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PubMed2004

Optimal identification of biochemical reaction networks.

Advances in biotechnology and computer science are providing the possibility to construct mathematical models for complex biological networks and systematically understand their properties. Traditional network identification approaches, however, cannot accurately recover the model parameters from the noisy laboratory measurements. This article introduces the concept of optimal identification (OI), which utilizes a global inversion algorithm to extract the full distribution of parameters consistent with the laboratory data. In addition, OI integrates suitable computational algorithms with experimental capabilities in a closed loop fashion to maximally reduce the breadth of the extracted parameter distribution. The closed loop OI procedure seeks out the optimal set of control chemical fluxes and data observations that actively filter out experimental noise and enhance the sensitivity to the desired parameters. In this fashion, the highest quality network parameters can be attained from inverting the tailored laboratory data. The operation of OI is illustrated by identifying a simulated tRNA proofreading mechanism, in which OI provides superior solutions for all the rate constants compared with suboptimal and nonoptimal methods.

Algorithms↗

PubMed2006

Computational methodologies for modelling, analysis and simulation of signalling networks.

This article is a critical review of computational techniques used to model, analyse and simulate signalling networks. We propose a conceptual framework, and discuss the role of signalling networks in three major areas: signal transduction, cellular rhythms and cell-to-cell communication. In order to avoid an overly abstract and general discussion, we focus on three case studies in the areas of receptor signalling and kinase cascades, cell-cycle regulation and wound healing. We report on a variety of modelling techniques and associated tools, in addition to the traditional approach based on ordinary differential equations (ODEs), which provide a range of descriptive and analytical powers. As the field matures, we expect a wider uptake of these alternative approaches for several reasons, including the need to take into account low protein copy numbers and noise and the great complexity of cellular organisation. An advantage offered by many of these alternative techniques, which have their origins in computing science, is the ability to perform sophisticated model analysis which can better relate predicted behaviour and observations.

Algorithms↗

PubMed1986

[Contraception and informatics. SELF, a system to aid medical decisions applied to the prescription of contraceptive methods].

SELF (systeme en logique floue = system in soft discware), developed by the Computer Sciences Laboratory of the Faculté de Médecine in Nancy, is, by comparison to many systems of assistance in medical decisions already existing, a comprehensive and simple unit enabling the construction and modification of basic knowledge as well as its questioning. The first application of SELF concerned the field of gynecology, by producing a system of assistance applied to the prescription of a contraceptive method. The systematic use of this computer program along with the traditional prescription of a contraceptive method, was tested for three months in the Regional Maternity Hospital by several physicians in the Gynecology Clinic. The system was extremely well accepted and the responses have generated numerous discussions between physicians leading to an improvement of SELF and a better rationalization of the prescription. The medical and paramedical personnel in training at the hospital found SELF to be a teaching tool which, on the basis of simulated cases, permits an easier and more concrete explanation of the practical management in advising or prescribing a contraceptive method.

Contraceptive Agents, Female↗

PubMed2005

[Computer-assisted facial reconstruction: recent developments and trends].

Three-dimensional (3D) craniofacial reconstruction can be a useful tool in the identification of an unknown body. The progress in computer science and the improvement of medical imaging technologies during recent years has had a significant impact on this domain. New facial soft tissue depth data have been obtained. New guidelines for facial feature properties such as nose projection, eye protrusion or mouth width, have been suggested, but also older theories and "rules of thumbs" have been critically evaluated based on digital technology. New fast, flexible and objective 3D reconstruction computer-based programs are in full development. Employing the newer technologies and permanently evaluating the obtained results will hopefully lead to more accurate reconstructions.

Algorithms↗

PubMed2026

Polyploidy Arithmetic.

