Human kidney glomerulus proteome and biomarker discovery of kidney diseases

The kidney glomerulus is the site of plasma filtration and production of primary urine in the kidney. The structure not only plays a pivotal role in ultrafiltration of plasma into urine but also is the locus of kidney diseases progressing to chronic renal failure. Patients afflicted with these glomerular diseases frequently progress to irreversible loss of renal function and inevitably require replacement therapies. The diagnosis and treatment of glomerular diseases are now based on clinical manifestations, urinary protein excretion level, and renal pathology of needle biopsy specimens. The molecular mechanisms underlying the progression of glomerular diseases are still obscure despite a great number of clinical and experimental studies. Proteomics is a particularly promising approach for the discovery of proteins relevant to physiological and pathophysiological processes, and has been recently employed in nephrology. Although until now most efforts of proteomic analysis have been conducted with urine, the biological fluid that is easily collected without invasive procedures, proteomic analysis of the glomerulus, the tissue most proximal to the disease loci, is the most straightforward approach. In this review, we attempt to outline the current status of clinical proteomics of the glomerulus and provide a perspective of protein biomarker discovery of glomerular diseases.     

A survey on histological image analysis-based assessment of three major biological factors influencing radiotherapy: proliferation, hypoxia and vasculature

Image analysis is a rapidly evolving field with growing applications in science and engineering. In cancer research, it has played a key role in advancing techniques of major diagnostic importance, minimising human intervention and providing vital clinical information. Especially in the field of tissue microscopy, the use of computers for the automated analysis of histological sections is becoming increasingly important. This paper presents an overview of various image analysis methodologies and summarises developments in this field, with great emphasis given on the assessment of three major biological factors known to influence the outcome of radiotherapy: proliferation, vasculature and hypoxia. A brief introduction followed by a survey is provided in each of these areas.     

Progress in systems ergonomics: a selective review

Abstract

The 1967 conference on the Human Operator in Complex Systems identified several developments required in systems ergonomics. Progress in four areas requiring development is reviewed, based on information from workshops and surveys of applications of systems ergonomics in military systems. It is concluded that there has been less progress than might have been hoped in the use of systems relevant criteria in systems ergonomics. Few applications have involved trade-offs between selection, training and equipment design. Task analysis techniques have not advanced, although their use may be changing. Although there appears to be general agreement on the major activities associated with systems ergonomics, the emphasis placed on those different activities may be changing as a result of technological developments. However, these technological developments are now providing opportunities for systems ergonomists to improve their tools and techniques.     

A critical review of approaches to human reliability analysis

This paper provides a critical analysis of four major approaches to human reliability assessment: THERP, the use of qualitative models of human performance, simulation methods, and methods based on classical reliability theory. Methodologically and conceptually, these approaches are more representative of a multidimensional than unified perspective to the problem of human reliability analysis and are considered to encompass many of the other methods that have been proposed. Recent developments in each of these areas and the growing concern for the consequences of human error in highly complex systems requires that these approaches be sufficiently understood in order to identify both their strengths and their shortcomings. Although no single approach is advocated, this review intends to provide insights that could suggest improvements to these methods as well as aid the analyst in selecting the approach most optimal for the situation in question. In addition, critical research needs are identified and summarized.     

Virtual human animation in natural language visualisation

Simulation motion of Virtual Reality (VR) objects and humans has experienced important developments in the last decade. However, realistic virtual human animation generation remains a major challenge, even if applications are numerous, from VR games to medical training. This paper proposes different methods for animating virtual humans, including blending simultaneous animations of various temporal relations with multiple animation channels, minimal visemes for lip synchronisation, and space sites of virtual human and 3D object models for object grasping and manipulation. We present our work in our natural language visualisation (animation) system, CONFUCIUS, and describe how the proposed approaches are employed in CONFUCIUS’ animation engine.     

