Supply chain relationships in local government in the United Kingdom: An exploratory study

Local government in the United Kingdom is undergoing a period of transformational change. The Modernising Local Government white paper “In Touch with the People” (DETR 1998) has instructed local councils to obtain best value in the delivery of local services and this includes re-examining and challenging the use of in-house support services. This paper reports on an exploratory study examining the concept of relationship marketing focusing on the relationship that exists between Middlesborough Council’s laboratory service and its customers and to what extent government regulations have affected and changed attitudes and behaviours towards each other One of the key aims of the research is to challenge the linear nature of the way in which the stages of a relationship are considered in favour of a circular model of the development of relationships. This examination is set in the context of the “enforced” nature of local authority relationships. Research findings indicate that the nature of the relationship can been seen as cyclical rather than linear and the nature of the relationship in terms of social distance needs to be reevaluated in a context where social distance itself remains a significant factor for local government employees as a mean of avoiding the scrutiny of inter-personal relationships.Relationship Marketing, United Kingdom, Local Government, Stages in the Relationship

Biography of Margaret Ann Prendergast

The following biography of Margaret Ann Prendergast reveals a life of a woman who remained in the shadow of her family. She appeared only infrequently in compari­son to the male predominance that was customary of the early and middle 19th Century. A glimpse at her character and .J tyle of livine is seen best through her male counterparts. These would include her maternal grandfather, Joachim Hartstein, her father, Tobias Vanzant Gray and her husband of 16 years, Pierce Butler Prendergast.https://digitalcommons.georgiasouthern.edu/sav-bios-lane/1151/thumbnail.jp

Doctor of Philosophy

dissertationPlatinum-based chemotherapy is the standard-of-care for non-small cell lung cancer. As with other chemotherapies, not all patients respond positively to treatment and almost all patients will develop chemotherapy-resistant disease. Using the KrasG12D-driven mouse model of lung adenocarcinoma, our lab identified upregulation of p53-induced with a death domain isoform 1 (Pidd1) in resistant tumors in response to long-term cisplatin chemotherapy treatment. Remarkably, PIDD1 expression in vitro induces p53-dependent resistance to cisplatin as well as other DNA, damaging chemotherapeutics. PIDD1 expression leads to assembly of large molecular weight complexes named PIDDosomes. The Caspase-2-PIDDosome is critical for PIDD1-induced chemotherapy resistance. Our lab demonstrated that the Caspase-2-PIDDosome dynamically regulates p53 activity via proteolytic modification of MDM2, the master negative regulator of p53. In unstressed cells, MDM2 binds to and ubiquitinates p53, targeting it for proteasomal degradation. Upon stress, Pidd1 is upregulated, ultimately leading to formation of the Caspase-2-PIDDosome, and subsequent Caspase-2 activation. Activated Caspase-2 cleaves MDM2 into two fragments: p60 and p30. p60 maintains the ability to bind p53, but cannot ubiquitinate p53, resulting in increased p53 protein stability. The role of the Caspase-2-PIDDosome in regulating the p53-MDM2 feedback loop is not well characterized in tumorigenesis or chemotherapy response. In this study, I utilize the KrasG12D-driven mouse model of lung adenocarcinoma to investigate tumorigenesis and chemotherapy response in Caspase-2-deficient and Pidd1-deficient mice. These data demonstrate that Caspase-2 is a tumor suppressor in lung adenocarcinoma primarily by inhibiting cell proliferation. Caspase-2-deficient tumors respond to chemotherapy; however, rapid tumor cell proliferation following treatment reduces the long-term therapeutic efficacy of chemotherapy. Unexpectedly, Pidd1-deficiency does not impact lung tumorigenesis or chemotherapy response. Mechanistic investigation in vitro revealed that ATM phosphorylation of PIDD1 is critical for Caspase-2-PIDDosome assembly, Caspase-2-mediated MDM2 cleavage, cell cycle arrest, and resistance to DNA damaging agents. This pathway is not modulated by exogenous MDM2 or its cleavage product p60. Further, pharmacological inhibition of the p53-MDM2 negative feedback-loop using nutlin-3 does not alter PIDD1-induced growth arrest or cisplatin resistance. Together these findings demonstrate that Caspase-2 and PIDD1 have distinct functions in vivo and elucidate the Caspase-2-PIDDosome signaling network in p53-dependent response to DNA damage

