bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of burden in spousal caregivers of individuals with Parkinson's disease
Authors:   , Lazarus Lewis A.
Published: July 2024

Parkinson's disease (PD) is a degenerative disease which affects approximately 1% of the population over the age of 55. PD is characterized by four typical symptoms which are: tremor, rigidity, slowness in active movements (bradykinesia), and disturbances in gait and balance. In addition, the deterioration in physical functioning is often accompanied with specific neurobehavioral changes such as, visuospatial and memory deficits. Since the disease is usually manifested in older adults, most patients with PD are married and when they become ill, it is likely that they will be cared for by a partner. This situation has implications for examining risk factors related to institutionalization, sources for intervention, and the costs of providing care in the home. Fifty-two spouses of individuals with idiopathic PD were administered a series of self-report questionnaires focusing on their own general health, coping style, level of depression, and burden. These spouses were also given an inventory examining their partner's level of dependency and neurobehavioral status. PD patients were administered a standardized, gross measure of dementia and a self-report measure of depression. The findings of this study indicated that, unlike caregivers of patients with Alzheimer's disease, spouses of PD patients were most burdened by the dependency of the patient in performing activities of daily living with the patient's cognitive impairment being less instrumental. There were no significant differences between husbands and wives in terms of subjective burden, depression, social problem-solving, and general physical health. Coping strategies did not significantly contribute to explaining the variance in burden scores, however, certain styles of coping were significantly and positively correlated with increases in subjective burden. Results are discussed in the context of previous studies of caregiver burden in other populations, and implications for future research efforts are presented.
Field deployable instrumentation for fast measurement of various atmospheric sulfur compounds in the parts per trillion range
Authors:   , Xu Nucleus H. , Bandy Alan R.
Published: July 2024

A field deployable instrumentation was developed for determining atmospheric dimethyl sulfide (DMS), dimethyl sulfoxide (DMSO), dimethyl sulfone (DMSO₂) and sulfur dioxide (SO₂) using atmospheric pressure ionization mass spectrometry (APIMS). Isotopically labeled analytes were used as internal standards. Detection limits below 1 part per trillion by volume (pptv) (S/N is >5 at 0.5 pptv background level) at one sample per second was achieved. Extensive laboratory studies were conducted to evaluate the instrument's sensitivity and stability as well as to simulate the real time measurements. This dissertation reports data from a first time deployment of the instrumentation at the South Pole in December 1998 and January 1999. Data from this deployment showed that this instrumentation had adequate performance in detecting all four species. In addition, methane sulfinic acid (MESA) was also observed in the atmosphere for first real time. The lowest concentrations of all four species occurred when the temperature inversion was strongest and greatest when the inversion was weakest or absent. This observation implies that the origin of these species is the free troposphere just above the inversion and not from local pollution. The most found concentrations for DMS, DMSO, DMSO₂, MESA and SO₂ were 0.7, 0.9, 1.2, 0.1 and 9 pptv. These field tests further suggest that our APIMS instrumentation be adequate for determining the fluxes of DMS and SO₂ by eddy correlation technique. Finally, in the South Pole data there was strong evidence that H₂O₂ and HNO₃ were observed as complexes with CO₃⁻. This implies that these species could be determined by APIMS if isotopically labeled standards of the species are used and a means of determining the blank is established.
Variation in vacancy rates, an empirical test using a new measure of intra-regional relocation
Authors:   , Murdoch Carter W. , Lester Bijou Yang
Published: July 2024

The role of intra-regional relocation in the real estate economic literature has been very limited due to the inaccessibility of accurate measures. This research serves as the first application, to the best of my knowledge, of a direct measure of the intent to relocate within a metropolitan statistical area in the proceeding 18 months. The traditional "American" approach and "European" approach relocation variables were tested to determine their explanatory power as to the variation in the intra-regional relocation rate. The results indicate that the traditional independent variables did in fact explain better than seventy-three percent of the variation in the intra-regional relocation rate. The new measure of intra-regional relocation was then applied to the award winning real estate finance and economics paper by Gordon et al. (1996). Thirteen MSA's were studied utilizing employment growth, unemployment, unexpected unemployment, treasury rate, type of industry, intra-regional relocation, gross rent, and the restrictiveness of regional development. The results indicate that the addition of the intra-regional relocation variable to the model developed by Gordon et al. vastly increased the explanatory power of the variation in vacancy rates during the declining phase of the real estate cycle.
Restriction mapping of mitochondrial DNA from cultured control and ethidium bromide resistant cells and new techniques for the analysis of DNA
Authors:   , Pirollo Kathleen
Published: July 2024

