Proteomics in clinical prostate research

The incidence of early prostate cancer (PCa) has increased rapidly in recent years. The majority of newly diagnosed PCa are in early tumor phase. Presently, we do not have adequate biomarkers to assess tumor aggressiveness in individual cases. Consequently, too many patients are given curatively intended treatment. An exploration of the human proteome may provide clinically useful markers. 2-DE has been successfully used for analysis of the protein phenotype using clinical samples. Proteins are separated according to size and charge, gels are compared by image analysis, protein spots of interest are excised, and proteins identified by MS. This method is exploratory and allows protein identification. However, low-abundance proteins are difficult to detect and 2-DE is currently too labor-intensive for routine use. In recent years, nongel based techniques, such as LC-MS, SELDI-MS, and protein arrays have emerged. They require smaller sample sizes and can be more automated than 2-DE. In this review, we describe studies of the protein expression of benign prostatic tissue and PCa, which is likely to serve as the first step in prognostic biomarker discovery. The prostate proteome is still far from a complete mapping which would enhance our understanding of PCa biology.     

Multibody dynamics as a tool for historical research

Ancient musical instruments can tell us much about the way composers of the past centuries wrote their music. Indeed, the sound and playing characteristics of historical instruments are often very different from those of the instruments we are used to. For example, in the case of the Viennese piano actions used by Mozart and his contemporaries, the so-called “escapement height” largely conditions the response of the instrument to the pianist’s touch. In this contribution, we aim to define how the Viennese action behaves when the escapement height, usually tuned by piano technicians, is changed.To do this, a multibody model containing the frame, the key, the hammer, the pawl, and the string has been developed. This paper describes how the model has been carried out; a special focus is put on the detection of the intermittent contacts between bodies, which may look easy in the real action, but is rather complex to model. The model is compared with high-speed imaging data and a parametric study of the escapement height is performed by adjusting the rest position of the pawl. The high sensitivity of this regulation is revealed as a shift of 1 mm of the pawl seems to induce a displacement of the escapement height of 20 mm. It is also shown that a strong but linear decrease of the maximal force between the hammer and the string appears when the escapement height increases.     

Interactive publication: The document as a research tool

The increasing prevalence of multimedia and research data generated by scientific work affords an opportunity to reformulate the idea of a scientific article from the traditional static document, or even one with links to supplemental material in remote databases, to a self-contained, multimedia-rich interactive publication. This paper describes our concept of such a document, and the design of tools for authoring (Forge) and visualization/analysis (Panorama). They are platform-independent applications written in Java, and developed in Eclipse¹ using its Rich Client Platform (RCP) framework. Both applications operate on PDF files with links to XML files that define the media type, location, and action to be performed. We also briefly cite the challenges posed by the potentially large size of interactive publications, the need for evaluating their value to improved comprehension and learning, and the need for their long-term preservation by the National Library of Medicine and other libraries.     

The Delphi method as a research tool: an example,design considerations and applications

The Delphi method has proven a popular tool in information systems research for identifying and prioritizing issues for managerial decision-making. However, many past studies have not adopted a systematic approach to conduct a Delphi study. This article provides rigorous guidelines for the process of selecting appropriate experts for the study and gives detailed principles for making design choices during the process that ensure a valid study. A detailed example of a study to identify key factors affecting the diffusion of e-commerce in Sub-Saharan Africa illustrates the design choices that may be involved. We conclude with suggestions for theoretical applications.     

On robust partial discriminant analysis as a decision-making tool with clinical and analytical chemical data

Classification is one of the fundamental goals of science and is basic to the diagnosis of disease. Unfortunately, classifying objects (e.g., patients) on the basis of clinical and/or laboratory experimental observations into various groups can be difficult when the groups overlap or contain outlying points. Recently, Broffitt, Randles, and co-workers proposed a procedure, robust partial discriminant analysis (RPDA) for dealing with such problems, but testing of the procedure was limited to Monte Carlo simulation. In this study, RPDA was applied to real data, in order to compare its effectiveness with ordinary discriminant analysis, as well as to determine if RPDA was a suitable procedure to use to classify chemical compounds on the basis of experimental observations and as a tool in the diagnosis of disease (in particular, multiple sclerosis and thyrotoxicosis), with data based on experimental and clinical observations. The resulting RPDA classifications were an improvement over those obtained from ordinary discriminant analysis.     

