Establishing a positional information assay for brain ventricle mutants and investigating the choroid plexuses in zebrafish

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 2004.Includes bibliographical references (leaves 36-38).The process by which the neural tube expands into three brain ventricles can be understood through genetic mutant analysis. Within the framework of a characterization of zebrafish mutants with brain ventricle phenotypes, I have developed an assay that looks for evidence of compromised gene expression patterns. I have shown that a cocktail of krox20, pax2a, shh, and zicl antisense RNA probes hybridizes to domains in the developing brain that reflect anterior, posterior, dorsal, and ventral axis specification. In addition, I have investigated the choroid plexus (CP) cells lining the brain ventricles in the zebrafish. Though we were unable to clearly identify the CP in the adult brain, we did identify two homologues in zebrafish of a conserved gene expressed in CP of vertebrates. We found that one of these genes, Drcpllb, was expressed from tailbud into early larva stage. Further, Drcpllb is expressed in neurula stage embryos in the anterior neural plate. Through these studies, we established an assay to analyze positional identity of cells in the neural tube and discovered a potential choroid plexus marker, shown its expression time course, and outlined its early expression pattern in the zebrafish.by Catherine D. Wolf.S.M

Shifting online: an exploratory study into PR consultants' attitude towards new media

This study set out to explore the current usage and knowledge of new media as a public relations tool and channel amongst practising public relations consultants in Australia. The research was motivated by a nationwide benchmarking study by de Bussy and Wolf (2009), which concluded that new media was an extremely low priority for Australian public relations practitioners. Taking into account the speed of change associated with new media adoption, the authors examine whether these findings are still true today. This study takes a qualitative approach, based on a critical analysis of semi-structured interviews with Western Australia (WA) based Registered Consultancy Group (RCG) members of the Public Relations Institute of Australia (PRIA) (n=7). Findings suggest a cautious attitude towards the benefits of new media amongst RCG consultants. This is largely based on the assertion that the dynamics of basic communication principles and theories have not changed and that there is consequently no perceived pressure to move into the new media sphere half heartedly

Multicultural communication in the Middle East: How a ‘young’ profession in a young but ancient region is adapting to the challenges of cross-cultural communication in an increasingly digital world

This paper provides first-hand insight into senior public relations (PR) professionals’ views on and attitudes towards digital communication in the UAE, a regional and global hub of cross-cultural and multicultural public relations and commerce. This study is part of a longitudinal and transnational project investigating PR professionals’ attitudes towards digital communication. The study began in 2010 in Western Australia and the original authors have since widened their focus (and collaboration with others) to include Singapore and now the UAE. When the study started in 2010 in Western Australia, the term ‘new media’ was used and some practitioners were not convinced of the strategic impact or importance of ‘new media’. Since that time, the explosion in digital communication and social media use by citizens (and the shrinking news desks of many media outlets) have meant communication practitioners can no longer ignore digital media. ‘New’ media is not so new anymore..

Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty.

PurposeMatrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis.MethodsProtein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas.ResultsLuminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients.ConclusionsMultiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization

Impairment in predictive processes during auditory mismatch negativity in ScZ: evidence from event-related fields

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities

A coherent optical link through the turbulent atmosphere

We describe the realization of a 5 km free space coherent optical link through the turbulent atmosphere between a telescope and a ground target. We present the phase noise of the link, limited mainly by atmospheric turbulence and mechanical vibrations of the telescope and the target. We discuss the implications of our results for applications, with particular emphasis on optical Doppler ranging to satellites and long distance frequency transfer.Comment: version 2, modified following comments from colleagues and reviewer

Tumor microenvironment in NSCLC suppresses NK cells function

NK cells, which contribute to tumor immunosurveillance, are present in the microenvironment of Non-Small-Cell Lung Carcinoma. However, they display strongly altered phenotype with decreased expression of NKp30, NKp80, DNAM-1, CD16 and ILT2, and impaired cytotoxic functions. The possible mechanisms leading to these defects are discussed

The Role of Systematic Reviews in Pharmacovigilance Planning and Clinical Trials Authorisation Application: Example from the SLEEPS Trial

BACKGROUND: Adequate sedation is crucial to the management of children requiring assisted ventilation on Paediatric Intensive Care Units (PICU). The evidence-base of randomised controlled trials (RCTs) in this area is small and a trial was planned to compare midazolam and clonidine, two sedatives widely used within PICUs neither of which being licensed for that use. The application to obtain a Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) required a dossier summarising the safety profiles of each drug and the pharmacovigilance plan for the trial needed to be determined by this information. A systematic review was undertaken to identify reports relating to the safety of each drug. METHODOLOGY/PRINCIPAL FINDINGS: The Summary of Product Characteristics (SmPC) were obtained for each sedative. The MHRA were requested to provide reports relating to the use of each drug as a sedative in children under the age of 16. Medline was searched to identify RCTs, controlled clinical trials, observational studies, case reports and series. 288 abstracts were identified for midazolam and 16 for clonidine with full texts obtained for 80 and 6 articles respectively. Thirty-three studies provided data for midazolam and two for clonidine. The majority of data has come from observational studies and case reports. The MHRA provided details of 10 and 3 reports of suspected adverse drug reactions. CONCLUSIONS/SIGNIFICANCE: No adverse reactions were identified in addition to those specified within the SmPC for the licensed use of the drugs. Based on this information and the wide spread use of both sedatives in routine practice the pharmacovigilance plan was restricted to adverse reactions. The Clinical Trials Authorisation was granted based on the data presented in the SmPC and the pharmacovigilance plan within the clinical trial protocol restricting collection and reporting to adverse reactions

Development of a Scalable Pharmacogenomic Clinical Decision Support Service

Advances in sequencing technology are making genomic data more accessible within the healthcare environment. Published pharmacogenetic guidelines attempt to provide a clinical context for specific genomic variants; however, the actual implementation to convert genomic data into a clinical report integrated within an electronic medical record system is a major challenge for any hospital. We created a two-part solution that integrates with the medical record system and converts genetic variant results into an interpreted clinical report based on published guidelines. We successfully developed a scalable infrastructure to support TPMT genetic testing and are currently testing approximately two individuals per week in our production version. We plan to release an online variant to clinical interpretation reporting system in order to facilitate translation of pharmacogenetic information into clinical practice