bluuebunny/crossref_metadata_2025 huggingface dataset:
A story of the AGEs
Authors:   , Loughlin Danielle T. , Artlett Carol , Blankenhorn Elizabeth P
Published: July 2024

Advanced glycation end products occur through nonenzymatic glycation of long lived proteins such as collagens. One precursor to these modifications, 3-deoxyglucosone (3DG), is elevated in patients with diabetes and contributes to the accumulation of advanced glycation end products on collagen and may potentiate the poor wound healing observed in these patients. Since wound repair is dependent on fibroblast migration, proliferation, and expression of extracellular matrix proteins, we examined the role of 3DG-modified type I collagen and the subsequent response of dermal fibroblasts to this modification. Initial studies showed that 3DG-collagen reduced the expression of essential growth factors in fibroblasts. Furthermore, fibroblasts increased their adherence and reduced their migration on 3DG-collagen, which was dependent on the activation of [alpha]1[beta]1 integrin and growth factor receptor signaling. Also, studies showed that 3DG-collagen induced oxidative stress and caspase-3 activation. Oxidative stress was found to be dependent on the upregulation of NAD(P)H oxidase 4, triggering endoplasmic reticulum stress, as assessed by the ER stress-induced apoptosis marker Growth Arrest and DNA Damage-inducible gene 153 (GADD153). 3DG-collagen activated GADD153 and caspase-3 via phosphorylation of p38 mitogen activated protein kinase (MAPK), and this was dependent on upstream reactive oxygen species. Investigations also demonstrated that 3DG-collagen-induced caspase-3 activation did not signal through the canonical receptor for advanced glycation end products but through [alpha]1[beta]1 integrin. Neutralization of [alpha]1[beta]1 integrin prevented 3DG-collagen-induced upregulation of the ER stress pathway; suggesting that 3DG-collagen signaling to the fibroblast was dependent on [alpha]1[beta]1 integrin. Additional studies investigated the role of p38 MAPK in controlling cell growth in fibroblasts cultured on 3DG-collagen. Studies demonstrated that p38 MAPK can promote either cell growth or cell death, and that this was dependent upon activation of upstream H-ras and ASK1. Cell growth on native collagen was dependent on p38 MAPK phosphorylation of AKT and ERK1/2. In contrast, 3DG-collagen decreased fibroblast migration, proliferation, and collagen expression through ER1C1/2 and AKT downregulation via p38 MAPK. Finally, meglumine attenuated the effects of 3DG-collagen on dermal fibroblasts. Taken together, these data indicate that 3DG-collagen negatively impacts dermal fibroblast migration, proliferation, and survival, and may play a significant role in chronic diabetic wounds.
An exploration of the relationship between executive functioning and stage of change in hospitalized pre-adolescents and adolescents
Authors:   , Greenstein Deanna
Published: July 2024

The rationale for admitting pre-adolescents and adolescents to psychiatric hospitals is based on the expectation that change will occur. Yet, not all pre-adolescents and adolescents admitted to in-patient units may be ready to change. The Transtheoretical Model addresses an individual's readiness for change and can predict the likelihood for change based on readiness. While frequently used with adults, the model has never been applied to pre-adolescents and adolescents involved in psychiatric treatment. Thus, one of the goals of this study was to provide descriptive information on the application of the Transtheoretical Model's stages of change to in-patient adolescents and pre-adolescents. A second goal was to examine the relationship between movement through the stages of change and executive functioning. Executive functions (e.g. attention, planning, and mental flexibility) have been shown to be deficient in subjects with the types of disorders treated on adolescent in-patient units. Because executive deficits can translate to impulsively acting out, poor attention and concentration, and poor planning abilities, an individual who manifests executive deficits may have more difficulty changing than an individual with intact executive functioning. Subjects included 89 adolescents and preadolescents admitted to a psychiatric inpatient unit. To determine stage of change, subjects were administered a measure of the stages of change (the University of Rhode Island Change Assessment Questionnaire) at admission and discharge. Subjects were also administered tests of planning, attention and mental flexibility. The results revealed that subjects were approximately equally distributed between the beginning stages of change and the later stages of change at admission and discharge. Additionally, there were significantly more subjects who did not progress a stage than subjects who did progress a stage. Analyses of variance revealed that there were no significant differences in planning, attention and mental flexibility between the group of subjects who did not progress a stage and the group of subjects who did. However, a Readiness to change score was negatively correlated with mental flexibility. The results are discussed in terms of their implications relative to the Transtheoretical model and the URICA.
Essays in mergers and acquisitions
Authors:   , Tran Anh Luong , Fich Eliezer M
Published: July 2024

