Regulation of anoikis by oncogenic pathways

Detachment of epithelial cells from matrix or attachment to an inappropriate matrix engages an apoptotic response known as anoikis, which prevents metastasis. Anoikis-resistance of tumor cells is critical for anchorage-independent growth and metastasis. Here we show two novel oncogenic pathways that confer resistance to anoikis in tumor cells. One pathway (chapter 2) signifies a new link between EMT and anoikis-resistance. In chapter 3, we present a new connection between inflammatory signaling pathways and anoikis-resistance. Cellular sensitivity to anoikis is compromised during the oncogenic epithelial-to-mesenchymal transition (EMT), through various mechanisms. Chapter 2 introduces a novel mechanism (NRAGE/TBX2/p14ARF) that is induced upon loss of E-cadherin and EMT, mediating anoikis resistance. The inflammatory-response transcription factor, NF-kB, contributes to anoikis-resistance and metastatic progression, through mechanisms that are understood incompletely. Deleted in Breast Cancer (DBC1) is over-expressed in several tumor types and correlates with a poorer prognosis in some cases. DBC1 suppressed anoikis in normal epithelial and breast cancer cell lines. Chapter 3 introduces a novel mechanism: DBC1 suppresses anoikis through enhancing canonical NF-kB signaling. This study will provide mechanisms for DBC1 to act as a tumor promoter, by providing a link between inflammation and anoikis-resistance and providing a potential target for anti-NF-eB/anti-cancer drugs

Geotechnical Laboratory Testing for 2-D FEM Analysis of Geomorphic and Planar Sloped Caps and Covers for Sustainable Mine Refuse Deposition

This thesis reports the findings of the application of Geomorphic Landform Design principles to the Royal Scot abandoned coarse coal refuse (CCR) pile located in Greenbrier County, West Virginia. The Royal Scot facility has many environmental concerns including severe erosion, acid-mine/rock drainage, and sediment transport. A cap and cover system is proposed to be implemented which incorporates the GLD principles. A two-layer cap and cover system will be used to reclaim the site and return it back to a stable state and reduce the production of acid-mine drainage. The system is composed of a hydraulic barrier composed of compacted CCR, and a compacted 80%/20% mixed growth layer. The 80/20 layer is composed of 80% CCR and 20% MGroTM material. The MGroTM is a short paper fiber material produced by the WestRock® paper mill in Covington, Virginia. This material provides the characteristics to allow for the growth of grass on the Royal Scot site. A suite of geotechnical laboratory testing was performed including, classification of the coarse coal refuse, compaction, permeability, and strength testing. The results showed that the compacted CCR could perform as a hydraulic barrier to reduce infiltration into the pile, and the strength for slope stability. The permeability of the CCR was in the magnitude of 10-6 to 10-7 cm/s, and the friction angle for CCR resulted in 25 degrees. The 80/20 growth layer had a permeability of 10-4 cm/s to allow water for growth, while the friction angle ranged from 10 to 16 degrees. Finite Element Modeling was performed on a geomorphic and conventional planar slope located on the site to analyze the cap and cover system for slope stability. The analysis consisted of seepage modeling, coupled with slope stability to get a worst-case scenario factor of safety after infiltration from a 100-year storm event had occurred. The geomorphic slope had increased infiltration compared to the conventional planar slope. The geomorphic slope produced higher factors of safety over 2.0, while the conventional planar slope attained factors of safety close to 1.5

Who Is (Communicatively More) Responsible Behind the Wheel? Applying the Theory of Communicative Responsibility to TAM in the Context of Using Navigation Technology

By examining how perceived usefulness and ease of use relate to the user’s perception (i.e., communicative responsibility), the communicative behavior of the navigation system (i.e., the landmarks used to give directions), and the context of driving (i.e., familiarity of the driving location), this study applies the theory of communicative responsibility to the technology acceptance model to better understand why users are more likely to adopt certain navigation technologies while driving. We hypothesized that users’ perceived symmetry in communicative responsibility independently and interactively (with communicative behavior of the navigation system and the driving situation) affects perceived ease of use and usefulness of the navigation system. Consequently, the perceived ease of use and usefulness may affect the user’s intention to use the navigation system. This study found that usefulness was a significant predictor of behavioral intention. While driving in a less familiar location, the drivers perceived the navigation system to be more useful. When the navigation system provided location-specific landmarks, such as the name of a local store, drivers who attributed more communicative responsibility to the system were likely to find it useful

Increased Prevalence of low High-density Lipoprotein Cholesterol (HDL-C) Levels in Korean Adults: Analysis of the Three Korean National Health and Nutrition Examination Surveys (KNHANES 1998–2005)

AbstractObjectivesHigh-density lipoprotein cholesterol (HDL-C) is an independent risk factor for cardiovascular diseases that has shown a remarkable increase, but little is known about the prevalence of low HDL-C in Korea. This study aimed to evaluate changing trends of low HDL-C prevalence, and indicate other risk factors associated with low HDL-C.MethodsWe selected subjects aged ≥20 years from the Korean National Health and Nutrition Examination Survey (KNHANES) 1998, 2001, and 2005 (n = 7962, 6436, and 6412). The mean level of HDL-C and the prevalence of low HDL-C was calculated, and cardiovascular risk factors associated with low HDL-C, as well as demographic, anthropometric, lifestyle, and nutrition factors, were assessed using the KNHANES 2005 data.ResultsMean HDL-C levels in men and women between KNHANES 1998 and 2005 decreased significantly, from 48.1 to 42.3 and from 51.6 to 47.1 mg/dL, respectively (both p < 0.001). The decrease was slightly less for women compared with men for the same period, and women had higher HDL-C levels at all periods. Covariate-adjusted OR revealed that body mass index, waist circumference, and non-alcohol drinker in both men and women were associated with low HDL-C levels by KNHANES 2005, as were employed and light physical activity in men and low fat intake in women.ConclusionThe prevalence of low HDL-C increased significantly from KNHANES 1998 to 2001 and 2005 (p < 0.001) in both men and women. body mass index, waist circumference, and non-alcohol drinker were identified as associated with low HDL-C in Korean adults

Decolonizing the U.S. Health Care System: Undocumented and Disabled after ACA

The Affordable Care Act (ACA) explicitly denies newly arrived documented and undocumented immigrants health insurance coverage, effectively making them the largest remaining uninsured segment of the U.S. population. Using mixed qualitative methods, our original research illustrates the health consequences experienced by uninsured, disabled undocumented immigrants as they navigate what they describe as an apartheid health care system. Critiquing the notion of immigrants as “public charges” or burdens on the system, our qualitative analysis focuses on Houston Health Action, a community-based organization led by and for undocumented, low-income disabled immigrants in Houston, Texas. Engaging a critical migration and critical disabilities studies framework, we use this valuable case to highlight contemporary contradictions in health care and immigration legislation and the embodied consequences of the intersecting oppressions of race, ability, immigration status, and health care access