Using structural equation modeling to assess two theoretical models that explain dropout

This study evaluated the relative fit of both Finn's (1989) Participation-Identification and Wehlage, Rutter, Smith, Lesko and Fernandez's (1989) School Membership models of high school completion to a sample of 4,597 eighth graders taken from the National Educational Longitudinal Study of 1988, (NELS:88), utilizing structural equation modeling techniques. This study found support for the importance of educational engagement as a factor in understanding academic achievement. The Participation-Identification model was particularly well fitting when applied to the sample of high school completers, dropouts (both overall and White dropouts) and African-American students. This study also confirmed the contribution of school environmental factors (i.e., size, diversity of economic and ethnic status among students) and family resources (i.e., availability of learning resources in the home and parent educational level) to students' educational engagement. Based on these findings, school social workers will need to be more attentive to utilizing macro-level interventions (i.e., community organization, interagency coordination) to achieve the organizational restructuring needed to address future challenges. The support found for the Participation-Identification model supports a shift in school social workers' attention from reactive attempts to improve the affective-interpersonal lives of students to proactive attention to their academic lives. The model concentrates school social work practices on the central mission of schools, which is educational engagement. School social workers guided by this model would be encouraged to seek changes in school policies and organization that would facilitate educational engagement. ^

Chilling damage in a changing climate in coastal landscapes of the subtropical zone: a case study from south Florida

Freeze events significantly influence landscape structure and community composition along subtropical coastlines. This is particularly true in south Florida, where such disturbances have historically contributed to patch diversity within the mangrove forest, and have played a part in limiting its inland transgression. With projected increases in mean global temperatures, such instances are likely to become much less frequent in the region, contributing to a reduction in heterogeneity within the mangrove forest itself. To understand the process more clearly, we explored the dynamics of a Dwarf mangrove forest following two chilling events that produced freeze-like symptoms, i.e., leaf browning, desiccation, and mortality, and interpreted the resulting changes within the context of current winter temperatures and projected future scenarios. Structural effects from a 1996 chilling event were dramatic, with mortality and tissue damage concentrated among individuals comprising the Dwarf forest's low canopy. This disturbance promoted understory plant development and provided an opportunity for Laguncularia racemosa to share dominance with Rhizophora mangle. Mortality due to the less severe 2001 event was greatest in the understory, probably because recovery of the protective canopy following the earlier freeze was still incomplete. Stand dynamics were static over the same period in nearby unimpacted sites. The probability of reaching temperatures as low as those recorded at a nearby meteorological station (≤3 °C) under several warming scenarios was simulated by applying 1° incremental temperature increases to a model developed from a 42-year temperature record. According to the model, the frequency of similar chilling events decreased from once every 1.9 years at present to once every 3.4 and 32.5 years with 1 and 4 °C warming, respectively. The large decrease in the frequency of these events would eliminate an important mechanism that maintains Dwarf forest structure, and promotes compositional diversity.

A framework for reliability assessment of ship hull damage under ship bow impact

Peer reviewed

A framework for reliability assessment of ship hull damage under ship bow impact

Peer reviewed

Dynamic method of stiffness identification in impacting systems for percussive drilling applications

Peer reviewed

Detection of seismic damage in buildings using time series analysis and pattern recognition

Peer reviewed

A framework for reliability assessment of ship hull damage under ship bow impact

Peer reviewed

Improved damage detectability in a wind turbine blade by optimal selection of vibration signal correlation coefficients

Piotr Omenzetter and Simon Hoell’s work within the Lloyd’s Register Foundation Centre for Safety and Reliability Engineering at the University of Aberdeen is supported by Lloyd’s Register Foundation. The Foundation helps to protect life and property by supporting engineering-related education, public engagement and the application of research.

