Thesis (M.S.)--University of Wisconsin -- La Crosse, 1984. / Includes bibliographical references (leaves 54-59).

<p>The physiology of the tumor microenvironment is characterized by lower oxygen (hypoxia), higher lactate, extracellular acidosis and glucose starvation. We examined the global, transcriptional cellular responses to each of these microenvironmental stresses in vitro, projected them onto clinical breast cancer patients' samples in vivo, and returned to perform further in vitro experiments to investigate the potential mechanisms involved in these stress responses. The reciprocal exchange of information was critical and advanced our understanding of the potential clinical relevance of cellular responses. </p> <p>Our expression array result showed that lactic acidosis induces a strong response, distinct from that of hypoxia in human mammalian epithelial cells (HMECs), indicating lactic acidosis is not only a by-product of hypoxia but has a unique role as a stimulant to cells in the tumor microenvironment. Cellular responses to lactosis and acidosis further demonstrated that acidosis was the main driving force in the lactic acidosis response. These responding gene signatures were then statistically projected into clinical breast cancer patients' expression data sets. The hypoxia response, as reported previously, was associated with bad prognosis, where as the lactic acidosis and acidosis responses, were associated with good prognosis. Additionally, the acidosis response could be used to separate breast tumors with high versus low aggressiveness based on its inversed correlation with metastatic character. We further discovered that lactic acidosis, in contrast to hypoxia, abolished Akt signaling. Moreover, it downregulated glycolysis and shifted energy utilization towards aerobic respiration.</p> <p>We continued to examine the cellular response to lactic acidosis temporally in MCF7 cells, a breast cancer cell line. The lactic acidosis response of MCF7 cells also showed the prognostic result of better clinical outcomes in datasets of breast cancer patients. The lactic acidosis responses of HMEC and MCF cells were highly correlated. Strikingly in MCF7 cells, lactic acidosis and glucose deprivation actually induced similar transcriptional profiles, with only a few genes being oppositely regulated. Furthermore, lactic acidosis, similar to glucose starvation, induced AMPK signaling and abolished mTOR. However, lactic acidosis and glucose deprivation induced opposite glucose uptake phenotypes. Lactic acidosis significantly repressed glucose uptake whereas glucose deprivation significantly induced it. Among the genes differentially regulated by these two stresses, thioredoxin-interacting protein (TXNIP) was among the most different. The negative regulatory role of TXNIP on glucose uptake has been demonstrated previously. In the cancer research field, TXNIP is recognized as a tumor suppressor gene. We observed that lactic acidosis induced TXNIP strongly and most importantly, TXNIP played a critical role in regulating glucose uptake in cells under lactic acidosis. Furthermore, MondoA, the transcription factor and glucose sensor previously reported to regulate TXNIP induction upon glucose exposure, was also responsible for regulating TXNIP under lactic acidosis. We demonstrated that TXNIP not only plays an important role in the lactic acidosis response but also has strong prognostic power to separate breast cancer patients based on survival.</p> / Dissertation

Small and very small slaughterhouses generally spray lactic acid for carcass decontamination utilizing a hand held sprayer. Even though this tool represents a very small investment, it may present important disadvantages such as uneven delivery of the spray over the carcass surface. If the decontamination treatment is not applied properly, the untreated areas of the carcass will still have high bacterial loads present and could be a source for recontamination of the areas that have been treated. A sanitizer spraying system (sanitizing halo system) was designed and assembled. The sanitizing halo system was tested at the Rosenthal Meat Science and Technology Center, Texas A&M University. Thirteen carcasses were split in halves. Thirteen halves were sampled and used as control after knife trimming and water wash; then they were sprayed with 2% L-Lactic at 55°C with the sanitizing halo system. The other 13 halves were sprayed by the RMSTC employees utilizing a hand held sprayer. Counts of aerobic and mesophilic bacteria obtained from carcasses sprayed with the sanitizing halo system and the hand held sprayer were both significantly lower than the control counts. In addition, coliforms counts were below the detectable limit for the sanitizing halo system and the hand held sprayer. After testing, the sanitizing halo system was installed at two small commercial slaughter plants processing beef and pork carcasses. At each slaughter plant, 24 carcass halves were treated with 2% L-Lactic at 55°C using the sanitizing halo system, and the other 24 halves were used as control. Mesophilic bacteria populations were reduced in beef and pork carcasses by 2.9 and 1.9 log cycles, respectively, after the lactic acid treatment. Also E. coli counts were significantly lower in the three regions sampled after application of the 2% L-Lactic acid with the sanitizing halo system. From the data collected during this study, we recommend the sanitizing halo system as a tool to reduce the bacterial loads on the surface of beef and pork carcasses. The use of this system should help small and very small slaughterhouses to improve food safety performance while providing cost-efficiency, simplicity, and convenience.

Thesis (Ph.D)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Collard, David M.; Committee Member: García, Andrés J.; Committee Member: Tolbert, Laren; Committee Member: Wang, Yadong; Committee Member: Weck, Marcus. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Dissertation (PhD)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.

Thesis (Ph. D.)--University of Pennsylvania, 1930. / Bibliography: p. 29.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xviii, 246 p.; also includes graphics (some col.) Includes bibliographical references (p. 207-222).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1952. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 106-112).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1949. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Abstracted in Dissertation abstracts, v. 16 (1956) no. 2, p. 211. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 72-79).