94 research outputs found
Statistically Optimal Force Aggregation for Coarse-Graining Molecular Dynamics
No full textMachine-learned coarse-grained (CG) models have the potential for simulating
large molecular complexes beyond what is possible with atomistic molecular
dynamics. However, training accurate CG models remains a challenge. A widely
used methodology for learning CG force-fields maps forces from all-atom
molecular dynamics to the CG representation and matches them with a CG
force-field on average. We show that there is flexibility in how to map
all-atom forces to the CG representation, and that the most commonly used
mapping methods are statistically inefficient and potentially even incorrect in
the presence of constraints in the all-atom simulation. We define an
optimization statement for force mappings and demonstrate that substantially
improved CG force-fields can be learned from the same simulation data when
using optimized force maps. The method is demonstrated on the miniproteins
Chignolin and Tryptophan Cage and published as open-source code.Comment: 44 pages, 19 figure
The 'true use of reading' : Sarah Fielding and mid eighteenth-century literary strategies.
No full textPhDThe aim of this thesis is to explore, by examining her life and
works, how Sarah Fielding (1710-68) established her identity as an author.
The definition of her role involves her notions of the functions of
writing and reading.
Sarah Fielding attempts to invite readers to form a sense of ties
by tacit understanding of her messages. As she believes that a work
of literature is produced through collaboration between the writer and
the reader, it is an important task in her view to show her attentiveness
toward reading practice. In her consideration of reading, she has two
distinct, even opposite views of her audience: on the one hand a familiar
and limited circle of readers with shared moral and cultural values and
on the other potential readers among the unknown mass of people. The
dual targets direct her to devise various strategies. She tries to
appeal to those who can endorse and appreciate her moral values as well
as her learning. Her writings and letters testify that she is sensitive
to the demands of the literary market, trying to lead the taste of readers
by inventing new forms.
The thesis opens with an overview of Sarah Fielding's career,
followed by a consideration of her critical attention to the roles of
reading. I go on to examine the narrative structures and strategies
she deploys, with a particular emphasis on her use of the epistolary
method. The following chapter deals with her attention to the reading
of the moral message tangibly embodied in her educational writing. It
is followed by an analysis of the activity which earned her a reputation
as a learned woman. Various as the forms of her works are, they invariably
reflect her attempt to balance herself between the two demands of
inventiveness and familiarity
Competition in network industries
No full textA wave of privatization is sweeping the globe, affecting about 100 countries and adding up to an average of more than $60 billion a year in business in the past decade. The challenge is to ensure that privatization yields clear benefits. Empirical studies suggest that ownership change by itself will often yield results, especially when it reduces government interference. But the regulation required in areas of natural monopoly can become overly intrusive and undermine progress. Real competition is required to generate sizable and lasting welfare improvements. But in infrastructure sectors, the introduction of competition is complicated by the existence of complex transport and communications networks. Debate about whether and how to introduce competition in network industries is sometimes heated. Certain questions recur: Will continuing regulation be needed? Whether and at what terms will private finance be forthcoming? The author argues that policymakers need to understand how competitive forces can be brought to bear in network industries. He explains the following: 1) common principles that are often lost in"technical"debates about specific sectors; 2) various methods for introducing competition in network industries; 3) competition for the market, and bidding for franchises; 4) options for competition for existing networks; 5) options for expanding competitive systems by decentralizing investment in new network capacity; 6) the option of allowing competition among multiple networks; and 7) the implications of these options for the sectors and for financing industry expansion. In case of doubt, he contends, policymakers should not restrict the entry of competitive firms in such networks. If they do, entry restrictions should be subject to an automatic test after a set period, and reviewed for costs and benefits.Economic Theory&Research,Decentralization,Markets and Market Access,Environmental Economics&Policies,Labor Policies,Education for the Knowledge Economy,Economic Theory&Research,Access to Markets,Markets and Market Access,Environmental Economics&Policies
Transient observations : the textualizing of St Helena through five hundred years of colonial discourse
No full textThis thesis explores the textualizing of the South Atlantic island of St Helena (a
British Overseas Territory) through an analysis of the relationship between
colonizing practices and the changing representations of the island and its
inhabitants in a range of colonial 'texts', including historiography, travel writing,
government papers, creative writing, and the fine arts.
Part I situates this thesis within a critical engagement with post-colonial
theory and colonial discourse analysis primarily, as well as with the recent
'linguistic turn' in anthropology and history. In place of post-colonialism's rather
monolithic approach to colonial experiences, I argue for a localised approach to
colonisation, which takes greater account of colonial praxis and of the continuous
re-negotiation and re-constitution of particular colonial situations.
Part II focuses on a number of literary issues by reviewing St Helena's
historiography and literature, and by investigating the range of narrative tropes
employed (largely by travellers) in the textualizing of St Helena, in particular
with respect to recurrent imaginings of the island in terms of an earthly Eden.
