bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of adult attachment and implications for relationship dissolution
Authors:   , Kilroy Valerie R. , Herbert James D
Published: July 2024

The present study assessed the relationship between attachment style and reasons for relationship dissolution. It was hypothesized that reasons for dissolution would form distinct factors representative of the attachment styles. Individuals classified into one of three attachment groups were expected to endorse the factor hypothesized to be theoretically related to their style significantly more than the remaining groups. It was also hypothesized that there would be intrarater consistency in dissolution reasons across individual raters' relationships. Ancillary hypotheses were proposed regarding convergent validity of the two attachment measures, the influence of parents, attachment history, social desirability and differences in length and number of relationships. Subjects were students from Hahnemann University in Philadelphia. Demographic data were reported. Subjects classified by attachment style were administered parental and attachment history questions followed by the Relationship Dissolution Index (RDI) and an abbreviated Marlowe-Crowne Social Desirability Scale. A factor analysis was performed on the RDI. Seven factors were extracted including "Avoidance" and "Anxious/Ambivalence" factors. No "Secure" factor emerged. ANOVAS were performed and subjects classified as avoidant on the two attachment measures endorsed the "Avoidance" factor significantly more than those classified as secure. Anxiously/ambivalently attached subjects did not endorse the "Anxious/Ambivalence" factor significantly more than the remaining groups. However, they endorsed the "Future Issues," and "Partner Pathology" factors significantly more than secure subjects and the "Compatibility Dissatisfaction" factor significantly more than the avoidant and secure groups. Only avoidant individuals showed some intrarater consistency on the RDI across relationships. As anticipated, substantial convergent validity was found between the two attachment measures and avoidant individuals had the shortest relationships. However, anxious/ambivalent subjects had the longest, contrary to expectation. No significant differences were found regarding number of relationships, degree of parental influence, length of parental marriage, degree of maternal/paternal acceptance or paternal mixed messages, relative to subjects' attachment style. Secure subjects perceived their parents' marriage as significantly higher in quality than anxious or avoidant individuals, partially supporting the hypotheses. Avoidant individuals reported significantly more rejection and mixed messages by mothers and rejection by fathers than secure subjects. These results were substantially consistent with the hypotheses. Finally, the effect of social desirability on responding was non-significant as expected. A discussion of the results and implications for future research was included.
Mechanisms inducing jet rotation in shear-formed shaped-charge liners
Authors:   , Segletes Steven Brian , Chou Pei Chi
Published: July 2024

This thesis is concerned with the mechanisms by which rotation may be introduced into the jet of a stationary shaped charge which employs a shear-formed liner. After a brief review of the past efforts in the area, an analysis is presented on the nature of jet rotation as it relates to the concept of shaped-charge jet spin compensation. Two mechanisms are introduced which have traditionally been considered likely candidates for inducing rotation in jets from shear-formed liners. These mechanisms are residual stress and mechanical anisotropy. Analytical, experimental and computational analyses are presented in an attempt to quantify the jet rotation rate that each respective mechanism is likely to effect, thus revealing the relative importance which should be attached to each mechanism. Results indicate that mechanical anisotropy in the shear-formed liner is the significant mechanism involved in producing a rotational jet from a stationary shaped charge.
Recrystallization texture in cold rolled copper
Authors:   , Necker Carl Theodore , Doherty Roger D , Rollett A. D.
Published: July 2024

The development of recrystallization textures in cold rolled copper has been characterized by x-ray diffraction, electron backscatter patterning (EBSP), calorimetry and microscopy. Two oxygen free electronic (OFE) copper plates, with initial grain sizes of 45 [mu]m (FG) and 105 [mu]m (CG), were unidirectionally cold rolled to six reductions yielding von Mises strains between 1.0 and 4.5. Samples were annealed to produce a range of partially recrystallized microstructures. The results of the x-ray diffraction analysis show that the recrystallization texture of the FG material ranges from random at the lower strains to a very strong cube texture, {001}<100>, better than 100X random, at high strains. The CG copper develops a similar set of recrystallization textures, only the textures are weaker than those of the equivalently strained FG copper. The EBSP results show that the average recrystallized cube grain size is always greater than the average non-cube grain size for any prior strain in both materials. This difference, at low strains, is due to the larger volume of twins affiliated with cube orientations as compared to non-cube orientations. At high strains, the difference is due to a combination of the volume of twins as well as the increase in the average size of the cube zones (grains are divided into zones defined by parent and twin orientations). The average size of cube grains increased while that of the non-cube grains decreased. The population of cube grains increased with increasing prior strain in both materials. It is suggested that the increasing population of cube zones is a result of the preferential nucleation of cube orientations that have undergone recovery, creating large stored energy differences between the cube orientations and neighboring deformation texture components. It is hypothesized that the increasing size advantage cube zones possess, especially at higher strains, is due to the ability of cube zones to grow without accumulating solute as rapidly as growing non-cube zones.
Understanding the Role of PaK1 in Zebrafish Development
Authors:   , Kelly Mollie Lynn , Chernoff Jonathan
Published: July 2024

