bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel functions of protein phosphatase 2A in Saccharomyces cerevisiae
Authors:   , McCourt Paula Cristina , Nickels Joseph T
Published: July 2024

Protein phosphatase 2A (PP2A) is a major serine/threonine protein phosphatase that plays a role in regulating cell cycle progression, cell growth, cytoskeleton dynamics and multiple signal transduction pathways from yeast to mammals. PP2A is a heterotrimeric protein complex consisting of A and B regulatory subunits and a catalytic C subunit. An additional species of PP2A can be activated by ceramide, and this complex is known as ceramide-activated protein phosphatase (CAPP). The CDC55 gene, in Saccharomyces cerevisiae, encodes for one of two B regulatory subunits of PP2A and the B subunit of CAPP. While identifying novel functions of PP2A, we found cells lacking the amphiphysin-like protein, Rvs161, require Cdc55 for viability under conditions of heat stress, and we linked this lethal genetic interaction to the endocytosis domain of Rvs 161. rvs161[delta] mutants are unable to thrive when stressed by glucose starvation or high salt and mutations in the sphingolipid biosynthetic pathway, including loss of Sur4, the very long chain fatty acid elongase, suppress these phenotypes. Cdc55 is required for sur4-dependent suppression of rvs161[delta] defects, including reinitiation of the endocytosis-dependent degradation of the a-factor receptor, Ste3. Overexpression of CDC55 can also remediate rvs161[delta] growth defects and restore Ste3 degradation or the endocytosis of lucifer yellow in rvs161[delta] cells even under high salt stress, but it can not remediate the actin polarization defects of these cells. Another novel function of PP2A involves Grr1, since cells lacking Grr1, an F-box subunit of the Skp1/Cdc53/F-box (SCF) ubiquitin ligase complex, require Cdc55 for viability. We linked this lethal genetic interaction to the degradation of the G1 cyclin, Cln2, a known substrate of the SCFGrr1 complex. Cln2 is less stable in cdc55[delta] mutants compared to wild type cells, and Cln2 phosphorylation or ubiquitination by the SCF complex are also required for the degradation of Cln2 in cdc55[delta] mutants. Our results suggest that Cln2 is hyperphosphorylated in cells lacking CDC55, causing an increase in its degradation, and cells lacking both CDC55 and GRR1 are inviable due to an accumulation of hyperphosphorylated Cln2. We propose that Cdc55-dependent PP2A regulates the phosphorylation state of Cln2, and, together with Rvs161, regulates a single cellular event, possibly endocytosis.
Comparisons of cellular senescence pathways
Authors:   , Kennedy Alyssa Lee , Adams Peter D.
Published: July 2024

Cellular senescence is a state of permanent growth arrest that is triggered in response to various cell stressors. These stressors include short telomeres (replicative senescence), DNA damage or activated oncogenes (oncogene-induced senescence). In the presence of these potentially tumor-promoting genetic aberrations, the cell permanently exits the cell cycle rather than continue to divide. In so doing, senescence serves as a tumor suppression mechanism. A critical component of the senescence program is formation of facultative heterochromatin, termed senescence associated heterochromatin foci (SAHF). These SAHF are thought to reinforce the senescence arrest by silencing proliferation-promoting genes. HIRA, a histone chaperone whose activity is regulated by WNT signaling, has been shown to be important for regulating formation of SAHF during senescence. In this thesis work, I set out to determine whether mouse cells have a functional HIRA mediated heterochromatin-formation pathway. We find that in mouse embryo fibroblasts (MEFs), the HIRA mediated heterochromatin pathway does not function as it does in human fibroblasts. In both mouse dermal fibroblasts with shortened telomeres or MEFs transduced with an activated RAS oncogene, there is no evidence of HIRA activation or SAHF formation. These results may contribute to the differences in tumor suppression capabilities between mouse and human. The second portion of this thesis work addresses differences between various oncogenes in their ability to induce senescence. Using primary human fibroblasts, I find that PI3K/AKT pathway activation differs from RAS activation in its ability to induce senescence. Specifically, activation of PI3K/AKT pathway induces a less robust growth arrest, does not induce formation of SAHF, does not lead to increased secretion of inflammatory mediators and also does not induce DNA damage. Additionally, we find that AKT is capable of antagonizing the effects of activated RAS on heterochromatin formation and HIRA activation. Finally, in an in vivo mouse model of RAS-induced senescence in the mouse pancreas, we show that PI3K pathway activation leads to abrogation of RAS-induced senescence and, consequently, rapid tumorigenesis. These findings elucidate critical differences between oncogenes in their ability to induce senescence, and also demonstrate a novel form of oncogene cooperation between these two potent oncogenic pathways.
Effects of GM1 administration on the neurochemistry, neuroanatomy and chronic behavior of MPTP-lesioned non-human primates with Parkinsonism
Authors:   , Pope-Coleman Anne Margaret , Schneider Jay S.
Published: July 2024

