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73 matches in the database. These are records: 1 - 30.

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1. Adams, Hadiya Annvela. EXAMINING SIGNER-SPECIFICITY EFFECTS IN THE PERCEPTION OF WORDS IN AMERICAN SIGN LANGUAGE.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► Variability in talker identity, which is commonly referred to as one type… (more)

▼ Variability in talker identity, which is commonly referred to as one type of indexical variation, has demonstrable effects on the speed and accuracy of spoken word recognition. In the current study, I conducted two experiments designed to examine whether talker variability has an effect on the perception of words in American Sign Language. Native and non-native signers participated in two long-term repetition-priming experiments in which they performed two separate blocks of lexical decision trials. In Experiment 1, all participants were native signers. In Experiment 2, all participants were late signers. In both experiments, all participants performed both an easy and a hard lexical decision task. In the easy lexical decision task, the non-signs did not resemble real signs, making the task relatively easy. In the hard lexical task, the non-signs resembled real signs, making the task relatively difficult. In both experiments, some of the signs (and non-signs) in the second block also appeared in the first block (primed conditions) and some were new stimuli that had not appeared in the first block (control condition). Half the primed stimuli were produced by the same signer in the two blocks (matched condition) and half were produced by a different signer (mismatched condition). Based on previous research in spoken word recognition, I made the following predictions: 1) primed stimuli would be responded to more quickly than unprimed stimuli, 2) signs in the match condition would be responded to more quickly than signs in the mismatch condition (i.e., a signer-specificity effect), and the signer-specificity effect was expected to be greater when processing was relatively slow, that is 3) in Experiment 2, with late signing participants, and 4) in the hard lexical decision task. The results inform theories and models of sign language perception, add to the knowledge of the circumstances in which variability is expected to have an effect on the recognition of words, and provide an opportunity to evaluate whether time-course effects in spoken word recognition extend to the visual perception of words in sign language. Advisors/Committee Members: McLennan, Conor.

Keywords: ASL, American Sign Language

2. ALHARBI, SAYER RASHED. THE ROLE OF BCL-2 FAMILY IN CLINICAL RESPONSE OF CHRONIC LYMPHOCYTIC LEUKEMIA.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► The anti-apoptotic Bcl-2 proteins regulate lymphocyte survival and are over-expressed in lymphoid… (more)

▼ The anti-apoptotic Bcl-2 proteins regulate lymphocyte survival and are over-expressed in lymphoid malignancies, including chronic lymphocytic leukemia (CLL). The small molecule inhibitor ABT-737 binds with high affinity to Bcl-2, Bcl-xl, and Bcl-w but with low affinity to Mcl-1, Bfl-1, and Bcl-b. The active analog of ABT-737, navitoclax, has shown a high therapeutic index in lymphoid malignancies; developing a predictive marker for it would be clinically valuable for patient selection or choice of drug combinations. We compared expression of anti-apoptotic Bcl-2 genes that are known to be targeted by ABT-737. Our findings reveal that the relative ratio of Mcl-1 and Bfl-1 to Bcl-2 expression provides a highly significant linear correlation with ABT-737 sensitivity (r = 0.6, P < .001). The (Mcl-1 + Bfl-1)/Bcl-2 ratio was validated in a panel of leukemic cell lines subjected to genetic and pharmacologic manipulations. We also tested whether anti-apoptotic Bcl-2 proteins can be used as prognostic marker in CLL, since the current prognostic markers, such as CD38 and ZAP70 fail to predict the clinical outcome in a substantial number of CLL patients. Our findings indicate that only high Bcl-xl expression is strongly correlated (P=0.002) with short treatment-free survival. Strikingly, Bcl-xl was able to identify patients with high risk in the ZAP70 negative and CD38 negative groups as well as in patients with normal/unknown p53 deletion, thus providing a very powerful prognostic value for CLL. Finally, we investigated the potential mechanism responsible for ABT-737 resistance in leukemic cell lines. Compared with parental cells, cells that have developed acquired resistance to ABT-737 showed increased expression of Mcl-1 due to increased protein stability. Interestingly, increased Mcl-1 levels sequester the BH3-only protein Bim which mediates resistance to ABT-737. These data therefore reveal novel insights into the role of anti-apoptotic Bcl-2 proteins in clinical response, acquired resistance, and tumor progression in CLL patients. Advisors/Committee Members: Almasan, Alex.

Subjects: Molecular Biology

Keywords: Apoptosis, Bcl-2 family, chronic lymphocytic leukemia, ABT-737

3. Amundsen, Kelly J. Mapping Riparian Vegetation in the Lower Colorado River Using Low Resolution Satellite Imagery.

Degree: MS, College of Sciences and Health Professions, 2010, Cleveland State University

► In the Western United States, monitoring water usage is a complex task… (more)

Subjects: Environmental Science; Remote Sensing

Keywords: Lower Colorado River Riparian; LCRAS; Saltcedar; Vegetation Mapping

4. Archacki, Stephen R. MOLECULAR IDENTIFICATION OF NOVEL GENES ASSOCIATED WITH ATHEROSCLEROSIS.

Degree: PhD, College of Sciences and Health Professions, 2011, Cleveland State University

► Despite the identification of the risk factors which lead to CAD, we… (more)

