| 1. |
- Andersson, Björn, et al.
(författare)
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Fast estimation of multiple group generalized linear latent variable models for categorical observed variables
- 2023
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Ingår i: Computational Statistics & Data Analysis. - : Elsevier. - 0167-9473 .- 1872-7352. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- A computationally efficient method for marginal maximum likelihood estimation of multiple group generalized linear latent variable models for categorical data is introduced. The approach utilizes second-order Laplace approximations of the integrals in the likelihood function. It is demonstrated how second-order Laplace approximations can be utilized highly efficiently for generalized linear latent variable models by considering symmetries that exist for many types of model structures. In a simulation with binary observed variables and four correlated latent variables in four groups, the method has similar bias and mean squared error compared to adaptive Gauss-Hermite quadrature with five quadrature points while substantially improving computational efficiency. An empirical example from a large-scale educational assessment illustrates the accuracy and computational efficiency of the method when compared against adaptive Gauss-Hermite quadrature with three, five, and 13 quadrature points.
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| 2. |
- Ankargren, Sebastian, et al.
(författare)
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On the equivalence of confidence interval estimation based on frequentist model averagingand least-squares for the full model in linear regression
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In many applications of linear regression models, model selection is vital. However, randomness due to model selection is commonly ignored in post-model selection inference. In order to account for the model selection uncertainty in these linear models, least squares frequentist model averaging has been proposed recently. In this paper, we show that the confidence interval from model averaging is asymptotically equivalent to the confidence interval from the full model. Furthermore, we demonstrate that this equivalence also holds in finite samples if the parameter of interest is a linear function of the regression coefficients.
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| 3. |
- Ankargren, Sebastian, et al.
(författare)
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On the least-squares model averaging interval estimator
- 2018
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Ingår i: Communications in Statistics - Theory and Methods. - : Informa UK Limited. - 0361-0926 .- 1532-415X. ; 47:1, s. 118-132
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Tidskriftsartikel (refereegranskat)abstract
- In many applications of linear regression models, randomness due to model selection is commonly ignored in post-model selection inference. In order to account for the model selection uncertainty, least-squares frequentist model averaging has been proposed recently. We show that the confidence interval from model averaging is asymptotically equivalent to the confidence interval from the full model. The finite-sample confidence intervals based on approximations to the asymptotic distributions are also equivalent if the parameter of interest is a linear function of the regression coefficients. Furthermore, we demonstrate that this equivalence also holds for prediction intervals constructed in the same fashion.
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| 4. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Björk, Petra, et al.
(författare)
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A novel conserved RNA-binding domain protein, RBD-1, is essential for ribosome biogenesis
- 2002
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 13:10, s. 3683-3695
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis of the ribosomal subunits from pre-rRNA requires a large number of trans-acting proteins and small nucleolar ribonucleoprotein particles to execute base modifications, RNA cleavages, and structural rearrangements. We have characterized a novel protein, RNA-binding domain-1 (RBD-1), that is involved in ribosome biogenesis. This protein contains six consensus RNA-binding domains and is conserved as to sequence, domain organization, and cellular location from yeast to human. RBD-1 is essential in Caenorhabditis elegans. In the dipteran Chironomus tentans, RBD-1 (Ct-RBD-1) binds pre-rRNA in vitro and anti-Ct-RBD-1 antibodies repress pre-rRNA processing in vivo. Ct-RBD-1 is mainly located in the nucleolus in an RNA polymerase I transcription-dependent manner, but it is also present in discrete foci in the interchromatin and in the cytoplasm. In cytoplasmic extracts, 20-30% of Ct-RBD-1 is associated with ribosomes and, preferentially, with the 40S ribosomal subunit. Our data suggest that RBD-1 plays a role in structurally coordinating pre-rRNA during ribosome biogenesis and that this function is conserved in all eukaryotes.
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| 6. |
- Björk, Petra, et al.
