Functional Analysis of Protein S-Palmitoylation Enzymes.

Protein S-palmitoylation is a dynamic, hydrophobic, post-translational modification of cysteine residues that is required for the spatiotemporal organization of hundreds of proteins. In turn, protein palmitoylation contributes to the composition of cellular membrane environments and plays fundamental roles in cancer, neurological disorders and many other human diseases. Despite its central function in human pathology, still, little is known about the enzymes that catalyze the addition (protein S-acyl transferases) and removal (S-acyl protein thioesterases) of this modification. The two enzyme families, DHHCs and LYPLAs, are thought to make up the so-called dynamic palmitoylation machinery in which dual action of acyltransferases and thioesterases promote proper membrane targeting for an expanding list of dynamically palmitoylated proteins. Indeed, a steady growth in studies of these enzymes is beginning to shed light on their biological functions, revealing that the interplay between these opposing catalysts may be more complex than previously thought. More specific tools for these enzymes can therefore provide a more complete molecular description of dynamic palmitoylation events and its regulation in various biological settings. The work presented in this thesis explores the chemical mechanisms and physiological roles of DHHCs and LYPLAs by developing, characterizing and employing novel tools for their study in the context of cancer biology. In the second chapter, the cellular targets of a widely-used, mechanism-based protein acyltransferase inhibitor are profiled and analyzed. In the third chapter, a mechanistic description of divergent thioesterase active-site ligand specificities is presented using both a structural and a kinetic approach. In the third chapter, novel acyl-protein thioesterase inhibitors are applied to define their roles in organizing cell junctions and suppressing metastatic transformation. One of the fundamental goals in this thesis is to address the limitations of current chemical tools of protein palmitoylation and provide a framework for the development of selective pharmacological agents to accelerate the study of this modification. From a physiological standpoint, this work offers novel insights into the in vivo functions of palmitoyl transferases and de-palmitoylases, highlighting the intricacies of the regulatory system governing the palmitoylation state of a given protein.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116725/1/davdad_1.pd

An exploration of information poverty : the early manifestation of information poverty in children

Information poverty is when individuals/demographic groups are unwilling or unable to access or share information. Information poverty has been recognised as a critical issue and a global challenge but is an understudied research area and children an understudied group. This study sought better understanding of information poverty and explored early manifestations of information poverty in children. As no empirical child information poverty studies existed, this study was exploratory. A literature review was undertaken alongside (in central Scotland) fieldwork with 156 children (6-8) and interviews with 17 parents and 17 teachers. Research questions were: What is information poverty and why does it occur? Do children experience information poverty and if so, why? After reviewing relevant literature, the researcher defined information poverty (as above) and determined that adolescent and adult information poverty can occur due to a lack of access to information, attitudes, behaviour and cultural context. This study’s empirical component evidenced children (6-8) experiencing information poverty - having unmet information needs; requiring adult support to obtain information and keeping information secret. Contributory factors to child information poverty were also evidenced: lacking skills, motivation and perseverance to obtain/share information; lacking source access; parents restricting information access; parents/teachers encouraging secrecy. Also evidenced was that not all children experienced information poverty and different factors contributed. Empirical findings supported Childers and Post’s (1975) barriers to information needs, searches, acceptance and use and Chatman’s (1996) information poverty theories. By evidencing that children (6-8) can experience information poverty this study makes an original contribution to understandings of information poverty, as existing empirical studies have only evidenced adolescents and adults living in impoverished information worlds. This is also the first empirical study to identify contributory factors to child information poverty and to determine that some of the same factors can contribute to child, adolescent and adult information poverty.Information poverty is when individuals/demographic groups are unwilling or unable to access or share information. Information poverty has been recognised as a critical issue and a global challenge but is an understudied research area and children an understudied group. This study sought better understanding of information poverty and explored early manifestations of information poverty in children. As no empirical child information poverty studies existed, this study was exploratory. A literature review was undertaken alongside (in central Scotland) fieldwork with 156 children (6-8) and interviews with 17 parents and 17 teachers. Research questions were: What is information poverty and why does it occur? Do children experience information poverty and if so, why? After reviewing relevant literature, the researcher defined information poverty (as above) and determined that adolescent and adult information poverty can occur due to a lack of access to information, attitudes, behaviour and cultural context. This study’s empirical component evidenced children (6-8) experiencing information poverty - having unmet information needs; requiring adult support to obtain information and keeping information secret. Contributory factors to child information poverty were also evidenced: lacking skills, motivation and perseverance to obtain/share information; lacking source access; parents restricting information access; parents/teachers encouraging secrecy. Also evidenced was that not all children experienced information poverty and different factors contributed. Empirical findings supported Childers and Post’s (1975) barriers to information needs, searches, acceptance and use and Chatman’s (1996) information poverty theories. By evidencing that children (6-8) can experience information poverty this study makes an original contribution to understandings of information poverty, as existing empirical studies have only evidenced adolescents and adults living in impoverished information worlds. This is also the first empirical study to identify contributory factors to child information poverty and to determine that some of the same factors can contribute to child, adolescent and adult information poverty

Migration motives and integration of international human resources of health in the United Kingdom: systematic review and meta-synthesis of qualitative studies using framework analysis

