bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and modeling study of preignition chemistry of hydrocarbons
Authors:   , Wang Suqing , Cernansky Nicholas Peter
Published: July 2024

Many practical engine problems such as knock in spark ignition engines and cold start in heavy duty diesel engines are related to an important preignition process-autoignition. Strong evidence has shown that preignition chemistry of hydrocarbons at low and intermediate temperatures plays a critical role in autoignition. A negative temperature coefficient (NTC) of reaction rate is observed for most fuels in this region, where the overall reactivity decreases as reaction temperature increases. Understanding the mechanism of NTC could help us to elucidate the chemistry controlling ignition. The NTC behavior is generally believed to result from a shift in dominance from alkylperoxies to conjugate alkenes in the NTC region. One special fuel, neopentane, does not have a conjugate alkene, but its cool flame behavior implies that it has NTC behavior as well. Obviously, the accepted mechanism of NTC behavior does not apply to this fuel. Therefore, elucidating the oxidation mechanism of neopentane could contribute to our basic understanding of preignition chemistry associated with autoignition and to refining the existing mechanisms and, hence, this fuel is examined in this research program. This study investigates the preignition chemistry of neopentane and butanes. The research includes both experimental and modeling efforts. In the experimental work, the detailed stable oxidation products of neopentane oxidation are obtained in a pressurized flow reactor over the temperature range of 610 ~ 810 K at the elevated pressure of 8 atmosphere, using a combination of on-line Fourier Transform Infrared Spectrometry and non-dispersive infrared analysis. The NTC behavior of neopentane oxidation has been confirmed and the temperature range of NTC has been determined. The detailed speciation profiles from neopentane oxidation are obtained and analyzed. The data from the experiments are examined and analyzed in light of the presently accepted neopentane oxidation mechanism. In the modeling work, the data collected from neopentane oxidation are applied to test and refine a detailed chemical kinetic neopentane oxidation mechanism developed at Lawrence Livermore National Laboratory. Also, the results of the detailed neopentane modeling work are compared with the results from propane. In another separate but related effort, a previously developed reduced chemical kinetic model describing the autoignition of primary reference fuels in our research engine is extended to the butanes. Finally, suggestions to improve the current hydrocarbon oxidation mechanism and reduced models are made based on this study.
Bacterial sarcosine oxidase
Authors:   , Kvalnes-Krick Kalla L.
Published: July 2024

Sarcosine oxidase from Corynebacterium sp. U-96, a soil organism isolated in Japan, is the first example of a flavoprotein containing both covalently bound flavin and noncovalently bound flavin (Hayashi et al., 1980, 1982; Suzuki, 1981). To determine whether the enzyme from the Japanese Corynebacterium was unique, the isolation of another corynebacterium which produces sarcosine oxidase was attempted. A Corynebacterium (Corynebacterium sp. P-1), isolated by a serial enrichment technique from Philadelphia soil samples, synthesizes sarcosine oxidase in large amounts when grown with sarcosine as sole carbon source. The enzyme, purified to electrophoretic homogeneity, contains 1 mol of noncovalently-bound flavin (flavin adenine dinucleotide (FAD)) plus 1 mol of covalently-bound flavin (8[alpha]-(N3-histidyl)-FAD) per mole of enzyme (Mr, 168,000). The flavin composition of the Philadelphia enzyme is identical to that of the Japanese enzyme. The two flavins appear to have different roles in catalysis. The Philadelphia enzyme, purified in the presence of protease inhibitors, exhibits an unusual quaternary structure, containing four dissimilar subunits (Mr, 100,000, 42,000, 20,000, and 6,000). The covalent flavin is attached to the next to the largest subunit. The same subunit composition is observed in Western blot analysis, when cell extracts of Corynebacterium sp. P-1 prepared in the presence of trichloroacetic acid are probed by a sarcosine oxidase specific antibody, indicating that the subunits are a genuine property of the enzyme as it exists in vivo. Enzymes containing 4 or more nonidentical subunits frequently exhibit complex functions, suggesting that sarcosine oxidase might have a broader metabolic role in corynebacteria. The fate of formaldehyde, produced during the oxidation of sarcosine, was investigated and shown to have a role in one-carbon metabolism. The enzyme binds tetrahydrofolate and, in the presence of sarcosine, catalyzes the synthesis of 5,10-methylenetetrahydrofolate. The enzymes exhibit many similarities but are distinguishable in electrophoretic studies. Immunologically, the enzymes were shown to be similar but not identical. The results indicate that the synthesis of a sarcosine oxidase containing both covalent and noncovalent flavin is not a particularly unusual event in corynebacteria.
Diastereoselective synthesis of protected secondary amines via reduction/alkylation or deprotonation/alkylation of N-diphenylphosphinylimines
Authors:   , Shin Hyun-shun , Hutchins Robert O.
Published: July 2024

