Efficient and Accurate Modeling of Conformational Transitions in Proteins: The Case of c-Src Kinase

The theoretical computational modeling of large conformational transitions occurring in biomolecules still represents a challenge. Here, we present an accurate "in silico" description of the activation and deactivation mechanisms of human c-Src kinases, a fundamental process regulating several crucial cell functions. Our results clearly show that by applying an efficient and automated algorithm able to drive the molecular dynamics (MD) sampling along the pathway between the two c-Src conformational states - the active state and the inactive state - it is possible to accurately describe, at reduced computational costs, the molecular mechanism underlying these large conformational rearrangements. This procedure, combining the MD simulations with the sampling along the well-defined principal motions connecting the two conformational states, allows to provide a description well beyond the present computational limits, and it is easily applicable to different systems where the structures of both the initial and final states are known

Sustainable fibre for sustainable fashion supply chains: where the journey to sustainability begins

Adopting a sustainable business model is an essential element of gaining competitive advantage. Specifically, the management of fashion and textile supply chains characterized by geographical extension requires paying particular attention to environmental and social sustainability. Following an analysis of the literature on sustainable supply chains in the fashion and textile industries, this qualitatively based research examines – from a supply chain perspective – the sustainability initiatives implemented by a yarn and garment producer through a single case study. Subsequently, the classification of potential sustainability initiatives is presented. From this investigation, several good practices for sustainable fashion supply chains can be identified, providing a reference point for similar companies. Keywords: sustainable fashion supply chain, sustainable textiles, closed loop supply chai

Reasoning About Liquids via Closed-Loop Simulation

Simulators are powerful tools for reasoning about a robot's interactions with its environment. However, when simulations diverge from reality, that reasoning becomes less useful. In this paper, we show how to close the loop between liquid simulation and real-time perception. We use observations of liquids to correct errors when tracking the liquid's state in a simulator. Our results show that closed-loop simulation is an effective way to prevent large divergence between the simulated and real liquid states. As a direct consequence of this, our method can enable reasoning about liquids that would otherwise be infeasible due to large divergences, such as reasoning about occluded liquid.Comment: Robotics: Science & Systems (RSS), July 12-16, 2017. Cambridge, MA, US

Considering the impact of situation-specific motivations and constraints in the design of naturally ventilated and hybrid buildings

A simple logical model of the interaction between a building and its occupants is presented based on the principle that if free to do so, people will adjust their posture, clothing or available building controls (windows, blinds, doors, fans, and thermostats) with the aim of achieving or restoring comfort and reducing discomfort. These adjustments are related to building design in two ways: first the freedom to adjust depends on the availability and ease-of-use of control options; second the use of controls affects building comfort and energy performance. Hence it is essential that these interactions are considered in the design process. The model captures occupant use of controls in response to thermal stimuli (too warm, too cold etc.) and non-thermal stimuli (e.g. desire for fresh air). The situation-specific motivations and constraints on control use are represented through trigger temperatures at which control actions occur, motivations are included as negative constraints and incorporated into a single constraint value describing the specifics of each situation. The values of constraints are quantified for a range of existing buildings in Europe and Pakistan. The integration of the model within a design flow is proposed and the impact of different levels of constraints demonstrated. It is proposed that to minimise energy use and maximise comfort in naturally ventilated and hybrid buildings the designer should take the following steps: 1. Provide unconstrained low energy adaptive control options where possible, 2. Avoid problems with indoor air quality which provide motivations for excessive ventilation rates, 3. Incorporate situation-specific adaptive behaviour of occupants in design simulations, 4. Analyse the robustness of designs against variations in patterns of use and climate, and 5. Incorporate appropriate comfort standards into the operational building controls (e.g. BEMS)

DS-SLAM: A Semantic Visual SLAM towards Dynamic Environments

Simultaneous Localization and Mapping (SLAM) is considered to be a fundamental capability for intelligent mobile robots. Over the past decades, many impressed SLAM systems have been developed and achieved good performance under certain circumstances. However, some problems are still not well solved, for example, how to tackle the moving objects in the dynamic environments, how to make the robots truly understand the surroundings and accomplish advanced tasks. In this paper, a robust semantic visual SLAM towards dynamic environments named DS-SLAM is proposed. Five threads run in parallel in DS-SLAM: tracking, semantic segmentation, local mapping, loop closing, and dense semantic map creation. DS-SLAM combines semantic segmentation network with moving consistency check method to reduce the impact of dynamic objects, and thus the localization accuracy is highly improved in dynamic environments. Meanwhile, a dense semantic octo-tree map is produced, which could be employed for high-level tasks. We conduct experiments both on TUM RGB-D dataset and in the real-world environment. The results demonstrate the absolute trajectory accuracy in DS-SLAM can be improved by one order of magnitude compared with ORB-SLAM2. It is one of the state-of-the-art SLAM systems in high-dynamic environments. Now the code is available at our github: https://github.com/ivipsourcecode/DS-SLAMComment: 7 pages, accepted at the 2018 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2018). Now the code is available at our github: https://github.com/ivipsourcecode/DS-SLA

Autonomous control procedures for shuttle rendezvous proximity operations

The results are presented of a study which uses fuzzy sets to model a Space Shuttle pilot's reasoning and actions while performing rendezvous proximity operation maneuvers. In this model fuzzy sets are used to simulate smooth and continuous actions as would be expected from an experienced pilot and to simulate common sense reasoning in the decision process. The present model assumes visual information available to the Shuttle pilot from the Shuttle Crew Optical Alignment Sighting (COAS) device and the overhead window and rendezvous radar sensor information available to him from an onboard display. This model will be used in a flight analysis simulator to perform studies requiring a large number of runs, each of which currently needs an engineer in the loop to supply the piloting decisions. This work has much broader implications in control of robots such as the Flight Telerobotic Servicer, in automated pilot control and attitude control, and in advisory and evaluation functions that could be used for flight data monitoring or for testing of various rule sets in flight preparation

Allosteric Conversation in the Androgen Receptor Ligand-Binding Domain Surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. Wepreviously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design. © 2012 by The Endocrie Society

Stacking-induced fluorescence increase reveals allosteric interactions through DNA

From gene expression to nanotechnology, understanding and controlling DNA requires a detailed knowledge of its higher order structure and dynamics. Here we take advantage of the environment-sensitive photoisomerization of cyanine dyes to probe local and global changes in DNA structure. We report that a covalently attached Cy3 dye undergoes strong enhancement of fluorescence intensity and lifetime when stacked in a nick, gap or overhang region in duplex DNA. This is used to probe hybridization dynamics of a DNA hairpin down to the single-molecule level. We also show that varying the position of a single abasic site up to 20 base pairs away modulates the dye–DNA interaction, indicative of through-backbone allosteric interactions. The phenomenon of stacking-induced fluorescence increase (SIFI) should find widespread use in the study of the structure, dynamics and reactivity of nucleic acids