Control systems R&D at BBN

The primary focus in this article is on BBN's theoretical and applied work on problems involving humans in the information processing and control loop of control systems. This article discusses the evolution and outcome of key technical developments, people involved, and the role of BBN's environment -computational, organizational, and human. The history of the long and productive R&D program from its early beginnings, circa 1960, to the end of the 1980s is the main focus of this article. The history includes efforts in developing decision aids for pilots and for advanced command and control applications, because these can be viewed as natural evolutions of earlier control work. In something of a departure from this main focus, multitarget tracking, which emerged from the control efforts, is discussed because it eventually resulted in major programs for BBN and illustrates how BBN's diverse research efforts and its environment lead to unexpected rewards.     

Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue

Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither are ideal predictors of drug behavior in humans. Improving in vitro systems for preclinical studies both from a technological and biological model standpoint thus remains a major challenge. This article describes how microfluidics can be exploited to come closer to this goal in combination with precision-cut liver slices (PCLS) as an improved organomimetic system. Recently, we developed a novel microfluidic-based system incorporating a microchamber for slice perifusion to perform drug metabolism studies with mammalian PCLS under continuous flow. In the present study, the viability and metabolism of human PCLS were assessed by the measurement of the leakage of liver-specific enzymes and metabolism of four different substrates: lidocaine, 7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone. All experiments were verified with well plates, an excellent benchmark for these experiments. Clearly, however, human tissue is not readily available, and it is worth considering how to perform a maximum number of informative experiments with small amounts of material. In one approach, the microfluidic system was coupled to an HPLC system to allow on-line monitoring and immediate detection of unstable metabolites, something that is generally not possible with conventional well-plate systems. This novel microfluidic system also enables the in vitro measurement of interorgan interactions by connecting microchambers containing different organ slices in series for sequential perfusion. This versatile experimental system has the potential to yield more information about the metabolic profiles of new drug candidates in human and animal tissues in an early stage of development compared with well plates alone.     

Visual modeling for Web 2.0 applications using model driven architecture approach

Mashup is now a major Web 2.0 technology because, rather than simply aggregating Web content, it combines various Web resources from other websites. Considering Web 2.0 mashups from a software engineering perspective, a visual modeling approach is crucial. Current Web 2.0 developments, however, do not support a conceptual modelling for Web 2.0 applications. This leads to inefficient development processes and a low potential for reuse. The Unified Modeling Language (UML) is a general-purpose modeling language that may be used in widely varying application domains. However, UML often lacks elements for modeling and representing concrete concepts of specific domains such as Web 2.0 mashup modeling. To address these shortcomings, this study proposes Web2.0MUML, a Model Driven Architecture (MDA) approach and UML profile for modeling Web 2.0 mashups. The Web2.0MUML profile extends UML by using a profile mechanism for Web 2.0 mashup modeling that presents the relevant structural properties of Web 2.0 at the conceptual level.     

The role of quantitative ADME proteomics to support construction of physiologically based pharmacokinetic models for use in small molecule drug development

Pharmacokinetics (PK) refers to the time course of drug concentrations in the body and since knowledge of PK aids understanding of drug efficacy and safety, numerous PK studies are performed in animals and humans during the drug development process. In vitro to in vivo extrapolation and physiologically based pharmacokinetic (PBPK) modeling are tools that integrate data from various in silico, in vitro, and in vivo sources to deliver mechanistic quantitative simulations of in vivo PK. PBPK models are used to predict human PK and to evaluate the effects of intrinsic factors such as organ dysfunction, age, and genetics as well as extrinsic factors such as co-administered drugs. In recent years, the use of PBPK within the industry has greatly increased. However, insufficient data on how the abundance of metabolic enzymes and membrane transporters vary in different human patient populations and in different species has been a limitation. A major advance is therefore expected through reliable quantification of the abundance of these proteins in tissues. This review describes the role of PBPK modeling in drug discovery and development, outlines the assumptions involved in integrating protein abundance data, and describes the advances made and expected in determining abundance of relevant proteins through mass spectrometric techniques.     

