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Unangax̂ Monumentality: Hunter-Fisher-Gatherer Transformations of the Rat Islands, Alaska, c. 4,000 BP–1,000 BP
Ph.D.This dissertation research project tested hypotheses about the relationships between hunter-fisher-gatherers and the landscape through an archaeological investigation of earth mounds in the western Aleutian Islands. These mounds were historically believed to be natural places of plant overgrowth that occurred in response to accumulations of bird guano. This project was developed after preliminary studies indicated that these earth mounds had cultural origins and that at least one earth mound was constructed by humans rather than birds. The goal of this project was to further explore the depositional history of the earth mounds and to investigate their relationship with known monumental construction in the eastern Aleutian Islands. The research focused on an investigation of how monumental earth mound constructions can signal and reinforce expressions of group-identity among prehistoric hunter-fisher-gatherer communities. The project combined archival, field, and laboratory research to investigate the cultural Rat Islands landscape. Field research occurred on Kiska and Amchitka over 18 days in June 2019. Four earth mound clusters were archaeologically tested with a soil probing auger, shovel tests, and trench excavations. Two earth mound soil columns were collected for soil chemistry analysis. Stratigraphic analysis and radiometric dating were employed in the investigation of the depositional history of 18 earth mounds. The spatial and temporal relationships between prehistoric occupation sites and earth mound clusters were examined through GIS based mapping. Comparative and statistical analyses were utilized to investigate the regional differences in mound deposition to provide insight to Unanga{ expressions of group-identity. Five new cultural earth mound sites were defined in the Rat Islands. Unprecedented high-resolution aerial imagery was captured at two of these sites by drone. Archaeological subsurface testing confirmed a cultural origin for at least three additional earth mounds. Organic materials were sent to the KECKS-CCAMS facility for radiocarbon dating which resulted in a project contribution of five new non-contemporaneous radiocarbon dates for the Rat Islands. Soil columns were sent to the Rutgers Soil Testing Laboratory and analyzed for available nutrients. The results revealed significant spikes in phosphorus that potentially aligns with the stratigraphic and material evidence of human activity. Results indicate that monumental earth mound construction is a pan-Aleutian tradition dating back to at least 3,700 years ago. The distribution of internal materials and the overall size and shape of the earth mounds were compared with data from eastern Aleutian monumental mounds. This comparative analysis highlighted regional trends in mound variation that align with the known proto-historic territorial boundaries of distinct identity-groups. The variations in earth mound style across the Aleutians are reflective of localized expressions of a broad trend. Broad but variable monumental earth mound construction is a well-known Indigenous American practice that spans the United States. This project extends the discussion of socionatural theories about hunter-fisher-gatherer impacts and monumental manipulations of the landscape into the western Aleutian Islands.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Evaluation of ΔNp63 Expression in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinom
M.S.Oral squamous cell carcinoma (OSCC) is by far the most common mucosal malignant neoplasm that arises in the head and neck, which accounts for more than 90% of all malignancies encountered in this anatomical region with the lateral border of the tongue being the most commonly affected area. Unfortunately, most patients with OSCC are diagnosed at a late stage of the disease. Despite the use of combined surgery and radiotherapy, still, there is 30% local or regional disease recurrence, 25% distal metastases, and a 40% five-year survival. Most often, progress to OSCC is preceded by oral epithelial dysplastic lesions such as leukoplakia and erythroplakia. Eventually, 16% to 36% of oral dysplasias transform into invasive OSCC. Thus, the need for early diagnosis and the development of robust biomarkers is of paramount importance. In recent years, studies from our lab and others have shed light upon the importance of the transcription factor p63 in the pathogenesis of oral dysplasia and SCC of different anatomical regions including the skin and the head and neck region. In fact, p63 overexpression or amplification is seen in more than 80% of OSCC. p63 is a member of the p53 tumor