No description available.

Master of Science / Department of Biochemistry / Jianhan Chen / Paul E. Smith / Intrinsically disordered proteins have been shown to be important in many physiological processes, including cell signaling, translation, and transcription. They are also associated with cancer, and neurodegenerative diseases. The tumor suppressor p53 contains several disordered regions, including the C-terminal negative regulatory domain (NRD). In cancer the function of p53 has been shown to be repressed by S100B(ββ) binding to p53-NRD. Binding of S100B(ββ) blocks acetylation and phosphorylation sites in the p53-NRD, which leads to tetramer dissociation and prevents p53 activation. NMR studies have shown that p53-NRD binds S100B(ββ) in a stable α-helix conformation. Interestingly, despite the well-converged and apparent rigid nature of the NMR structure ensemble, a majority of intermolecular NOEs used to calculate the NMR ensemble are very weak (≥6 Å). The final NMR structures also contains unsatisfied buried charged residues at the binding interface. It’s plausible that the p53-S100B(ββ) complex is more dynamic than previously believed. The goal of the study is to determine the potential conformational heterogeneity in p53-S100B(ββ) complex using molecular modeling. For this, five diverse structures were selected from the 40-member NMR ensemble. For each initial conformation, we performed 100 ns molecular dynamic simulations in explicit solvent to explore the structure and dynamics of the p53-NRD in complex with S100B(ββ). Several analytical tools were used to characterize the p53-NRD conformation, including root-mean squared deviation (RMSD), root-mean squared fluctuation (RMSF), and residue helicity. The accuracy of the simulations was mainly assessed by comparing with experimental NOEs. The results show that, even though the ensemble is heterogeneous it satisfies 82% of the experimental NOEs. Clustering analysis further suggests that many conformational sub-states coexist for this complex, and individual clusters appear to satisfy only subsets of NOE distances. Importantly, the buried surface analysis demonstrates that the heterogeneous ensemble generated from MD provides similar shielding of key residues, which include post-translational modification residues needed for p53 activation. This study also demonstrates that atomistic simulations can provide important insights into structure and dynamics of IDPs for understanding their biological function.

The work in this thesis aims to gain fundamental understanding of several important types of disordered systems, including liquids, supercritical fluids and amorphous solids on the basis of extensive molecular dynamics simulations. I begin with studying the diffusion in amorphous zirconolite, a potential waste form to encapsulate highly radioactive nuclear waste. I find that amorphization has a dramatic effect for diffusion. Interestingly and differently from previous understanding, diffusion increases as a result of amorphization at constant density. Another interesting insight is related to different response of diffusion of different atomic species to structural disorder. I calculate activation energies and diffusion pre-factors which can be used to predict long-term diffusion properties in this system. This improves our understanding of how waste forms operate and provides a quantitative tool to predict their performance. I subsequently study the effects of phase coexistence and phase decomposition in Y-stabilized zirconia, the system of interest in many industrial applications including in encapsulating nuclear waste due to its exceptional resistance to radiation damage. For the first time I show how the microstructure emerges and evolves in this system and demonstrate its importance for self-diffusion and other properties. This has not been observed before and is important for better understanding of existing experiments and planning the new ones. I subsequently address dynamical properties of subcritical liquids and supercritical fluids. I start with developing a new empirical potential for CO2 with improved performance. Using this and other potentials, I simulate the properties of supercritical H2O, CO2 and CH4 and map their Frenkel lines in the supercritical region of the phase diagram. I observe that the Frenkel line for CO2 coincides with experimentally found maxima of solubility and explain this finding by noting that the Frenkel line corresponds to the optimal combination of density and temperature where the density is maximal and the diffusion is still in the fast gas-like regime. This can serve as a guide in future applications of supercritical fluids and will result in their more efficient use in dissolving and extracting applications. I extend my study to collective modes in liquids. Here, my simulations provide first direct evidence that a gap emerges and evolves in the reciprocal space in transverse spectra of liquids. I show that the gap increases with temperature and is inversely proportional to liquid relaxation time. Interestingly, the gap emerges and evolves not only in subcritical liquids but also in supercritical fluids as long as they are below the Frenkel line. Given the importance of phonons in condensed matter physics and other areas of physics, I propose that the discovery of the gap represents a paradigm change. There is an active interest in the dynamics of liquids and supercritical fluids, and I therefore hope that my results will quickly stimulate high-temperature and high-pressure experiments aimed at detecting and studying the gap in several important systems.