Polyploidy occurs in plants and animals, and is an important force in speciation and genome evolution. The main focus of this paper is the following fundamental question that was recently posed by Huber and Maher: Given the ploidy numbers of a collection of extant species, or their ploidy profile, what is the smallest number of hybridizations needed in any evolutionary history for these species to completely represent these numbers? In this paper, we shall show that this question can be rephrased in terms of addition chains and the closely related addition sequences, which have been studied for over a century in mathematics and computer science. These are sequences of natural numbers that start with 1, so that each number in the sequence larger than 1 is the sum of two other numbers arising earlier in the sequence. In our first main result, we show that finding the smallest number of hybridization events to explain a ploidy profile, or the hybrid number, is equivalent to solving the so-called addition sequence problem. This immediately implies that computing the hybridization number is computationally intractable. Even so, it also leads to new connections to representing polyploid evolution using networks. More specifically, in our second main result we show that ploidy profiles representable by tree-child networks are exactly the addition chains, implying a polynomial-time algorithm for identifying these profiles. We then consider beaded tree-child networks, which permit the representation of autopolyploidy events, and in our third main result we provide a greedy polynomial-time algorithm to decide whether a given profile can be realized by such a network. We expect that our results can be leveraged in future work through, for example, making use of known algorithms for computing short addition sequences to give bounds for the hybrid number, and in guiding network reconstruction for polyploid species.

Polyploidy↗

PubMed1989

[Cardiac imaging using magnetic resonance].

Today, two types of cardiac imaging may be obtained in MRI. The spin-echo technique with ECG dependency permits to obtain multiple sections in all spatial planes; the morphology of the heart cavities may then be evaluated as well as the condition of the myocardium (thickness, signal, movements). The gradient-echo technique permits a quick imaging or cine-MRI. 16 to 32 images per cardiac cycle are obtained: therefore, analysis of the flows, turbulence and regurgitations. Early developments involve computer sciences: automatic analysis of the heart cavities (volume, stroke volume, etc.) and regurgitations in order to quantify them. Comparative trials show a good correlation with standard explorations. Late developments at 4-5 years: these are newly acquired techniques such as echo planar (spirals of Fourier's plane) permitting to obtain in one second, 8 stages of the heart cycle. This would then be a true and fast cardiac recording. The same techniques of computer analysis will permit to obtain precise measurements.

Coronary Circulation↗

PubMedDate not supplied

A virtual instrument (VI) for haemodynamic management in ICU and during surgery.

Systolic pressure variations (SPV) during mechanical ventilation and its single components, related to short apnea, reflect changes of the volemic condition of the patient. To introduce their determination during clinical monitoring for different fluid states and for different tidal volumes, they must be computed on-line without introducing interference with standard activities. A system computing on-line systolic pressure variation during mechanical ventilation, connected to standard monitoring devices, has been proposed. It is based on a notebook PC implemented with graphical software comprising a user panel in the form of a virtual instrument and is able to acquire, process and present signals from different instruments utilized in ICU and during surgery. It can be used as a base to assess the ability of computed parameters helpful in clinical decision. The use of a notebook PC and open software allows operators, even if non-expert in computer science, to test and implement this, as well as other innovative tools in clinical practice.

Blood Pressure Determination↗

PubMed1988

Recent advances in computer image generation simulation.

An explosion in flight simulator technology over the past 10 years is revolutionizing U.S. Air Force (USAF) operational training. The single, most important development has been in computer image generation. However, other significant advances are being made in simulator handling qualities, real-time computation systems, and electro-optical displays. These developments hold great promise for achieving high fidelity combat mission simulation. This article reviews the progress to date and predicts its impact, along with that of new computer science advances such as very high speed integrated circuits (VHSIC), on future USAF aircrew simulator training. Some exciting possibilities are multiship, full-mission simulators at replacement training units, miniaturized unit level mission rehearsal training simulators, onboard embedded training capability, and national scale simulator networking.

Aviation↗

PubMed2000

Spatio-logical processes in intracellular signalling.

