bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitogen induced changes in MAPK signal transduction pathways as a function of age
Authors:   , Li Min , Sierra Felipe
Published: July 2024

It has long been observed that the proliferative capacity of aged lymphocytes decreases with aging. This decreased proliferation correlates with a diminished IL-2 production, which is an important growth factor not only for T cells, but also for B cells. Several signaling pathways, including Ca²⁺/PKC and MAPK, are activated upon T or B cell receptor ligation. Specifically, MAPK pathways are known to be critical for the proliferation of both T and B cells. The objective of my thesis project is to understand the molecular mechanisms underlying the decreased IL-2 production and lymphocyte proliferation observed with aging. As our main approach, we have specifically explored the effect of age on the activation of two MAPK pathways of signal transduction, the ERK and JNK pathways. Limited studies in the literature suggest the existence of some early signaling defects with age in T lymphocytes activated via the TCR/CD3 complex. These early events can be circumvented through the use of PMA plus CaI, which lead to a rise in intracellular free calcium and activation of PKC, respectively. It has been shown that the age-related defect in both T and B cell proliferation is still apparent when cells are stimulated by PMA plus CaI, suggesting the existence of other defects located downstream of the early events. We hypothesise that at least some of these further defects are still located within the signal transduction cascades, but further downstream than previously described. As a model, we have used both rat and mouse splenic lymphocytes, which were stimulated with PMA plus A23187. Thus, our focus was mainly on events that occur downstream of receptor-proximal events. Our results confirm our hypothesis that splenic lymphocytes from old rats and mice have disturbances in both the ERK and JNK signal transduction pathways, which are evident even when the receptor-proximal defects are bypassed. Furthermore, we have identified defects in MEK activation, as well as downstream of the ERK and JNK kinases, at the level of the transcription factors c-Jun and ATF-2. Further studies conducted in purified T- or B-cell-depleted lymphocytes from young animals indicate that there is no difference in their capacity to respond to PMA plus CaI induction. Based on these results, we predict that the defects in MAP kinase activity we have observed in mixed lymphocytes affect both T and B cells. However, extrapolation of data from the literature also allows us to predict that the T cell compartment is likely to be more affected than B cells, because function of the B cell compartment is only marginally affected by aging. The decrease in MAPK activation during aging is likely to play a significant role in the diminished lymphoproliferation observed in older individuals.
Parental psychosocial correlates of mealtime behavior in children with cystic fibrosis
Authors:   , Kaplan Mara , Graham Julie Landel
Published: July 2024

Research indicates that children with cystic fibrosis (CF) demonstrate problematic mealtime behaviors and dietary compliance difficulties. Also, studies have described the prevalence of certain parental psychosocial factors within chronically ill and/or CF populations. However, available research has not yet assessed the relationship between mealtime behaviors of parents and their children with CF and parental psychosocial functioning. Moreover, few investigations have examined the direct impact of parent and child mealtime behaviors on nutritional status of children with CF. Parental psychosocial factors related to mealtime behaviors in families of children with CF were examined. Relationships between mealtime behavior problems and nutritional and growth status were also evaluated. Fifty parents and their children partook in a 10-minute mealtime observation and parents completed a battery of psychosocial questionnaires, as well as provided three day food logs of their child's calorie intake. Children were in very good health and parents generally reported functioning well, however they demonstrated limited knowledge of behavioral management skills. Parents did report significantly worse perceptions of their children's mealtime behavior compared to a normative sample. Observational data showed that parents and children in this sample generally displayed appropriate mealtime behavior, however, parents tended not to engage in any positive reinforcement during meals. Multiple regression analyses revealed that specific parent and child factors may be predictive of specific observed and perceived mealtime interactions. Hypotheses regarding relationships between mealtime behaviors and food intake and growth status were only partially supported. Exploratory analyses are discussed and clinical implications are provided.
Evolution of recrystallization textures in an aluminum alloy
Authors:   , Kashyap Kishore T. , Doherty Roger D
Published: July 2024