GM1 ganglioside has previously been shown to produce behavioral improvement in non-human primates, made parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrdine (MPTP). The first part of this dissertation sought to further characterize the neuroanatomical and neurochemical effect of GM1 treatment in non-human primates made rapidly parkinsonian with MPTP. The studies examined the number of residual TH-positive neurons and the expression of tyrosine hydroxylase (TH) mRNA per neuron in the ventral mesencephalon. The densities of dopamine D1 and D2 receptors were assessed to examine GM1 effects on postsynaptic receptors in the striatum. The density of GABAA receptors in the globus pallidus as well as enkephalin and substance P mRNA expression in the striatum were evaluated to determine GM1's effect on basal ganglia output pathways. The results of these studies showed, in comparison with saline-treated control animals, GM1 administration resulted in a greater number of residual DAergic neurons, increased TH mRNA expression in residual DAergic neurons, reduced levels of striatal DA D1 receptor binding and ENK mRNA expression, increased striatal Sub P mRNA expression, and increased GABAA receptor binding in the GPe. The second part of this dissertation examined the effects of GM1 treatment in a slowly progressing model of PD, as well as assessed the sequelae of parkinsonian symptoms. Chronic low dose MPTP was administered to non-human primates over a two+ year period. During the first 26 weeks the animals were given only MPTP and the sequelea of early cognitive and motor deficits was assessed using various behavioral tasks. GM1 treatment was than added to the MPTP administration for 90 weeks. The chronic treatment effects of GM1 as compared to the progression of deficits in an untreated group were followed. The results showed that early intervention with GM1 reverses early-appearing cognitive deficits, may protect against further cognitive decline and may slow the progression of parkinsonian motor symptoms as parkinsonism progresses. Together, with recent positive data from clinical trials of GM1 in PD this evidence suggests the usefulness of GM1 treatment in both the early and late stages of Parkinson's disease.
Evaluation of a computer-based learning program in anesthesia
Authors:   , Violand Paul J.
Published: July 2024

Computer-based learning (CBL) has been a component of medical education for years. However, there is little in the literature that supports the use of CBL in anesthesia education or its effectiveness as a teaching alternative. This study was designed to develop an original CBL program for students of anesthesia, to test its effectiveness compared to a standard lecture format, and to assess its acceptability by students. A CBL program entitled Introduction to the Pharmacodynamics and Pharmacokinetics of Neuromuscular Blocking and Reversal Agents was developed using a computer authoring program. Fifty-two first year nurse anesthesia students were randomized to either a lecture or computer group. Both groups completed a multiple choice pretest. Following completion of their learning sessions, both groups took a standardized posttest. The CBL group also completed a semantic-attitude differential questionnaire that measured students' attitude toward the CBL program. There was no significant difference in the posttest scores between the two groups. However, there was a significant improvement in the overall scores between the pre and posttest within groups. Learning occurred in both the CBL and lecture groups. The results of the semantic-attitude questionnaire showed that students ranked the CBL program high in all three categories measured. CBL can be an important adjunct to the education of students and further application appears warranted.
Development of an instrument to evaluate the capacity of elderly persons to make personal care and financial decisions
Authors:   , Anderer Stephen J.
Published: July 2024

Evaluations of the competency of elderly individuals for guardianship proceedings have been criticized frequently in legal and mental health literature. This study describes the development and evaluation of a measure of the abilities of elderly individuals to make decisions in situations commonly confronting elderly persons for whom guardianship is sought. Before the study began, a legal analysis was conducted of statutory standards in all fifty states and the District of Columbia for determining competency in guardianship proceedings. This analysis provided the foundation for the study, which took place in two stages: (1) initial development of the instrument ensuring content validity; and (2) evaluation of reliability and validity. The test was developed in stage one through a situational analysis combining theory with interviews and surveys of legal and mental health professionals. The resulting instrument-the Decisionmaking Instrument for Guardianship (DIG)-consists of eight vignettes followed by a structured interview. The vignettes are problem situations commonly confronted by elderly individuals for whom guardianship is considered. The structured interview was based on contemporary problem-solving theories and earlier instruments. A detailed scoring system, including a manual, was developed. In stage two, a sample of 61 subjects from ages 61 to 90 were administered the DIG, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of neuropsychological tests, the Block Design and Vocabulary subtests of the WAIS-R, and a modified version of the Thinking Rationally About Treatment (TRAT-2) instrument (a measure of competence to provide informed consent). Complete data were obtained for 56 subjects. Internal consistency for the DIG as measured by coefficient alpha was.9158. When the scores of two research assistants on ten DIG protocols were compared with the researcher's scores, the interscorer reliability coefficients were.9704 and.9613 The correlations between the DIG and the TRAT-2 Block Design subtest (.6406), CERAD (.5940), and Vocabulary subtest (.5425) were all significant (p<.001) and provided support for the construct validity of the DIG. The DIG is a promising tool for further research and may prove useful to clinicians, although it cannot be viewed as a definitive measure of competency in guardianship proceedings.
Regulation of HIV-1 LTR driven gene expression within a chromatin-based microenvironment
Authors:   , Shah Sonia , Wigdahl Brian
Published: July 2024