Closed-drift thruster investigations

Recent data obtained from a second generation closed-drift thruster design, employing Hall current acceleration is outlined. This type device is emphasized for electric propulsion for geocentric mission applications. Because geocentric mission profiles are best achieved with a specific impulse range of 1000 to 2000 s, closed-drift thrusters are well suited for this application, permitting time payload compromises intermediate of those possible with either electrothermal or electrostatic devices. A discussion is presented of the potential advantages of using a 1000 to 2000 s device for one way orbit raising of nonpower payloads. Because closed-drift thruster operation is not space charge limited, and requires only one power circuit for steady state operation, their application is technically advantageous. Beam, plasma and thrust characteristics are detailed for a range of operating conditions

Are cocaine-seeking “habits” necessary for the development of addiction-like behavior in rats?

Drug self-administration models of addiction typically require animals to make the same response (e.g., a lever-press or nose-poke) over and over to procure and take drugs. By their design, such procedures often produce behavior controlled by stimulus-response (S-R) habits. This has supported the notion of addiction as a “drug habit”, and has led to considerable advances in our understanding of the neurobiological basis of such behavior. However, for addicts to procure drugs, like cocaine, often requires considerable ingenuity and flexibility in seeking behavior, which, by definition, precludes the development of habits. To better model drug-seeking behavior in addicts we first developed a novel cocaine self-administration procedure (the Puzzle Self-Administration Procedure; PSAP) that required rats to solve a new puzzle every day to gain access to cocaine, which they then self-administered on an Intermittent Access (IntA) schedule. Such daily problem-solving precluded the development of S-R seeking habits. We then asked whether prolonged PSAP/IntA experience would nevertheless produce ‘symptoms of addiction’. It did, including escalation of intake, sensitized motivation for drug, continued drug use in the face of adverse consequences and very robust cue-induced reinstatement of drug-seeking, especially in a subset of ‘addiction-prone’ rats. Furthermore, drug-seeking behavior continued to require dopamine neurotransmission in the core of the nucleus accumbens (but not the dorsolateral striatum). We conclude that the development of S-R seeking habits is not necessary for the development of cocaine addiction-like behavior in rats

Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75023/1/j.1460-9568.1999.00576.x.pd

The role of dopamine in the accumbens core in the expression of Pavlovian‐conditioned responses

The role of dopamine in reward is a topic of debate. For example, some have argued that phasic dopamine signaling provides a prediction‐error signal necessary for stimulus–reward learning, whereas others have hypothesized that dopamine is not necessary for learning per se , but for attributing incentive motivational value (‘incentive salience’) to reward cues. These psychological processes are difficult to tease apart, because they tend to change together. To disentangle them we took advantage of natural individual variation in the extent to which reward cues are attributed with incentive salience, and asked whether dopamine (specifically in the core of the nucleus accumbens) is necessary for the expression of two forms of Pavlovian‐conditioned approach behavior – one in which the cue acquires powerful motivational properties (sign‐tracking) and another closely related one in which it does not (goal‐tracking). After acquisition of these conditioned responses (CRs), intra‐accumbens injection of the dopamine receptor antagonist flupenthixol markedly impaired the expression of a sign‐tracking CR, but not a goal‐tracking CR. Furthermore, dopamine antagonism did not produce a gradual extinction‐like decline in behavior, but maximally impaired expression of a sign‐tracking CR on the very first trial, indicating the effect was not due to new learning (i.e. it occurred in the absence of new prediction‐error computations). The data support the view that dopamine in the accumbens core is not necessary for learning stimulus–reward associations, but for attributing incentive salience to reward cues, transforming predictive conditional stimuli into incentive stimuli with powerful motivational properties. Ongoing debate exists about dopamine’s exact role in reward‐related processes. We took advantage of natural individual variation in the degree to which reward cues are attributed with motivational value, and asked whether dopamine in the core of the nucleus accumbens is necessary for the performance of two forms of Pavlovian conditioned approach behavior ‐ one in which the cue acquires powerful motivational properties (sign‐tracking) and another related one in which it does not (goal‐tracking). We found that blocking dopamine transmission within the core impaired the expression of sign‐tracking responses, but not goal‐tracking responses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93510/1/j.1460-9568.2012.08217.x.pd