The theory for the evolution of recrystallization textures has, however been controversial. There are two rival hypotheses to explain the evolution of recrystallization textures, one is the oriented nucleation hypothesis and the other is the oriented growth hypothesis. The present work attempts to resolve this dispute by studying the evolution of cube texture in a commercial purity aluminum alloy, ALCOA's PO815. The electron backscattering pattern (EBSP) technique has been employed to determine the crystallographic orientation of individual recrystallizing grains. Recrystallization of the warm deformed aluminum was selected for detailed study. Very high densities of cube grains were formed in the early stages of recrystallization. For example at 10% recrystallization 76% of cube nuclei were found compared to the expected random frequency of 4%. Cube oriented new grains were no larger than the new grains of other orientations. Even in the fully recrystallized condition the cube grains were no larger in size compared to grains with other orientations. The cube grains were found to nucleate within cube oriented deformation bands. The bands of cube oriented deformed material that were the source of the cube nuclei were spaced about 200-300 [mu]ms apart-a spacing comparable to the final recrystallized grain size. The orientation of the deformed material adjacent to the cube bands was also studied but no significant correlation could be found. There was also no clear correlation between those cube bands that gave many cube nuclei and the orientation of the adjacent deformed material. In particular the S-component which is 40[degrees] about <111> from cube was not particularly associated with cube bands giving many nuclei. The intensity of cube texture measured by EBSP in the partially recrystallized sample gave pole figures and ODFs that showed a strong cube texture intensity that was actually somewhat higher than the intensity observed in the fully recrystallized samples measured either by EBSP or X-ray methods. This fall in cube intensity may be associated with the result, obtained here from studies of recrystallization kinetics, that further nucleation of new grains occurred during the later stages of recrystallization. (Abstract shortened with permission of author.).
Fraud risk assessments of independent auditors
Authors:   , Kozloski Thomas M. , Jaenicke Henry R.
Published: July 2024

Generally accepted auditing standards require that, during the planning stage of the audit, the auditor consider and assess the likelihood that the financial statements are materially misstated. Research has indicated that auditors may have limited experience with financial statements that are materially misstated. This may be particularly true for financial statements that are misstated due to fraud. Research in psychology has suggested that, when faced with a novel, difficult, or ill-structured problem, individuals may use analogical reasoning (reasoning by analogy) as a problem-solving tool. An individual who uses analogical reasoning as a strategy to attempt to solve a problem (the target analog) will attempt to retrieve from memory a similar problem encountered or solved in the past (the source analog). Then, based on the perceived similarity of source and target, characteristics of the source may then be mapped to the target in an attempt to make inferences about the target problem and its solution. This study examines, in an experimental setting using practicing auditors as participants, the influence of surface and structural similarity features on analogical transfer from a source analog to a target analog in the context of the auditor's assessment of the risk of fraud. The effect of increased levels of risk in the target analog on analogical transfer is also examined. Results of the study indicate that auditors will transfer knowledge regarding the assessment of the overall risk of fraudulent financial reporting from a surface-similar source fraud risk assessment to a target fraud risk assessment. As expected, auditors did not exhibit transfer relating to the overall risk of fraudulent financial reporting when provided with a structurally similar source analog. Auditors did not transfer knowledge regarding the audit planning response to the fraud risk assessment. Increased fraud risk in the target analog did not influence auditors' risk assessments.
Rigid and flexible control of eating
Authors:   , Timko C. Alix , Lowe Michael R
Published: July 2024

The goals of obesity treatment are to decrease weight by not only changing behaviors associated with eating (place, tempo, type of food) but also by increasing restraint. Cognitive restraint is a way of approaching eating with the cognitive intent to restrict intake in order to lose or maintain body weight. Westenhoefer and colleagues broke restraint into two types of control over eating, namely rigid and flexible control (1991, 1994, 1996, 1999). Preliminary scales designed to measure these types of control have shown that flexible control (FC) over eating is correlated with greater degrees of weight loss, low BMI, and low susceptibility to eating problems. The opposite is true for rigid control (RC). The current study was designed to investigate the role of RC and FC in a weight loss program that entailed both a rigid diet phase and a flexible maintenance phase. Two sets of mediation analyses were employed to investigate the role of RC and FC throughout the program. In the diet phase, baseline RC and FC were tested as predictors of weight loss, and the average number of non-diet sanctioned kcals consumed was tested as the mediator. Results indicted that the consumption of excess calories did not affect weight loss and therefore could not serve as a mediator. Additionally, FC was found to predict smaller weight losses; and RC was found to have no relationship with weight loss. In the maintenance phase, change in control scores from pre-test to week 14 were used as predictors, with change in disinhibition scores (DIS) from pre-test to week 14 used as the mediator. Change in weight during the maintenance phase was the dependent variable. Results indicated that decreases in DIS mediated the effects of increases in FC on weight lost during the maintenance phase. Greater increases in FC during the first 14 weeks predicted better weight maintenance during the latter half of treatment. Exploratory analyses revealed that FC at post-treatment was a marginally significant predictor of poorer weight maintenance. Overall, FC predicted smaller weight losses leading to questions regarding the appropriateness of a rigid diet for those with high FC.
Support effects in ethylene oxidation catalysis
Authors:   , Lee James Kwok-kit
Published: July 2024