Part III examines the nature of colonial 'possession' by tracing the island's
gradual appropriation by the Portuguese, Dutch and English in the sixteenth and
early seventeenth century and the settlement policies pursued by the English
East India Company in the late seventeenth and early eighteenth century.
Part IV provides an account of the changing perceptions, by visitors and
colonial officials alike, of the character of the island's inhabitants (from the late
eighteenth to the early twentieth century) and assesses the influence that these
perceptions have had on the administration of the island and the political status of
its inhabitants (in the mid- to late twentieth century).
Part V, the conclusion, reviews the principal arguments of my thesis by
addressing the political implications of post-colonial theory and of my own
research, while also indicating avenues for further research.
A localised and detailed exploration of colonial discourse over a period of
nearly five hundred years, and a close analysis of a consequently wide range of
colonial 'texts', has confirmed that although colonising practices and
representations are far from monolithic, in the case of St Helena their continuities
are of as much significance as their discontinuities
Реконструкция книжного собрания уральского горнозаводчика XVIII века А.Ф. Турчанинова
No full textThe article discusses the monograph of E.P. Pirogova, dedicated to the reconstruction of the private library of the Ural owner of mines A.F. Turchaninov (1704—1787). The monograph is based on the unique source — the detailed inventory of property compiled in 1789. The document allowed to create the catalog of the Russian part of the collection and the review of foreign books. The monograph also includes the archaeographic publication of inventory materials related to the books and other printed products. The author of the monograph introduced into scientific circulation the detailed information about one of the largest private libraries in Russia in the second half of the 18th century and probably the most significant in the Urals in that historical period. It allows us to refute the existing view in historiography about the ceremonial nature of A.F. Turchaninovʼs book collection. Now the owner of mines and metallurgical works can be considered as an active and thoughtful collector of books and user of his own library, familiar with the cultural practices of the Era of Enlightenment.В статье рассматривается монография Е.П. Пироговой, посвященная реконструкции личной библиотеки уральского горнозаводчика А.Ф. Турчанинова (1704—1787). Она основана на уникальном источнике — подробной описи имущества, составленной в 1789 году. Документ позволил создать каталог русской части собрания и обзор иностранных книг. В монографии также осуществлена археографическая публикация материалов описи, касающихся книг и другой печатной продукции. В научный оборот введена подробная информация об одной из крупнейших частных библиотек в России второй половины XVIII в. и, вероятно, самой значительной на Урале в этот исторический период. Она позволяет опровергнуть бытующую в историографии версию о парадном характере книжного собрания А.Ф. Турчанинова. Теперь заводчика можно рассматривать как активного и вдумчивого собирателя книг, пользовавшегося своей библиотекой, знакомого с культурными практиками эпохи Просвещения
Heterogeneous continuous dynamic Bayesian networks with flexible structure and inter-time segment information sharing
No full textUnderstanding physical drivers of the 2015/16 marine heatwaves in the Northwest Atlantic
No full text© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Perez, E., Ryan, S., Andres, M., Gawarkiewicz, G., Ummenhofer, C. C., Bane, J., & Haines, S. Understanding physical drivers of the 2015/16 marine heatwaves in the Northwest Atlantic. Scientific Reports, 11(1), (2021): 17623, https://doi.org/10.1038/s41598-021-97012-0.The Northwest Atlantic, which has exhibited evidence of accelerated warming compared to the global ocean, also experienced several notable marine heatwaves (MHWs) over the last decade. We analyze spatiotemporal patterns of surface and subsurface temperature structure across the Northwest Atlantic continental shelf and slope to assess the influences of atmospheric and oceanic processes on ocean temperatures. Here we focus on MHWs from 2015/16 and examine their physical drivers using observational and reanalysis products. We find that a combination of jet stream latitudinal position and ocean advection, mainly due to warm core rings shed by the Gulf Stream, plays a role in MHW development. While both atmospheric and oceanic drivers can lead to MHWs they have different temperature signatures with each affecting the vertical structure differently and horizontal spatial patterns of a MHW. Northwest Atlantic MHWs have significant socio-economic impacts and affect commercially important species such as squid and lobster.The work was supported by a Woods Hole Oceanographic Institution Summer Student Fellowship (to E.P.) through the National Science Foundation (NSF) REU under grant OCE-1852460, a Feodor-Lynen Fellowship by the Alexander von Humboldt Foundation and the WHOI Postdoctoral Scholar program (to S.R.), NSF grants OCE-1924041 (to M.A.) and OCE-1851261 (to G.G.) and OCE-1558920 (to J.B. and H. Seim at the Univ. of North Carolina), ONR grant N-14-19-1-2646 (to G.G.), and the James E. and Barbara V. Moltz Fellowship for Climate-Related Research (to C.C.U.)
Machine learned coarse-grained protein force-fields: Are we there yet?