This dissertation studies mergers and acquisitions in which managerial compensation may give right to problems between principal and agent. In chapter 2, I focus on firms formed for the sole purpose of making an acquisition. These firms, also known as Special Purpose Acquisition Companies (SPACs), often exhibit a unique compensation system for their managers. I document that in SPACs managers do not receive any compensation unless these SPACs complete an acquisition. I test whether such compensation structure prompts SPAC managers to engage in bad acquisitions. My findings indicate that, because of the way SPACs are regulated and monitored, these companies make better acquisitions and pay a lower price for their targets. The third chapter studies the effects of golden parachutes to chief executive officers (CEOs) of firms that receive takeover bids. A key innovation in this study is that it addresses the relative importance of parachutes to CEOs. That is the effect of parachute payments on the personal wealth of the chief executives. I find that the size of parachutes is an inverse function of the takeover premiums paid for publicly traded targets. The results of this chapter contribute to the debate on the effectiveness of the compensation contract given to top managers in public companies. The last chapter studies companies that grant their CEOs unscheduled stock options during private merger negotiations. The results indicate that these last-minute options substitute for golden parachutes and compensate target CEOs for benefits they forfeit because of the merger. Targets granting unscheduled options are more likely to be sold but they also earn lower premiums. In contrast, firms that buy targets that engage in this compensation practice earn higher returns upon their merger announcement. Together, these results imply a transfer of wealth from target shareholders to bidder shareholders. The evidence in this chapter adds to the literature studying the effects of acquisition related exit compensation to top managers of firms that are taken over. JEL classification. G34 Keywords. Acquisitions; Executive Compensation; Corporate Governance.
Design and fabrication of liquid crystal waveguides using photolithography
Authors:   , Herbert Sylvia Lee , Fontecchio Adam
Published: July 2024

Recent innovations in fiberoptic communications have developed a need for improved optical switching between cables. Current optical switches are expensive and challenging to manufacture. This thesis focuses on the design and creation of a liquid crystal waveguide using photolithography to allow for inexpensive and simple switching devices that can be integrated directly into fiberoptic networks. Liquid crystal (E7) acts as the guides within a polymer matrix (NOA 65). The theory and parameters of this experiment are described, as well as the fabrication and characterization of the liquid crystal waveguides. Results show that stable waveguides can be made using 35-40% liquid crystal E7 with 60-75% polymer NOA 65 at 90 C and 20 Watt UV light.
Demand driven production and distribution
Authors:   , Mallya Sudhirkumar N. , Burton J
Published: July 2024

The decisions regarding production, inventory and distribution planning are made independent of each other in most organizations. In reality, however, these decisions are interdependent. Existing inventory models consider the trade off between fixed reorder and variable inventory holding costs. In an Electronic Data Interchange (EDI) environment, a significant portion of the reordering cost is the transportation cost. In a multicommodity, multiple location distribution network, the transportation cost of a commodity can vary greatly depending on the ordering pattern of other commodities and locations nearby. Even in production planning, in the context of a supply chain network, manufacturing lot sizes and their timings depend on the demands, which are, in effect, the planned dispatches to various locations in different periods from the production facility. In an EDI environment, one can take advantage of these interrelationships by integrating the vehicle routing, inventory management and production planning decisions for all commodities at all locations, in order to minimize total logistic costs. The basic aim of this research is three fold; First, a "Demand Driven Production and Distribution" (DDPD) operating concept is developed for a multicommodity production and distribution scenario. Second, a mixed integer programming model is developed so as to combine the decisions regarding the production plans, delivery quantities and vehicle routes to meet the demands for all commodities at all locations. Third, an efficient solution procedure is developed using a modified Lagrangian relaxation approach in a branch-and-bound framework, to solve the mixed integer programming model. Computational results show that the modified Lagrangian relaxation is fast enough for all practical purposes. Branch-and-bound procedure can be used to arrive at the optimal solution. It is also shown that substantial savings in total logistic costs can be achieved by using the proposed DDPD approach.
Performance contrast analysis in the detection of malingering
Authors:   , Zigler Lanie Y. , Williams Joseph M
Published: July 2024

Malingering is a conscious attempt to falsely represent or exaggerate the presence of physical or psychological symptoms for financial or other compensation. Malingering is extremely common among patients referred for evaluation of mild traumatic brain injury, estimates range from 33 to 60 percent of all patients complaining of persistent postconcussive symptoms. One aspect of malingering that has not been systematically examined is the tendency of malingering patients to produce patterns of symptoms and test performances that are discrepant from known patterns of illness. The following study examined an empirical method for summarizing such discrepancies called, Performance Contrast Analysis. The procedure uses multiple regression analyses to generate expected patterns of performance derived from premorbid status and interrelationships of subtests of the Wechsler Adult Intelligence Scale - Revised, a common clinical neuropsychological test used to examine traumatic brain injury. The derived expected scores for four groups of subjects were compared: Nonmalingering Uninjured, Malingering Uninjured, Injured in Litigation and Injured not in Litigation. It was hypothesized that the Malingering Uninjured and Injured in Litigation groups would show the greatest discrepancy scores. Results were consistent with hypotheses for the contrast based upon WAIS-R subtests: the Uninjured Malingering group had the greatest discrepancy, followed by the Injured in Litigation. The Injured not in Litigation group was similar to the Nonmalingering Uninjured subjects. The formula based on premorbid status was also statistically significant but not as discriminating as the subtest contrast. These results clearly suggest that malingering subjects are much more likely to violate known patterns of relationships embodied in the WAIS-R subtests. Performance Contrast Analysis based upon these subtests should serve as a unique clinical tool in the detection of malingering.
Characterization of proteins that interact with the amino-termius of the plasmodium merozoite surface protein 1 (MSP-1)
Authors:   , Mello Kerrianne , Bergman Lawrence W
Published: July 2024

