Biopharming the SimpliRED™ HIV diagnostic reagent in barley, potato and tobacco

This is the first report of an antibody-fusion protein expressed in transgenic plants for direct use in a medical diagnostic assay. By the use of gene constructs with appropriate promoters, high level expression of an anti-glycophorin single-chain antibody fused to an epitope of the HIV virus was obtained in the leaves and stems of tobacco, tubers of potato and seed of barley. This fusion protein replaces the SimpliRED™ diagnostic reagent, used for detecting the presence of HIV-1 antibodies in human blood. The reagent is expensive and laborious to produce by conventional means since chemical modifications to a monoclonal antibody are required. The plant-produced fusion protein was fully functional (by ELISA) in crude extracts and, for tobacco at least, could be used without further purification in the HIV agglutination assay. All three crop species produced sufficient reagent levels to be superior bioreactors to bacteria or mice, however barley grain was the most attractive bioreactor as it expressed the highest level (150 μg of reagent g-1), is inexpensive to produce and harvest, poses a minuscule gene flow problem in the field, and the activity of the reagent is largely undiminished in stored grain. This work suggests that barley seed will be an ideal factory for the production of antibodies, diagnostic immunoreagents, vaccines and other pharmaceutical proteins.

The relationship between kurtosis- and envelope-based indexes for the diagnostic of rolling element bearings

The coupling of kurtosis based-indexes and envelope analysis represents one of the most successful and widespread procedures for the diagnostics of incipient faults on rolling element bearings. Kurtosis-based indexes are often used to select the proper demodulation band for the application of envelope-based techniques. Kurtosis itself, in slightly different formulations, is applied for the prognostic and condition monitoring of rolling element bearings, as a standalone tool for a fast indication of the development of faults. This paper shows for the first time the strong analytical connection which holds for these two families of indexes. In particular, analytical identities are shown for the squared envelope spectrum (SES) and the kurtosis of the corresponding band-pass filtered analytic signal. In particular, it is demonstrated how the sum of the peaks in the SES corresponds to the raw 4th order moment. The analytical results show as well a link with an another signal processing technique: the cepstrum pre-whitening, recently used in bearing diagnostics. The analytical results are the basis for the discussion on an optimal indicator for the choice of the demodulation band, the ratio of cyclic content (RCC), which endows the kurtosis with selectivity in the cyclic frequency domain and whose performance is compared with more traditional kurtosis-based indicators such as the protrugram. A benchmark, performed on numerical simulations and experimental data coming from two different test-rigs, proves the superior effectiveness of such an indicator. Finally a short introduction to the potential offered by the newly proposed index in the field of prognostics is given in an additional experimental example. In particular the RCC is tested on experimental data collected on an endurance bearing test-rig, showing its ability to follow the development of the damage with a single numerical index.

Development of a new signal processing diagnostic tool for vibration signals acquired in transient conditions

The diagnostics of mechanical components operating in transient conditions is still an open issue, in both research and industrial field. Indeed, the signal processing techniques developed to analyse stationary data are not applicable or are affected by a loss of effectiveness when applied to signal acquired in transient conditions. In this paper, a suitable and original signal processing tool (named EEMED), which can be used for mechanical component diagnostics in whatever operating condition and noise level, is developed exploiting some data-adaptive techniques such as Empirical Mode Decomposition (EMD), Minimum Entropy Deconvolution (MED) and the analytical approach of the Hilbert transform. The proposed tool is able to supply diagnostic information on the basis of experimental vibrations measured in transient conditions. The tool has been originally developed in order to detect localized faults on bearings installed in high speed train traction equipments and it is more effective to detect a fault in non-stationary conditions than signal processing tools based on spectral kurtosis or envelope analysis, which represent until now the landmark for bearings diagnostics.

Signal Processing Diagnostic Tool for Rolling Element Bearings Using EMD and MED

The signal processing techniques developed for the diagnostics of mechanical components operating in stationary conditions are often not applicable or are affected by a loss of effectiveness when applied to signals measured in transient conditions. In this chapter, an original signal processing tool is developed exploiting some data-adaptive techniques such as Empirical Mode Decomposition, Minimum Entropy Deconvolution and the analytical approach of the Hilbert transform. The tool has been developed to detect localized faults on bearings of traction systems of high speed trains and it is more effective to detect a fault in non-stationary conditions than signal processing tools based on envelope analysis or spectral kurtosis, which represent until now the landmark for bearings diagnostics.

Diagnostic of Rolling Element Bearings with Envelope Analysis in Non-Stationary Conditions

In the field of rolling element bearing diagnostics, envelope analysis has gained in the last years a leading role among the different digital signal processing techniques. The original constraint of constant operating speed has been relaxed thanks to the combination of this technique with the computed order tracking, able to resample signals at constant angular increments. In this way, the field of application of this technique has been extended to cases in which small speed fluctuations occur, maintaining high effectiveness and efficiency. In order to make this algorithm suitable to all industrial applications, the constraint on speed has to be removed completely. In fact, in many applications, the coincidence of high bearing loads, and therefore high diagnostic capability, with acceleration-deceleration phases represents a further incentive in this direction. This chapter presents a procedure for the application of envelope analysis to speed transients. The effect of load variation on the proposed technique will be also qualitatively addressed.