Part A. Stereoselectively protected secondary amines are prepared by reduction of a variety of substituted cyclohexyl N-diphenyphosphinylcyclohexylidineimines with lithium-tri-sec -butylborohydride approach of which is found to occur from the less sterically hindered equatorial face leading to the corresponding axial lithium anions, followed by the treatment with methyliodide. In the same way, the stereoselectively protected secondary amines are prepared by alkylation of the corresponding axial/equatorial lithiated anions, which are produced from stereoselectively formed axial and equatorial substituted N-diphenylphosphinylcyclohexylamines reduced by L-selectride or t-butylamine-borane complex, respectively under basic conditions such as n-butyl lithium or KHDMS yielded the corresponding lithium anions which were reacted with alkyl halides to afford the corresponding stereoselectively protected N-alkylated secondary amines. Part B. Alkylation of N-diphenylphosphinyl imines is a direct and facile route for obtaining the protected secondary N-diphenylphosphinyl amines. The addition of organolithium to N-diphenylphosphinyl imines formed the anion of N-diphenylphosphinyl amides which can serve as nucleophiles. The subsequent alkylation of the anion of N-diphenylphosphinyl amides with alkyl halides provided the corresponding alkylated N-diphenylphosphinyl amides. The synthesis of simple protected secondary amines which were produced from N-diphenylphosphinyl aldehyde imines were used as electrophiles to react with orgnometallic reagents such as n-BuLi, PhLi, and CH3Li to form the anion which was alkylated to the corresponding amides by treatment with alkyl halides.
3D structure estimation from images with applications in object tracking and recognition
Authors:   , Zhang Chongzhen , Cohen Fernand S
Published: July 2024

3D object structure estimation is important in object tracking, object recognition, video-conferencing, and scene analysis. This dissertation considers the problem of structure estimation from images with applications in vehicle tracking and face recognition. First, I present a new approach to object tracking by the convex hull vertices of the segmented object over the sequence of frames. The structure of the convex vertices and the 3D motion of the moving object are obtained through the tracking process. The second part of this thesis concentrates on the face structure estimation and recognition. A 3D face structure is extracted from a few image views of a human face taken at prior unknown poses by appropriately morphing a generic 3D face. A cubic explicit polynomial in 3D is used to morph a generic face into the specific face structure. The choice of the morphing function (a cubic polynomial) was dictated by the nature of the differences in shape between the face surfaces. The estimation of a 3D face structure as well as the view poses is achieved through the use of a distance map metric. The use of this metric avoids either resorting to the formidable task of establishing feature point correspondences in the image views, or even more severely, relying on the extremely view-sensitive image intensity (texture). Automatic Face Recognition (AFR) is one of the most successful applications of image analysis and understanding. However, recognition of faces under varying pose remains one challenging issue in AFR. This work introduces an approach to the task of identifying a person in the database from an arbitrary image. The estimation of the 3D face structure allows the creation of a 3D face database, from which the feature-based recognition is achieved after pose estimation. It also allows the synthesis of a virtual face to be matched with the test image in intensity-based face identification. Finally a mechanism that fuses the feature-based face classifier with intensity-based classifier is also presented for achieving classification rates that surpass those obtained by each classifier on its own.
Navigation in a metaphorical computer interface
Authors:   , Wozny Lucy , Strong Gary W.
Published: July 2024

Today, many computer systems are designed with a metaphorical user interface, on the assumption that the similarity between the referent and target domains will make the systems easier to learn and use. In fact, research shows that metaphorical similarity is potentially detrimental when solving problems because the computer system cannot be completely isomorphic to the metaphor on which it is drawn. Learners of a "metaphorical" computer system are the subjects in this study. Three primary questions are addressed. First, are there differences in problem solving behavior among learners? Second, can performance differences be attributed to different mental models of the system? Third, can performance differences be traced to the level of a subject's computer knowledge? The data collection instruments are a computer experience survey, screen reconstruction and description exercises, and unobtrusive mouse-click and key stroke monitoring. A metaphorical user interface based on a Yellow Pages directory was developed with both metaphorical and non-metaphorical navigation methods. Sixty-seven subjects solved six tasks without prior training, were trained in a non-metaphorical navigation method, and then solved eight additional tasks. A cluster analysis, analyzing unobtrusive mouse-click data, generates striking results. Three groups of subjects with distinct interaction preferences are evident: metaphorical "page-turning", semi-metaphorical "icon-clicking", and non-metaphorical "page-jumping". While the literature would indicate that increasing computer experience would have a positive effect on experience. Neither are there differences among subjects in the measures of their initial declarative and procedural knowledge of the system. This study indicates that there are significant differences among people introduced to a metaphorical computer system that are not based on prior computer experience or solely on the metaphor employed.
An empirical test of the frontal lobe hypothesis of schizophrenia
Authors:   , Kamrowski-Poppen Bradley Joseph , Zillmer Eric
Published: July 2024