Hi-tech for construction projects

The Hi-Tech industries today seem to be symbolised by two major developments, the supercomputer and the robot, but as yet the construction industry has benefitted little from such developments. Construction is a Mid-tech industry in a Hi-tech world, an industry with static productivity levels for two decades now, but an industry under increasing pressure from foreign construction developments to innovate. The wide array of technologies available to the industry tends to defeat the clarity of purpose necessary for change, and so an attempt is made to focus on a few key options.     

Progress and prospects of the human–robot collaboration

Recent technological advances in hardware design of the robotic platforms enabled the implementation of various control modalities for improved interactions with humans and unstructured environments. An important application area for the integration of robots with such advanced interaction capabilities is human–robot collaboration. This aspect represents high socio-economic impacts and maintains the sense of purpose of the involved people, as the robots do not completely replace the humans from the work process. The research community’s recent surge of interest in this area has been devoted to the implementation of various methodologies to achieve intuitive and seamless human–robot-environment interactions by incorporating the collaborative partners’ superior capabilities, e.g. human’s cognitive and robot’s physical power generation capacity. In fact, the main purpose of this paper is to review the state-of-the-art on intermediate human–robot interfaces (bi-directional), robot control modalities, system stability, benchmarking and relevant use cases, and to extend views on the required future developments in the realm of human–robot collaboration.     

The Digital Thesis: Recent Developments in Practice-Based PhD Research in Art & Design

This paper describes the recent developments in the use of digital media in the research process. It concentrates on the use of these media in practice-based PhD research in Art & Design, drawing on the experience gained at the Centre for Research in Art & Design, Gray's School of Art. The digital thesis is now a reality. The features of two examples of a digital thesis are described. The paper discusses the key considerations in developing such a document: benefits and limitations; general issues concerning planning, structure, and content; specific considerations for the design of the digital thesis, including navigation, required technology and support, different formats and development time. The paper concludes by speculating on issues for future developments.     

Proteomic approaches for discovery of new targets for vaccine and therapeutics against visceral leishmaniasis

Visceral leishmaniasis (VL) is the most devastating type caused by Leishmania donovani, Leishmania infantum, and Leishmania chagasi. The therapeutic mainstay is still based on the antiquated pentavalent antimonial against which resistance is now increasing. Unfortunately, due to the digenetic life cycle of parasite, there is significant antigenic diversity. There is an urgent need to develop novel drug/vaccine targets against VL for which the primary goal should be to identify and characterize the structural and functional proteins. Proteomics, being widely employed in the study of Leishmania seems to be a suitable strategy as the availability of annotated sequenced genome of Leishmania major has opened the door for dissection of both protein expression/regulation and function. Advances in clinical proteomic technologies have enable to enhance our mechanistic understanding of virulence/pathogenicity/host-pathogen interactions, drug resistance thereby defining novel therapeutic/vaccine targets. Expression proteomics exploits the differential expression of leishmanial proteins as biomarkers for application towards early diagnosis. Further using immunoproteomics efforts were also focused on evaluating responses to define parasite T-cell epitopes as vaccine/diagnostic targets. This review has highlighted some of the relevant developments in the rapidly emerging field of leishmanial proteomics and focus on its future applications in drug and vaccine discovery against VL.     

Human–robot interaction in industrial collaborative robotics: a literature review of the decade 2008–2017

ABSTRACT

Currently, a large number of industrial robots have been deployed to replace or assist humans to perform various repetitive and dangerous manufacturing tasks. However, based on current technological capabilities, such robotics field is rapidly evolving so that humans are not only sharing the same workspace with robots, but also are using robots as useful assistants. Consequently, due to this new type of emerging robotic systems, industrial collaborative robots or cobots, human and robot co-workers have been able to work side-by-side as collaborators to accomplish tasks in industrial environments. Therefore, new human–robot interaction systems have been developed for such systems to be able to utilize the capabilities of both humans and robots. Accordingly, this article presents a literature review of major recent works on human–robot interactions in industrial collaborative robots, conducted during the last decade (between 2008 and 2017). Additionally, the article proposes a tentative classification of the content of these works into several categories and sub-categories. Finally, this paper addresses some challenges of industrial collaborative robotics and explores future research issues.     

