Digital Commons Network^™

Differential Activity Of The Kras Oncogene By Method Of Activation: Implications For Signaling And Therapeutic Intervention, Nathan Ihle

Dissertations and Theses (Open Access)

Despite having been identified over thirty years ago and definitively established as having a critical role in driving tumor growth and predicting for resistance to therapy, the KRAS oncogene remains a target in cancer for which there is no effective treatment. KRas is activated b y mutations at a few sites, primarily amino acid substitutions at codon 12 which promote a constitutively active state. I have found that different amino acid substitutions at codon 12 can activate different KRas downstream signaling pathways, determine clonogenic growth potential and determine patient response to molecularly targeted therapies. Computer modeling of the KRas structure …

Induction Of Stronger And Long Lasting Vaccine Immunity To Tuberculosis, Pearl Bakhru

Dissertations and Theses (Open Access)

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell …

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

Dissertations and Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect …

Regulation Of The Heat Shock Response By Thiol-Reactive Compounds In The Yeast Saccharomyces Cerevisiae, Yanyu Wang

Dissertations and Theses (Open Access)

Cells govern their activities and modulate their interactions with the environment to achieve homeostasis. The heat shock response (HSR) is one of the most well studied fundamental cellular responses to environmental and physiological challenges, resulting in rapid synthesis of heat shock proteins (HSPs), which serve to protect cellular constituents from the deleterious effects of stress. In addition to its role in cytoprotection, the HSR also influences lifespan and is associated with a variety of human diseases including cancer, aging and neurodegenerative disorders. In most eukaryotes, the HSR is primarily mediated by the highly conserved transcription factor HSF1, which recognizes target …

Exploring The Impact Of Decreased Ampk Pathway Activity On Brain Injury Outcome, Julia L. Hill

Dissertations and Theses (Open Access)

Each year, 150 million people sustain a Traumatic Brain Injury (TBI). TBI results in life-long cognitive impairments for many survivors. One observed pathological alteration following TBI are changes in glucose metabolism. Altered glucose uptake occurs in the periphery as well as in the nervous system, with an acute increase in glucose uptake, followed by a prolonged metabolic suppression. Chronic, persistent suppression of brain glucose uptake occurs in TBI patients experiencing memory loss. Abberant post-injury activation of energy-sensing signaling cascades could result in perturbed cellular metabolism. AMP-activated kinase (AMPK) is a kinase that senses low ATP levels, and promotes efficient cell …

Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf

Dissertations and Theses (Open Access)

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …

Characterization Of A Novel Role For The To Usled- Like Kinase In Kinetochore Assembly And Function In Caenorhabditis Elegans, Jessica M. De Orbeta

Dissertations and Theses (Open Access)

Chromosome segregation is a critical step during cell division to avoid aneuploidy and promote proper organismal development. Correct sister chromatid positioning and separation during mitosis helps to achieve faithful transmission of genetic material to daughter cells. This prevents improper chromosome partitioning that can potentially result in extrachromosomal fragments, increasing the tumorigenic potential of the cells. The kinetochore is a protenaicious structure responsible for the initiation and orchestration of chromosome movement during mitosis. This highly conserved structure among eukaryotes is required for chromosome attachment to the mitotic spindle and failure to assemble the kinetochore results in aberrant chromosome segregation. Thus elucidating …

Evaluation Of Polymer Gel Dosimeters For Measurements Of Dose And Let In Proton Beams, Kevin M. Vredevoogd

Dissertations and Theses (Open Access)

This project assessed the effectiveness of polymer gel dosimeters as tools for measuring the dose deposited by and LET of a proton beam. A total of three BANG® dosimeter formulations were evaluated: BANG®-3-Pro-2 BANGkits™ for dose measurement and two BANG®-3 variants, the LET-Baseline and LET-Meter dosimeters, for LET measurement. All dosimeters were read out using an OCT scanner. The basic characteristics of the BANGkits™ were assessed in a series of photon and electron irradiations. The dose-response relationship was found to be sigmoidal with a threshold for response of approximately 15 cGy. The active region of the dosimeter, the volume in …

Characterization Of Selective Inhibition Of Adenylyl Cyclase Activity By Small Molecule Inhibitor Nky80, Cameron S. Brand

Dissertations and Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. Decreasing AC5 activity has been shown to have potential therapeutic benefit, including reduced stress on the heart, pain relief, and attenuation of morphine dependence and withdrawal behaviors. However, AC structure is well conserved, and there are currently no isoform selective AC inhibitors in clinical use.

