A sequential Monte Carlo framework for adaptive Bayesian model discrimination designs using mutual information

In this paper we present a unified sequential Monte Carlo (SMC) framework for performing sequential experimental design for discriminating between a set of models. The model discrimination utility that we advocate is fully Bayesian and based upon the mutual information. SMC provides a convenient way to estimate the mutual information. Our experience suggests that the approach works well on either a set of discrete or continuous models and outperforms other model discrimination approaches.

Rodent Scope: A User-Configurable Digital Wireless Telemetry System for Freely Behaving Animals

This paper describes the design and implementation of a wireless neural telemetry system that enables new experimental paradigms, such as neural recordings during rodent navigation in large outdoor environments. RoSco, short for Rodent Scope, is a small lightweight user-configurable module suitable for digital wireless recording from freely behaving small animals. Due to the digital transmission technology, RoSco has advantages over most other wireless modules of noise immunity and online user-configurable settings. RoSco digitally transmits entire neural waveforms for 14 of 16 channels at 20 kHz with 8-bit encoding which are streamed to the PC as standard USB audio packets. Up to 31 RoSco wireless modules can coexist in the same environment on non-overlapping independent channels. The design has spatial diversity reception via two antennas, which makes wireless communication resilient to fading and obstacles. In comparison with most existing wireless systems, this system has online user-selectable independent gain control of each channel in 8 factors from 500 to 32,000 times, two selectable ground references from a subset of channels, selectable channel grounding to disable noisy electrodes, and selectable bandwidth suitable for action potentials (300 Hz–3 kHz) and low frequency field potentials (4 Hz–3 kHz). Indoor and outdoor recordings taken from freely behaving rodents are shown to be comparable to a commercial wired system in sorting for neural populations. The module has low input referred noise, battery life of 1.5 hours and transmission losses of 0.1% up to a range of 10 m.

Open Access and Research Conference 2013: Discovery, Impact and Innovation (Event report)

Event report on the Open Access and Research 2013 conference which focused on recent developments and the strategic advantages they bring to the research sector.

Bits and bumps : gender, comedy and the body.

This paper examines some of the ways in which gender impacts upon contemporary physical comedy. According to the late Christopher Hitchens (2007, 2), women are too concerned with the seriousness of their reproductive responsibility to make good comedy; as slapstick film director Mack Sennett (in Dale, 2000, 92) maintained: “No joke about a mother ever got a laugh”. This article proposes a method of understanding what happens to the body in the comic moment, then draws upon Kristeva’s notion of abjection to help understand how gender inflects the creation of physical comedy.

Entrenchment of GIS technology for enterprise solutions in Maryland's state and local government

Beginning in 1974, the State of Maryland created spatial databases under the MAGI (Maryland's Automated Geographic Information) system. Since that early GIS, other state and local agencies have begun GISs covering a range of applications from critical lands inventories to cadastral mapping. In 1992, state agencies, local agencies, universities, and businesses began a series of GIS coordination activities, resulting in the formation of the Maryland Local Geographic Information Committee and the Maryland State Government Geographic Information Coordinating Committee. GIS activities and system installations can be found in 22 counties plus Baltimore City, and most state agencies. Maryland's decision makers rely on a variety of GIS reports and products to conduct business and to communicate complex issues more effectively. This paper presents the status of Maryland's GIS applications for local and state decision making.

The ‘Indigenous Australian’ theme in the Australian Curriculum English : necessary or not?

On Friday 10 January 2014 Education Minister Christopher Pyne formally announced a review of the inaugural Australian curriculum. In his three and half minute televised justification, Pyne (2014) identified a number of criticisms of the national curriculum document, including the ‘necessity to have themes’ of ‘Australia’s place in Asia, Indigenous Australia and sustainability’. It is the second of these themes that we consider as ALEA’s Hot Topic for March 2014. We respond to Pyne’s momentary musing of the necessity of the ‘Indigenous Australian’ theme in the Australian Curriculum with a particular focus on the discipline of English. In the nomenclature of the Australian Curriculum, Assessment and Reporting Authority’s Australian Curriculum (ACARA, 2013), we are of course referring to the ‘cross curriculum priority’ of ‘Aboriginal and Torres Strait Islander histories and cultures’.

Macromolecular engineering via RAFT chemistry : from sequential to modular design

Sequential Design Molecular Weight Range Functional Monomers: Possibilities, Limits, and Challenges Block Copolymers: Combinations, Block Lengths, and Purities Modular Design End-Group Chemistry Ligation Protocols Conclusions

Technoeconomic analysis of renewable aviation fuel from microalgae,Pongamia pinnata, and sugarcane

Technoeconomic analysis of renewable aviatin fuels has not been widely considered, despite the increasing global attention that the field has received. We present three process models for production of aviation fuel from microalgae, Pongamia pinnata, and sugarcane molasses. The models and assumptions have been deposited on a wiki (http://qsafi.aibn.uq.edu.au) and are open and accessible to the community. Based on currently available long-term reputable technological data, this analysis indicates that the biorefinieries processing the microalgae, Pongamia seeds, and sugarcane feedstocks would be competitive with crude oil at $1343, $374, and $301/bbl, respectively. Sensitivity analyses of the major economic drivers suggest technological and market developments that would bring the corresponding figures down to $385, $255, and $168/bbl. The dynamic nature of the freely accessible models will allow the community to track progress toward economic competitiveness of aviation fuels from these renewable feedstocks.

