VictorJuiz/thesis huggingface dataset:
Personality Traits and Dynamic Variables Associated with Types of Aggression in High Security Forensic Psychiatric Inpatients

The Dangerous and Severe Personality Disorder (DSPD) initiative in England and Wales, underway since 2000, provides specialized care to high risk personality disordered individuals in prison and secure psychiatric facilities. Entry to the service, for a capacity nationwide total of approximately 300 individuals at four sites, is determined in part by risk (whether or not the individual is more likely than not to commit an offence that might be expected to lead to serious physical or psychological harm from which the victim would find it hard to recover). This requires valid procedures for assessing risk to determine individuals’ suitability for entry into and transfer out of the service. Yet little is known about the validity of current risk assessment tools and personality measures with the DSPD population. One of the studies reported, the first of its kind with the DSPD population, described a prospective evaluation of the predictive accuracy of the HCR-20, VRS, Static-99, and Risk Matrix 2000 with 44 admissions to the DSPD unit at a high security forensic psychiatric hospital. Consistent with hypotheses, all tools predicted damage to property. HCR-20 Total and scale scores predicted interpersonal physical aggression with structured final risk judgments also predicting repetitive (2+ incidents of) interpersonal physical aggression. HCR-20 Risk Management scores were significantly associated with imminence of interpersonal physical aggression. The second study described a prospective evaluation of the predictive accuracy of Psychopathy Checklist-Revised Factor and Facet scores as well as scores for Cluster B traits using the International Personality Disorder Examination with the same sample. Partial support for hypotheses was found. Only Borderline PD dimension scores predicted damage to property. Histrionic PD predicted interpersonal physical aggression, and Histrionic, Borderline, and Antisocial PDs all predicted repetitive interpersonal physical aggression. Factor 1 and Facets 1 and 2 were also significant predictors of interpersonal physical aggression. Factor 1 and Histrionic PD scores were also significantly associated with imminence of this type of aggression. Results were discussed in terms of the practical utility of these tools with high risk forensic psychiatric inpatients and the functional link (between personality disorder and violence) criterion for DSPD service entry.

Keywords: inpatient
aggression
personality
dynamic risk
Advisor: Ducharme, Joseph
Affective Processing in Major Depressive Disorder: Neuroanatomical Correlates of State and Trait Abnormailities

Patients with MDD demonstrate impairments in various components of affective processing, which are believed to persist in the remitted phase of the illness and are believed to underlie the vulnerability for future relapse. Despite advances in neuropsychiatry, the neuroanatomical site of action of various treatment modalities remains unclear, leaving clinicians without an algorithm to guide optimal treatment selection for individual patients. This thesis sought to characterize differences in brain activation during affective processing between MDD treatment responders (RS) and non-responders (NR) by combining clinical and neuroimaging variables in a repeat-measure functional magnetic resonance imaging (fMRI) investigation. We induced increases in positive and negative affect using visual stimuli under fMRI conditions in 21 MDD subjects and 18 healthy controls (HC). Based on previous neuroimaging investigations and preclinical animal data, we hypothesized that increased activation of the amygdala and the pregenual cingulate during negative affect induction (NAI), and decreased activity of the ventral striatum during positive affect induction (PAI), would differentiate ultimate NR from RS. Following the first scan, treatment with fluoxetine and olanzapine was initiated in the MDD group, with follow-up scans at one- and six-weeks thereafter. We hypothesized that decreases in depressive symptoms would be associated with decreased activation of the ventromedial prefrontal cortex (PFC) and amygdala during NAI and increased activation of the hippocampus during PAI. Eleven MDD subjects met criteria for clinical remission at study endpoint. Based on trait differences between MDD and HC, we hypothesized that differences observed during NAI would be limited to brain regions involved in regulation of the affective state, including the dorsolateral PFC and the anterior midcingulate cortex. The results of the analyses confirmed the a-prior hypotheses and additionally demonstrated differential activation of the insular, medial temporal, and premotor cortex during repeat PAI and NAI between HC, RS, and NR. These findings provide: i) a neuroanatomical target of successful antidepressant therapy during PAI/NAI; ii) a differential effect of depressive symptoms and dispositional affect on brain activation during PAI/NAI; and iii) an a-prior method to differentiate RS from NR, and iv) demonstrate the need for additional treatment to prevent relapse in the remitted state.