This study measures the electron-induced luminescence (cathodoluminescence) for various samples of fused silica. With a band gap of ~8.9 eV, visible and near-IR (NIR) luminescence occurs only if there are states (localized defect or trap states) within the forbidden band gap for electrons to occupy. A model is presented based on the electronic band structure and defect density of states—used to explain electron transport in highly disordered insulating materials—which has been extended to describe the relative cathodoluminescent intensity and spectral bands as a function of incident beam energy and current density, sample temperatures, and emitted photon wavelength. Tests were conducted on two types of disordered SiO2 samples, the first type containing two variations: (i) thin (~60 nm) coatings on reflective metal substrates, and (ii) ~80 μm thick bulk samples. Luminescence was measured using a visible range SLR CCD still camera, a VIS/NIR image-intensified video camera, a NIR video camera, and a UV/VIS spectrometer. Sample temperature was varied from ~295 K to 40 K. The results of these tests were fit with the proposed model using saturation dose rate and mean shallow trap energy as fitting parameters and are summarized below. First, each incident energy has a corresponding penetration depth, or range, which determines the fraction of energy absorbed in the material. In the thinner samples, the range exceeds the thickness of the sample; therefore, the intensity decreases with increasing energy. However, for the thicker samples, the range is less than the sample thickness and the intensity increases linearly with incident energy. Next, at low current densities, luminescent intensity is linearly proportional to incident current density through the dose rate. At very high current densities, saturation is observed. Finally, the overall luminescent intensity increased exponentially as T decreased, until reaching an optimum temperature, where it falls off to zero (as the model predicts). The spectra show four distinct bands of emitted photon wavelengths, corresponding to four distinct energy distributions of defect states within the band gap, each behaving differently with temperature. The response of each band to temperature is indicative of the extent to which it is filled.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2006. / Title from title screen (site viewed on Feb. 5, 2007). PDF text: 117 p. : ill. UMI publication number: AAT 3216343. Includes bibliographical references. Also available in microfilm and microfiche format.

<p>The overarching goal of this study is to enhance the current understanding of how college students with disordered eating experience alcohol. The study focuses on negative consequences, drinking behaviors, alcohol expectancies, and outcomes to a high-risk drinking prevention program. Taking a novel perspective to examine these problem behaviors, the current study uses a national sample of college students (N=8,095) who participated in an internet-based alcohol prevention program (AlcoholEdu for College, www.outsidetheclassoom.com). Multiple multivariate analyses were conducted. The results found that male and female college students with disordered eating are a high-risk drinking population. They reported higher rates of binge drinking, experienced more negative alcohol consequences, and engaged in more risky drinking behaviors and less protective drinking behaviors than college students without disordered eating. Additionally, most but not all, college students with disordered eating endorsed higher alcohol expectancies. College students with mild disordered eating also reported slightly worse outcomes to the program than students without disordered eating. The results suggest that college students with disordered eating should be targeted as a high-risk drinking population.</p> / Dissertation

No description available.

Thesis (Ph. D.)--Lehigh University, 2001. / Includes vita. Includes bibliographical references (leaves 97-108).

Objectives: The objective of this project is to examine the effectiveness of non-pharmacological intervention - behavioral therapy for ADHD children so as to determine whether this is as an alternative medical therapy for ADHD children. Background: Attention Deficit and Hyperactivity Disorder (ADHD) is the most common neurobehavioral disease in child. Symptoms can continue through adolescence and adulthood. Children suffering from ADHD disorders have symptoms of hyperactivity, failure to concentrate on activities and poor behavioral control. There are three sub-types of ADHD disorder, namely; hyperactive dominant type, inattentive dominant type and combined type. There are increasing numbers of children who are referred to child psychiatrists with an ADHD diagnosis internationally. In Hong Kong, ADHD contributes the majority of patients seen in child psychiatric clinics. The prevalence rate of ADHD in Hong Kong is 6.1% in primary school students and represents a similar rate to that reported worldwide. Methods: A literature search was conducted via Medline, PubMed and Google, to find relevant studies reviewing the effectiveness of non-pharmacological interventions for ADHD children. Result: Nine articles were identified that matched the inclusion criteria for this review. These studies concern behavioral interventions for ADHD children and include a range of behavioral and cognitive behavioral approaches. Two of these nine articles provided evidence that for pre-school children aged up to six years old, parent-training programs were effective in improving ADHD symptoms. Six of these nine articles provided evidence that for school aged children providing mixed Cognitive Behavioral Therapy (CBT) and Social Skills Training (SST) along with parallel group sessions for parents are beneficial to ADHD children. One of these nine articles provided evidence that CBT is beneficial in adopting appropriate coping skills in ADHD children. Conclusions: In views of the concerns about use of drug therapy for ADHD, behavioral intervention appears to be feasible and potentially effective as an alternative medicine for children with ADHD. / published_or_final_version / Public Health / Master / Master of Public Health

Time deficit in people with ADHD has been consistently found, but the underlying mechanism remains unclear. The present study aimed to investigate whether divided attention and selective attention are the causes for the deficit; and whether duration judgment performance was related to everyday temporal behaviour. 20 children with ADHD and 23 control children (mean age = 9 years 5 months) matched on age and IQ with no significant difference in working memory were tested. Experiment 1 used retrospective and prospective paradigms with arithmetic tasks. We compared time reproduction and arithmetic performances of the two groups across paradigms and found the expected interaction on the arithmetic performance but not the main effects of group or paradigm, and the interaction on time reproduction. Experiment 2 consisted of different event structures with simple motor tasks. We compared time reproduction of the two groups across structures and found the expected main effect of group and interaction effect but not main effect of structures. Furthermore, our results only provided limited support for the relationship between duration judgment and everyday temporal behaviour. The present findings suggest that aspects of attention remains promising as potential causes for time deficit in ADHD. / published_or_final_version / Educational Psychology / Master / Master of Social Sciences