Port-Hamiltonian control of fully actuated underwater vehicles

This chapter presents a novel control strategy for trajectory tracking of underwater marine vehicles that are designed using port-Hamiltonian theory. A model for neutrally buoyant underwater vehicles is formulated as a PHS, and then the tracking controller is designed for the horizontal plane-surge, sway and yaw. The control design is done by formulating the error dynamics as a set-point regulation port-Hamiltonian control problem. The control design is formulated in two steps. In the first step, a static-feedback tracking controller is designed, and the second step integral action is added. The global asymptotic stability of the closed loop system is proved and the performance of the controller is illustrated using a model of an open-frame offshore underwater vehicle.

Mechanism‐based selection of a potent kallikrein‐related peptidase 7 inhibitor from a versatile library based on the sunflower trypsin inhibitor SFTI‐1

Potent and specific enzyme inhibition is a key goal in the development of therapeutic inhibitors targeting proteolytic activity. The backbone-cyclized peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be engineered to achieve both these aims. SFTI-1's mechanism of inhibition is unusual in that it shows fast-on/slow-off kinetics driven by cleavage and religation of a scissile bond. This phenomenon was used to select a nanomolar inhibitor of kallikrein-related peptidase 7 (KLK7) from a versatile library of SFTI variants with diversity tailored to exploit distinctive surfaces present in the active site of serine proteases. Inhibitor selection was achieved through the use of size exclusion chromatography to separate protease/inhibitor complexes from unbound inhibitors followed by inhibitor identification according to molecular mass ascertained by mass spectrometry. This approach identified a single dominant inhibitor species with molecular weight of 1562.4 Da, which is consistent with the SFTI variant SFTI-WCTF. Once synthesized individually this inhibitor showed an IC50 of 173.9 ± 7.6 nM against chromogenic substrates and could block protein proteolysis. Molecular modeling analysis suggested that selection of SFTI-WCTF was driven by specific aromatic interactions and stabilized by an enhanced internal hydrogen bonding network. This approach provides a robust and rapid route to inhibitor selection and design.

Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Energy-based motion control of marine vehicles using interconnection and damping assignment passivity-based control : a survey

This paper reviews some recent results in motion control of marine vehicles using a technique called Interconnection and Damping Assignment Passivity-based Control (IDA-PBC). This approach to motion control exploits the fact that vehicle dynamics can be described in terms of energy storage, distribution, and dissipation, and that the stable equilibrium points of mechanical systems are those at which the potential energy attains a minima. The control forces are used to transform the closed-loop dynamics into a port-controlled Hamiltonian system with dissipation. This is achieved by shaping the energy-storing characteristics of the system, modifying its interconnection structure (how the energy is distributed), and injecting damping. The end result is that the closed-loop system presents a stable equilibrium (hopefully global) at the desired operating point. By forcing the closed-loop dynamics into a Hamiltonian form, the resulting total energy function of the system serves as a Lyapunov function that can be used to demonstrate stability. We consider the tracking and regulation of fully actuated unmanned underwater vehicles, its extension to under-actuated slender vehicles, and also manifold regulation of under-actuated surface vessels. The paper is concluded with an outlook on future research.

Evaluation of BMP-2 gene-activated muscle grafts for cranial defect repair

Large, osseous, segmental defects heal poorly. Muscle has a propensity to form bone when exposed to an osteogenic stimulus such as that provided by transfer and expression of cDNA encoding bone morphogenetic protein-2 (BMP-2). The present study evaluated the ability of genetically modified, autologous muscle to heal large cranial defects in rats. Autologous grafts (8 mm � 2 mm) were punched from the biceps femoris muscle and transduced intraoperatively with recombinant adenovirus vector containing human BMP-2 or green fluorescent protein cDNA. While the muscle biopsies were incubating with the vector, a central parietal 8 mm defect was surgically created in the calvarium of the same animal. The gene-activated muscle graft was then implanted into the cranial defect. After 8 weeks, crania were examined radiographically, histologically, and by micro-computed tomography and dual energy X-ray absorptiometry. Although none of the defects were completely healed in this time, muscle grafts expressing BMP-2 deposited more than twice as much new bone as controls. Histology confirmed the anatomical integrity of the newly formed bone, which was comparable in thickness and mineral density to the original cranial bone. This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone. � 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1095–1102, 2012

Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin : evaluation in a rat segmental defect model

Objective To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 μg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.