▼ Despite the identification of the risk factors which lead to CAD, we hypothesize there are novel genes to be identified that cause dysfunctional mechanisms leading to disease. For these discoveries, we utilized the genechip also referred to as a microarray. We did expression profiling of coronary arteries from human patients with and without disease and identified 56 genes. The association of 49 genes with CAD appears to be novel, and they included genes: ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, ß2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-α-induced protein 2 (B94), and flavocytochrome 558. It is well-known that IMAs are resistant to the development of atherosclerosis, whereas the coronary arteries are athero-prone. The contrasting properties of these arteries provides an innovative strategy to identify the gene(s) that may play important roles in the development of CAD. We found 29 genes with a significant difference in their expression levels between IMA and the coronary artery which included the TES gene encoding Testin. Using assays relevant to atherosclerosis, we showed that the knockdown of TES expression by siRNA promoted oxLDL-mediated monocyte adhesion to endothelial cells (EC), EC migration, and the transendothelial migration of monocytes, while the over-expression of TES in ECs blunted these processes. These results define a new molecular determinant (TES) for CAD and establish a novel role for TES. We also investigated the gene expression of the ECs harvested from IMA and Cor to further distinguish these arteries’ differential sensitivities to the develop atherosclerosis. The most statistically significant gene identified was the adenosine A2B receptor (A2B). Consequently, A2B was selected for follow-up functional studies to define its role(s) in ECs and how it may promote a resistance to atherosclerosis. We showed that the over-expression of the A2B receptor blunted processes relevant to the atherosclerosis. In sum, expression profiling offered us the opportunity to identify novel genes that may be related to atherosclerosis. The identification of genes associated with this disease may lead to more aggressive interventions to halt the disease process of atherosclerosis by understanding the underlying genetic processes. Advisors/Committee Members: Wang, Wang.

Subjects: Genetics

Keywords: cardiovacular disease, genetics, genechip, expression profiling

5. Badipatla, Visweswararao. Disintegration of Tablets and Capsules Measured by Isothermal Thermal Mechanical Analysis and Macrophotography.

Degree: MS, College of Sciences and Health Professions, 2011, Cleveland State University

► The current United States Pharmacopoeia (USP) test for tablet and encapsulated drug… (more)

Subjects: Analytical Chemistry

6. Bani Hani, Saleem A. M.Sc, Ph.D. Semen Quality and Chemical Oxidative Stress; Quantification and Remediation.

Degree: PhD, College of Sciences and Health Professions, 2011, Cleveland State University

► The necessary multi-step process to prepare human semen for assisted reproduction (AR)… (more)

Subjects: Analytical Chemistry; Biomedical Research; Medicine

Keywords: Assisted reproduction; human spermatozoa; semen quality; reactive oxygen species; oxidative stress; antioxidants; L-carnitine; nitric oxide.

7. Basuroy, Tupa. Intricate RNA:RNA Interactions In U12-dependent Nuclear Pre-mRNA Splicing.

Degree: MS, College of Sciences and Health Professions, 2011, Cleveland State University

► Coding regions or exons of most human genes are interrupted by noncoding… (more)

Subjects: Biology; Molecular Biology

Keywords: RNA-RNA interactions; 65K-C-RRM protein; nuclear pre-mRNA splicing; U12-type or minor splicing; U6atac snRNA

8. Biesan, Orion R. Normative Data Collection and Comparison of Performance on the Poreh Naming Test to the Boston Naming Test.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► Although word-finding difficulty is commonly self-reported by older adults, there are no… (more)

Subjects: Clinical Psychology

Keywords: Boston Naming Test; confrontation naming test; latency; word-finding abilities; naming; aging

9. Cai, Xiaohan. ï»¿Development of Bioanalytical Methods for Clinical Applications and Drug Screening.

Degree: PhD, College of Sciences and Health Professions, 2011, Cleveland State University

► In the past decade, bioanalytical method development has become an integral part… (more)

▼ In the past decade, bioanalytical method development has become an integral part of clinical diagnosis, biomarker discovery, and drug discovery and development. The new and emerged bioanalytical technologies allow the quantitative and qualitative analysis of small molecules and biomolecules with high sensitivity and specificity. Specifically, the bioanalytical methods based on LC-MS and methylation-specific PCR are well suited for detecting low-abundance metabolites, proteins, and DNA in biofluids and tissues for biomarker investigation. They offer great clinical promises for early diseases diagnosis and therapeutic interventions. Besides, the LC-MS/MS quantitative method is essential for the estimation of pharmacokinetic and toxicological properties in drug screening. In this work, modern bioanalytical technologies, together with their applications from biomarker discovery and validation in metabonomics, genomics and proteomics to drug discovery, were reviewed. Dependent on the type of molecules analyzed, different methods were established to achieve accurate and reliable detection. LC-MS/(MS) methods were developed and validated for quantitative analysis of bile acids and anti-cancer agent JCC76. The former has been successfully applied in a clinical study for the diagnosis of inflammatory bowel diseases; and the latter has been utilized in a pharmacokinetics study for drug screening and optimization. In terms of proteomics profiling, a LC-MS/MS method was demonstrated for comparative analysis of serum peptides with the successful identification of a potential biomarker for ovarian cancer. Lastly, a comprehensive DNA methylation profiling for hepatocellular carcinoma was conducted through methylation-specific PCR methods. These methods enabled sensitive and specific detection of DNA hypermethylation on several tumor-associated genes. In addition, this work discussed a major challenge of matrix effect in quantitative method development. Possible solutions were proposed for matrix effect prevention and troubleshooting. Moreover, standard addition coupled with internal standard method and optimizing sample extraction method was illustrated for compensating or minimizing matrix effect in chapter II and chapter III, respectively. Advisors/Committee Members: Guo, Baochuan.

Subjects: Chemistry

Keywords: LC-MS(/MS); method development; proteomics; gene methylation

10. Chalagalla, Srinivas. Design, Synthesis and Characterization of Oriented Glyco-Affinity Macroligands for Glyco-Capturing, Glycomics and Glycoproteomics Applications.