Merozoite surface protein 1 (MSP-1) is a large molecular weight protein expressed on the surface of the malaria merozoite in a non-covalent complex with other protein molecules. MSP-1 undergoes a series of proteolytic processing events but a precise biological role for the various proteolytic fragments of MSP-1 or for the additional proteins present in the complex is not known. Through the use of the yeast-two hybrid system, we have isolated genes encoding proteins that interact with a region of the amino terminal proteolytic fragment of MSP-1 from the mouse parasite Plasmodium yoelii. This analysis has led to the isolation of two sequence-related molecules, one of which is the P. yoelii homologue of MSP-7 originally described in Plasmodium falciparum. In P. yoelii we have designated these sequences PyMSP-7 and PyMSRP-2. Immunofluorescence studies co-localize these proteins with PyMSP-1 and each other to the surface of late stage P. yoelii 17XL parasites. Immunization with PyMSRP-2, but not PyMSP-7, can protect mice against P. yoelii 17XL lethal challenge even though RT-PCR data suggests there is 2 fold more message present for PyMSP-7 during infection. Blast analysis of the P. falciparum database has revealed that there are 6 related protein molecules present in this species encoded near each other on chromosome 13 and 3 related protein molecules in P. berghei. In P. falciparum , we have designated these molecules MSP-7 and MSRP 2-5. Analysis of the P. yoelii and P. berghei databases indicates a similar chromosomal organization for the genes in the mouse parasite species. The three P. falciparum sequences with the highest degree of homology to the P. yoelii sequences isolated in the two-hybrid screen have been characterized at the molecular level (MSRP 1-3). Expression analysis indicated that the mRNAs are expressed at varying levels in the different asexual stages. Immunofluorescence studies co-localized the expression of the MSRP molecules and the amino-terminal portion of MSP-1 to the surface of trophozoites and schizonts. In vitro binding experiments confirm the interaction between MSRP-1, MSRP-2, and the amino-terminal region of P. falciparum MSP-1.
Joint Models of Longitudinal and Time-to-Event data for Prediction of Life Expectancy Using Age Related Biomarkers
Authors:   , Khutoryansky Natalie , Kriete Andres
Published: July 2024

The identification of biomarkers that can help in making an estimation of the expected lifespan of an individual is an active area in aging research. Mathematical modelling based on longitudinal experimental data is a very helpful tool in this respect. One of the promising directions in discovering and mathematical description of such relationships is the statistical joint modeling of longitudinal aging biomarker variables and time to events. This work reviews joint models for longitudinal data and survival data available in statistical literature for clinical trials that may be useful in relating biomarkers profiles and aging. In contrast to previous publications, specifically for mouse datasets concentrating on the linear trend of these biomarkers over age, this work implemented a more advanced longitudinal analysis based on a repeated measures ANOVA model with age as a discrete factor. The second novelty for the longitudinal biomarker analysis of the mouse dataset is in considering an individual animal as a subject instead of a strain as a subject, which increases the statistical power of the analysis and make consequent conclusions more convincing. The final survival analysis connecting the immune biomarkers with lifespan of mice has detected the most influential biomarker-age interaction factors for survival of the mice that may be useful in human aging research.
A high speed VLSI architecture for the discrete haar wavelet transform
Authors:   , Becker Peter Edward , Johnson Jeremy Russell
Published: July 2024

An alternative to strictly time- or frequency-domain analysis, wavelets provide a multiresolution analysis of signals for input to processing such as edge detection, compression, and pattern recognition. High speed VLSI architectures are necessary for real-time processing of large data sets. Presented here is such an architecture for the Haar wavelet transform, the simplest and easiest wavelet to understand. From this base model, a generalization of the architecture to other wavelets is discussed, as well.
Regulation of neuronal CXCR4 signaling by opioids
Authors:   , Sengupta Rajarshi , Meucci Olimpia
Published: July 2024