Proper neural crest development and migration is critical during embryonic development, but the molecular mechanisms regulating this process remain incompletely understood. As zebrafish maintain transparency throughout development, they can be utilized to aid in developmental studies. This thesis explores the role of p21-actived kinase-1 (Pak1) in zebrafish development. Morpholino technology was utilized to knock down Pak1 in the zebrafish embryo resulting in neural crest defects, characterized by a linear heart tube and outflow tract blockage, impaired melanophore development and migration, and aberrant cartilage structure, with associated defects in neural crest cell migration. Through the injection of mRNA, these defects could be rescued by human Pak1, but not a kinase dead form suggestive that the function of Pak1 is conserved between humans and fish and that Pak1 is operating as a kinase and not as a scaffolding protein, a role which has been previously implicated. Further rescue experiments show that the protein kinase Erk, which plays a central role in a number of key developmental processes in vertebrates, was regulated by Pak1 in the developing neural crest. Additional rescue experiments show that activated Erk signals by phosphorylating the transcription factor Gata6 on a conserved serine residue to promote neural crest migration and proper formation of craniofacial structures, pigment cells, and the outflow tract of the heart. These data suggest a previously unrecognized and essential role for Pak1 as an Erk activator, and Gata6 as an Erk target, during neural crest development.
Improvement of wound healing with nonthermogenic ultrasound
Authors:   , Shi Wenyao
Published: July 2024

Chronic wounds such as pressure ulcers (bedsores), burns, diabetic ulcers etc. are a major challenge in health care, inflicting enormous suffering disability and expense. A variety of physical modalities have been advocated to improve the healing of wounds, including ultrasonic, galvanic, magnetic and light stimulation. Therapeutic ultrasound has been used to improve wound healing for over half a century; but its efficacy is still controversial. For ethical reasons, human clinical studies of wound healing are difficult to control; and most animal studies have used rodents or lagomorphs whose skin is not well comparable to that of human patients. A total 340 wounds in 35 mature Yucatan miniature swine, an animal whose skin resembles that of humans very closely, were studied to investigate the effects of ultrasound energy on wound healing. The goals of this research are: (1) Establish an appropriate animal model which is analogous to human beings for the wound healing study. (2) Evaluate the efficacy of ultrasound treatment of wound healing in the established animal model. (3) Investigate the optimal protocol of ultrasound treatment if it is effective to wound healing. (4) Apply methods for the in vivo study of biological effects of ultrasound to explore the mechanisms of ultrasound wound healing improvement. Five ultrasound treatment regimens with different intensities and frequencies were tested. Many non-invasive and invasive methods, such as digital image wound area measurement, transepidermal water loss measurement, mechanical strength test of skin sample and pathological examination, were used to evaluate the wound healing effects. The results indicate that the general effect of non-thermal ultrasound energy is beneficial to wound healing in this swine model; the different regimens tested appear not in equal effect with some more promising than others although further research confirmation is necessary; and the using of more than one ultrasound regimen at different stages of wound healing indicates a promising direction for future research. The possible mechanisms of ultrasound bio-effects involved in wound healing have also been studied and discussed.
Anticipatory postural adjustments in children with cerebral palsy and children with typical development during forward reach tasks in standing
Authors:   , Liu Wen-yu
Published: July 2024

The aim of this project was to explore the role of anticipatory postural adjustment (APA) in children with cerebral palsy (CP) and children with typical development (TD). A sample of convenience with 65 children, 37 with TD and 28 with CP, was included in this project. Using a repeated measures design, the following tasks in standing were examined: self-paced reaching at a comfortable speed and reaching as fast as possible to a stationary ball and reactive reaching to a moving ball. The APA activities were assessed by kinematic, electromyography, and center of pressure measurements. In addition, in order to explore relationships between clinical measures and laboratory measurements of APA activities, several clinical measures were also tested in this project. The major findings were as follows. First, regardless of age, children with TD produced spatial direction-specific APA patterns, such as posterior center of pressure excursion, and modulated the temporal and quantitative features of APA activities. A close relationship existed between the onset of APA activities and the initiation of reach movement. In addition, with increasing age, quicker and larger APA activities were noted in children with TD. Second, although children with CP used similar spatial direction-specific APA patterns as children with TD, APA activities in most children with CP were slower and smaller than children with TD. Furthermore, twelve out of 28 children with CP showed longer time delays between initiation of reach movement and onset of APA activities. Third, fair to excellent relationships between the three clinical measures and APA activities were noted. These three clinical measures were the functional reach test, the timed up and go test, and an upper extremity coordination test. Finally, among children with CP, APA activities were presented differently based upon several clinical factors, such as walking experience, vision problem, and severity of disability. The overall findings suggest that refinement of APA control in children with CP was different from children with TD. Further research needs to identify other influencing factors, which can interfere APA refinement in children with CP in order to develop effective intervention strategies.
Sp1 Nontranscriptionally Regulates Centrosome Number
Authors:   , Flashner Samuel
Published: July 2024