The role of support in selective oxidation of ethylene over supported silver catalysts has been investigated by studying the effects of silver crystallite size on the catalytic activity of silver supported on various oxides with low to high BET surface area in ethylene oxidation reactions, and by measuring the catalytic activity of pure and modified supports in ethylene oxide isomerization/oxidation reactions. The specific activity as well as selectivity of the supported silver catalysts have been found to be strong functions of the silver crystallite size. The size effects observed are different depending on the supports used. The different effects have been explained in terms of surface oxide formation, distribution of various crystallographic planes, and metal-support interaction. Except for (alpha)-Al(,2)O(,3), all the supports used in the preparation of supported silver catalysts in this work have been found to catalyze the isomerization and oxidation of ethylene oxide. The non-selective nature of silver supported on these supports is mainly due to the further reaction of ethylene oxide to acetaldehyde and carbon dioxide on the support surfaces. Alkali impregnation of the support effectively suppressed ethylene oxide isomerization. Oxidation of ethylene oxide, however, increased initially with alkali impregnation but decreased with increase in alkali concentration. The concept of acid-base bifunctional catalysis has been invoked to explain these results. Alkali impregnation of supported silver catalysts was not found to be beneficial to ethylene epoxidation due to alkali poisoning of active silver sites.
Memory Consolidation and Interference Resistance with Sleep Disturbances
Authors:   , Corbitt Charles Brandon , Coletta Maria C
Published: July 2024

Daytime functional impairments in primary insomnia remain subjective in nature due to the lack of consistent, objective measurements of impaired daytime functioning. Once specific domains of impairment can be defined with accurate neuropsychological measures, better treatments for performance deficits will be able to be designed. Declarative memory consolidation is a domain of functioning that remains understudied within populations that report primary sleep disturbances. This experiment examined verbal declarative memory consolidation in college-aged participants using an (A-B, A-C) future interference paradigm. There were 28 participants divided into two groups with 13 participants in a sleep-disturbed group and 15 participants in a healthy control group. The sleep-disturbed group met both the quantitative research criteria (Lichstein, Durrence, Taylor, Bush, & Riedel, 2003) and Insomnia Severity Index criteria. This design was utilized in an attempt to detect differences in delayed recall of word-pair associate lists, both before and after interference testing in a two-way factorial repeated measures ANCOVA design. It was hypothesized that recall would decrease after interference testing. Both groups did experience significantly decreased delayed recall after interference testing, however there were no significant differences between groups. These results suggest that the sleep-disturbed students from this study do not have impaired declarative memory consolidation or impaired resistance to future interference, relative to their healthy peers. The findings from this study provide important implications for the future search for daytime impairments in primary insomnia.
Stability studies of low part per million carbon monoxide standards in steel cylinders
Authors:   , Denyszyn Robert B.
Published: July 2024

This stability study was based on the potential reaction of low ppm carbon monoxide with the various oxides found on steel cylinder surfaces. Analytical and sampling methods were developed to measure the stability of low ppmv CO standards so that CO measurements at the 20 ppmv level could be made with a precision of 0.1% at the 0.95 confidence interval. To confirm the changes in CO concentration, a cryogenic sampling system was developed to concentrate the CO(,2) formed during the reaction. The concentrated samples were analyzed on a G. C. methanization FID system. Oxygen, water and other variables which were known to play a significant role in the overall reaction were also monitored. Carbon monoxide stability was evaluated under five different surface cylinder treatments. One treatment was found to significantly improve the stability of carbon monoxide from a batch concentration change of -1.0% relative/year to -0.1% relative/year. Twenty-one additional CO stability experiments were performed to evaluate the influence of the three predominant iron oxides found on steel surfaces, FeO, Fe(,2)O(,3), Fe(,3)O(,4). At 14,000 kPa, all three oxides were also found to be active at room temperature. Oxygen was found to play a significant role in the rate of CO change. In some cases, increasing the O(,2) content from < 0.02 ppmv to only 5 ppmv changed the rate of CO change/year by an order of magnitude. Gas phase H(,2)O concentration significantly decreased the reactivity of all oxides.
When silenced voices speak
Authors:   , Dudek Jonathan Adam , Nezu Christine M.
Published: July 2024