Intelligent e-business: from technology to value

E-business is the point where economic value creation and information technology come together. The Internet and the World Wide Web in particular have emerged as major driving forces in changing our economy. Business executives are now aware that information technology is a key strategic factor in industry, not just a tool to increase business-as-usual efficiency. This has happened over just a few years, but most of Internet business's socioeconomic impact likely lies ahead. These developments have led to the quick growth of scientific interest and activities related to e-business. Given these developments' pace and depth, big challenges and opportunities exist for applying intelligent systems technology and methodology. In fact, e-business has several distinct characteristics that make investigating the deployment of intelligent systems technology highly attractive.     

The Visual Analysis of Human Movement: A Survey

The ability to recognize humans and their activities by vision is key for a machine to interact intelligently and effortlessly with a human-inhabited environment. Because of many potentially important applications, “looking at people” is currently one of the most active application domains in computer vision. This survey identifies a number of promising applications and provides an overview of recent developments in this domain. The scope of this survey is limited to work on whole-body or hand motion; it does not include work on human faces. The emphasis is on discussing the various methodologies; they are grouped in 2-D approaches with or without explicit shape models and 3-D approaches. Where appropriate, systems are reviewed. We conclude with some thoughts about future directions.     

A model of pathways to artificial superintelligence catastrophe for risk and decision analysis

Abstract

An artificial superintelligence (ASI) is an artificial intelligence that is significantly more intelligent than humans in all respects. Whilst ASI does not currently exist, some scholars propose that it could be created sometime in the future, and furthermore that its creation could cause a severe global catastrophe, possibly even resulting in human extinction. Given the high stakes, it is important to analyze ASI risk and factor the risk into decisions related to ASI research and development. This paper presents a graphical model of major pathways to ASI catastrophe, focusing on ASI created via recursive self-improvement. The model uses the established risk and decision analysis modelling paradigms of fault trees and influence diagrams in order to depict combinations of events and conditions that could lead to AI catastrophe, as well as intervention options that could decrease risks. The events and conditions include select aspects of the ASI itself as well as the human process of ASI research, development and management. Model structure is derived from published literature on ASI risk. The model offers a foundation for rigorous quantitative evaluation and decision-making on the long-term risk of ASI catastrophe.     

Handling temporal heterogeneous data for content-based management of large video collections

Video document retrieval is now an active part of the domain of multimedia retrieval. However, unlike for other media, the management of a collection of video documents adds the problem of efficiently handling an overwhelming volume of temporal data. Challenges include balancing efficient content modeling and storage against fast access at various levels. In this paper, we detail the framework we have built to accommodate our developments in content-based multimedia retrieval. We show that not only our framework facilitates the development of processing and indexing algorithms but it also opens the way to several other possibilities such as rapid interface prototyping or retrieval algorithm benchmarking. Here, we discuss our developments in relation to wider contexts such as MPEG-7 and the TREC Video Track.This work is funded by EU-FP6 IST-NoE SIMILAR () and the Swiss NCCR IM2 (Interactive Multimodal Information Management).     

The impact of distributed computing on education

In this paper, developments in digital computer technology since the early Fifties are reviewed briefly, and the parallelism which exists between these developments and developments in analysis and design procedures of structural engineering is identified. The recent trends in digital computer technology are examined in order to establish the fact that distributed processing is now an accepted philosophy for further developments. The impact of this on the analysis and design practices of structural engineering is assessed by first examining these practices from a data processing standpoint to identify the key operations and data bases, and then fitting them to the characteristics of distributed processing. The merits and drawbacks of the present philosophy in educating structural engineers are discussed and projections are made for the industry-academia relations in the distributed processing environment of structural analysis and design. An ongoing experiment of distributed computing in a University environment is described.