The psychology and neurobiology of addiction: an incentive–sensitization view

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75373/1/j.1360-0443.95.8s2.19.x.pd

Amphetamine-evoked gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK/MAPK signaling cascade

The environmental context in which psychostimulant drugs are experienced influences their ability to induce immediate early genes (IEGs) in the striatum. When given in the home cage amphetamine induces IEGs predominately in striatonigral neurons, but when given in a novel test environment amphetamine also induces IEGs in striatopallidal neurons. The source of the striatopetal projections that regulate the ability of amphetamine to differentially engage these two striatofugal circuits has never been described. We report that transection of corticostriatal afferents selectively blocks, whereas enhancement of cortical activity with an ampakine selectively augments, the number of amphetamine-evoked c- fos -positive striatopallidal (but not striatonigral) neurons. In addition, blockade of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling cascade preferentially inhibits the number of amphetamine-evoked c- fos -positive striatopallidal neurons. These results suggest that glutamate released from corticostriatal afferents modulates the ability of amphetamine to engage striatopallidal neurons through an ERK/MAPK signaling-dependent mechanism. We speculate that this may be one mechanism by which environmental context facilitates some forms of drug experience-dependent plasticity, such as psychomotor sensitization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66343/1/j.1471-4159.2004.02712.x.pd

Vitals rates and seasonal movements of two isolated greater sage-grouse populations in Utah\u27s West Desert

Declines in greater sage-grouse (Centrocercus urophasianus; hereafter, sage-grouse) populations in Utah over the last century parallel range-wide trends. However, little is known about the ecology of sage-grouse populations that inhabit Utah’s naturally fragmented habitats. Utah’s West Desert sage-grouse populations occupy sagebrush (Artemisia spp.) habitats that are geographically separated by the Great Salt Lake, and largely confined to the Sheeprock and Deep Creek watersheds. From 2005 to 2006, we monitored sage-grouse that were radio-collared in each watershed to determine the factors affecting the vital rates in these isolated populations. Livestock grazing by domestic cattle was the dominate land use, and mammalian predator control for livestock protection was conducted in both watersheds. Corvid control was conducted only in the Sheeprock watershed. During the study, we identified 6 leks that had not been previously documented. Seasonal migration patterns for individual radio-collared sage-grouse in both watersheds varied across the sites. Habitat structure metrics were similar at brood-rearing and random sites for both areas. Nesting and brood success and the ratio of chicks per successful brood were higher for both populations in 2005 than 2006. We attributed these annual differences in vital rates to seasonal variation in precipitation. Spring precipitation in 2005 was twice the 30-year average following a 5 year drought. However, chick recruitment estimates for both populations regardless of year were lower than reported in the published literature. Adult sage-grouse survival rate estimates in Sheeprock and Deep Creek watersheds were lower and higher, respectively, than published reports indicated. These differences may reflect a difference in meso-predators communities. Sage-grouse conservation strategies in both areas should continue to emphasize protection of brood-rearing and seasonal habitat, but the risk of population extirpation as a consequence of extended droughts predicted by climate change models and the invasion of small meso-predators may remain problematic for these populations