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Flooding is one of the fatal natural hazards frequently generating serious impact to infrastructures. As yet, its characteristics are expected to be changing with the changing of global climate. This paper identifies the spatio-temporal correlation patterns of disruptions by flooding hazards at the county-level for the Deep South in the United States, particularly the state of Arkansas. The frequency of each flooding disruption calculated as time series, is generated from flooding records within research period of 1998-2013. A set of quality control procedures including duplicated data check, spatial outliers check, and homogeneity test is applied prior to the regression analysis. The spatial characteristic of those disruptions is identified by mapping them, while their temporal characteristic is assessed using correlation coefficient defined in this paper. Accordingly, greater correlation of disruptions by flooding is found with the decreasing of the distance between for most pairs of the locations throughout the study period.

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There remains a pressing need for the development of effective drugs that meet the clinical needs for cancer treatment, and inhibition of telomere length maintenance by disrupting human telomerase is a proven and tractable target for suppression of cancer cell growth. In response to the lack of currently available small molecules with efficacy against human telomerase, we developed a genetically and chemically tractable cell-based system in which S. cerevisiae is used to streamline the search for novel human telomerase inhibitors. Our results confirmed that yeast cell growth was rapidly inhibited upon induction of functional human telomerase at the telomere. This inducible growth arrest was used as a read-out for a high-throughput chemical screen for human telomerase inhibitors based on their ability to restore growth in the yeast system. From a library consisting of small, bioactive and cell-permeable compounds of diverse structure, we identified three novel “drug-like” compounds that inhibited the activity of native and recombinant telomerase complexes in vitro. “Validation assays” also confirmed the novel inhibitors were free of uncharacterized adverse effects against yeast and human cell models, thus confirming the specificity of these novel inhibitors against human telomerase target. This surrogate yeast model has therefore proven to be a cost-effective alternative to accelerate the search for human telomerase inhibitors, which we hope will serve to streamline the identification of further lead compounds effective against human cancer.

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It is now well established that a wide range of natural and anthropogenic chemicals present in the aquatic environment have the potential to disrupt the endocrine system of many organisms. In fish, many of these effects appear to be of a feminising nature, including stimulation of vitellogenin production and induction of intersex. In piscivorous birds these so called endocrine disrupting contaminants have been shown to impair reproduction, influencing reproductive behaviour, sex ratio, eggshell thickness and reproductive success. The effects seen in fish have been associated with high levels of oestrogenic activity in the effluent from waste water treatments works (WwTWs), but few studies have focused on the effects of WwTWs effluents on birds. In this thesis, the effects of effluents from WwTWs on fish and birds were investigated in the Tamar catchment, SW England. The work spanned making detailed assessment on the oestrogenic and anti-androgenic activity of 3 WwTWs effluents, using a variety of water sampling techniques and applying both recombinant yeast oestrogen screen (YES) and recombinant yeast androgen screen (anti-YAS) bioassays to quantify the different hormonal activities. A survey was undertaken of the hormonal activities at 13 sites to determine concentrations of contaminants in the surface waters throughout the Tamar catchment, using both recombinant yeast screens and targeted analytical chemistry for specific pollutants (LC/MS-TOF and GCMS). An ELISA was developed to quantify vitellogenin (VTG) in the bullhead (our study fish sentinel) as a biomarker of oestrogen exposure, and evidence of endocrine disruption was investigated in wild populations of the bullhead, Cottus gobio and the dipper, Cinclus cinclus. Macroinvertebrates from upstream and downstream of three WwTW's effluent discharges and from three sampling sites were also sampled as an index of overall water quality in the Tamar catchment, and as an assessment of food availability for the bullheads and dippers. For the studies on the hormonal activities in three WwTWs in the Tamar catchment, samples were collected by both spot and passive sampling; passive samplers (in replicate) were placed in the effluent discharges for a three week period, and collected on days 7, 14 and 21, spot samples were taken simultaneously. Measurement of total oestrogenic and total anti-androgenic activity was conducted using the YES and anti-YAS, respectively. Spot and passive samples were collected from 13 sites within the Tamar catchment (sampling sites were >2 km downstream