1,191 research outputs found
Supplemental_Material_for_Hull-Ryde_et_al – Supplemental material for Identification of Cosalane as an Inhibitor of Human and Murine CC–Chemokine Receptor 7 Signaling via a High-Throughput Screen
No full textSupplemental material, Supplemental_Material_for_Hull-Ryde_et_al for Identification of Cosalane as an Inhibitor of Human and Murine CC–Chemokine Receptor 7 Signaling via a High-Throughput Screen by Emily A. Hull-Ryde, Melissa A. Porter, Kenneth A. Fowler, Dmitri Kireev, Kelin Li, Catherine D. Simpson, Maria F. Sassano, Mark J. Suto, Kenneth H. Pearce, William Janzen and James M. Coghill in SLAS Discovery</p
DS_DISC844569 – Supplemental material for A General TR-FRET Assay Platform for High-Throughput Screening and Characterizing Inhibitors of Methyl-Lysine Reader Proteins
No full textSupplemental material, DS_DISC844569 for A General TR-FRET Assay Platform for High-Throughput Screening and Characterizing Inhibitors of Methyl-Lysine Reader Proteins by Justin M. Rectenwald, P. Brian Hardy, Jacqueline L. Norris-Drouin, Stephanie Cholensky, Lindsey I. James, Stephen V. Frye and Kenneth H. Pearce in SLAS Discovery</p
The Monks of Westminster
No full textFor this 1916 work, Archdeacon E. H. Pearce searched through the extensive muniments of Westminster Abbey to provide a list of all the known members of the monastic community until the Dissolution. Over 700 individuals are included, with all the information about them available to the author. While the list is not complete, and the use of other sources would add additional names for the early period, Pearce completed a remarkable achievement. Westminster was a substantial foundation, with an average community of 47 for the fourteenth and fifteenth centuries. About half of these, who held some office or function, are naturally better documented than ordinary monks. Scholarship was evidently valued by the abbey, although the majority of the writings evidenced were on the history of the community rather than theological or literary works. Some monks were supported at Oxford, but little is known of the education offered to the remainder.</jats:p
Playing Ethnography: A study of emergent behaviour in online games and virtual worlds
No full textThis study concerns itself with the relationship between game design and emergent social behaviour in massively multiplayer online games and virtual worlds. This thesis argues for a legitimisation of the study of ‘communities of play’, alongside communities perceived as more ‘serious’, such as communities of interest or practice. It also identifies six factors that contribute to emergent social behaviour and investigates the relationship between group and individual identity, and the emergent ways in which these arise from and intersect with the features and mechanics of the game worlds themselves.
Methodology: Under the rubric of ‘design research’, this study was conducted as an ethnographic intervention, an anthropological investigation that deliberately privileged the online experience whilst acknowledging the performative nature of both game play and the research process itself. The research was informed by years of professional practical experience in game design and playtesting, as well as by qualitative methods derived from the fields of Anthropology, Sociology, Computermediated Communications and the emerging field of Game Studies. The process of conducting the eighteen-month ethnographic study followed the progress of a sub-set of members of the ‘Uru Diaspora,’ a group of 10,000 players who were made refugees when the massively multiplayer game ‘Uru: Ages Beyond Myst’ was closed in February of 2004. Uru refugees immigrated into other virtual worlds, using their features and capabilities to create ethnic communities that emulated the culture, artefacts and environments of the original Uru world. Over time, players developed ‘hybrid’ cultures, integrating the Uru culture with that of their new homes, and eventually creating entirely new Uru and Myst-inspired content.
The outcome is the identification of six factors that serve as ‘engines for emergence’ and discusses their relationship to each other, to game design, and to emergent behaviour.
These include:
• Play Ecosystems: Fixed-Synthetic vs. Co-Created Worlds: Online games and virtual worlds exist along a spectrum, with environments entirely authored by the designer at one end, and those comprised primarily of player-created content and assets on the other, with a range of variations between. The type of world will impact the sort of emergent behaviour that occurs, and worlds that include player-created content will be more inclined to promote emergent behaviour.
• Communities of Play: Distributed groups formed around play demonstrate distinct characteristics based on shared values and play styles. The study describes in detail one such play community, and analyses the ways in which its characteristic play styles drove its emergent behaviours.
• The Social Construction of Avatar Identity: Individual avatar identity is constructed through an emergent process engaging social feedback.
• Intersubjective Flow: A social reading of the psychological notion of ‘flow’ that describes the way in which flow dynamics occur in a social context through play.
• Productive Play: Countering the traditional contention that play is inherently ‘unproductive’ as some scholars suggest, the thesis argues that play can be seen as a form of cultural production, as well as fulcrum for creative activity.
• Porous Magic Circles and the ‘Ludisphere’: The magic circle, which bounds play activities, is more porous than game scholars had previously believed. The term ‘ludisphere' is used to describe the larger context of aggregated play space via the Internet. Also identified are leakages between ‘virtual worlds’ and ‘real life’.