The FBI's National Center for the Analysis of Violent Crime (NCAVC) recently cited an increase in consultations involving serial, or multiple, homicide of female prostitutes, including anecdotal evidence of distinct victimology and crime scene differences among the victims. Of particular interest to the NCAVC was whether such variables (e.g., work location, body disposal method) could classify a deceased prostitute case as being either "single" (i.e., the only victim of a murderer) or "serial" (i.e., one of several victims of a murderer) in nature. Because this phenomenon had not been examined empirically, this exploratory study investigated differences between samples of serial and single prostitute homicide victims. The NCAVC's anecdotal data and variables excerpted from relevant research literatures were included in an instrument designed for the study, the Prostitute Homicide Questionnaire (PHQ; Dudek & Nezu, 2000). Psychopathy was measured retrospectively with the Psychopathy Checklist-Revised (PCL-R; Hare, 1991 c). Efforts were made throughout the study to control error variance. Trained raters eyed 123 closed homicide files (49 single and 74 serial victims, respectively) submitted from U.S. law enforcement agencies, completing both instruments. The study's aims were largely fulfilled. Significant bivariate relationships between victim groups and conceptual blocks of included variables were demonstrated, including expected trends from the examined literatures. Although most prostitute victims were crack cocaine addicts, serial victims evidenced a more chronic pattern of abuse and risk behaviors, resembling so-called "crack whores" (Ratner, 1993a), while single victims resembled traditional street prostitutes. Although the perpetrators resembled each other superficially, having lengthy criminal histories and elevated psychopathy levels, the serial killers differed markedly "under the surface," evidencing sexual motivations, deviant interests, and a high likelihood for sexual aggression (Hanson & Bussiere, 1996, 1998). Serial offender subgroups were identified, differing in their socioeconomic status, criminal sophistication, and exhibition of sadistic and idiosyncratic crime scene behaviors. Single offenders were nonsexually motivated, murdering victims spontaneously during interpersonal disputes involving substances. Although low sample size precluded multivariate analyses, odds ratio calculations facilitated victim classification, and empirical profiles of the murderers and victims were derived. Replication with a larger, more representative sample of prostitute victims and murderers is recommended.
Structural basis of HIV-1 GP120 dual receptor site antagonism by peptide triazoles
Authors:   , Tuzer Sinan Ferit , Chaiken Irwin
Published: July 2024

Acquired Immune Deficiency Syndrome (AIDS) is a lethal disease that can only be controlled with life-long treatment with anti-retroviral drugs. AIDS is caused by infection with the Human Immunodeficiency Virus 1 (HIV-1) and eventual depletion of helper T-cells and the immune system. New antiretroviral regimens are needed in treatment of HIV-1 infection as multi-drug resistance continues to plague current treatments. The entry step of HIV has been an elusive target due to conformational masking of neutralization sites on the viral envelope proteins gp120 and gp41. Currently, two entry inhibitors are approved only for treatment-experienced patients due to potential for tropism switch, viral resistance and lack of improvement over current regimens. Dual antagonist peptide triazoles (PT) are a novel class of gp120 antagonist peptides that inhibit interactions of gp120 with both its primary receptor CD4 and its co-receptor CCR5 or CXCR4. In order to determine their mode of action, we converted multiple residues at and near a putative peptide binding site to alanine and screened them for induced effects on PT binding and inhibition. Selected mutants that varied by an order of magnitude or more from WT were purified and also expressed in virus, and tested for their effects on direct binding and inhibition by the PT KR21. The results defined a new, putative PT binding site overlapping with that of CD4. We further investigated the use of the CD4 binding site by PTs and overall found alternate use of residues in this site by the PT vs. CD4. We also observed that PT binding resulted in multiple conformation-sensitive antibody epitopes being inaccessible, including epitopes that are enhanced by CD4 and/or lie outside the PT hot-spot. These results argue for an alternative use of the CD4 binding site and allosteric inhibition of gp120 that results from it, and support the proposed PT binding site as all epitopes that overlapped with this site were inhibited, while linear epitopes that did not overlap were not affected. A structurally defined antibody paratope with extensive contacts to all PT site residues suggests a mode of binding and inhibition by the PTs.
Removal of organic pollutants by ozonation
Authors:   , Yurteri Coskun , Gurol Mirat D.
Published: July 2024

The research presented in this dissertation is focused on the use of ozone for the elimination of man-made organic micropollutants from drinking waters and waste effluents requiring advanced treatment. The primary objective of the research was to develop a mathematical model which can simulate the physical transport and chemical oxidation phenomena prevailing during the process of ozonation. The process model is comprised of a set of concentration profiles defined in liquid and gas phases. The profile equations for ozone and the targeted trace organic compound are based on differential mass balances, and adhere to the principles of continuity. The model is analyzed for its special cases and for its sensitivity to various process parameters. A systematic methodology is developed for the estimation of the necessary model parameters. A set of laboratory experiments is carried out to test the validity of the developed process model. According to the mathematical model developed in this study, the efficiency of the process depends on several kinetic and operational factors. In particular, the reactivity and volatility of the targeted pollutants may have a strong effect on process performance. The chemical quality of the raw water, mass-transfer and hydrodynamic characteristics of the reactor, and various operational variables, such as the influent ozone concentration in the feed gas, water loading rate, and gas-to-liquid ratio, are among other factors controlling the removal of trace organic pollutants. Two process parameters are identified to describe the kinetics of ozone-induced oxidation reactions: (i) the specific ozone utilization rate, w (hr-1), of the raw water to be treated, and (ii) the total oxidation constant, kT (M-1.s-1), of the organic compounds to be removed from the water. As an integral part of the research, bench-scale, as well as predictive, techniques are proposed for the evaluation of the w and kT constants in raw waters contaminated with various synthetic organic micropollutants. Combined with the developed parameter estimation methodology, the process model constitutes a particularly powerful engineering tool. In addition to efficiency comparisons under different operational conditions and reactor configurations, the model can also be used to make performance and cost comparisons between ozonation and other alternative technologies.
Auditor independence
Authors:   , Vinciguerra Barbara M. , Jaenicke Henry R.
Published: July 2024