Heterologous desensitization is a potential mechanism involved in the regulation of chemokine receptors. The chemokine CXCL12 and its receptor CXCR4, also a HIV co-receptor, play a significant role in neuronal development and homeostasis. Studies from our lab have shown that mu-opioid agonists, such as DAMGO and the endogenous peptide endomorphin-1 inhibit the neuroprotective action of CXCL12 in cultured rat cortical fleurons. Here we studied the cellular and molecular mechanisms behind opiate action and identified a novel mediator of the effect of opioids on CXCR4 signaling in vivo. Briefly, we show that the inhibitory action of opioids is due to a direct effect on neurons (i.e. flot glia-mediated) and requires prolonged mu-opioid receptor (MOR) stimulation. CXCR4-induced G[alpha]i and G[beta][gamma] activities are both suppressed following DAMGO treatment as indicated by analysis of different downstream targets regulated by CXCL12. GTP[gamma]S incorporation assays in brain suces also indicate a reduced coupling of CXCR4 to G[alpha]i in the cortex and hippocampus of morphine-treated rats. Furthermore, morphine pretreatment inhibits pro-survival signaling in cortical cultures. In addition, treatment of cultured neurons with morphine or DAMGO also leads to a decrease in the ligand-induced CXCR4 phosphorylation. Overall these findings point to a deficit of CXCR4 activation in opioid-treated neurons. Interestingly, initial studies with brain tissue samples from HIV and control patients show a reduction of CXCR4 phosphorylation (pS339) in HIV+ patients with neurological problems as compared to HIV- control and neurologically normal HIV+ individuals, suggesting that impairment in CXCR4 may lead to neuronal dysfunction in humans. Finally, we demonstrate for the first time the involvement of the ubiquitous peptide ferritin heavy chain (FHC) in mediating opioids' action on CXCR4 signaling. Treatment of cortical neurons with DAMGO or morphine up-regulates FHC levels through activation of MOR. Elevated FHC levels are also detected in cortical tissue from rats treated with morphine. The FHC increase temporarily correlates with the reduction of CXCR4-mediated responses while inhibition of FHC expression by siRNA prevents the effect of opioids on CXCR4. Altogether, these data suggest that opiates interfere with normal CXCR4 function in the brain and may exacerbate progression to neuroAIDS in HIV-positive drug users.
Deposition of wear resistant steel surfaces by the plasma rotating electrode coating process
Authors:   , Kim Michael Robert , Smith Ronald W.
Published: July 2024

A high-deposition rate thermal spray method was investigated for the purpose of coating aluminum cylinder bores with a wear resistant surface. This method, the plasma rotating electrode coating system (PROTEC) utilized transferred-arc melting of a rapidly rotating consumable electrode to create a droplet stream via centrifugal atomization. A cylindrical substrate was placed around the rotating rod, in the flight path of the droplets, to deposit a coating onto the internal surface of the cylinder. Selected coatings of 1045 steel deposited by the PROTEC coating method exhibited lower wear loss in lubricated sliding than wire-arc sprayed carbon steel coatings and gray cast iron. Splat cohesion was shown to be a significant factor in the wear resistance of PROTEC coatings. The relationship between deposition enthalpy and cooling rate of the coating was found to have the greatest effect on coating microstructure, and the coating cohesion. The most rapidly solidified coatings showed inferior splat cohesion in comparison to coatings that cooled more slowly. The increase in splat cohesion with decreased cooling rate was accompanied by the formation of a directionally oriented coating microstructure, likely formed during cellular solidification of the coating. A model describing the thermal state of the deposition process was used to predict the deposition conditions that would result in a cellular structure, and the level of splat cohesion required to produce a wear resistant coating.
The relationship of executive functioning and moral reasoning to treatment retention and outcome among urban cocaine abusers
Authors:   , Piatt Andrea L. , Williams Joseph M
Published: July 2024

This study examined the executive functioning and moral reasoning of 41 very poor, urban, predominantly minority, crack cocaine users at the time of intake into a cocaine treatment program, and related these abilities to indices of cocaine treatment retention and outcome. The following neuropsychological battery was administered to 31 men and 10 women an average of 6 days following admission: Wisconsin Card Sorting Test (WCST), Alternate Uses Test (AUT), Trail Making Tests, Controlled Oral Word Association Test (FAS), and the Defining Issues Test (moral reasoning). Results indicated that the sample as a whole performed within the Average range on all executive functioning measures employed. Executive functioning scores were modestly correlated with the number of days subjects were active in treatment (TDT) and the number of counseling sessions attended (CSA) with better executive functioning being positively related to better retention in treatment. However, executive functioning was not associated with treatment outcome as determined by the percentage of clean urine samples (PCU) subjects provided and by the greatest number of consecutive clean urine (CCU) samples that subjects attained. Moral reasoning was modestly related to the Trail Making Test, but to none of the treatment retention or outcome measures. Limitations and directions for future research are discussed.
Resource requirements and competitive abilities of diatoms from the greater Yellowstone ecosystem for silicon and nitrogen
Authors:   , Roh Heuichan , Kilham Susan Soltau
Published: July 2024

