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8alpha(+) DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.
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| 4. |
- Reiling, Linda, et al.
(author)
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Targets of complement-fixing antibodies in protective immunity against malaria in children
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Journal article (peer-reviewed)abstract
- Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.
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| 5. |
- Dand, Nick, et al.
(author)
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Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
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In: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
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Journal article (peer-reviewed)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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| 6. |
- Höök, Kristina, et al.
(author)
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Soma-based design theory
- 2017
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In: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : ACM. - 9781450346566 ; , s. 550-557
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Conference paper (peer-reviewed)abstract
- Movement-based interaction design is increasingly popular, with application domains ranging from dance, sport, gaming to physical rehabilitation. In a workshop at CHI 2016, a set of prominent artists, game design-ers, and interaction designers embarked on a research journey to explore what we came to refer to as "aesthetics in soma-based design". In this follow-up work-shop, we would like to take the next step, shifting from discussing the philosophical underpinnings we draw upon to explain and substantiate our practice, to form our own interaction design theory and conceptualisations. We propose that soma-based design theory needs practical, pragmatic as well as analytical study -- otherwise the felt dimension will be missing. We will consider how such tacit knowledge can be articulated, documented and shared. To ground the discussion firmly in the felt experience of our own practice, the work-shop is organised as a joint practical design work session, supported by analytical study.
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| 7. |
- Mir, Zahid Mohammad, et al.
(author)
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Numerical and Experimental Analysis of Self-Protection in Reinforced Concrete due to Application of Mg–Al–NO2 Layered Double Hydroxides
- 2020
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In: Advanced Engineering Materials. - : Wiley-VCH Verlag. - 1438-1656 .- 1527-2648.
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Journal article (peer-reviewed)abstract
- Concrete possesses an intrinsic chloride binding capacity. Chloride ions from the environment bind with the hydrated cementitious phases in the form of bound chlorides. The contribution of chemically bound chlorides toward increasing the service life of concrete structures is vital as they help in slowing down the chloride diffusion in the concrete thereby delaying reinforcement depassivation. The authors attempt to increase the chloride binding capacity of concrete by adding a small amount of Mg–Al–NO2 layered double hydroxides (LDHs) with the objective to delay reinforcement corrosion and by this to considerably extend the service life of concrete structures situated in harsh environments. This study presents numerical and experimental analysis of the action of LDH in concrete. Formation factor is used to determine the effective chloride diffusion coefficient. In addition, the chloride binding isotherms together with Poisson–Nernst–Planck equations are used to model the chloride ingress. A comparable chloride binding is observed for concrete with and without Mg–Al–NO2, depicting only a slight chloride uptake by Mg–Al–NO2. Further investigations are conducted to understand this behavior by studying the stability and chloride entrapping capacity Mg–Al–NO2 in concrete. © 2020 The Authors.
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| 8. |
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| 9. |
- Mueller, Kristina M, et al.
(author)
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Impairment of Hepatic Growth Hormone and Glucocorticoid Receptor Signaling Causes Steatosis and Hepatocellular Carcinoma in Mice
- 2011
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In: Hepatology. - : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 54:4, s. 1398-1409
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Journal article (peer-reviewed)abstract
- Growth hormone (GH)-activated signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid (GC)-responsive glucocorticoid receptor (GR) are important signal integrators in the liver during metabolic and physiologic stress. Their deregulation has been implicated in the development of metabolic liver diseases, such as steatosis and progression to fibrosis. Using liver-specific STAT5 and GR knockout mice, we addressed their role in metabolism and liver cancer onset. STAT5 single and STAT5/GR double mutants developed steatosis, but only double-mutant mice progressed to liver cancer. Mechanistically, STAT5 deficiency led to the up-regulation of prolipogenic sterol regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator activated receptor gamma (PPAR-gamma) signaling. Combined loss of STAT5/GR resulted in GH resistance and hypercortisolism. The combination of both induced expression of adipose tissue lipases, adipose tissue lipid mobilization, and lipid flux to the liver, thereby aggravating STAT5-dependent steatosis. The metabolic dysfunctions in STAT5/GR compound knockout animals led to the development of hepatic dysplasia at 9 months of age. At 12 months, 35% of STAT5/GR-deficient livers harbored dysplastic nodules and similar to 60% hepatocellular carcinomas (HCCs). HCC development was associated with GH and insulin resistance, enhanced tumor necrosis factor alpha (TNF-alpha) expression, high reactive oxygen species levels, and augmented liver and DNA damage parameters. Moreover, activation of the c-Jun N-terminal kinase 1 (JNK1) and STAT3 was prominent. Conclusion: Hepatic STAT5/GR signaling is crucial for the maintenance of systemic lipid homeostasis. Impairment of both signaling cascades causes severe metabolic liver disease and promotes spontaneous hepatic tumorigenesis.
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