Specificity protein 1 (Sp1) is a highly conserved transcription factor ubiquitously expressed in mammalian tissues. Sp1 regulates a myriad of processes including cell cycle progression, apoptosis and the DNA damage response. Sp1 is overexpressed in many cancer types and is a poor prognostic indicator. RNAi-induced knockdown of Sp1 results in elevated continuous chromosome missegregation, also known as whole chromosomal instability (CIN). CIN is a major characteristic of cancer and is associated with poor patient prognosis. Therefore, understanding the relationship between Sp1 and CIN could have strong therapeutic impact. One potential mechanism linking Sp1 depletion and CIN is centrosome amplification, a phenomenon shown to contribute to CIN. Previously, we reported that Sp1 localizes to the centrosome and that depletion of Sp1 results in centrosome amplification (Astrinidis, et al 2010). Further, this process appears to be independent of Sp1's function as a transcription factor. A truncated form of Sp1 lacking the N-terminal 182 amino acids, which retains 91% of Sp1's transcriptional activity, fails to localize to the centrosome and fails to rescue the supernumerary centrosome phenotype we see in Sp1 depleted cells. We show here that the 182 amino acid N-terminal portion of Sp1 can localize to the centrosome. Importantly, this mutant is not transcriptionally active, indicating that Sp1 transcriptional activity is not required for its centrosomal localization. Further, RNAi-mediated depletion of full length Sp1 and re-expression of this this N-terminal mutant can rescue the supernumerary centrosome phenotype. Taken together, these data indicate that Sp1 regulates centrosome number in a non-transcriptional manner.
Characterization of merozoite surface protein-8 and evaluation of its potential as a blood-stage malaria vaccine candidate
Authors:   , Shi Qifang , Burns James M.
Published: July 2024

Plasmodium yoelii merozoite surface protein-8 ( PyMSP-8) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein with a C-terminal double epidermal growth factor (EGF)-like domain. PyMSP-8 is expressed throughout the blood-stage and co-localizes with merozoite surface protein-1 (MSP-1), a major vaccine candidate, on the merozoite surface in the late-stage schizont. Immunization with recombinant PyMSP-8 (rPyMSP-8) induced protection against normocyte-associated but not reticulocyte-associated P. yoelii malaria. This protection is antibody-dependent and requires non-polymorphic conformational B-cell epitopes. Interestingly, rPyMSP-8 binds to the surface of both mouse normocytes and reticulocytes, but not human erythrocytes. Moreover, this binding cannot be inhibited by protective antibodies, suggesting that PyMSP-8 plays a role in merozoite invasion, but that MSP-8 specific neutralizing antibodies may not confer protection by disrupting a specific receptor-ligand interaction. Because the double EGF-like domains of MSP-1 and MSP-8 have been proposed to play similar function(s) during blood-stage parasite development, presumably in merozoite invasion process, a chimeric antigen composed of the C-terminus of PyMSP-1 and the full-length PyMSP-8 was constructed in order to improve overall vaccine efficacy. As expected, immunization with this chimeric antigen induced solid protection against lethal P. yoelii 17XL infection. However, no improvement in protection against reticulocyte-restricted nonlethal P. yoelii 17X challenge was observed. Therefore, MSP-specific antibodies seem to only suppress P. yoelii parasite growth in normocytes but not reticulocytes. By comparing gene expression patterns of P. yoelii 17XL parasites from PyMSP-8 immunized animals versus adjuvant control animals, we conclude that these parasites altered their host cell preference to reticulocytes by the differential expression of sets of parasite proteins expressed on the merozoite surface as well as the surface of infected erythrocytes, and therefore escaped the MSP-8 specific neutralizing antibodies. In conclusion, MSP-8 is a promising vaccine candidate. Inclusion of MSP-8 improves the protective efficacy of an MSP-1 based vaccine against normocyte-associated parasites. However, parasites may limit efficacy of MSP-based vaccines by alternation of their host cell preference. Thus, additional targets such as antigens expressed on the surface of infected erythrocytes or antigens associated with reticulocyte invasion may need to be included in future multivalent vaccine trials.
Personality and neuropsychological functioning in non-demented patients with Parkinson's Disease
Authors:   , Resh Robyn J.
Published: July 2024

The literature on Parkinson's disease (PD) has included a discussion of a unique constellation of personality traits exhibited by patients both premorbidly and after the onset of the disease. Menza and colleagues have argued that damage to the dopaminergic system in PD results in a profile of personality traits characterized by low novelty seeking behaviors. This study further investigated the role of dopamine in personality functioning in non-demented PD patients using the Temperament and Character Inventory (TCI). The TCI scale, Novelty Seeking, is theoretically sensitive to dopamine activity. It was predicted that PD subjects would report significantly less novelty seeking behaviors for current and premorbid personality functioning in comparison to age-matched arthritic controls and healthy controls. In addition, the PD subjects were rated by their caregivers on the TCI. The relationship between personality and neuropsychological functioning in PD patients was also investigated. In general, results failed to find a unique PD personality profile characterized by low novelty seeking nor a relationship between personality and neuropsychological functioning. The degree to which methodological differences between this study and that of previous research were responsible for the findings is discussed. Implications for further research are proposed.
Characterization of T cell lines and T cell clones to plasmodium chabaudi adami
Authors:   , Brake David Alan
Published: July 2024

