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Search Results: 1 - 10 of 5188 matches for " Nicholas Knowlton "
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Statistical monitoring of weak spots for improvement of normalization and ratio estimates in microarrays
Igor Dozmorov, Nicholas Knowlton, Yuhong Tang, Michael Centola
BMC Bioinformatics , 2004, DOI: 10.1186/1471-2105-5-53
Abstract: We developed a multistep procedure for analysis of mRNA expression data that robustly identifies the additive noise in a microarray experiment. This analysis is predicated on the fact that additive noise signals can be accurately identified by both distribution and statistical analysis.Identification of additive noise in this manner allows exclusion of noncorrelated weak signals from regression-based normalization of compared profiles thus maximizing the accuracy of these methods. Moreover, genes expressed at very low levels can be clearly identified due to the fact that their expression distribution is stable and distinguishable from the random pattern of additive noise.Microarrays are powerful and cost-effective tools for large-scale analysis of gene expression. While the utility of this technology has been established [1,2], analytical methods are evolving and a matter of contention. Key among the more controversial aspects is the treatment of data from weak spots, which significantly influences outcomes. For example, ratio analysis is commonly employed to determine expression differences between two samples. However any procedure that uses raw intensities to infer relative expression is limited due to the fact that accuracy is signal level dependent, with variation increasing dramatically for low intensity signals [1,3]. Several methods have been developed to diminish the influence of additive noise. One solution is to ignore any genes whose transcripts are present at a low total abundance, to exclude weak spots – arbitrarily (in Kooperberg etal., [3] an intensity cutoff was used such that the relative error in ratios was less than 25%) or with some statistical procedures [4,5]. Other methods proposed for discriminating expressed genes from those not expressed, such as the method of Greller and Tobin [6], are suitable only for bimodal distributions in which the distribution of intensities for these two subsets are non-overlapping, unlike many empirical data sets
Rapid Prototyping as Method for Developing Instructional Strategies for Supporting Computer-Mediated Communication Among University Students
Dave Knowlton
The Journal of Scholarship of Teaching and Learning , 2006,
Analysis of the interaction of extracellular matrix and phenotype of bladder cancer cells
Mikhail G Dozmorov, Kimberly D Kyker, Ricardo Saban, Nicholas Knowlton, Igor Dozmorov, Michael B Centola, Robert E Hurst
BMC Cancer , 2006, DOI: 10.1186/1471-2407-6-12
Abstract: Five bladder cancer cell lines and one immortalized, but non-tumorigenic, urothelial line were grown on Matrigel, a cancer-derived ECM, on SISgel, a normal-derived ECM, and on plastic, where the only ECM is derived from the cells themselves. The transcriptomes were analyzed on an array of 1186 well-annotated cancer derived cDNAs containing most of the major pathways for malignancy. Hypervariable genes expressing more variability across cell lines than a set expressing technical variability were analyzed further. Expression values were clustered, and to identify genes most likely to represent biological factors, statistically over-represented ontologies and transcriptional regulatory elements were identified.Approximately 400 of the 1186 total genes were expressed 2 SD above background. Approximately 100 genes were hypervariable in cells grown on each ECM, but the pattern was different in each case. A core of 20 were identified as hypervariable under all 3 growth conditions, and 33 were hypervariable on both SISgel and Matrigel, but not on plastic. Clustering of the hypervariable genes showed very different patterns for the same 6 cell types on the different ECM. Even when loss of cell cycle regulation was identified, different genes were involved, depending on the ECM. Under the most permissive conditions of growth where the malignant phenotype was fully expressed, activation of AKT was noted. TGFβ1 signaling played a major role in the response of bladder cancer cells to ECM. Identification of TREs on genes that clustered together suggested some clustering was driven by specific transcription factors.The extracellular matrix on which cancer cells are grown has a major effect on gene expression. A core of 20 malignancy-related genes were not affected by matrix, and 33 were differentially expressed on 3-dimensional culture as opposed to plastic. Other than these genes, the patterns of expression were very different in cells grown on SISgel than on Matrigel or even pla
Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG)
Marcia R Saban, Cindy Simpson, Carole Davis, Gemma Wallis, Nicholas Knowlton, Mark Frank, Michael Centola, Randle M Gallucci, Ricardo Saban
BMC Immunology , 2007, DOI: 10.1186/1471-2172-8-6
Abstract: C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to test whether intravesical BCG would alter bladder cytokine gene expression.Acute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-α treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1β, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and IL-17RB.To the best of our knowledge, the present work is the first to report that BCG induces an increase in the IL-17 family genes. In addition, BCG induces a unique type of persisting bladder inflammation different from TNF-α, LPS, and, most likely, other classical pro-inflammatory stimuli.Intravesical Bacillus Calmette-Guerin (BCG) has been presented as a promising option for treatment of interstitial cystitis [1]. However, intravesical BCG is best known as the most effective agent for the treatment of high-grade superficial bladder cancer [2-4]. In this context, BCG is used to reduce both the recurrence rate of bladder tumor and to diminish the risk of its progression [2,3]. As an adjunct to transurethral
Canid Social Structure and Density Dependence Improve Predator-Prey Models of Canis latrans and Lepus californicus in Curlew Valley, UT  [PDF]
Shannon Kay, Jim Powell, Frederick Knowlton
Open Journal of Ecology (OJE) , 2015, DOI: 10.4236/oje.2015.54011
Abstract: Prominent examples of predator-prey oscillations between prey-specific predators exist, but long-term data sets showing these oscillations are uncommon. We explored various models to describe the oscillating behavior of coyote (Canis latrans) and black-tailed jackrabbits (Lepus californicus) abundances in a sagebrush-steppe community in Curlew Valley, UT over a 31-year period between 1962 and 1993. We tested both continuous and discrete models which accounted for a variety of mechanisms to discriminate the most important factors affecting the time series. Both species displayed cycles in abundance with three distinct peaks at ten-year intervals. The coupled oscillations appear greater in the mid-seventies and a permanent increase in the coyote density seems apparent. Several factors could have influenced this predator-prey system including seasonality, predator satiation, density dependence, social structure among coyotes, and a change in the coyote bounty that took place during the course of data collection. Maximum likelihood estimation was used to obtain parameter values for the models, and Akaike Information Criterion (AIC) values were used to compare models. Coyote social structure and limiting resources in the form of density-dependence and satiation seemed to be important factors affecting population dynamics.
Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects
Diana M. Lee, Kenneth W. Jackson, Nicholas Knowlton, Joshua Wages, Petar Alaupovic, Ola Samuelsson, Aso Saeed, Michael Centola, Per-Ola Attman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022360
Abstract: The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol. In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls.
Brief FASD prevention intervention: physicians' skills demonstrated in a clinical trial in Russia
Tatiana Balachova, Barbara L Bonner, Mark Chaffin, Galina Isurina, Vladimir Shapkaitz, Larissa Tsvetkova, Elena Volkova, Irina Grandilevskaya, Larissa Skitnevskaya, Nicholas Knowlton
Addiction Science & Clinical Practice , 2013, DOI: 10.1186/1940-0640-8-1
Abstract: The paper describes the intervention protocol and addresses questions about the feasibility of a brief FASD prevention intervention delivered by OB/GYN at women's clinics in Russia. Brief physician intervention guidelines and two evidence-based FASD prevention interventions were utilized to design a brief dual-focused physician intervention (DFBPI) appropriate to Russian OB/GYN care. The questions answered were whether trained OB/GYN physicians could feasibly deliver DFBPI during women's routine clinic visits, whether they maintained skills over time in clinical settings, and which specific intervention components were better maintained. Data were collected as part of a larger study aimed at evaluating effectiveness of DFBPI in reducing AEP risk in non-pregnant women. Methods of monitoring the intervention delivery included fidelity check lists (FCL) with the key components of the intervention completed by physicians and patients and live and audio taped observations of intervention sessions. Physicians (N= 23) and women (N= 372) independently completed FCL, and 78 audiotapes were coded.The differences between women's and physicians' reports on individual items were not significant. Although the majority of physician and patient reports were consistent (N=305), a discrepancy existed between the reports in 57 cases. Women reported more intervention components missing compared to physicians (p<0.001). Discussing barriers was the most difficult component for physicians to implement, and OB/GYN demonstrated difficulties in discussing contraception methods.The results supported the feasibility of the DFBPI in Russia. OB/GYN physicians trained in the DFBPI, monitored, and supported were able to implement and maintain skills during the study. In addition to the alcohol focus, DFBPI training needs to have a sufficient component to improve physicians' skills in discussing contraception use.
Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment
Mark Frank, Shirley Wang, Amita Aggarwal, Nicholas Knowlton, Kaiyu Jiang, Yanmin Chen, Ryan McKee, Brad Chaser, Timothy McGhee, Jeanette Osban, James N Jarvis
BMC Medical Genomics , 2009, DOI: 10.1186/1755-8794-2-9
Abstract: RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.In silico models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.Genome-based technologies provide us with an unprecedented capacity to understand complex biological systems and their relationship to health and disease. This is especially true for complex biological traits (e.g., atherosclerosis, hypertension), which have largely eluded our understanding using conventional, reductionist approaches. Indeed, even single-gene traits have demonstrated previously unsuspected levels of complexity when scrutinized through the lens of whole-genome technologies [1-3]Chronic inflammatory diseases such as rheumatoid arthritis (RA) and juvenile dermatomyositis (JDM) are examples of human diseases whose etiologies and pathogenic mechanisms remain incompletely understood. Once thought to be purely "autoimmune" diseases
Promoting Liberal Arts Thinking through Online Discussion: A Practical Application and its Theoretical Basis
Dr. Dave S. Knowlton
Educational Technology & Society , 2002,
Abstract: Addressing Carsten and Worsfold's (2000) assertion that online learning eliminates the possibility for "liberal learning," the author of this paper describes the context and guidelines for an online discussion assignment that he used as a faculty member at a liberal arts college. The purpose of this assignment was to help students engage in personal development by examining the ways course content manifested itself in their own lives. After describing the assignment guidelines, the author connects the assignment to numerous theories that are often associated with "liberal arts" learning. This theoretical explication includes connections to the need for a synthesis between the personal and professional selves, notions of constructing knowledge, and online discussion's placement within the writing process. The implication of this article is that the instructional strategies embedded in an online discussion, not the online environment itself, sustains a liberal education.
Reading American Fat in France : Obesity and Food Culture
Laura Knowlton – Le Roux
European Journal of American Studies , 2007, DOI: 10.4000/ejas.1363
Abstract: One of the least flattering images that America is now associated with in France and in other European countries is a ballooning stomach. Pictures of overweight American children and adults are regularly used in French TV news, shows and in the print media. Every campaign against obesity in the land of gourmandise cites the latest statistics on the overweight population in the United States. “Obésité: la France sur la voie des Etats-Unis,” warned Le Monde in the headline of its two-page sprea...
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