Human immunodeficiency virus type 1 (HIV-1) gene expression is driven by the long terminal repeat (LTR), which contains binding sites that interact with multiple host and viral factors. Selective pressures within the host as well as the low efficiency of reverse transcriptase lead to genetic alterations within the viral genome resulting in viral quasispecies that can be differentially regulated and can potentially form niches within specific cell types and tissues. Previous studies identified a single nucleotide polymorphism (SNP) within C/EBP site I (3T, C-to-T change at position 3 of the site) that correlated with HIV-1-associated dementia. In addition, our current patient cohort shows a SNP within Sp site III (5T, C-to-T change at position 5 of the site) that occurs as frequently as the consensus subtype B sequence. Stably transfected cell lines were developed using bone marrow progenitor, T, and monocytic cell lines (TF-1, Jurkat, and U-937, respectively) to explore the LTR phenotype associated with these genotypic changes from an integrated microenvironment. The LAI LTRs were coupled to the green fluorescent protein (GFP), and polyclonal HIV-1 LTR-GFP stable cell lines were developed. In the stably transfected TF-1 and U-937 cells the 3T/5T-containing LTR was associated with a lower expressing phenotype, that can be induced to high levels of gene expression, following stimulation and/or in the presence of Tat. To examine the mechanism of basal and stimulated LTR driven gene expression, as well as epigenetic modifications that may control it, clones were derived from each population of cells. The clones were examined with respect to basal transcription, cytokine treatment, Tat transactivation, and epigenetic controls. Results suggest that non-expressing clones within monocytic cell lines cannot be induced to express under all conditions. However, the nonexpressing LAI 3T and LAI 5T Jurkat clone genotypes could be induced into expression with both proinflammatory cytokine treatment as well as with epigenetic modification. Results demonstrate that epigenetic modifications to viral and host DNA, cellular phenotype, and genetic variation may determine the overall level of LTR activity and potential to be activated from a quiescent state.
Molecular basis of resistance to sterol biosynthesis inhibitors in Candida species and Saccharomyces cerevisiae
Authors:   , Henry Karl Woodman , Edlind Thomas D
Published: July 2024

The incidence of infection due to the yeast Candida albicans has risen dramatically over the last two decades and is due to an increase in the number of immunocompromised individuals. The most common treatment for candidiasis is the use of azole antifungals which inhibit ergosterol biosynthesis. The widespread use of these drugs in treatment and prophylaxis resulted in the emergence of resistance to this class of antifungals. Their fungistatic activity contributes to both treatment failure and the development of resistance. Relatedly, in vitro studies with C. albicans reveal tolerance, even at high azole concentrations. This thesis examines the role of transcriptional regulation of specific yeast genes potentially involved in resistance or tolerance to azoles and other sterol biosynthesis inhibitors. The research focused on three areas: (i) the role of drugs used in the treatment of opportunistic pathogens on the transcription of C. albicans multidrug efflux pumps which resulted in decreased sensitivity to azole antifungals, (ii) the transcriptional response of genes involved in ergosterol biosynthesis to inhibitors of this pathway, and (iii) the identification of factors that regulate the expression of ergosterol biosynthesis genes and consequently affect sensitivity to azoles and other inhibitors of this pathway. It was discovered that two drugs used to treat AIDS-related opportunistic infections, sulfadiazine and albendazole, increased the expression of genes encoding the C. albicans multidrug efflux pumps Cdr1p and Cdr2p. This was correlated with decreased sensitivity to azole antifungals and suggests a potential mechanism for the higher incidence of C. albicans treatment failure and resistance in AIDS patients. Inhibitors of three different enzymes involved in fungal sterol biosynthesis increased the expression of C. albicans ERG genes encoding multiple enzymes in this pathway. Tolerance to antifungals that target this pathway is often observed in Candida species, and it is likely that ERG upregulation contributes to this tolerance. Understanding the mechanisms of sterol gene regulation in yeast may provide rational approaches to reducing resistance and developing new antifungal treatments. Using the model yeast Saccharomyces cerevisae, it was found that the transcriptional repressor Rox1p plays a role in regulating ergosterol biosynthesis genes and affects sterol biosynthesis inhibitor sensitivity.
Factors affecting juror decisionmaking in repressed-memory cases
Authors:   , Rosen Adam Paul , Bersoff Donald N
Published: July 2024