Activation of both cellular and humoral immune mechanisms is required for resolution of acute malaria. Extensive research utilizing monoclonal antibodies has led to the identification and cloning of plasmodial antigens, some of which induced neutralizing and protective antibodies. However, little effort has focused on T cell-dependent immune mechanisms activated during acute infection. To explore cell-mediated immune mechanisms in host defense against malaria, a murine model system in which antibody-independent mechanisms of immunity are known to play a major role was utilized. Splenic T lymphocytes obtained from Plasmodium chabaudi adami -immune mice were maintained in vitro by using IL2-containing medium and frequent antigenic stimulation. T cell lines and T cell clones were characterized for their surface phenotype, antigen reactivity, lymphokine secretion, and ability to confer protection to P. chabaudi adami in reconstituted mice. T cell lines were predominantly Thy1.2+, Lyt1+, Lyt2-, and maintained both antigen specificity and MHC restriction in vitro. These IL2-dependent immune T cell lines were effective in adoptively transferring protection to both athymic nude mice and sublethally irradiated recipients. The protective response was dose dependent, parasite-specific, and was abrogated by pretreatment of the transferred cells with anti-Thy1.2 and complement. Individual T cell clones derived by limiting dilution from protective T cell lines were assayed for their capacity to adoptively transfer protection to P. chabaudi adami infected nude mice. One clone, CTR2.1, and subclones derived from it, allowed nude mice to resolve their acute infections. CTR2.1 displayed a L3T4+, Lyt2- surface phenotype and secreted IL2 and gamma-interferon in response to soluble antigen and homologous antigen presenting cells in vitro. Immune nude mice grafted with either CTR2.1 or a T cell line were unresponsive when sensitized and challenged with DNFB. Moreover, T cell reconstituted mice were deficient in secreting antibody against the T-dependent nonmalarial antigen KLH, except during resolution of acute infection. In contrast, sera from these immune mice contained multiple IgG antibody specificities when analyzed by radioimmunoprecipitation using metabolically labelled P. chabaudi adami antigens. Collectively, these results suggest that T cell lines and T cell clones obtained from P. chabaudi adami -immune mice, propagated and expanded in vitro, retain antigen specificity and adoptive protective activity in vivo.
Metabolic interventions delay cellular senescence
Authors:   , Nacarelli Timothy , Sell Christian
Published: July 2024

Cellular homeostasis is progressively diminished in multiple tissues during aging. Proliferation-arrested senescent cells accumulate within tissues and contribute towards reduced maintenance and repair and increased inflammation, a universal hallmark of age-related pathologies. Indeed, senescent cells are found at sites of age-related pathologies and thought to be a major contributor to aging and susceptibility to disease. In addition to the inability to divide and pro-inflammatory function, senescent cells exhibit distinct mitochondrial and metabolic changes. Studies have raised the possibility that senescent cells are metabolically reprogrammed and require these changes for the induction and maintenance of the senescent state. Highlighting a reciprocal relationship between mitochondrial dysfunction and cellular senescence, we show that mitochondrial stress can induce cellular senescence by signaling through the mTORC1 pathway. Rapamycin treatment and methionine restriction are two of the most effective and consistent regimens that extend the lifespan of rodents and have been shown to delay cellular senescence, extending the replicative lifespan of cells in vitro. Each intervention provides resistance to mitochondrial stress and alterations that induce and accompany cellular senescence. We show that rapamycin treatment and methionine restriction have complementary effects when simultaneously administered and extend replicative lifespan further than either regimen alone. Combinatorial rapamycin treatment and methionine restriction altered status of nutrient sensing pathways including inhibition of mTORC1 signaling and activation of GCN2 signaling, resulting in enhanced autophagy and mitochondrial biogenesis with enrichment in particular mitochondrial regulatory proteins including UCP2. These alterations were associated with enhanced mitochondrial function and metabolic flexibility that may aid in the bioenergetic demand for cellular maintenance and proliferation, resulting in improved cellular longevity. Through improving mitochondrial homeostasis, combinatorial rapamycin treatment and methionine restriction metabolically intervene with cellular aging and senescence, and have potential in slowing the aging process in vivo.
An Injectable Hydrogel for the Replacement of Nucleus Pulposus Tissue and Treatment of Degenerative Disc Disease
Authors:   , Cochran David B. , Lowman Anthony M.
Published: July 2024