Classical models of intracellular signalling describe how small changes in a cell's external environment can bring about major changes in cellular activity. Recent findings from experimental biology indicate that many intracellular signalling systems show a high level of spatial organisation. This permits the modification, by protein kinase or protein phosphatase action, of specific subsets of intracellular proteins - an attribute that is not addressed in classical signalling models. Here we use ideas and concepts from computer science to describe the information processing nature of intracellular signalling pathways and the impact of spatial heterogeneity of their components (e.g. protein kinases and protein phosphatases) on signalling activity. We argue that it is useful to view the signalling ecology as a vast parallel distributed processing network of agents operating in heterogeneous microenvironments, and we conclude with an overview of the mathematical and semantic methodologies that might help clarify this analogy between biological and computational systems.

Models, Biological↗

PubMed2001

Computational models of cells and tissues: machines, agents and fungal infection.

Computational models have been of interest in biology for many years and have represented a particular approach to trying to understand biological processes and phenomena from a systems point of view. Much of the early work was rather abstract and high level and probably seemed to many to be of more philosophical than practical value. There have, however, been some advances in the development of more realistic models and the current state of computer science research provides us with new opportunities through both the emergence of models that can model seriously complex systems and also the support that modern software can give to the modelling process. This paper describes a few of the early simple models and then goes on to look at some new ideas in the area with a particular application drawn from the world of mycology. Some general principles relating to how new and emerging computational techniques can help to represent and understand extremely complex models conclude the paper.

Computational Biology↗

PubMed2000

Comparison of three methods for measuring the time spent in physical activity.

PURPOSE: Three methods for measuring time spent in daily physical activity (PA) were compared during a 21-d period among 83 adults (38 men and 45 women). METHODS: Each day, participants wore a Computer Science and Applications, Inc. (CSA) monitor and completed a 1-page, 48-item PA log that reflected time spent in household, occupational, transportation, sport, conditioning, and leisure activities. Once a week, participants also completed a telephone survey to identify the number of minutes spent each week in nonoccupational walking and in moderate intensity and hard/very hard-intensity PA. Data were analyzed using descriptive statistics and Spearman rank-order correlations. Three equations developed to compute CSA cut points for moderate and hard/very hard PA were also compared with the PA logs and PA survey. RESULTS: There was modest to good agreement for the time spent in different PA intensity categories between the three CSA cut point methods (r = 0.43-0.94, P < 0.001). Correlations between the CSA and PA logs ranged from r = 0.22 to r = 0.36, depending on the comparisons. Correlations between the survey items and PA logs were r = 0.26-0.54 (P < 0.01) for moderate and walking activities and r < 0.09 (P > 0.05) for hard/very hard activities. Correlations between the survey items and the CSA min per day varied according to the method used to compute the CSA intensity cut points. CONCLUSIONS: The results were consistent with findings from other PA validation studies that show motion sensors, PA logs, and surveys reflect PA; however, these methods do not always provide similar estimates of the time spent in resting/light, moderate, or hard/very hard PA.

Activities of Daily Living↗

PubMed1984

Diagnostic, therapeutic, didactic, data bank utilization of computerized monitoring in a critical care center.

At the beginning of their discovery informatic technique procedures and methodologies generated a great wave of hopes for progress in theoretical and practical fields of human activity, but when passing to concrete application, an ebb phase followed. Recent theoretical and technical progress, however, has generated an enormous new up-surge of interest for applications of informatic processing in all fields of science. Medicine in the last three decades has gone through the same phases observed in other disciplines. In the ICU the potentiality of exploitation of the informatic techniques appeared enormous, however, initially from a practical point of view it found only limited, sectorial experimentation and implementation, but afterwards a limited and slow process of parcellar infiltration, the high tide of informatic, has broken the dam and deeply advanced in its territory, obliging the staff to a great effort of cultural and technical updating to cope with it. After recalling some of the history of Computer Science or Informatic, even if history was only yesterday, we will present some examples of the hand made experience of an ICU, (namely ours) with limited economical resources, and whose interest in this field arises from actual needs, personal interest and enthusiasm of a staff who works, on its free time, after fulfilling its stressing routine.

