478 research outputs found
Magnetotelluric imaging of anisotropic crust near Fort McMurray, Alberta: implications for engineered geothermal system development
Viability for the development of an engineered geothermal system (EGS) in the oilsands region near Fort McMurray, Alberta, is investigated by studying the structure of the Precambrian basement rocks with magnetotellurics (MT). MT data were collected at 94 broad-band stations on two east–west profiles. Apparent resistivity and phase data showed little variation along each profile. The short period MT data detected a 1-D resistivity structure that could be identified as the shallow sedimentary basin underlain by crystalline basement rocks to a depth of 4–5 km. At lower frequencies a strong directional dependence, large phase splits, and regions of out-of-quadrant (OOQ) phase were detected. 2-D isotropic inversions of these data failed to produce a realistic resistivity model. A detailed dimensionality analysis found links between large phase tensor skews (∼15°), azimuths, OOQ phases and tensor decomposition strike angles at periods greater than 1 s. Low magnitude induction vectors, as well as uniformity of phase splits and phase tensor character between the northern and southern profiles imply that a 3-D analysis is not necessary or appropriate. Therefore, 2-D anisotropic forward modelling was used to generate a resistivity model to interpret the MT data. The preferred model was based on geological observations of outcropping anisotropic mylonitic basement rocks of the Charles Lake shear zone, 150 km to the north, linked to the study area by aeromagnetic and core sample data. This model fits all four impedance tensor elements with an rms misfit of 2.82 on the southern profile, and 3.3 on the northern. The conductive phase causing the anisotropy is interpreted to be interconnected graphite films within the metamorphic basement rocks. Characterizing the anisotropy is important for understanding how artificial fractures, necessary for EGS development, would form. Features of MT data commonly interpreted to be 3-D (e.g. out of OOQ phase and large phase tensor skew) are shown to be interpretable with this 2-D anisotropic model
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Data Transformations for Inference with Linear Regression: Clarifications and Recommendations
Data transformations have been promoted as a popular and easy-to-implement remedy to address the assumption of normally distributed errors (in the population) in linear regression. However, the application of data transformations introduces non-ignorable complexities which should be fully appreciated before their implementation. This paper adds to existing Practical Research and Assessment Evaluation (PARE) publications on data transformations by providing a broad overview underlying the use of data transformations for the specific purpose of statistical inference and interpreting meaningful effect sizes. Data transformations not only potentially change the scale of the transformed variable; they also alter the fundamental relationships among variables while simultaneously changing the distribution of the errors. Given these repercussions, we clarify the nature of certain data transformations and strongly recommend the use of data transformations when they can enhance the interpretation of effect sizes. Accessed 5,515 times on https://pareonline.net from October 11, 2017 to December 31, 2019. For downloads from January 1, 2020 forward, please click on the PlumX Metrics link to the right
Using Dynamic Graphics to Teach the Sampling Distribution with Active Learning
The sampling distribution and the Central Limit Theorem (CLT) are the basis for many statistical procedures and inferences. Despite their ubiquitous nature in statistics, these concepts are some of the most abstract and difficult for students to understand. To foster a deeper understanding of these concepts, a web-based application was created that uses dynamic graphics to illustrate the concepts and engage students with active learning. We provide an outline of three in-class activities using the web application to promote the learning of population distributions, simple random sampling, sampling variability, the idea of a statistic, the sampling distribution, the Law of Large Numbers, and the CLT. These in-class activities tie the concepts together and place emphasis on their role as building blocks of statistical inference. By linking abstract theoretical concepts together before introducing statistical inference, the web application facilitates statistical thinking that students can utilize both inside and outside the classroom
Chromatinized Protein Kinase C-θ: Can It Escape the Clutches of NF-κB?
We recently provided the first description of a nuclear mechanism used by Protein Kinase C-theta (PKC-θ) to mediate T cell gene expression. In this mode, PKC-θ tethers to chromatin to form an active nuclear complex by interacting with proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase LSD1, and the adaptor molecule 14-3-3ζ at regulatory regions of inducible immune response genes. Moreover, our genome-wide analysis identified many novel PKC-θ target genes and microRNAs implicated in T cell development, differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip analysis and have now identified a transcription factor motif containing NF-κB binding sites that may facilitate recruitment of PKC-θ to chromatin at coding genes. Furthermore, NF-κB association with chromatin appears to be a prerequisite for the assembly of the PKC-θ active complex. In contrast, a distinct NF-κB-containing module appears to operate at PKC-θ targeted microRNA genes, and here NF-κB negatively regulates microRNA gene transcription. Our efforts are also focusing on distinguishing between the nuclear and cytoplasmic functions of PKCs to ascertain how these kinases may synergize their roles as both cytoplasmic signaling proteins and their functions on the chromatin template, together enabling rapid induction of eukaryotic genes. We have identified an alternative sequence within PKC-θ that appears to be important for nuclear translocation of this kinase. Understanding the molecular mechanisms used by signal transduction kinases to elicit specific and distinct transcriptional programs in T cells will enable scientists to refine current therapeutic strategies for autoimmune diseases and cancer
Amine functionalization of cholecyst-derived extracellular matrix with generation 1 PAMAM dendrimer
This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Biomacromolecules, copyright © American Chemical Society after peer review. To access the final edited and published work, see http://pubs.acs.org/doi/pdf/10.1021/bm701055k.A method to functionalize cholecyst-derived extracellular matrix (CEM) with free amine groups was established in an attempt to improve its potential for tethering of bioactive molecules. CEM was incorporated with Generation-1 polyamidoamine (G1 PAMAM) dendrimer by using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide and N-hydroxysuccinimide cross-linking system. The nature of incorporation of PAMAM dendrimer was evaluated using shrink temperature measurements, Fourier transform infrared (FTIR) assessment, ninhydrin assay, and swellability. The effects of PAMAM incorporation on mechanical and degradation properties of CEM were evaluated using a uniaxial mechanical test and collagenase degradation assay, respectively. Ninhydrin assay and FTIR assessment confirmed the presence of increasing free amine groups with increasing quantity of PAMAM in dendrimer-incorporated CEM (DENCEM) scaffolds. The amount of dendrimer used was found to be critical in controlling scaffold degradation, shrink temperature, and free amine content. Cell culture studies showed that fibroblasts seeded on DENCEM maintained their metabolic activity and ability to proliferate in vitro. In addition, fluorescence cell staining and scanning electron microscopy analysis of cell-seeded DENCEM showed preservation of normal fibroblast morphology and phenotype
Predictors of Preference for Hospice Care Among Diverse Older Adults
The purpose of this study was to identify predictors of preference for hospice care and explore whether the effect of these predictors on preference for hospice care were moderated by race
Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms
BackgroundAsthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.ObjectiveWe performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.MethodsSixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.ResultsSignificant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.ConclusionThe evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies
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