Degenerative Disc Disease is a problem that affects the mechanical properties of the intervertebral disc due to the dehydration of the nucleus pulposus. Current operational treatment methods are simply aimed at relieving pain, rather than restoring mobility or biomechanical function. A preventative treatment of nucleus replacement is a promising alternative because it is non invasive and can potentially restore full motor function to the patient. Polyvinyl alcohol(PVA) I Polyvinyl pyrroliodone(PVP) I Polyethylene glycol (PEG) hydrogels can be utilized for its ability to be a melted solution at elevated temperatures, and gellation upon cooling to body temperature after implantation. Previous research has also indicated that these PVAIPVPIPEG hydrogels exhibit the required mechanical properties to serve as a full nucleus replacement. In this study, a series of gels consisting of different PEG concentrations were tested in an ex vivo environment to determine their set time and gelling characteristics. It was determined that all four tested solutions were found to set after 20 minutes. A 4 week study was conducted to determine the stability of these formulations using a swelling media of PBS, DI water, and a 0.12 MPa osmotic PEG solution. Of these, all four formulations were shown to be the most stable over the 4 week period in the PEG solution, and reached equilibrium after 1 week. The samples swollen in PEG also exhibited nearly the same characteristics as the gels which were implanted in the ex vivo model for a period of 3 days. Healthy nucleus tissue was extracted from calf spines and subjected to the same swelling study in order to make comparisons with the implanted gels. The nucleus tissue increased in volume by approximately 10-15% in the PBS and DI water solutions. However, the tissue volumes decreased by 30% in the PEG solution, indicating the osmotic pressures were not in equilibrium. Lastly, a set of control samples were tested that were not implanted into the ex vivo model. The higher densities and lower water content at every time point indicate the importance of these hydrogels setting in a biological environment in order to accurately determine their in vivo characteristics.
The chemistry of sulfenic acids
Authors:   , Billmers Robert Lee
Published: July 2024

Sulfenic acids (RSOH) were generated by flash vacuum pyrolysis (FVP) of sulfoxides (RS(O)R) and their relative reactivities were determined by reaction with alkenes and alkynes. Although thiosulfinates (RS(O)SR) are formed in almost all reactions that are believed to involve sulfenic acid intermediates, the ratio of thiosulfinate to trapped adduct can be used as an indication of sulfenic acid reactivity. Using this ratio, it was determined that substituents capable of forming hydrogen bonds placed ortho to an aromatic sulfenic acid afforded an increase in sulfenic acid stability. It was also determined that ortho substituents with active hydrogens (e.g. OH, CH(,2)OH) provided no stabilizing effect. The importance of six- versus a seven-membered hydrogen bonded ring for the stabilization of sulfenic acids is also discussed. Attempts to stabilize aromatic sulfenic acids were performed by placing large substituents at the 2- and 6-positions; however, these sulfenic acids could be neither isolated nor detected. Such is the case of 2,4,6-trineopentylbenzenesulfenic acid, which upon generation by FVP produced 2-tert-butyl-4,6-dineopentylbenzo[b]thiete, as the major product. This represents a novel reaction of sulfenic acids, namely 1,4 dehydration. Using a modified FVP, in which the cold finger condenser was replaced with a cryo-tip equipped with NaCl windows, the IR of sulfenic acids could be obtained. By using this apparatus, it has been demonstrated that sulfenic acids exist in two tautomeric forms at low temperatures. However, at temperatures above -70(DEGREES)C, sulfenic acids tend to favor the O-protonated form. By using 2-arenesulfonyl-3-aryloxaziridines in the oxidation of thiols, it was possible to demonstrate for the first time the existence of 2-methyl-2-propanesulfenic acid, generated by oxidation of 2-methyl-2-propanethiol and trapped with methyl propiolate. The "(alpha)-effect" nucleophilicity of sulfenic acids was qualitatively demonstrated in the oxidation of 2-methyl-2-propane, (alpha)-toluene-, benzene- and p-fluorobenzenethiols. The mechanism for oxidation and reactions of the resulting sulfenic acids were determined by NMR (('1)H, ('13)C, ('19)F).
Poly(styrene-alt-maleic acid) (PSMA) as an inhibitor of human immunodeficiency virus type 1 (HIV-1) infection and as a partner in safe and effective combination microbicides
Authors:   , Pirrone Vanessa , Wigdahl Brian
Published: July 2024