Keywords: major depressive disorder
neuroimaging
antipsychotic
antidepressant
olanzapine
fluoxetine
functional magnetic resonance imaging
response
affect
affective processing
Advisor: Kennedy, Sidney H.
McIntyre, Roger S.
Morphology, Phylogeny, and Evolution of Diadectidae (Cotylosauria: Diadectomorpha)

Based on dental, cranial, and postcranial anatomy, members of the Permo-Carboniferous clade Diadectidae are generally regarded as the earliest tetrapods capable of processing high-fiber plant material; presented here is a review of diadectid morphology, phylogeny, taxonomy, and paleozoogeography. Phylogenetic analyses support the monophyly of Diadectidae within Diadectomorpha, the sister-group to Amniota, with Limnoscelis as the sister-taxon to Tseajaia + Diadectidae. Analysis of diadectid interrelationships of all known taxa for which adequate specimens and information are known—the first of its kind conducted—positions Ambedus pusillus as the sister-taxon to all other forms, with Diadectes sanmiguelensis, Orobates pabsti, Desmatodon hesperis, Diadectes absitus, and (Diadectes sideropelicus + Diadectes tenuitectes + Diasparactus zenos) representing progressively more derived taxa in a series of nested clades. In light of these results, it is recommended herein that the species Diadectes sanmiguelensis be referred to the new genus Oradectes, Diadectes absitus be referred to the new genus Silvadectes, and Diasparactus be synonymized with Diadectes to produce Diadectes zenos. The phylogenetic hypothesis also reveals an evolutionary history leading to more efficient oral processing within the lineage, with successive nodes characterized by features indicative of a high-fiber diet. Within Diadectomorpha, diadectids constitute the majority of the species, suggesting that the advent of herbivory resulted in a relatively rapid radiation of species within the group, producing a clade that is markedly more species-rich than other, non-herbivorous diadectomorph taxa. An extensive review of Permo-Carboniferous tetrapod-bearing localities does, however, indicate that diadectids were not a key component of the fauna, discovered at fewer than 50 percent of the sites reviewed. These results counter suggestions that the evolution of Diadectidae led to the formation of the modern terrestrial ecosystem—where a large crop of herbivores supports a much smaller number of carnivores—during the Late Carboniferous and Early Permian.

Keywords: Diadectidae
diadectid
Carboniferous
Pennsylvanian
herbivory
Permian
Advisor: Reisz, Robert R.
Intercellular Feedback in Hematopoiesis

Despite the importance of inter-cellular (between cell) communication networks in regulating homeostasis in multicellular organisms, very little is known about their topology, dynamics, or functional significance. Inter-cellular communication networks are particularly relevant in stem cell biology, as stem cell fate decisions (self-renewal, proliferation, lineage specification) are tightly regulated based on physiological demand. Using human blood stem cell cultures as an experimental paradigm, we present an integrated experimental and computational approach to interrogate a hierarchically organized tissue network. We have developed a novel mathematical model of blood stem cell development incorporating cell-level kinetic parameters as functions of secreted molecule-mediated inter-cellular networks. By relation to quantitative cellular assays, our model is capable of predictively simulating many disparate features of both normal and malignant hematopoiesis, relating internal parameters and microenvironmental variables to measurable cell fate outcomes. Through integrated in silico and experimental analyses we show blood stem and progenitor cell fate is regulated by cell-cell feedback, and can be controlled non-cell autonomously by dynamically perturbing inter-cellular signalling. Furthermore, we have compiled genome-scale molecular profiles (transcriptome and secretome), publicly available databases, and literature mining to reconstruct soluble factor-mediated inter-cellular signalling networks regulating cell fate decisions. We find that dynamic interactions between positive and negative regulators, in the context of tuneable cell culture parameters, tip the balance between stem cell supportive vs. non-supportive conditions. The cell-cytokine interactions can be summarized as an antagonistic positive-negative feedback circuit wherein stem cell self-renewal is regulated by a balance of megakaryocyte-derived stimulatory factors vs. monocyte-derived inhibitory factors. To understand how the experimentally identified positive and negative regulatory signals are integrated at the intra-cellular level, we define a literature-derived blood stem cell self-renewal network wherein these extracellular signals converge for coherent processing into cell fate decisions. In summary, this work demonstrates the utility of integrating experimental and computational methods to explore complex cellular systems, and represents the first attempt to comprehensively elucidate non-autonomous signals balancing stem cell homeostasis and regeneration.