Degree: PhD, College of Sciences and Health Professions, 2011, Cleveland State University

► Cell surface carbohydrates existing as parts of glycoproteins, glycolipids, and other conjugates… (more)

▼ Cell surface carbohydrates existing as parts of glycoproteins, glycolipids, and other conjugates present the first information about cell to the outside world and are intimately involved in various biological events such as intercellular communication, and molecular and cellular targeting. However, mechanisms of most processes at the molecular level are still unclear. Therefore, it is very important to develop carbohydrate-specific binding molecules for rapid, efficient, sensitive purification and accurate analysis of complex carbohydrate structures as well as their functions. Furthermore, carbohydrate-specific binding molecules can be expected to be used in medical diagnostic applications for carbohydrate biomarkers. In this thesis study, oriented and multivalent carbohydrate-binding macromolecules were designed and developed based on a chain-end functionalized boronic acid-containing polymer (boropolymer) for glyco-capturing, glycomics and glycoproteomics applications. Namely, a biotin chain end and O-cyanate chain-end functionalized boropolymers were synthesized via aryalamine initiated cyanoxyl-mediated free radical polymerization in a one-pot fashion. The resultant boropolymers were characterized by 1H-NMR and 13C NMR spectroscopy. In our first study we demonstrated the efficient glyco-capturing followed by direct MALDI mass spectrometry identification of the captured carbohydrate by using magnetic beads functionalized with the biotin boropolymer via streptavidin/biotin interaction. In our second study we demonstrated oriented and covalent immobilization of O-Cyanate chain-end functionalized boropolymer on to amine-modified solid surfaces and its specific glyco-capturing capacity by QCM and AFM techniques. We further studied the multivalent interactions of the immobilized O-Cyanate chain end functionalized boropolymer with five different carbohydrate conjugated AuNPs. Our studies showed that different carbohydrates have different binding constants. Furthermore, the multivalent binding between carbohydrates and boropolymer was reversible and allowed the regeneration of boropolymer surface for sequential capture and release of the carbohydrate analytes. This oriented multivalent glyco-affinity ligands could be used for efficient carbohydrate and glyco-conjugates purification and identification and thus is expected to constitute a core strategy of glycomics and glycoproteomics targeting glyco-protein. Advisors/Committee Members: Sun, Xue-Long.

Subjects: Chemistry

Keywords: boropolymer; carbohydrates; Boronic acid; AuNPs; chain-end; functionalized

11. Chirico, Marie M. Relationship Between Internal Homonegativity and Self-Harm Behaviors.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► The Lesbian, Gay, and Bisexual (LGB) population has been shown to have… (more)

Subjects: Clinical Psychology; Psychology

Keywords: Lesbian; Gay; Bisexual; Self Harm; Internal Homonegativity

12. Das, Priyanka. Study of the L13a residues required for ribosomal function.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► Ribosome biogenesis, a fundamental process, occurs in the nucleolus. It involves incorporation… (more)

▼ Ribosome biogenesis, a fundamental process, occurs in the nucleolus. It involves incorporation and association of ribosomal proteins (r-proteins) in the ribosomal subunit. Despite its obligatory and critical role in cellular function, the explicit mechanism of incorporation of different r-proteins into the pre-ribosome is not well understood. Using mammalian cell and r-protein L13a as our model, this study addresses the function and mechanism of r-protein incorporation during ribosome maturation. Published results from our laboratory showed the requirement of the release of L13a from the 60S ribosome to silence a cohort of inflammatory proteins directly at the level of translation thus showing the significant potential of this mechanism to resolve inflammation. To get further insight into the mechanism of its release, it is essential to identify the domain of L13a and the subcellular site required for ribosome incorporation. Homology modeling of human L13a with the crystal structure of prokaryotic L13, predicted some amino acid residues that could bind to ribosomal RNA (rRNA). Consistent with this model, a combined experimental approach involving ribosome incorporation assay of recombinant L13a and RNA immunoprecipitation have identified Arg at position 68 and Arg-Lys-Arg at position 59-60-61 as potential interaction site with 60S subunit. We have performed immunofluorescence studies to test whether the incorporation defective mutant L13a failed to translocate to the nucleolus, the site of ribosome biogenesis. L13a harboring the mutation of Arg at position 68 to Ala translocate to the nucleolus, but however alters the nucleolar morphology. In contrast L13a with the mutation of Arg-Lys-Arg at position 59-60-61 to Ala-Ala-Ala is nucleolar translocation incompetent. These studies also identified that incorporation of L13a during ribosome biogenesis occurs at the stage of 90S pre-ribosome formation. Previous studies from our laboratory showed an essential role of L13a in rRNA methylation. In these studies we identified L13a as an interacting partner of Fibrillarin containing C/D box snoRNP complex, thus showing a strong rationale of L13a as a rRNA methylation factor. Most importantly, these studies also showed that incorporation of L13a in the 60S subunit is restricted only during ribosome biogenesis and not after maturation. Advisors/Committee Members: Mazumder, Barsanjit.

