35 research outputs found
Both androgen receptor and glucocorticoid receptor are able to induce prostate-specific antigen expression, but differ in their growth-stimulating properties of LNCaP cells
Androgen receptor-positive LNCaP cells were stably transfected with a rat
glucocorticoid receptor (GR) expression plasmid. Ligand-binding studies in
the generated cell lines revealed high-affinity binding of the cognate
ligands to their receptors. Transfection experiments with the newly
derived cell lines showed that, like androgen receptor, GR can induce
activity of a prostate-specific antigen promoter fragment linked to the
luciferase gene. Similarly, dexamethasone can stimulate expression of
endogenous prostate-specific antigen messenger RNA. Cell proliferation
could be induced by R1881. In contrast, dexamethasone treatment of the
GR-positive sublines had no stimulatory effect on cell growth. Using the
differential display technique, a so far unknown complementary DNA
fragment, designated 21.1, specifically induced by androgens and not by
glucocorticoids, has been identified. In conclusion, the newly generated
cell lines, together with the parental LNCaP cell line, form an attractive
system with which to study the mechanism of specificity of steroid hormone
regulation of gene expression
Predicting amyloid-beta pathology in the general population
INTRODUCTION: Reliable models to predict amyloid beta (Aβ) positivity in the general aging population are lacking but could become cost-efficient tools to identify individuals at risk of developing Alzheimer's disease. METHODS: We developed Aβ prediction models in the clinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study (n = 4,119) including a broad range of easily ascertainable predictors (demographics, cognition and daily functioning, health and lifestyle factors). Importantly, we determined the generalizability of our models in the population-based Rotterdam Study (n = 500). RESULTS: The best performing model in the A4 Study (area under the curve [AUC] = 0.73 [0.69â0.76]), including age, apolipoprotein E (APOE) Îľ4 genotype, family history of dementia, and subjective and objective measures of cognition, walking duration and sleep behavior, was validated in the independent Rotterdam Study with higher accuracy (AUC = 0.85 [0.81â0.89]). Yet, the improvement relative to a model including only age and APOE Îľ4 was marginal. DISCUSSION: Aβ prediction models including inexpensive and non-invasive measures were successfully applied to a general populationâderived sample more representative of typical older non-demented adults.</p
Water waves generated by a moving bottom
Tsunamis are often generated by a moving sea bottom. This paper deals with
the case where the tsunami source is an earthquake. The linearized water-wave
equations are solved analytically for various sea bottom motions. Numerical
results based on the analytical solutions are shown for the free-surface
profiles, the horizontal and vertical velocities as well as the bottom
pressure.Comment: 41 pages, 13 figures. Accepted for publication in a book: "Tsunami
and Nonlinear Waves", Kundu, Anjan (Editor), Springer 2007, Approx. 325 p.,
170 illus., Hardcover, ISBN: 978-3-540-71255-8, available: May 200
Modelling the cascade of biomarker changes in progranulinârelated frontotemporal dementia
AbstractBackgroundProgranulin related frontotemporal dementia (FTDâGRN) is a fast progressive disorder, in which pathophysiological changes precede overt clinical symptoms in only a short time period. Modelling the cascade of multimodal biomarker changes aids in understanding the etiology of this disease, enables monitoring of individual mutation carriers, and would give input for diseaseâmodifying treatments. In this crossâsectional study, we estimated the temporal cascade of biomarker changes for FTDâGRN, in a dataâdriven way.MethodWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy nonâcarriers. Of the symptomatic subjects, 17 had behavioural variant FTD (bvFTD), 16 presented as nonâfluent variant primary progressive aphasia (nfvPPA). The selected biomarkers for establishing the cascade of changes were neurofilament light chain, regional grey matter volumes, fractional anisotropy of white matter tracts, and cognitive domains. We used a dataâdriven analysis called discriminative eventâbased modelling (Venkatraghavan, NeuroImage, 2019) with a novel modification to its Gaussian Mixture Model (GMM) called Siamese GMM, to estimate the cascade of biomarker changes for FTDâGRN. Using crossâvalidation, we estimated disease severities of individual mutation carriers in the test set based on their progression along the biomarker cascade established on the training set.ResultNeurofilament light chain and white matter tracts were the earliest biomarkers to become abnormal in FTDâGRN mutation carriers. Attention and executive functioning were also affected early on in the disease process. Based on the estimated individual disease severities, presymptomatic mutation carriers could be distinguished from symptomatic mutation carriers with a sensitivity of 95% and specificity of 100% in the crossâvalidation experiment. There was a high correlation (r=0.94, p<0.001) between estimated disease severity and years since symptom onset in nfvPPA, but not in bvFTD (r=0.33, p=0.46).ConclusionIn this study, we unravelled the temporal cascade of multimodal biomarker changes for FTDâGRN. Our results suggest that axonal degeneration is one of the first disease events in FTDâGRN, which calls for designing disease modifying treatments that strengthens the axons. We also demonstrated a good delineation between symptomatic and presymptomatic carriers using the estimated disease severities, which suggest that our model could enable monitoring of individual mutation carriers
Note on Burgers' theorem in the elasticity theory of dislocations
Aerospace Engineerin
Notes on the unsteady rectilinear motion of a perfect gas VIII general theory and general waves in a homentropic gas
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Notes on the unsteady rectilinear motion of a perfect gas: III Homogeneous solutions of the Lagrancian Equations of motion
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