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PubMed1992

Enzymes as molecular automata: a reflection on some numerical and philosophical aspects of the hypothesis.

Enzymes, by means of their properties of specific recognition and allosteric modulation, are able to integrate many separate processes into systemic units with coherent functions; in a sense, they have to be considered as the true organizers of the cytoplasmic processes. In this respect, the present article describes a simple model, based on binary variables and automata theory, which simulates the basic regulatory performance of the modulated enzyme. The model admits a variety of modifications and improvements; it also suggests some original lines of thought on which to reflect about the organization and collective phenomena of the networks of enzymes. In discussing the connection of this 'molecular automata' hypothesis with other areas of present-day theoretical biology, a fertile panorama of initiatives appear. A special partnership between Information Science (computation) and Biology is developing.

Cell Compartmentation↗

PubMed1992

The status of cognitive neuroscience.

Cognitive neuroscience rests on findings, methods, and theory from three fields: experimental psychology, systems-level neuroscience, and computer science. The strong trend over the past few years has been for a greater integration across these fields. The influence of this interdisciplinary approach on current research on memory, perception, and language will be illustrated.

Animals↗

PubMed2006

Pharmacophotonics: utilizing multi-photon microscopy to quantify drug delivery and intracellular trafficking in the kidney.

The recent introduction of multi-photon microscopy coupled with advances in optics, computer sciences and the available fluorophores used to label molecules of interest have empowered investigators to study the dynamic events within the functioning kidney at cellular and subcellular levels. This emerging technique, with improved spatial and temporal resolution and sensitivity, enables investigators to follow the cell specific uptake of large and small molecules, determine the mode of cellular uptake, intracellular trafficking and drug metabolism in complex heterogeneous organs such as the kidney over time. Repeat determinations over seconds to hours to days allow for multiple observations within the same animal, thereby minimizing animal use and inter-animal variability. This can be particularly useful for preclinical studies. Furthermore, the ability to obtain volumetric data (3-D) makes quantitative 4-D (time) analysis possible. Finally, up to three fluorophores can be visualized simultaneously allowing for three different or interactive processes to be observed and resolved.

Animals↗

PubMed2005

Screening for physical activity in family practice: evaluation of two brief assessment tools.

BACKGROUND: Physical activity (PA) is relevant to the prevention and management of many health conditions in family practice. There is a need for an efficient, reliable, and valid assessment tool to identify patients in need of PA interventions. METHODS: Twenty-eight family physicians in three Australian cities assessed the PA of their adult patients during 2004 using either a two- (2Q) or three-question (3Q) assessment. This was administered again approximately 3 days later to evaluate test-retest reliability. Concurrent validity was evaluated by measuring agreement with the Active Australia Questionnaire, and criterion validity by comparison with 7-day Computer Science Applications, Inc. (CSA) accelerometer counts. RESULTS: A total of 509 patients participated, with 428 (84%) completing a repeat assessment, and 415 (82%) accelerometer monitoring. The brief assessments had moderate test-retest reliability (2Q k=58.0%, 95% confidence interval [CI]=47.2-68.8%; 3Q k=55.6%, 95% CI=43.8-67.4%); fair to moderate concurrent validity (2Q k=46.7%, 95% CI=35.6-57.9%; 3Q k=38.7%, 95% CI=26.4-51.1%); and poor to fair criterion validity (2Q k=18.2%, 95% CI=3.9-32.6%; 3Q k=24.3%, 95% CI=11.6-36.9%) for identifying patients as sufficiently active. A four-level scale of PA derived from the PA assessments was significantly correlated with accelerometer minutes (2Q rho=0.39, 95% CI=0.28-0.49; 3Q rho=0.31, 95% CI=0.18-0.43). Physicians reported that the assessments took 1 to 2 minutes to complete. CONCLUSIONS: Both PA assessments were feasible to use in family practice, and were suitable for identifying the least active patients. The 2Q assessment was preferred by clinicians and may be most appropriate for dissemination.

Adolescent↗

PubMed2006

Temporal representation and reasoning in medicine: Research directions and challenges.