Computers↗

PubMed2006

Why there should be more science Nobel prizes and laureates - And why proportionate credit should be awarded to institutions.

The four science Nobel prizes (physics, chemistry, medicine/physiology and economics) have performed extremely well as a method of recognizing the highest level of achievement. The prizes exist primarily to honour individuals but also have a very important function in science generally. In particular, the institutions and nations which have educated, nurtured or supported many Nobel laureates can be identified as elite in world science. However, the limited range of subjects and a maximum of 12 laureates per year mean that many major scientific achievements remain un-recognized; and relatively few universities can gather sufficient Nobel-credits to enable a precise estimate of their different levels of quality. I advocate that the Nobel committee should expand the number of Nobel laureates and Prize categories as a service to world science. (1) There is a large surplus of high quality prize candidates deserving of recognition. (2) There has been a vast expansion of research with a proliferation of major sub-disciplines in the existing categories. (3) Especially, the massive growth of the bio-medical sciences has created a shortage of Nobel recognition in this area. (4) Whole new fields of major science have emerged. I therefore suggest that the maximum of three laureates per year should always be awarded in the categories of physics, chemistry and economics, even when these prizes are for diverse and un-related achievements; that the number of laureates in the 'biology' category of physiology or medicine should be increased to six or preferably nine per year; and that two new Prize categories should be introduced to recognize achievements in mathematics and computing science. Together, these measures could increase the science laureates from a maximum of 12 to a minimum of 24, and increase the range of scientific coverage. In future, the Nobel committee should also officially allocate proportionate credit to institutions for each laureate, and a historical task force could also award institutional credit for past prizes.

Chemical Phenomena↗

PubMed2007

Interdisciplinary innovations in biomedical and health informatics graduate education.

OBJECTIVES: Biomedical and health informatics (BHI) is a rapidly growing domain that relies on the active collaboration with diverse disciplines and professions. Educational initiatives in BHI need to prepare students with skills and competencies that will allow them to function within and even facilitate interdisciplinary teams (IDT). This paper describes an interdisciplinary educational approach introduced into a BHI graduate curriculum that aims to prepare informatics researchers to lead IDT research. METHODS: A case study of the "gerontechnology" research track is presented which highlights how the curriculum fosters collaboration with and understanding of the disciplines of Nursing, Engineering, Computer Science, and Health Administration. Gerontechnology is a new interdisciplinary field that focuses on the use of technology to support aging. Its aim is to explore innovative ways to use information technology and develop systems that support independency and increase quality of life for senior citizens. As a result of a large research group that explores "smart home" technologies and the use of information technology, we integrated this new domain into the curriculum providing a platform for computer scientists, engineers, nurses and physicians to explore challenges and opportunities with our informatics students and faculty. RESULTS: The interdisciplinary educational model provides an opportunity for health informatics students to acquire the skills for communication and collaboration with other disciplines. Numerous graduate and postgraduate students have already participated in this initiative. The evaluation model of this approach is presented. CONCLUSION: Interdisciplinary educational models are required for health informatics graduate education. Such models need to be innovative and reflect the needs and trends in the domains of health care and information technology.

Aged↗

PubMed1998

[A new concept in surgery of the digestive tract: surgical procedure assisted by computer, from virtual reality to telemanipulation].

Surgical simulation increasingly appears to be an essential aspect of tomorrow's surgery. The development of a hepatic surgery simulator is an advanced concept calling for a new writing system which will transform the medical world: virtual reality. Virtual reality extends the perception of our five senses by representing more than the real state of things by the means of computer sciences and robotics. It consists of three concepts: immersion, navigation and interaction. Three reasons have led us to develop this simulator: the first is to provide the surgeon with a comprehensive visualisation of the organ. The second reasons is to allow for planning and surgical simulation that could be compared with the detailed flight-plan for a commercial jet pilot. The third lies in the fact that virtual reality is an integrated part of the concept of computer assisted surgical procedure. The project consists of a sophisticated simulator which must include five requirements: a) visual fidelity, b) interactivity, c) physical properties, d) physiological properties, e) sensory input and output. In this report we describe how to obtain a realistic 3D model of the liver from bi-dimensional 2D medical images for anatomical and surgical training. The introduction of a tumor and the consequent planning and virtual resection is also described, as are force feedback and real-time interaction.

