Reasoning about goal-directed real-time teleo-reactive programs

The teleo-reactive programming model is a high-level approach to developing real-time systems that supports hierarchical composition and durative actions. The model is different from frameworks such as action systems, timed automata and TLA+, and allows programs to be more compact and descriptive of their intended behaviour. Teleo-reactive programs are particularly useful for implementing controllers for autonomous agents that must react robustly to their dynamically changing environments. In this paper, we develop a real-time logic that is based on Duration Calculus and use this logic to formalise the semantics of teleo-reactive programs. We develop rely/guarantee rules that facilitate reasoning about a program and its environment in a compositional manner. We present several theorems for simplifying proofs of teleo-reactive programs and present a partially mechanised method for proving progress properties of goal-directed agents. © 2013 British Computer Society

Computational Design and Optimization of Non-Circular Gears

We study a general form of gears known as non‐circular gears that can transfer periodic motion with variable speed through their irregular shapes and eccentric rotation centers. To design functional non‐circular gears is nontrivial, since the gear pair must have compatible shape to keep in contact during motion, so the driver gear can push the follower to rotate via a bounded torque that the motor can exert. To address the challenge, we model the geometry, kinematics, and dynamics of non‐circular gears, formulate the design problem as a shape optimization, and identify necessary independent variables in the optimization search. Taking a pair of 2D shapes as inputs, our method optimizes them into gears by locating the rotation center on each shape, minimally modifying each shape to form the gear's boundary, and constructing appropriate teeth for gear meshing. Our optimized gears not only resemble the inputs but can also drive the motion with relatively small torque. We demonstrate our method's usability by generating a rich variety of non‐circular gears from various inputs and 3D printing several of the

The Simplex Algorithm for the Rapid Identification of Operating Conditions During Early Bioprocess Development: Case Studies in FAb' Precipitation and Multimodal Chromatography

This study describes a data-driven algorithm as a rapid alternative to conventional Design of Experiments (DoE) approaches for identifying feasible operating conditions during early bioprocess development. In general, DoE methods involve fitting regression models to experimental data, but if model fitness is inadequate then further experimentation is required to gain more confidence in the location of an optimum. This can be undesirable during very early process development when feedstock is in limited supply and especially if a significant percentage of the tested conditions are ultimately found to be sub-optimal. An alternative approach involves focusing solely upon the feasible regions by using the knowledge gained from each condition to direct the choice of subsequent test locations that lead towards an optimum. To illustrate the principle, this study describes the application of the Simplex algorithm which uses accumulated knowledge from previous test points to direct the choice of successive conditions towards better regions. The method is illustrated by two case studies; a two variable precipitation example investigating how salt concentration and pH affect FAb' recovery from E. coli homogenate and a three-variable chromatography example identifying the optimal pH and concentrations of two salts in an elution buffer used to recover ovine antibody bound to a multimodal cation exchange matrix. Two-level and face-centered central composite regression models were constructed for each study and statistical analysis showed that they provided a poor fit to the data, necessitating additional experimentation to confirm the robust regions of the search space. By comparison, the Simplex algorithm identified a good operating point using 50% and 70% fewer conditions for the precipitation and chromatography studies, respectively. Hence, data-driven approaches have significant potential for early process development when material supply is at a premium

A Comparison of Centering Algorithms in the Astrometry of Cassini Imaging Science Subsystem Images and Anthe’s Astrometric Reduction

In the CAVIAR software package, a standard tool for astrometry of images from the Cassini imaging science subsystem (ISS), Gaussian fitting is used to measure the centre of point-like objects, achieving a typical precision of about 0.2 pixels. In this work, we consider how alternative methods may improve on this. We compare three traditional centroiding methods: two-dimensional Gaussian fitting, median, and modified moment. Results using 56 selected images show that the centroiding precision of the modified moment method is significantly better than the other two methods, with standard deviations for all residuals in sample and line of 0.065 and 0.063 pixels, respectively, representing a factor of over 2 improvement compared to Gaussian fitting. Secondly, a comparison of observations using Cassini ISS images of Anthe is performed. Anthe results show a similar improvement. The modified moment method is then used to reduce all ISS images of Anthe during the period 2008–2017. The observed-minus-calculated residuals relative to the JPL SAT393 ephemeris are calculated. In terms of α × cos(δ) and δ in the Cassini-centred international celestial reference frame, mean values of all residuals are close to 0 km, and their standard deviations are less than 1 km for narrow angle camera images, and about 4 km for wide angle camera images

A Framework for Assessing the Solutions in Chromatographic Process Design and Operation for Large Scale Manufacture

Chromatographic separation of biopharmaceuticals is complex and tools for the prediction of performance and the trade-offs necessary for efficient operation are limited and time-consuming. This complexity is due to the large number of possible column aspect ratios that satisfy process and economic needs. This paper demonstrates a framework for the design and analysis of chromatographic steps. The functionalities are illustrated by application to a Protein A separation where the effects of column diameter, bed length and linear flow rate on cost of goods (COG/g) and productivity (g/h) are investigated so as to identify the optimal operating strategy. Results are presented as a series of ‘windows of operation’ to address key design and operating decisions. The tool allows the designer to customise limiting constraints based on product and process specific knowledge. Results indicate the significant impact on COG/g of column over-sizing and how this can be balanced by increased levels of productivity

A Framework for Assessing the Solutions in Chromatographic Process Design and Operation for Large Scale Manufacture

Chromatographic separation of biopharmaceuticals is complex and tools for the prediction of performance and the trade-offs necessary for efficient operation are limited and time-consuming. This complexity is due to the large number of possible column aspect ratios that satisfy process and economic needs. This paper demonstrates a framework for the design and analysis of chromatographic steps. The functionalities are illustrated by application to a Protein A separation where the effects of column diameter, bed length and linear flow rate on cost of goods (COG/g) and productivity (g/h) are investigated so as to identify the optimal operating strategy. Results are presented as a series of ‘windows of operation’ to address key design and operating decisions. The tool allows the designer to customise limiting constraints based on product and process specific knowledge. Results indicate the significant impact on COG/g of column over-sizing and how this can be balanced by increased levels of productivity

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Recovering Functional Mechanical Assemblies from Raw Scans

This paper presents a method to reconstruct a functional mechanical assembly from raw scans. Given multiple input scans of a mechanical assembly, our method first extracts the functional mechanical parts using a motion-guided, patch-based hierarchical registration and labeling algorithm. The extracted functional parts are then parameterized from the segments and their internal mechanical relations are encoded by a graph. We use a joint optimization to solve for the best geometry, placement, and orientation of each part, to obtain a final workable mechanical assembly. We demonstrated our algorithm on various types of mechanical assemblies with diverse settings and validated our output using physical fabrication

Publisher Correction: Liquid phase blending of metal-organic frameworks

The original version of this Article contained an error in Figure 1b, where the blue ‘(ZIF-4-Zn)0.5 (ZIF-62)0.5 blend’ data curve was omitted from the enthalpy response plot. This has now been corrected in both the PDF and HTML versions of the Article