Structural and Functional Analysis of the Caspase –dependent and –independent Domains of the X-linked Inhibitor of Apoptosis Protein in Inflammatory Breast Cancer Tumor Biology

Inflammatory breast cancer (IBC) is an extremely rare but highly aggressive form of breast cancer characterized by the rapid development of therapeutic resistance leading to particularly poor survival. Our previous work focused on the elucidation of factors that mediate therapeutic resistance in IBC and identified increased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein (XIAP), to correlate with the development of resistance to chemotherapeutics. Although XIAP is classically thought of as an inhibitor of caspase activation, multiple studies have revealed that XIAP can also function as a signaling intermediate in numerous pathways. Based on preliminary evidence revealing high expression of XIAP in pre-treatment IBC cells rather than only subsequent to the development of resistance, we hypothesized that XIAP could play an important signaling role in IBC pathobiology outside of its heavily published apoptotic inhibition function. Further, based on our discovery of inhibition of chemotherapeutic efficacy, we postulated that XIAP overexpression might also play a role in resistance to other forms of therapy, such as immunotherapy. Finally, we posited that targeting of specific redox adaptive mechanisms, which are observed to be a significant barrier to successful treatment of IBC, could overcome therapeutic resistance and enhance the efficacy of chemo-, radio-, and immuno- therapies. To address these hypotheses our objectives were: 1. to determine a role for XIAP in IBC pathobiology and to elucidate the upstream regulators and downstream effectors of XIAP; 2. to evaluate and describe a role for XIAP in the inhibition of immunotherapy; and 3. to develop and characterize novel redox modulatory strategies that target identified mechanisms to prevent or reverse therapeutic resistance.

Using various genomic and proteomic approaches, combined with analysis of cellular viability, proliferation, and growth parameters both in vitro and in vivo, we demonstrate that XIAP plays a central role in both IBC pathobiology in a manner mostly independent of its role as a caspase-binding protein. Modulation of XIAP expression in cells derived from patients prior to any therapeutic intervention significantly altered key aspects IBC biology including, but not limited to: IBC-specific gene signatures; the tumorigenic capacity of tumor cells; and the metastatic phenotype of IBC, all of which are revealed to functionally hinge on XIAP-mediated NFκB activation, a robust molecular determinant of IBC. Identification of the mechanism of XIAP-mediated NFκB activation led to the characterization of novel peptide-based antagonist which was further used to identify that increased NFκB activation was responsible for redox adaptation previously observed in therapy-resistant IBC cells. Lastly, we describe the targeting of this XIAP-NFκB-ROS axis using a novel redox modulatory strategy both in vitro and in vivo. Together, the data presented here characterize a novel and crucial role for XIAP both in therapeutic resistance and the pathobiology of IBC; these results confirm our previous work in acquired therapeutic resistance and establish the feasibility of targeting XIAP-NFκB and the redox adaptive phenotype of IBC as a means to enhance survival of patients.

Structural and Biochemical Dissection of the Trehalose Biosynthetic Complex in Pathogenic Fungi

Trehalose is a non-reducing disaccharide essential for pathogenic fungal survival and virulence. The biosynthesis of trehalose requires the trehalose-6-phosphate synthase, Tps1, and trehalose-6-phosphate phosphatase, Tps2. More importantly, the trehalose biosynthetic pathway is absent in mammals, conferring this pathway as an ideal target for antifungal drug design. However, lack of germane biochemical and structural information hinders antifungal drug design against these targets.

In this dissertation, macromolecular X-ray crystallography and biochemical assays were employed to understand the structures and functions of proteins involved in the trehalose biosynthetic pathway. I report here the first eukaryotic Tps1 structures from Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) with substrates or substrate analogs. These structures reveal the key residues involved in substrate binding and catalysis. Subsequent enzymatic assays and cellular assays highlight the significance of these key Tps1 residues in enzyme function and fungal stress response. The Tps1 structure captured in its transition-state with a non-hydrolysable inhibitor demonstrates that Tps1 adopts an “internal return like” mechanism for catalysis. Furthermore, disruption of the trehalose biosynthetic complex formation through abolishing Tps1 dimerization reveals that complex formation has regulatory function in addition to trehalose production, providing additional targets for antifungal drug intervention.