Restriction endonucleases were used to analyze themitochondrial DNA (mt DNA) from the following cultured cells: (1) control BHK cells (BHK(,21)/C(,13)); (2) these same cells transformed by Rous Sarcoma Virus (RSV) (C(,13)/B(,4)) and each of these made resistant to the intercalating dye ethidium bromide (EB); (DIAGRAM, TABLE OR GRAPHIC OMITTED... PLEASE SEE DAI) respectively. The mt DNA from LVG outbred Syrian hamsters was also analyzed and mapped. Comparison of the patterns generated with fifteen different enzymes showed no differences between the mitochondrial genomes of the four cell lines or the parental hamster indicating that in these cells EB resistance is not due to any large alterations in the mitochondrial genome. During these investigations we observed that the restriction of native Syrian hamster mt DNA by various endonucleases was inhibited, to differing degrees, by the presence of increasing concentrations of EB or propidium iodide (PI), which led to the development of a procedure for the study of drug-DNA interactions with native DNA. Enzyme inhibition was found to be more sensitive to the presence of PI than EB. The degree of inhibition was also found to be independent of the type of cut made by the enzyme. We found that the sequences 5'-G-C-3' and 5'-A-T-3' within the enzyme recognition sites were the most sensitive to the presence of the dyes in accordance with published data on the ease of dye binding to dinucleotides. The observation that not all the restriction sites for an enzyme within a DNA molecule appear to have equal sensitivity to the dye facilitates mapping of the mt genome. A modification of the nick translation procedure was developed whereby already restricted DNA was adsorbed onto a nitrocellulose square and then subjected to the normal nick translation procedure. The labeled DNA was then electrophoretically transferred from the nitrocellulose into a 1% agarose slab gel and autoradiographed. The binding of the DNA to the nirtocellulose apparently protects it from degredation into small fragments as is usually the case during nick translation in solution. This procedure was found to be sensitive enough to detect nanogram quantities of DNA with a specific activity of 1 x 10('5) cpm/ug DNA.
Functional analyses of microtubule severing proteins in the central nervous system
Authors:   , Qiang Liang , Baas Peter W
Published: July 2024

The configuration and behavior of microtubules are essential for the neuron to achieve its unique highly polarized cell shape. The mobility of microtubules renders a significant plasticity for their organization in developing neurons. However, only short microtubules are mobile, while long ones are stationary. To date, two microtubule-severing proteins, known as P60-katanin and spastin, have been identified to cut the long microtubules into short pieces in neurons. Despite the well-documented significance for microtubule organization during neuronal development, little evidence has been obtained regarding microtubule-severing. My dissertation investigates the functions of microtubule-severing proteins in developing neurons and the means by which they are regulated temporally and spatially. There are three specific aims. Aim 1: Investigate whether certain microtubule-associate proteins (MAPs) can provide microtubules protection against P60-katanin and identify the main protectors in the axon. Aim 2: Test whether spastin and P60-katanin participate differently in the formation of axonal branches. Aim 3: Directly test the "cut and run" model for microtubule reconfiguration during neuronal morphogenesis. Aim 1 includes two sets of studies. The first one utilized RFL-6 fibroblasts to investigate the capacity of individual MAPs to protect microtubules against P60-katanin. The second one utilized hippocampal neurons to identify the main axonal protectors. These studies revealed that tau, MAP2 and MAP4, but not MAP1b, provide strong protection for microtubules against P60-katanin. Tau was key protector in the axon. Aim 2 combined overexpression and knock-down strategies to compare the impact both of the severing-proteins on the formation of axonal branches and the microtubule array. We identified that there may be two different microtubule-severing modes ("P60-katanin-based" mode and "spastin-based" mode) that contribute to neuronal morphogenesis. Aim 3 utilized live-cell imaging to analyze the frequency of microtubule-transport corresponding to different levels of microtubule-severing. The microtubule-severing effect of extracellular signal inducing neuronal morphological changes was investigated via western blots. In addition, various spastin truncations were applied to show the microtubule-severing activity of the molecule is essential its impact on neuronal morphology. These studies validate the various predictions of microtubule "cut and run" and demonstrate the tight regulation of "cut and run" is critical to neuronal morphogenesis.
Development of a multi-layer metallization scheme using titanium nitride as a diffusion barrier
Authors:   , Kumar Nalin , Pourrezaei Kambiz
Published: July 2024