Subjects: Molecular Biology

Keywords: L13a; ribosome biogenesis; rRNA methylation

13. Das, Vaijayanti. STRUCTURAL BASIS OF LMAN1 CARGO CAPTURE IN ER & RELEASE IN ERGIC.

Degree: MS, College of Sciences and Health Professions, 2012, Cleveland State University

► Proteins destined for secretion, after folding and the initial modification in the… (more)

▼ Proteins destined for secretion, after folding and the initial modification in the endoplasmic reticulum (ER), are transported to the ERGIC and then to Golgi stacks, before being sorted into their final destinations. Collectively these proteins that move through the secretory pathway are known as cargo proteins. Some of the soluble cargo proteins require cargo receptors to be efficiently packaged into vesicles exiting the ER. Evidence for the presence of such receptors in mammals came from the studies of a genetic disorder called the combined deficiency of factor V (FV) and factor VIII (FVIII) or F5F8D. F5F8D patients have mutations in either of the two genes - LMAN1 or MCFD2. LMAN1 and MCFD2 form a receptor complex that facilitates the ER to Golgi transport of FV and FVIII. Distinct binding sites for FV and FVIII exist on LMAN1 and MCFD2, but the specific location of these binding sites are not known. Ambiguity exists on the mechanism of cargo release by LMAN1 and MCFD2. Like FV and FVIII, other LMAN1 cargos (cathepsin C, Z and α-1 antitrypsin) are also glycosylated. Thus the sugar binding activity of carbohydrate recognition domain (CRD) of LMAN1 is presumably important for the recognition of the cargo glycoprotein. Using biochemical approaches we determined the locations of sugar binding sites and their importance in cargo binding. We successfully purified the CRD of LMAN1 using a denaturation/refolding protocol. Using isothermal titration calorimetry (ITC) assay, we confirmed that our purified CRD is a functional protein by its ability to bind to 2 calcium ions. ITC assay also provided insight on the effect of pH on binding ability of CRD to calcium as well as revealed the binding affinity of CRD towards its ligand α1-2 mannobiose. In collaboration with Dr. Saurav Misra's lab, we solved the structure of mannobiose bound CRD which revealed key amino acids involved in ligand binding. Mutations of these amino acids in LMAN1 were constructed to reconfirm their importance in sugar binding in vivo. These biochemical studies will provide a useful insight into the mechanism of cargo binding in the ER and release in the ERGIC and Golgi. Advisors/Committee Members: Zhang, Bin.

Subjects: Biochemistry

Keywords: Mechanism of protein trafficking in the early secretory pathway

14. Dawson, Nicole T. What Factors Predict Falls in Cognitively Impaired Older Adults?.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► A significant amount of research has been conducted to identify possible risk… (more)

▼ A significant amount of research has been conducted to identify possible risk factors and causes of falls in older adults as well as implementing interventions in efforts to reduce the incidence of falls in this population. Falls accounted for 2 million non-fatal injuries to adults over the age of 65 in 2007 while over $19 billion is spent annually on direct medical costs. Most of the literature is representative of healthy, community-dwelling adults while a much smaller amount is reserved for the subpopulation of older adults with cognitive impairment. Cognitively impaired adults are twice as likely to fall as healthy older adults. There are several theories that attempt to explain this increased risk including decreased executive function, decreased visual attention, difficulty with dual-task resource allocation, fear of falling and reduced awareness of deficits. The current study examined these theories directly by having cognitively impaired older adults (N=55) complete a cognitive assessment (Mini-Mental State Examination, clock-drawing test, serial 3-retro, categorical naming task and counting dots) as well as using a dual-task paradigm to assess resource allocation using the 10-meter walk test. Awareness of deficits was measured using a modified version of the Anosognosia Questionnaire-Dementia while fear of falling was assessed using the Short Falls Efficacy Scale-International. The number of falls incurred over the last 12 months was used as the criterion variable. Bivariate correlation and multiple linear regression analyses were conducted to identify significant independent predictors of falls as well as the most parsimonious model of predictors in this population of cognitively impaired older adults. No significant relationships were found between falls and the predictor variables of working memory, verbal fluency, visual attention, gait velocity, and awareness of deficits. Dual-task cost was not predictive of falls in this sample. Visual attention measured in the single condition was found to be significantly different between single fallers and recurrent fallers. More research is needed to further evaluate this possible relationship as well as continue search for possible unique identifiers of falls in the cognitively impaired older adult in efforts to identify areas amenable to interventions. Possible directions of future research are discussed. Advisors/Committee Members: Judge, Katherine S.

15. DeGirolamo, Gregory J. Impact of Sequence and Cognitive Aging On Spatial Learning From Ground Level and Aerial Perspectives.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► This study examined the impact of healthy aging on two important factors… (more)

Subjects: Cognitive Psychology; Developmental Psychology; Experimental Psychology

Keywords: spatial Learning, aging, navigation, map, ground-level, aerial, route, survey

16. Donaldson, Maria J. Change Detection Ability in Naturalistic Scenes: Are Object Appearances or Disappearances easier to Detect when Disappearances should be more Noticeable?.

Degree: MA, College of Sciences and Health Professions, 2011, Cleveland State University

► Onset primacy is a robust phenomenon in which appearance of new objects… (more)

Subjects: Psychology

17. Dorf, Alexander E. The Impact of Motivational Systems on Dynamic Inconsistency in Risk Taking.

Degree: MA, College of Sciences and Health Professions, 2011, Cleveland State University

► Every day we are confronted with risky decisions in which the rewards… (more)

18. El-Khoury, Joe M. Chronic Kidney Disease: Vitamin D Treatment Regimens and Novel Assay Development for Kidney and Cardiovascular Function Biomarkers.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► Chronic kidney disease (CKD) is highly prevalent in the US population and… (more)