Keywords: stem cell
network
Advisor: Zandstra, Peter W.
Investigation of Atypical Binding Behaviours of the SH3 Domain of the Yeast Protein, Fus1p

The yeast Fus1p SH3 domain recognizes non-PXXP motif targets. This is contrary to most SH3 domains, which recognize PXXP-containing sequences. In this thesis, I characterized atypical binding of the Fus1p SH3 domain and provide insight into atypical SH3 domain interactions. I demonstrated that the Fus1p SH3 domain binds R(S/T)(S/T)SL-containing peptides derived from yeast proteins, Bnr1p and Ste5p. Through mutagenesis studies and comparisons to other SH3 domains, I showed that the Fus1p SH3 domain utilizes a portion of the same binding surface as typical SH3 domains. However, the PXXP-binding surface is debilitated in the WT domain by the substitution of unusual residues at three key conserved positions. By replacing these residues, I created a version of the Fus1p SH3 domain that binds a PXXP-containing peptide with extremely high affinity. Based on my data and analysis, I clearly delineated two distinct surfaces comprising the typical SH3 domain binding interface, and show that one of these surfaces is the primary mediator of almost every “non-canonical” SH3 domain-mediated interaction. I demonstrated that the Fus1p SH3 domain also binds Bni1p and Pea2p through yeast two-hybrid experiments, which do not contain either PXXP or R(S/T)(S/T)SL motifs. Through mutagenesis studies and two-hybrid experiments, I showed that the Fus1p SH3 domain utilizes a binding surface comprised of two sub-surfaces to interact with Bni1p and Pea2p. The sub-surfaces include the same portion of the binding surface in typical SH3 domains utilized in R(S/T)(S/T)SL binding of the Fus1p SH3 domain, and a novel binding site. I also showed that the protein binding surface of the Fus1p SH3 domain has a role(s) for efficient mating. Based on my findings in this thesis, I propose that dramatic alterations in SH3 domain specificity can be simply explained as a modulation of the binding strengths of sub-binding sites within the binding surface.

Keywords: SH3 domain
protein interactions
Advisor: Davidson, Alan R.
On the Permeabilisation and Disruption of Cell Membranes by Ultrasound and Microbubbles

Therapeutic efficacy of drugs depends on their ability to reach the treatment target. Drugs that exert their effect within cells are constrained by an inability to cross the cell membrane. Methods are being developed to overcome this barrier including biochemical and biophysical strategies. The application of ultrasound with microbubbles increases the permeability of cell membranes allowing molecules, which otherwise would be excluded, to enter the intracellular space of cells; a phenomenon known as sonoporation. This thesis describes studies aimed at improving our understanding of the mechanism underpinning sonoporation and of the exposure parameters affecting sonoporation efficiency. Cancer cells (KHT-C) in suspension were exposed to ultrasound and microbubbles – total of 97 exposure conditions. The effects on cells were assessed through uptake of cell-impermeable molecules (10 kDa to 2 MDa FITC-dextran), cell viability and microscopic observations of the plasma membrane using flow cytometry, colony assay and electron microscopy techniques. Sonoporation was a result of the interaction of ultrasound and microbubbles with the cell membrane. Disruptions (30-100 nm) were generated on the cell membrane allowing cell impermeable molecules to cross the membrane. Molecules up to 2 MDa in size were delivered at high efficiency (~70% permeabilisation). Sonoporation was short lived; cells re-established their barrier function within one minute, which allowed compounds to remain inside the cell. Following uptake, cells remained viable; ~50% of sonoporated cells proliferated. Sonoporation efficiency depended on ultrasound and microbubble exposure conditions. Microbubble disruption was a necessary but insufficient indicator of ultrasound-induced permeabilisation. The exposure conditions can be tailored to achieve a desired effect; cell permeability of ~70% with ~25% cell death versus permeability of ~35% with ~2% cell death. In addition, sonoporation depended on position in the cell cycle. Cells in later stages were more prone to being permeabilised and killed by ultrasound and microbubbles. This study indicated that sonoporation can be controlled through exposure parameters and that molecular size may not be a limiting factor. However, the transient nature may necessitate that the drug be in close vicinity to target cells in sonoporation-mediated therapies. Future work will extend the investigation into in vivo models.

Keywords: Ultrasound Therapy
Sonoporation
Drug Delivery
Microbubble contrast agent
Advisor: Burns, Peter N.
Experimental Investigations of Physical and Chemical Processes at Air-ice Interfaces

