The Foundry: the DNA synthesis and construction Foundry at Imperial College.

The establishment of a DNA synthesis and construction foundry at Imperial College in London heralds a new chapter in the development of synthetic biology to meet new global challenges. The Foundry employs the latest technology to make the process of engineering biology easier, faster and scalable. The integration of advanced software, automation and analytics allows the rapid design, build and testing of engineered organisms

Registry of BioBricks Models using CellML

A poster presented at BioSysBio 2007 and at SB3.0One of the main goals in Synthetic Biology is to assess the feasibility of building novel biological systems from interchangeable and standardized parts. In order to collect and share parts, a Registry of standardized DNA BioBricks[1] has been established at MIT. BioBricks can be assembled to form devices and systems to operate in living cells. Design of reliable devices and systems would benefit from accurate models of system function. To predict the function of systems built from many parts, we need to have accurate models for the parts and mechanisms to easily compose those part models into a system model. Therefore, in parallel to increasing the number of parts available and characterising them experimentally, a logical extension to the Registry would be to build a Registry of BioBrick models to complement the physical parts

Layering genetic circuits to build a single cell, bacterial half adder

Background: Gene regulation in biological systems is impacted by the cellular and genetic context-dependent effects of the biological parts which comprise the circuit. Here, we have sought to elucidate the limitations of engineering biology from an architectural point of view, with the aim of compiling a set of engineering solutions for overcoming failure modes during the development of complex, synthetic genetic circuits. Results: Using a synthetic biology approach that is supported by computational modelling and rigorous characterisation, AND, OR and NOT biological logic gates were layered in both parallel and serial arrangements to generate a repertoire of Boolean operations that include NIMPLY, XOR, half adder and half subtractor logics in a single cell. Subsequent evaluation of these near-digital biological systems revealed critical design pitfalls that triggered genetic context-dependent effects, including 5′ UTR interferences and uncontrolled switch-on behaviour of the supercoiled σ54 promoter. In particular, the presence of seven consecutive hairpins immediately downstream of the promoter transcription start site severely impeded gene expression. Conclusions: As synthetic biology moves forward with greater focus on scaling the complexity of engineered genetic circuits, studies which thoroughly evaluate failure modes and engineering solutions will serve as important references for future design and development of synthetic biological systems. This work describes a representative case study for the debugging of genetic context-dependent effects through principles elucidated herein, thereby providing a rational design framework to integrate multiple genetic circuits in a single prokaryotic cell.Published versio

A Forward-Design Approach to Increase the Production of Poly-3-Hydroxybutyrate in Genetically Engineered Escherichia coli

Biopolymers, such as poly-3-hydroxybutyrate (P(3HB)) are produced as a carbon store in an array of organisms and exhibit characteristics which are similar to oil-derived plastics, yet have the added advantages of biodegradability and biocompatibility. Despite these advantages, P(3HB) production is currently more expensive than the production of oil-derived plastics, and therefore, more efficient P(3HB) production processes would be desirable. In this study, we describe the model-guided design and experimental validation of several engineered P(3HB) producing operons. In particular, we describe the characterization of a hybrid phaCAB operon that consists of a dual promoter (native and J23104) and RBS (native and B0034) design. P(3HB) production at 24 h was around six-fold higher in hybrid phaCAB engineered Escherichia coli in comparison to E. coli engineered with the native phaCAB operon from Ralstonia eutropha H16. Additionally, we describe the utilization of non-recyclable waste as a low-cost carbon source for the production of P(3HB)

Statistical Properties of the Interbeat Interval Cascade in Human Subjects

Statistical properties of interbeat intervals cascade are evaluated by considering the joint probability distribution $P(\Delta x_2,\tau_2;\Delta x_1,\tau_1)$ for two interbeat increments $\Delta x_1$ and $\Delta x_2$ of different time scales $\tau_1$ and $\tau_2$. We present evidence that the conditional probability distribution $P(\Delta x_2,\tau_2|\Delta x_1,\tau_1)$ may obey a Chapman-Kolmogorov equation. The corresponding Kramers-Moyal (KM) coefficients are evaluated. It is shown that while the first and second KM coefficients, i.e., the drift and diffusion coefficients, take on well-defined and significant values, the higher-order coefficients in the KM expansion are very small. As a result, the joint probability distributions of the increments in the interbeat intervals obey a Fokker-Planck equation. The method provides a novel technique for distinguishing the two classes of subjects in terms of the drift and diffusion coefficients, which behave differently for two classes of the subjects, namely, healthy subjects and those with congestive heart failure.Comment: 5 pages, 6 figure

