Evolutionary conservation of homeodomain-binding sites and other sequences upstream and within the major transcription unit of the Drosophila segmentation gene engrailed.

The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.

Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers.

We developed a polymerase chain reaction DNA amplification system using two distinct consensus oligonucleotide primer sets for the improved detection and typing of a broad spectrum of human genital papillomavirus (HPV) sequences, including those of novel viruses. The system incorporates one primer set designed to amplify a highly conserved L1 domain and a second primer set designed to amplify a domain within the E6 gene. We used this system to analyze 48 fixed, paraffin-embedded tissue sections (41 specimens from 33 cervical carcinomas, four normal cervical tissues, and several control tissues) for the presence of HPV DNA. HPV sequences were detected in all carcinoma samples and none of the control samples. Hybridization analyses showed that the results obtained with the two amplification schemes concurred completely. This approach allowed rapid confirmation of typing results and may improve the likelihood of detecting a wide variety of HPV sequences, including those of novel HPVs.

Synthetic vision and emotion calculation in intelligent virtual human modeling.

The virtual human technique can already provide vivid and believable human behaviour in more and more scenarios. Virtual humans are expected to replace real humans in hazardous situations to undertake tests and feed back valuable information. This paper will introduce a virtual human with a novel collision-based synthetic vision, short-term memory model and a capability to implement emotion calculation and decision making. The virtual character based on this model can 'see' what is in its field of view (FOV) and remember those objects. After that, a group of affective computing equations have been introduced. These equations have been implemented into a proposed emotion calculation process to enlighten emotion for virtual intelligent humans.

Emotion-affected decision making in human simulation.

Human modelling is an interdisciplinary research field. The topic, emotion-affected decision making, was originally a cognitive psychology issue, but is now recognized as an important research direction for both computer science and biomedical modelling. The main aim of this paper is to attempt to bridge the gap between psychology and bioengineering in emotion-affected decision making. The work is based on Ortony's theory of emotions and bounded rationality theory, and attempts to connect the emotion process with decision making. A computational emotion model is proposed, and the initial framework of this model in virtual human simulation within the platform of Virtools is presented.

Modeling human behaviors and reactions under dangerous environment.

This paper describes the framework of a real-time simulation system to model human behavior and reactions in dangerous environments. The system utilizes the latest 3D computer animation techniques, combined with artificial intelligence, robotics and psychology, to model human behavior, reactions and decision making under expected/unexpected dangers in real-time in virtual environments. The development of the system includes: classification on the conscious/subconscious behaviors and reactions of different people; capturing different motion postures by the Eagle Digital System; establishing 3D character animation models; establishing 3D models for the scene; planning the scenario and the contents; and programming within Virtools Dev. Programming within Virtools Dev is subdivided into modeling dangerous events, modeling character's perceptions, modeling character's decision making, modeling character's movements, modeling character's interaction with environment and setting up the virtual cameras. The real-time simulation of human reactions in hazardous environments is invaluable in military defense, fire escape, rescue operation planning, traffic safety studies, and safety planning in chemical factories, the design of buildings, airplanes, ships and trains. Currently, human motion modeling can be realized through established technology, whereas to integrate perception and intelligence into virtual human's motion is still a huge undertaking. The challenges here are the synchronization of motion and intelligence, the accurate modeling of human's vision, smell, touch and hearing, the diversity and effects of emotion and personality in decision making. There are three types of software platforms which could be employed to realize the motion and intelligence within one system, and their advantages and disadvantages are discussed.

A computer modelling system for the biomechanical interaction in product design.

We introduce our system approach to rehabilitation engineering in which the user product interaction is emphasised. We then discuss a computer based approach to the problems of design making use of analysis software for the mechanical interaction. Our developing system for design, making use of anthropometric data and mechanisms analysis, is placed in the context of ergonomics and occupational biomechanics. We report our initial case study of this approach.

Recent applications of a computer based modelling system for biomechanical interactions.

We discuss developments in our previously reported system for the modelling of the biomechanical interaction between people and products. The mass properties of the artefact are obtained and used to construct a computer model which includes both an android modelling the user and the product. This system developed as part of of a continuing collaboration, initially focussed on design methodologies in rehabilitation engineering. A description of the techniques used is given in our paper and related to ergonomics and occupational biomechanics after validating the approach in a pilot study we subsequently proposed to include a wider range of consumer products while continuing the work on rehabilitation engineering. Examples from case studies are investigated and used to refine the technique. These progressed from a heavy concrete breaker through to the design of domestic electrical; appliances, in the latter work although the loadings are not excessive in general use there are situations, especially those involving specific users such as elderly people, in which the design of the product may be inappropriate In each case we construct a model from the anthropometric data and refine the model where necessary to take into account special constraints imposed on the user. Recent results together with refinements to our technique are discussed.

An integrated approach to rehabilitation engineering education: the development of a new masters programme at Brunel University.

We report on a new multidisciplinary course at Master's Level; a joint venture between the Department of Design at Brunel University. U.K. and Brunel Institute for Bioengineering. The Bachelor of Science degree in Industrial Design at Brunel includes an important proportion of technological courses such as mechanics and electronics. The MSc course, which is modular, continues to embrace a wide range of disciplines but it also seeks to bring together graduates from traditional engineering backgrounds in addition to those from arts based design courses. Appropriate elements are offered in order to allow access into unfamiliar disciplines. One novel and valuable aspect of the course is the way in which graduates from diverse backgrounds, having complementary experience and skills will be studying and developing projects alongside one another. Although much of the academic content will be through the department of Design and the Faculty of Technology, the Brunel Institute for Bioengineering will play a major role in the provision of modules in Rehabilitation Studies and in the generation and supervision of projects. This project work will therefore be carried out within the Rehabilitation Engineering Unit at Brunel Institute for Bioengineering. The course to be discussed has been developed at Brunel University in the department of Design in conjunction with The Brunel institute for Bioengineering.