OBJECTIVE: The main aim of this paper is to propose and discuss promising directions of research in the field of temporal representation and reasoning in medicine, taking into account the recent scientific literature and challenging issues of current interest as viewed from the different research perspectives of the authors of the paper. BACKGROUND: Temporal representation and reasoning in medicine is a well-known field of research in the medical as well as computer science community. It encompasses several topics, such as summarizing data from temporal clinical databases, reasoning on temporal clinical data for therapeutic assessments, and modeling uncertainty in clinical knowledge and data. It is also related to several medical tasks, such as monitoring intensive care patients, providing treatments for chronic patients, as well as planning and scheduling clinical routine activities within complex healthcare organizations. METHODOLOGY: The authors jointly identified significant research areas based on their importance as for temporal representation and reasoning issues; the subjects were considered to be promising topics of future activity. Every subject was addressed in detail by one or two authors and then discussed with the entire team to achieve a consensus about future fields of research. RESULTS: We identified and focused on four research areas, namely (i) fuzzy logic, time, and medicine, (ii) temporal reasoning and data mining, (iii) health information systems, business processes, and time, and (iv) temporal clinical databases. For every area, we first highlighted a few basic notions that would permit any reader--including those who are unfamiliar with the topic--to understand the main goals. We then discuss interesting and promising directions of research, taking into account the recent literature and underlining the yet unresolved medical/clinical issues that deserve further scientific investigation. The considered research areas are by no means disjointed, because they share common theoretical and methodological features. Moreover, subjects of imminent interest in medicine are represented in many of the fields considered. CONCLUSIONS: We propose and discuss promising subjects of future research that deserve investigation to develop software systems that will properly manage the multifaceted temporal aspects of information and knowledge encountered by physicians during their clinical work. As the subjects of research have resulted from merging the different perspectives of the authors involved in this study, we hope the paper will succeed in stimulating discussion and multidisciplinary work in the described fields of research.

Artificial Intelligence↗

PubMed2006

On the legacy of W.S. McCulloch.

In this paper, we review McCulloch's legacy, from his early work in neurophysiology, and its relationship to his philosophical quest for an 'experimental epistemology' to his role in the cybernetics movement during the 1940s and 1950s and his contributions to the development of computer science and communication theory. There are three parts in chronological sequence. First, the period up to his work at Yale University with Dusser de Barenne, where he concentrated on the experimental study of the functional organization of sensory cortex. Second, the time of his Psychiatric Chair at the University of Chicago and the organization of the Macy Foundation Conferences. To this period corresponds the genesis and publication of the most influential and quoted work by McCulloch and Pitts: A Logical Calculus of the Ideas Immanent in Neurons Activity. Third, the period of his research activity at the Massachussetts Institute of Technology where he, Lettvin, Maturana and Pitts produced epochmaking papers on epistemological neurophysiology, the modelling of the reticular formation and other work with da Fonseca and Moreno-Díaz. We finally refer to the International Conference that took place in McCulloch's memory at the 25th anniversary of his death. Our main conclusion is that McCulloch's writings are still a source of inspiration from neurophysiology to artificial intelligence and robotics.

Artificial Intelligence↗

PubMed2005

Prognostic/predictive factors in breast cancer.

This can be an exciting time for pathologists and cytopathologists as we refine or knowledge of prognostic/predictive factors in breast cancer. We can become more visible in our role as consultants to the other physicians, and more engaged in our role as re-searchers. Recent advances in computer science, coupled with the availability of new biological markers, now provide unique opportunities for us to expand our diagnostic abilities and also predict the biologic behavior of a given tumor. Thus, we must become more familiar with emerging concepts and technologies in different disciplines.

Axilla↗

PubMed2006

Modelling, property verification and behavioural equivalence of lactose operon regulation.

Understanding biochemical pathways is one of the biggest challenges in the field of molecular biology nowadays. Computer science can contribute in this area by providing formalisms and tools to simulate and analyse pathways. One formalism that is suited for modelling concurrent systems is Milner's Calculus of Communicating Systems (CCS). This paper shows the viability of using CCS to model and reason about biochemical networks. As a case study, we describe the regulation of lactose operon. After describing this operon formally using CCS, we validate our model by automatically checking some known properties for lactose regulation. Moreover, since biological systems tend to be very complex, we propose to use multiple descriptions of the same system at different levels of abstraction. The compatibility of these multiple views can be assured via mathematical proofs of observational equivalence.

Lactose↗

PubMed2006

Assessment of Internet-based tele-medicine in Africa (the RAFT project).

