181 research outputs found
Towards Automated Benchmarking of Atomistic Forcefields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive
Atomistic molecular simulations are a powerful way to make quantitative
predictions, but the accuracy of these predictions depends entirely on the
quality of the forcefield employed. While experimental measurements of
fundamental physical properties offer a straightforward approach for evaluating
forcefield quality, the bulk of this information has been tied up in formats
that are not machine-readable. Compiling benchmark datasets of physical
properties from non-machine-readable sources require substantial human effort
and is prone to accumulation of human errors, hindering the development of
reproducible benchmarks of forcefield accuracy. Here, we examine the
feasibility of benchmarking atomistic forcefields against the NIST ThermoML
data archive of physicochemical measurements, which aggregates thousands of
experimental measurements in a portable, machine-readable, self-annotating
format. As a proof of concept, we present a detailed benchmark of the
generalized Amber small molecule forcefield (GAFF) using the AM1-BCC charge
model against measurements (specifically bulk liquid densities and static
dielectric constants at ambient pressure) automatically extracted from the
archive, and discuss the extent of available data. The results of this
benchmark highlight a general problem with fixed-charge forcefields in the
representation low dielectric environments such as those seen in binding
cavities or biological membranes
MI5 and the Cold War in South-East Asia: Examining the Performance of Security Intelligence Far East (SIFE), 1946-1963
From 1946â1963, MI5 operated a South-East Asian regional headquarters in Singapore: Security Intelligence Far East (SIFE). This article responds to growing interest in theatre-level intelligence organisation and the importance of intelligence to Britainâs Cold War and decolonisation by examining the performance of SIFE. On the organisational level, SIFE was strongest when it remained wedded to its charter functions and closely adhered to the priorities of its principal consumer: the Commissioner-General for South-East Asia. Its assessments were influential in shaping decision-makersâ understandings of key regional developments, although this did not always translate into public policy. Lastly, SIFE enjoyed success in developing lasting liaison relationships to cement British influence, but failed to utilise these to improve its intake of raw intelligence
An Anthropology of Intellectual Exchange: Interactions, Transactions and Ethics in Asia and Beyond
Dialogues, encounters and interactions through which particular ways of knowing, understanding and thinking about the world are forged lie at the centre of anthropology. Such âintellectual exchangeâ is also central to anthropologistsâ own professional practice: from their interactions with research participants and modes of pedagogy to their engagements with each other and scholars from adjacent disciplines. This collection of essays explores how such processes might best be studied cross-culturally. Foregrounding the diverse interactions, ethical reasoning, and intellectual lives of people from across the continent of Asia, the volume develops an anthropology of intellectual exchange itself
Intracellular connections between basal bodies promote the coordinated behavior of motile cilia
Hydrodynamic flow produced by multiciliated cells is critical for fluid circulation and cell motility. Hundreds of cilia beat with metachronal synchrony for fluid flow. Cilia-driven fluid flow produces extracellular hydrodynamic forces that cause neighboring cilia to beat in a synchronized manner. However, hydrodynamic coupling between neighboring cilia is not the sole mechanism that drives cilia synchrony. Cilia are nucleated by basal bodies (BBs) that link to each other and to the cell\u27s cortex via BB-associated appendages. The intracellular BB and cortical network is hypothesized to synchronize ciliary beating by transmitting cilia coordination cues. The extent of intracellular ciliary connections and the nature of these stimuli remain unclear. Moreover, how BB connections influence the dynamics of individual cilia has not been established. We show by focused ion beam scanning electron microscopy imaging that cilia are coupled both longitudinally and laterally in the ciliat
Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks
Free energy calculations are rapidly becoming indispensable in
structure-enabled drug discovery programs. As new methods, force fields, and
implementations are developed, assessing their expected accuracy on real-world
systems (benchmarking) becomes critical to provide users with an assessment of
the accuracy expected when these methods are applied within their domain of
applicability, and developers with a way to assess the expected impact of new
methodologies. These assessments require construction of a benchmark - a set of
well-prepared, high quality systems with corresponding experimental
measurements designed to ensure the resulting calculations provide a realistic
assessment of expected performance when these methods are deployed within their
domains of applicability. To date, the community has not yet adopted a common
standardized benchmark, and existing benchmark reports suffer from a myriad of
issues, including poor data quality, limited statistical power, and
statistically deficient analyses, all of which can conspire to produce
benchmarks that are poorly predictive of real-world performance. Here, we
address these issues by presenting guidelines for (1) curating experimental
data to develop meaningful benchmark sets, (2) preparing benchmark inputs
according to best practices to facilitate widespread adoption, and (3) analysis
of the resulting predictions to enable statistically meaningful comparisons
among methods and force fields
The United Kingdom and British Empire: A Figurational Approach
Drawing upon the work of Norbert Elias and the process [figurational] sociology perspective, this article examines how state formation processes are related to, and, affected by, expanding and declining chains of international interdependence. In contrast to civic and ethnic conceptions, this approach focuses on the emergence of the nation/nation-state as grounded in broader processes of historical and social development. In doing so, state formation processes within the United Kingdom are related to the expansion and decline of the British Empire. That is, by focusing on the functional dynamics that are embedded in collective groups, one is able to consider how the UKâs âstateâ and âimperialâ figurations were interdependently related to changes in both the UK and the former British Empire. Consequently, by locating contemporary UK relations in the historical context of former imperial relationships, nationalism studies can go âbeyondâ the nation/nation-state in order to include broader processes of imperial expansion and decline. Here, the relationship between empire and nationalism can offer a valuable insight into contemporary political movements, especially within former imperial groups
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