The recent surge in litigation involving supposed "repressed memories" has presented legal fact-finders with formidable challenges in sorting out truth from fiction. The lack of resolution in the mental health fields regarding the viability of memory repression and veridical memory recovery has made expert testimony in these areas of questionable value in resolving cases. Jurors are often left with equivocal impressions of both the facts and of the state of scientific knowledge in this area. This circumstance leaves jurors more likely to resolve repressed-memory cases based upon their own predilections and/or prejudices. The current study reviews the history of trial by jury, the historical recognition of jury bias and various attempts to assess and limit its impact. It is asserted that repressed-memory cases represent a unique circumstance in which the risk of verdict being determined by juror bias is greater than in other types of cases. These reasons arise from evidentiary ambiguity deriving from: (a) the length of time between the alleged offense and the claim, (b) the typical absence of eyewitnesses and/or physical evidence and (c) the scientific uncertainty as to the validity of memory recovery, and (d) the emotionally provocative nature of the allegations. The current study employed three variants of a repressed-memory trial vignette based upon an actual trial. One-hundred and twenty jurors (60 men, 60 women) responded to one of the three vignettes, which varied in evidence strength. Jurors also responded to a questionnaire which included demographic, attitudinal, experiential and personality measures. Statistically significant prediction of verdict and ratings of defendant culpability were obtained by evidence strength, belief in repression and media-exposure related views regarding the viability of veridical memory recovery. Marginally significant prediction was obtained for juror child sexual abuse history and juror self-ratings of feminism. Gender was predictive of verdict only in the strong and weak evidentiary conditions. Application of these findings by practicing lawyers and/or judges is discussed. It is asserted that no single variable from this list should be viewed as cause for automatic exclusion of jurors. Rather, some combination of variables, each predicting the same verdict, should be taken as a caution of possible bias in a juror and should prompt closer questioning of that juror as to his or her ability to render a verdict based upon the evidence. Finally, the study further supports previous findings that evidence strength is the strongest determinant of verdict choice.
Lifespan Mechanisms
Authors:   , Lerner Chad Ashyr , Sell Christian
Published: July 2024

The aging process involves a trade-off between growth and reproduction on the one hand and maintenance and repair on the other. In times of plenty, organisms must take advantage of the availability of nutrients for growth and reproduction. However, the utilization of resources for anabolic needs occurs at the expense of maintenance processes necessary to maintain homeostasis. When nutrients are scant, cells switch from growth to stress resistance and repair. In eukaryotes, the Target of Rapamycin (TOR) has a central role in controlling this switch. TOR is responsive to nutrient availability as well as growth factor signaling. IGF-1 and Insulin-like signaling, stimulates TOR kinase activity to regulate protein translation and cell growth. Reduced TOR activity or IGF-1 signaling are features of several models of increased longevity. Our mice are hypomorphic for the IGF-1 allele. These mice are smaller in size and exhibit increased lifespan. The precise mechanism by which reduced Insulin-like signaling affects the state of the cell and supports an increased lifespan is not well understood. Using IGF-1 deficient mice and primary human fibroblasts, we have observed that reduced IGF-1 or impairment of mTOR activity with rapamycin slows growth and enhances autophagy. Under conditions of reduced TOR activity by rapamycin, mitochondrial function is improved along with an increase in mitochondrial mass and mitochondrial gene expression. Furthermore, the expression and turnover of the adaptor protein p62/SQSTM1 appears to be required for the stability and expression of Nrf2(NEF2L) and Tfam, two factors important for mitochondrial homeostasis. Rapamycin treated cells are also resistant to oxidative stress, likely due to increased Nrf2 activity and do not accumulate mitochondria with impaired membrane potential, an effect which is dependent on autophagy. These results suggest that reduced signaling through TOR benefits mitochondrial function and homeostasis, and reveals a new role for p62 as a factor in the mammalian retrograde response.
Medication management in individuals with Persistent Schizophrenia
Authors:   , Johnson Karen Elizabeth , Spiers Mary Virginia
Published: July 2024

Participants for this study consisted of 41 male schizophrenics between the ages of 18 and 65 who were Forensic or Ex-Forensic residents living in an inpatient psychiatric facility. Each participant completed a battery of neuropsychological tests, a questionnaire regarding knowledge of, and attitude towards medication, and a practical, experimental measure, The Cognitive Screening for Medication Self-Management (CSMS). Each participant was also rated on an item from the Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCI-PANSS) which relates to lack of insight and judgment. The purpose of this study was to determine if individuals with persistent schizophrenia demonstrated cognitive difficulties directly related to medication management. A second goal of this study was to identify which variables, from the assessment instruments, proved to be the best predictors of level of success in a 3 Phase medication program. It was hypothesized, and the results of this study substantiated, that individuals with persistent schizophrenia demonstrate difficulties with frontal lobe/executive functions such as novel problem solving, semantic clustering, mental flexibility, organizational and planning abilities as well as with acquisition and recall of information and prospective memory abilities. Regression analyses produced five variables that were able to account for 62.2% of the variance in terms of level of success in the Medication Education and Management Program. Implications for the study are discussed in terms of potentially using a practical dose planning task from the CSMS as a screening device to detect which individuals are likely to be successful with medication management.
Transcriptional regulation of tissue-specific expression of the platelet [alpha]IIb gene
Authors:   , Shou Yaping , Poncz Mortimer
Published: July 2024