of effluent discharges). Additionally, liquid chromatography mass spectrometry time-of-flight (LC/MS-TOF) was used to measure the concentration of oestrone (E1), 17β-oestrodiol (E2) and 17α-ethinylestradiol (EE2) in each sample. Gas chromatography mass spectrometry (GCMS) was used to measure the concentration of individual PBDE and PCB congeners in the spot samples only. Levels of oestrogenic and anti-androgenic activity observed in the WwTWs effluent were comparable with those measured in effluents in the UK and in other countries. Surface waters of the Tamar, away from the WwTWs effluent discharges, contained very little oestrogenic activity (<1.1 ng E2 EQs L-1), and anti-androgenic activity was undetectable. Quantification of oestrogenic activity using passive samplers showed an increasing amount of total oestrogenic activity between days 7 and 21 when measured by the both the YES and LC/MS-TOF. Low levels of PBDE congeners 47, 99, 100, 138 and 153 were detected in the spot samples taken from the Tamar catchment, with BDE 47 being the most abundant. In contrast PCBs were undetectable. Neither PBDEs nor PCBs were detected in any of the extracts from the passive samples. No assay was available to measure VTG (one of the most widely used biomarkers of oestrogen exposure in fish) in the bullhead and so an enzyme linked immunosorbant assay (ELISA) was developed for application to studies on wild bullheads in the Tamar catchment. The bullhead vitellogenin (bh-VTG) ELISA was developed successfully, and proved to be sensitive and robust, with a detection range between 10.5 and 300 ng bh-VTG mL-1 (undiluted), comparing favourably with other fish VTG ELISAs. Plasma VTG concentrations measured in male bullheads (collected from the same sites as for the water samples) ranged from below the limit of detection to 990 ng bh-VTG mL-1. Whether these upper levels in the range reflected VTG induction was difficult to conclude. Because of this controlled caged exposures with bullheads and trout were used to assess the relative levels of oestrogenicity in two key WwTWs effluent discharges and to determine the response sensitivity of the bullheads (and trout) to those effluents. These controlled exposures found no responses in plasma VTG in bullheads (ranging between 126 and 934 ng bh-VTG mL-1) suggesting a lack of sensitivity for VTG induction. This was supported by the inability to induce VTG in fish held in the laboratory and treated with steroidal oestrogens. For the effluent exposures on the caged rainbow trout, it was also found that there was no significant induction of VTG, a species normally sensitive to oestrogens. These findings may indicate that the fish were highly stressed due to the river being in spate and the movement of the cages during the controlled exposures. It may also be the case, however, that the use of immature female rainbow trout with a highly variable baseline plasma VTG concentration may prevent any detection of a response. There were no signs of sexual disruption in any of the gonads analysed from either male or female wild bullheads, demonstrating that any hormonal activity present in the catchment away from the WwTWs effluents was not sufficient to induce adverse effects on reproductive development. An interesting feature noted in the male testes of the bullheads was the presence of spermatid masses, which have been recorded in 10 other Cottidae species, but not previously in the bullhead. For the studies on dippers, eggs were collected from the nests of breeding dippers to measure for sperm numbers and morphology from sperm trapped in the perivitelline membrane (PVM), and the yolks were analysed for PBDEs, PCBs and organochlorine pesticides (OCPs) by GCMS, for E1, E2, and EE2 by LC/MS-TOF. Eggs of the dipper were collected from nests at the 13 sampling sites, plus an additional three sites and over three years of field study. The number of sperm trapped in the PVM ranged between three and 188, with a mean of 68.78 ± 8.78 SE. Dipper sperm had not previously been characterised, and was found to be similar to other passerine sperm, in that the head was helical, complemented by a mitochondrial helix or keel, which continued in a spiral around the flagellum. Sperm were classed as ‘abnormal’ if they did not adhere to this typical structure. No assessment of motility could be made in relation to the structural abnormalities seen. Contaminants in the dipper eggs were dominated by BDE 99, an unusual result considering the dippers aquatic lifestyle. PCB 153 was the most common PCB, and p,p’-DDE was the most abundant OCP; all other pesticides tested were below the limit of detection, as were the levels of all three steroid oestrogens. There was inter- and intra-nest variability between contaminant burdens in all eggs as well as the number of sperm trapped in the PVM, but there was no relationship between sperm number and the level of contaminant loadings in the eggs. There were no correlations between contaminants and oestrogenic activity measured in the water samples, and plasma VTG concentrations in bullheads or contaminant loadings in eggs, or indeed sperm number. Analysis of macroinvertebrate assemblages proved that the surface waters of the Tamar catchment were of ‘very good’ quality, even in close proximity to WwTWs effluent discharges.