Preclinical microbicide development efforts have focused on the development of the polyanionic compound poly(styrene-alt-maleic acid) (alt-PSMA). In vitro experiments demonstrated that alt-PSMA is a potent inhibitor of infection by R5 and X4 strains of HIV-1. alt-PSMA was shown to be an effective inhibitor of HIV-1 laboratory strains and clinical isolates, as well as both cell-free and cell-associated forms of infectivity. In keeping with the development of a safe inhibitor, alt-PSMA was also characterized as having low cytotoxicity. High levels of HIV-1 inhibition and low levels of cytotoxicity were confirmed in assays using primary human peripheral blood mononuclear cells (PBMCs). Furthermore, in compound washout experiments designed to mimic product leakage and the loss of active compounds following application, there were no adverse effects associated with the use of alt-PSMA. This was not true of other polyanionic HIV-1 inhibitors (including carrageenan, cellulose sulfate, and polystyrene sulfonate), which caused increases in HIV-1 infection subsequent to compound removal in experiments using cell lines and human PBMCs in conjunction with R5 and X4 viruses. The favorable attributes of alt-PSMA-potent inhibition of HIV-1, low cytotoxicity, no adverse effects in washout assays-suggested the continued development of alt-PSMA not only as a single agent but also as a component of a combination microbicide. The successes achieved using highly active antiretroviral therapy (HAART) have suggested that higher efficacy can be achieved by using compound combinations in microbicides. In investigations of potential compound combinations, the activity of alt-PSMA was assessed in combination with a fusion inhibitor (cyanovirin), an entry inhibitor (polystyrene sulfonate), or a reverse transcriptase inhibitor (efavirenz). Analyses performed using CalcuSyn and MacSynergy software indicated that the greatest degree of synergistic antiviral activity was achieved by the combination of alt-PSMA and cyanovirin. These results suggest that synergy with alt-PSMA is established in a combination that also includes a compound with a similar but non-overlapping mechanism of action. These combination studies, as well as experiments focused on the activity of alt-PSMA as a single compound, strongly indicate that alt-PSMA is a compound that deserves further assessment as a potential candidate microbicide and a partner in a combination microbicide.
Age-associated changes in influenza A virus-specific CD8-positive lymphocyte responses in C57BL/6 mice
Authors:   , Po John Leander Zapanta , Murasko Donna
Published: July 2024

The objective of influenza vaccine is the generation of neutralizing antibodies that will block infection by binding to influenza virus proteins that are required for virus entry into host cells. In the event that antibodies do not neutralize all influenza virus particles, infection will occur and will require cytotoxic T lymphocytes (CTLs) to kill infected cells. The goal of this project was to determine if the age-associated decrease in influenza-specific CTL responses was due to a quantitative defect in virus-specific CD8+ T cells. Young (6mo) and old (22mo) C57BL/6 mice were infected with influenza A virus and assessed either during a primary infection or during a secondary virus infection subsequent to immunization. Using MHC tetramers loaded with the immunodominant nucleoprotein (NP) peptide from influenza A virus, we examined the frequency of virusspecific CD8+ pulmonary T cells and their qualitative expression of various activation markers using flow cytometry. In addition, we assessed effector function using cytotoxicity assays and intracellular interferon (IFN-[gamma]) production. Even though we observed a correlation between lung and spleen in virus-specific lymphocytes expressing the activation marker, CD25 and the phenotype associated with immunological memory, CD44hi/CD62Llo, there was no correlation in either the percentage of influenza-specific CD8+ lymphocytes or cytotoxic activity between spleen and lung of individual infected animals. Collectively, our observations demonstrate that virus-specific CD8+ lymphocyte responses in the spleen do not reflect the responses in the lungs of mice infected with influenza A virus, and highlights the importance of assessing immune responses at the site of infection as opposed to locations distant from the local response. We determined that the age-associated decrease in virus-specific CTL activity was associated with a decrease and a delay in the expansion of virus-specific CD8+ T cells during primary influenza infection. Importantly, qualitative examination of CD8+ T cells during primary influenza infection showed that virus-specific CD8+ lymphocytes from young and old mice were phenotypically similar, in the percent expression of the costimulatory receptor, CD28, the activation marker, CD25, and the CD44hi/CD62Llo phenotype. (Abstract shortened by UMI.).
An analysis of ternary relationships in entity-relationship modeling
Authors:   , Jones Trevor H.
Published: July 2024

Entity-relationship (ER) modeling has become a recognized aspect of information analysis. Within the paradigm, one of the areas that has not been formally investigated is the ternary relationship. Ternary relationships in ER models continue to be constructs which are misunderstood by educators, difficult to apply for practitioners and problematic in their interpretation to relational schemas. The work analyzes the implicit logic of ternary relationships and how their dynamics are affected by imposing binary constraints between the participating entities. It provides a new construct which allows the recognition and modeling of Semantically Constraining Binary (SCB) relationships. This analysis also allows the development of the Implicit Binary Cardinality (IBC) rule, which addresses the implicit binary relationships within unconstrained ternary relationships. We then investigate the logic of allowing binary constraints within ternary relationships, and the implicit cardinalities required by these impositions. We provide an exhaustive listing of all allowable and disallowed ternary/binary cardinality combinations. We develop two heuristics which govern this process: the Explicit Binary Permission (EBP) rule and the Implicit Binary Override (IBO) rule. As a result of these finding we also provide the Binary Cardinality Propagation (BCP) rule. Having completed the analysis of the dynamics of ternary relationships, we then provide an analysis of ternary decompositions based on binary constraint impositions. We provide templates for lossless and functional dependency preserving decompositions, together with relevant proofs. We provide two heuristics addressing potential decompositions: The Constrained Ternary Decomposition (CTD) rule and the Unconstrained Ternary Decomposition (UTD) rule. The UTD rule has a corollary addressing the ability to model 4th and 5th normal forms. Additionally, we provide three additional sections. One extends the heuristics developed in the ternary relationship analysis to n-ary relationships (>3). The second addresses the difference between the findings in conceptual modeling and the applicability to logical modeling within the relational paradigm. The third looks at examples and applications involving ternary relationships. We then suggest an algorithm detailing the use, logical checking and potential subsequent decomposition of ternary relationships.
Regulation of tyrosine hydroxylase gene expression by aFGF and co-activators in the developing neurons
Authors:   , Guo Zheng
Published: July 2024