As the VLSI dimensions approach 1[mu]M and smaller size, reliability of the contact metallizations is degraded due to spiking and interdiffusion between silicon and aluminum. The deposition and properties of reactively sputtered thin films were investigated for their use in integrated circuits as a diffusion barrier in the Al/TiN/Ti/Si metallization scheme. The effect of deliberate introduction of oxygen and variation of deposition parameters such as applied substrate bias and nitrogen partial pressure on the film properties was studied, and the films were characterized by RBS, AES, XPS, SEM and TEM. Depending on the sputtering parameters, two distinctly different types (brown and golden) of titanium nitride films were obtained. The golden colored films (G films) have dense microstructure and high compressive stress, while the brown films (B films) have columnar grain structure with inter-grain voids, 5-8% oxygen contamination and very small intrinsic stress. A new model based on the microstructure of thin films for the generation of intrinsic stress in sputtered thin films is presented. To examine the diffusion barrier properties of these films, Kelvin cross structures were fabricated on SOS wafers with contact holes of sizes varying from 1.0[mu]m x 0.5[mu]m to 3.0[mu]m x 3.0[mu]m in size. Different metallization schemes such as Al/Si, Al/TiN/Si, Al/TiN/Ti/Si and Al/TiOxNy/Ti/Si in the temperature range 450-600[degrees]C were compared for contact resistivity and reliability during heat-treatment. The statistical data on the failure rate and contact resistance is presented. Also, the failure analysis of the failed contacts is described. It was found that the G films are better diffusion barriers for silicon diffusion than the B films, but their effectiveness is reduced due to the formation of Al3Ti compound during heat-treatment. The incorporation of oxygen in the TiN barrier film reduces the contact failure rate by grain boundary stuffing and by inhibiting the formation of Al3Ti. Based on the results of this research, a new metallization scheme (Al/TiN(B)/TiN(G)/Ti/Si is proposed and shown to have excellent thermodynamic and electric properties.
Optimization of the formability of 70:30 brass and the elimination of the wedge defect in cartridge cases
Authors:   , Schmidt Frederick Edward
Published: July 2024

Cartridge brass has served as a consummate model material to evaluate structure-property relationships. Compared to steel as a sheet metal for forming, brass is equal in engineering importance yet basic anisotropy, crystallographic texture and grain size relationships are unavailable. This compendium fulfills the need for mechanical property, texture and formability data for a comprehensive grain size 10 to 300 [mu]m range and processing conditions. The dissertation broadly develops the analysis of microstructure relationships through deformation for the Olsen, Swift and Fukui cup tests, and drawability of cartridge cases. Microhardness, a tenacious high resolution grid method for measuring strain, and differential scanning calorimetry were developed as quantitative procedures to assess formability. These methods significantly advance the analysis of brass and can be applied to any forming process, e.g. extrusion, forging, et al. A progressive deep-draw finite element model "DRAWNG" developed by Battelle for large ordnance artillery shells has been successfully modified for small caliber cartridge cases. Process simulation research to optimize both batch and progressive draw have been accomplished for conical dies in a double action transfer type press. The model incorporates material parameters for flow stress, work hardening, anisotropy and friction values as interface shear stress. An insidious cartridge case defect characterized by a wedge shaped slip plane has been investigated. The defects are oriented parallel to the length of the cartridge and initiate on the inside diameter as shear bands. During the high speed taper forming operation, a wedge defect is formed that exhibits a transgranular white layer that is conclusively adiabatic shear. The focus of a comprehensive deep-drawing optimization was the Small Caliber Ammunition Modernization Program (SCAMP). Two unique capabilities of the SCAMP manufacturing system are: (1) instantaneous on-line sampling at 1200 cases/minute and (2) eddy current inspection at six cartridge case locations. Statistical process optimization tests were executed to isolate the shear band formation directly with tool design, die friction and case cup metallurgy. These wedge defects were successfully eliminated by SCAMP process optimization and precise grain size control of the preform cartridge case cups.
The relationship between partner social support and premenstrual symptoms
Authors:   , Schwartz Cynthia B. , Lowe Michael R
Published: July 2024

The purpose of this study was to examine the relationship between premenstrual symptoms and partner social support for women who complain of premenstrual distress. Inverse associations were found between partner social support and both premenstrual and postmenstrual symptoms, as was predicted. However, contrary to the author's hypotheses, the postmenstrual association was larger; yet, this difference was not significant. Only the postmenstrual association remained significant when the association of relationship conflict was partialed out. The premenstrual relationship between partner support and symptoms was only significant for women who reported lower levels of symptomatology; however, the correlation was not significantly different than the correlation for the high symptom group. Also, contrary to the author's hypotheses, partner social support specific to the premenstrual phase was not significantly associated with premenstrual symptoms. In conclusion, women who perceive lower levels of available support from their significant others are more susceptible to experiencing distressing emotional and physical symptoms in both the premenstrual and postmenstrual phases. The implication for future research directions will be discussed.
The pre-ictal manifestations of oxygen neurotoxicity
Authors:   , Watanabe Tomas A. A. , Rapp Paul E
Published: July 2024