(författare)
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Specific combinations of SR proteins associate with single pre-messenger RNAs in vivo and contribute different functions
- 2009
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 184:4, s. 555-568
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Tidskriftsartikel (refereegranskat)abstract
- Serine/arginine-rich (SR) proteins are required for messenger RNA (mRNA) processing, export, surveillance, and translation. We show that in Chironomus tentans, nascent transcripts associate with multiple types of SR proteins in specific combinations. Alternative splicing factor (ASF)/SF2, SC35, 9G8, and hrp45/SRp55 are all present in Balbiani ring (BR) pre-messenger ribonucleoproteins (mRNPs) preferentially when introns appear in the pre-mRNA and when cotranscriptional splicing takes place. However, hrp45/SRp55 is distributed differently in the pre-mRNPs along the gene compared with ASF/SF2, SC35, and 9G8, suggesting functional differences. All four SR proteins are associated with the BR mRNPs during export to the cytoplasm. Interference with SC35 indicates that SC35 is important for the coordination of splicing, transcription, and 3' end processing and also for nucleocytoplasmic export. ASF/SF2 is associated with polyribosomes, whereas SC35, 9G8, and hrp45/SRp55 cosediment with mono-ribosomes. Thus, individual endogenous pre-mRNPs/mRNPs bind multiple types of SR proteins during transcription, and these SR proteins accompany the mRNA and play different roles during the gene expression pathway in vivo.
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| 7. |
- Borgegard, Tomas, et al.
(författare)
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Alzheimers Disease: Presenilin 2-Sparing gamma-Secretase Inhibition Is a Tolerable A beta Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Secretase inhibition represents a major therapeutic strategy for lowering amyloid beta (A beta) peptide production in Alzheimers disease (AD). Progress toward clinical use of gamma-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The gamma-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between A beta production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1(PS1) over PS2 subclass of gamma-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain A beta levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious gamma-secretase targeting strategy for AD.
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| 8. |
- Borgegård, Tomas, et al.
(författare)
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Alzheimer's Disease : Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering Strategy
- 2012
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17297-17305
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibition represents a major therapeutic strategy for lowering amyloid β (Aβ) peptide production in Alzheimer's disease (AD). Progress toward clinical use of γ-secretase inhibitors has, however, been hampered due to mechanism-based adverse events, primarily related to impairment of Notch signaling. The γ-secretase inhibitor MRK-560 represents an exception as it is largely tolerable in vivo despite displaying only a small selectivity between Aβ production and Notch signaling in vitro. In exploring the molecular basis for the observed tolerability, we show that MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of γ-secretases and is tolerable in wild-type mice but causes dose-dependent Notch-related side effect in PS2-deficient mice at drug exposure levels resulting in a substantial decrease in brain Aβ levels. This demonstrates that PS2 plays an important role in mediating essential Notch signaling in several peripheral organs during pharmacological inhibition of PS1 and provide preclinical in vivo proof of concept for PS2-sparing inhibition as a novel, tolerable and efficacious γ-secretase targeting strategy for AD.
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| 9. |
- Cao, Chunzheng, et al.
(författare)
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Bayesian inference in a heteroscedastic replicated measurement error model using heavy-tailed distributions
- 2017
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Ingår i: Journal of Statistical Computation and Simulation. - : Informa UK Limited. - 0094-9655 .- 1563-5163. ; 87:15, s. 2915-2928
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a multivariate heteroscedastic measurement error model for replications under scale mixtures of normal distribution. The model can provide a robust analysis and can be viewed as a generalization of multiple linear regression from both model structure and distribution assumption. An efficient method based on Markov Chain Monte Carlo is developed for parameter estimation. The deviance information criterion and the conditional predictive ordinates are used as model selection criteria. Simulation studies show robust inference behaviours of the model against both misspecification of distributions and outliers. We work out an illustrative example with a real data set on measurements of plant root decomposition.
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| 10. |
- Cao, Chunzheng, et al.
(författare)
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Improved likelihood ratio tests in a measurement error model for multivariate replicated data
- 2020
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Ingår i: Communications in Statistics - Theory and Methods. - : TAYLOR & FRANCIS INC. - 0361-0926 .- 1532-415X. ; 49:5, s. 1025-1042
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement error model for multivariate replicated data and focus on the improved likelihood ratio tests for parameters of interest. By assuming that the random terms follow the scale mixtures of normal distributions, the model can bring robust inference and can target on both error-prone and error-free covariates. We derive modified versions from the original likelihood ratio statistics to achieve better asymptotic properties with high degree of accuracy. Simulation studies are conducted to display finite sample behavior as compared to the unmodified counterpart. The practical utility is illustrated through a root decomposition data.
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