Open Access Theses and Dissertations

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You searched for +publisher:"Penn State University" +contributor:("W. Brian Reeves, Committee Member"). Showing records 1 – 3 of 3 total matches.

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Penn State University

1. Domthong, Uthumporn. A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/23318 

In many clinical studies, Lin’s concordance correlation coefficient (CCC) is a common tool to assess the level of agreement of a continuous response measured under two different conditions. However, the complicating feature is that the assay for measuring a specific biomarker typically cannot provide accurate numerical values below the lower limit of detection (LLD), which results in left-censored data. In addition, the CCC is based on a squared distance function, and it can be very sensitive to the effects of the outliers. In this work, we propose a new class of bivariate survival functions based on functions of univariate survival functions and univariate cumulative hazard functions. We focus on using the univariate Weibull distribution to obtain a bivariate Weibull survival function. The likelihood function can be determined via this new class of bivariate Weibull survival functions.Then, we take a parametric approach to derive the estimates of the means, variances, and covariance to construct the CCC. This new class of bivariate survival functions can be extended to the situation with p > 2 random variables. The maximum likelihood method based on three distributions, (1) bivariate Weibull distributions (2) bivariate Farlie-Gumbel-Morgenstern distributions and (3) bivariate lognormal distributions, were evaluated via simulation studies. The simulation results confirmed that overall in terms of accuracy, that is small relative bias, the estimator of CCC based on FGM-Weibull works relatively well in general cases when the correlation is not too strong even with the high percentage of censoring. For a skewed underlying distribution with moderate or weaker correlation between two variables, the CCC estimated by a FGM-Weibull model is more robust. However, when the data are generated from the bivariate lognormal, the ML approach based on the bivariate lognormality assumption still performs best. Finally, we use data from an ancillary study of the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Consortium, and an asthma clinical trial for demonstration. Advisors/Committee Members: Vernon Michael Chinchilli, Dissertation Advisor/Co-Advisor, Lan Kong, Committee Member, Tonya Sharp King, Committee Member, W. Brian Reeves, Committee Member, David Spencer Phelps, Committee Member.

Subjects/Keywords: concordance correlation coefficient (CCC); lower limit of detection (LLD); Weibull distribution; The maximum likelihood method

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Domthong, U. (2014). A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23318

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Domthong, Uthumporn. “A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data.” 2014. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/23318.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Domthong, Uthumporn. “A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data.” 2014. Web. 03 Mar 2021.

Vancouver:

Domthong U. A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/23318.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Domthong U. A New Class of Bivariate Weibull Distribution to accommodate the Concordance Correlation coefficient for Left-censored Data. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23318

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

2. Bao, Jialing. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12670 

Meprin metalloproteases have been implicated in a number of normal developmental and pathological processes. However, it has been difficult to establish the cellular and molecular basis for the biological role of meprin metalloproteases in health and disease, possibly because of the large number of metalloproteases, many having overlapping substrate specificities. A number of important biological molecules have been demonstrated to be meprin substrates in vitro, such as extracellular matrix and cytokines. With the development of congenic mice lacking meprin activity, it has been possible to relate in vitro results with in vivo data to examine cellular and molecular processes. The hypothesis of the thesis work is that meprins relax epithelial barriers by cleaving tight junction proteins, and facilitate monocyte migration. The study demonstrated that homomeric meprin A and meprin B cleaved the tight junction protein occludin, but not claudin-4, in membrane fractions from MDCK cells. Meprin A, but not meprin B, added exogenously to MDCK monolayers cleaved occludin. Meprin A, but not meprin B, cleaved recombinant occludin extracellular loops, and the cleavage site was determined in the first extracellular loop of occludin. Different cleavage site preferences at extracellular regions explain the different results between meprin A and meprin B to cleave occludin in intact cells and cell extacts. The biological relevance of the in vitro experiments was demonstrated by studies in cell culture, in vivo and ex vivo. Meprin A disrupted the immunostaining of tight junction proteins occludin and ZO-1 on MDCK monolayers. In addition, meprin A impaired the barrier function of MDCK monolayers, as shown by increased small molecule flux and decreased transepithelial electrical resistance. To elucidate the role of meprin A in acute urinary tract infections, meprin A was infused into the mouse bladder and the effects on bladder epithelium wall was investigated. The results showed that active meprin A increased the permeability of the epithelium as demonstrated by the influx of a fluorescene dye. The hypothesis that meprin A disrupts epithelial barriers and facilitates monocyte migration was further investigated by co-culturing monocytes with MDCK monolayers and measuring monocyte migration. Monocytes from mice lacking meprin A (meprin KO) were less able to migrate through MDCK monolayers than monocytes from wild-type mice. It is concluded that the capability of meprin A to disrupt epithelial barriers is one important factor by which meprin A modulates inflammation. Advisors/Committee Members: Judith S Bond, Dissertation Advisor/Co-Advisor, Gail Lynn Matters, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, W. Brian Reeves, Committee Member, Harriet C Isom, Committee Member.