Solution-processed bilayer photovoltaic devices with nematic liquid crystals

The cross-linking of polymerisable liquid crystalline semiconductors is a promising approach to solution-processable, multilayer, organic photovoltaics. Here we demonstrate an organic bilayer photovoltaic with an insoluble electron-donating layer formed by cross-linking a nematic reactive mesogen. We investigate a range of perylene diimide (PDI) materials, some of which are liquid crystalline, as the overlying electron acceptor layer. We find that carrier mobility of the acceptor materials is enhanced by liquid crystallinity and that mobility limits the performance of photovoltaic devices. © 2013 © 2013 Taylor & Francis

Novel liquid crystalline organic semiconducting oligomers incorporating N-heterocyclic carbazole moieties for fluorescent OLEDs

A novel class of nematic liquid crystalline organic semiconducting oligomers incorporating N-heterocyclic carbazole moieties has been synthesised using simple and highly efficient reaction pathways. The electroluminescent colour of these novel oligomers can be varied in a controlled manner by molecular design. The values of the ionization potential and the electron affinity of these electroluminescent oligomers can also be matched by structural design to the HOMO energy level of the electron-blocking layer and the LUMO energy level of electron-transporting layer in the OLEDs to create low charge-injection barriers for electrons and holes, respectively leading to electroluminescence with an efficacy up to 4.1 cd A-1

Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA

BACKGROUND: Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. METHOD: Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. RESULTS: A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. CONCLUSIONS: ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting hospitals to effectively manage time and resources in clinical pathway

Implications of flexible spacer rotational processes on the liquid crystal behavior of 4,5-dihydroisoxazole benzoate dimers

The synthesis of some novel non-symmetric liquid crystal dimers, {3-[4-(octyloxyphenyl)]-4,5-dihydroisoxazol-5-yl}alkyl 4-(decyloxy)benzoates (5a–d) and 4-{3-[4-(octyloxyphenyl)]-4,5-dihydroisoxazol-5-yl}alkyl 4-{[6-(octyloxy)naphthalen-2-yl]ethynyl}benzoate (9a–d), are reported. The liquid-crystalline properties, theoretical calculations based on the conformational aspects of the flexible alkyl spacer and X-ray experiments are discussed. The syntheses of the key intermediates, 2-{3-[4-(octyloxy)phenyl]-4,5-dihydroisoxazol-5-yl}alkanol (3a–d), presenting the flexible alkyl spacer were achieved through [3+2] cycloaddition reactions between nitrile oxides, which were generated in situ by oxidation of the respective aromatic oximes, and dipolarophile alkenols (CH2[double bond, length as m-dash]CH(CH2)nOH, n = 1, 2, 3, and 4). The benzoates 5a–d were synthesized through esterification of 3a–d and p-n-decyloxybenzoic acid (4). The esters 9a–d were synthesized through derivatization of isoxazolines 3a–d into 4-{3-[4-(octyloxyphenyl)]-4,5-dihydroisoxazol-5-yl}alkyl 4-bromobenzoate (7a–d) followed by a Sonogashira reaction with 2-ethynyl-6-octyloxynaphthalene (8). 5a and 5b showed a monotropic smectic C phase. 9a/c displayed a enantiotropic nematic (N) mesophase, whereas 9b/d showed a monotropic nematic mesophase. No mesophase was observed for 7a–d. An odd–even effect was observed for 5a–d and 9a–d associated with the crystal to isotropic phase transition and crystal to nematic phase, respectively, as the length of the spacer was increased from 1 to 4 carbon atoms. The transitional properties were higher for odd-numbered members (n = 1 and 3) for all of the series studied. The X-ray data of compounds 5a and 5b are in agreement with polarizing optical microscopy observations with the assignment of an SmC mesophase. Density functional theory calculations using the B3LYP hybrid functional with the level 6-311G(d,p) basis set were performed for molecules 5a–d to correlate the conformation of the flexible spacer and the transitional properties. The conformational analysis showed that the most stable conformation for 5a–d is one where all of the carbon atoms of the flexible spacer are orientated at 180° (antiperiplanar orientation) except for 5a because the spacer is too short. The odd-numbered members have a more bent shape and are less elongated molecules than the even-numbered members. Thus, mesomorphic behavior is dictated by the conformational constraint imposed by the flexible spacer on the mesogenic groups

American Society for Echocardiography Software Suite for Verification and

The imminent balloting of the draft DICOM 3.0 module on ultrasound represents a major step forward in the progress of digital storage formats for echocardiography. In this paper, we discuss a software suite soon to be released into the public domain for reading, parsing and verifying DICOM 3.0 ultrasonic objects. The software is designed to allow the user to verify that a Jle consisting of digital ultrasound data, claiming DlCOM 3.0 conformance, does in fact adhere to the standard. A graphical user-interface for the software suite is also provided, allowing the playback of cin& mode images in real-time on standard computer hardware, and across a TCP/IP network