The several diatom species used in my study, Asterionella formosa Hass., Aulacoseira subarctica (O. Mull.), Fragilaria crotonensis Kitt. Hass., Stephanodiscus minutulus Kutzing, Stephanodiscus niagarae Ehrenb., and Stephanodiscus yellowstonensis Theriot and Stoermer, were originally isolated from the Lewis, Jackson and Yellowstone lakes. Information on the nutrient kinetics of diatoms under either silicon or nitrogen limitation was obtained for use in a Monod model and in a variable internal stores model of growth. Short-term batch culture growth experiments were fit to the Monod model and long-term semicontinuous culture experiments were fit to the variable internal stores model. The results of both batch and steady state culture methods agree. For Si-limited experiments, S. minutulus is better able to grow at low silicon concentrations than other species, as predicted by its lower K for Si-limited growth. F. crotonensis and A. formosa had the lowest requirement for growth under nitrogen limitation. Nutrient competition experiments were performed in continuous cultures at 15°C and various Si: N ratios. The results generally, but not always, confirmed the predictions based on the Monod relationship for each species. In cultures with all six species silicon-limited (Si: N = 0.25), S. minutulus dominated as predicted. At intermediate Si: N ratios, several species coexisted because each species needs a different resource requirement for either silicon or nitrogen. F. crotonensis dominated as Kilham et al. (1996) predicted at high Si: N ratio when all six species were nitrogen-limited. Clones of these two species (S. niagarae and S. yellowstonensis) isolated for the Yellowstone lakes showed clear differences in their nitrogen physiology, with S. yellowstonensis being able to grow at much lower N levels compared.
Role of O-GlcNAc transferase in cancer cell metastasis and metabolism
Authors:   , Lynch Thomas P. , Reginato Mauricio J , Clifford Jane
Published: July 2024

Cancer cells universally increase glucose and glutamine consumption leading to the altered metabolic state known as the Warburg effect; one metabolic pathway, highly dependent on glucose and glutamine, is the hexosamine biosynthetic pathway. Increased flux through the hexosamine biosynthetic pathway leads to increases in the post-translation addition of O-G1cNAc on various nuclear and cytosolic proteins. A number of these target proteins are implicated in cancer and, recently, O-GlcNAcylation was shown to play a role in breast cancer; however, O-GlcNAcylation in other cancers remains poorly defined. Here, we show OGT is overexpressed in prostate cancer compared to normal prostate epithelium, and OGT protein and O-GIcNAc levels are elevated in prostate carcinoma cell lines. Reducing O-GlcNAcylation in PC3-ML cells was associated with reduced expression MMP-2, MMP-9, and VEGF, resulting in inhibition of invasion and angiogenesis. OGT-mediated regulation of invasion and angiogenesis was dependent upon regulation of the oncogenic transcription factor FoxM1, a key regulator of invasion and angiogenesis, as reducing OGT expression led to increased FoxM1 protein degradation. Conversely, overexpression of a FoxM1 degradation-resistant mutant abrogated OGT RNAi-mediated effects on invasion, MMP levels, angiogenesis, and xiv VEGF expression. Using a mouse model of metastasis, we found reduction of OGT expression blocked bone metastasis. In addition to the regulation of metastasis, we show that OGT is a central factor for the glycolytic shift seen in cancer cells. RNAi-mediated knockdown and pharmacological inhibition of OGT leads to impaired glucose uptake, lactate production, and decreased ATP levels in cancer cells. We demonstrate that reducing OGT levels leads to decreased levels of HIF-1 protein and transcriptional targets, including GLUT1. This decrease in HIF-1 levels results in metabolic stress leading to increased LKB1 and AMPK activation and mTOR inhibition. Regulation of HIF-1 and GLUT1 is critical for OGT-mediated inhibition of growth and glycolysis, as overexpression of stable HIF-1 mutant rescues metabolic defects and growth in OGT-depleted cancer cells. Taken together, these data indicate, for the first time, that flux through HBP, via O- GlcNAcylation, connects with key nutrient sensing pathways regulating cancer metabolism through, in part, regulating a key metabolic regulator HIF-1. Altogether, these data suggest that, as cancer cells alter glucose and glutamine levels, O-GIcNAc modifications and OGT levels become elevated and are required for regulation of malignant properties, implicating OGT as a novel therapeutic target in the treatment of cancer.
Anti-gal immunoglobulin genes
Authors:   , Wang Le , Galili Uri
Published: July 2024