Subjects/Keywords: Meprin; Tight junctions; Occludin; Epithelial barrier; Monocyte

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bao, J. (2012). Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12670

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Bao, Jialing. “Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.” 2012. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/12670.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Bao, Jialing. “Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.” 2012. Web. 03 Mar 2021.

Vancouver:

Bao J. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/12670.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bao J. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/12670

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

3. Yura, Renee E. MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8602 

Meprin metalloproteases, composed of alpha and/or beta subunits, consist of membrane-bound and secreted forms that are abundantly expressed in kidney and intestinal epithelial cells. They are also expressed in the skin and in certain populations of leukocytes. Meprins have been implicated in several inflammatory diseases, such as renal ischemia, diabetic nephropathy, and inflammatory bowel disease, indicating a role for these enzymes in modulation of the immune response. Prior to the initiation of this work, extensive information about the structure and in vitro behavior of the meprins was known, but little was known about their in vivo roles in immune modulation. These studies are the first to demonstrate a relationship between the inflammatory response and the meprins in both systemic and bladder challenge models. The aim of this work was to determine the role of meprins in the host response to gram-negative uropathic Escherichia coli (E. coli). Initial studies demonstrated marked increases in meprin alpha expression in the urine of women with active urinary tract infections (UTIs), implicating meprin involvement in the host response to bacterial infections. To examine further the role of meprins in the host response to UTI, meprin alpha knockout (alphaKO) and wild-type (WT) mice were challenged with a transurethral inoculation of uropathic E. coli. In this localized model of inflammation, bladder myeloperoxidase (MPO) activity, bladder weight, and bladder permeability were significantly less in alphaKO compared to WT mice after induction of UTI. These data indicate that meprin A is pro-inflammatory, contributing to leukocyte infiltration, edema, and epithelial damage. To determine whether the action of meprin A was the result of a direct interaction with E. coli, extensive in vitro studies were carried out. Meprin A did not decrease the binding of E. coli to bladder cells in culture, nor did it degrade the pili that are responsible for the attachment of E. coli to the bladder epithelium. No evidence of direct interactions between meprin A and E. coli has been found, indicating that the differential response observed in meprin alphaKO mice in comparison to WT is indirect and likely involves the immune system. A large component of the immune response to E. coli is directed toward lipopolysaccharide (LPS) in the bacterial cell wall. Therefore, the responses of meprin alphaKO, meprin beta knockout (betaKO), meprin alphabeta double knockout (alphabetaKO), and WT mice after intraperitoneal (i.p.) LPS challenge were examined. Genotype-specific differences in response to LPS were observed as early as 1 h after challenge with 2.5 mg/kg i.p. E. coli LPS. Meprin alphaKO mice displayed a decreased systemic response to LPS compared to WT mice and meprin betaKO mice, as indicated by lower blood urea nitrogen (BUN) levels, lower serum TNFalpha levels, and less severe hypothermia, implicating meprin in modulation of the host immune response to endotoxin. These data are consistent with those from UTI studies,… Advisors/Committee Members: Judith S Bond, Committee Chair/Co-Chair, Sarah Bronson, Committee Member, Robert G Levenson, Committee Member, Andrea Manni, Committee Member, W. Brian Reeves, Committee Member.

Subjects/Keywords: meprins; metalloproteases; lipopolysaccharide; urinary tract infection; transgenic mouse models

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yura, R. E. (2008). MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8602

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Yura, Renee E. “MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI .” 2008. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/8602.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Yura, Renee E. “MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI .” 2008. Web. 03 Mar 2021.

Vancouver:

Yura RE. MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/8602.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yura RE. MEPRIN METALLOPROTEASES MODULATE THE HOST RESPONSE TO ESCHERICHIA COLI . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8602

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.