suppressor family and encodes for two major isoforms; TAp63 and ΔNp63, with ΔNp63 being the critical and predominant protein expressed in the epidermis and other epithelial tissues. Unlike other members of the p53 family, ΔNp63 acts as a proto-oncogene that when overexpressed leads to increase cell proliferation and inhibition of growth arrest signals. Overall, the oncogenic properties of ΔNp63 suggest that it may serve as a biomarker for OSCC progression. Given the importance of p63 in SCC, we sought to determine the pattern and levels of p63 expression in oral epithelial dysplasia and OSCCs cases using standard immunohistochemical staining in order to assess ΔNp63 usefulness as a potential biomarker for premalignant lesions. Fifty-one biopsy cases of human oral tissues were obtained from archives of The Department of Oral and Maxillofacial Pathology, University at Buffalo. The study consisted of six different categories including: mild epithelial dysplasia (n=10), moderate epithelial dysplasia (n=10), severe epithelial dysplasia (n=10), well-differentiated OSCC (n=10), moderately-differentiated OSCC (n=7) and poorly-differentiated OSCC (n=4) with a total of thirty cases of oral epithelial dysplasia (n=30) and twenty-one cases of OSCC (n=21). Immunohistochemical staining of ΔNp63 showed nuclear immunoreactivity in all cases with significantly increased ΔNp63 expression compared to the normal oral mucosa. The presence of strong ΔNp63 expression in areas beyond the parabasal cells suggests that these keratinocytes have an increased proliferative potential and aberrant differentiation, which in turn would predispose the cells to malignant transformation, and therefore may play an important role as a potential marker for premalignancy.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Microaggressions Experienced by Self-Identified Women and Non-Binary People of Color Employed by Human Service Agencies: An Exploratory, Mixed Methods Study
Ph.D.There is limited research examining the effects of microaggression in the workplace, although employment constitutes a large proportion of many people's lives (Cortina, 2008). There are not yet any studies of workplace microaggressions at human service organizations, which are based in professions that have a responsibility to foster environments conducive to providing equitable services. Further research is needed about the effects of microaggressions experienced by employees of human service organizations in order to acknowledge and address subtle workplace discrimination (Holder, Jackson, & Ponterotto, 2015). This mixed methods study applied an intersectional approach to explore the nature and frequency of microaggressions experienced by self-identified women and non-binary people of color employed by human service agencies.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Influence of Paracrine Signaling on Neoplastic Induction in Human Oligodendrocyte Progenitor Cells
M.S.Understanding the origin and cause of tumorigenesis is crucial in the development of new targeted drugs. Multiple mutations are usually required to drive neoplastic transformation which can lead to cancer. Glioblastoma (GBM) is considered to be one of the deadliest type of cancers. WHO classifies GBM as grade IV tumor and has a median survival rate of 12-15 months. It is also the most aggressive form of cancer and accounts for ~80% of malignant brain tumors. Glioma is the most frequent primary brain tumor in adults. While the precise cell of origin remains unknown, studies have shown that oligodendrocyte progenitor cells (OPCs) facilitate malignant glioma. Genomic studies of human glioma have identified three common signaling pathways that are often mutated in GBM. Mutations in three tumor suppressors, p53, PTEN and RB, represent the most common genes that are mutated in each pathway. Previous studies in our lab have shown that over-expression of presumptive dominant negative tumor suppressor (dnTS) proteins alters the morphology of human OPCs (hOPCs) cells and increases the capacity for self-renewal and rate of proliferation in vitro. However, the contribution of individual pathways to hOPC dysregulation and their necessity for tumorigenesis and malignant progression from hOPCs is still unknown. We first examined the effect of expression of individual dnTS proteins on the rate of hOPC proliferation. As shown previously, over-expression of all three dnTS proteins resulted in hyperproliferation of hOPCs in vitro. However, only dominant negative p53 (dnp53) expression was sufficient to induce cell-cycle entry and hyper-proliferation in human OPCs and this occurred regardless of growth factor supplementation. As expression level of dnTS proteins may not be sufficient to result in functional blockade, we decided to take a knockout approach