The synthesis of EMG signals based on considerations of signal spectra.

In this paper we investigate the effect on the spectra of an EMG signal due to changes in the parameters, which control motor unit (MU) firing sequences. To enable this analysis we start by developing a computer-based model of the motor unit activation potential (MUAP) to enable the generation of artificial surface electromyography (EMG) signals. By adjusting the parameters used in the generation of the synthetic EMG we can investigate the effect of a single parametric change on the resultant spectrum. The parameters and range of values we investigated were determined after a literature review. The synthetic EMGs are compared to actual EMG signals collected from the biceps muscle of males subjects aged between 18 to 32, years all without any known neuromuscular disease, disabilities or injuries to the elbow joint.

Modelling soft tissue for kinematic analysis of multi-segment human body models.

Traditionally biomechanical models represent the musculoskeletal system by a series of rigid links connected by rigidly defined rotational joints. More recently though the mechanics of joints and the action of soft tissues has come under closer scrutiny: biomechanical models might now include a full range of physiological structures. However, soft tissue representation, within multi-segment human body models, presents significant problems; not least in computational speed. We present a method for representing soft tissue physiology which provides for soft tissue wrapping around multiple bony objects; while showing forces at the insertion points, as well as normal reactions due to contact between the soft and bony tissues. These soft tissue representations may therefore be used to constrain the joint, as ligaments would, or to generate motion, like a muscle, so that joints may be modelled which more accurately simulate musculoskeletal motion in all degrees of freedom--rotational and translational. This method produces soft tissues that do not need to be tied to a certain path or route between the bony structures, but may move with the motion of the model; demonstrating a more realistic analysis of soft tissue activity in the musculoskeletal system. The combination of solid geometry models of the skeletal structure, and these novel soft tissue representations, may also provide a useful approach to synthesised human motion.

Modeling the interactions between a prosthetic socket, polyurethane liners and the residual limb in transtibial amputees using non-linear finite element analysis.

Continuing earlier studies into the relationship between the residual limb, liner and socket in transtibial amputees, we describe a geometrically accurate non-linear model simulating the donning of a liner and then a socket. The socket is rigid and rectified and the liner is a polyurethane geltype which is accurately described using non-linear (Mooney-Rivlin) material properties. The soft tissue of the residual limb is modelled as homogeneous, non-linear and hyperelastic and the bone structure within the residual limb is taken as rigid. The work gives an indication of how the stress induced by the process of donning the rigid socket is redistributed by the liner. Ultimately we hope to understand how the liner design might be modified to reduce discomfort. The ANSYS finite element code, version 5.6 is used.

Sequence conservation in the protein coding and intron regions of the engrailed transcription unit.

Engrailed (en) is a gene involved in proper segmentation of the Drosophila embryo. The predicted en protein contains a homeodomain and regions rich in polyalanine, polyglutamine, polyglutamate/aspartate and serine. We have taken an evolutionary approach to define which regions may be of fundamental importance by examining the D. virilis genomic sequence homologous to the D. melanogaster en primary transcription unit. Sequence homology begins at the first ATG of a long open reading frame yielding proteins of 584 and 552 amino acids for the D. virilis and D. melanogaster proteins, respectively. The predicted amino acid sequence can be divided into conserved and non-conserved domains. The C-terminal 30% of the protein (which includes the homeodomain) is completely conserved. In the N-terminal 70% of the protein, the overall conservation is 71%, but non-conservative amino acid changes occur in clusters and there are short stretches of highly conserved sequence. A region rich in glutamate and aspartate is conserved and has homology to an 18-amino acid sequence present in members of the myc family of proteins. Major differences in the size of the two proteins occur in regions of non-conserved repeated sequences. In the introns of the engrailed transcription units there are long stretches of conservation, suggesting this DNA may be of functional importance.

Autonomic nervous system dysfunction in severe tetanus: current perspectives.

The enigma of autonomic nervous system dysfunction in severe tetanus is discussed in the light of recent and older evidence concerning the nature and action of tetanus toxin, its clinical effects, and therapy. Some suggestions for the pathogenesis and management of the cardiovascular disturbances are made.

Identification of the thymidine kinase gene of feline herpesvirus: use of degenerate oligonucleotides in the polymerase chain reaction to isolate herpesvirus gene homologs.

Feline herpesvirus 1 (FHV) is the causative agent of viral rhinotracheitis in cats. Current vaccination programs employing attenuated live and killed FHV vaccines have been effective in reducing the incidence of this disease. As an initial step in the development of recombinant FHVs for use in the vaccination of cats, we have identified the thymidine kinase (TK) gene of this feline-specific alphaherpesvirus. Comparisons of the amino acid sequences of other herpesvirus TK proteins have shown that these proteins are highly divergent, sharing only short regions of imperfect amino acid identity. We have used the polymerase chain reaction method of DNA amplification to increase the specificity associated with the use of short, highly degenerate oligonucleotide probes derived from regions of imperfect amino acid conservation. These methods were used to isolate the TK gene of FHV and should prove to be useful in the identification of new members of other viral and cellular gene families. A recombinant FHV bearing a deletion in the identified TK gene was constructed and shown to possess the expected TK- phenotype. The FHV TK gene is located at a position of approximately 40% in the long unique component of the FHV genome. The location of the TK gene and the location and orientation of flanking FHV genes, homologs of herpes simplex virus type 1 UL24 and UL22, are conserved among alphaherpesviruses.