Sampling molecular conformations and dynamics in a multiuser virtual reality framework

Copyright © 2018 The Authors, some rights reserved. We describe a framework for interactive molecular dynamics in a multiuser virtual reality (VR) environment, combining rigorous cloud-mounted atomistic physics simulations with commodity VR hardware, which we have made accessible to readers (see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic-level precision, the structures and dynamics of complex molecular structures “on the fly” and to interact with other users in the same virtual environment. A series of controlled studies, in which participants were tasked with a range of molecular manipulation goals (threading methane through a nanotube, changing helical screw sense, and tying a protein knot), quantitatively demonstrate that users within the interactive VR environment can complete sophisticated molecular modeling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically three-dimensional. This framework should accelerate progress in nanoscale molecular engineering areas including conformational mapping, drug development, synthetic biology, and catalyst design. More broadly, our findings highlight the potential of VR in scientific domains where three-dimensional dynamics matter, spanning research and education

Association of elevated urinary miR-126, miR-155, and miR-29b with diabetic kidney disease

Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary miRNAs represent a potential source of novel noninvasive disease sentinels. We profiled 754 miRNAs in pooled urine samples from DKD patients (n = 20), detecting significantly increased miR-126, miR-155, and miR-29b compared with controls (n = 20). These results were confirmed in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD, and 41 controls: miR-126 (2.8-fold increase; P < 0.0001), miR-155 (1.8-fold increase; P < 0.001), and miR-29b (4.6-fold increase; P = 0.024). Combined receiver operating characteristic curve analysis resulted in an area under the curve of 0.8. A relative quantification threshold equivalent to 80% sensitivity for each miRNA gave a positive signal for 48% of DKD patients compared with 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsy specimens, followed by quantitative RT-PCR, detected miR-155 in glomeruli and proximal and distal tubules, whereas miR-126 and miR-29b were most abundant in glomerular extracts. Subsequent experiments showed miR-126 and miR-29b enrichment in glomerular endothelial cells (GEnCs) compared with podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumor necrosis factor-α and transforming growth factor-β1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs

The retreat from locative overgeneralisation errors : a novel verb grammaticality judgment study

Whilst some locative verbs alternate between the ground- and figure-locative constructions (e.g. Lisa sprayed the flowers with water/Lisa sprayed water onto the flowers), others are restricted to one construction or the other (e.g. *Lisa filled water into the cup/*Lisa poured the cup with water). The present study investigated two proposals for how learners (aged 5–6, 9–10 and adults) acquire this restriction, using a novel-verb-learning grammaticality-judgment paradigm. In support of the semantic verb class hypothesis, participants in all age groups used the semantic properties of novel verbs to determine the locative constructions (ground/figure/both) in which they could and could not appear. In support of the frequency hypothesis, participants’ tolerance of overgeneralisation errors decreased with each increasing level of verb frequency (novel/low/high). These results underline the need to develop an integrated account of the roles of semantics and frequency in the retreat from argument structure overgeneralisation

Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers

This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al., 2015) and is intended to provide the rubric for peer review. Thus, it is directed towards authors, reviewers and editors. Explanations for many of the requirements were outlined previously and are not restated here. The new guidelines are intended to replace those published previously. The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards

Children Use Statistics and Semantics in the Retreat from Overgeneralization

How do children learn to restrict their productivity and avoid ungrammatical utterances? The present study addresses this question by examining why some verbs are used with un- prefixation (e.g., unwrap) and others are not (e.g., *unsqueeze). Experiment 1 used a priming methodology to examine children's (3–4; 5–6) grammatical restrictions on verbal un- prefixation. To elicit production of un-prefixed verbs, test trials were preceded by a prime sentence, which described reversal actions with grammatical un- prefixed verbs (e.g., Marge folded her arms and then she unfolded them). Children then completed target sentences by describing cartoon reversal actions corresponding to (potentially) un- prefixed verbs. The younger age-group's production probability of verbs in un- form was negatively related to the frequency of the target verb in bare form (e.g., squeez/e/ed/es/ing), while the production probability of verbs in un- form for both age groups was negatively predicted by the frequency of synonyms to a verb's un- form (e.g., release/*unsqueeze). In Experiment 2, the same children rated the grammaticality of all verbs in un- form. The older age-group's grammaticality judgments were (a) positively predicted by the extent to which each verb was semantically consistent with a semantic “cryptotype” of meanings - where “cryptotype” refers to a covert category of overlapping, probabilistic meanings that are difficult to access - hypothesised to be shared by verbs which take un-, and (b) negatively predicted by the frequency of synonyms to a verb's un- form. Taken together, these experiments demonstrate that children as young as 4;0 employ pre-emption and entrenchment to restrict generalizations, and that use of a semantic cryptotype to guide judgments of overgeneralizations is also evident by age 6;0. Thus, even early developmental accounts of children's restriction of productivity must encompass a mechanism in which a verb's semantic and statistical properties interact

Modeling in the design and analysis of a hit-to-kill rocket guidance kit

This thesis presents several computer models used in the design and analysis of a Hit-to-Kill Rocket Guidance Kit (HRGK). The HRGK proposed as an inexpensive add on kit has the potential of converting unguided 2.75" diameter rockets into precision weapons against non-tank targets. A Naval Postgraduate School design team recently participated in a nation-wide graduate student competition for the design of such a kit. The design and analysis process led the author to develop and use various computer models and simulations. This thesis documents three distinct types of computer models found useful in the design. The first, operational effectiveness modeling, established the cost effectiveness of the NPS HRGK. The second was related to the preliminary sizing of various design aspects ensuring the proper flow down of system requirements into design specifications. The third was a six degree of freedom (6DOF) simulation, developed to perform detailed analyses of the HRGK's performance. Although the models presented in this thesis pertain to the HRGK, the basic principles apply to the design or evaluation of other missile systems, and this thesis provides general insights regarding the benefits and limitations of computer modeling in missile designhttp://archive.org/details/modelingindesign00wonnApproved for public release; distribution is unlimited

Geolocation with error analysis using imagery from an experimental spotlight SAR

This dissertation covers the development of a geometry-based sensor model for a specific monostatic spotlight synthetic aperture radar (SAR) system—referred to as the ExSAR (for experimental SAR). This sensor model facilitates single- and multiple-image geopositioning with error analysis. It allows for the use of known ground control points in refining the collection geometry parameters (a process called image resection) and for the subsequent geopositioning of other points using the resected image. Theoretically, the model also allows for the potential recovery of bias-like, persistent errors common across multiple images. The model also includes multi-image correspondence equations to aid in the cross-image identification of conjugate points. The sensor model development begins with a generic, theoretical approach to the modeling of spotlight SAR. A closed-form solution to the range and range-rate condition equations and the corresponding error propagation equation are presented. (The SAR condition equations have traditionally been solved iteratively.) The application of the closed-form solution in the image-to-ground and ground-to-image transformations is documented. The theoretical work also includes a preliminary error sensitivity analysis and a treatment of the spotlight SAR resection process. The ExSAR-specific model is established and assessed with an extensive set of images collected using the experimental radar over arrays of ground control points. Using this set, the imagery metadata elements are assessed, and the optimal element set for geopositioning is determined. The ExSAR imagery is shown to be transformed to the ground plane in only one dimension. The eventual ExSAR sensor model is used with known elevations and single-image geopositioning to show a horizontal accuracy of 8.23 m (rms). With resection using five ground-surveyed control points per image, the horizontal accuracy of reserved check points is 0.45 m (rms). Resections using the same points, but recovering fewer geometry parameters produced nearly equal accuracies. Three-dimensional geopositioning was shown feasible using the model and multiple images. Correspondence curve equations were developed and tested. These define the expected location of a conjugate point in overlapping imagery. This work includes extensive explanatory appendices, including preliminary work with bistatic SAR modeling. The experimental data set and MATLAB ® code are available