▼ Chronic kidney disease (CKD) is highly prevalent in the US population and has high incidence of cardiovascular and all-cause mortality. A known complication of CKD is secondary hyperparathyroidism that is caused by bone and mineral imbalances, including vitamin D deficiency. Supplementation of CKD patients with vitamin D is based on guidelines issued by the Kidney Disease Quality Outcomes Initiative (K/DOQI), which recommend administration of vitamin D2 in variable doses depending on the severity of vitamin D deficiency. Retrospective and pilot studies have shown that vitamin D2 was not as effective as vitamin D3 in treating vitamin D deficiency. In Chapter I, we investigated the effectiveness of vitamin D2 versus vitamin D3 treatment in resolving vitamin D deficiency in the pre-dialysis CKD population. This study was a double blinded, randomized, single center study that involved 22 CKD subjects. Data showed that vitamin D3 elicited a more rapid increase in 25-hydroxyvitamin D (25OHD) levels than vitamin D2, but both forms became equivalent in terms of the number of people who reached target 25OHD levels by the end of study. Glomerular filtration rate (GFR) is the best overall index of kidney function. GFR is determined by measuring the urinary clearance of a radioactive exogenous biomarker, such as iothalamate, or estimated (eGFR) by measuring creatinine and adjusting for race, gender and age using equations. There are several known limitations to using creatinine-based equations and radioactive substances exposure for eGFR and GFR determinations. In the remaining Chapters, solutions are proposed for measurement of GFR and eGFR, which involve liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chapter II discusses this technique and the process of development and validation of bioanlaytical methods by LC-MS/MS. Chapter III introduces a LC-MS/MS method for the measurement of L-arginine, symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA). SDMA was correlated with biomarkers of kidney function, while ADMA was correlated with biomarkers of cardiovascular disease. Chapter IV introduces a new LC-MS/MS method for the measurement of non-radioactive iothalamate to replace existing radioactive measurements for GFR determination. This method is very simple, fast, sensitive and selective and has shown good correlation with radioactive measurement of GFR. Advisors/Committee Members: Wang, Sihe.

Subjects: Biochemistry; Chemistry; Medicine

Keywords: Vitamin D; ADMA; SDMA; GFR; iothalamate; chronic kidney disease; CKD; liquid chromatography; mass spectrometry; method development

19. Ellison, Lisa. Treatment of Co-Morbid Chronic Pain and Substance Use Disorders.

Degree: MA, College of Sciences and Health Professions, 2011, Cleveland State University

► Chronic pain affects approximately 15% of the adult population with substance use… (more)

Subjects: Psychology

20. Fang, Fang. Gain-of-function mutations in SCN5A gene lead to type-3 long QT syndrome.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► Type-3 long QT syndrome, which is related to type 5 voltage-gated sodium… (more)

▼ Type-3 long QT syndrome, which is related to type 5 voltage-gated sodium channel alpha subunit (SCN5A) mutation, has been identified since 1995. LQTS mutation in SCN5A is a gain-of-function mutation producing late sodium current, INa,L. Brugada mutation in SCN5A is a loss-of-function causing INa decrease. Whereas, the mechanism for Dilated Cardiomyopathy mutations in SCN5A is still not fully understood. N1325S is one of the first series of mutations identified for type-3 LQTS. Our lab created a mouse model for LQTS by expressing SCN5A mutation N1325S in the mouse hearts (TG-NS) and a matched experimental control line with overexpression of wild- type SCN5A (TG-WT). There are some interesting findings in TG-NS mice: (i) Intracellular sodium (Na+) level is higher in TG-NS myocytes compared with TG-WT myocytes. (ii) Ca2+ handling is abnormal in TG-NS myocytes, but not in TG-WT myocytes. (iii) Apoptosis was also found in TG-NS mouse heart tissue, but not in TG-WT hearts. These results provoke the hypothesis that gain-of-function mutation N1325S in SCN5A leads to LQTS through abnormal cytosolic Ca2+ homeostasis. Another LQTS mutation in SCN5A R1193Q was identified in 2004 and the electrophysiological property is similar to other gain-of-function SCN5A mutations. The transgenic mouse model for this mutation was also established and the surface Electrocardiogram (ECG) results indicate longer corrected QT interval also present in transgenic mice carrying R1193Q mutation. Besides, quinidine, an anti-arrhythmic medication, can cause arrhythmic symptoms such as premature ventricular contraction (PVC), premature atrial contraction (PAC) and atrioventricular (AV) block in R1193Q transgenic mice. In order to further study the relationship between abnormal Ca2+ handling and the type of SCN5A mutation, either gain-of-function or loss-of-function, we have chosen HL-1 cells, a cell line with indefinite passages in culture with all the adult cardiac phenotypes. The similar abnormal Ca2+ handling was also identified in HL-1 cells expressing N1325S mutation but not in those cells expressing wild-type SCN5A gene. Since we hypothesized that the abnormal Ca2+ handling is caused by INa,L created by gain-of-function mutation, either in HL-1 cells or in isolated TG-NS myocytes, I then use INa,L blocker ranolazine, a clinical trial medication for LQT patients, to specifically block INa,L. After the blockage of INa,L, the abnormal Ca2+ handling was rescued in both isolated myocytes from TG-NS mice and HL-1 cells expressing N1325S mutation. Finally, several different types of SCN5A mutations related to different types of heart diseases were selected and the Ca2+ handling was tested in transfected HL-1 cells. Advisors/Committee Members: Wang, Qing.