Schizophrenia has long been thought to be characterized by a set of behavioral and cognitive deficits which suggests frontal lobe involvement. A study was done making direct comparisons between schizophrenics and individuals with localized prefrontal lobe injuries. Twenty-one schizophrenics and 19 focal frontals were compared using MANOVA procedures to a healthy control reference group. Both clinical groups displayed neuropsychological impairments on a variety of cognitive skills, with primary deficits in executive control and verbal learning. Further MANOVA between the clinical groups indicated a lack of a difference between the schizophrenics and focal frontals as a group. Subdividing the frontal group, it was found that there was no observed difference between the profiles of schizophrenics and left frontal patients, whereas both of these groups displayed significantly more impairment in verbal learning than the right frontal group. These data fail to support a difference between the neuropsychological profiles seen in localized left prefrontal injury and schizophrenia. Executive control deficits, and the impact impaired organization and lower depth of processing has on verbal learning, are thought to be a major factor in both these profiles. It is believed that frontal lobe injury, particularly left prefrontal injury, provides an adequate model for the deficits of schizophrenia, and support the frontal lobe hypothesis of schizophrenia. Potential confounding factors and directions for further research are discussed.
A model of adherence in type 2 diabetes mellitus
Authors:   , Kutz David J.
Published: July 2024

Type 2 diabetes is identified by insulin resistance and beta cell dysfunction. Commonly, an individual with Type 2 diabetes will produce insulin, but it is ineffective in controlling blood glucose levels within the normal range. Epidemiological studies have indicated that Type 2 diabetes affects approximately 5 million people in the United States alone. The treatment of Type 2 diabetes involves a number of factors that invariably compel the patient to make life-long behavioral changes. These include following strict dietary and exercise regimens, as well as checking one's blood glucose levels and taking insulin. Through extensive research, it has been determined that many patients do not follow their prescribed treatment plans. Previous studies have alluded to varying psychosocial factors in explaining why certain individuals adhere more to their doctors' recommendations than others. The current study examined the role that a number of psychosocial variables may have played in affecting adherence behaviors in two populations of patients with Type 2 diabetes mellitus. The studies' psychosocial variables included the patient-practitioner relationship (PPR), coping style, social support, psychological distress, perceived stress, and SES. Ultimately, it was discovered that when individuals were satisfied with interpersonal aspects of their medical care they were receiving in their endocrinology clinics, they were more likely to adhere to treatment recommendations. Furthermore, it was discovered that when patients were less likely to utilize avoidance as a means by which to cope with their illness, they tended to adhere more to prescribed treatment regimens. It was also indicated that general satisfaction with medical care, as well as the perceived level of social support the patients felt they obtained, contributed to adherence practices.
Trunk muscle and motor control impairments in patients with lumbar instability
Authors:   , Silfies Sheri P.
Published: July 2024

While a majority of back pain patients recover within a short period of time, some develop chronic low back pain (CLBP). One plausible cause of CLBP is lumbar instability, which is presumably associated with osteoligamentous laxity or damage. Given Panjabi's model of spinal stabilization and supporting evidence that remaining subsystems can compensate for attenuated passive structures, the assessment of trunk muscle performance and motor control warrants exploration. The purposes of this study were to examine the trunk active and motor control subsystems for differences between CLBP subgroups with and without evidence of spinal instability and asymptomatic subjects by assessing: (1) fatigue; (2) activation levels; and (3) onset timing and sequence of activation. To examine localized trunk extensor muscle fatigue, spectral electromyography (EMG) changes were analyzed during a sustained isometric contraction at 80% of maximum voluntary activation. Subjects with CLBP attributed to lumbar instability demonstrated less fatigability than the healthy control group. This may be the result of adaptation in the musculature that allows improved ability to provide spinal stability during short periods of submaximal activation. There were no significant differences in between subgroups of CLBP. To examine trunk muscle activation patterns and synergist coactivation levels, normalized EMG amplitude was compared across groups during a functional reaching task. The CLBP group with instability demonstrated higher levels of muscle activity (rectus abdominus and external oblique) and altered abdominal synergistic coactivation patterns around a neutral standing position. These alterations in muscle recruitment may indicate motor control dysfunction of the local trunk stabilizing muscles. Again, no differences were found between the two CBLP subgroups. To examine trunk muscle onset timing and sequence of activation, a model of self-generated center of mass perturbation was achieved by having the subject perform a unilateral arm raise. All three groups demonstrated feedforward activation of the lumbar multifidus presumably to control anterior displacement of the body's center of mass. These data also suggest a lack of preparatory activation of the external oblique muscles in the CLBP with evidence of lumbar instability, which may indicate poor frontal and transverse plane stability of the lumbar spine during performance of asymmetrical movements.
Reactive pressureless infiltration technique for Cu-alloy/TiB₂ and other In Situ composites
Authors:   , Shtessel Victoriya
Published: July 2024