Proteomics in chronic wound research: potentials in healing and health

Chronic wounds, such as venous and diabetic leg ulcers, represent a significant health and financial burden to individuals and healthcare systems. In worst-case scenarios this condition may require the amputation of an affected limb, with significant impact on patient quality of life and health. Presently, there are no clinical biochemical analyses used in the diagnosis and management of this condition; moreover few biochemical therapies are accessible to patients. This presents a significant challenge in the efficient and efficacious treatment of chronic wounds by medical practitioners. A number of protein-centric investigations have analyzed the wound environment and implicated a suite of molecular species predicted to be involved in the initiation or perpetuation of the condition. However, comprehensive proteomic investigation is yet to be engaged in the analysis of chronic wounds for the identification of molecular diagnostic/prognostic markers of healing or therapeutic targets. This review examines clinical chronic wound research and recommends a path toward proteomic investigation for the discovery of medically significant targets. Additionally, the Supporting Information documents associated with this review provide the first comprehensive summary of protein-centric, small molecule and elemental analyses in clinical chronic wound research.     

Positive reinforcement as a quality tool

Many quality practitioners rely on auditing to verify compliance of process changes. However, when our division used a positive reinforcement approach to verify compliance, we saw deeper institutionalization of the desired organizational change.     

Kinetic modelling as a tool for the design of a vascular bioartificial pancreas: feedback between modelling and experimental validation

A bioartificial pancreas is a system which contains isolated islets of Langerhans protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to lymphocytes and immunoglobulins. However, it is necessary to design a device which performs as a closed-loop insulin delivery system, more specifically which rapidly responds to a change in the recipient's blood glucose concentration by an appropriate change in insulin release. We have designed a system intended to be connected as an arteriovenous shunt of the recipient; islets are placed between two flat ultrafiltration membranes, and blood circulates successively above the upper, and below the lower, membrane, in reverse direction. A complete kinetic model of glucose transfer from blood to the islet compartment, of insulin generation by the islets displaying a biphasic insulin pattern, and of insulin transfer into the bloodstream was described, and parameters were calculated on the basis of experimental data obtained when islets of Langerhans were perfused in vitro with a synthetic buffer. The resulting calculations indicated that both diffusional and convective transfers were involved in glucose and insulin mass transfer across the membrane, the contribution of diffusion being the most important. The geometry of the system was therefore modified in order to decrease the resistance to flow inside the blood channel. This should increase, at a given hydrostatic pressure, the blood flow rate, and thereby improve the diffusional transfer of insulin. This should also decrease the thrombogenicity of the device.(ABSTRACT TRUNCATED AT 250 WORDS)     

The compiler as a validation and evaluation tool

Like a processor executes flawlessly at different frequencies, a compiler should produce correct results at any optimization level. The Intel^® Itanium^® processor family with its new features, like the register stack engine and control- and data speculation, provides new and unique challenges for ported software and compiler technology. This paper describes validation and evaluation techniques that can be employed in compilation tools and can help to get a cleaner port of an application, a more robust compilation system and even insights into performance tuning opportunities. Using Itanium as a specific example, the paper explains why the register stack engine (RSE), the large register file, or control- and data speculation can potentially expose bugs in poorly written or compiled software. It then demonstrates validation and evaluation techniques to find or expose these bugs. An evaluation team can employ them to find, eliminate and evaluate software bugs. A compiler team can use them to make the compiler more stable and robust. A performance analysis team can use them to uncover performance opportunities in an application. We demonstrate our validation and evaluation techniques on code examples and provide run-time data to indicate the cost of some of our methods.     

Generalized B-splines as a tool in isogeometric analysis

The concept of isogeometric analysis has been proposed in [13], where NURBS are considered as basis of the analysis, thanks to their ability to construct an exact geometric model in several practical applications and to their popularity in commercial CAD systems. In this paper we propose an alternative to the rational model presenting an isogeometric analysis approach based on generalized B-splines. Geometric models exactly represented by generalized B-splines include those generated by NURBS. Moreover, generalized B-splines possess all fundamental properties of algebraic B-splines (and NURBS) including classical refinement processes as h–p–k refinements. Finally, since generalized B-splines are not confined to rational functions, they behave completely similar to algebraic B-splines with respect to differentiation and integration. This seems to be of interest in the treatment of some relevant problems.     