No full textThe successful recent application of machine learning methods to scientific problems includes the learning of flexible and accurate atomic-level force-fields for materials and biomolecules from quantum chemical data. In parallel, the machine learning of force-fields at coarser resolutions is rapidly gaining relevance as an efficient way to represent the higher-body interactions needed in coarse-grained force-fields to compensate for the omitted degrees of freedom. Coarse-grained models are important for the study of systems at time and length scales exceeding those of atomistic simulations. However, the development of transferable coarse-grained models via machine learning still presents significant challenges. Here, we discuss recent developments in this field and current efforts to address the remaining challenges
Integrative multi-omic cancer profiling reveals DNA methylation patterns associated with therapeutic vulnerability and cell-of-origin
No full textWe thank InPrint for the editing, Matthew A. Wyczalkowski for feedback on figures, and BioRender for diagrams. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) is supported by the National Cancer Institute of the National Institutes of Health under award numbers U24CA210955, U24CA210985, U24CA210986, U24CA210954, U24CA210967, U24CA210972, U24CA210979, U24CA210993, U01CA214114, U01CA214116, and U01CA214125 as U24CA210972 to D.F. L.D. and S.P. and Contract GR0012005 to L.D. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201500003I, Task Order HHSN26100064. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. Study Conception & Design: W.L. R.J.L. R.J. S.F. and L.D.; Performed Experiment or Data Collection: W.L. R.L. I.K. E.D. Y.L. S.S. and M.W.; Computational, Multi-omic, & Statistical Analyses: W.L, R.J.L. E.P. Y.S. A.G. and X.L.; Data Interpretation & Biological Analysis: W.L, R.J.L. R.G.J. S.M.F. E.P. Y.G. R.L. M.W. and H.S.; Writing - Original Drafts: W.L. and R.J.L.; Writing - Review & Editing: W.L. R.J.L. R.J. S.F. E.P. Y.G. M.C.W. Y.S. A.G. X.L. Y.L. D.R.M. K.R. A.L. A.R. and L.D.; Supervision: W.L. and L.D.; Administration:W.L. S.P. D.F. H.R. D.R.M. K.R. A.L. A.R. and L.D. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. During the preparation of this work the author(s) used ChatGPT to enhance its readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.We thank InPrint for the editing, Matthew A. Wyczalkowski for feedback on figures, and BioRender for diagrams. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) is supported by the National Cancer Institute of the National Institutes of Health under award numbers U24CA210955, U24CA210985, U24CA210986, U24CA210954, U24CA210967, U24CA210972, U24CA210979, U24CA210993, U01CA214114, U01CA214116, and U01CA214125 as U24CA210972 to D.F., L.D., and S.P., and Contract GR0012005 to L.D. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201500003I, Task Order HHSN26100064. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development and is closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors and matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head and neck, and endometrium to identify aberrant methylation associated with RNA and protein abundance changes and build a Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers including hypomethylated FGFR2 in endometrial cancer. We showed that hypermethylated STAT5A is associated with pervasive regulon downregulation and immune cell depletion, suggesting that epigenetic regulation of STAT5A expression constitutes a molecular switch for immunosuppression in squamous tumors. We further demonstrated that methylation subtype-enrichment information can explain cell-of-origin, intra-tumor heterogeneity, and tumor phenotypes. Overall, we identified cis-acting DNA methylation events that drive transcriptional and translational changes, shedding light on the tumor's epigenetic landscape and the role of its cell-of-origin
Treasures of the University : an examination of the identification, presentation and responses to artefacts of significance at the University of St Andrews, from 1410 to the mid-19th century; with an additional consideration of the development of the portrait collection to the early 21st century
No full textSince its foundation between 1410 and 1414 the University of St Andrews has acquired what can be considered to be ‘artefacts of significance’. This somewhat nebulous phrase is used to denote items that have, for a variety of reasons, been deemed to have some special import by the University, and have been displayed or otherwise presented in a context in which this status has been made apparent.
The types of artefacts in which particular meaning has been vested during the centuries under consideration include items of silver and gold (including the maces, sacramental vessels of the Collegiate Church of St Salvator, collegiate plate and relics of the Silver Arrow archery competition); church and college furnishings; artworks (particularly portraits); sculpture; and ethnographic specimens and other items described in University records as ‘curiosities’ held in the University Library from c. 1700-1838.
The identification of particular artefacts as significant for certain reasons in certain periods, and their presentation and display, may to some extent reflect the University's values, preoccupations and aspirations in these periods, and, to some degree, its identity. Consciously or subconsciously, the objects can be employed or operate as signifiers of meaning, representing or reflecting matters such as the status, authority and history of the University, its breadth of learning and its interest and influence in spheres from science, art and world cultures to national affairs.
This thesis provides a comprehensive examination of the growth and development of the University's holdings of 'artefacts of significance' from its foundation to the mid-19th century, and in some cases (especially portraits) beyond this date. It also offers insights into how the University viewed and presented these items and what this reveals about the University of St Andrews, its identity, which changed and developed as the living institution evolved, and the impressions that it wished to project
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