Thesis advisor: Richard M. Kearney / This dissertation exposes the significance of ‘self-disruption’ in ethical development (the process of understanding how to flourish), especially as incited through conversation. By ‘self-disruption’, I mean the experience of being torn away from self-concern (which is a self-reflective enterprise) by something other. ‘Self-concern’ here refers to one’s attachment to one’s projects and plans—including the future self that one seeks to produce (qua preservation of its current identity). This study engages the history of ethical thinking, but it is not antiquarian. To make my case, I primarily rely on Emmanuel Levinas’s ethical metaphysics and critically interpret and draw from insights within 1) Kant’s account of the moral self, 2) Aristotle’s account of the virtuous soul, and 3) the teleological account of the self that we find in contemporary virtue ethics. My claim is that what is latent in each of these accounts is the pivotal role of having one’s attention arrested by ‘the other’, and that fostering this phenomenon belongs to the work of moral philosophy understood as moral cultivation. This research homes in on key discussions within Anglo-American ethics, particularly those that stem from the reevaluation of the nature and task of moral philosophy in the 20th-century. I am skeptical as to whether the resulting Aristotelian virtue ethics is as radical as its advocates claim, and I challenge its reliance on narrative coherence. I do not seek to deny the narrative dimensions of self-understanding, but I do want to underscore the ethical importance of welcoming their disruption. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Philosophy.

The increasing awareness of, and concern over, possible terrorist attacks using biological threats has increased attention and efforts for safeguarding U.S. agriculture. Whether intentional or unintentional, a biological event likely would cause substantial consequences well beyond the U.S. agricultural sector with considerable economic, social, and political costs. One significant impact would involve trade disruptions. This dissertation investigates biosecurity risk impacts with a focus on animal disease outbreaks using data from recent U.S. and Canada bovine spongiform encephalopathy (BSE) cases. An empirical study was carried out on the impact of the North American BSE cases. Using a time series approach, this study detected a significant structural break during the second half of 2003 when two BSE cases were confirmed in North America. Results showed that U.S. beef prices responded to the disruptions in cattle and beef trade caused by the BSE cases. The ban on beef and cattle imports from Canada and the ban on U.S. beef exports were major contributors to the fluctuation in beef prices. This showed that trade disruptions following the BSE discoveries in North America resulted in a supply shift and affected the movement of beef prices afterwards. The study did not find strong evidence that the 2003 North American BSE cases and associated trade disruptions greatly affected per capita beef consumption. In turn, a simulation study was conducted to examine the impact of major BSE outbreaks, associated trade disruptions, and demand shifts on U.S. welfare and the livestock industry. Six alternative scenarios were simulated and compared with the base scenario where there was no trade disruption and demand shift. The six scenarios consisted of various combinations of cattle and beef trade restrictions, livestock production adjustment, and beef demand shift. When beef and cattle trade, and market demand are greatly reduced in the wake of the BSE events in both Canada and the U.S., the impact on the U.S. welfare, meat trade, and regional livestock production would be the greatest. Beef price and production could reduce by 26% and 16% respectively. Regional impact on beef and livestock production would also be substantial in this case.