Professional standards require auditors to be independent in the performance of attestation services. Recently, the SEC and some private sector groups have expressed concern that pressure to maintain and develop business may erode an individual auditor's objectivity and independence when making audit judgments. The profession contends that although the pressure to compromise independence may exist, the presence of safeguards such as peer-review, firm-level quality control practices, and auditor professionalism serve to mitigate this risk. This dissertation examines whether a consultation review requirement, a firm-level safeguard to independence, will reduce auditor bias in the presence of economic self-interest incentives. In addition, the roles of perceived pressure and moral development on auditor judgment are examined using the General Model of Pressures in the Accounting Profession (DeZoort and Lord, 1997). Experienced auditors from national and international accounting firms were given a case study where an audit client was proposing an aggressive accounting treatment. Client retention concerns and consultation review requirement were manipulated in the case. Results indicate that client retention concerns, consultation review requirement, and their interaction had a significant effect on the auditor's judgment as to whether an accounting treatment was appropriate in the circumstances. Results regarding the allowability of the treatment under GAAP and the likelihood of accepting the proposed accounting treatment were mixed. Perceived pressure from the firm had a positive relationship to the likelihood of accepting the proposed accounting treatment, the assessment of the allowability of the accounting treatment under GAAP, and the assessment of the appropriateness of the treatment in the circumstances. Results do not support an interaction effect of moral development with perceived pressure.
Peer acceptance in elementary school children
Authors:   , Gorski Jo Anne Barbara , Nezu Arthur M.
Published: July 2024

Problem-solving ability has been found to relate to behavioral adjustment in children. Prior research has found that effectiveness, appropriateness, and less aggressive solutions to hypothetical social problems were significant predictors of behavioral adjustment. The lack of behavioral alternatives due to poor problem-solving skills may lead to aggression which, in turn, may lead to rejection by peers. A coherent theory has not yet been established which accounts for the relationship between peer acceptance and behavioral adjustment. Both peer acceptance and problem-solving skills have been significantly related to behavioral adjustment. The purpose of the present study was to determine whether the relationship between peer acceptance and behavioral adjustment is really accounted for by problem-solving skills. For example, children who have demonstrated better problem-solving skills tend to be more popular, whereas children with poor problem-solving skills are less popular. The less popular children are those who tend to be more aggressive and disruptive. The current study used sociometric ratings and nominations among 119 elementary school children (7-13 years) to establish three peer status groups (popular, average, unpopular). Teacher ratings were used to measure behavioral adjustment for subjects. The results of a Multivariate Analysis of Variance supported prior research and found that behavioral adjustment was significantly related to peer status. A second analysis was performed in the same way, only using problem-solving ability and age as covariates. Although age was a significant covariate, problem-solving ability did not significantly mediate the relationship between peer acceptance and behavioral adjustment. The implications of this finding were discussed in support of the reputational bias theory which may be a larger factor in mediating the relationship between behavioral adjustment and peer relationships. Further studies should continue to examine the role which problem-solving skills may have in this relationship.
General input balancing and model reduction
Authors:   , Mesko Joseph Paul , Gray W. Steven
Published: July 2024

In linear system theory, the controllability and observability Gramians arise naturally in many problems pertaining to realization theory, optimal control and reduced order modeling. In 1993, Scherpen generalized the notion of Gramians to the nonlinear setting via the controllability and observability energy functions and demonstrated their usefulness in model reduction problems for smooth systems that were strongly accessible and zero-state observable. However, the property of zero-state observability is not shared by a large class of systems which are otherwise observable when driven by almost any input function. The research described in this thesis offers a new approach to the nonlinear model reduction problem. Specifically, the condition of zero-state observability is relaxed and a more general type of observability energy function is defined. This approach is also considered to be more natural to model reduction problems where there is significant uncertainty in the applied input signal due to controller inaccuracies (e.g., finite word-length effects, sampling), actuator inaccuracies or random disturbances. The new theory and algorithms for the general nonlinear model reduction problem were then applied to linear and bilinear systems.
The role of fractalkine in the early stages of skeletal metastasis from prostate and breast cancer
Authors:   , Jamieson Whitney L. , Fatatis Alessandro
Published: July 2024