P-site inhibitors inhibit AC directly at the catalytic site, but with an uncompetitive or noncompetitive mechanism. Due to this mechanism and nanomolar potency in cell-free systems, attempts at ligand-based drug …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations and Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Homology Cloning, Heterologous Expression And Characterization Of A New Channelrhodopsin, Sing-Yi Hou

Dissertations and Theses (Open Access)

Channelrhodopsins are phototaxis receptors in the plasma membranes of motile unicellular algae. They function as light-gated cation channels and this channel activity has been exploited to trigger action potentials in neurons with light to control neural circuits (“optogenetics"). Four channelrhodopsins were identified in two algal species, Chlamydomonas reinhardtii and Volvox carteri, with known genome sequences; each species contains 2 channelrhodopsins, one absorbing at longer wavelengths and one at shorter wavelengths, named CrChR1 and CrChR2, respectively. Our goals are to expand knowledge of channelrhodopsin mechanisms and also to identify new channelrhodopsins from various algal species with improved properties …

Development Of A Beam-Specific Planning Target Volume And A Robust Plan Analysis To Ol For Proton Therapy, Peter Park

Dissertations and Theses (Open Access)

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations and Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Tmc Library Holiday Hours; New Class Offered At The Library: Creating Your Own Ebooks; New Mobile Resources Library Guide, Vol, 10 (11), Texas Medical Center Library

Insider Express (2003-2013)

No abstract provided.

Related Resources, Children At Risk

Journal of Applied Research on Children: Informing Policy for Children at Risk

Related Resources for Volume 3, Issue 2: Measuring Success in Public Education.

Resource Review Of Walking The Equity Talk: A Guide For Culturally Courageous Leadership In School Communities, Tamara M. Chung Constant, Laura A. Valdiviezo

Journal of Applied Research on Children: Informing Policy for Children at Risk

Resource Review of: Walking the Equity Talk: A Guide for Culturally Courageous Leadership in School Communities by Robert Brownell II.

The New Futuro College Plan: Facilitating College Access, Elizabeth Romero

Journal of Applied Research on Children: Informing Policy for Children at Risk

Built on a free, bilingual, "high-touch, high-tech" platform, New Futuro has created a robust community of Latino students and parents, non-profit organizations, education institutions, government agencies, and corporations to connect those that need help with those that provide it. One of the resources developed by New Futuro is a proprietary 10-Steps College Plan that provides structured information targeted to Latino students and families to help them prepare, apply and pay for college.

The Problem With Value-Added Measurement, Gary Rubinstein

Journal of Applied Research on Children: Informing Policy for Children at Risk

Measuring student learning through standardized tests is a lot harder than modern education reformers would have you believe.

The Need For Balanced Methods Of Measuring Performance, Michelle Rhee

Journal of Applied Research on Children: Informing Policy for Children at Risk

Michelle Rhee weighs in on measuring success in pubic education.

Commentary On "Alternative Strategies For Identifying High-Performing Charter Schools In Texas", Robin J. Lake

Journal of Applied Research on Children: Informing Policy for Children at Risk

In the last few years policy makers and practitioners nationally have shown much interest in identifying, recognizing, and replicating successful charter schools, many of which are showing that they can educate low-income and otherwise at-risk students remarkably well. However past efforts to identify high performing schools have been problematic. Using these systematic, rigorous value-added methods, the authors identify 44 Open Enrollment charter schools that merit a “high-performer” rating. Nearly all of those campuses identified serve a disadvantaged student population. The article also finds that most of those high performers are highly cost-effective, earning high ratings on the cost-efficiency measures. The …

Commentary On "Expanded Learning Time In Schools", Mike Feinberg

Journal of Applied Research on Children: Informing Policy for Children at Risk

As co-founder of KIPP, I know from experience and research that more time in school works. A well-designed extended-time program can help underserved students catch up academically, and prepare them for the rigors of higher education. Implementing extended time more widely poses challenges, but there are also creative solutions to these challenges.

Commentary On: "For Safety's Sake: A Case Study Of School Security Efforts And Their Impact On Education Reform", Harris Sokoloff

Journal of Applied Research on Children: Informing Policy for Children at Risk

Invited commentary on the article "For Safety’s Sake: A Case Study of School Security Efforts and their Impact on Education Reform" by Rachel Garver and Pedro Noguera.

The Relationship Of Provincial Economic Level And Child Injury Mortality In Thailand: A Cross-Sectional Analysis In A Middle Income Country, Adisak Plitponkarnpim, Ragnar Andersson, Kristen A. Conner, Huiyun Xiang, Gary Smith

Journal of Applied Research on Children: Informing Policy for Children at Risk

The objective of this cross-sectional study was to examine the relationship of provincial economic development indices with incidences of child injury mortality in Thailand from 1999 - 2001. All injury deaths among children age 1-14 years were included. The independent variables included gross provincial product per capita (GPP/c), poverty and inequality indices, material and social deprivation indices, population in rural/ urban areas, and migration. Due to multicollinearity of such variables, the 76 provinces were categorized by GPP/c quartile, and means of overall injury, drowning, and transport-related mortality rates were compared among quartile groups. Spearman’s rho correlation between GPP/c and injury …

Commercial Sexual Exploitation And Missing Children In The Coastal Region Of Sao Paulo State, Brazil, Gilka Jorge Figaro Gattás, Claudia Figaro-Garcia, Tatiana Savoia Landini, Richard J. Estes