Subjects: Biology; Chemistry; Genetics; Health Sciences

Keywords: Arrhythmia; LQTS; Cardiac sodium channel; SCN5A; Late sodium current; Calcium overload; Calcium handling; Calcium transient

21. Fominaya, Adam W. Preliminary Analysis of the Geriatric Intelligence Test.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► The Wechsler Abbreviated Scale of Intelligence was not designed specifically for older… (more)

Subjects: Gerontology; Psychological Tests

Keywords: Intelligence; IQ; Wechsler; Aging; Geriatric; gerontology; test development; WAIS-IV; WASI

22. French, Jessica Autumn. The Parasympathetic Nervous System in Human Heart Failure.

Degree: MS, College of Sciences and Health Professions, 2011, Cleveland State University

► Heart failure (HF) affects 5.8 million Americans and is characterized by an… (more)

▼ Heart failure (HF) affects 5.8 million Americans and is characterized by an inability of the heart to pump blood throughout the body. In a non-diseased state, the sympathetic (SNS) and parasympathetic nervous systems (PNS) innervate the heart to regulate rate and force of contraction. Actions of the PNS on the cardiovascular system are mediated via the vagus nerve, releasing acetylcholine which binds muscarinic receptors on cardiomyocytes. The SNS has been found to be overstimulated in HF, with the role of the PNS in HF unclear. We hypothesized that the PNS is dysregulated in HF, resulting in a change of muscarinic receptor densities. We measured total muscarinic receptor density on non-failing and failing human heart samples, and determined if demonstrated differences were reversed through mechanical unloading with a left ventricular assist device (LVAD). Through radioligand binding assays, we found a significant increase in receptor density in failing human heart samples compared to control (275.8 ± 11.9 versus 194.1 ± 17.3 fmol/mg protein; p<0.01), along with an increase in receptor density in failing with LVAD support samples(315.8 ± 23.9 versus 194.1 ± 17.3 fmol/mg protein; p<0.001). We also measured M1-M4 receptor subtypes on a subset of these samples. While the percent of M1, M2, and M4 receptor subtypes did not significantly change between non-failing, failing, and failing with LVAD support samples, the percent of M3 was significantly decreased in failure (8.61 ± 1.65 versus 13.56 ± 2.16 %; p<0.05) and increased back to non-failing percents in the failing + LVAD group (16.65 ± 0.72 versus 8.61 ± 1.65 % in failure; p<0.01). Muscle function analysis was also performed. Acetylcholine and isoproterenol were used to determine if a change in total muscarinic receptor density in groups related to a change in functional response on fresh trabecular muscles; with and without SNS stimulation. Recovery in contractile parameters without SNS stimulation on ACh-treated muscles, and greater negative inotropic and chronotropic effects on ACh-treated muscles with SNS stimulation provide evidence that total muscarinic receptor density changes elicit different responses on the failing human heart. Advisors/Committee Members: Moravec, Christine S.

Subjects: Biology

Keywords: parasympathetic nervous system; muscarinic receptors; heart failure; left ventricular assist device

23. Fruscella, Jeffrey Allen. THERMAL ANALYSIS AS AN IMPORTANT RESEARCH TOOL FOR COLLEGES AND UNIVERSITIES.

Degree: MS, College of Sciences and Health Professions, 2011, Cleveland State University

► Three experiments were performed to demonstrate that thermal analysis is an important… (more)

Subjects: Analytical Chemistry

Keywords: thermal analysis, thermogravimetry, differential scanning calorimetry, thermal mechanical analysis, education, resinkit, milk of magnesia, aldohexose monosaccharide, thermal expansion, decomposition, glass transition

24. FUAT, BICER. CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory bladder condition with… (more)

▼ Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory bladder condition with unknown pathophysiology. Chronic pelvic pain is one of the most important and disturbing symptoms of IC/PBS, beside urinary frequency, urgency, and nocturia. Increased amounts of mast cells (MCs) and CCL2 have been found in bladder tissue and urine, respectively. Whether or not there is a causal relationship between CCL2, MCs, and pelvic pain in IC/PBS is unknown. Methods: Female BALB/c mice were immunized with a peptide consisting of residues 65-84 of the bladder urothelium-specific protein uroplakin 3A to induce experimental autoimmune cystitis (EAC), a model for human IC/PBS. Referred visceral pelvic pain was measured using von Frey monofilaments at different times after immunization. Lidocaine was instilled into the bladder, colon and uterus to locate the source of the pelvic pain. CCL2 expression in tissues was measured by qRT-PCR and ELISA, and MCs in the bladder were quantified by toluidine blue staining. An MC stabilizer (cromolyn sodium), histamine H1 receptor blocker (cetirizine), and histamine H2 receptor blocker (ranitidine) were administered orally to show the relation of MCs with the pain. CCL2-/- and CCR2-/- mice, and CCR2 (CCL2 receptor) antagonist treatment were used to delineate the causative effect of CCL2 on MC accumulation and chronic pelvic pain. Results: All mice immunized with the uroplakin 3A peptide developed pelvic pain within 5 days and up to 40 days after immunization. Lidocaine alleviated the pain only when it was installed into the bladder of EAC mice, confirming the bladder origin of the pain. The amounts of CCL2 mRNA and protein, and the numbers of MCs were markedly increased in bladder tissue up to 40 days after immunization with peptide compared with controls. Administrations of cromolyn sodium and ranitidine significantly decreased pelvic pain in the model. Moreover, immunization did not establish chronic pelvic pain or accumulation of MCs in MCP-1-/- or CCR2-/- mice, compared with wild type mice. Conclusion: CCL2 has a vital role in causing chronic pelvic pain through accumulation of MCs in this newly created EAC mouse model, and might be an essential player in the pathogenesis of human IC/PBS. Advisors/Committee Members: Daneshgari, Firouz.