Both prostate and breast cancers metastasize to the bone with high propensity. Skeletal metastases significantly reduce patients' quality of life and represent a common lethal complication of neoplastic disease. Currently, no preventive or curative treatments for metastasis are available. Therefore, the advent of novel, effective therapies to impede metastatic dissemination is highly needed. Chemokines are a class of small, chemotactic cytokines that have been strongly implicated in metastasis. Among this family of proteins is fractalkine (CX3CL1, FKN), a unique chemokine that exists not only in a soluble form but also as a membrane-anchored molecule. In its membrane-bound form, FKN has been shown to mediate adhesion of cells expressing its receptor, CX 3CR1. FKN also acts as a chemo-attractant when cleaved from the membrane into a soluble protein. This dissertation describes the role of FKN and CX3CR1 in skeletal metastases from prostate and breast cancer . Expression and regulation of FKN in the bone has not been previously described. Shown here are data identifying FKN in cultured bone cells and ex vivo human tissue and bone marrow. Also described is a previously unknown mechanism of FKN cleavage in bone cells, via androgen stimulation, which could be important in the extravasation of prostate cancer into the bone. Furthermore, a novel in vivo mouse model of early experimental metastasis is described here in which fluorescent human cancer cells inoculated in the blood circulation can be identified in bone in progression from single cells to macroscopic tumors. This in vivo model has provided evidence that extravasation occurs rapidly after arrival of cancer cells to the bone. Finally, critical experiments combining our model of metastasis with molecular and genetic manipulation of FKN or CX3CR1 demonstrate that this pair plays a significant role in adhesion of cancer cells to the bone marrow sinusoids as well as their extravasation into the bone stroma. Overall, data produced by this research project strongly implicate FKN and CX3CR1 in skeletal metastasis. The work presented in this dissertation represents solid evidence that FKN and CX3CR1 should be evaluated as potential therapeutic targets for the prevention of skeletal dissemination of prostate and breast cancers.
The dynamic mechanical properties of Spectra and Kevlar fiber reinforced composities
Authors:   , Yu Jenny Zhaoxia
Published: July 2024

This thesis describes an effort to characterize the dynamic mechanical properties of Spectra[registered]/Kraton and Kevlar[registered]/epoxy composites based on the characterization of the unidirectional lamina of the same materials. The microstructure of unidirectional lamina (UD) is in between the fiber/matrix level and the composite level. The UD lamina as a 3-dimensional transversely isotropic linearly viscoelastic material was fully characterized. Using the UD lamina as a building block, the viscoelastic behaviors of multidirectional laminates and 3-D braided composites were predicted by modifying and expanding the classical lamination theory and Fabric Geometry Model to include viscoelastic effect, respectively. The time dependent viscoelastic properties of UD lamina of Spectra[registered]/Kraton and Kevlar[registered]/epoxy were determined by combining experimental and micromechanics methods. The high frequency domain properties E11'([omega]) E22'([omega]) and G12'([omega]) were generated by using the Dynamic Mechanical Analyzer (DMA). The DMA results were verified by performing three-point bend and impulse excitation tests. Long time stress relaxation properties of the UD lamina in the time domain were also measured by DMA. The results obtained by the various techniques were shown to correlate well. Poisson's ratio [nu]12([omega]) and [nu]23([omega]) were calculated using the micromechanics model. The Debye equation was selected to recover time domain relaxation moduli function from frequency domain complex moduli by using inverse Fourier Transformation. The full relaxation moduli functions of the evaluated composites which combine high frequency data (transient data) and long time data were obtained. The established viscoelastic constitutive relationship covering a broad time scale was used for the prediction of the viscoelastic properties of several laminates and 3-D braided composite. The prediction has good agreement with the test results. The overall trend agrees with the prediction. It was found that Spectra composites exhibit significant strain rate dependence, resulting in extraordinary high Moduli value comparable with that of diamond in the high strain rate region (13,546 m/s) and much higher than that of the Kevlar composite. The low Tg -70 [degrees]C) of the matrix for Spectra/Kraton composite ensures that the dynamic data obtained at high frequency includes the high damping region.
Usual mobility methods of children with cerebral palsy
Authors:   , Tieman Beth , Palisano Robert J
Published: July 2024

