Development and evaluation of an automated annotation pipeline and cDNA annotation system

Manual curation has long been held to be the gold standard for functional annotation of DNA sequence. Our experience with the annotation of more than 20,000 full-length cDNA sequences revealed problems with this approach, including inaccurate and inconsistent assignment of gene names, as well as many good assignments that were difficult to reproduce using only computational methods. For the FANTOM2 annotation of more than 60,000 cDNA clones, we developed a number of methods and tools to circumvent some of these problems, including an automated annotation pipeline that provides high-quality preliminary annotation for each sequence by introducing an uninformative filter that eliminates uninformative annotations, controlled vocabularies to accurately reflect both the functional assignments and the evidence supporting them, and a highly refined, Web-based manual annotation tool that allows users to view a wide array of sequence analyses and to assign gene names and putative functions using a consistent nomenclature. The ultimate utility of our approach is reflected in the low rate of reassignment of automated assignments by manual curation. Based on these results, we propose a new standard for large-scale annotation, in which the initial automated annotations are manually investigated and then computational methods are iteratively modified and improved based on the results of manual curation.

Automated layout of small lattices using layer diagrams

Good quality concept lattice drawings are required to effectively communicate logical structure in Formal Concept Analysis. Data analysis frameworks such as the Toscana System use manually arranged concept lattices to avoid the problem of automatically producing high quality lattices. This limits Toscana systems to a finite number of concept lattices that have been prepared a priori. To extend the use of formal concept analysis, automated techniques are required that can produce high quality concept lattice drawings on demand. This paper proposes and evaluates an adaption of layer diagrams to improve automated lattice drawing. © Springer-Verlag Berlin Heidelberg 2006.

Towards rope shovel automation operation information system

The road to electric rope shovel automation is marked with technological innovations that include an increase in operational information available to mining operations. The CRCMining Shovel Operator Information System not only collects machine operational data but also provides the operator with knowledge-of-performance and influences his/her performance to achieve higher productivity with reduced machine duty. The operator’s behaviour is one of the most important aspects of the man-machine interaction to be considered before semi- or fully-automated shovel systems can be realised. This paper presents the results of the rope shovel studies conducted by CRCMining between 2002 and 2004, provides information on current research to improve shovel performance and briefly discusses the implications of human-system interactions on future designs of autonomous machines.

An automated failure mode and effect analysis based on high-level design specificication with behavior trees

Formal methods have significant benefits for developing safety critical systems, in that they allow for correctness proofs, model checking safety and liveness properties, deadlock checking, etc. However, formal methods do not scale very well and demand specialist skills, when developing real-world systems. For these reasons, development and analysis of large-scale safety critical systems will require effective integration of formal and informal methods. In this paper, we use such an integrative approach to automate Failure Modes and Effects Analysis (FMEA), a widely used system safety analysis technique, using a high-level graphical modelling notation (Behavior Trees) and model checking. We inject component failure modes into the Behavior Trees and translate the resulting Behavior Trees to SAL code. This enables us to model check if the system in the presence of these faults satisfies its safety properties, specified by temporal logic formulas. The benefit of this process is tool support that automates the tedious and error-prone aspects of FMEA.

The threat of predictable and unpredictable pain: Differential effects on central nervous system processing?

Central nervous system performance is disrupted by pain and by the threat of pain. It is not known whether disruption caused by the threat of pain is dependent on the likelihood of pain occurring. We hypothesised that when a painful stimulus is possible but unpredictable central nervous system performance is reduced, but when the pain is predictable and unavoidable it is not. Sixteen healthy subjects performed a reaction time task during predictable and unpredictable conditions (100% and 50% probability of pain, respectively). Group data showed increased reaction time with the threat of pain by 50 ms (95% Cl 16 to 83 ms) for the predictable condition and 46 ms (95% CI 12 to 80 ms) for the unpredictable condition (p < 0.01 for both), but there was no difference between predictable and unpredictable conditions (p = 0.41). However, individual data showed that there was a differential effect in 75% of subjects (p < 0.05 for all) and that there was a greater effect of predictable pain for some subjects and a greater effect of unpredictable pain for others. Reaction time was related to reported anxiety (r = 0.49, p = 0.02 for both conditions). The predictability of a painful stimulus may have a differential effect on central nervous system performance within individuals, but anxiety about the impending pain appears to be important in determining this effect.

Quantum interference effects in a cavity QED system

We consider the effect of quantum interference on population distribution and photon statistics of a cavity field interacting with dressed states of a strongly driven three-level atom. We analyse three coupling configurations of the cavity field to the driven atom, with the cavity frequency tuned to the outer Rabi sideband, the inner Rabi sideband and the central frequency of the 'singly dressed' three-level atom. The quantum doubly dressed states for each configuration are identified and the population distribution and photon statistics are interpreted in terms of transitions among these dressed states and their populations. We find that the population distribution depends strongly on quantum interference and the cavity damping. For the cavity field tuned to the outer or inner Rabi sidebands the cavity damping induces transitions between the dressed states which are forbidden for the ordinary spontaneous emission. Moreover, we find that in the case of the cavity field coupled to the inner Rabi sideband the population distribution is almost Poissonian with a large average number of photons that can be controlled by quantum interference. This system can be considered as a one-atom dressed-state laser with controlled intensity.