Symbolic measures of complexity provide a quantitative characterization of the sequential structure of symbol sequences. Promising results from the application of these methods to the analysis of electroencephalographic (EEG) and event-related brain potential (ERP) activity have been reported. Symbolic measures used thus far have two limitations, however. First, because the value of complexity increases with the length of the message, it is difficult to compare signals of different epoch lengths. Second, these symbolic measures do not generalize easily to the multichannel case. We address these issues in studies in which both single and multichannel EEGs were analyzed using measures of signal complexity and algorithmic redundancy, the latter being defined as a sequence-sensitive generalization of Shannon's redundancy. Using a binary partition of EEG activity about the median, redundancy was shown to be insensitive to the size of the data set while being sensitive to changes in the subject's behavioral state (eyes open versus eyes closed). The covariance complexity, calculated from the singular value spectrum of a multichannel signal, was also found to be sensitive to changes in behavioral state. Statistical separations between the eyes open and eyes closed conditions were found to decrease following removal of the 8 to 12 Hz content in the EEG, but still remained statistically significant. Use of symbolic measures in multivariate signal classification is described.
Viral model for tumor pathogenesis in CNS
Authors:   , Gordon Jennifer , Khalili Kamel
Published: July 2024

The human polyomavirus, JCV, is the causative agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal human demyelinating disease. PML results from the cytolytic destruction of oligodendrocytes, the myelin producing cells of the nervous system. JCV has also been shown to be tumorigenic in several animal models. Transgenic mice expressing the JCV early protein, T-antigen, develop poorly differentiated neural crest origin tumors. Intracerebral inoculation of JCV into newborn hamsters induces medulloblastomas, astrocytomas, and primitive neuroectodermal tumors. Further, inoculation of the virus into the brains of non-human primates, owl and squirrel monkeys, results in astrocytomas and glioblastoma multiforme. Several case reports have associated JCV with human CNS tumors in patients with concomitant PML, suggesting a possible role for JCV in the induction of human tumors. In vitro studies on cells generated from a JCV-induced hamster brain tumor have identified individual clonal populations of tumor cells which differ in their growth characteristics, morphology, and level of expression of JCV T-antigen. Hamsters intracerebrally inoculated with these clonal cells were subjected to MRI followed by multispectral tissue segmentation analysis in order to develop a non-invasive model for the imaging of CNS pathology. Further, two distinct lines of transgenic mice containing the coding sequence for JCV T-antigen under its own promoter were generated and characterized histologically. One such line developed inheritable neuroectodermal origin tumors suggestive of neuroblastomas, while the other line developed aggressive pituitary neoplasms. In one of the transgenic lines, an association between the transgene T-antigen, and the tumor suppressor protein, p53 has been demonstrated. Finally, JCV T-antigen was detected within an oligoastrocytoma of an immunocompetent, HIV-1 negative patient. The use of animal models of tumorigenesis induced by JCV to elucidate mechanisms of cellular transformation and to aide in the development of non-invasive diagnostic procedures is discussed. In addition, the potential role of JCV in induction of human tumors is addressed. Further, possible mechanisms by which JCV may exert its oncogenic potential via alteration of cellular growth control pathways in both humans and experimental animals is discussed.
Experimental study of soil erosion control systems
Authors:   , Rustom Rifat Naim Hashem , Weggel John R
Published: July 2024

A laboratory experimental rainfall/runoff/infiltration system has been constructed to evaluate the performance of different erosion control systems on steep slopes under reproducible, controlled conditions. The system can investigate the performance of erosion control systems during very early stages of a rainstorm. Thus the fundamental mechanism of how various erosion control systems work can be investigated. The system is comprised of a rainfall-producing module, a soil/erosion-control-system test flume, and a measurement/data collection system. The rainfall module can produce rainfall intensities approaching 254 mm/hr. (10 in/hr.) with an average spatial coefficient of variation of only 4% over a wide range of rainfall intensities. The experimental results obtained using the system represent measurements of surface runoff and sediment yield resulting from nominal rainfall intensities of 50, 125 and 200 mm/hr. (2, 5 and 8 in/hr.) on the upper reaches of a 1 on 2.5 and of a 1 on 4 slopes. Data include the characteristic rising limb of the S-hydrograph, the equilibrium discharge, and the typical recession curve after cessation of rainfall. Results are obtained for unprotected soil slopes and for slopes protected by 12 different natural and geosynthetic erosion control systems. The analysis is focused on the behavior of each erosion control system and how it acts to control raindrop impact and soil detachment, how it reduces flow velocities, and ultimately how it controls sediment detachment and loss from the test plot (short-term performance). The analysis is limited to erosion control systems on the upper reaches of unvegetated relatively steep slopes. The hydraulic characteristics of the erosion control systems were determined based on parametric models obtained for the rising and receding limbs of the overland flow hydrograph. Also, dimensionless retardance and friction coefficients for the erosion control systems investigated were derived from a modified version of Izzard's model for retardance coefficient.
Obesity and physical functioning in chronic kidney disease
Authors:   , Kibe Lucy Wachera , Sell Randall L
Published: July 2024