Reactive Pressureless Infiltration (RPI) was achieved successfully by the in situ synthesis of Cu-Mn/TiB₂ composite materials. RPI-processed Cu-Mn/TiB₂ composite materials with 7 to 40 v/o TiB₂ exhibit microstructures with fine (0.5-5 [mu]m) and evenly dispersed reinforcement and high room temperature strength and hardness. Infiltration occurs spontaneously at relatively low temperatures (980-1050°C), and does not require complex processing equipment. Primary factors which alter phase composition and microstructure of the MMCs are enthalpy and relative free energy of reinforcement formation, initial powder size, processing temperature and matrix wettability of the reinforcement. Employment of the matrix assisted displacement reaction between the Cu-Ti liquid and MnB₂: MnB₂ + Cu-Ti [yields] TiB₂ + Cu-Mn ensures in situ formation of fine TiB₂ particulates in the Cu-Mn matrix. The reaction also provides for the spontaneous infiltration of the solid MnB₂ preform by Cu-Ti liquid due to wettability. The process can be carried out below the melting point of the Cu because alloying Cu with Mn decreases the liquidus temperature of the alloy and causes diffusional melting of the infiltration front. Possible mechanisms for the evolution of the microstructure during processing are proposed and analyzed. The study demonstrates that TiB₂ is formed by interfacial reaction: Ti + MnB₂ = TiB₂ + Mn. A detailed kinetic model of the reactive pressureless infiltration is proposed. The model evaluates the diffusion, infiltration and reaction processes and predicts the infiltration rate, the thickness of the reacted layer as a function of time, the rate of reaction of TiB₂ formation and the concentration profile of each component in the reactive layer. The model establishes the effects of processing parameters such as reaction time and temperature, wetting of the preform by the melt, preform porosity, preform composition and volume fraction of reinforcement on the infiltration kinetics. It also establishes the limiting stages of infiltration. The proposed model shows good agreement with experimental results and provides a tool for analysis of infiltration kinetics in reactive systems. It may be applied to other systems for different chemistries, properties and geometries to establish process feasibility.
Do hope and social support influence self-esteem in early stage dementia?
Authors:   , Cotter Valerie T. , Gonzalez Elizabeth W
Published: July 2024

Statement of the problem. A diagnosis of early stage dementia typically results in feelings of loss, social stigma and uncertainty placing major demands on the coping strategies for the individual. Recent studies indicate that they manage the illness and its emotional impact through a series of processes that progress through stages of awareness, coping, and evaluation. They acknowledge and actively seek to understand and adjust to current and future loss of memory, independence, previous roles and lifestyle, as well as feelings of depression and frustration, and its potential for negative beliefs about the self. The purpose of this study was to examine the relationships between hope and social support on state self-esteem in individuals with early stage dementia. Procedure & methods. The study employed a cross-sectional, correlational design. The sample was recruited from two neurology practices, two continuing care retirement communities and the Alzheimer's Association early stage dual support groups. Data was collected using the Herth Hope Index, Social Support Questionnaire Short Form, State Self-Esteem Scale, and a demographic data form. Results. Fifty-three participants, predominantly female (68%), older-aged (80.8 ±7.8 years) and with mild stage dementia (MMSE 25.5 ±3.5) completed the study. Hope was significantly related to state self-esteem (p < .001), and the relationship was of moderate strength (r = .49). There was no statistically significant relationship between social support satisfaction and state self-esteem (rs = .18, p = .30). Regression results showed that the overall association was statistically significant, F (2, 50) = 8.32, p < .001, and together hope and social support satisfaction accounted for 25% of the variance in state self-esteem. However, only hope made a statistically significant, unique contribution to the estimation of state self-esteem ([beta] = .49, p < .001). Social support satisfaction was not significant to the prediction of state self-esteem ([beta] = .12, p = .383). There was no interaction effect between hope and social support satisfaction on state self-esteem. Conclusions. Hope and social support satisfaction are psychosocial factors which contribute to higher levels of self-esteem in early stage dementia. Future investigation is warranted to explore predictors of self-esteem and other important components of self-concept.
Thrombospondin-1 promotes tumor cell invasion by up-regulating matrix metalloproteinase-9 expression
Authors:   , Wang Thomas Nien-Tsu , Tuszynski George P.
Published: July 2024