Anti-Gal is a natural antibody present in all humans. It interacts specifically with the carbohydrate structure Gal[alpha]1-3Gal[beta]1-4GlcNAc-R (termed a-galactosyl or [alpha]-gal epitope). As much as 1% of circulating immunoglobulins in human display anti-Gal specificity. The overall objective of the project is to explore the molecular aspects of the anti-Gal production as a model of immune competence in humans, particularly in elderly population. The immediate goal of this study was to understand the immunoglobulin genes involved in this antibody production. This interest emerged from our first part of the study which established an age-associated decrease in anti-Gal affinity in human populations. Since the immunoglobulin concentration in sera of our samples did not change significantly between young and elderly populations, we hypothesized that the low affinity in elderly may result from the lack or excess of somatic mutations or may be caused by the use of inappropriate germline genes. As a first step toward investigating this hypothesis, the second part of our study focused on generation of human anti-Gal mAb by EBV transformation and examining the immunoglobulin genes within several monoclonal cell lines. The results revealed that the utilization of VH genes for the anti-Gal production was biased in that eight of nine anti-Gal B cell clones from seven young individuals used VH3 family genes and one used a VH1 gene. Further, the occurrence of somatic mutations in these genes was demonstrated. To obtain more information on anti-Gal V genes and enhance our ability to study anti-Gal genes, we initiated the use of phage display technology. Preliminary, two combinatorial phage display libraries constructed from young healthy individuals were screened for anti-Gal phage/Fab. Two phage clones displaying anti-Gal specificity were isolated. While the sequences of heavy chains of two clones belong to the same VH3 family, the two light chains used distinct light chain gene families, i.e. V[kappa] and V[lambda] respectively. Both clones contained somatic mutations as well. We hypothesize that the restricted use of VH3 genes for anti-Gal production may be the result of functional constraints imposed by the need of a suitable structural motif for specific interaction with the [alpha]-galactosyl epitope. This study has provided a valuable insight into the gene structures responsible for the anti-Gal production.
The effect of thrombospondin-1 on tumor cell metastasis
Authors:   , John Anitha Sara , Tuszynski George P.
Published: July 2024

Thrombospondin-1 (TSP-1) is a 450 kDa glycoprotein involved in a variety of processes, including cell adhesion, tumor progression, and angiogenesis. Many laboratories cite evidence that TSP-1 serves as an inhibitor of angiogenesis and tumor metastasis; however, evidence from our laboratory and from that of others show that TSP-1 is actually a potent stimulator of tumor progression and has a biphasic role with regards to angiogenesis. Evidence from our laboratory include: (1) TSP-1 promotes lung metastasis in a murine model; (2) TSP-1 modulates tumor cell adhesion; and (3) TSP-1 modulates proteolytic enzyme levels in human tumor cells and these enzymes influence tumor cell invasion. Some of the enzymes modulated by TSP-1 include components of the plasmin/plasminogen system and also matrix metalloproteinase 9 (MMP-9). The work presented here examined two aspects of TSP-1 mediated tumor progression including the capacity of TSP-1 to maintain a controlled proteolytic environment necessary for tumor cell in invasion and the capacity of TSP-1 to modulate tumor cell adhesion to the extracellular matrix. Chapter 2 describes a series of experiments designed to show that TSP-1 upregulates tissue inhibitor of metalloproteinase 1 (TIMP-1), the physiological inhibitor of MMP-9. We show through western and ELISA analysis that TSP-1 modulates TIMP-1 production in a dose dependent manner. In addition, TSP-1 is able to up-regulate TIMP-1 message as well. This property of TSP-1 through a series of antibody and peptide inhibition studies was found to be associated with the CSVTCG domain of type I repeats of TSP-1. Chapter 3 of this thesis describes the novel discovery that TSP-1 is able to regulate breast cancer cell adhesion to components of the ECK specifically laminin. TSP-1 is able to up-regulate expression of the integrin [special characters omitted] subunit which is the [special characters omitted] subunit of a group of laminin receptors, [special characters omitted] and [special characters omitted] integrins. This property of TSP-1 was observed at both the message and protein levels of a series of stably transfected MDA-MB-435 breast carcinoma cells. These cells are able to produce varying levels of TSP-1 and this expression pattern correlated with [special characters omitted] expression in these cells. Functionally, cells with higher TSP-1 production showed increased adhesion to laminin and also increased invasion through a laminin matrix. TSP-1 is a complex molecule with many different functions. Despite the controversy surrounding this molecule in the fields of tumor progression and aniogenesis, we maintain the role of TSP-1 as a potentiator of tumor cell metastasis. The hypothesis presented here is that TSP-1 modulates tumor cell progression through: (1) creating a controlled proteolytic environment necessary for tumor invasion through the up-regulation of (TIMP-1) and (2) modulating tumor cell adhesion to laminin through the up-regulation of [special characters omitted] integrin. (Abstract shortened by UMI.).
Affine invariants for image registration and object recognition using cross-weighted moments and convex hull
Authors:   , Yang Zhengwei , Cohen Fernand S
Published: July 2024

A new class of global relative and absolute affine invariants is presented for dealing with the problem of affine invariant image matching and registration from discrete scattered data. These affine invariants are derived based on a novel concept of cross-weighted moments which use an affine invariant cross-weight function with a fractional weight factor. The fractional weight factor makes it possible to arrive at low order (zeroth order) affine invariants which are more robust than the higher order regular moment affine invariants. The affine invariant cross-weight function directly exploits the area invariance of the affine transformation. For object matching, a classifier based on a Euclidean distance error measure between the cross-weighted moment affine invariants of the original image and those of the affine transformed test image is used. From the zero and first order cross-weighted moments, we also obtained unique closed-form solutions to the affine transformation parameters without requiring any feature point correspondence information. The equations used to find the affine transformation parameters are linear algebraic. For the partial scene matching and image registration problem, a novel class of local affine invariants derived from the convex hull of the scattered feature point set is derived. They also make direct use of the area (volume) invariance property associated with the affine transformation, and share the attractive properties of the convex hull, namely, the affine invariance, the local controllability, and the data reduction properties. Because of the local nature of these invariants, the appearance and/or disappearance of parts of the scene are effectively dealt with. All the proposed methods and procedures have been tested on a variety of synthesized and real image data and been found to be robust and encouraging.
The development and psychometric evaluation of the AIDS Knowledge Scale (AKS-DD) for individuals with developmental disabilities
Authors:   , Moore Sharon J.
Published: July 2024