Abstract Objective The aim of this review was to examine the migration motives, the barriers to and facilitators of integration of international dental graduates, compared with nurses and doctors in the United Kingdom. Methods Electronic databases Ovid MEDLINE, EMBASE, PubMed, Web of Knowledge and OECD publications were systematically searched for English language publications from January 2000 to January 2017. A total of 31 qualitative studies were selected and quality appraised and meta-synthesis of the qualitative data was carried out using framework synthesis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to present the findings. Results There were no studies on migration motives and one study on integration experiences of international dentists in the UK. The nursing literature had the highest volume and quality of evidence on nursing workforce, whilst there was limited literature on international doctors in the UK. Migration of health professionals to the UK is determined by personal and professional factors, together with source country-specific and UK drivers. Active recruitment, post graduate training and financial gain act as strong common macro, meso and micro drivers that perpetuate migration into the UK, but the extent to which each of these drivers influence nurses’ and doctors’ migration is different. Integration experiences for international nurses and doctors differed based on their source country experiences and the work environment they entered. Nurses reported a wider knowledge and skills gap, more multi-level discrimination and less career progression compared to the doctors. The migrants’ integration experiences depend on their cultural awareness, discrimination exposure, English language and communication skills, social and professional support networks, social integration and personal attributes. Conclusion Migration of international health professionals is motivated by macro, meso and micro drivers at the international, national, professional and personal levels. The UK has strong common macro pull factors which attract nurses, doctors and dentists and may impact on the effectiveness of policies to restrict their migration. The integration experiences of nurses and doctors differ and further research is required to understand the integration experiences of dentists, in order to retain these professionals by tailoring policies to each of these professions

SIMULATION AND IMPLEMENTATION OF ELLIPTICAL MICRO STRIP ANTENNA AT 750MHZ

In telecommunication industry, several types of antennas are used. The most common of which are the micro strip patch antennas (also known as printed antennas) or patch antenna. Patch antennas can be used in many types of communications links that may have varied requirements. A single patch antenna provides a maximum directive gain of around 6-9 dBi. We can design it to work at multiple frequencies. It is available in various shapes and configuration, most common of which is a rectangular micro strip antenna (RMSA).In this project we are designing single fed annular ring micro strip ntenna. The software used to model and simulate the micro strip patch antenna is ZeelandInc’s IE3D software. IE3D is a full-wave electromagnetic simulator based on the method of moments. It analyzes 3D and multilayer structures of general shapes. It has been widely used in the design of MICs, RFICs, patch antennas, wire antennas, and other RF/wireless antennas. An evaluation version of the software will be used to obtain the results

SMARTPARK-Intelligent Parking Application using Image Processing

The Review paper discusses about the growing problem of car parking in urban areas due to the growing population .Due to growing population the number of vehicles has increased simultaneously and because of the limited parking lots, the problem of car parking is proliferating. In order to stop this, a system has been proposed to provide whole extensive proof based on growing urbanization, increasing traffic flow and technology growth for implementing innovative help and services to public transport system with aim to accelerate local social wealth by providing a mobile phone application for real time scanning and searching for available parking area and tracking the vacancy in the parking lot using existing technologies i.e. CCTV cameras. By having the image of the area, the particular car park slots can be detected and thereafter the processed information can be used as to guide the driver to an empty parking slot which will save his time. The whole idea is to make car parking more efficient and less tedious for the drivers

Krukenberg tumor in a young female arising from a primary adenocarcinoma of stomach: a case report

Krukenberg tumor is a malignancy of ovary that metastasizes from a primary site. Krukenberg tumors are uncommon and account for less than 2% of all ovarian tumors. It is usually a bilateral involvement of ovaries from the metastatic deposit from adenocarcinoma of the stomach. Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare. Here, we reported a very rare case of bilateral Krukenberg tumors of the ovaries arising from a primary adenocarcinoma of the stomach in a 20 year old Indian female

Wnt signalling in prostate cancer stem-like cells

The work reported in this thesis describes the characterisation of cell derived colonies from cancer cell lines and mechanisms of a key signalling pathway within these. PC3 cells were cultured at clonal density and resultant colony formation objectively described. Wnt signalling was investigated in colony types using a live [Ca2+]i assay. Exploratory work regarding ion channel gene and protein expression in 3 prostate cancer cell lines was performed. Preliminary investigation on the effects of MPRC (membrane potential regulating compounds) was performed using a cell proliferation assay. PC3 prostate cancer cells form distinct colonies with different morphologies. These different colony types can be characterised using quantitative parameters such as cell density and percentage cellularity, unlike previously employed visual only characteristics. PC3 cells form two types of colonies from a single cell. In this thesis these are termed holo/meroclones and paraclones. Cells within both colony types respond to Wnt activation, demonstrated by a response in free intracellular calcium [Ca2+]i . In addition, there is a suggestion of increased expression of, and translocation into the nucleus of the transcription factor co- activator β-catenin again in response to both Wnt 5A and Wnt 9B in both colony types. The characteristics of Wnt induced calcium release vary between different types of colonies. This is the first report of Wnt mediated [Ca2+]i release in response to both Wnt 5A and Wnt 9B in different PC3 colony types and the first report suggestive of β-catenin translocation following Wnt activation in colonies derived from stem-like cells