Manifestations of preoperational reasoning on similar programming tasks

In this research paper, we study a simple programming problem that only requires knowledge of variables and assignment statements, and yet we found that some early novice programmers had difficulty solving the problem. We also present data from think aloud studies which demonstrate the nature of those difficulties. We interpret our data within a neo-Piagetian framework which describes cognitive developmental stages through which students pass as they learn to program. We describe in detail think aloud sessions with novices who reason at the neo-Piagetian preoperational level. Those students exhibit two problems. First, they focus on very small parts of the code and lose sight of the "big picture". Second, they are prone to focus on superficial aspects of the task that are not functionally central to the solution. It is not until the transition into the concrete operational stage that decentration of focus occurs, and they have the cognitive ability to reason about abstract quantities that are conserved, and are equipped to adapt skills to closely related tasks. Our results, and the neo-Piagetian framework on which they are based, suggest that changes are necessary in teaching practice to better support novices who have not reached the concrete operational stage.

The effect of varying diagnostic terminology within patient discharge information on expected mild traumatic brain injury outcome

This study aimed to determine if systematic variation of the diagnostic terminology embedded within written discharge information (i.e., concussion or mild traumatic brain injury, mTBI) would produce different expected symptoms and illness perceptions. We hypothesized that compared to concussion advice, mTBI advice would be associated with worse outcomes. Sixty-two volunteers with no history of brain injury or neurological disease were randomly allocated to one of two conditions in which they read a mTBI vignette followed by information that varied only by use of the embedded terms concussion (n = 28) or mTBI (n = 34). Both groups reported illness perceptions (timeline and consequences subscale of the Illness Perception Questionnaire-Revised) and expected Postconcussion Syndrome (PCS) symptoms 6 months post injury (Neurobehavioral Symptom Inventory, NSI). Statistically significant group differences due to terminology were found on selected NSI scores (i.e., total, cognitive and sensory symptom cluster scores (concussion > mTBI)), but there was no effect of terminology on illness perception. When embedded in discharge advice, diagnostic terminology affects some but not all expected outcomes. Given that such expectations are a known contributor to poor mTBI outcome, clinicians should consider the potential impact of varied terminology on their patients.

Comparing skin biopsy with confocal microscopy : diagnostic yield of nerve fiber density

Background and aims: The assessment of intra-epidermal nerve fiber density (IENFD) in skin biopsies and corneal nerve fiber density (CNFD) using corneal confocal microscopy (CCM) provides promising techniques to detect small nerve fiber damage in patients with peripheral neuropathy. To help define the clinical utility of each of these techniques in patients with diabetic neuropathy we have assessed sensitivity and specificity of IENFD and CNFD in predicting the following: 1) diabetic polyneuropathy (DPN); 2) risk of foot ulceration (RFU); 3) initial small fiber neuropathy (iSFN); 4) severe small fiber neuropathy (sSFN)...

The IKBALS project: multi-modal reasoning in legal knowledge based systems

In attempting to build intelligent litigation support tools, we have moved beyond first generation, production rule legal expert systems. Our work integrates rule based and case based reasoning with intelligent information retrieval. When using the case based reasoning methodology, or in our case the specialisation of case based retrieval, we need to be aware of how to retrieve relevant experience. Our research, in the legal domain, specifies an approach to the retrieval problem which relies heavily on an extended object oriented/rule based system architecture that is supplemented with causal background information. We use a distributed agent architecture to help support the reasoning process of lawyers. Our approach to integrating rule based reasoning, case based reasoning and case based retrieval is contrasted to the CABARET and PROLEXS architectures which rely on a centralised blackboard architecture. We discuss in detail how our various cooperating agents interact, and provide examples of the system at work. The IKBALS system uses a specialised induction algorithm to induce rules from cases. These rules are then used as indices during the case based retrieval process. Because we aim to build legal support tools which can be modified to suit various domains rather than single purpose legal expert systems, we focus on principles behind developing legal knowledge based systems. The original domain chosen was theAccident Compensation Act 1989 (Victoria, Australia), which relates to the provision of benefits for employees injured at work. For various reasons, which are indicated in the paper, we changed our domain to that ofCredit Act 1984 (Victoria, Australia). This Act regulates the provision of loans by financial institutions. The rule based part of our system which provides advice on the Credit Act has been commercially developed in conjunction with a legal firm. We indicate how this work has lead to the development of a methodology for constructing rule based legal knowledge based systems. We explain the process of integrating this existing commercial rule based system with the case base reasoning and retrieval architecture.

Reasoning paradigms in legal decision support systems

In this paper we discuss the strengths and weaknesses of a range of artificial intelligence approaches used in legal domains. Symbolic reasoning systems which rely on deductive, inductive and analogical reasoning are described and reviewed. The role of statistical reasoning in law is examined, and the use of neural networks analysed. There is discussion of architectures for, and examples of, systems which combine a number of these reasoning strategies. We conclude that to build intelligent legal decision support systems requires a range of reasoning strategies.

Beyond rule based reasoning - the meaning and use of cases

Commercial legal expert systems are invariably rule based. Such systems are poor at dealing with open texture and the argumentation inherent in law. To overcome these problems we suggest supplementing rule based legal expert systems with case based reasoning or neural networks. Both case based reasoners and neural networks use cases-but in very different ways. We discuss these differences at length. In particular we examine the role of explanation in existing expert systems methodologies. Because neural networks provide poor explanation facilities, we consider the use of Toulmin argument structures to support explanation (S. Toulmin, 1958). We illustrate our ideas with regard to a number of systems built by the authors

Deductive, inductive and analogical reasoning in legal decision support systems

In this paper we provide an overview of a number of fundamental reasoning formalisms in artificial intelligence which can and have been used in modelling legal reasoning. We describe deduction, induction and analogical reasoning formalisms, and show how they can be used separately to model legal reasoning. We argue that these formalisms can be used together to model legal reasoning more accurately, and describe a number of attempts to integrate the approaches.