The primary purpose of this study was to observe the relationship between muscle activation of the right hand with the force produced at the fingertips in an isometric precision pinch tracking task. Thirty right-handed subjects, 15 males and 15 females, with a mean age 23.5 (SD 3.5) years, free from any neurological disorder or physical ailment, had a pair of electromyography (EMG) electrodes placed over the first dorsal interosseous (FDI) muscle, which acts on the index finger, while performing a pinch force tracking task scaled to 20% maximum voluntary contraction (MVC). The tracking task was chosen because it created a continuously increasing force application to 20% MVC and then decreasing force release from 20% MVC at a prescribed rate in both cases of 6.66% MVC force per second. In addition to showing increases in EMG activation of the FDI with increases in force, the results revealed that muscle activation for a given force level was generally greater for force application than for force release. This may be due dynamics of muscle contraction or to patterns of multiple muscle coordination. / text

DNA diagnostics are important technologies in molecular and cellular biology. By allowing identification of specific sequences, DNA-based diagnostics potentially provide more accurate and rapid results than protein- or antigen-based diagnostics, primarily because phenotypic changes come much later than changes in genotype. Despite this advantage, there are fewer diagnostic or imaging systems that target DNA than those targeting proteins, antibodies, or antigens.Each type of DNA-based diagnostic has its own, unique set of limitations; however, most can be attributed to issues related to sequence restriction, signal detection, specificity, or some combination thereof. For example, while PCR-based methods allow amplification and assessment of specific DNA sequences, they lack the ability to report information of specific cells, or cell types, within the heterogeneous pool of cells typically found in a tumor biopsy. In addition, none of the currently available DNA detection methods has the potential to be utilized in living cells, a disadvantage which limits the potential applications.The work presented here describes the design and development of a new methodology for the detection of specific double-stranded DNA sequences. This detection method is based on the concept that two inactive fragments of a reporter protein, each coupled to engineered zinc finger DNA-binding motifs, are able to reassemble and form an active complex in the presence of a predefined DNA sequence. This system, designated sequence-enabled reassembly (SEER), can achieve single base-pair specificity, and has the potential to be utilized in living cells.In this dissertation, we discuss the efforts from constructing to refining the system, as well as the future applications of SEER in diagnostics and therapeutics. Chapter I will provide an introduction to DNA detection methods, on which the principles of the SEER system are based. Chapter II describes the design and construction of an enzymatic SEER system, SEER-LAC, using beta-lactamase as the enzyme. In Chapter III, we outline the in vitro characterization of the SEER-LAC system, followed by its optimization in Chapter IV. Chapter V illustrates the efforts to develop SEER system for mammalian cell culture applications. In the final chapter, the future developments and applications of SEER are discussed.

Each member of the protein kinase C (PKC) family activates cell signaling pathways with different and sometimes opposing cell functions, such as cell division, migration, or death. Because of the importance of these processes in human diseases and disorders like cancer, stroke, and Alzheimer’s disease, there is a need for drugs which modify the action of PKC. However, drug design is difficult due to the complicated nature of PKC regulation. To better understand the differential regulation of PKC activity, these studies probe the structure, dynamics, and reactivity of one of the domains responsible for PKC regulation, C1B. C1B binds signaling molecules and translocates PKC to membranes in order to release the kinase domain from inhibition. Mutagenesis and ligand-binding assays monitored with fluorescence and nuclear magnetic resonance (NMR) techniques show that a single variable residue in C1B dramatically affects the sensitivity to signal activators. Investigation of the domain structure and dynamics using NMR revealed the identity of this residue alters the dynamics of the activator binding loops, without changing the structure. NMR studies of the C1B variants in membrane-mimicking micelles showed this residue also changes the interaction of the regulatory domain with lipids. These results demonstrate PKC isoforms have evolved specific functions by tuning dynamics and membrane affinity. Alternatively, PKC can be activated by reactive oxygen species by a mechanism that does not require binding of signaling molecules or membrane localization. To investigate the role of C1B in this type of signaling, the regulatory domain reactivity is monitored via NMR and gel electrophoresis. These studies reveal a particular cysteine residue in C1B that is most reactive, an alternative conformation of C1B in which this residue is more exposed, and modification of C1B leads to unfolding and zinc loss. Because the regulatory domains are responsible for auto-inhibition of the kinase domain, C1B unfolding provides a plausible explanation for activation of PKC by reactive oxygen species. The relation of the intrinsic C1B properties to the activation of PKC can be used to develop drugs with a single mechanism and to better understand how closely related signaling proteins develop specific functions.