I also present here the structure of the Tps2 N-terminal domain (Tps2NTD) from C. albicans, which may be involved in the proper formation of the trehalose biosynthetic complex. Deletion of the Tps2NTD results in a temperature sensitive phenotype. Further, I describe in this dissertation the structures of the Tps2 phosphatase domain (Tps2PD) from C. albicans, A. fumigatus and Cryptococcus neoformans (C. neoformans) in multiple conformational states. The structures of the C. albicans Tps2PD -BeF3-trehalose complex and C. neoformans Tps2PD(D24N)-T6P complex reveal extensive interactions between both glucose moieties of the trehalose involving all eight hydroxyl groups and multiple residues of both the cap and core domains of Tps2PD. These structures also reveal that steric hindrance is a key underlying factor for the exquisite substrate specificity of Tps2PD. In addition, the structures of Tps2PD in the open conformation provide direct visualization of the conformational changes of this domain that are effected by substrate binding and product release.

Last, I present the structure of the C. albicans trehalose synthase regulatory protein (Tps3) pseudo-phosphatase domain (Tps3PPD) structure. Tps3PPD adopts a haloacid dehydrogenase superfamily (HADSF) phosphatase fold with a core Rossmann-fold domain and a α/β fold cap domain. Despite lack of phosphatase activity, the cleft between the Tps3PPD core domain and cap domain presents a binding pocket for a yet uncharacterized ligand. Identification of this ligand could reveal the cellular function of Tps3 and any interconnection of the trehalose biosynthetic pathway with other cellular metabolic pathways.

Combined, these structures together with significant biochemical analyses advance our understanding of the proteins responsible for trehalose biosynthesis. These structures are ready to be exploited to rationally design or optimize inhibitors of the trehalose biosynthetic pathway enzymes. Hence, the work described in this thesis has laid the groundwork for the design of Tps1 and Tps2 specific inhibitors, which ultimately could lead to novel therapeutics to treat fungal infections.

Sequence and Structural Determinants of Specificity Differences between Paralogous Transcription Factors

Transcription factors (TFs) control the temporal and spatial expression of target genes by interacting with DNA in a sequence-specific manner. Recent advances in high throughput experiments that measure TF-DNA interactions in vitro and in vivo have facilitated the identification of DNA binding sites for thousands of TFs. However, it remains unclear how each individual TF achieves its specificity, especially in the case of paralogous TFs that recognize distinct target genomic sites despite sharing very similar DNA binding motifs. In my work, I used a combination of high throughput in vitro protein-DNA binding assays and machine-learning algorithms to characterize and model the binding specificity of 11 paralogous TFs from 4 distinct structural families. My work proves that even very closely related paralogous TFs, with indistinguishable DNA binding motifs, oftentimes exhibit differential binding specificity for their genomic target sites, especially for sites with moderate binding affinity. Importantly, the differences I identify in vitro and through computational modeling help explain, at least in part, the differential in vivo genomic targeting by paralogous TFs. Future work will focus on in vivo factors that might also be important for specificity differences between paralogous TFs, such as DNA methylation, interactions with protein cofactors, or the chromatin environment. In this larger context, my work emphasizes the importance of intrinsic DNA binding specificity in targeting of paralogous TFs to the genome.

Effect of road quality in structural health monitoring under operational conditions

The effect of unevenness in a bridge deck for the purpose of Structural Health Monitoring (SHM) under operational conditions is studied in this paper. The moving vehicle is modelled as a single degree of freedom system traversing the damaged beam at a constant speed. The bridge is modelled as an Euler-Bernoulli beam with a breathing crack, simply supported at both ends. The breathing crack is treated as a nonlinear system with bilinear stiffness characteristics related to the opening and closing of crack. The unevenness in the bridge deck considered is modelled using road classification according to ISO 8606:1995(E). Numerical simulations are conducted considering the effects of changing road surface classes from class A - very good to class E - very poor. Cumulant based statistical parameters, based on a new algorithm are computed on stochastic responses of the damaged beam due to passages of the load in order to calibrate the damage. Possibilities of damage detection and calibration under benchmarked and non-benchmarked cases are considered. The findings of this paper are important for establishing the expectations from different types of road roughness on a bridge for damage detection purposes using bridge-vehicle interaction where the bridge does not need to be closed for monitoring.