Previous studies from this laboratory have demonstrated that the catecholamine (CA) biosynthetic Enzyme tyrosine hydroxylase (TH) can be induced in non-CA neurons of the striatum by the synergistic interaction of acidic fibroblast growth factor (aFGF) and a number of different co-activators (dopamine, TPA, IBMX/forskolin). In my study, I sought to determine the underlying molecular mechanisms for this novel expression by identifying the relevant cis-acting DNA sequences of TH gene and transcription factors. To do so, cultures of E14 rat striatum were grown one day in culture in defined medium prior to treatment with aFGF (100ng/ml) and/or dopamine (20 uM), TPA (200 nM), IBMX (0.25 mM)/forskolin (50 uM). Sixty minutes after stimulation, cultures were harvested, nuclear extracts were prepared and analyzed by gel shift, supershift assays and Western blotting. We found that the binding of transcription factors to the TH-AP-1, TH-CRE-2, TH-TATA was increased by aFGF and co-activator stimulation as compared to control (media only), while the binding of TH-CRE proteins remained unchanged. To further investigate the components of the TH-AP-1, TH-CRE, TH-CRE-2 protein complexes, supershift assays using antibodies to specific transcription factors were performed. We discovered that in the TH-AP-1 site, the binding of Fos-B and Jun-D was increased, c-Fos and other unknown Fos was recruited to the AP-1 site, decrease in binding of ATF-2 and CREM was also revealed, while the binding of c-Jun remained the same after stimulation by aFGF and co-activators. However, stimulation of the cultures with aFGF and co-activators also resulted in the novel recruitment of c-Fos; the increased binding of ATF-2 and CREM to the TH-CRE site, although the c-Jun and Jun-D existed in the same amount within CRE protein complexes in stimulated striatal neurons as compared to the control. In addition, we also found the increase in binding of CREM to the TH-CRE-2 site following the treatment with aFGF and co-activators, even though the majority of CRE-2 protein complexes is still unknown. Therefore, we concluded that the protein complexes of AP-1, CRE, and CRE-2 interact directly or indirectly with the basal transcription complexes to initiate the novel expression of TH gene in striatal neurons by aFGF and co-activators.
MMPI-2 and neuropsychological indicators of malingering in traumatic brain injury litigants
Authors:   , Sari Dana Janette , Spiers Mary Virginia
Published: July 2024

Clinical neuropsychologists are increasingly being called upon to determine the presence or absence of cognitive dysfunction in the arena of brain injury litigation. Given the tremendous amount of external incentive, the possibility of malingering must be addressed. Unlike prior research which utilizes analog studies or the circular reasoning of using tests to determine malingerers, the current study examines the performance of individuals identified as malingering by external and objective means. Performance of these documented malingerers (n = 14) was compared to both a brain injury sample not in litigation (n = 15) and a brain injury sample pursing compensation related to their injury (n = 15). Demographic comparisons revealed that the malingering group is significantly older than either control group. Also, the malingering group and the group of subjects not malingering but in litigation had significantly less years of education than those subjects not pursing litigation related to their brain injury. There was no significant difference between the two control groups on any of the measures examined. In contrast, the group of documented malingerers performed more poorly than the two control groups at a p < .01 level on the F Scale of the MMPI-2; Sensory Perceptual Examination of the Halstead-Reitan Battery; Logical Memory I and II and Visual Reproduction I and II of the WMS-R; and total items recalled and total rows in correct location on the Rey 15 Item Test, and at a p < .05 level on the Speech Sounds Perception Test of the Halstead-Reitan Battery. The only variables on which the malingerers did not perform more poorly than the control groups were the FBS Scale of the MMPI-2 and the Seashore Rhythm Test. Current results are compared to prior research endeavors and commonalities and discrepancies are reviewed. Significant demographic differences between groups are discussed in relation to possible indicators of malingering and implications for future research are discussed.
The molecular properties of apoliprotein E
Authors:   , Segall Mark Louis
Published: July 2024

We examined the effects of apolipoprotein E domain structure and polymorphism on the kinetics of solubilization (clearance) of dimyristoyl-phosphatidylcholine multilamellar vesicles. This second order reaction consisted of two simultaneous kinetic phases; it also exhibited saturable kinetics when the apolipoprotein concentration was increased at a constant lipid concentration. Rigid connections between [alpha]-helices in the four-helix bundle formed by the 22-kDa N-terminal domain of apoE reduced the reaction rate. In contrast, the more flexible interhelical connections in apo AI and the 10-kDa C-terminal domain of apoE promoted rapid solubilization of DMPC MLV. Full-length apoE3 reacted at about half the rate of the C-terminal domain alone. This decrease occurred because the hinge region probably decreased the interhelical flexibility of the 10-kDa domain and because both domains are conformationally restricted when covalently linked. Furthermore, the MLV surface affinities and reaction rates of the N-terminal domain fragments of the three common apoE isoforms tended to vary inversely with the stabilities of these fragments. These results confirm the importance of apoE's structure on the kinetics of lipid interaction. They suggest that flexibility in an apolipoprotein molecule increases the time-averaged surface area, thereby increasing the rate of phospholipid solubilization.
Anatomical characterization of inhibitory local circuit neurons in the anterior cingulate cortex of rats following repeated exposure to amphetamine or nicotine
Authors:   , Mohila Carrie Ann , Onn Shao-Pii
Published: July 2024

