Local protein structure prediction using discriminative models

BACKGROUND: In recent years protein structure prediction methods using local structure information have shown promising improvements. The quality of new fold predictions has risen significantly and in fold recognition incorporation of local structure predictions led to improvements in the accuracy of results. We developed a local structure prediction method to be integrated into either fold recognition or new fold prediction methods. For each local sequence window of a protein sequence the method predicts probability estimates for the sequence to attain particular local structures from a set of predefined local structure candidates. The first step is to define a set of local structure representatives based on clustering recurrent local structures. In the second step a discriminative model is trained to predict the local structure representative given local sequence information. RESULTS: The step of clustering local structures yields an average RMSD quantization error of 1.19 Å for 27 structural representatives (for a fragment length of 7 residues). In the prediction step the area under the ROC curve for detection of the 27 classes ranges from 0.68 to 0.88. CONCLUSION: The described method yields probability estimates for local protein structure candidates, giving signals for all kinds of local structure. These local structure predictions can be incorporated either into fold recognition algorithms to improve alignment quality and the overall prediction accuracy or into new fold prediction methods

The functional network in predictive biology : predicting phenotype from genotype and predicting human disease from fungal phenotype

textThe ability to predict is one of the hallmarks of successful theories. Historically, the predictive power of biology has lagged behind disciplines like physics because the biological world is complex, challenging to quantify, and full of exceptions. However, in recent years the amount of available data has expanded exponentially and biological predictions based on this data become a possibility. The functional gene network is a quantitative way to integrate this data and a useful framework for making biological predictions. This study demonstrates that functional networks capture real biological insight and uses the network to predict both subcellular protein localization and the phenotypic outcome of gene knockouts. Furthermore, I use the functional network to evaluate genetic modules shared between diverse organisms that lead to orthologous phenotypes, many that are non-obvious. I show that the successful predictions of the functional network have broad applicability and implications that range from the design of large-scale biological experiments to the discovery of genes with potential roles in human disease.Institute for Cellular and Molecular Biolog

Early Neanderthal social and behavioural complexity during the Purfleet Interglacial: handaxes in the latest Lower Palaeolithic.

Only a handful of ‘flagship’ sites from the Purfleet Interglacial (Marine Isotope Stage 9, c. 350-290,000 years ago) have been properly examined, but the archaeological succession at the proposed type-site at Purfleet suggests a period of complexity and transition, with three techno-cultural groups represented in Britain. The first was a simple toolkit lacking handaxes (the Clactonian), and the last a more sophisticated technology presaging the coming Middle Palaeolithic (simple prepared core or proto-Levallois technology). Sandwiched between were Acheulean groups, whose handaxes comprise the great majority of the extant archaeological record of the period – these are the focus of this study. It has previously been suggested that some features of the Acheulean in the Purfleet Interglacial were chronologically restricted, particularly the co-occurrence of ficrons and cleavers. These distinctive forms may have exceeded pure functionality and were perhaps imbued with a deeper social and cultural meaning. This study supports both the previously suggested preference for narrow, pointed morphologies, and the chronologically restricted pairing of ficrons and cleavers. By drawing on a wide spatial and temporal range of sites these patterns could be identified beyond the handful of ‘flagship’ sites previously studied. Hypertrophic ‘giants’ have now also been identified as a chronologically restricted form. Greater metrical variability was found than had been anticipated, leading to the creation of two new sub-groups (IA and IB) which are tentatively suggested to represent spatial and perhaps temporal patterning. The picture in the far west of Britain remains unclear, but the possibility of different Acheulean groups operating in the Solent area, and a late survival of the Acheulean, are both suggested. Handaxes with backing and macroscopic asymmetry may represent prehensile or ergonomic considerations not commonly found on handaxes from earlier interglacial periods. It is argued that these forms anticipate similar developments in the Late Middle Palaeolithic in an example of convergent evolution

The early middle Palaeolithic of Britain; origins, technology and landscape

This thesis examines technological behaviour during the early British Middle Palaeolithic (Late OIS 9-7), as reflected by lithic artefacts. The British data-set, whilst containing few high-resolution sites providing information relevant to ethnographic-scale behavioural reconstruction, actually forms a valuable corpus of well-contextualised locales within a tightly constrained chronostratigraphic framework. Lithic artefacts from these sites can be used to address broader questions concerning the emergence and nature of particular "Middle Palaeolithic" behaviours; specifically, the emergence of, and variability within, Levallois technology in Britain, and increasing complexity in the organisation of technology in the landscape. The assemblages analysed in this thesis comprise the nine best-preserved British sites dated to this period, which can be placed within secure chronological, geographical and ecological contexts. Whilst previous surveys have emphasised the typological composition of such assemblages, this thesis considers the specific technological behaviours evident at particular locales, in terms of which stages of lithic reduction are represented, what specific Levallois preparatory and exploitation strategies were applied, and how the choices between such options are explicable. On this basis, it is possible to discuss the development of a technologically complex treatment of particular places in the landscape during the early Middle Palaeolithic, linked to the increased transport and curation of particular Levallois products. Whilst on a European scale, such patterns are seen as typical of the Middle Palaeolithic but are essentially undated; this study shows that such behaviours are apparent from at least OIS 8 onwards in Britain, with concomitant implications for our understanding of developing Middle Palaeolithic behaviours in Europe