A Delay Vector Variance based marker for an output-only assessment of structural changes in tension leg platforms

Although aspects of power generation of many offshore renewable devices are well understood, their dynamic responses under high wind and wave conditions are still to be investigated to a great detail. Output only statistical markers are important for these offshore devices, since access to the device is limited and information about the exposure conditions and the true behaviour of the devices are generally partial, limited, and vague or even absent. The markers can summarise and characterise the behaviour of these devices from their dynamic response available as time series data. The behaviour may be linear or nonlinear and consequently a marker that can track the changes in structural situations can be quite important. These markers can then be helpful in assessing the current condition of the structure and can indicate possible intervention, monitoring or assessment. This paper considers a Delay Vector Variance based marker for changes in a tension leg platform tested in an ocean wave basin for structural changes brought about by single column dampers. The approach is based on dynamic outputs of the device alone and is based on the estimation of the nonlinearity of the output signal. The advantages of the selected marker and its response with changing structural properties are discussed. The marker is observed to be important for monitoring the as- deployed structural condition and is sensitive to changes in such conditions. Influence of exposure conditions of wave loading is also discussed in this study based only on experimental data.

Structural and functional vulnerability to elevated pCO2 in marine benthic communities

The effect of elevated pCO2/low pH on marine invertebrate benthic biodiversity, community structure and selected functional responses which underpin ecosystem services (such as community production and calcification) was tested in a medium-term (30 days) mesocosm experiment in June 2010. Standardised intertidal macrobenthic communities, collected (50.3567°N, 4.1277°W) using artificial substrate units (ASUs), were exposed to one of seven pH treatments (8.05, 7.8. 7.6, 7.4, 7.2, 6.8 and 6.0). Community net calcification/dissolution rates, as well as changes in biomass, community structure and diversity, were measured at the end of the experimental period. Communities showed significant changes in structure and reduced diversity in response to reduced pH: shifting from a community dominated by calcareous organisms to one dominated by non-calcareous organisms around either pH 7.2 (number of individuals and species) or pH 7.8 (biomass). These results were supported by a reduced total weight of CaCO3 structures in all major taxa at lowered pH and a switch from net calcification to net dissolution around pH 7.4 (Omega calc = 0.78, Omega ara = 0.5). Overall community soft tissue biomass did not change with pH and high mortality was observed only at pH 6.0, although molluscs and arthropods showed significant decreases in soft tissue. This study supports and refines previous findings on how elevated pCO2 can induce changes in marine biodiversity, underlined by differential vulnerability of different phyla. In addition, it shows significant elevated pCO2-/low pH-dependent changes in fundamental community functional responses underpinning changes in ecosystem services.

Seawater carbonate chemistry, structural and chemical characteristics of the seagrass Thalassia testudinum in an situ CO2 enrichment experiment

Seagrasses commonly display carbon-limited photosynthetic rates. Thus, increases in atmospheric pCO2, and consequentially oceanic CO2(aq) concentrations, may prove beneficial. While addressed in mesocosms, these hypotheses have not been tested in the field with manipulative experimentation. This study examines the effects of in situ CO2(aq) enrichment on the structural and chemical characteristics of the tropical seagrass, Thalassia testudinum. CO2(aq) availability was manipulated for 6 months in clear, open-top chambers within a shallow seagrass meadow in the Florida Keys (USA), reproducing forecasts for the year 2100. Structural characteristics (leaf area, leaf growth, shoot mass, and shoot density) were unresponsive to CO2(aq) enrichment. However, leaf nitrogen and phosphorus content declined on average by 11 and 21 %, respectively. Belowground, non-structural carbohydrates increased by 29 %. These results indicate that increased CO2(aq) availability may primarily alter the chemical composition of seagrasses, influencing both the nutrient status and resilience of these systems.