The purpose of this dissertation was to examine usual mobility methods of children with cerebral palsy (CP) in the home, school, and outdoors/community settings. Mobility is needed in activities of daily living and limitations in mobility may impact participation in society. Even though interventions are often provided in natural environments, knowledge of the impact of environmental setting on mobility is limited. The subjects were 307 children with CP, ages 6-14 years who participated in a longitudinal study, randomly selected from 19 centers, and stratified by age and Gross Motor Function Classification System (GANEFS) level. Measures included the GANEFS, parent-completed questionnaire on children's usual mobility methods, and the Gross Motor Function Measure. The first study indicated differences in gross motor capability and parent report of performance of mobility methods in children with CP. Among children with CP who have similar capability, there were differences in performance across settings. The second study demonstrated among children within the same GANEFS level, the variability of mobility methods across settings. Children performed higher-ranked mobility methods at home (requiring the most gross motor control), lower-ranked mobility methods at school, and the lowest-ranked mobility methods (requiring the least gross motor control) in the outdoors/community. The third study provides evidence for nonlinear changes in mobility over time in children with CP. During the first 1 1/2-2 1/2 years, mobility methods increased to higher-ranked methods, while in the second 1 1/2-2 years, mobility methods were unchanged or decreased to lower-ranked methods. The changes in mobility methods over time did not differ across settings. The findings indicate that environmental setting has an impact on the usual mobility methods of children with CP. The examination of children with CP should include capability and/or performance measures, depending on the purposes of examination. Performance should be measured specific to settings where children function, including the contextual features and personal factors that may influence mobility. Intervention should address the factors contributing to mobility, such as environmental adaptations and child-related factors. Screening of children with CP should occur at regular intervals so that interventions can address the changes in mobility.
Mechanisms involved in the regulation of the axonal cytoskeleton during NGF-induced axon branching
Authors:   , Spillane Mirela , Gallo Gianluca
Published: July 2024

The formation of a complex and functional neuronal circuitry depends on the ability of neuronal processes to extend over long distances and through complex environments to synapse with their targets. Further augmentation of the nervous system innervation is achieved by collateral branching of axonal shafts. Branching enables single axons to make connections with multiple neurons within the same or different nervous system regions. Insight into the signaling mechanisms underlying de novo formation of axon branches during embryogenesis may reveal therapeutic targets in promoting or preventing branching during regeneration in the context of nervous system injury. In vitro and in vivo, axon collateral branches arise through the maturation of transient finger-like protrusions, termed axonal filopodia. In turn, axonal filopodia emerge from dynamic axonal accumulations of actin filaments, termed F-actin patches. The mechanisms of neuronal filopodia formation are poorly understood. In this thesis, I show that the actin related protein (Arp) 2/3 complex plays a significant role in the formation of axonal actin patches, filopodia and branches formed in response to nerve growth factor (NGF). The Arp2/3 complex is shown to target to actin patches through immunocytochemistry, live-cell imaging analysis and platinum replica electron microscopy of actin filament organization in patches. Inhibition of Arp2/3 function impaired formation of axonal filopodia and branches in vitro and in vivo. Furthermore, branching induced by NGF requires intra-axonal synthesis of Arp2/3 complex subunits and the upstream regulators, cortactin and Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1). NGF, through phosphoinositide 3-kinase (PI3K) signaling, increases axonal levels of Arp2, cortactin, and WAVE1 in axons severed from their cell bodies in a manner sensitive to translation inhibition. Supporting these findings, using PCR-based methods in purified axonal preparations, we detected axonal mRNAs of these three proteins. Cortactin over-expression induces sensory axon collateral branch and filopodia formation in the living spinal cord of chicken embryos. Collectively, these data identify a cellular signaling mechanism for branch formation and link the intraaxonal protein synthesis of cytoskeletal proteins to defined cytoskeletal structures, providing a new mechanism of NGF effect on axonal morphogenesis.
Peripheral mechanisms related to the anorectic action of serotonergic stimulation
Authors:   , Eberle-Wang Kim
Published: July 2024

These studies describe mechanisms by which peripheral serotonin (5-HT) reduces food intake in rats. Experiments compared mechanisms recruited by 5-HT to those of a model satiety system mediated by cholecystokinin (CCK). Initial studies examined whether stimulation of CCK-A receptors was required for anorexia following systemic 5-HT. Pretreatment of animals with the CCK-A receptor antagonist, devazepide, blocked CCK-stimulated anorexia but did not alter 5-HT-induced reductions in food intake. These studies demonstrated that mechanisms recruited by 5-HT, unlike CCK, were independent of CCK-A receptor stimulation. Additional studies examined whether an intact abdominal vagus nerve was required to elicit anorexia following peripherally-administered 5-HT. After vagotomy, CCK-mediated anorexia was blocked, but in the same animals, the effect of 5-HT on food intake was unaltered. Thus, unlike, CCK, peripheral 5-HT reduced food intake by vagally-independent mechanisms. The surgeries were verified immunohistochemically using anti-neurofilament protein to stain axons. Final studies considered the actions of 5-HT on the pylorus as one gastric site where 5-HT might act to alter feeding. These studies characterized the pharmacological profile for 5-HT-induced contraction of the pylorus in vitro. The complete response-curve for 5-HT-induced contraction of the pylorus was generated using a classical smooth muscle assay. Antagonist studies revealed that the 5-HT-stimulated contraction was blocked by diltiazem, ketanserin, xylamidine, and methysergide, but was insensitive to tetrodotoxin, ICS 205-930, prazosin, devazepide, and (-)pindolol pretreatment. Thus, it was inferred that a 5-HT2-type receptor, located on smooth muscle, mediated contraction to 5-HT in rat pylorus. The pharmacology of 5-HT-induced contraction of the pylorus agrees with in vivo studies demonstrating a peripheral 5-HT2 receptor mechanism mediating the anorectic action of peripheral 5-HT in rats. This correlation justifies further functional studies examining the pylorus as a site where peripheral 5-HT might alter feeding in rats. Overall, this thesis defines peripheral mechanisms for 5-HT control of feeding by dissociating its actions from those of CCK, providing the basis for future investigations of the sites of action of peripheral 5-HT in controlling ingestive behavior.
Physicians' abortion attitudes and intentions regarding future practice
Authors:   , Saporito Karen Alberts , Bersoff Donald N
Published: July 2024

