Beyond the Genome: genomics research ten years after the human genome sequence

A report on the meeting 'Beyond the Genome', Boston, USA, 11-13 October 2010

Geocellular railway drainage systems: physical and numerical modelling

The importance of resilient railway infrastructure is paramount when considering the increased likelihood of extreme weather and flash flood events in coming years. One of the main causes of instability of railway tracks is excess water in the trackbed, particularly when it is at or above the interface of the ballast and subgrade. Conventional drainage systems are susceptible to clogging and deterioration. Resilient track drainage systems should therefore have sufficient capacity to allow water to dissipate quickly, but they should also be designed to ensure long-term operation with minimal or easily performed maintenance. This paper presents results from an investigation of a potential new railway drainage system using geocellular components. In the paper, the development of a large scale physical model is described which represents a full scale unit cell of a sleeper-to-sleeper track substructure. The physical model includes ballast and subgrade layers, under-track and lateral drainage systems, rainfall simulation, and instrumentation. Results demonstrate the relative hydraulic response of the drainage system with and without the geocellular components. The paper also describes the development of a numerical model of the track subgrade and drainage system, which was first calibrated and verified using experimental data from the physical model, then extended to study the effect of certain parameters on the hydraulic response of the railway track. Results indicate that the under-track geocellular drainage system offers potential benefits in terms of maintaining a lower water table level within the subgrade as well as in aiding the migration of fines out of the ballast

Elastic-brittle-plastic behaviour of shale reservoirs and its implications on fracture permeability variation: an analytical approach

Shale gas has recently gained significant attention as one of the most important unconventional gas resources. Shales are fine-grained rocks formed from the compaction of silt and clay sized particles and are characterised by their fissured texture and very low permeability. Gas exists in an adsorbed state on the surface of the organic content of the rock and is freely available within the primary and secondary porosity. Geomechanical studies have indicated that, depending on the clay content of the rock, shales can exhibit a brittle failure mechanism. Brittle failure leads to the reduced strength of the plastic zone around a wellbore, which can potentially result in wellbore instability problems. Desorption of gas during production can cause shrinkage of the organic content of the rock. This becomes more important when considering the use of shales for CO2 sequestration purposes, where CO2 adsorption-induced swelling can play an important role. These phenomena lead to changes in the stress state within the rock mass, which then influence the permeability of the reservoir. Thus, rigorous simulation of material failure within coupled hydro-mechanical analyses is needed to achieve a more systematic and accurate representation of the wellbore. Despite numerous modelling efforts related to permeability, an adequate representation of the geomechanical behaviour of shale and its impact on permeability and gas production has not been achieved. In order to achieve this aim, novel coupled poro-elastoplastic analytical solutions are developed in this paper which take into account the sorption-induced swelling and the brittle failure mechanism. These models employ linear elasticity and a Mohr–Coulomb failure criterion in a plane-strain condition with boundary conditions corresponding to both open-hole and cased-hole completions. The post-failure brittle behaviour of the rock is defined using residual strength parameters and a non-associated flow rule. Swelling and shrinkage are considered to be elastic and are defined using a Langmuir-like curve, which is directly related to the reservoir pressure. The models are used to evaluate the stress distribution and the induced change in permeability within a reservoir. Results show that development of a plastic zone near the wellbore can significantly impact fracture permeability and gas production. The capabilities and limitations of the models are discussed and potential future developments related to modelling of permeability in brittle shales under elastoplastic deformations are identified

Implicit Geometry and Interaction Embeddings Improve Few-Shot Molecular Property Prediction

