THE FUNCTION OF ERBIN, A SCAFFOLD PROTEIN, AS A TUMOR SUPPRESSOR IN COLON CANCER

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play important roles in orchestrating cell signaling. Here, we show that Erbin functions as a tumor suppressor in colon cancer. Analysis of Erbin expression in patient specimens reveals that Erbin is downregulated at both mRNA and protein levels in tumor tissues. Functionally, knockdown of Erbin disrupts epithelial cell polarity and increases cell proliferation in 3D culture. In addition, silencing Erbin results in an increase in the amplitude and duration of signaling through Akt and RAS/RAF pathways. Moreover, Erbin-loss induces epithelial-mesenchymal transition (EMT), which coincides with a significant increase in cell migration and invasion. Erbin interacts with KSR1 and displaces it from the RAF/MEK/ERK complex to prevent signaling propagation. Furthermore, genetic deletion of Erbin in Apc knockout mice promotes tumorigenesis and significantly reduces survival. Tumor organoids derived from Erbin/Apc double knockout mice have increased tumor initiation potential along with increased Wnt target gene expression as seen by qPCR. Collectively, the studies within this dissertation identify Erbin as a negative regulator of EMT and tumor progression by directly suppressing Akt and RAS/RAF signaling in vivo

Substantial Equivalency and the Future of Fair Housing in Ohio, Symposium: New Strategies in Fair Housing

This article reviews recent Ohio court decisions and discusses their potential impact on the continued certification of the state\u27s fair housing law as “substantially equivalent.” It also addresses several responsive steps being taken by the Ohio Civil Rights Commission in order to re-establish the rights and responsibilities under the state\u27s fair housing law

Helium in Stream Water as a Volcanic Monitoring Tool

We show that synoptic sampling of streams can be used to characterize volcanic volatiles in groundwater over large spatial scales. Synoptic sampling of dissolved noble gases, 222Rn, major ions, and stream discharge was carried out along a 30 km reach of the Gibbon River, near Norris Geyser Basin in Yellowstone National Park, USA. Groundwater discharge location, volume, and composition were estimated by constrained calibration of a stream flow and solute transport model. Estimated groundwater composition from stream modeling was compared to shallow groundwater concentrations measured in nearby springs. 3He, 222Rn, and Cl− aq signatures in the Gibbon River are indicative of groundwater discharge with a volcanic signature along the study reach. Stream water noble gas isotopic composition has similar isotopic mixing patterns to springs. The model-estimated composition of groundwater discharging to the Gibbon agrees well with observed groundwater composition from nearby springs for all modeled analytes. We present the first observations of elevated mantle helium in stream water and show that stream water can be used as a convenient collection point to estimate spatially distributed groundwater composition and to monitor changes in volatile flux over large spatial areas. These results offer the possibility that stream surveys in volcanic terrain could be a new method for distributed volcanic monitoring at the catchment scale and beyond

Ethical Considerations of Autonomous Weapon Systems

When autonomous weapons systems become operationally superior to alternatives (such as human soldiers), they will be deployed in international warfare. Moral and ethical considerations have not prevented the development and use of new technologies in war historically. The dangers posed by autonomous weapons systems (AWS) are unlikely to deter emboldened illiberal regimes and offer noteworthy military advantages, barring the moral implications of their use. Significant military benefits offered by such weapons virtually require all states to secure investment and development in these platforms. However, AWS represent consequential challenges to conventional ethical frameworks that establish accountability and ensure discriminatory conduct during warfare. AWS are controlled by necessarily opaque software inhibiting our understanding of the system’s capacity to discriminate between civilian, friend, and enemy. Epistemologically, we lack reliable, scientific evidence regarding the accuracy of machine perception, while humans do not understand the statistical learning models of second-generation AI to trust in their autonomous decision-making in the unstructured contemporary combat environment. Artificial intelligence cannot stand trial for war crimes, nor do we have the capacity to assign blame within the chain of command due to accountability gaps. These serious ethical concerns merit deliberation. Thus, it would be prudent to develop novel frameworks to update considerations of jus en bello to account for the possibly destabilizing effects of AWS that exclude humans from decision-making processes. These frameworks would chiefly incorporate a method through which AWS could be proven to be capable of discrimination and an oversight structure for aportioning blame if a lapse occurs