Subjects: Biochemistry; Biology; Health Sciences; Medicine; Molecular Biology; Neurosciences

Keywords: CCL2; MCP-1; Chronic Pelvic Pain; Mast Cell; Experimental Autoimmune Cystitis; IC/PBS; Uroplakin 3A; Bladder

25. Given, Steven G. Cross Product Generalizability of Shopping Site Judgments.

Degree: MA, College of Sciences and Health Professions, 2012, Cleveland State University

► The purpose of this study was to examine the generalizability of attribute… (more)

▼ The purpose of this study was to examine the generalizability of attribute performance and attribute importance ratings across product classes. Data were collected, with the use of an online survey, from 313 respondents of which 287 were U.S. college students and 26 were close acquaintances of the research team. Seventy-four percent of respondents were male, all respondents had at least four years of internet use experience, and 44% claim to make at least one online shopping purchase per month. Twenty-six web site attributes were selected from the Variegated Inventory of Site Attributes (VISA) (Blake, Hamilton, Neuendorf & Murcko, 2010) to be rated for attribute performance and attribute importance by respondents in this study. Attribute performance ratings were gathered based on www.Frys.com for the consumer electronic product class and www.Powells.com for the bookstore product class. Also, attribute importance ratings were gathered for the consumer electronic product class, the bookstore product classes, and the general importance domain. An exploratory factor analysis and a series of confirmatory factor analyses were used to identify, confirm, and provide marginal evidence for the generalizability of an underlying four factor, 22 attribute performance structure across the consumer electronic and bookstore product classes. On the other hand, this study failed to identify an underlying attribute importance structure with the use of an exploratory factor analysis. As a result, no structural level assessments of the generalizability of attribute importance ratings could be assessed. Repeated measures MANOVA analyses revealed that the majority of web site features are rated significantly differently across product classes for both performance and importance. Ð¡orrelation analyses demonstrated that the relationship between attribute ratings for the book and consumer electronic product classes tended to be stronger for performance than importance. Also, attribute importance correlations varied across the domains of book, consumer electronic, and general importance. Advisors/Committee Members: Blake, Brian.

Subjects: Psychology

Keywords: e-commerce; online shopping; attribute judgments; generalizability; performance; importance; e-tailer; web sites; websites; VISA; Books; Electronics; Online Survey

26. Grilli, Suzanne M. Perceived Difficulty in a Fitts Task.

Degree: MA, College of Sciences and Health Professions, 2011, Cleveland State University

► This study provided a detailed investigation of perceived difficulty (PD) in a… (more)

▼ This study provided a detailed investigation of perceived difficulty (PD) in a Fitts task. The Fitts task has been used to study Fitts’s law, which shows that movement time (MT) is related to the information constraints of the movement (Fitts’s Index of Difficulty, ID) such that there is a positive, linear relationship between MT and ID and MTs are similar when the scale of the movement requirements vary but ID is equal (scale invariance). According to Fitts’s law, Fitts’s ID provides an index of objective difficulty; does Fitts’s ID also provide an index of subjective difficulty? The main goal of this study was to address this question. It was hypothesized that the characteristics of the MT-ID relation described by Fitts’s law extend to the PD-ID relation. This hypothesis was addressed in two experiments, both including a variety of ID and scale conditions. In Experiment 1, participants (N = 20) assessed performance difficulty in prospective action; in Experiment 2, participants (N = 40) assessed performance difficulty in imagined and actual action. The results from both experiments supported the hypothesis. The support was limited, however; under certain conditions, there was evidence of a non-linear PD-ID relation and scale variance for PD. Thus, within limits, Fitts’s ID provides an index of subjective difficulty in prospective, imagined, and actual action. In Experiment 2, MTs were collected in addition to the PD judgments. It was hypothesized that MT is superior to ID in predicting PD and that MT mediates the relationship between PD and ID. The results supported these hypotheses for many participants in both action conditions, but particularly in imagined action. An additional finding was that participants’ PD judgments in imagined and actual action were very similar. In conclusion, participants’ PD judgments relate more to the outcome of their action experience (i.e., MT) than the information constraints of the action (i.e., ID). Furthermore, actual experience in the task, and the external feedback that accompanies actual experience, does not have much of an effect on participants’ PD judgments. It appears that internal feedback influences participants’ PD judgments in both imagined and actual action. Advisors/Committee Members: Slifkin, Andrew.

Subjects: Behavioral Psychology; Cognitive Psychology; Experimental Psychology; Psychology

Keywords: perceived difficulty; Fitts's law; Fitts's Index of Difficulty; Fitts task; prospective action; imagined action; subjective difficulty

27. Hale, James. ROLE OF THE THROMBOSPONDIN - CD36 – HISTIDINE RICH GLYCOPROTEIN PATHWAY IN TUMOR GROWTH AND ANGIOGENESIS.

Degree: PhD, College of Sciences and Health Professions, 2012, Cleveland State University

► Cancer is typically thought of as an uncommon disease, in which solid… (more)

28. Hans, Krystal R. Insect Signature Indicating Corpse Movement From Urban to Rural Areas of Northeast Ohio.

Degree: MS, College of Sciences and Health Professions, 2011, Cleveland State University

► The distribution of insects geographically may provide evidence that indicates the movement… (more)

Subjects: Biology; Ecology; Entomology

Keywords: Blow flies; decomposition; forensic

29. Heitkamp, Stacey. Preservice Teacher Awareness of Risk Factors for Student Suicide.

Degree: MA, College of Sciences and Health Professions, 2011, Cleveland State University

► Suicide is the third leading cause of death among adolescents in the… (more)