I föreliggande uppsats var syftet att i en mixad design med kontroll- och behandlingsgrupp, undersöka om psykofysiologisk strategiträning kan hjälpa individer att hantera stress samt förbättra sin prestationsförmåga i pressade situationer inom golfputtning. Strategiträningen innefattade en kombination av andning-, rörelse och kognitivt beteende. Resultatparametrar var a) fingertemperatur som indikerar förändringar i det sympatiska nervsystemet och b) ett protokoll som mätte prestationsdata. Data har analyserats med hjälp av ANOVA ”repeated measures” i SPSS.Huvudresultatet visar signifikant fingertemperaturskillnad mellan behandlings- och kontrollgruppen. Slutsatsen i denna studie är att denna intränade strategi sannolikt kan användas för att reducera risken att bli stressad i en pressad situation och därmed öka prestationseffektiviteten. / In the present study the aim was to investigate, in a mixed treatment- and control design, effects of a behavioral strategy on coping with stress in stressful situations and particularly golf putting. The behavioral strategy contented integrated breathing-, movement and cognitive behaviors. The outcome parameters were a) finger temperature indicating changes in the lymphatic nervous system and b) a protocol measuring performance results. Data was analyzed with help of ANOVA”repeated measures” in a SPSS-program. The main results showed significant differences in finger temperature between the treatment and the control groups. The conclusion was that training of the strategy used in this study probably can be used to increase efficacy in golf putting.

Bakgrund: Fingersmärta är ett centralt besvär hos personer aktiva inom klättersport. Det råder idag brist på studier som beskriver förekomsten av fingersmärta hos klättrare. Syfte: Beskriva och jämföra skillnad mellan en grupp klättrare med fingersmärta och en grupp klättrare utan fingersmärta avseende olika individ- och klätterspecifika faktorer. Metod: Studien är en enkätstudie med en icke-experimentell design av tvärsnittstyp. Populationen bestod av 472 deltagare som via ett icke slumpmässigt bekvämlighetsurval fått svara på en elektronisk eller manuellt insamlad enkät. Resultat: Ingen signifikant skillnad fanns mellan de två testade grupperna avseende kön, ålder, BMI och antal aktiva år inom klättring. En signifikant skillnad fanns mellan grupperna avseende svårighetsgrad inom klättring. Konklusion: Den enda faktorn som är signifikant vid jämförelse mellan klättrare med och utan fingersmärta är avseende svårighetsgrad inom klättring. Övriga faktorer var icke signifikanta vilket inte stämmer överens med tidigare gjorda studier inom ämnet. Vidare studier kring faktorer som skulle kunna påverka fingersmärta hos klättrare efterfrågas. / Background: Finger pain is a common problem among climbers. There is currently a lack of studies regarding what could affect the incidence of finger pain in climbers. Aim: Describe and compare the difference between climbers with and without finger pain regarding individual- and climbing specific factors. Method: The study had a non-experimental design with a cross-sectional type. The population consisted of 472 participants, asked to respond to a survey through a nonrandom sample of convenience selection. Results: No significant difference was found between the two groups tested regarding gender, age, BMI and years of climbing. A significant difference was in level of difficulty when climbing. Conclusion: In this study, the only examined factor that is statistically significant is the level of difficulty when climbing. The other factors examined were not significant, wich does not correlate with previous studies in the subject. Further studies about factors that might affect finger pain in climbers is requested.

Doctor of Philosophy (PhD) / Gene expression is known to be regulated at the level of transcription. Recently, however, there has been a growing realisation of the importance of gene regulation at the post-transcriptional level, namely at the level of pre-mRNA processing (5’ capping, splicing and polyadenylation), nuclear export, mRNA localisation and translation. Erythroid krüppel-like factor (Eklf) is the founding member of the Krüppel-like factor (Klf) family of transcription factors and plays an important role in erythropoiesis. In addition to its nuclear presence, Eklf was recently found to localise to the cytoplasm and this observation prompted us to examine whether this protein has a role as an RNA-binding protein, in addition to its well-characterised DNA-binding function. In this thesis we demonstrate that Eklf displays RNA-binding activity in an in vitro and in vivo context through the use of its classical zinc finger (ZF) domains. Furthermore, using two independent in vitro assays, we show that Eklf has a preference for A and U RNA homoribopolymers. These results represent the first description of RNA-binding by a member of the Klf family. We developed a dominant negative mutant of Eklf by expressing its ZF region in murine erythroleukaemia (MEL) cells. We used this to investigate the importance of this protein in haematopoietic lineage decisions by examining its effect on the multipotent K562 cell line. We provide evidence that Eklf appears to be critical not only for the promotion of erythropoiesis, but also for the inhibition of megakaryopoiesis.

Thesis (Ph. D.)--University of Sydney, 2004. / Title from title screen (viewed 14 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Molecular and Microbial Biosciences, Faculty of Science. Includes bibliographical references. Also available in print form.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Typescript. Bibliography: p. 115-134.

Thesis (M.S.)--Rochester Institute of Technology, 2006. / Typescript. Includes bibliographical references (leaves 47-48).

Universiẗat, Diss., 2005--Düsseldorf. / Erscheinungsjahr an der Haupttitelstelle : 2004.