The integrin [alpha]IIb gene is expressed in a megakaryocyte-specific fashion. This dissertation study has characterized an Sp1-binding silencer element between -145 bp and -125 bp in the immediate promoter region of the rat [alpha]IIb gene that may contribute to the tissue-specific nature of the [alpha]IIb gene expression. Transient transfection studies showed that deletion of this element not only resulted in increased reporter gene expression in megakaryocytic cell lines but also induced high levels of expression in non-megakaryocytic cell lines that normally do not express [alpha]IIb gene. By electrophoretic mobility gel shift assays (EMSA), it was shown that a single nuclear complex was formed ubiquitously at this site in all the cells tested. A Southwestern blot and EMSA studies using an Sp1-consensus probe, anti-Sp1 and anti-Sp3 antibodies, and recombinant Sp1 protein consistently suggested that this silencer element bound Sp1. Moreover, by point mutation studies, the Sp1-binding activity at this site was shown to correlate directly with its silencing effect on expression. An identical nuclear complex involving Sp1 formed with the homologous human [alpha]IIb promoter region, suggesting the conservation of this silencer element between species. It was also found that the silencing activity of this element was position-dependent. It suggests that local interactions between Sp1 and other bound nuclear proteins may be important for the negative regulation of the [alpha]IIb gene expression by this silencer element. It is proposed that Sp1 bound to the silencer site silences the [alpha]IIb gene in all tissues, and only in megakaryocytic cells this inhibition is overcome by additional sequences further upstream that may bind tissue-specific factors. This dissertation also presents transient expression data from both cell lines and primary rat bone marrow culture that a 3 kb 5'-flanking region of the rat [alpha]IIb gene appears to have similar tissue-specificity and promoter strength with the 912 bp of the [alpha]IIb promoter sequence. The establishment of five transgenic mouse lines for a prokaryotic [beta]-gal reporter gene driven by the 912 bp of the rat [alpha]IIb promoter is also reported in this dissertation. The megakaryocyte-specific expression of the transgenic [beta]-gal gene was not seen in all these lines tested by X-Gal staining. It suggests that the 912 bp promoter region may not be adequate to direct high-levels of tissue-specific expression of the [alpha]IIb gene in a chromosomal environment.
Inhibition of macrophage-induced, antigen-specific T lymphocyte proliferation by poly I:C
Authors:   , Kirschmann Dawn A. , Murasko Donna
Published: July 2024

Peritoneal macrophages (M[phi]) from mice treated with poly I:C prior to pulsing with antigen, fail to induce antigen-specific T cell proliferation. The current study investigated the mechanism of this inhibition. The inhibition of T cell proliferation was shown to be antigen-specific and was not limited to one particular H-2 type or to one antigen. This inhibition is not mediated by the generation of prostaglandins, other soluble suppressor factors, or suppressor/cytotoxic M[phi]. These results suggested that poly I:C treated M[phi] failed to produce activation signals required for stimulation of T cell proliferation. Poly I:C treated, KLH-pulsed M[phi] were activated as demonstrated by a decrease in the specific activity of ectoenzymes, decreased expression of the M[phi]-specific cell surface marker F4/80 and increased cytoplasmic vacuolarization. However, the ability of poly I:C treated, KLH-pulsed M[phi] to spread on plastic was delayed compared to saline treated, KLH-pulsed controls. The addition of IL-1, IL-2, IL-6 or combinations of IL-1 and IL-6 to cultures could not reverse the inhibition of antigen-specific T cell proliferation. Further, the expression of class II major histocompatibility (Ia) molecules by poly I:C treated, KLH-pulsed was similar to that expressed on saline-treated, KLH-pulsed M[phi]. The ability of poly I:C treated M[phi] to induce the proliferation of an antigen-specific T cell hybridoma, but not primary, resting T cells suggested that poly I:C did not affect the processing of antigen, but rather may be modulating a signal necessary for the induction of resting T cell proliferation. The proliferation of KLH-immune T cells cultured with poly I:C treated M[phi] could be restored by the addition of allogeneic M[phi] (allo-M[phi]). This increased proliferation was not due to the stimulation by alloantigens, since the restoration of antigen-specific T cell proliferation by allo-M[phi], but not the allogeneic response, was abrogated by pretreatment of allo-M[phi] with poly I:C. These results are consistent with the hypothesis that poly I:C may modulate the expression of a cell surface costimulatory molecule on peritoneal M[phi] that is required for the activation and/or proliferation of resting T cells.
Modeling and evaluation of fiber-fed microcellular systems
Authors:   , Koshy Binu John , Shankar P Mohana
Published: July 2024