Since abortion became legal in the U.S. in 1973, the number of abortions performed annually has been relatively stable, while the number of abortion providers has drastically decreased. As a result, women and girls must overcome financial, travel, and other obstacles to obtain abortions. This lengthens the time of the pregnancy, thus increasing the medical and psychological risks of abortion. Alternatively, they may not be able to locate a provider and then have an unwanted child, who is at increased risk of abuse and neglect. The decrease in abortion providers has prompted the American Council of Graduate Medical Education to require abortion training in obstetrics and gynecology residency programs. Factors associated with physicians' abortion performance have been examined, and physicians' abortion attitudes have been found to correlate with abortion performance. This study examines differences between first and second trimester abortion attitudes among U.S. obstetrics and gynecology residents, and explores factors contributing to their abortion attitudes including training experiences. Residents' attitudes are used because they reflect current influences on newly trained physicians. Factors related to physicians' intentions to perform abortions including clinic violence, low reimbursement and legal restrictions on doctor-patient relations are also addressed. The results indicate that in addition to religious affiliation, religious intensity, and gender, training experiences were significantly related to abortion attitudes in all residents surveyed. In residents with experience performing abortion, the number of abortions performed and negative emotional responses to performing abortions were also related to abortion attitudes. Abortion attitudes, training experiences and religious intensity were significantly related to abortion intentions in the entire sample of residents. In residents with experience performing abortions, negative emotional response to providing abortions and concern about harassment from antichoice activists were also significantly related to abortion intentions. When explaining the variance in residents' training experiences, the availability of training and residents' intentions to provide abortions in the future were more important than abortion attitudes, suggesting that the more training is available, the more residents will participate, not just based on a supportive abortion attitude. Thus, the relationship between abortion attitudes and training is likely interactional and deserves further research. Also, training experiences, negative emotional responses to providing abortion, and concern about harassment are all factors which can be addressed to increase physicians' performance of abortion. Implications for training programs and future research are discussed.
Optimization of conductivity parameters of EEG head models using implanted sources in the human cranium
Authors:   , Taylor Steve A.
Published: July 2024

Accurate analytical EEG localization of neural signals could help reduce the need for surgery in some epilepsy patients. In order to achieve accurate EEG localization of neural signals using analytical techniques, it is imperative to know the head model's conductivity parameters. As new and more accurate head models are developed, their conductivity parameters must be specified. However, because the conductivities of human head tissue have never been determined to any appreciable extent, no standard approach has been available. In this dissertation, model tuning is introduced as a means to specify the optimal conductivity parameters of an arbitrary EEG head model through a nonlinear least squares fit of the head model to in vivo EEG measurements. This method eliminates the difficulties of obtaining fresh human head tissue samples on which to measure conductivity and the subsequent problem of translating these measured conductivities into the conductivity parameters for the given EEG head model. Model tuning makes use of intracranial depth electrodes that are stereotactically implanted into an epilepsy patient for diagnostic purposes. A known current is applied between two selected contacts on one of the depth electrodes to create a known artificial neural signal. Potential measurements are then acquired using EEG electrodes placed on the epilepsy patient's scalp. Model tuning was tested on the four shell model with the participation of three epilepsy patients who had received depth electrode implants. The conductivity parameters that were empirically determined through model tuning were 0.2872, 1.2707, 0.0026, and 0.2048 for brain, CSF, skull, and scalp. To illustrate the kinds of questions that can be addressed with model tuning, it was hypothesized that the four shell model conductivity parameters specified by model tuning would lead to more accurate localization. The localization accuracy of the four shell model using the new conductivity parameters was tested against that of the four shell model using the standard conductivity parameters. The difference in localization accuracy was insignificant, showing that the hypothesis was wrong. This result can be attributed to the geometric shortcomings of the four shell model. With the possibility of noninvasive model tuning, EEG head models could be routinely customized to each individual for even better localization accuracy. Because of these advancements, the use of analytical EEG localization to reduce the need for surgery in some epilepsy patients seems a real possibility.