Significant efforts have been made to understand the molecular and cellular mechanisms involved in tumor cell invasion. Matrix metalloproteinases (MMPs) represent a family of zinc containing enzymes which degrade extracellular matrix components, allowing cells to traverse connective tissue efficiently during tumor cell invasion. Although matrix metalloproteinase-9 (MMP-9) has been shown to play an important role in tumor metastasis, the mechanism of MMP-9 activation is unknown. We hypothesize that thrombospondin-1 (TSP-1), an adhesive glycoprotein found in malignant tumor tissue, up-regulates MMP-9 expression and production in tumor cells thereby permitting tumor cell invasion of collagen. In the following studies, we showed that TSP-1 promotes tumor cell adhesion and invasion. We demonstrate that TSP-1 promotes in vitro tumor cell invasion in three different lines of human breast cancer cells with no effect on benign breast tumor cells. Furthermore, antibodies against TSP-1 and antibodies against a TSP-1 receptor inhibited tumor cell invasion in vitro. In addition, mice inoculated with breast cancer cells in the peritoneal cavity were treated with antibodies against a TSP-1 receptor. No micrometastases developed in the treatment groups. These results suggest that anti-TSP-1 receptor antibody inhibited breast tumor colony development by blocking in vivo adherence, and possibly, invasion. In our final series of experiments, we demonstrated by gelatin zymography and Western blot analysis that TSP-1 up-regulates MMP-9 production. Furthermore, TSP-1 up-regulated MMP-9 expression as demonstrated by mRNA analysis. Antibodies against MMP-9 similarly inhibited TSP-1 stimulated breast cancer cell invasion of collagen in our in vitro model. We conclude that TSP-1, through the up-regulation of MMP-9 expression, production and activation, promotes tumor cell invasion of collagen. We speculate that TSP-1 may play an important role in tumor cell invasion of the basement membrane. Stromal TSP-1, found in higher concentrations adjacent to tumor cells or cancer tissue may stimulate MMP-9 production by the tumor cells or adjacent fibroblasts necessary for tumor cell invasion. Future studies need to be conducted to determine the mechanism of how TSP-1 up-regulates MMP-9 production and the intricate cell-cell and cell-matrix interaction during metastasis.
The effect of management and auditor reports on internal control on financial analysts' perceptions and decisions
Authors:   , O'Reilly-Allen Margaret
Published: July 2024

In recent years, management and auditor reporting on internal control has been considered by the Securities and Exchange Commission and by numerous private sector organizations as a means to improve the reliability of financial statements. This study provides empirical evidence concerning whether such reports achieve this objective. The study involved an experiment that examined whether management and auditor reports on internal control affected financial analysts' perceptions and decisions associated with measures of financial statement reliability. The independent variables in the study were the type of report on internal control issued (a management assertion issued in compliance with the COSO guidelines, an unqualified attestation opinion issued in compliance with the current attestation standards, and a report issued by the auditor that reports directly on internal control rather than on management's assertion) and the reporting threshold used (material weakness and reportable condition). The methodology involved mailing case studies to the financial analysts. The case studies provided financial statements and the related notes; the auditor's unqualified report on the financial statements; and a brief summary of the industry, company, and lines of business for a hypothetical company. All information was held constant except for the presence of or version of the report on internal control The analysts provided their perceptions of the reliability of the company's financial statements, the effectiveness of internal control over financial reporting, the credit risk associated with a new bond issue of the company, and their decision to recommend the bond issue as a buy, sell, or hold to a portfolio manager. A multivariate analysis of variance (MANOVA) and analysis of variance (ANOVA) were the statistical tests used to analyze the relationships between the independent and dependent variables. The results of the study indicated that all versions of the auditor's report on internal control significantly affected the respondents' perceptions about the reliability of financial statements and the effectiveness of internal control. Management reports on internal control, however, did not affect these perceptions. The results also indicated that neither management nor auditor reports on internal control affected perceptions of credit risk or the buy, sell, or hold recommendation.
Probing the architecture of the Serotonin 5-HT₃ receptor ligand-binding domain
Authors:   , Nyce Heather L. , White Michael M
Published: July 2024

The serotonin 5-HT₃ receptor (5-HT₃R) is a member of the cys-loop family of ligand-gated ion channels. Functional receptors are pentamers and the ligand-binding domain is composed of contributions from six non-contiguous loops (A-F) that converge at subunit-subunit interfaces. 5-HT₃R's are found in bath the central and peripheral nervous systems and receptor antagonists have proven effective in the treatment of irritable bowel syndrome (IBS) and emesis due to cancer chemotherapy or anesthesia. This dissertation employs the combination of site-directed mutagenesis, double-mutant cycle analysis and homology modeling as a way to map the functional architecture of the 5-HT₃R ligand-binding domain. Two regions are examined: Loop A residues (I127, E129, F130, V131, D132, V133, K135 and S136) and four residues located within 6 A of the bound antagonist in a ligand-receptor model (T181, S182, H185 and E236). Antagonists of differing structure were used to determine the spatial orientation of residues in the binding site and double-mutant cycle analysis indicated residue involvement in ligand-binding. Mutation of E129 and H185 to alanine and E236 to aspartate abolished surface expression and prevented ligand binding. Mutation of the other residues resulted in specific binding of radioligand and small changes in affinity of antagonists for the receptor; however, double-mutant cycle analysis is only consistent with residues E236 and T181 making a direct physical contact with the antagonists d-tubocurarine (dTC) and granisetron, respectively. When combining previous data linking regions of dTC to 5-HT₃R residues R92 and N128 with the knowledge that dTC is a rigid molecule of known three-dimensional structure, the present data allow for the addition of a third spatial constraint (E236) to the arrangement of residues in the 5-HT₃R ligand-binding domain and permit the creation of a more accurate homology model. The use of antagonists as "molecular rulers", in conjunction with double-mutant cycle analysis of mutant receptors, permits the spatial mapping of residues in the ligand-binding domain. The identification of specific residues involved in ligand-binding, as well as classification of residues near the binding site but not directly involved in binding, is essential for building a more accurate model of the 5-HT₃R ligand-binding domain that may aid in the future development of 5-HT₃R-selective therapeutic agents.
Working with semantic memory
Authors:   , Littlefield Lauren Montenegro , Hewett Thomas Taysum
Published: July 2024