Toward Pedagogy of "Play" for the Mande Bala

A theoretical model is proposed that posits "play" as both the long-term goal of bala learning, and as the means through which the short-term steps toward that goal can best be achieved. Play is defined in two different ways. In the first sense it is an orchestrating of means and ends in which means are at the centre of interest. In this sense, play is a goal of bala learning. In the second sense, play is defined (using the framework of Applied Behaviour Analysis) as: activities that (a) are inherently reinforcing (and not inherently punishing), and (b) do not eventuate extinction, escape, or avoidance. In this sense, play is conceived as one possible means through which to achieve pedagogical goals. The case is made that Mande bala music is especially well suited to a pedagogy of "play" owing to its intrinsic (musical) characteristics. The pedagogical framework for the study is James Popham and Eva Baker's "empirical model of instruction," which allows for a systematic evaluation of pedagogical methods. Although the model proposed is supported by empirical evidence and has a strong rational underpinning, the model itself is not tested in the present study, but rather, is herein articulated (via illustrative case studies depicting the learning of various bala patterns through digitally mediated meansbooks, CDs, DVDs, etc.) An argument is built to support the notion that in comparison with traditional, immersion-based pedagogical modalities, the digital mediation of bala teaching eventuates a pedagogical loss, but that this pedagogical loss can be attenuated through a more "playful" pedagogical approach

Utopian fantasies of the perfected imperial prospect and fractured images of unresolved ambivalence and unsuppressed resistance : the Groote Schuur landscape considered as an imperial dream topography of Cecil John Rhodes, 1890-1929

The Groote Schuur landscape, probably more than anywhere else in South Africa, is a truly hybrid landscape. Many sets of big ideas were at play on this landscape between 1890 and 1929. At the end of the nineteenth century, Cecil Rhodes brought ideas of paternalism, imperialism and empire to the Estate and notions of creating a European space in Africa; Groote Schuur would be a meeting point where Africa and Europe would fuse in the same frame, where the wildness of Africa and the empire would energise the classicism of European civilisation. The idea of Britain in Africa perhaps found its most expressive form in the establishment of the European styled University of Cape Town on the slopes of a distinctly African mountain. As W J T Mitchell argues, landscape should be "seen more profitably as something like the dreamwork of Imperialism, unfolding its own movement in time and space from a central point of origin and folding back on Itself to disclose both utopian fantasies of the perfected imperial prospect and fractured images of unresolved ambivalence and unsuppressed resistance". Furthermore, this landscape is complicated by the dynamic shifts and changes that occurred in social and political thought during this period. Ideas on paternalism, of Britain having a pastoral role in Africa, were increasingly overshadowed by ideas of indirect rule and nationalism after Union in 1910 and then by the beginnings of ideas on absolute racial separation. A sense of trusteeship was increasingly supplanted by ideas of partnership between coloniser and colonised. These contestations are all played out on the landscape, just as they were in other fields and are complicated further by the enduring legacy of Rhodes. Intention: In this mini dissertation I will examine in detail four elements of the Groote Schuur Estate to see how these "big ideas" of dream topographies are played out on this specific landscape. 1890 is a natural starting point for my project since this was the year in which Rhodes took up permanent residency at Groote Schuur, acquired property that extended from "Mowbray southwards to Constantia" and began shaping the landscape according to his will. However, I have extended my study beyond the year of Rhodes' death in 1902, to 1929. This later date was the year that the University of Cape Town moved into its new Groote Schuur campus, and celebrated its centenary anniversary here. The event was seen as marking the conclusion of one of Rhodes' earlier dreams; the founding of a "teaching University in the Cape Colony... under the shadow of Table Mountain"