The most widespread evidence of environmental endocrine disruption in aquatic wildlife is from the feminising effects of oestrogenic endocrine disrupting compounds. However, very little is known of the effects of these chemicals (and others) upon freshwater molluscs found in our river and lakes. This thesis aimed at evaluating the effects of treated sewage effluent upon the reproductive and developmental cycle of a range of commonly found European freshwater gastropod molluscs. Initial mesocosm experiments were undertaken to test a range of mollusc species for their the suitability to the experimental system, and to test adult snails for their reproductive and developmental responses during spring to summer time. With suitable species chosen, P.corneus, a pulmonate species (sequential hermaphrodite), and V. Viviparus a prosobranch species (dioeious; separate sexes), full reproductive output was assessed over summertime and into autumn, along with developmental responses amongst the F1 generation of snails. My results suggest that the affects of effluent upon the reproductive and developmental cycle of P. corneus are strongly mitigated by both day length and water temperature (day length is most important with V. viviparus); results are sensitive to seasonal effects. However, at the peak of reproduction mid summer, P. corneus produced significantly more egg masses in effluent (100% effluent particularly), and more than one parameter of reproduction was affected. Egg masses were significantly smaller in effluent and contained significantly fewer eggs per mass. Further, there were indications that total reproductive output was increased (100% effluent significantly) in effluent compared to the river water control. In the prosobranch species V. viviparus results were less convincing, however, in 100% effluent a second reproductive peak occurred that was not seen in river water. Further, in both species there was a failure of certain reproductive parameters to observe the normal seasonal decline towards winter. In P. corneus there was a failure to stop producing egg masses in effluent, in V. viviparus the second reproductive peak in effluent could also threaten their survival with winter approaching. Developmental effects in the F1 generation were the subject of preliminary investigations, however, F1 V. viviparus demonstrated a higher than normal incidence of intersex (male and female developmental features) in effluent, and P. corneus appeared to have disturbed reproductive function (disturbance of both male and female reproductive function in the ovotestis). Therefore, both of these species of molluscs demonstrated that they are sensitive to the effects of effluent in mesocosm studies. However, we need to understand much more about their responses to effluent; in particular whether these effects could have repercussions for wild mollusc populations, and whether these effects could occur over more than one generation of snail threatening the survival of wild populations of molluscs.

The recent proliferation of personal wireless devices has led to the emergence of disruption-tolerant networks (DTNs), which are characterized by intermittent connectivity among some or all participating nodes and a consequent lack of contemporaneous end-to-end paths between the source and consumer of information. However, the success of DTNs as a communication paradigm is critically dependent on the following challenges being addressed: (1) How to enable popular but demanding applications, such as video-on-demand, to operate in such constrained network settings, and (2) How to incentivize individual devices to cooperate when network operation is only possible under, or greatly benefits from cooperation. In this dissertation, we present a novel set of protocols and develop real systems that effectively meet the above challenges. We make the following contributions: First, we design and implement a novel system for enabling high bandwidth content distribution in vehicular DTNs by leveraging infrastructure access points (APs). We predict which APs will soon be visited by a vehicular node and then proactively push content-of-interest to those APs. Our replication schemes optimize content delivery by exploiting Internet connectivity, local wireless connectivity, node relay connectivity and mesh connectivity among APs. We demonstrate the effectiveness of our system through trace-driven simulation and Emulab emulation using real taxi and bus traces. We further deploy our system in two vehicular networks: a fourteen AP 802.11b network and a four AP 802.11n network with smartphones and laptops as clients. Second, we propose an incentive-aware routing protocol for DTNs. In DTNs, routing takes place in a store-and-forward fashion with the help of relay nodes. If the nodes in a DTN are controlled by rational entities, such as people or organizations, the nodes can be expected to behave selfishly by attempting to maximize their utilities and conserve their resources. Since routing is inherently a cooperative activity, system operation will be critically impaired unless cooperation is incentivized. We propose the use of pair-wise tit-for-tat (TFT) as a simple, robust and practical incentive mechanism for DTNs. We then develop an incentive-aware routing protocol that allows selfish nodes to maximize their own performance while conforming to TFT constraints. / text