The Semantic Judgment Test (SJT) is a simple measure of semantic memory processing, modeled after Khomskaya and Skakun's definition paradigm (1985) and devised to study how nonepisodic, explicit memory processing is disrupted by frontal pathology. The concept of working-with-memory (WWM) can be used as a theoretical tool to describe frontal lobe executive memory processing. The rationale is that novel, rule-based processing (in this case, the ability to select the most meaningful attributes of word stimuli) requires frontal mediation. To test this idea, a semantic memory battery was administered to 20 frontally lesioned participants and 20 healthy controls matched by sex, age, and education. The SJT correlated with known measures of frontal functioning and working memory. Furthermore, the SJT differentiated between frontal lesioned and comparison groups with frontals exercising markedly poorer selectivity in word definition and tending to endorse tangential words as central to defining primary stimulus words. The obtained findings lend support for the elaborated theory of working memory, with the frontal lobes as the executors of semantic information processing.
Parents' reactions to two Pennsylvania commitment laws for minors
Authors:   , Zaplac Trudi
Published: July 2024

One hundred twenty-eight adult residents of Pennsylvania completed a brief opinion questionnaire on procedural justice aspects of two commitment laws for minors. The Mental Health Commitment (MHC) law allowed parental control over the commitment decision. The Substance Abuse Commitment (SAC) law required judicial control over the commitment decision. Subjects found the parental control-MHC law to be more fair than the judicial control-SAC law. Subjects were more satisfied with an unfavorable outcome (denial of commitment) under the parental control-MHC law than they were with an unfavorable outcome under the judicial control-SAC law. Multiple regression analyses indicated that when the effect of control over outcome was controlled statistically, perceptions of fairness were determined by elements of procedural justice theory (voice, neutrality of decision-maker, and respect/dignity afforded parents). Neither control over outcome nor procedural justice theory was a significant predictor of satisfaction with an unfavorable outcome under either law. Findings suggest that procedural justice theory does not explain reactions to parent-child disputes as well as it explains other kinds of disputes. These results support the application of procedural justice theory to perceptions of fairness, but not to satisfaction with unfavorable outcomes in parent-child disputes that are subjected to resolution by a third party decision-maker.
Unique iodine metabolic pathway activates the Aryl Hydrocarbon Receptor Pathway in the MCF-7 human breast cancer cell line
Authors:   , Stoddard Frederick Rhode , Brooks Ari D
Published: July 2024

The protective effect of iodine on breast cancer and its importance in normal breast physiology has been well established through multiple studies. Iodine deficiency leads to breast dysplasia in animal models while iodine replacement can reverse iodine deficient induced dysplasia. Additionally, high iodine diets have been shown to inhibit cancer promotion in various animal models. Epidemiologic data demonstrating that areas with high iodine diets, such as Asia, have a low incidence of breast cancer suggests that iodine plays a role in human breast physiology. This is further supported by evidence that Iodine supplementation can relieve symptoms from certain benign breast diseases in human studies. Together, these data supports a role of iodine in maintaining healthy breast tissue and preventing early dysplastic and malignant changes. However, despite the strong evidence that iodine plays an important role in normal breast physiology, there are few studies that describe iodine's mechanism of action or target pathways within the breast. Microarray data identified Cytochrome P450 1A1 (CYP1A1) and other estrogen metabolizing enzymes as key genes altered in response to iodine/iodide treatment in an MCF7 in-vitro model. We found CYP1A1 up regulation to be specific to iodine (12) but not iodide (I-) in a dose and time dependent manner. Subsequently we identified the aryl hydrocarbon receptor (AhR), the key regulator of CYPA1A1, as a key mediator of iodine induction of CYP1A1. Finally, iodine gene expression profiling demonstrates significant, albeit more selective, overlap with dioxin, the prototypic ligand of the AhR. This thesis elucidates the first step in the iodine metabolic pathway and unites it to the AhR pathway, a well studied, albeit poorly understood pathway. Identifying the AhR as a key mediator of the iodine response not only affords a more direct approach to future studies on iodine but also provides key data that will hopefully help elucidate critical components of the AhR pathway. Identifying iodine's mechanisms of actions and understanding its role in human physiology will help us identify the consequences of whole-body iodine deficiency and enter an era where iodine is utilized in accordance with its true physiologic import.
A spectral stochastic model of virus transport in aquifers
Authors:   , Rehmann Linda L. Campbell , Welty Claire
Published: July 2024