The objectives of this paper on the Réseau Afrique Francophone de Télémédecine (RAFT) project are the evaluation of feasibility, potential, problems and risks of an Internet-based tele-medicine network in developing countries of Africa. The RAFT project was started in Western African countries 5 years ago and has now extended to other regions of Africa as well (i.e. Madagascar, Rwanda). A project for the development of a national tele-medicine network in Mali was initiated in 2001, extended to Mauritania in 2002 and to Morocco in 2003. By 2006, a total of nine countries are connected. The entire technical infrastructure is based on Internet technologies for medical distance learning and tele-consultations. The results are a tele-medicine network that has been in productive use for over 5 years and has enabled various collaboration channels, including North-to-South (from Europe to Africa), South-to-South (within Africa), and South-to-North (from Africa to Europe) distance learning and tele-consultations, plus many personal exchanges between the participating hospitals and Universities. It has also unveiled a set of potential problems: (a) the limited importance of North-to-South collaborations when there are major differences in the available resources or the socio-cultural contexts between the collaborating parties; (b) the risk of an induced digital divide if the periphery of the health system in developing countries is not involved in the development of the network; and (c) the need for the development of local medical content management skills. Particularly point (c) is improved through the collaboration between the various countries as professionals from the medical and the computer science field are sharing courses and resources. Personal exchanges between partners in the project are frequent, and several persons received an education at one of the partner Universities. As conclusion, we can say that the identified risks have to be taken into account when designing large-scale tele-medicine projects in developing countries. These problems can be mitigated by fostering South-South collaboration channels, by the use of satellite-based Internet connectivity in remote areas, the appreciation of local knowledge and its publication on-line. The availability of such an infrastructure also facilitates the development of other projects, courses, and local content creation.

Africa↗

PubMed2006

Defining the expert ICU nurse.

This paper explores the concept of expertise in intensive care nursing practice from the perspective of its relationship to the current driving forces in healthcare. It discusses the potential barriers to acceptance of nursing expertise in a climate in which quantification of value and cost containment run high on agendas. It argues that nursing expertise which focuses on the provision of individualised, holistic care and which is based largely on intuitive decision-making cannot and should not be reduced to being articulated in positivist terms. The principles of abduction or fuzzy logic, derived from computer science, may be useful in assisting nurses to explain in terms, which others can comprehend, the value of nursing expertise.

Art↗

PubMed2005

Proteomic approaches in the search for disease biomarkers.

Significant technological advances in protein chemistry, physics and computer sciences in the last two decades have greatly improved protein separation methodologies, such as electrophoresis and chromatography, and have established mass spectrometry (MS) as an indispensable tool for protein study. The goal of this review is to provide a brief overview of the recent improvements in these methodologies and present examples from their application in proteome analysis and search for disease biomarkers.

Biomarkers↗

PubMed2005

TB subunit vaccines--putting the pieces together.

The search for a new and improved vaccine against tuberculosis (TB) is currently a very active field of research, which in the last 10 years has benefited tremendously from the completed Mycobacterium tuberculosis genome and the progress in molecular biology and computer science. In this review, we discuss how Genomics, Proteomics and Transcriptomics have accelerated the pace of antigen discovery and vaccine development and have changed this field completely, resulting in the identification of a large number of antigens with potential in TB vaccines. The next phase of this work has now started--putting the most relevant molecules back together as fusion molecules and cocktails. This requires carefully monitoring aspects as immunodominance, recognition in different populations as well as vaccine manufacturing.

Antigens, Bacterial↗

PubMed2005

Challenges in real-life emotion annotation and machine learning based detection.

Since the early studies of human behavior, emotion has attracted the interest of researchers in many disciplines of Neurosciences and Psychology. More recently, it is a growing field of research in computer science and machine learning. We are exploring how the expression of emotion is perceived by listeners and how to represent and automatically detect a subject's emotional state in speech. In contrast with most previous studies, conducted on artificial data with archetypal emotions, this paper addresses some of the challenges faced when studying real-life non-basic emotions. We present a new annotation scheme allowing the annotation of emotion mixtures. Our studies of real-life spoken dialogs from two call center services reveal the presence of many blended emotions, dependent on the dialog context. Several classification methods (SVM, decision trees) are compared to identify relevant emotional states from prosodic, disfluency and lexical cues extracted from the real-life spoken human-human interactions.

Artificial Intelligence↗

PubMed2005

A new mathematical process for the calculation of average forms of teeth.

STATEMENT OF PROBLEM: Qualitative visual inspections and linear metric measurements have been predominant methods for describing the morphology of teeth. No quantitative formulation exists for the description of dental features. PURPOSE: The aim of this study was to determine and validate a mathematical process for calculation of the average form of first maxillary molars, including the general occlusal features. MATERIAL AND METHODS: Stone replicas of 174 caries-free first maxillary molar crowns from young patients ranging from 6 to 9 years of age were measured 3-dimensionally with a laser scanning system at a resolution of approximately 100,000 points. Then, the average tooth was computed, which captured the common features of the molar's surface quantitatively. This new method adapts algorithms both from computer science and neuroscience to detect and associate the same features and same surface points (correspondences) between 1 reference tooth and all other teeth. In this study, the method was tested for 7 different reference teeth. The algorithm does not involve any prior knowledge about teeth and their features. RESULTS: Irrespective of the reference tooth used, the procedure yielded average teeth that showed nearly no differences (less than +/-30 microm). CONCLUSION: This approach provides a valid quantitative process for calculating 3-dimensional (3D) averages of occlusal surfaces of teeth even in the event of a high number of digitized surface points. Additionally, because this process detects and assigns point-wise feature correspondences between all library teeth, it may also serve as a basis for a more substantiated principal component analysis evaluating the main natural shape deviations from the 3D average.