Background. Chronic kidney disease (CKD), obesity and disability are important public health concerns. Specific guidelines for obesity management and physical functioning screening for CKD patients are lacking. We examined differences in adiposity, body mass index (BMI) and physical functioning between CKD patients and healthy controls. Methods. Baseline data from the Chronic Renal Insufficiency (CRIC) study in 514 CKD patients and 232 controls age 21-79 years. Fat mass index and fat free mass index (FMI, FFMI (kg/m2)) were computed from whole body dual-energy X-ray absorptiometry. BMI was measured as weight(kg)/height(m)2. Physical functioning was scored using the Short Physical Performance Battery (SPPB). Using general linear models to control for age, gender and race, we compared FMI, BMI and FFMI between CKD patients and controls. Additional models tested group differences in FMI within BMI categories. Ordinal logistic regression models determined odds ratios (OR) of patients with CKD having low or medium (as opposed to high) SPPB scores. Results. Moderate CKD patients had 26% greater FMI, 12% higher BMI and 37% more FFMI than controls. Severe CKD patients had 17% more FMI, 7% higher BMI and 5% less FFMI compared to controls. Within normal, overweight and severe obese BMI categories, FMI did not differ between CKD patients and controls. However, in obese BMI category, FMI was significantly lower in severe CKD patients compared to controls (B=-0.17, p=0.004, 95%Cl (-0.28 to -0.06). CKD patients were more likely to have poor physical functioning compared to controls. However, the OR was modified by age and BMI category. With increasing age, and with increasing BMI, the effect of CKD on SPPB scores diminished. Therefore, younger patients, and patients with lower BMI had greater odds of poor physical functioning. Conclusions. CKD patients are more likely to have higher adiposity, be more obese and have poor physical functioning than controls. BMI is a reliable tool for monitoring obesity in patients with CKD. The effect of CKD on physical functioning is greater in younger patients and in less obese patients. Implications. Clinical, public health, and policy guidelines for obesity management and screening for declining physical functioning in CKD patients are needed.
Modeling quenching of precipitation strengthened alloys
Authors:   , Staley James Thomas , Doherty Roger D
Published: July 2024

Products of precipitation strengthened alloys characteristically lose their ability to develop peak properties as the rate of the quench from the solution temperature is reduced. An analytical model was developed which improved on a previous model to predict mechanical properties of such materials from time-temperature-property, TTP, C-curves and a cooling curve. Whereas the previous model was limited to predicting corrosion mode, strength, and hardness, the new model is capable of predicting toughness as well. Moreover, the revised model is inherently more accurate in predicting properties of material that is cooled under conditions that produce low properties. The model was evaluated using plate of an experimental Al-Cu-Li-Zr alloy and was related to a physical model. Effects on structure and properties of time at temperatures between the solvus and aging temperatures were determined using isothermal quenching techniques. Both strength and toughness measured in T8 temper progressively decreased with increasing time at temperature until they asymptotically approached a level which was temperature dependent. Loss in the ability to develop strength with increasing time at temperature was attributed to a loss in copper and lithium by precipitation of T1, TB, and [theta]', while loss in toughness was attributed to precipitation of T1 phase in grain and subgrain boundaries. The loss in toughness at particular strength levels depended on the isothermal quench temperature because the morphology of the T1 precipitate depended on temperature. The property, time, and temperature data were used to determine constants in a TTP C-curve equation. Properties after continuous cooling were predicted by summing effects which occurred at the isothermal quenching temperatures. In contrast to the previous model, this model recognized that the driving force for precipitation at each temperature was a function of the amount of solute remaining in solution and the amount that can precipitate at that temperature. The results indicate that the new model is an improvement and is useful for technological applications. As part of this investigation, a method was also developed for producing continuous-cooling-property, CCP, curves from TTP C-curves.
Self-perception of memory confidence among individuals with anxiety disorders
Authors:   , Zarro Jacqueline M.
Published: July 2024