Few-shot learning is a promising approach to molecular property prediction as supervised data is often very limited. However, many important molecular properties depend on complex molecular characteristics -- such as the various 3D geometries a molecule may adopt or the types of chemical interactions it can form -- that are not explicitly encoded in the feature space and must be approximated from low amounts of data. Learning these characteristics can be difficult, especially for few-shot learning algorithms that are designed for fast adaptation to new tasks. In this work, we develop molecular embeddings that encode complex molecular characteristics to improve the performance of few-shot molecular property prediction. Our approach leverages large amounts of synthetic data, namely the results of molecular docking calculations, and a multi-task learning paradigm to structure the embedding space. On multiple molecular property prediction benchmarks, training from the embedding space substantially improves Multi-Task, MAML, and Prototypical Network few-shot learning performance. Our code is available at https://github.com/cfifty/IGNITE

Recombinant bromelain production in Escherichia coli: process optimization in shake flask culture by response surface methodology

Bromelain, a cysteine protease with various therapeutic and industrial applications, was expressed in Escherichia coli, BL21-AI clone, under different cultivation conditions (post-induction temperature, L-arabinose concentration and post-induction period). The optimized conditions by response surface methodology using face centered central composite design were 0.2% (w/v) L-arabinose, 8 hr and 25°C. The analysis of variance coupled with larger value of R2 (0.989) showed that the quadratic model used for the prediction was highly significant (p < 0.05). Under the optimized conditions, the model produced bromelain activity of 9.2 U/mg while validation experiments gave bromelain activity of 9.6 ± 0.02 U/mg at 0.15% (w/v) L-arabinose, 8 hr and 27°C. This study had innovatively developed cultivation conditions for better production of recombinant bromelain in shake flask culture

Heterologous expression of Bromelain in Escherichia coli

In spite of the fact that commercial bromelain supplements are available in the market, to date, none of them are produced and formulated from recombinant forms. They are extracted and purified (often partially) from the stem and fruit of pineapple. This makes the production of bromelain very difficult, less reliable, often contaminated and expensive. In this study, a recombinant bromelain from BL21 A clone was expressed as soluble and insoluble active enzyme. Maximum activity was observed at 4-hour post induction with 0.2% L-arabinose and over 60% of the enzyme was found to be expressed in soluble form. The enzyme fractions were purified using Nickel-NTA spin column. Purification fold and % yield of the purified lysate were found to be 35 and 75% respectively. SDS-PAGE results showed that the purified bromelain exhibited a single band with molecular weight of about 45kDa

Risk indicators for dental caries using the International Caries Detection and Assessment System (ICDAS)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73802/1/j.1600-0528.2006.00369.x.pd

Evaluation of a brief tailored motivational intervention to prevent early childhood caries

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87108/1/j.1600-0528.2011.00613.x.pd

Analysis of particle contact using frustrated total internal reflection

Within the field of soil mechanics a continuum assumption is generally adopted in order to avoid the complications of modelling micro-mechanical behaviour. However, certain constitutive behaviour can only be explained by investigating particle level interactions. Numerical investigations, such as those using the Discrete Element Method (DEM) to model soil particles as clusters of spheres, have delivered a greater understanding of the micro-mechanical behaviour. One of the limiting factors in current DEM approaches is modelling of the particle–particle or particle–surface contact behaviour. Hence, an experimental methodology has been developed and used to study particle–surface contact behaviour. The experimental methodology involves loading particles onto a piece of sapphire glass and observing the resulting contact area. In order to distinguish between the contacted area and the rest of the particle, the principle of frustrated total internal reflection and evanescent waves was used which results in only objects in very close proximity to the glass being illuminated and visible. This methodology hence allows the number of contacts and the area of those contacts to be tracked during loading and over time. This paper presents the validation of the experimental methodology by comparing the observed contact behaviour of plastic beads against Hertzian contact theory. In addition, the results from tests on sand samples are presented which show a density of 0.40 and 0.80 contacts per D250 for coarse and fine grained sand respectively at an isotropic stress state which subsequently increases to 0.90 to 1.00 contacts per D250 at peak deviatoric stress. It was also found that the fine sand particle contacts carried a maximum load of approximately 0.27 N per contact whereas the coarser sand was able to carry substantially higher loads