In response to the AIDS crisis, HIV/AIDS prevention programs are being promoted nationwide. Therefore, there is a need to develop instruments for measuring individuals' AIDS knowledge. A review of the literature indicates that no instrument has yet been specifically developed to assess AIDS knowledge within the developmentally disabled population. This study presents the development and preliminary psychometric evaluation of the AIDS Knowledge Scale For Individuals With Developmental Disabilities (AKS-DD). Two phases of research were involved in this study. During phase I, a behavioral-analytic approach was used during the content validation process. Groups of experts were asked to validate item content and to determine if items were understandable to persons with mild mental retardation. An informal testing was conducted on a group of 20 individuals with mild mental retardation to ensure feasibility of administration. The final instrument consisted of a 5-item pretest, 25 items with a yes-no format, and several demographic items. During phase II, the AKS-DD was administered to an initial sample of 100 adult individuals with mild mental retardation in community-based settings for a preliminary evaluation of its psychometric properties. A series of analyses of variance (ANOVAS) of AKS-DD initial and retest scores indicated no significant differences regarding gender, marital status, race, living arrangement, and level of education. An exploratory factor analysis suggested that the AKS-DD can be regarded as a heterogeneous instrument. To evaluate temporal stability, the AKS-DD was administered to a subset of 50 individuals from the initial sample on two occasions spaced approximately 4 to 5 weeks apart. A test-retest reliability coefficient of.86 was obtained. Results suggest that the AKS-DD appears to have adequate initial psychometric properties and that it is a stable measure of AIDS knowledge among individuals with developmental disabilities. The results also suggest that the AKS-DD may serve as a useful measure when evaluating the impact of HIV/AIDS prevention programs. The present findings support the need for continuing efforts to provide HIV/AIDS education for the developmentally disabled population.
Determinants of innovation in U.S. public libraries
Authors:   , Wong-Martinez Carlos Gabriel
Published: July 2024

The goal of this thesis is to participate in and continue a line of research which examines the relationships between organizational innovation and organizational performance. Specifically, the public libraries of the two-hundred largest cities in the United States are analyzed. The innovations under study are the seven major computer-based innovations made available to libraries by library automation firms during the period 1969-1990. Data collection methods included survey questionnaire and published records. A model of organization performance is built based on two main constructs, environment and organizational structure. The model posits that the organizational decision to adopt an innovation is not taken in a vacuum. External (environmental) factors as well as internal (organizational structure) factors have a definite impact on such decisions. Equally important, the adoption of an innovation is not an end in itself. Rather, it is a mean to reach an ulterior goal, i.e. organizational performance. The model is time-based. It recognizes that the different factors exercise lagged rather than immediate effects. The tenability of the model and that of eleven hypotheses were tested via path analysis. The model was confirmed despite that only eight of twenty-three hypothesized paths were confirmed. Hierarchical regression was applied to test for the possibility of interaction relationships. The results of the hierarchical regression analysis agreed with those of path analysis. No significant relationship was found between organizational innovation and organizational performance. Interaction effects were virtually inexistent. A second path analytic model was built based on a refinement of the original model. The second model unveiled the importance of city's population as the main environmental factor. Once again a significant relationship between organizational innovation and organizational performance was not found. A disaggregate measure of organizational innovation made clear that particular library automation innovations do have a significant relationship with measures of library performance. Libraries that have adopted the on-line cataloging system showed a larger than average number of items circulated. Circulation is also fostered by the synergistic effect of the on-line circulation system with the acquisitions, on-line cataloging, and on-line public access catalog systems.
Behavioral and biochemical distinctions in the pharmacology of two common hallucinogens
Authors:   , Schindler Emmanuelle A. D. , Harvey John A
Published: July 2024