Investigations examining memory functioning among individuals with obsessive-compulsive disorder (OCD) and social phobia (SP) have yielded divergent findings. Confidence in memory ability among those with OCD has been demonstrated to be poor relative to comparison groups, and there is some indication that this may be true for individuals with SP. The present study was conducted in order to further examine memory confidence among individuals with anxiety disorders. Thirty-one participants with OCD, twenty-nine with SP, and a comparison group of thirty-two individuals without anxiety (NAC) were recruited for this study. Two memory measures, the Inventory of Everyday Memory Experiences and the Memory Self-Efficacy Questionnaire were utilized. It was hypothesized that persons with OCD would report greater incidence of forgetting and poorer self-perception of memory ability in comparison to the SP and the NAC groups. It was further hypothesized that the SP group would not significantly differ from the NAC group. However, analyses revealed that individuals with SP demonstrated poorer self-perception of ability on more than half of the memory measure subscales compared to the NAC group, whereas the OCD group significantly differed from the NAC group on one third of the subscales. In addition, the two clinical groups did not differ significantly from one another on any of the subscales. After applying a second set of exclusion criteria to control for comorbidity of anxiety between the two clinical groups, significant differences between the SP and the NAC group remained, but the significant differences between the OCD and NAC groups disappeared. Clinical implications of these findings and suggestions for further research are discussed.
Systemic cohesion and flexibility
Authors:   , Gibson Theresa L. , McGuffin Patrick W.
Published: July 2024

Family functioning variables, such as systemic interactions, are believed to be at the core of the ontogenetics of physical child abuse, and such variables may serve as fundamental elements in future prevention efforts. However, there is a paucity of theoretically-based research addressing the relationship between variables of family functioning and the risk for physical child abuse. The Circumplex Model of family functioning (1979) is a model encompassing three core interactional dimensions of familial functioning: cohesion, flexibility, and communication. Using the Circumplex Model of family functioning, the current study examined families at high- and low-risk for physical child abuse (PCA). The goal of this study was to pinpoint systemic variables associated with child abuse potential by measuring the shared variance with variables of family functioning, so that future research may eventually move toward interventions based on the Circumplex Model for families at risk for child abuse. The sample included 84 parent and adolescent (age 12-18) pairs presenting at an urban mental health clinic in Richmond, Virginia. Subjects were family dyads, including adolescents and their parents or caregivers. Data obtained via questionnaires completed by parents and adolescents included: Family Adaptability and Cohesion Evaluation Scales (FACES-II), Parent-Adolescent Communication Scale (PACS), Family Inventory of Life Events and Changes (FILE), and Child Abuse Potential Inventory (CAPI; completed by parents only). A clinician-report of family functioning, the Clinical Rating Scale (CRS) was also obtained yielding information on the family's cohesion, flexibility, overall family functioning, and communication. The study purported that families at high risk for PCA would present with more dysfunctional interactional patterns as defined by the Circumplex Model of family functioning. Results suggest that several measures of the Circumplex Model and the CAPI share a small to moderate, but significant, amount of variance. While consistent and significant relationships emerged between these two measures utilizing parent-report, indicating that families at high-risk for child abuse were more likely to describe dysfunctional interactional patterns, adolescent-report of family functioning yielded few significant results. These preliminary findings serve to begin the building of a foundation for a family systems perspective to understanding child abuse.
A Tale of Two Regulators
Authors:   , Matthias Kathryn A. , Rest Richard F
Published: July 2024

Responsible for an estimated 820,000 new infections and health care costs totaling $1.1 billion every year in the United States alone, Neisseria gonorrhoeae is a leading cause of microbial-associated morbidity and is the second most commonly sexually-transmitted bacterial pathogen worldwide. Although the bacterial niche is relegated solely to the human host, the local environment (e.g. presence or absence of normal flora, immune effectors, hormones, etc.) and the interaction of the bacteria with host cells function to activate expression of genes that are required for growth and survival. Type IV pili (Tfp), for example, are important factors in initial cell-adhesion and are required for infectivity in vivo. In contrast, expression of Lipooligosaccharide (LOS) sialyltransferase (Lst), a surface-expressed enzyme that catalyzes LOS sialylation, is important for bacterial survival in the bloodstream or during acute infection when the innate immune response is initiated to promote bacterial clearance. Gaining an understanding of the molecular mechanisms by which these factors are regulated is critical for evaluating their potential as therapeutic vaccine targets. In this study, we examined the effects of two transcriptional regulators, CrgA and Rsp, on expression of Tfp and Lst. Deletion of either crgA or rsp resulted in lack of full induction of the primary pilin gene, pilE, in a manner that was not dependent on cell-adhesion. Rsp, specifically, was demonstrated to promote transcriptional activation by binding to an upstream activator sequence in the pilE promoter. Deletion of crgA, but not rsp, also induced overexpression of Lst, which correlated with enhanced survival in serum killing assays, a protective effect suggestive of diminished complement deposition conveyed by LOS sialylation. Although cervical cell-adhesion promoted lst down-regulation in the wild type strain, these effects were CrgA-independent, suggesting the presence of multiple lst-specific regulators and indicating that, while cell-adhesion plays a large role in control of Tfp production, expression of Lst is predominantly important in planktonic bacteria.
Identification and investigation of two novel MDM2 binding proteins
Authors:   , Vlatkovic Nikolina , Boyd Mark T.
Published: July 2024