The demands of the burgeoning mobile traffic, coupled with the scarcity of spectral resources, has led to the saturation of the conventional (Macrocells) cellular systems. In this regard, the concept of cell-splitting was proposed to enhance the system capacity, and has resulted in the microcellular systems. The optical fiber, due to its large bandwidth and low-loss, has been proposed to facilitate the low-cost deployment of microcells. Due to its flexibility and simplicity, the subcarrier multiplexing scheme (SCM) has been proposed as the mode of optical transport of the RF signals. The effects of fading and other nondeterministic phenomena in the wireless channel, mandate a very high dynamic range of the optical link in the uplink (mobile to base station). However, SCM-based systems are limited in their dynamic range due to the presence of nonlinearities (NLs) in the optical link. Therefore, it is imperative that any feasibility-study of the fiber-optic microcellular (FOM) systems consider the statistical effects of the wireless channel and the NLs in the lightwave link. The modeling and evaluation of FOM systems is presented from a bit error rate (BER) and probability of outage point of view. The models quantitatively predict the effects of the NLs of the optical link and the time-variant multipath nature of the wireless channel. Spread-spectrum techniques are proposed and investigated to alleviate the system impairments.
Cloning, molecular characterization and altered expression of human twist during in vitro senescence of human diploid fibroblasts
Authors:   , Wang Sherry M. , Cristofalo Vincent J
Published: July 2024

Aging (senescence) is the occurrence of deleterious, cumulative, and apparently universal changes in living organisms that lead to an increased probability of morbidity and death. The limited proliferative potential of human diploid fibroblasts is considered as a model for this process, and this perception has provided the foundation for current approaches to the study of aging at the cellular level. The theories of cellular aging mechanism have been grouped into two distinctive categories: accumulation of random damages (extrinsic), and alteration of genetic control (intrinsic). Both may play a role both in in vivo aging and in the process of cellular aging. In our studies, we have emphasized on the possible role of altered genetic regulation during the cellular aging process. Several differentially expressed genes have been isolated from a subtracted library of young and senescent WI-38 human fetal lung-derived fibroblasts. I report here the cloning, sequencing and characterization of one of these differentially expressed genes, human twist. H-twist mRNA is overexpressed in young quiescent versus senescent human diploid fibroblasts. Twist genes have been characterized in different species including Drosophila, Xenopus, and mouse. They encode basic helix-loop DNA-binding transcription factors that play crucial roles in mesoderm development. The H-twist gene encodes a protein of 201 amino acids with 96% amino acid sequence identity to mouse twist, and 100% sequence conservation in the DNA-binding region among all species in which it has been characterized. The expression of human twistis primarily observed in mesoderm-derived cell lines and tissues. This expression patern is consistent with previous studies of the twist gene in Drosophila, Xenopus mouse, and suggests a fundamental role of the twist gene in mesoderm formation. I have also studied the pattern of H-twist expression as a function of in vitro lifespan in human diploid fibroblasts (HDF). H-twist is found to be preferentially expressed in young, Go cultures, and addition of fresh serum to these cultures results in a rapid repression of H-twist expression. This repression depends on the presence of growth factors, specifically EGF, and requires protein synthesis. Studies of mRNA stability, using actinomycin D or [alpha]-amanitin indicate a similar decay rate of H-twist mRNA in both young and senescent cells, suggesting that the differential expression of H-twist in young versus old is not primarily regulated at the level of possible role of mRNA turnover. Further exploration of H-twist on growth inhibition. This potential role of H-twist as a negative growth regulator suggests an important function in the control of fundamental processes such as cell proliferation, differentiation, senescence, and tumor formation.
Characterization of the YLR190w gene product in the yeast Saccharomyces cerevisiae
Authors:   , Metera Kimberly A. , Bergman Lawrence W
Published: July 2024

Pho85p, a nonessential Cyclin Dependent Kinase (CDK), associates with two cyclins Pc16p and Pc17p, but the function of either complex is unknown. A yeast genome wide two-hybrid screen performed by Fields and co-workers suggested that an uncharacterized open reading frame (ORF) named YLR190w interacts with Pc16p. Recently, YLR190w has been renamed MMR1 at the Saccharomyces Genome Database, therefore, we will refer to YLR190w as MMR1. We have performed a two-hybrid screen to isolate proteins that interact with Mmr1p and have shown that this protein interacts with the carboxyl terminal tail of Myo2p, an essential Class V myosin, and confirmed that Pc16p does indeed interact with Mmr1p. Using epitope tagged versions of Mmr1p we have found that this protein localizes to the area of the bud in yeast. Further studies with synchronous cell cultures show that this localization moves from the point of a newly formed bud through the bud neck. Myo2p has been implicated in playing a key role in the transport of vesicles from the mother cell to the bud and numerous published studies have shown that Myo2p also localizes to sites of polarized cell growth. Our immunofluorescence data show these two proteins co-localize to the same areas. We also examined the protein expression of Mmr1p as it has been shown to localize in a polarized manner and interact with the Pc16p-Pho85p kinase complex. In wild type cells, we found that Mmr1p appears as a single band in early time points after release from [alpha] factor treatment, and at later time points, Mmr1p appears as a doublet. This doublet was subsequently to be shown to be a result of phosphorylation. Results from western analysis of synchronized cells from both pho85[delta] and pc16[delta]pc17[delta] cells suggest that Pho85p is not the kinase responsible for the stage specific phosphorylation of Mmr1p. These results also indicate that Pc16p and Pc17p play a role in this phosphorylation. The work presented here begins to elucidate the function of Mmr1p in the cell.
Structure/function analysis of the putative lipid transporter Arv1 and investigation of its role in polarized growth in Saccharomyces cerevisiae
Authors:   , Villasmil Michelle Luan , Nickels Joseph T
Published: July 2024

