Brain-Penetrating Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 in vitro

Histone deacetylases (HDACs) play an important role in the epigenetic control of gene expression in both normal and cancer cells. Previous studies have demonstrated that pharmaceutical inhibition of HDACs can kill and/or suppress the growth of cancer cells. RG2833 is a HDAC inhibitor that targets specific HDACs known to be active in cancer cells. Melanoma cells have previously been shown to respond to HDAC inhibitors that are structurally similar to RG2833. We hypothesized that the inhibition of HDAC activity by RG2833 would result in the reduced growth and/or death of cells from the malignant melanoma cell lines SK-MEL-5 and SK-MEL-28. To test our hypothesis, we exposed SK-MEL-5 and SKMEL-28 cells to increasing concentrations of RG2833. We found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer

Phenotypic and genotypic characterisation of Clostridium Difficile

Clostridium difficile is at present one of the most common nosocomial infections in the developed world. Hypervirulent strains (PCR ribotype 027) of C. difficile which produce enhanced levels of toxins have also been associated with other characteristics such as a greater rate of sporulation and resistance to fluoroquinolones. Infection due to C. difficile PCR ribotype 027 has also been associated with greater rates of morbidity and mortality. The aim of this thesis was to investigate both the phenotypic and genotypic characteristics of two populations of toxigenic clinical isolates of C. difficile which were recovered from two separate hospital trusts within the UK. Phenotypic characterisation of the isolates was undertaken using analytical profile indexes (APIs), minimum inhibitory concentrations(MICs) and S-layer protein typing. In addition to this, isolates were also investigated for the production of a range of extracellular enzymes as potential virulence factors. Genotypic characterisation was performed using a random amplification of polymorphic DNA(RAPD) PCR protocol which was fully optimised in this study, and the gold standard method, PCR ribotyping. The discriminatory power of both methods was compared and the similarity between the different isolates also analysed. Associations between the phenotypic and genotypic characteristics and the recovery location of the isolate were then investigated. Extracellular enzyme production and API testing revealed little variation between the isolates; with S-layer typing demonstrating low discrimination. Minimum inhibitory concentrations did not identify any resistance towards either vancomycin or metronidazole; there were however significant differences in the distribution of antibiogram profiles of isolates recovered from the two different trusts. The RAPD PCR protocol was successfully optimised and alongside PCR ribotyping, effectively typed all of the clinical isolates and also identified differences in the number of types defined between the two locations. Both PCR ribotyping and RAPD demonstrated similar discriminatory power; however, the two genotyping methods did not generate amplicons that mapped directly onto each other and therefore clearly characterised isolates based on different genomic markers. The RAPD protocol also identified different subtypes within PCR ribotypes, therefore demonstrating that all isolates defined as a particular PCR ribotype were not the same strain. No associations could be demonstrated between the phenotypic and genotypic characteristics observed; however, the location from which an isolate was recovered did appear to influence antibiotic resistance and genotypic characteristics. The phenotypic and genotypic characteristics observed amongst the C. difficile isolates in this study, may provide a basis for the identification of further targets which may be potentially incorporated into future methods for the characterisation of C. difficile isolates

Brain-Penetrating Histone Deacetylase Inhibitor RG2833: A Potential Malignant Melanoma Growth Suppressor

Histone deacetylases (HDACs) play an important role in the epigenetic control of gene expression in both normal and cancer cells. Previous studies have demonstrated that pharmaceutical inhibition of HDACs can kill and/or suppress the growth of cancer cells. RG2833 is a HDAC inhibitor that targets specific HDACs known to be active in cancer cells. Melanoma cells have previously been shown to respond to HDAC inhibitors that are structurally similar to RG2833. We hypothesized that the inhibition of HDAC activity by RG2833 would result in the reduced growth and/or death of cells from the malignant melanoma cell lines SK-MEL-5 and SK-MEL-28. To test our hypothesis, we exposed SK-MEL-5 and SKMEL-28 cells to increasing concentrations of RG2833. We found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer

Modulating electronic and optical properties of monolayered MoS2 by covalent mono- and bisfunctionalization

By employing first-principles simulations, we present theoretical predictions regarding the modification of structural, electronic and optical properties of 2H- and 1T′-MoS2 monolayers by covalent mono- and bisfunctionalization. Specifically, non-aromatic groups (–F, –NH2, –CH3, –CH2CH2 CN and –CH2CH2 OH) and aromatic (–Ph, –PhNO2 and PhOH) groups are utilized for monofunctionalization, and –F/–NH2, –NH2/–CH3 and –CH3/–Ph for bisfunctionalization. The stability of functionalized 2H- and 1T′-MoS2 monolayers mainly depends on the bonded groups and their surface coverage. In particular, the mixed bisfunctionalization with –F/–CH3 and –NH2/–CH3 groups enhances the stability of 2H-MoS2 through the formation of intermolecular hydrogen bonds. Both 2H- and 1T′-MoS2 can serve not only as electron donors, but also as electron acceptors, subject to the charge transfer behavior of the attached groups. Furthermore, mono- and bisfunctionalization are predicted to be efficient approaches to control the electronic band gaps in 2H- and 1T′-MoS2, where the corresponding values can be tuned by varying the coverage of the absorbed groups. At the same time, the choice of the chemical groups and their coverage also effectively determines the optical adsorption range and intensity. Therefore, our work shows that chemical functionalization of 2D materials with varying coverage can be an important approach to extend the scope of 2D materials in specific electronic and optoelectronic applications

Examining Gender Equity in Newspaper Coverage of West-Central Ohio High School Basketball Games

Across eight high school basketball seasons between 2000 and 2010, we investigated the coverage of over 300 high school basketball games and compared the quantity of coverage allotted to boys’ and girls’ teams within two west-central Ohio newspapers.   Unlike previous investigations on media coverage of high school sports, we restricted our sample to coverage of actual games and did not include feature articles about individual athletes, coaches, or booster clubs, and we determined article length by counting the number of words used in each article.   We found that boys’ games received two to three times the length of coverage of girls’ games.   Media coverage of girls’ games was also less likely to include a photograph and tended to begin lower on the sports page.   We discuss the potential implications of ignoring girls’ high school athletics within community media.

Public Relations for the Not-For-Profit Professional Resident Theatre: An Examination of Four Models

This study seeks to determine how public relations is practiced in the not-for-profit professional resident theatre and determine if the style of practice in use is the most advantageous for the current environment. The study examines literature in three areas: General public relations, public relations in the not-for-profit world, and oublic relations in theatre management. During analysis of this material, the practice of public relations in the not-for-profit professional resident theatre is placed within the framework of Grunig\u27s four models of public relations. According to Grunig, if selling tickets is the goal, then theatre should fit within the first model, the press agentry/publicity model. This model is characterized by the use of propaganda, practice of one-way communication with the message coming from the organization to the public; use of little or no research except ticket counting, and few formal evaluation methods. Analysis of the literature supports this conclusion. The idea is then advanced, supported by the literature review, that practice of a more sophisticated model of public relations--the two-way symmetrical model--would be beneficial to theatre. This model uses two-way communication balanced in its origination points between the organization and the public, and places high priority on research and evaluation. To test this conclusion, a case study of a representative theatre, Cincinnati Playhouse in the Park, was conducted. The study involved a review of current promotional and other written materials and personal interviews with the theatre\u27s public relations director and the managing d1rector. Findings determined that although Playhouse management voiced a concern (and written goals agreed) for the theatre to maintain a presence in the community, promoting the artistic, cultural literacy, and educational life of the area, few systems were in place to ensure that result. There were no formal evaluation methods in use for productions or overall organizational performance, nor were there any research methods in place. The only formal method for measuring success was found to be ticket counting. This finding suggested that Cincinnati Playhouse in the Park currently practices public relations fitting the press agentry/publicity model although their published goals-call for practice of the two-way symmetric model