using CRISPR/Cas9. As such, we cloned and produced lentiviral CRISPR/Cas9 vectors that targeted PTEN and RB. Upon transfection with the resultant plasmids, TLCv2-RB1 and TLCv2-PTEN, we were able to achieve induction of these plasmids in HEK 293T cells. We extracted genomic DNA and protein from the transfected cells for sequencing and to check the protein expression respectively. Genomic DNA sequencing and decreased protein expression, compared to the wild type, showed possible mutation in transfected HEK 293T cells. However, due to COVID restrictions, it was not possible to investigate the potential for CRISPR/Cas9-mediated mutation to induce neoplastic transformation by hOPCs. To summarize, we found that hOPCs proliferate at a higher rate when exposed to mutant p53 tumor suppressor gene and developed lentiviral vectors to inactive PTEN and RB1 in hOPCs. More research is required to determine the effectiveness of this approach and investigate the effects of combined inactivation in hOPCs.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Effects of Mesenchymal Transition on Sensitivity of Breast Cancer Cells to LT-IIc
M.S.The epithelial to mesenchymal transition (EMT) is a cellular program wherein epithelial cells acquire motility and invasiveness, similar to the activity of mesenchymal cells. Triple negative breast cancer (TNBC) is the most lethal form of breast cancer, with a high rate of metastasis, recurrence and mortality. LT-IIc is a bacterial enterotoxin that induces cytotoxicity in mesenchymal transformed (TM12T) but not epithelioid (TM12) clonally derived mouse breast cancer cell lines. It induces toxicity in and human breast cancer cell lines with a mesenchymal TNBC phenotype as well. The purpose of this thesis was to test the hypothesis that the mesenchymal phenotype is sufficient for inducing sensitivity to LT-IIc. To test this hypothesis, we used in vitro models of EMT induction. In the normally LT-IIc resistant epithelial MCF10A and MCF-7 cell lines, TGF-beta treatment alone was not sufficient to induce lasting EMT. A commercial EMT- media supplement targeting the TGF beta plus cadherin-dependent signaling pathway successfully induced EMT. This transition was confirmed by changes in cellular morphology and differential expression of epithelioid versus mesenchymal markers. After the transition, cells were observed to lose their epithelial morphology, and to adopt a mesenchymal-like appearance. The epithelial marker (E-cadherin) was reduced after EMT treatment and the presence of mesenchymal markers (transcription factors SNAI, ZEB1) was observed. The transitioned cells were tested for LT-IIc susceptibility by induction of cellular vacuolization (indicating induction of autophagy and blocking of lysosomal progression), and MTT assay. The LT-IIc holotoxin, (catalytic A subunit and ganglioside binding B5 pentamer) was compared to the B5 pentamer alone. Induction of EMT was sufficient to induce LT-IIc vacuolization and cytotoxicity, and cells were more sensitive to killing by the B5 pentamer than the holotoxin. These results suggest that LT-IIc-targeted ganglioside signaling pathways may be novel targets for chemotherapy of mesenchymal TNBC.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Understanding the Effect of Polymer Morphology on Gas Transport Characteristics
Ph.D.Polymeric gas separation membranes represent an attractive approach to separate carbon dioxide (CO2) from fuel gas (natural gas, syngas, etc.) due to their simplicity, compactness, and energy-efficiency. The thrust of this dissertation consists of critically examining the morphology of polymers practiced for commercial membranes, identifying the fundamental contributions of gas sorption and diffusivity towards permeability, and tailoring morphology appropriately to maximize separation performance. To achieve these objectives, semi-crystalline cellulose acetates (CAs) and amorphous polybenzimidazoles (PBI) were studied individually for CO2/CH4 separation and H2/CO2 separation, respectively. In the CAs study, we demonstrate that bulk crystallinity can be suppressed by reducing film thickness (confinement) or blending CAs optimally, which contributes to higher CO2 permeability via higher diffusivity and solubility. The first part of our study focuses on cellulose diacetate (CDA), and the effect of confinement on crystallinity/gas transport properties. The second part centers around the effect of blending CDA with cellulose triacetate (CTA) in conjunction with the effect of confinement on crystallinity/gas transport properties. The findings in both studies shed light on a long-standing puzzle regarding the discrepancy in gas transport properties between bulk CA films (20 µm) and commercial CA membranes comprised of a thin selective layer (50-200 nm). In the PBI study, the