The function of the putative lipid transporter, Arv1, is essential at high temperatures and in mutants unable to esterify sterols in the yeast Saccharomyces cerevisiae. Deletion of ARV1 results in defects in sphingolipid metabolism, sterol trafficking, and GPI biosynthesis. Our studies focused on examining the role of Arv1 in yeast cell growth. We used structure/function analysis to dissect the multiple roles of Arv1 during yeast conjugation, growth under heat stress, and growth in the presence of antifungal drug compounds. Here we demonstrate that arv1 cells are mating defective because of a failure to effectively recruit the MAPK scaffold Ste5 to the plasma membrane. Failure to polarize phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) likely contributes to the mislocalization of Ste5 during the mating response in arv1. These defects ultimately lead to the inability of arv1 cells to generate shmoos or mate. We also show that arv1 cells are highly sensitive to antifungal drug compounds including the polyene compound nystatin and the azole compounds fluconazole and miconazole. Structure/function analysis of Arv1 identified critical residues required for Arv1 function during growth at high temperature and in the presence of antifungal drugs. Using targeted mutagenesis of conserved residues and charged-to-alanine scanning mutagenesis, L13, C27, 147, R58 H59, N63, H68 K71, K146 K147, and K205 H206 were found to be essential for Arv1 function. To gain a better understanding of Arv1 function, membrane topology studies were initiated; we found that the conserved Arv1 homology domain (AHD) is cytosolic and that Arv1 has a large ER luminal loop. Finally, we discovered that the increased sensitivity to azole compounds observed in arv1 cells may be attributed to decreased protein levels of the azole target Erg11. Importantly, the conserved AHD was shown to be required for all Arv1 functions tested.
Formation, levitation and evaporation of unsupported liquid fuel droplet clusters
Authors:   , Liu Song , Choi Mun Young , Ruff Gary A.
Published: July 2024

Evaporation and combustion experiments using arrays of droplets seek to provide a link between single droplet phenomena and the behavior of complex spray systems. Both single droplet and droplet array studies have been conducted in microgravity to better isolate the droplet interaction phenomena and eliminate or reduce the confounding effects of buoyancy-induced convection. In most experiments involving droplet arrays, the droplets are supported on fibers to keep them stationary and close together prior to combustion. The presence of the fiber, however, disturbs the combustion process by introducing a source of heat transfer and asymmetry into the configuration. As the number of drops in a droplet array increases, supporting the drops on fibers becomes less practical because of the cumulative effect of the fibers on the combustion process. In this thesis, recent works related to the single drop and droplet array evaporation and combustion, unsupported droplet and droplet cluster formation, and microgravity combustion experiments are reviewed. A unique experiment in which unsupported droplet clusters are formed in normal gravity has been developed and the design concepts and test results are presented and discussed. The results of droplet cluster formation and levitation tests and investigations of the acoustic field are also presented. The current 1-g equipment has been used to investigate the inter-droplet effects of a droplet cluster supported in an acoustic field. Droplet size, inter-droplet distance and evaporation rate were measured and compared with theoretical models. It was found that the single droplet evaporation results are consistent with previous studies and compared well with the single droplet evaporation models. Direct experimental results of multiple droplet evaporation were obtained and compared with a point source method. Based on the 1-g test results, the experimental apparatus will be incorporated into a drop tower rig where experiments can be performed in a microgravity environment.
The Perceived Impact of Professional Development on the Development of Instructional Coaches
Authors:   , Steinbacher-Reed Christina , Miller O'Neal Michel L.
Published: July 2024

Over the past decade, instructional coaching has quickly asserted itself as one of the leading professional development models of the 21st Century. While there is a growing demand for instructional coaches, some believe that many coaches are not provided with the training they need to be effective in their new role (Brown, Stroh, Fouts, & Baker, 2005; Tschannen-Moran & Tschannen-Moran, 2011). The purpose of this descriptive research study is to explore the types of professional development provided to Pennsylvania's instructional coaches by documenting and analyzing the quantity, quality, and perceived impact of trainings offered to Pennsylvania instructional coaches. The sample was limited to Pennsylvania coaches and "instructional coaching" was defined in accordance with Jim Knight's definition which describes an instructional coach as an onsite professional developer who works with teachers to help them incorporate research based instructional practices across all content areas (2007). This mixed-methods study utilized an online questionnaire to document the professional development experiences of instructional coaches throughout Pennsylvania. The three-part questionnaire included a section on demographics, professional development experiences, and open-ended responses. The professional development section of the questionnaire asked participants to identify topics in which they had been trained, characteristics of the training, and their perceived impact that the training had on their development as an instructional coach. Descriptive statistics were used to analyze the data and report the findings. The findings were organized by demographics data, content of professional development, quality of professional development and impact of professional development. The demographic data found that the sample represented a wide- variety of coaching initiatives from across the state. While the content of subjects' professional development did include topics from the PA Coaching Competencies, there was not substantial participation in topics related to effective coaching practices. When coaches did participate in professional learning, they reported that the training met multiple characteristics of effective professional development. Coaches also noted that coach-to-coach support was the most valuable form of professional learning. In regards to the impact of professional development, most coaches reported that the training they have received has had a moderate to large impact on their development as a coach.
Narrow band optical filter for lidar
Authors:   , Yang Guangning
Published: July 2024