Journal of Applied Research on Children: Informing Policy for Children at Risk

The commercial sexual exploitation of children (CSEC) has emerged as one of the world’s most heinous crimes. The problem affects millions of children worldwide and no country or community is fully immune from its effects. This paper reports first generation research of the relationship that exists between CSEC and the phenomenon of missing children living in and around the coastal regions of the state of Sao Paulo, Brazil, the country’s richest State. Data are reported from interviews and case records of 64 children and adolescents, who were receiving care through a major youth serving non-governmental organization (NGO) located in the …

When Policy Opportunity Is Not Enough: College Access And Enrollment Patterns Among Texas Percent Plan Eligible Students, Catherine Horn, Stella M. Flores

Journal of Applied Research on Children: Informing Policy for Children at Risk

In 1998, Texas initiated a bold new statewide university admission policy aimed at increasing college access for traditionally underserved students in the state. House Bill 588 (known as the Texas Top 10 Percent Plan (TTPP)) guaranteed automatic admission to the college or university of their choice for all top performing students in Texas public high schools. Fourteen years after the plan’s implementation, we see great strides and complexities in understanding student outcomes as a result of the percent plan. However, the legal controversy over the percent plan both in Texas and other states incorporating similar yet distinctly motivated alternative admissions …

Alternative Strategies For Identifying High-Performing Charter Schools In Texas, Lori L. Taylor, Paige C. Perez

Journal of Applied Research on Children: Informing Policy for Children at Risk

The Obama administration's recurring policy emphasis on high-performing charter schools begs the obvious question: how do you identify a high-performing charter school? That is a crucially important policy question because any evaluation strategy that incorrectly identifies charter school performance could have negative effects on the economically and/or academically disadvantaged students who frequently attend charter schools. If low-performing schools are mislabeled and allowed to persist or encouraged to expand, then students may be harmed directly. If high-performing schools are driven from the market by misinformation, then students will lose access to programs and services that can make a difference in their …

Expanding Learning Time In Schools: Considering The Challenges Of Implementation And The Potential Impact, David Farbman

Journal of Applied Research on Children: Informing Policy for Children at Risk

Considering the broader context of school reform that is seeking education strategies that might deliver substantial impact, this article examines four questions related to the policy and practice of expanding learning time: (a) why do educators find the standard American school calendar insufficient to meet students’ educational needs, especially those of disadvantaged students? (b) how do educators implement a longer day and/or year, addressing concerns about both educational quality and costs? (c) what does research report about outcomes of expanding time in schools? and (d) what are the future prospects for increasing the number of expanded-time schools? The paper examines …

Comparing Campus Discipline Rates: A Multivariate Approach For Identifying Schools With Significantly Different Than Expected Exclusionary Discipline Rates, Eric A. Booth, Miner P. Marchbanks Iii, Dottie Carmichael, Tony Fabelo

Journal of Applied Research on Children: Informing Policy for Children at Risk

Campus behavior management is important for ensuring classroom order and promoting positive academic outcomes. Previous studies have shown the importance of individual student and campus personnel characteristics and campus context for explaining campus discipline rates (e.g., rates of suspension and expulsion). Assessing campus discipline rates, while controlling for these individual and campus characteristics, is important for the monitoring, evaluation, and intervention role of policymakers as well as state and federal level education agencies.

Systems or metrics exist that measure other student outcomes (i.e., academic performance) with controls for individual and campus characteristics, but none exist that monitor these differences for …

For Safety’S Sake: A Case Study Of School Security Efforts And Their Impact On Education Reform, Rachel Garver, Pedro Noguera

Journal of Applied Research on Children: Informing Policy for Children at Risk

Several studies have shown that the need to create safe and orderly schools has increasingly been addressed in a manner that disconnects these priorities from broader concerns related to student success, school culture, and child development. In this paper, we explore the consequences of expanding security procedures in response to an incident involving interracial conflict at an urban high school in the United States. We offer this case study to demonstrate how the primacy placed on safety and security resulted in the neglect of other important educational goals, such as academic engagement and a positive school culture. Through an analysis …

The Comprehensive Assessment Of Leadership For Learning: A Next Generation Formative Evaluation And Feedback System, Carolyn Kelley, Richard Halverson

Journal of Applied Research on Children: Informing Policy for Children at Risk

Recent developments in federal policy have prompted the creation of state evaluation frameworks for principals and teachers that hold educators accountable for effective practices and student outcomes. These changes have created a demand for formative evaluation instruments that reflect current accountability pressures and can be used by schools to focus school improvement and leadership development efforts. The Comprehensive Assessment of Leadership for Learning (CALL) is a next generation, 360-degree on-line assessment and feedback system that reflect best practices in feedback design. Some unique characteristics of CALL include a focus on: leadership distributed throughout the school rather than as carried out …