The Mdm2 oncoprotein acts primarily by inhibiting the transcriptional activation function of the p53 tumor suppressor protein. Binding of Mdm2 to p53 is required for this effect. However, it has been shown that forms of Mdm2 exist that cannot bind to p53, but are still competent to transform cells. In addition, it has been shown that Mdm2 can bind to several other proteins including the cell cycle regulators E2F-1/DP1, pRB and p19Arf. Anteceding the identification of these binding proteins, our laboratory performed a yeast two-hybrid (Y2H) screen to identify novel Mdm2 binding proteins. A large a number of candidate interacting clones were identified. This thesis describes the development of a robust in vitro assay for testing candidate Mdm2 binding proteins and the initial characterization of two such proteins: the catalytic subunit of DNA polymerase &egr; and a novel protein MBP-1 (Mdm2 binding protein-1). Results of mapping studies for the regions of each of these proteins that are involved in these interactions are presented. We were able to confirm the interaction of the catalytic subunit of DNA polymerase &egr; with Mdm2 by co-immunoprecipitation, using both transfected cells andn from HeLa cell nuclear extract. Finally, initial attempts to examine the functional consequence(s) of the interaction between Mdm2 and the catalytic subunit of DNA polymerase &egr; are also presented.
Fracture behavior of boron/aluminum laminates at room and elevated temperatures
Authors:   , Madhukar Madhu S.
Published: July 2024

This thesis presents the results of a detailed and comprehensive research work, both experimental and analytical, on the deformation characteristics and fracture behavior of boron/aluminum composites at room and elevated temperatures. Emphasis has been placed on subjects associated with the load-deformation curves of center-notched laminates, including the elastic region, damage initiation, damage progression, notched strength, notch sensitivity, and failure mechanisms and processes. A variety of nondestructive and destructive experimental techniques are employed: the interferometric displacement gage to obtain the precise crack opening displacement; acoustic emission to monitor damage initiation and progression and determine the failure mechanisms and processes in real-time; and the conventional techniques to characterize the mechanical behavior of a material. Analytically, predictions of deformation characteristics and notch sensitivity are made. Existing models of fracture behavior in composites are reviewed in sufficient detail and predictions based on these models are compared with experiments. Special attention has been given on analyzing the deformation characteristics of unidirectional center-notched boron/aluminum. A new model is developed which incorporates the matrix nonlinearity. A detailed parametric analysis has been performed on this new model to determine the effect of numerous variables (e.g. matrix properties, fiber diameter, volume fraction, crack length and test temperature) on the stress concentration factors, inelastic zone length, crack opening displacement, damage initiation, and notch sensitivity. A very good agreement is obtained between the predictions of the proposed model and experiments. In this study the proper test methodology for new composite systems has been established. The applicability of a variety of analytical procedures to metal-matrix composites has been critically evaluated, and a comprehensive data base on the deformation characteristics of boron/aluminum composites is established. The results of this research also provide future directions for the study of MMC as well as offering improved criteria for tailoring material properties to meet the specific design requirements.
Sphingolipid mediated changes in cell growth in Saccharomyces cerevisiae
Authors:   , Swain Evelyn Joan , Clifford Jane , Nickels Joseph T
Published: July 2024

The studies described in this text have examined how sphingolipids regulate cell growth in the single cell eukaryote Saccharomyces cerevisiae . Towards this end, Chapters 1 and 2 have examined the mechanism of coordinate regulation of sphingolipid and sterol metabolism. Our studies included genetic and biochemical analyses of yeast mutant strains. In the case of Chapter 1, the temperature-sensitive sterol biosynthetic mutant, erg26-1, is the focus of study. Chapter 2 concentrates on the analysis of the putative sterol-binding protein, Arv1p, by utilizing a mutant strain lacking the ARV1 gene. Additionally, studies in Chapter 3 examine the impact of altered sphingolipid biosynthesis on glucose metabolism. For these studies we focus on elucidating the cellular mechanisms responsible for the observed genetic interaction between the RVS161 and SUR4 genes. The Rvs161p is an actin-cytoskeletal protein involved in endocytosis, and cells lacking Rvs161p exhibit growth defects on low concentrations of glucose. Sur4p is a very long chain fatty acid elongase required for proper sphingolipid biosynthesis, and deletion of the SUR4 gene suppresses the low glucose defects seen in the rvs161 mutant cells. These studies taken together provide important insights into basic eukaryotic cellular processes, that may lead to treatment modalities applicable to type II diabetes and cardiovascular disease.
The hepatitis B virus X protein elevates cytosolic calcium signals by modulating mitochondrial calcium uptake
Authors:   , Yang Bei , Bouchard Michael
Published: July 2024