Hallucinogens have undergone relatively sparse scientific exploration in the past half-century, which has limited their clinical application and left them a pharmacological mystery. Serotonin2A (5-HT2A) receptors and the frontocortical brain region have strong ties to both hallucinogenesis and psychosis, a condition that hallucinogens mimic. As a tool to study psychosis and improve therapy, the basic pharmacology of hallucinogens must first be scrutinized. This thesis addressed this need by examining both behavioral and biochemical aspects of two common hallucinogens, LSD and DOI. The behavioral measure of drug-elicited head bobs (HBs) was used for its strong relationship to frontocortical 5HT2A receptors. The biochemical measure of PI hydrolysis, a major second messenger signal resulting from 5-HT2A receptor activation, was also analyzed. Rabbits were injected with either LSD or DOI and observed for HBs. Frontocortical tissue of naive rabbits was used to determine receptor binding affinities, study the effects of acute in vivo drug injection, and measure hallucinogen-induced PI hydrolysis. Some rabbits were treated chronically with DOI and various measures taken at different time points during recovery. Finally, hallucinogens were infused directly into the medial prefrontal cortex to study the role of this brain area in mediating HBs. Whereas HBs elicited by systemic DOI are mediated by several receptors, including 5-HT2A, 5-HT1A, dopaminel (D1), and D2 receptors, HBs produced by systemic LSD are only mediated by 5-HT2A and D1 receptors. In contrast to DOI, LSD demonstrated non-competitive, pseudo-irreversible binding at frontocortical 5-HT2A receptors. Both hallucinogens induced PI hydrolysis in rabbit frontocortical tissue, but the LSD and DOI signals were 5-HT2C- and 5HT2A-mediated, respectively. Finally, inhibition of the rate limiting enzyme for PI hydrolysis abolished DOI, but not LSD, HBs in the frontal cortex. In summary, DOI uses a 5-HT2A - PI hydrolysis mechanism to elicit HBs, whereas LSD uses 5-HT2A receptors independent of PI hydrolysis. Ultimately, dopaminergic receptor activation may be the final step in behavior, suggesting a role for dopamine in hallucinogenesis. The distinctions between LSD and DOI provide new insight into hallucinogen pharmacology, supporting the complex nature of human psychosis and warranting further investigation into the mechanism of action of these agents.
The role of dopamine neurotransmission in concussion-induced working memory deficits
Authors:   , Laskowski Robert Anthony , Raghupathi Ramesh
Published: July 2024

Concussion is a traumatically-induced short-lived neurological dysfunction lacking visible structural abnormalities via standard neuroimaging, with an estimated annual incidence of 1.6-3.8 million cases. Approximately 20-30% of mild traumatic brain injuries in the 8-19 year-old age group are concussions, resulting primarily from contact sports. A major consequence of concussion is impairment of working memory, which typically resolves in 7-10 days. I developed a model of concussion in the juvenile rat which is neurologically equivalent to the adolescent human. Impact over the frontal cortex of 5-week-old male rats resulted in working memory deficits over the first 3 days post-injury which was associated with blunted evoked field potentials and decreased synaptic transmission within the anterior cingulate cortex at 1 day post-injury. Although overt degenerative changes were not observed, blood-brain barrier permeability along with reactive astrocytosis was apparent underneath the site of impact. The neurotransmitter dopamine plays an important role in regulating working memory and has been implicated in post-traumatic cognitive dysfunction in adult animals. Concussion in the juvenile rat resulted in a four-fold increase in extracellular dopamine within 5 minutes which led an internalization of the D1 receptor at 6 hours post-injury; administration of the D1 antagonist SCH23390 blocked injury-induced receptor internalization but did not affect working memory impairment. In contrast, treatment of brain-injured rats with the partial D1 receptor agonist SKF38393 resulted in an improved working memory function. At 3-7 days post-injury, there was a decrease in tyrosine hydroxylase expression which was accompanied by an increase in the surface expression of the D1 receptor. Interestingly, the evoked field potentials in slices from brain-injured rats were not restored with exogenous dopamine and were less sensitive to SCH23390 suggesting a possible D1 receptor dysfunction. Similarly, evoked field potentials at 1 day post-injury appeared to be less sensitive to the D2 receptor antagonist sulpiride; preliminary observations suggest that sulpiride may exacerbate post-traumatic working memory deficits. In contrast, the D2 agonist bromocriptine did not affect post-concussion working memory impairment. Collectively, my data suggest that dopamine may play an important role in concussion-induced cognitive disturbances and may provide strategies for improving function in the acute post-traumatic period.
A dynamic relaxation finite element method for metal forming processes
Authors:   , Wu Longwu
Published: July 2024

This thesis discusses an application of the Dynamic Relaxation (DR) method to metal forming problems. The DR method is a numerical iteration method in which a Finite Element or Finite Difference dynamic computer program is adopted by adding an artificial damping term to the equation of motion. Then the equation of motion is integrated with respect to time. With a properly chosen damping constant, both acceleration and velocity approach zero and the system converges to the equilibrium state that is the static solution to the external applied load. In this thesis the DR method is used in conjunction with a dynamic Finite Element Method (FEM) program using direct integration without global stiffness matrix. Because of the fact that the global stiffness matrix is not constructed in the calculation, the CPU time, as well as storage used to update and to factorize the global stiffness matrix, is saved. The method studied in this thesis is suitable to large deformation and large strain solid mechanics problems of elastic or elastic-plastic material with any forms of hardening feature. The theory of DR is described and example problems such as simple upsetting and ring compression are discussed. Also high velocity compression of a cylinder is simulated, the simulation demonstrates that both static and dynamic problems can be attacked by a unified program.