Studies were performed to characterize the physical nature of the air-ice interface, and to clarify its role in processes that occur there. A glancing-angle Raman probe was developed to monitor hydrogen bonding at atmospheric interfaces; we saw enhanced hydrogen-bonding on ice compared to on water. Using glancing-angle laser-induced fluorescence (LIF), we determined that small acids and bases dissociated to similar extents at air-water and air-ice interfaces, but aromatic compounds were less well solvated at air-ice interfaces, resulting in self-association even at low surface coverages. We measured uptake kinetics of organic compounds using LIF and Raman spectroscopy. The uptake kinetics can be adequately fit by a single-exponential growth equation, but in order to properly describe the self-association of aromatics observed at the air-ice interface, equations accounting for self-association should be incorporated into the uptake model. A simple model was developed for naphthalene which included terms for self-association; good fits to the observed growth of intensity from monomeric and self-associated naphthalene were obtained. Direct photolysis of aromatics was faster at air-ice interfaces than in bulk ice or aqueous solution. While red shifts in the absorption spectra of benzene and naphthalene at air-ice interfaces could explain their enhanced reactivity there, the enhanced anthracene photolysis kinetics on ice are likely due to enhanced absorption cross sections or photolysis quantum yields, or to a different photolysis mechanism there. Oxidation rates of aromatics by photo-formed hydroxyl radicals are suppressed at air-ice interfaces, but not in bulk ice. Similarly, gas-phase OH reacts rapidly with aromatics at air-water interfaces, but no reaction is observed at air-ice interfaces. Conversely, the reactivity of ozone toward phenanthrene is enhanced there. This is not due to temperature effects or to enhanced partitioning of ozone to ice. Ozonation of bromide is also more rapid at air-ice interfaces than at air-water interfaces at environmentally relevant bromide concentrations. This enhancement could be due to exclusion of bromide to the air-ice interface during freezing. The rapid reactions of ozone with bromide and phenanthrene at air-ice interfaces suggest that both reactions could be atmospherically important.

Keywords: Ice
QLL
Chemistry
Heterogeneous
Photolysis
Halogen activation
PAHs
Environmental Chemistry
Atmospheric Chemistry
Advisor: Donaldson, D. James
Holy Body, Wholly Other: Sanctity and Society in the Lives of Irish Saints

“Holy Body, Wholly Other: Sanctity and Society in the Lives of Irish Saints” focuses on the ways in which Ireland’s hagiographers portrayed holy otherness in the Lives of their subjects, using the Latin vitae, the vernacular bethada and the Lives containing both languages that survive from the 600s through the end of the fourteenth century. This study considers three broad themes, namely the transition of a sanctified essence into a holy body and the resulting alteration of an otherwise mortal form into a wholly other, the saintly prosecution of vengeance against those who wrong the body Christian and the enactment of hagiographical healing to bring the community of the faithful back to full integrity. These themes are analyzed within the social and cultural context of medieval Ireland, and are particularly compared with the biblical, apocryphal, heroic and legal writings of the Irish Middle Ages. Depictions of male and female saints are also compared and contrasted, as are the shifts in such depictions that occur between Latin and Irish narratives. Throughout the Lives the language of the laws of church and society inform the saint’s portrait, firmly situating these holy men and women within the sphere of medieval Ireland. Elements of Irish sanctity are drawn from vernacular heroic saga, but the predominant influence upon the Lives of Ireland’s sanctified is a powerful combination of apocryphal and canonical scriptures, demonstrating that Irish holiness can only have emanated from heaven. This combination, moreover, differs between male and female saints and between Latin and Irish Lives; holy men are modeled very strongly upon both Old and New Testament figures, while lady saints are painted more in the hues of imitatio Christi. Further, Latin vitae follow patterns capable of speaking to both Irish and non-Irish audiences alike, while vernacular Lives observe models that needed to appeal only to the Irish themselves.

Keywords: Ireland
Irish hagiography
hagiography
medieval
hagiology
saints
Irish saints
saints' lives
sanctity
vitae
bethada
saintly vengeance
miracles
saintly healing
holiness
holy body
saints' cults
early Ireland
Advisor: Dooley, Ann
Herren, Michael
Sources and Fate of Organochlorine Pesticides in North America and the Arctic

Atmospheric transport and air-water exchange of organochlorine pesticides (OCPs) were investigated in temperate North America and the Arctic. OCPs studied were hexachlorocyclohexanes (HCHs, a-, b- and g-isomers), components of technical chlordane (trans- and cis-chlordane, trans-nonachlor), dieldrin, heptachlor exo-epoxide and toxaphene. Air and water samples were taken on cruises in the Great Lakes and Arctic to determine concentrations and gas exchange flux direction and magnitude. The Henry’s law constant, which describes the equilibrium distribution of a chemical between air and water, was determined for several OCPs as a function of temperature and used to assess the net direction of air-water exchange. Air samples were collected in Alabama to investigate southern U.S. sources of OCPs. Chemical markers (isomers, and enantiomers of chiral OCPs) were employed to infer sources and trace gas exchange. Elevated air concentrations of toxaphene and chlordanes were found in Alabama relative to the Great Lakes, indicating a southern U.S. source. Profiles of toxaphene compounds in air were similar to those in soil by being depleted in easily degraded species, suggesting that soil emissions control air concentrations. Gas exchange fluxes in the Great Lakes indicated near-equilibrium between air and water with excursions to net volatilization or deposition. Net volatilization of a-HCH from the Arctic Ocean was traced by evasion of non-racemic a-HCH into the atmosphere.

Keywords: organochlorine pesticides
air-water gas exchange
toxaphene
hexachlorocyclohexanes
Advisor: Bidleman, Terry F.