System level dynamics of post-translational modifications

Attempts to characterize cellular behaviors with static, univariate measurements cannot fully capture biological complexity and lead to an inadequate interpretation of cellular processes. Significant biological insight can be gleaned by considering the contribution of dynamic protein post-translational modifications (PTMs) utilizing systems-level quantitative analysis. High-resolution mass spectrometry coupled with computational modeling of dynamic signal–response relationships is a powerful tool to reveal PTM-mediated regulatory networks. Recent advances using this approach have defined network kinetics of growth factor signaling pathways, identified systems level responses to cytotoxic perturbations, elucidated kinase–substrate relationships, and unraveled the dynamics of PTM cross-talk. Innovations in multiplex measurement capacity, PTM annotation accuracy, and computational integration of datasets promise enhanced resolution of dynamic PTM networks and further insight into biological intricacies

Exploring flow experiences in cooperative digital gaming contexts

Given the social nature of digital gaming, an investigation into social processes underpinning the experiences within social contexts of play is greatly warranted. The current research explored the underpinnings of “group flow” within cooperative-based gaming. In particular, this was intended to provide insight into the social processes which facilitate flow experiences in these contexts. This was achieved through a questionnaire in which gamers (N = 76) provided retrospective open-ended accounts of flow during cooperative gaming. Additionally, quantitative data was obtained on flow and post-gameplay mood within this experience, as well as in solo gaming for comparative analysis. Thematic analysis of the qualitative responses revealed a number of factors which determined the experience of flow. These were; effective communication and team-work and task relevant knowledge of group members. Additionally, although flow was found to be lower in cooperative versus solo gaming, no differences in post-gameplay mood were observed. These findings aid conceptual development of facilitators of group flow in cooperative gaming, with insights into how this may extend to other cooperative activities. Additionally, they also provide new practical insight for representatives in the gaming industry on how gaming may be developed with the aim of promoting positive shared group experiences

Separating hyperfine from spin-orbit interactions in organic semiconductors by multi-octave magnetic resonance using coplanar waveguide microresonators

Separating the influence of hyperfine from spin-orbit interactions in spin-dependent carrier recombination and dissociation processes necessitates magnetic resonance spectroscopy over a wide range of frequencies. We have designed compact and versatile coplanar waveguide resonators for continuous-wave electrically detected magnetic resonance, and tested these on organic light-emitting diodes. By exploiting both the fundamental and higher-harmonic modes of the resonators we cover almost five octaves in resonance frequency within a single setup. The measurements with a common pi-conjugated polymer as the active material reveal small but non-negligible effects of spin-orbit interactions, which give rise to a broadening of the magnetic resonance spectrum with increasing frequency

Understanding player experience in social digital games : the role of social presence

Including others in a playful activity fundamentally changes the concept of play into social play. This thesis focuses on social play in digital gaming. Previous studies have revealed the crucial part of social interaction in play, as the intrinsic need to belong seems to be the core motivation for engaging in such activities. Besides interacting with the game and focusing on the game content, gamers are confronted with emotions, behaviours, opinions and performances of others that can easily be perceived when playing side by side (co-located co-play). However, the widespread penetration of the Internet also allows for social play without the restriction of co-players having to be in the same room (mediated co-play). In online co-play settings a smaller amount of social information can be exchanged compared to co-located co-play. These settings therefore differ in the way gamers can interact with each other, which has an influence on how digital gaming is experienced. Focus groups, contextual inquiries, and four experimental studies were employed to uncover which aspects of social play in digital gaming make mediated and co-located co-play feel different. The first study was conducted to explore the motivations of gamers to physically meet others to play digital games, compared to meeting them online. Based on interpersonal communications, focus groups and contextual inquiries, findings revealed that the appeal of co-located above online co-play results from the sociable, warm, sensitive, personal and intimate interactions that are possible when playing side-byside. Furthermore, co-located co-play offers the possibility to experience social fun before and after game play, which often is not afforded in online co-play. The first lab experiment was conducted to empirically demonstrate to what extent player experience is influenced by the way co-players are present; e.g. as a virtual (human controlled), mediated or co-located co-player. Results on self-reports indicated that playing sidebyside significantly adds to the enjoyment and involvement in games compared to playing against a virtual (i.e. computer controlled) or distant co-player. These results could be explained by introducing the concept of social presence, which is defined as the feeling of being together with another individual. Results demonstrated that social presence mediated the enjoyment in social play. In the second and third lab experiment the possibilities for verbal and non-verbal interaction were manipulated between coplayers in co-located co-play. One experiment investigated this for competitive play; a the other for collaborative play. Self-reports showed that interactions through auditory cues positively influenced player experience. Interestingly, the presence of visual cues of one’s co-player had no significant influence on play. Observation data of players confirmed that audio cues (e.g., talking, laughing) were far more often used than visual cues (e.g., eye contact, making gestures); visual cues were only used before and after play. Furthermore, we demonstrated that social presence – due to interaction by audio cues – mediates the enjoyment in social play. A final lab experiment was conducted to investigate the importance of the connection between players through the game for our results in the previous chapters. In this experiment players were colocated, but not always played together and/or were not always able to see each other’s scores. Results showed that a subjective shared experience increases the strength of the social connection between players, and positively affects feelings of social presence, enjoyment and involvement. Similar to the previous findings, social presence mediated the increase in feelings of enjoyment and involvement. In sum, our set of studies offered empirical support for when, why and how social interaction influences players’ experience in co-play settings. Furthermore, the results indicate the importance of social presence as a mediating factor of enjoyment and involvement in social play. This provides new theoretical insights for communication experiences in other media, and social presence in general. Furthermore, findings may be useful to game designers who may want to enhance players’ experiences in during digital play