Spin squeezing as a measure of entanglement in a two-qubit system

We show that the two definitions of spin squeezing extensively used in the literature [M. Kitagawa and M. Ueda, Phys. Rev. A 47, 5138 (1993) and D.J. Wineland , Phys. Rev. A 50, 67 (1994)] give different predictions of entanglement in the two-atom Dicke system. We analyze differences between the definitions and show that the spin squeezing parameter of Kitagawa and Ueda is a better measure of entanglement than the commonly used spectroscopic spin squeezing parameter. We illustrate this relation by examining different examples of a driven two-atom Dicke system in which spin squeezing and entanglement arise dynamically. We give an explanation of the source of the difference using the negativity criterion for entanglement.

Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens

This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)-the causative agents of rheumatic fever and subsequent rheumatic heart disease-was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.

Immobilization of aluminum chloride on MCM-41 as a new catalyst system for liquid-phase isopropylation of naphthalene

A great deal of effort has been made at searching for alternative catalysts to replace conventional Lewis acid catalyst aluminum trichloride (AlCl3). In this paper, immobilization of AlCl3 on mesoporous MCM-41 silica with and without modification was carried out. The catalytic properties of the immobilized catalyst systems for liquid-phase isopropylation of naphthalene were studied and compared with those of H/MCM-41 and H/mordenite. The structures of the surface-immobilized aluminum chloride catalysts were studied and identified by using solid-state magic angle spinning nuclear magnetic resonance (MAS NMR), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption, and X-ray diffraction (XRD) techniques. The catalytic activity of the immobilized catalysts was found to be similar to that of acidic mordenite zeolite. A significant enhancement in the selectivity of 2,6-diisopropylnaphthalene (2,6-DIPN) was observed over the immobilized aluminum chloride catalysts. Immobilization of aluminum chloride on mesoporous silica coupled with surface silylation is a promising way of developing alternative catalyst system for liquid-phase Friedel-Crafts alkylation reactions. (C) 2002 Elsevier Science B.V. All rights reserved.

Analysis of the phase behavior of the aqueous poly(ethylene glycol)-Ficoll system

The PEG-Ficoll polymer phase system is one that has been overlooked in the past for biotechnology applications because of the stability of its emulsions. However, new applications, such as emulsion coating of cells, are appearing that rely on this very property. Ficoll is highly polydisperse and multimodal with three distinct Ficoll peaks in gel permeation chromatography. As a result, the transition between one-phase and two-phase systems is blurred and the binodials obtained through turbidometric titration and tie-line analysis differ significantly. Moreover, since the three Ficoll peaks partition differently, tie-line analysis cannot be described by a simple model of the aqueous two-phase system. A simple modification to the model allowed for excellent fit, and this modification may prove well-suited for the many practical cases where aqueous two-phase systems fail to display parallel tie-lines as implicitly assumed in the simpler model.

SimuMap: a computational system for spatial modelling

The paper presents a computational system based upon formal principles to run spatial models for environmental processes. The simulator is named SimuMap because it is typically used to simulate spatial processes over a mapped representation of terrain. A model is formally represented in SimuMap as a set of coupled sub-models. The paper considers the situation where spatial processes operate at different time levels, but are still integrated. An example of such a situation commonly occurs in watershed hydrology where overland flow and stream channel flow have very different flow rates but are highly related as they are subject to the same terrain runoff processes. SimuMap is able to run a network of sub-models that express different time-space derivatives for water flow processes. Sub-models may be coded generically with a map algebra programming language that uses a surface data model. To address the problem of differing time levels in simulation, the paper: (i) reviews general approaches for numerical solvers, (ii) considers the constraints that need to be enforced to use more adaptive time steps in discrete time specified simulations, and (iii) scaling transfer rates in equations that use different time bases for time-space derivatives. A multistep scheme is proposed for SimuMap. This is presented along with a description of its visual programming interface, its modelling formalisms and future plans. (C) 2003 Elsevier Ltd. All rights reserved.

A review of the first year's experience with an automatic message-routing system for low-cost telemedicine

The Swinfen Charitable Trust has used email for some years as a low-cost telemedicine medium to provide consultant support for doctors in developing countries. A scalable, automatic message-routing system was constructed which automates many of the tasks involved in message handling. During the first 12 months of its use, 1510 messages were processed automatically. There were 128 referrals from 18 hospitals in nine countries. Of these 128 queries, 89 (70%) were replied to within 72 h; the median delay was 1.1 day. The 39 unanswered queries were sent to backup specialists for reply and 36 of them (92%) were replied to within 72 h. In the remaining three cases, a second-line (backup) specialist was required. The referrals were handled by 54 volunteer specialists from a panel of over 70. Two system operators, located 10 time zones apart, managed the system. The median time from receipt of a new referral to its allocation to a specialist was 0.2 days (interquartile range, IQR, 0.1-0.8). The median interval between receipt of a new referral and first reply was 2.6 days (IQR 0.8-5.9). Automatic message handling solves many of the problems of manual email telemedicine systems and represents a potentially scalable way of doing low-cost telemedicine in the developing world.