Automatic differentiation as a tool in engineering design

Automatic Differentiation (AD) is a tool that systematically implements the chain rule of differentiation to obtain the derivatives of functions calculated by computer programs. In this paper, it is assessed as a tool for engineering design. The paper discusses the forward and reverse modes of AD, their computing requirements, as well as approaches to implementing AD. It continues with the application of two different tools to two medium-size structural analysis problems to generate sensitivity information typically necessary in an optimization or design situation. The paper concludes with the observation that AD is to be preferred to finite differencing in most cases, as long as sufficient computer storage is available; in some instances, AD may be the alternative to consider in lieu of analytical sensitivity analysis.     

Poetry as a cross-cultural analysis and sensitizing tool in design

AI & SOCIETY - The overall trend toward globalization in design, greatly enhanced by digital technologies, has raised issues and challenges on how to preserve the cultural differences and...     

The effects of an interactive videodisc training program in classroom observation skills used as a teaching tool and as a learning tool

In higher education, instruction is typically teacher-directed through traditional lecture formats and assignments with predetermined criteria. Through hypermedia-based materials, new ways of learning are possible based on learner control and self-directed instruction; such approaches require personal goal-setting, nonlinear exploration of materials, context-based problem solving, and progress monitoring. For students to learn in new ways, instructors have to teach in new ways. Teachers cannot simply take new hypermedia applications and implement them within existing approaches if higher level outcomes are to be realized. The findings in this study are consistent with previous research studies which demonstrate equal or better learning using hypermedia-based instructional materials when students are allowed learner control. If the learning profile for each student determines the effective use of an application, then hypermedia is best implemented as a learning tool.     

Online x-ray atlas as a reference tool

Received: 12 March 1997 / Revised: 15 June 1997 / Accepted: 5 August 1997     

Research into accidents as a design tool

Product liability legislation presses to gain more insight into the occurrence of accidents with consumer products, to the benefit of both producers and consumers. In this paper research is presented that was carried out in order to provide this insight. The research consisted of recording the reconstruction of accidents by the victims. The design relevance of the comprehensive data was assessed by a panel of industrial designers. The results are discussed in view of the development of a method that is actually applicable by industrial designers, in order to anticipate possible ways of use that might result in accidents. It is argued that the availability and the application of such a method would not only contribute to the prevention of accidents, but might also positively affect the marketing position of a product.     

Using the LIS as a strategic tool

A major shift in emphasis is now occurring in pathology informatics, the subdiscipline within pathology that focuses on automated information management. This shift involves a much greater emphasis on both the strategic value of the pathology database and high-level applications running on the laboratory information system (LIS).     

Robustification as a tool in modeling biochemical reaction networks

Biological functions have evolved to become robust against a multitude of perturbations such as gene mutations, intracellular noise and changes in the physical and chemical environment. This robustness should be reflected in models of the underlying biochemical networks, and robustness analysis has consequently been established as an important tool for model validation in systems biology. However, while robustness analysis can be used to invalidate a given model, it does not support the postulation of model modifications that can serve to improve the robustness. Herein we propose a method for this purpose, based on computing the sensitivity of the robustness with respect to generic dynamic perturbations applied to the individual network edges. To quantify robustness we compute the smallest simultaneous change in the activity of the network nodes that induces a bifurcation in the network, resulting in a qualitative change in the network behavior. The proposed method can be used to identify network interactions with the most significant impact on the overall robustness of a given function. By considering the impact of adding new nodes and edges, the method can also be used to postulate the presence of important unmodeled components and interactions. The focus here is on biological functions related to bistable switches and sustained oscillations, and the proposed methodology is demonstrated through application to metabolic oscillations in white blood cells and bistable switching in MAPK signal transduction. The classical Goodwin model of oscillations in a simple gene regulatory network is used for illustration throughout the paper.