▼ Suicide is the third leading cause of death among adolescents in the United States. Given this, it is imperative that those who have regular contact with members of the youth population be able to recognize and identify those youth who are at risk for suicide. Part of the process of identifying suicidal adolescents requires having knowledge about adolescent suicide and about those factors that place certain adolescents at greater risk for completing suicide than others. One group of professionals who are in an optimal position to detect at-risk youth is schoolteachers. Fifty-four undergraduate students who were studying to obtain teaching licensure at a large public university completed the Adolescent Suicide Behavior Questionnaire (ASBQ), an instrument that measures knowledge about adolescent suicide across five content areas (Scouller & Smith, 2002; Smith & Scoullar, 2001).Undergraduate students also completed items from the eight clinical scales of the Suicide Opinion Questionnaire (SOQ), a measure that assesses attitudes toward suicide (Domino, 2005; Domino et al., 1982, 1988-89). On average, preservice teachers scored approximately 61% of ASBQ items correctly. Preservice teachers were the most informed about the warning signs of adolescent suicide and were the least informed about demographic and statistical information related to adolescent suicide. Preservice teachers in Middle Childhood and Secondary Education answered significantly more items correctly on the ASBQ than preservice teachers in Early Childhood Education. Preservice teachers with classroom teaching experience answered significantly more ASBQ items correctly than preservice teachers without this experience. Only 59.3% of all preservice teachers recognized that secondary school teachers are in a good position to detect the risk factors for suicide in their students. Responses to the SOQ indicated that preservice teachers were either conflicted or unsure about their attitudes toward suicide along several different attitudinal dimensions. However, preservice teachers tended to disagree with the attitudes that people have the right to take their own lives and that suicide is an aggressive act. Findings from this study point to the need for better or more education for preservice teachers in the area of adolescent suicide as they prepare for their future roles as teachers of youth. Advisors/Committee Members: Kahana, Boaz.

Subjects: Education; Educational Psychology; Mental Health; Middle School Education; Psychology; Secondary Education; Teacher Education

Keywords: adolescent suicide; risk factors; preservice teachers; teachers

30. Hribar, James Anthony. Capillary Gradient Chromatofocusing-Mass Spectrometry: A Sensitive Approach for Protein Analysis.

Degree: PhD, College of Sciences and Health Professions, 2011, Cleveland State University

► Gradient chromatofocusing-mass spectrometry is a new technique for protein analysis recently introduced… (more)

▼ Gradient chromatofocusing-mass spectrometry is a new technique for protein analysis recently introduced by our research group. Capable of separating and identifying proteins according to pI values and molecular weight, gradient chromatofocusing-mass spectrometry has been achieved by integrating a new ion-exchange chromatography technique called gradient chromatofocusing with a newly discovered buffer system that promotes mass spectrometry detection. Differing from traditional ion-exchange chromatography techniques, gradient chromatofocusing employs specific low molecular weight, volatile buffer components that are introduced onto an ion-exchange HPLC column by programming a binary gradient pumping system to deliver the correct proportions of acidic mobile phase to overcome buffering of the column’s stationary phase initially equilibrated with a basic mobile phase thus creating a linear pH gradient through the column. Offering greater control of the slope of the pH gradient and improving separation capabilities through usage of buffers at higher concentrations, gradient chromatofocusing buffer systems offer compatibility with mass spectrometry detection that is not possible using polyampholyte buffers commonly used with traditional ion-exchange chromatography techniques. This compatibility led to the first reporting of ion-exchange chromatography being interfaced with mass spectrometry by a previous group member who used a 2.1 mm i.d DEAE weak anion-exchange column and a 25 mM buffer system consisting of ammonium bicarbonate, pyridine, lactic acid and acetic acid. Furthermore, the focus of this dissertation will be to develop an optimized capillary gradient chromatofocusing-mass spectrometry system (Chapter 4) capable of detecting at the low-levels associated with proteomics by miniaturizing the HPLC system (Chapter 2) and effectively operating with the lowest buffer concentrations possible to generate linear pH gradients to promote compatibility with the mass spectrometer (Chapter 3). Similar to capillary gradient chromatofocusing, other commonly used protein characterization techniques separate proteins according to charge before determining the molecular mass by introducing analytes into a mass spectrometer preferably using capillary chromatography. Advantages and considerations for using capillary columns will be discussed in Chapter 1. In Chapter 2, sensitivity gains and detection limits were compared for various DEAE weak anion-exchange columns with inner diameters ranging from 255 µm to 508 µm using UV detection. Comparison of sensitivity gains using 255 and 508 µm i.d. columns gave results as theoretically expected. Novel to the completion of the work in this study is the packing of PEEK columns in-house using a pressurized column packing technique and development of an on-line pH measurement system for measuring pH gradients prior to analysis of proteins. In Chapter 3, various trials of generating linear pH gradients with various buffer systems are displayed with goals of selecting a buffer system with the lowest concentrations of buffer components possible to promote mass spectrometry compatibility. Linear pH gradients were achieved by reducing concentrations of the initial buffer system composed of ammonium bicarbonate, pyridine, lactic acid and acetic acid from 25 mM to 10 mM by trial and error programming of the gradient system. Efforts were also directed towards including additional buffer components such as collidine to minimize pH drops in unbuffered regions of the gradient resulting from reduced buffering capacity when reducing buffer concentrations. Capable of providing the buffering capacity needed to generate linear pH gradients, the buffer system containing collidine was not used based upon inaccurate pK values determined for proteins, undesirable UV absorbance and shortened lifetime of columns due to incompatibilities with this buffer component. In Chapter 4, the optimized capillary gradient chromatofocusing system using a 255 µm i.d. DEAE weak anion-exchange column with a 10 mM ammonium bicarbonate, pyridine, lactic acid and acetic acid buffer system was defined and interfaced with an electrospray ionization triple quadrupole mass spectrometer for detection. Significant improvements are emphasized using the optimized capillary gradient chromatofocusing-mass spectrometry system opposed to the gradient chromatofocusing-mass spectrometry system initially introduced. Detection limits have been reduced significantly and pK values were determined using the optimized capillary GCF-MS system thus showing the utility of this qualitative and quantitative tool in the field of proteomics. Advisors/Committee Members: Anderson, David.

Subjects: Analytical Chemistry

Keywords: HPLC, LC-MS, protein analysis

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