combined effects of phosphoric acid (H3PO4) doping and carbonization on the morphology and H2/CO2 separation characteristics of PBI-derived carbon molecular sieves (CMS) are systematically studied. We demonstrate that harnessing the power of acid doping can significantly increase the CMS size-sieving abilities by tightening the precursory PBI polymer chains prior to carbonization, while carbonization can greatly increase both H2 permeability and H2/CO2 selectivity by rearranging the PBI morphology to favor H2 permeation. This approach shows that doping and carbonization can synergistically enhance the CMS H2 permeability and H2/CO2 selectivity, and overcomes the fundamental permeability/selectivity tradeoff. Overall, the CMS were optimized by fine-tuning the doping level and the carbonization temperature, and exhibit performance well-beyond the Robeson upper bound.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
The Evaluation of Viable Bacterial Retention on Sutures After Three Different Mouthrinse Treatments
M.S.In the oral cavity, sutures are continuously bathed in saliva containing approximately 7.5x108 microorganisms/ml which can attach to the suture surface and lead to prolonged infection. Chlorhexidine mouthrinse is considered to be the gold standard for antibacterial treatment in dentistry. However, it can have several negative side-effects in the mouth, such as discoloration on teeth surfaces and oral mucosa. An aqueous solution of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymers has been proposed by researchers to suppress oral bacterial adhesion to surfaces of teeth. In addition to increasing the possibility of infection due to bacterial adhesion, the presence of sutures on the oral wound can also increase postoperative complication, such as pain, swelling, and trismus. The aim of this thesis research was to evaluate whether a 5% aqueous solution of MPC can decrease retention and/or viability of oral bacteria from two different types of sutures that are commonly used in oral surgery: polypropylene and silk. This study also investigated whether the presence of a knot in the suture affects removal and/or viability of the oral bacteria from the sutures. This in vitro study was done by incubating the sutures in a mixture of TSB broth and freshly human pooled saliva for approximately 24 hours. The sutures then were treated by shaking for 90 seconds with 3 mouthrinses: chlorhexidine as a positive control, 5% MPC solution, or phosphate buffered saline (PBS) as a negative control. After treatments, the sutures were put into fresh TSB broth and incubated for 24 hours. The bacterial retention and/or viability was evaluated by measuring the turbidity of broth using a 1951 USAF Resolution Target. Contact angle analysis, scanning electron microscopy (SEM)/ energy dispersive x-ray spectroscopy (EDS), and infrared spectroscopy were used to characterize the suture materials and mouthrinse solutions. There was no significant difference in retention or viability of bacteria from the sutures after MPC mouthrinse treatment compared to the PBS control. However, chlorhexidine treatment resulted in significantly less bacterial viability compared to both MPC and PBS solutions. Whether chlorhexidine treatment also affected bacterial retention on the sutures cannot be determined from the protocol used in this study. Silk knot sutures presented the most bacteria retention/viability, whereas polypropylene straight sutures had the least in bacterial retention/viability. Chlorhexidine was the most effective antibacterial mouthrinse compared to 5% MPC and PBS mouthrinses. Type of suture materials and post-surgical mouthrinses should be considered while treating patients at high risk for infection.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
William Blake and the Net of Religion
M.A.This thesis will explore the development of ideas about religion through the literary career of William Blake, with an eye toward the present and our current understanding and response to notions of religion and religiosity in the modern world. In an ever-changing social and intellectual landscape, the conventional understanding of what it means to "be religious" is being challenged, and likewise are the religious institutions which have stood for centuries at the forefront of global spirituality being forced to adapt to a changing landscape. Following a brief examination of religion as a general human phenomenon, in both the past and present, I will focus predominantly on Blake's career, beginning with a pair of brief early texts, All Religions are One and There is No Natural Religion, in which Blake establishes, in the former, his outlook on religion as a universal principle of the human psyche and, in the latter, his objection to the development of contemporary movements which placed humanity itself at the center of. Their religious impulses. Following this, I will apply the understanding obtained in those two texts to an analysis of Blake's more robust "prophetic canon" in an exploration of the poet's personal myth system. The focus will predominantly focus on a trio of Blake's most significant original characters: Urizen, Los, and Orc, and the cycle of human suffering and redemption which is represented in their strife with one another. At last I will arrive at an approximation of the personal religious ideology suggested in Blake's canon, and assess some of its implications and applications to the modern reader.