This thesis presents derivation of a spectral stochastic model of field-scale virus transport in heterogeneous, saturated, granular porous media. The effects of small-scale spatial variability in aquifer parameters (e.g., hydraulic conductivity, pore water velocity) as well as virus attachment, detachment, and inactivation parameters on large-scale transport are evaluated. The stochastic mean model is developed from a simple coupled system of local-scale free virus transport and attached virus conservation equations containing transport phenomena expressions obtained from existing literature. The resultant mean equations are found to differ significantly from the local-scale equations, including, for example, modified advection, dispersion, attachment and detachment coefficients, as well as additional macroscopic gradient terms. These macroscopic effective parameters are complex functions of the local-scale transport processes. In order to fully understand the implications of the mean model and its sensitivity to input parameters, numerical simulations of the derived mean equations were conducted. In general, the mean transport model predicts significantly earlier breakthrough than the equivalent local-scale model. As the degree of heterogeneity (variance of the natural-logarithm hydraulic conductivity distribution) is increased, breakthrough occurs successively earlier to such a degree that for a highly heterogeneous aquifer, virus breakthrough can actually precede that of a tracer. Such behaviour has been observed in field and laboratory experiments, and has been attributed to the size exclusion effect. Increasing aquifer heterogeneity also results in decreased model sensitivity to the ratio of free to attached virus inactivation rates, most likely due to decreased residence time resulting from faster transport in higher hydraulic-conductivity lenses. Both the stochastic mean model and the local model are found to be more sensitive to the inactivation rate of the attached viruses than that of the free viruses, indicating that incorporating different rate constants for free and attached viruses is important. As the mean aquifer hydraulic conductivity is increased, the mean model shows less sensitivity to other input parameters such as InK variance and colloid diameter. Mean and modified local breakthrough curves differ the most for the least conductive aquifers studied. Because a more conductive aquifer would experience fewer interactions between colloids and its larger grains (i.e., less filtration), spatial variability would be expected to have less of a role than in a low-conductivity aquifer in which significant interactions occur between colloids and grain surfaces.
Molecular aspects of a phosphate carrier of Plasmodium falciparum
Authors:   , Bhaduri-McIntosh Sumita , Sylvester James E.
Published: July 2024

Glycolysis is the primary source of energy in erythrocytic stages of malarial parasites and mitochondrial contribution to the ATP pool via oxidative phosphorylation is believed to be absent. While there is no direct evidence for mitochondrial ATP synthesis yet, some of the recent studies seem to indicate its existence. Several components are necessary for mitochondrial oxidative phosphorylation. We have isolated the gene for one such component, a nuclear gene encoding the Plasmodium falciparum homologue of the mitochondrial phosphate carrier (PfMPC). The encoded protein is a member of the family of mitochondrial anion transport proteins which includes proteins such as the adenine nucleotide carrier (ADP/ATP carrier), the uncoupling protein, and the oxoglutarate carrier. Sequence analysis of PfMPC revealed it to be an integral membrane protein with six transmembrane domains, and with significant homology to MPC from other organisms. A 2 kb RNA was detected by Northen blot analysis at similar levels in both asexual and sexual stages, suggesting the presence of PfMPC in both these stages. These results indicate that malarial parasites possess a critical component required for oxidative phosphorylation, and that this component is expressed in asexual stages. Furthermore, analysis of asexual stage-specific PfMPC transcript indicated that its levels are regulated such that it is at a minimum in ring stages and gradually builds up to a peak in late trophozoites. These observations parallel the expected increase in demand for energy within the parasites in late trophozoites. Import studies of PfMPC protein into heterologous mitochondria demonstrated its ability to be imported into mitochondria and thus provided indirect evidence for its mitochondrial location. Direct evidence in the form of antibody studies and functional studies in malarial parasite is lacking. In the absence of evidence to the contrary, other location and hence other unknown functions of PfMPC cannot be ruled out. Information regarding PfMPC transcription are consistent with the suggestion that erythrocytic stages of malarial parasites may possess a potential for mitochondrial ATP synthesis. Although not a primary source, mitochondria in malarial parasites may serve as a secondary source of energy.
The role of transcription factor SP1 in apoptosis
Authors:   , Torabi Behzad , Clifford Jane
Published: July 2024