A narrow-band, gate-able matched optical filter with large extinction ratio and high transmission is required for ocean lidar applications at wavelength of 532 nm. Two types of filters, the induced dichroism excited-state atomic line (IDEAL) and excited state anomalous Faraday dispersion optical filter (ESFADOF), are studied. They are operating on the 4P1/2 to 8S1/2 excited states transition line of potassium vapor and a narrow band at 532 nm. The measured critical features of the IDEAL filter are: 1.3 GHz (i.e..01A) narrow pass band, approximately 45% peak transmission, high extinction coefficient in the order of 10-5, very fast rise time (<3ns) and a 15 ns decay time determined by resonant enhanced two photon transition. The physical mechanism of the IDEAL filter operation is explained in terms of resonant enhanced two photon transition. Good agreement between experiment and the derived theoretical model is achieved. The pertinent features of the excited (ESFADOF) filter were measured to be: approximately 15% peak transmission, high extinction coefficient in the order of 10-5, very fast rise time (<3ns), and a decay time in the tens of microsecond range governed by resonant photon trapping. The physical processes contributing to the ESFADOF filter action are resonant photon trapping and Faraday anomalous dispersion. The experimental results confirmed theoretical predictions. The applications of these filters are discussed in terms of improving the lidar system performance. Specifically, the narrow bandwidth of these filters eliminates the background noise caused by stray solar radiation and thereby enhances the dynamic range of the lidar system. Furthermore the fast efficient gating of the filters minimizes reflection from the ocean surface, which is several orders of magnitude higher than the return signal from underwater targets.
The economic integration of the Asia Pacific Region
Authors:   , Stone Susan F. , Jeon Bang Nam
Published: July 2024

This dissertation presents three major findings. First is that the Asia Pacific Region (APR) is economically integrated and the relationship is stronger at the regional level than bilateral level. Second, trade is regionally dependent and regional dynamics again outweigh any bilateral relationships. The third finding was the complementary relationship between trade and Foreign Direct Investment flows in the APR. Given the strong regional impact on trade, and the strong impact trade has on FDI, it is concluded that regional forces impact FDI through trade. This work extends the research on the role geography plays in determining patterns of trade and investment. The investigation thus far has been limited to the impact of formal regional arrangement on these variables. However, there need not be a formal arrangement for geography to play a part in trade and investment patterns. The existence of a regional bias in these flows in the absence of a formal regional arrangement is called Regionalization. Thus work has shown that region plays a part in determining APR trade and investment patterns and that Regionalization is at work in the area. The degree of economic integration in the region is shown through the linkages among the macroeconomies of the countries in the study. These economies include Hong Kong, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand. They were shown to share common long run trends in their output, interest rates and price levels variables. Evidence of common trends were stronger on a multilateral, or group, basis than in bilateral relationships. The existence of integration is shown through the existence of common trends while regional importance is evidenced through strong multilateral links. Regional impact on trade was evidenced through strong multilateral linkages in exports, import and total trade flows. The gravity equation provided consistent proof of a regional impact beyond simple distance factors. Foreign direct Investment was also shown to be regionally dependent. Finally, trade and foreign direct investment were shown to have a significant and complementary relationship in the region.
Psychological type
Authors:   , Drogin Eric York , Swift Marshall
Published: July 2024

This dissertation purposes a practice-oriented framework for the role of the lawyer/clinical psychologist (LCP) in consultation to the legal profession. It reviews the psychological perspective on lawyers and the legal profession, spotlighting the effects of alcoholism in the legal profession and both legal and psychological attempts to remedy those effects. Theoretical and practical aspects of the role of the psychologist as mental health consultant are examined. Differences in psychological type among three categories of lawyers (271 practicing lawyers, 128 Judges, and 84 administrative Attorneys) are examined with the use of archival data from administrations of the Myers-Briggs Type Inventory. Results confirm predictions derived from the psychological literature, that differing prevalences of personality type and aspects of personality type can be discerned for each of the specializations, with an overall emphasis on thinking at the expense of feeling, and an overall prevalence of combinations of thinking and judging. Relevance to psycholegal consultation by LCPs and implications for future research are discussed.