Notes on sexuality and space

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 87).Very little has been written on sexuality in architectural scholarship. Sexuality & Space (Princeton Architectural Press, 1992) contains the proceedings of an eponymous 1990 conference at Princeton University, and was both the first and last book-length publication dedicated to a comprehensive discourse on sexual identity within the discipline of architecture. While symposium organizer and proceedings editor Beatriz Colomina writes in the proceedings' introduction that the occasion's effort to "raise the question of 'Sexuality and Space'" was but "one small event" in an ongoing discourse, that discourse failed to materialize. To the extent that feminist theorists conspicuously ignored in architectural discourse and practice are addressed by Sexuality & Space, the "interdisciplinary exchange in which theories of sexuality are reread in architectural terms and architecture is reread in sexual terms," by its essays, asserts the very silence that its inquiry ostensibly alleviated. By carefully examining the constative impact of literary style within the publication Sexuality & Space-that is, by looking at how the use of language, therein, impacts that document's inscription of its intellectual and historical context-I have come to a better understanding of how that publication was both the beginning and end of the conversation it sought to inaugurate. "Notes on Sexuality and Space" investigates three related essays from that publication: Laura Mulvey's "Pandora: Topographies of the Mask and Curiosity," Beatriz Colomina's "The Split Wall: Domestic Voyeurism," and Mark Wigley's "Untitled: The Housing of Gender." Each investigated essay has been given a corresponding chapter. My method has been close reading, or the sustained interpretation of brief passages of text. Paying close attention to individual words, syntax, and the order in which ideas unfold as they are read, I have developed a comprehensive narrative of how these three essays, together, both instantiate and negate a shared discourse. To these ends, this thesis raises serious questions about what it means to have historiography after silence, and what it means to re-open an already closed discourse.by Samuel Ray Jacobson.S.M

Amazonian plants from ethnomedicine to biotechnology through pharmaceutical biology approaches: a PhD experience in connecting forest with laboratory

The South american Natives, Shuar and Achuar people and their ethnomedical culture constitute the background subject of the Phd research, performed both in Ecuador (Salesian Politechnic University, Quito), and in Italy (Pharmaceutical biology labs, University of Ferrara). Based on ethnomedical responses, Piper aduncum, Maytenus macrocarpa, Schinus molle, Tecoma stans and Eugenia hallii were chosen as amazonian plant species subject of the research. AIMS The research has been focused on: − checking the presence of endophytic fungi in plants; − isolating and subculturing pure endophytic strains; − checking the biotransformation capacity of the isolated endophytes on pure compounds; the most performing endophytes were also tested on phytocomplexes and pure chemicals obtained by the plant from which the fungi were isolated; − phytochemical characterization and bioactivity assays of plant extracts: P. aduncum. − METHODS Biotransformations. Fresh aerial plant parts were properly washed in sanitizing solutions and in vitro cultured using adequate solid media to isolate endophytes. (+/-)-cis-bicyclo[3.2.0]hept-2-en-6-one, acetophenone, 1-indanone, 2-furyl methyl ketone, 2-methylcyclopentanone, 2-methylcyclohexanone, 2- methoxycyclohexanone were chosen as substrate model for biotransformations. The cultures were sampled after 1, 3, 7, 10 days of culturing, and ethyl acetate extracted to verify by GC-MS the presence of possible biotransformation products. Biotransformations were also checked on P. aduncum whole essential oil and on dillapiol, cis-ocimene, piperitone, (-)-terpinen-4-ol as most abundant chemicals. Chemical fingerprinting of P. aduncum essential oil. Steam distillation was adopted to obtain the essential oil, then characterized by GC-MS, NMR analyses. In vitro bioassays of P. aduncum essential oil. Antimicrobial activities were checked in vitro using proper agarized media to reach MIC. Antioxidant capacities were checked through DPPH test, ABTS and photochemiluminescence assays. Born's turbidimetric method and Writhing test were respectively adopted to check platelet-aggregation and anti-nociceptive properties. Mutagenic, antimutagenic properties and toxicity were assayed using classical and modified Ames test. MAIN RESULTS 364 fungal strains were in vitro isolated. Among all, 5 strains performed biotransformations on acetophenone to (S)-1-phenylethanol, with important yields (78-97%) and enantiomeric excess (78- 100%). Three strains gave also phenols probably by enzymatic reactions (Baeyer-Villiger oxidations). 15 fungal strains gave the lactones (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one and (-)-(1R,5S)-3- oxabicyclo[3.3.0]oct-6-en-2-one from (+/-)-cis-bicyclo[3.2.0]hept-2-en-6-one, probably as result of monooxygenase activation. Phytochemical characterization of P. aduncum essential oil has evidenced dillapiol as the most abundant terpene, followed by cis-ocimene, piperitone and terpinen-4-ol. Only cisocimene and piperitone gave several biotransformation products through dehydrogenation and hydroxylation reactions. The essential oil has evidenced non-mutagenic properties and interesting antifungal and antioxidant activities. CONCLUSIONS Several endophytic fungal strains from Amazonian plants were isolated and checked for biotransformations on pure chemicals and on P. aduncum essential oil. Data obtained will be useful for possible following patents about micro-organisms able to transform pharmaceutically interesting chemicals. Taxonomical characterization of the most performing fungal strains is still in progress. P. aduncum essential oil can be considered genotoxically safe and provides interesting antifungal and antioxidant properties, supporting its ethnomedical use as cicatrising and disinfectant crude drug and suggesting an extension of its employ as preservative ingredient

Probabilistic methods in the analysis of protein interaction networks

Imperial Users onl