STROKE PARAMETERS AND ARM COORDINATION IN COMPETITIVE UNILATERAL ARM AMPUTEE FRONT CRAWL SWIMMERS

The aims of this study were to: (1) determine the changes in stroke parameters and arm coordination as a function of swimming speed; and (2) examine the relationships between stroke parameters and arm coordination, for competitive unilateral arm amputee front crawl swimmers. Thirteen highly-trained swimmers (3 male, 10 female) were filmed underwater from lateral views during six increasingly faster 25 m front crawl trials. Increases in swimming speed were achieved by an increase in stroke frequency which coincided with a decrease in stroke length. All swimmers showed asymmetric coordination between their affected and unaffected arm pulls, which was not affected by an increase in swimming speed up to maximum. The fastest amputee swimmers used higher stroke frequencies and less catch-up coordination before their affected arm pull, when compared to the slower swimmers. Reducing the time delay before initiating the affected arm pull appears to be beneficial for successful swimming performance

The Effect of Foreclosures on Crime in Indianapolis, 2003-2008

Author's manuscript made available in accordance with the publisher's policy.Objective Until recently, few studies have examined the relationship between home foreclosures and crime. Foreclosures are one major source of neighborhood instability and can be expected to affect crime from several theoretical perspectives. Some recent research has found conflicting results on whether foreclosures cause crime. Method This study examines whether foreclosures are a robust predictor of crime and whether the effect of foreclosures on crime varies across neighborhood contexts. We estimate fixed-effects negative binomial models using geocoded Indianapolis foreclosure and crime data for 2003–2008 to predict crime counts in 1,000 feet × 1,000 feet square grid cells. Result Foreclosures exhibit consistent positive effects on indices of overall, property, and violent UCR-reported (where UCR is Uniform Crime Report) offenses in a cell and rape, aggravated assault, and burglary counts. In addition, foreclosures had greater effects on reported UCR crimes in stable neighborhoods, especially those with more owner-occupied homes. Conclusion Foreclosures were a robust predictor of crime in the current study

Intra and Inter-Neighborhood Income Inequality and Crime

Author's manuscript made available in accordance with the publisher's policy.One important factor in many macro-level theories of crime is income inequality. Although research generally shows that low levels of neighborhood income are associated with crime, research studies have been less clear on whether income inequality is a robust, independent predictor of crime, particularly in small area studies, and few studies have explicitly considered income inequality between neighborhoods, and those that do typically focus on homicide. The current study examines whether within and between neighborhood income inequality is associated with variation in violent and property crime. We employ geocoded Uniform Crime Report data from the Indianapolis police department and economic and demographic characteristics of the population from the American Community Survey for 2005–2009. Consistent with prior research, lower levels of income were associated with higher violent and property crime counts. Within-tract income inequality was also associated with higher Uniform Crime Reports violent and property crimes in most models. Results also showed that the ratio of tract income levels to neighboring tracts is associated with variation in crime. Thus, both local and nearby income inequality affect crime. Implications for theory and policy are discussed

The Spatial Extent of the Effect of Foreclosures on Crime

Author's manuscript made available in accordance with the publisher's policy.Although neighborhood stability has long been considered a substantial determinant of crime, foreclosures have not been the subject of concerted research among criminologists until recently. A number of recent studies have examined the linkage between home foreclosures and crime. Though generally finding a significant relationship, studies have used different approaches and units of analysis. This variation led us to examine the spatial extent to which foreclosures affect a relatively small surrounding area. In this paper, we consider the spatial extent of the foreclosure effect on crime by estimating fixed effect negative binomial models using geocoded UCR data for 2003–2008 and foreclosure data to predict crime counts using the number of foreclosures within various small area radii. Results show that, independently and jointly, foreclosures are a predictor of crime up to at least a distance of 2250 feet. Importantly, that effect declines with distance. We conclude with a discussion of the implications of those findings