By identifying these factors and attempting to trace their roots in game design, the study aims to contribute a new approach to the making and analysis of user experience and creativity ‘in game’. The thesis posits that by achieving a deeper cultural understanding of the relationship between design and emergent behaviour, it is possible to make steps forward in the study of ‘emergence’ itself as a design
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Nonparametric Segment Detection
No full textIn computer and robotic vision point clouds from depth sensorshave to be processed to form higher-level concepts such as lines,planes, and objects. Bayesian methods formulate precisely prior knowledgewith respect to the noise and likelihood of points given a line, plane,or object. Nonparametric methods also formulate a prior with respectto the number of those lines, planes, or objects. Recently, a nonparametricBayesian method has been proposed to perform optimal inferencesimultaneously over line fitting and the number of lines. In this paperwe propose a nonparametric Bayesian method for segment fitting. Segmentsare lines of finite length. This requires 1.) a prior for line segmentlengths: the symmetric Pareto distribution, 2.) a sampling method thathandles nonconjugacy: an auxiliary variable MCMC method. Resultsare measured according to clustering performance indicators, such asthe Rand Index, the Adjusted Rand Index, and the Hubert metric. Surprisingly,the performance of segment recognition is worse than that ofline recognition. The paper therefore concludes with recommendationstowards improving Bayesian segment recognition in future woMathematical Physic
On the indicator of weak sustainability
No full textFacing the difficulties of measuring sustainability, Pearce and Atkinson proposed the Pearce-Atkinson (P-A) indicator, which provides an important direction or method of sustainability measurement. Although the weak sustainability rule is limited in its real world relevance, Pearce and Atkinson's research results show that it can yield some useful insights of sustainability into a system from some aspects. With the improvement of the P-A indicator, it will become more practically useful. At the same time, we should pay more attention to the study of the P-A indicator method with Amsberg's continuum, which will make the indicator for measurement of sustainability change gradually from "weak' to practically "strong'. -from Author
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New Brazilian Forms of Hyla
No full textContents: Text -- Photographs -- ReferencesThe author describes three new species and three new subspecies of Hyla,
found during her work toward a monograph of the species of Hyla which
occur in Brazil. The new species are: Hyla adenoderma from Rondonia territory;
H. longilinea from the high mountains at Pogos de Caldas, Minas
Gerais; and H. egleri from Belem do Para. The last-named is a northern representative
of the forms belonging to the group of H. catharinae from the
southern and southeastern serras. The new subspecies are: H. duartei caldarum
from Pogos de Caldas; H. raddiana joaquini from the highest and
most southern part of the state of Santa Catarina; and H. rubra orientalis
from the Atlantic coastal area of Brazil.Texas Memorial Museu
Equivalence between best responses and undominated
No full textFor games with expected utility maximizing players whose strategy sets are finite, Pearce (1984) shows that a strategy is strictly dominated by some mixed strategy, if and only if, this strategy is not a best response to some belief about opponents' strategy choice. This note generalizes Pearce's (1984) equivalence result to games with expected utility maximizing players whose strategy sets are arbitrary compact sets.
APPLYING mRNA DISPLAY TO DISCOVER MAGE-A4 INHIBITORS AND STRUCTRUAL BASIS OF LIGAND SELECTIVITY
No full textMAGE proteins are cancer testis antigens (CTAs) that are characterized by a highly conserved MAGE homology domain (MHD) and are increasingly being found to play pivotal roles in promoting aggressive cancer types. MAGE-A4, in particular, increases DNA damage tolerance and chemoresistance in a variety of cancers by stabilizing the E3-ligase RAD18 and promoting trans-lesion synthesis (TLS). Inhibition of the MAGE-A4:RAD18 axis could sensitize cancer cells to chemotherapeutics like platinating agents. We use mRNA display of thioether cyclized peptides to identify a series of potent and highly selective macrocyclic inhibitors of the MAGE-A4:RAD18 interaction. Co-crystal structure indicates that these inhibitors bind in a pocket that is conserved across MHDs but take advantage of A4-specific residues to achieve high isoform selectivity. Cumulatively, our data represent the first reported inhibitor of the MAGE-A4:RAD18 interaction and establishes biochemical tools and structural insights for the future development of MAGE-A4 targeted cellular probes. mRNA display of macrocyclic peptides has proven itself to be a powerful technique to discover high affinity ligands for a protein target. However, the number of cyclization chemistries demonstrated to be compatible with mRNA display are currently limited. Tyrosinase is a copper-dependent oxidase that oxidizes tyrosine phenol to an electrophilic ortho-quinone, which is readily attacked by cysteine thiol. Here we show that peptides containing tyrosine and cysteine are rapidly cyclized upon tyrosinase treatment. Characterization of the cyclization reveals it to be widely applicable to multiple macrocycle sizes and scaffolds. Lastly, we combine tyrosinase mediated cyclization with mRNA display to discover new macrocyclic ligands targeting MAGE-A4. Identified macrocycles potently inhibit the MAGE-A4 binding axis with nanomolar IC50 values. Importantly, macrocyclic ligands show clear advantage over non-cyclized analogs with ~40 fold or greater decrease in IC50 values. Overall, we demonstrate tyrosinase catalyzed peptide macrocyclization and incorporate the reaction into our mRNA display platform to explore novel chemical space.Doctor of Philosoph
Technology Development for Inhibitor Discovery of Chromatin Associated Proteins Linked to Lysine Methylation
No full textThe identification of molecules that tightly bind to therapeutically relevant targets remains one of the biggest challenges in biomedical research. Continued development of discovery technologies that are cost effective, fast, reliable, and reproducible are essential for the development of new tool compounds and potential therapeutics. These features are particularly important for academic discovery programs which rely heavily on grant-based funding. A target-class driven strategy for discovery of potent and selective inhibitors is an approach adopted by many academic and industrial labs. Development of multiple, complementary strategies for hit discovery and characterization can greatly enhance the speed and dependability of biomedical research. Herein, is the description of a series of technologies developed and applied to chromatin associated proteins involved in either the recognition or placement of methyl groups upon lysine residues of histone tails. A generalized TR-FRET assay panel, a label-free mass-spectrometry catalytic assay, and a focused DNA-Encoded Library platform and their applications are summarized.Doctor of Philosoph
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