Repeated administration of drugs of abuse, including psychostimulants, leads to progressive increases in the psychomotor stimulatory effects of these drugs. This increase in drug effect is known as psychomotor sensitization and is believed to model drug addiction, as the neural systems that mediate psychomotor sensitization are also believed to mediate the rewarding aspects of drugs of abuse. Anatomical and electrophysiological studies have revealed that repeated administration of amphetamine (AMPH) results in changes in the prefrontal cortex (PFC) consistent with modified synaptic organization and enhanced cortical connectivity with subcortical structures. Using anatomical techniques, the present study examines changes in classes of local circuit interneurons in the anterior cingulated cortex (ACC) of rats following exposure to drugs of abuse, in particular, the psychostimulant AMPH, which may contribute to the cortical pathophysiology observed in drug addiction. We observed selective increases in the density of parvalbumin (PV), but not calbindin (CB) or calretinin (CR), immunoreactive (ir) interneurons in the ACC of AMPH-treated rats at 1-day and 7-day withdrawal. Consistent with the idea that mesocortical DA is critically involved in neural changes following exposure to drugs of abuse, we observed a selective increase in PV-ir interneurons in the ACC following repeated treatment with apomorphine (D1/D2 agonist) and SKF-38393 (D1 agonist) at 1-day, but not at 7-day, withdrawal from drug treatment. Additionally, we observed an increase in CRF-ir puncta in the ACC of AMPH-treated rats at 7-day, but not at 1-day, withdrawal that were found to surround PV-ir cells, but not CB-, CR-, or glutamate-containing cell bodies. To further examine alterations in GABA interneurons following exposure to drugs of abuse, we performed similar studies in rats exposed to the psychostimulant drug of abuse nicotine (NIC). We observed selective increases in the density of both PV- and CR- (but not CB-) it interneurons in the ACC of rats receiving chronic oral administration of nicotine at Q-day withdrawal, with no changes in the densities following 7-day withdrawal. In summary, we revealed the PV-ir class of interneurons is selectively altered in the ACC following AMPH treatment; these alterations are mediated, at least in part, by dopamine-receptor stimulation. Furthermore, CRF-mediated pathways may mediate changes in PV-ir interneurons that persist into AMPH withdrawal. Moreover, chronic nicotine treatment appears to selectively alter PV- and CR-ir only during the treatment period. Together these studies indicate that changes in PV-ir interneurons may be a common link in cortical deficits observed following exposure to drugs of abuse.
The effects of damage to and surgical repair of the lateral ankle ligaments on the passive flexibility of the hindfoot
Authors:   , LaPointe Stephan Joseph
Published: July 2024

The purpose of this study was to investigate the effects of damage to the lateral collateral ligaments of the ankle and their subsequent surgical repair on the three dimensional passive flexibility characteristics of the hindfoot. For this purpose, tests were conducted on six fresh cadaver legs prior to and following serial sectioning of the anterior talofibular ligament (ATFL) followed by the calcaneofibular ligament (CFL) and after performing four surgical procedures (Evans, Watson-Jones, Chrisman-Snook and Burks). Five patients with ankle injuries were also tested for comparison with the in-vitro data. The tests were performed with a mechanical linkage that permitted the manual application of forces and torques about the ankle and recorded these values as well as the resulting motion. Flexibility parameters were defined and quantified in each direction from this data. The tests performed on the ankles included loading them in the internal/external rotation, inversion/eversion and anterior drawer directions. The results of the in-vitro study indicated that both an isolated rupture of the ATFL and combined ATFL & CFL damage produced statistically significant changes in flexibility. These flexibility parameters provided a basis for differentiating between an isolated ATFL injury and a combined ATFL & CFL injury as follows. For an isolated ATFL injury a significant increase in flexibility in anterior drawer direction is present. There was no significant increase in inversion flexibility or coupling with this injury. However, when both ligaments were involved the increase in inversion flexibility and in the amount of coupling became significant. Of the surgical procedures the Evans provided the closest approximation of the intact ankle in the inversion and anterior drawer directions. However, increases in stiffness beyond the normal ankle were seen in internal rotation with this procedure and the Chrisman-Snook and Watson-Jones. The Burks procedure, did improve the flexibility characteristics of the injured ankle without limiting flexibility in any direction. The results of the flexibility tests conducted on the five patients were consistent with the changes in flexibility seen in the in-vitro results of the ligament deficient ankles.