A developmentally regulated translational control pathway establishes the meiotic chromosome segregation pattern

Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow a single S phase. Errors in progression from meiosis I to meiosis II lead to aneuploid and polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that the conserved kinase Ime2 regulates the timing and order of the meiotic divisions by controlling translation. Ime2 coordinates translational activation of a cluster of genes at the meiosis I–meiosis II transition, including the critical determinant of the meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates translational control through the meiosis-specific RNA-binding protein Rim4. Rim4 inhibits translation of CLB3 during meiosis I by interacting with the 5′ untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase activity rises and triggers a decrease in Rim4 protein levels, thereby alleviating translational repression. Our results elucidate a novel developmentally regulated translational control pathway that establishes the meiotic chromosome segregation pattern.American Cancer Society (Post-doctoral Fellowship)Virginia and D.K. Ludwig Fund for Cancer Research (Post-doctoral Fellowship)National Institutes of Health (U.S.) (Grant GM62207

Phosphotyrosine Signaling Analysis in Human Tumors Is Confounded by Systemic Ischemia-Driven Artifacts and Intra-Specimen Heterogeneity

Tumor protein phosphorylation analysis may provide insight into intracellular signaling networks underlying tumor behavior, revealing diagnostic, prognostic or therapeutic information. Human tumors collected by The Cancer Genome Atlas program potentially offer the opportunity to characterize activated networks driving tumor progression, in parallel with the genetic and transcriptional landscape already documented for these tumors. However, a critical question is whether cellular signaling networks can be reliably analyzed in surgical specimens, where freezing delays and spatial sampling disparities may potentially obscure physiologic signaling. To quantify the extent of these effects, we analyzed the stability of phosphotyrosine (pTyr) sites in ovarian and colon tumors collected under conditions of controlled ischemia and in the context of defined intratumoral sampling. Cold-ischemia produced a rapid, unpredictable, and widespread impact on tumor pTyr networks within 5 minutes of resection, altering up to 50% of pTyr sites by more than 2-fold. Effects on adhesion and migration, inflammatory response, proliferation, and stress response pathways were recapitulated in both ovarian and colon tumors. In addition, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intratumoral spatial heterogeneity and pTyr dynamic response to ischemia varied dramatically between tumors collected from different patients. Overall, these findings reveal unforeseen phosphorylation complexity, thereby increasing the difficulty of extracting physiologically relevant pTyr signaling networks from archived tissue specimens. In light of this data, prospective tumor pTyr analysis will require appropriate sampling and collection protocols to preserve in vivo signaling features.National Institutes of Health (U.S.) (Grant U24 CA159988

A packet radio system for an industrial data network.

Thesis (M.Sc.Eng.)-University of Natal, 1992.This project was undertaken for a commercial electronics company, CONTROL LOGIC (CONLOG) which is involved in the research, design, development and manufacture of data acquisition, control, energy management and automotive equipment. Currently CONLOG uses an inhouse token passing local area network CONET for industrial data communications.The need had arisen to provide a means of data communication amongst widely geographically distributed remote terminal units (RTUs) generating demands at a very low duty cycle. A need for communications between RTUs and a centralised controller was also required. In addition to this, multihop communications between the RTUs was required. Packet switching using a broadcast radio network provides an efficient means of achieving this. An investigation into to the various media access control protocols and contention techniques using packet radio was carried out. The various media access techniques were compared with respect to throughput and normalised delay. This led to the selection of a media access scheme for the packet radio network using RTUs. A protocol specification control is centralised or Interconnect Organisation.The switching protocol (OSI) for the packet radio network, in which distributed, was done. The architechure of specified adheres to the Open Systems model of the International Standards.An experimental packet switching radio network was implemented using the protocol specification defined above. The packet radio network (PACNET) uses existing off the shelf radios and purpose built hardware for the remote terminal units. The thesis describes methods of data communications suitable for widely dispersed industrial data communications, the selection of the packet switching media access methods and control protocols, and the design and implementation of the prototype system