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Optimum Receiver Design for Internet-of-Things (IoT) with LoRa Transmission Signals
M.S.Recent advances in Internet of Things (IoT), Machine to Machine (M2M) communications have increased the demand of low power wide area networks (LPWAN) technologies. Different standards have been published to meet this requirements. LoRa (acronym for Long Range) being the leading standard amongst them has gained high research interest. LoRa is developed and patented by Semtech. This thesis focuses on the physical layer of LoRa known as LoRa PHY or simply LoRa. LoRa transmission signals are analysed in baseband domain. These signals are viewed as basis signal set and the vector model of LoRa signals is presented. The contribution of this thesis also lies on Additive White Gaussian Noise (AWGN) analysis for IoT systems. AWGN is analysed in baseband domain and a generalised expression for baseband noise correlation is derived. The baseband AWGN is further projected on to the basis signal set to get the noise vector representation for LoRa signals. The later part of this thesis focuses on the receiver of the LoRa system. An existing receiver design is reviewed and an alternative receiver design is proposed based on optimum MAP detector. Firstly, the received signal is projected onto the basis signal set to get the vector representation. Since the noise components are correlated, Multivariate Gaussian random distribution was used to obtain the noise vector distribution. The MAP detector was presented in vector domain. Efficient implementation of the proposed receiver is then presented with the help of a filter and splitter. To evaluate the performance of the proposed receiver, both existing and proposed receivers are simulated in Matlab with AWGN channel. Both correlated and uncorrelated noise are considered for simulation. Bit error rate (BER) performance comparison was carried for the 2 receivers for 10^5 symbols with varying parameters like bandwidth and spreading factor.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Under-Consumption of Water by Thirsty Sucrose-Maintained Rats
Ph.D.Rats that have never had anything but a 5% sucrose solution to drink from weaning until testing in adulthood under-consume water relative to water-maintained controls when challenged with subcutaneous hypertonic saline (HS). This project was designed to clarify if this is because the fluid that is consumed early in life determines adult drinking behavior, or because the fluid that is consumed most recently changes the drinking response. Furthermore, we tested whether or not sucrose consumption needs to be exclusive, and whether the changes in consumption affect hydration. To this end, we manipulated which fluid (water or sucrose) was available and evaluated the effect of changing the available fluid 1 or 7 weeks after weaning, or providing 1-hr daily access to sucrose while otherwise only having water available. In adulthood, rats were tested in three ways: 1) given either water or sucrose to drink after HS injection, 2) given water or sucrose after overnight fluid deprivation, and 3) given both fluids to drink simultaneously after HS injection. Some groups underwent all three tests, and others only the first test. Finally, plasma osmolality was measured after HS injection. We found that sucrose need not be exclusive to see under-consumption of water, but 1-hr daily access is not sufficient to cause differences in intake. The amount of water that rats drank was determined by the fluid the rats had the week before testing. Perturbations in burst number and size, likely indicative of changes in postingestive and orosensory feedback, were often present despite normalized intake after one week of drinking water. Rats that under-consumed water after HS challenge failed to bring plasma osmolality back to baseline two hours after injection. Together, these data demonstrate that drinking water is subject to negative contrast effects in thirsty rats accustomed to drinking sucrose, and that this negatively impacts their hydration.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*