Sp1 is a ubiquitous transcription factor that regulates many genes involved in cellular proliferation, cell cycle, DNA damage, apoptosis and senescence. Earlier work in this lab demonstrated that Sp1 is phosphorylated by ATM kinase in response to DNA damage. At high levels of DNA damage, Sp1 was observed to be degraded. This work was directed at determining the mechanism and significance of Sp1 degradation. High levels of DNA damage or activation of the extrinsic apoptotic pathway by TRAIL, resulted in caspase-mediated cleavage of Sp1. Further analysis revealed that caspase cleavage of Sp1 in cell free or cell systems is at aspartic acid 183, a site which has not been shown previously to be targeted by caspases. Sp1 with mutation at residue 183 from aspartic acid to alanine is resistant to cleavage, and ectopic expression of Sp1 D183A renders cells resistant to apoptotic stimuli, indicating that Sp1 cleavage is involved in the induction of apoptosis. We also observed that lowering levels of transcription factor Sp1 with RNAi significantly reduces apoptosis in response to various apoptotic stimuli. Whether these effects were due modulation of transcription of factors involved in apoptosis was further explored. We have identified pro-apoptotic Bd-2 family member Bid as a transcriptional target of Sp1. Depletion of Sp1 by RNAi significantly reduced levels of Bid protein and mRNA, whereas, over-expression of Sp1 increased Bid RNA and protein levels. We used chromatin immunoprecipitation to demonstrate that Sp1 binds to the BID promoter in the same region previously shown to be bound by p53. The regulation of Bid by Sp1 is p53 independent, based on the finding that Bid was induced by Sp1 over-expression in SAOS-2 cells, which are p53-/-; moreover, the depletion of Sp1 had no effect on p53 levels. Knockdown of SO or Bid significantly reduced apoptosis in response to UV and TRAIL. Taken together, these findings suggest that Sp1 is involved in regulation of apoptosis through caspase-mediated cleavage and transcriptional regulation of Bid. Many traditional chemotherapies and new therapeutic approaches target apoptosis initiation. The regulation of Bid and apoptosis by SO may provide a therapeutic target for cancer therapy.
Understanding O-GlcNAc transferase Regulation of SIRT1 in Breast Cancer Cells
Authors:   , Lu Tong , Reginato Mauricio J
Published: July 2024

Breast cancer is a deadly disease that is commonly diagnosed in women. There are many subtypes, including hormone dependent and hormone independent breast cancers. These various subtypes all eventually develop resistance to drug treatment. Thus, it is important to identify new therapeutic targets for breast cancer treatment. An area that holds promise is cancer metabolism. Cancer cells have an altered metabolic state known as the Warburg effect in which a majority of the consumed glucose is used for aerobic glycolysis even in the presence of oxygen. This process allows for cancer cells to produce the necessary material for biomass production. The enzyme O-GlcNAc transferase (OGT) has been shown to be elevated in breast cancers, resulting in increased O-GlcNAcylation. OGT is required for breast cancer cell growth and invasion. Our lab has recently shown that OGT regulates breast cancer cell invasion via the longevity protein SIRT1. Here, we identify the molecular pathway that OGT regulates SIRT1 in breast cancer cells. We show that the nutrient sensor 5' adenosine monophosphate-activated protein kinase (AMPK) plays a major role in SIRT1 regulation. Glucose deprivation, OGT inhibition and treating cells with AMPK activators induce expression of SIRT1 in breast cancer cells. In addition, we show that reducing levels of OGT in breast cancer cells leads to activation of AMPK. This activation is required for increasing levels and activity of SIRT1 as treatment with AMPK inhibitor blocked SIRT1 levels and activity in multiple breast cancer cells examined. In addition, using mouse embryonic cells containing AMPK knockout, we show that OGT regulation of SIRT1 requires AMPK. Taken together, our data suggests that OGT, and O-GlcNAcylation, controls levels and activity of SIRT1 in breast cancer cells through regulation of AMPK activity.
HIV-1 Disease, Substance Abuse and HCV Co-infection
Authors:   , Parikh Nirzari , Wigdahl Brian
Published: July 2024

Substance abuse, including the use of cocaine and cannabinoids, is a significant risk factor for exposure to human immunodeficiency virus type 1 (HIV-1) and the development of acquired immune deficiency syndrome, as well as hepatitis C virus (HCV) exposure, infection, and disease. HIV-1, along with HCV, share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Thus, co-infection with HIV-1 and HCV is common and may be impacted by chronic substance abuse during the course of disease. This thesis evaluated the relationship between illicit drug use and HIV-1 disease severity in HIV-1-infected patients enrolled in the DREXELMED HIV/AIDS Genetic Analysis Cohort, whose drug histories have been recorded longitudinally. Since, cocaine and cannabinoids are known to have immunomodulatory effects, the cytokine profiles of preferential non-users (PN), preferential cocaine (PCo) and preferential cannabinoid (PCa) users as well as multi-drug (MD) users were analyzed utilizing Luminex technology to understand the effects of drugs on cytokine modulation and HIV-1 disease severity. This analysis culminated in the development of a novel biostatistical model, which allowed defining the effects of specific drugs. Overall, PN and PCa users had better health as compared to PCo and MD users, with respect to normally assessed clinical parameters associated with HIV-1 disease and in fact, cannabinoids appeared to show a potential neuroprotective effect. Among the 30 cytokines investigated, differential levels of cytokines were established within these populations; cocaine use associated with an increase in Th2 cytokines, IL-4 and IL-10, and GM-CSF, while cannabinoid use associated with an increase in the Th1 collective panel as well the cytokines IL-113 and IL-1RA, and IL-2. Since over 40% of the cohort was co-infected with HCV, the impact of co-infection with HCV on the HIV-1 pathogenic process was compared in these patients. Comparing HIV-1 mono-infection with HIV-1/HCV co-infection allowed defining the detrimental effect of HCV co-infection as it relates to the associated immune response during the course of this complex interplay, in the background of substance abuse. Therefore, understanding the complex interplay between HIV-1, HCV, and drugs of abuse is essential to define HIV-1 disease within these patients.