Anatomy, Cross-Sectional↗

PubMed2005

Three-dimensional cranio-facial reconstruction in forensic identification: latest progress and new tendencies in the 21st century.

Three-dimensional (3D) cranio-facial reconstruction can be useful in the identification of an unknown body. The progress in computer science and the improvement of medical imaging technologies during recent years had significant repercussions on this domain. New facial soft tissue depth data for children and adults have been obtained using ultrasound, CT-scans and radiographies. New guidelines for facial feature properties such as nose projection, eye protrusion or mouth width, have been suggested, but also older theories and "rules of thumbs" have been critically evaluated based on digital technology. New fast, flexible and objective 3D reconstruction computer programs are in full development. The research on craniofacial reconstruction since the beginning of the 21st century is presented, highlighting computer-aided 3D facial reconstruction. Employing the newer technologies and permanently evaluating and (re)questioning the obtained results will hopefully lead to more accurate reconstructions.

Face↗

PubMed1997

[A new concept in digestive surgery: the computer assisted surgical procedure, from virtual reality to telemanipulation].

Surgical simulation increasingly appears to be an essential aspect of tomorrow's surgery. The development of a hepatic surgery simulator is an advanced concept calling for a new writing system which will transform the medical world: virtual reality. Virtual reality extends the perception of our five senses by representing more than the real state of things by the means of computer sciences and robotics. It consists of three concepts: immersion, navigation and interaction. Three reasons have led us to develop this simulator: the first is to provide the surgeon with a comprehensive visualisation of the organ. The second reason is to allow for planning and surgical simulation that could be compared with the detailed flight-plan for a commercial jet pilot. The third lies in the fact that virtual reality is an integrated part of the concept of computer assisted surgical procedure. The project consists of a sophisticated simulator which has to include five requirements: visual fidelity, interactivity, physical properties, physiological properties, sensory input and output. In this report we will describe how to get a realistic 3D model of the liver from bi-dimensional 2D medical images for anatomical and surgical training. The introduction of a tumor and the consequent planning and virtual resection is also described, as are force feedback and real-time interaction.

Computer Simulation↗

PubMed2000

A rapid heuristic algorithm for finding minimum evolution trees.

The minimum sum of branch lengths (S), or the minimum evolution (ME) principle, has been shown to be a good optimization criterion in phylogenetic inference. Unfortunately, the number of topologies to be analyzed is computationally prohibitive when a large number of taxa are involved. Therefore, simplified, heuristic methods, such as the neighbor-joining (NJ) method, are usually employed instead. The NJ method analyzes only a small number of trees (compared with the size of the entire search space); so, the tree obtained may not be the ME tree (for which the S value is minimum over the entire search space). Different compromises between very restrictive and exhaustive search spaces have been proposed recently. In particular, the "stepwise algorithm" (SA) utilizes what is known in computer science as the "beam search," whereas the NJ method employs a "greedy search." SA is virtually guaranteed to find the ME trees while being much faster than exhaustive search algorithms. In this study we propose an even faster method for finding the ME tree. The new algorithm adjusts its search exhaustiveness (from greedy to complete) according to the statistical reliability of the tree node being reconstructed. It is also virtually guaranteed to find the ME tree. The performances and computational efficiencies of ME, SA, NJ, and our new method were compared in extensive simulation studies. The new algorithm was found to perform practically as well as the SA (and, therefore, ME) methods and slightly better than the NJ method. For searching for the globally optimal ME tree, the new algorithm is significantly faster than existing ones, thus making it relatively practical for obtaining all trees with an S value equal to or smaller than that of the NJ tree, even when a large number of taxa is involved.

Algorithms↗