Design automation of microfluidic droplet sorting platforms

Both basic research and biological design require high throughput screening to parse through the massive amounts of variants generated in experiments. However, the cost and expertise needed for use of such technology limit accessibility. Simple and reproducible designs of a sorting platform would reduce the barrier for implementation of affordable bench-top screening platforms. Droplet microfluidics present a promising approach for automating biology, reducing reaction volumes to picoliter droplets and allowing for deterministic manipulation of samples. Droplet microfluidics have been used extensively for high throughput screening and directed evolution, yet limitations in fabrication have prevented the characterization needed for a design tool and subsequent widespread adoption. Here, we present a finite element analysis (FEA) model-based design framework for dielectrophoretic droplet microfluidic sorters and its preliminary experimental validation. This framework extends previous work from our group creating microfluidic designs tools, increasing their usability in the lab

Metadynamics for Training Neural Network Model Chemistries: a Competitive Assessment

Neural network (NN) model chemistries (MCs) promise to facilitate the accurate exploration of chemical space and simulation of large reactive systems. One important path to improving these models is to add layers of physical detail, especially long-range forces. At short range, however, these models are data driven and data limited. Little is systematically known about how data should be sampled, and `test data' chosen randomly from some sampling techniques can provide poor information about generality. If the sampling method is narrow `test error' can appear encouragingly tiny while the model fails catastrophically elsewhere. In this manuscript we competitively evaluate two common sampling methods: molecular dynamics (MD), normal-mode sampling (NMS) and one uncommon alternative, Metadynamics (MetaMD), for preparing training geometries. We show that MD is an inefficient sampling method in the sense that additional samples do not improve generality. We also show MetaMD is easily implemented in any NNMC software package with cost that scales linearly with the number of atoms in a sample molecule. MetaMD is a black-box way to ensure samples always reach out to new regions of chemical space, while remaining relevant to chemistry near $k_bT$. It is one cheap tool to address the issue of generalization

Measuring between-farm variation in Culicoides (Diptera: Ceratopogonidae) density, the vectors of bluetongue virus

Culicoides midges are ubiquitous on farms in the UK, but little research has explored their abundance, an important determinant of disease risk. Models to explain and predict variation in their abundance are needed for effective targeting of control methods against bluetongue (BT) and other Culicoides-borne diseases. Midge abundances were estimated using light traps on 35 farms in north Wales. Culicoides catches were combined with remotely-sensed ecological correlates, and on-farm host and environmental data, within a general linear model. Local-scale variation in abundance exhibited an almost 500-fold difference between farms in maximum Obsoletus Group catches. The variance explained was consistently high for the BT vector species (81% for Obsoletus Group; 80% for Pulicaris Group, 73% for C. pulicaris, 74% for C. punctatus). The abundance of all vector species increased with the number of sheep on farms, but this relationship was missing from any of the non-vector models. At a large spatial scale, there is significant variation in Culicoides Obsoletus Group abundance, which undermines attempts to record their nationwide distribution in larger scale models. A prior survey should be undertaken for farms with high Culicoides catches within a sampling area and stability in catch size should be checked between seasons and years. (Résumé d'auteur

Evaluation of the Researcher Development Program (RDP) of the Primary Health Care Research, Evaluation and Development (PHCRED) Strategy: The Fellows’ perspective

This study examines the extent to which the Researcher Development Program (RDP) has impacted on knowledge, attitudes and practice in relation to research and to develop a profile of RDP participants. RDP fellows (appointed between 2005 and 2009) were invited to complete an on-line survey which looked at issues such as previous research experience, research training and activities during the RDP and time allocated to RDP

The limits of simulating gas giant entry at true gas composition and true flight velocities in an expansion tube

Due to high entry velocities when entering gas giant planets in the solar system (20-50 km/s), simulating gas giant entry in ground testing facilities is a complex problem. This paper details an investigation to simulate radiating Uranus entry flow conditions in a superorbital expansion tube facility. Theoretical calculations show that the X2 expansion tube at the University of Queensland can simulate Uranus entry at 20 km/s. This paper provides the justification for an experimental campaign that has been partially completed, but is still being analysed

Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

Development of patient information leaflets for fixed, removable, and functional appliances for Arabic-speaking orthodontic patients

Objective: To develop Orthodontic Patient Information Leaflets (PILs) in Arabic. Material &amp; method: This study included five phases starting with Arabic translation of existing British Orthodontic Society leaflets; initial face validation with three orthodontists; content validation with ten orthodontists; final face validation with ten orthodontists, five postgraduate students, and ten patients; and re-translation to English prior to comparing the new documents with the original PILs to verify that all the necessary information were included. The content validity index (CVI) assessed item level (I-CVI) and scale level (S-CVI). Results: The three Arabic PILs were face validated with inclusion of mini-screws, rapid maxillary expansion, and interproximal reduction. Content validity was perfect with no item I-CVI < 0.80. The S-CVI/Ave for PIL Fixed Appliances = 0.98, PIL Removable Appliances = 0.98 and PIL Functional Appliances = 0.97. In the final face validation, the three leaflets received 100% agreement from all observers for consistency of leaflet format and style, clarity, readability and use of adequate phrases. Finally, the leaflets were re-translated and the information was checked by native English speakers to ensure the completeness of information. There were no discrepancies and face validity was excellent. Conclusion: Valid PILs for Arabic-speaking patients undergoing orthodontic treatment with fixed, removable, and functional appliances have been developed

Intraspecific variability modulates interspecific variability in animal organismal stoichiometry.

Interspecific differences in organismal stoichiometry (OS) have been documented in a wide range of animal taxa and are of significant interest for understanding evolutionary patterns in OS. In contrast, intraspecific variation in animal OS has generally been treated as analytical noise or random variation, even though available data suggest intraspecific variability in OS is widespread. Here, we assess how intraspecific variation in OS affects inferences about interspecific OS differences using two co-occurring Neotropical fishes: Poecilia reticulata and Rivulus hartii. A wide range of OS has been observed within both species and has been attributed to environmental differences among stream systems. We assess the contributions of species identity, stream system, and the interactions between stream and species to variability in N:P, C:P, and C:N. Because predation pressure can impact the foraging ecology and life-history traits of fishes, we compare predictors of OS between communities that include predators, and communities where predators are absent. We find that species identity is the strongest predictor of N:P, while stream or the interaction of stream and species contribute more to the overall variation in C:P and C:N. Interspecific differences in N:P, C:P, and C:N are therefore not consistent among streams. The relative contribution of stream or species to OS qualitatively changes between the two predation communities, but these differences do not have appreciable effects in interspecific patterns. We conclude that although species identity is a significant predictor of OS, intraspecific OS is sometimes sufficient to overwhelm or obfuscate interspecific differences in OS