Algorithms↗

PubMed1987

Surgical treatment of familial polyposis. The ileal reservoir/anal pull-through.

The success of the procedure is evaluated by the number of bowel movements the patient has in a 24-hour period. Nine or more in 24 hours is considered poor; the average postoperative patient has five to six. As the patient's functional results improve, he is generally more at ease in social and work environments. He can govern his own routine to a great extent, rather than being tied to the bathroom. Usually, the patient can return to work in about four weeks after the ileostomy takedown. Generally, these patients seem to be satisfied with the results of their surgery. One study noted that 92% of the patients studied stated they would not hesitate to have the same operation again if faced with the same options. For the first few months postoperatively, Billy was somewhat apprehensive that he would have an "accident." He did not report any, though. He also did not leak any stools, even at night. Now, more than a year after the surgery, Billy has about four to six bowel movements a day and continues to take psyllium hydrophilic mucilloid daily. He has occasional mild irritation of the perianal skin. He has also gained 15 pounds. Billy returned to college to complete his senior year six months postoperatively. He took a full course load and planned to graduate in August 1987 with a degree in computer science. He reported that, "I'm doing very well. I just forget I had surgery."

Adenomatous Polyposis Coli↗

PubMed2001

Improved process control alarm operation.

Alarms are the main connection from the automation to the operator, when addressing process operation outside of its normal function. They are often as much a source of operator overload and consternation as help. Better engineering of the relative role of the operator and automation would materially help overcome the difficulties. Expert systems have been proposed as a solution. But Expert systems are really another form of automation. There remains that aspect of the alarms, which must address our inability to cover and understand a possibly larger domain of the operation not appropriate to traditional controls or present-day automation. Appropriate tools for this domain must support operator discretion and initiative. The paper suggests a set of such general, computer science based, tools requiring only the most basic configuration. They are viewed as implemented on top of those properly detailed alarm displays and interlocks, which reflect the more formal plant operating policies. They include: (a) Various forms of alarm logging and trending; (b) Short, automatically generated, word summaries of alarm activity, which allow low level data to propagate to the highest levels, including: one word and priority summaries; (c) Causal alarm pattern analyses that help the operator to predict or diagnose alarm behavior; (d) Automatic adaptation of alarms and alarm limits to varying process situations; (e) Uniform use of alarm policies to simplify alarm configuration.

Journal Article↗

PubMed2002

Distributed structure-searchable toxicity (DSSTox) public database network: a proposal.

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, Structure-Activity Relationship (SAR) model development, or building of chemical relational databases (CRD). The distributed structure-searchable toxicity (DSSTox) public database network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: (1) to adopt and encourage the use of a common standard file format (structure data file (SDF)) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; (2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data sources with potential users of these data from other disciplines (such as chemistry, modeling, and computer science); and (3) to engage public/commercial/academic/industry groups in contributing to and expanding this community-wide, public data sharing and distribution effort. The DSSTox project's overall aims are to effect the closer association of chemical structure information with existing toxicity data, and to promote and facilitate structure-based exploration of these data within a common chemistry-based framework that spans toxicological disciplines.

Carcinogens↗

PubMed2003

Integrating mind and brain: Warren S. McCulloch, cerebral localization, and experimental epistemology.

Recently, historians have focused on Warren S. McCulloch's role in the cybernetics movement during the 1940s and 1950s, and his contributions to the development of computer science and communication theory. What has received less attention is McCulloch's early work in neurophysiology, and its relationship to his philosophical quest for an 'experimental epistemology' - a physiological theory of knowledge. McCulloch's early laboratory work during the 1930s addressed the problem of cerebral localization: localizing aspects of behaviour in the cerebral cortex of the brain. Most of this research was done with the Dutch neurophysiologist J.G. Dusser de Barenne at Yale University. The connection between McCulloch's philosophical interests and his experimental work can be expressed as a search for a physiological a priori, an integrated mechanism of sensation.

Brain↗