Approximately 350 million individuals are chronically infected with the hepatitis B virus (HBV). Chronic HBV infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental function of HBx is the elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of IP3-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduces HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication.
Non-Operative Anterior Cruciate Ligament Rehabilitation for Individuals Participating in High Level Physical Activity
Authors:   , Fitzgerald G. Kelley , Snyder-Mackler Lynn
Published: July 2024

Non-operative anterior cruciate ligament rehabilitation programs have not been successful in returning physically active individuals to pre-injury physical activity levels. Two reasons for poor success of these programs are: (1) inadequate criteria for selecting appropriate patients for non-operative management, and, (2) lack of emphasis in rehabilitation programs on neuromuscular control of dynamic knee stability. The purpose of this project was to improve the success of non-operative anterior cruciate ligament management of physically active individuals by addressing the issues of patient selection and emphasis of neuromuscular control of dynamic knee stability in rehabilitation. Two studies were conducted in an effort to meet the project objectives. The first study was done to develop and test a clinical screening examination that could distinguish patients who were good candidates for non-operative management, from those who were not, after anterior cruciate ligament rupture. The results of this study indicated that the incidence of episodes of giving way at the knee, the score on a self report knee function survey, a self report rating of global knee function, and the score on a single leg, timed hop test could distinguish patients who were good candidates for non-operative management, from those who were not, after anterior cruciate ligament rupture. The second study was a randomized clinical trial to test the effectiveness of a treatment program designed to improve neuromuscular control of dynamic knee stability (perturbation training) in returning highly active individuals to pre-injury levels of function, after anterior cruciate ligament rupture. Only subjects who met the criteria for participation in non-operative management, based on the screening examination developed in the first study, participated in the randomized clinical trial. The results of the randomized clinical trial indicated that subjects receiving the perturbation training were almost five times more likely to succeed in returning to pre-injury activity levels than those who did not receive the perturbation training. Incorporating the screening examination and perturbation training procedures in non-operative anterior cruciate ligament rehabilitation programs significantly improved treatment success compared to previously reported non-operative treatment outcomes in physically active individuals with anterior cruciate ligament rupture. New treatment guidelines were established for non-operative management of anterior cruciate ligament rupture in physically active individuals, based on the results of this project.
The Molecular Mechanisms that Regulate Translational Repression Under Hypoxia and Glucose Deprivation
Authors:   , Thomas Jeff , Johannes Gregg J
Published: July 2024

The inefficient tumor vasculature and high glucose metabolism often found in tumor cells will likely result in tumor microenvironments that have limited availability of oxygen and glucose. Our studies showed that prolonged exposure to hypoxia (>16 hr, 1.0% 02) results in pronounced translational repression in PC3 cells. This delay in translational repression reflects the time needed for glucose to be depleted, since we found that both hypoxia and glucose deprivation (HGD) are required for translational repression. This HGF mediated translational repression is primarily modulated by elF2a phosphorylation, which in turn blocks ternary complex formation and suppresses translation by > 80%. The work presented in this thesis focuses on the molecular events that are responsible for the phosphorylation of elF2a during HGD. We found the PKRlike endoplasmic reticulum kinase (PERK) is responsible for the phosphorylation of elF2a during HGD. This PERK activation correlates with a 10-fold reduction of ATP compared to glucose deprived and glucose replete normoxic cells. Glucose addition or reoxygenation of cells exposed to HGD results in restoration of ATP levels, inactivation of PERK, reduction in elF2a phosphorylation, and translational recovery. To determine if the accumulation of mis-folded proteins in the lumen of the endoplasmic reticulum (ER) causes activation of PERK during HGD, PC3 cells were treated with the protein synthesis inhibitor cycloheximide prior to HGD. Our data demonstrates that inhibition of protein synthesis (which will prevent the accumulation of mis-folded proteins in the ER) did not prevent PERK activation during HGD. This data strongly suggests that PERK activation during HGD is independent of the accumulation of mis-folded proteins in the ER and is most likely a consequence of ATP depletion. Since tumors commonly have regions that are deprived of oxygen and glucose, understanding the pathways activated in response to these dual stresses may provide pertinent information on the growth and progression of tumors.