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PubMed1996

A New Family of Multivalued Networks.

This paper introduces a new family of multivalued neural networks. We have interpreted the Hopfield network as encoding the same/different information of elements of binary patterns in the connections and developed a scheme which encodes bigger/smaller information of multivalued patterns in the connections with the aid of signum function. The model can be constructed as an autoassociative memory (multivalued counterpart of Hopfield) or heteroassociative memory (multivalued counterpart of BAM). We have used Lyapunov stability analysis in showing the stability of networks. In simulations the energy surface topography of the model is compared to that of Hopfield. Also, asymptotic stability and basin of attraction of the stored patterns are examined. The proposed model can also be used in solving the optimization problems. Mapping a problem on to the network is relatively easy compared to the Hopfield model because of the multivalued representation. Very good results are obtained in traveling salesperson problem simulations. Copyright 1996 Elsevier Science Ltd.

Journal Article↗
PubMed2025

Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study.

BACKGROUND: Rising antimicrobial resistance of Helicobacter pylori is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in H pylori and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin. METHODS: In this retrospective phenotypic and genotypic observational study, we included 1011 H pylori whole-genome sequences and strains of known geographical origin from the H pylori Genome Project (HpGP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 HpGP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify 23S rRNA and gyrA variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, 23S rRNA 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, gyrA A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype-phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete HpGP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the HpGP genomes and 768 whole-genome sequences retrieved from the US National Center for Biotechnology Information Sequence Read Archive repository. Associations between resistance genotypes, H pylori subpopulations, and minimum inhibitory concentrations (MICs) were tested. FINDINGS: Clarithromycin-resistant and levofloxacin-resistant HpGP strains were estimated with a sensitivity and specificity of 100%, with all confidence intervals ranging from 96% to 100%. The combined analysis (n=1779) found the highest prevalence of clarithromycin resistance in the western Pacific region (173 [51·2%] of 338 in southeast Asia and 75 [29·8%] of 252 in eastern Asia), north African region (seven [38·9%] of 18), and western Asian region (12 [31·6%] of 38), whereas the highest prevalence of levofloxacin resistance was found in south Asia (14 [51·85%] of 27), Central America (48 [38·7%] of 124), eastern Europe (four [36·4%] of 11), and southern Africa (three [33·3%] of nine). Similarly, 23S rRNA and gyrA genotypes are variable across H pylori subpopulations. MIC values changed depending on the specific mutation in 23S rRNA (mean clarithromycin MIC 24·61 mg/L [95% CI 12·27-36·96] for 2143A→G and 142·25 mg/L [95% CI 77·88-206·61] for 2142A→G) and gyrA (mean levofloxacin MIC 9·66 mg/L [95% CI 6·75-12·56] for mutations on codon 91, and 27·97 mg/L [95% CI 25·82-30·11] for mutations on codon 87). INTERPRETATION: Mutations in specific genes are reliable indicators to clarithromycin and levofloxacin resistance in H pylori, making them useful markers for the development of diagnostic assays and molecular monitoring. Our results suggest that using clarithromycin and levofloxacin empirically, without previous susceptibility testing, is unsuitable in all geographical regions covered by this study. FUNDING: Intramural Research Program of the US National Cancer Institute, the European Research Council, and the Spanish Ministry of Science and Innovation.

Helicobacter pylori↗
PubMed2003

Self-correction mechanism for path integration in a modular navigation system on the basis of an egocentric spatial map.

Classical Computer Science approaches to navigation by autonomous robots continue to make good progress. However, we have only a limited understanding of how navigation is implemented in the neural networks of animals, which still perform very much better in navigational tasks than robots. In this paper we explore the implementation of neural network based navigation in a simple robot. We use a modular navigation system that contains separate representations of visual input and the path integration process. These representations are combined to influence the behavior of a robot. Both representations are encoded within recurrent neuronal networks. The outputs of the representations are vectors of polar values that encode the location of the nearest object, or of a specific place in the environment. The robot manoeuvres in relation to these attended locations, in the context of its egocentric spatial map. During ego-motion towards a goal, the network representation of the goal moves in a counter-movement due to applied motor feedback. The robot's position is continuously compared against its visual input, and mismatches between the visually perceived goal position and its spatial representation are corrected.

Ego↗
PubMed1997

The functional matrix hypothesis revisited. 1. The role of mechanotransduction.

The periodic incorporation of advances in the biomedical, bioengineering, and computer sciences allow the creation of increasingly more comprehensive revisions of the functional matrix hypothesis. Inclusion of two topics, (1) the mechanisms of cellular mechanotransduction, and (2) biologic network theory, permit this latest revision; presented here in two interrelated articles. In this first article, the several possible types of intracellular processes of mechanotransduction are described. These translate the informational content of a periosteal functional matrix stimulus into a skeletal unit (bone) cell signal. The correlation between the strengths of the endogenous electrical fields produced by muscle skeletal muscle activity, and those to which bone cells maximally respond are stressed. Further, a physical chain of macromolecular levers, connecting the extracellular matrix to the bone cell genome is described, suggesting another means of epigenetic regulation of the bone cell genome, including its phenotypic expression.

Adaptation, Physiological↗
PubMed2001

Proactive health computing.

In an analysis departing from the global health situation, the foundation for a change of paradigm in health informatics based on socially embedded information infrastructures and technologies is identified and discussed. It is shown how an increasing computing and data transmitting capacity can be employed for proactive health computing. As a foundation for ubiquitous health promotion and prevention of disease and injury, proactive health systems use data from multiple sources to supply individuals and communities evidence-based information on means to improve their state of health and avoid health risks. The systems are characterised by: (1) being profusely connected to the world around them, using perceptual interfaces, sensors and actuators; (2) responding to external stimuli at faster than human speeds; (3) networked feedback loops; and (4) humans remaining in control, while being left outside the primary computing loop. The extended scientific mission of this new partnership between computer science, electrical engineering and social medicine is suggested to be the investigation of how the dissemination of information and communication technology on democratic grounds can be made even more important for global health than sanitation and urban planning became a century ago.

Artificial Intelligence↗
PubMed2005

[The current mind-brain theories in analytical philosophy of mind and their epistemic significance for psychiatry].

This article begins with an orientational survey of the historical evolution of analytical philosophy of mind (APM) which was formulated in the last 40 years as "philosophy of mind" in the Anglo-Saxon scientific-cultural world and which, in the meantime, dominates to a great extent contemporary German philosophy. Then there follows a discussion of the currently most popular mind-brain theories in philosophy. In comparison to the more marginal dualist variants (interactionism, epiphenomenalism, parallelism), it is mainly the monistic positions of non-reductive, reductive and eliminative materialism and the materialist functionalism underlying it, which determines analytical philosophy of mind and its influence on psychopathology and psychiatry. Under the additional influence of modern brain research methods, particularly neuroimaging, it is progressively developing into a subdiscipline of neuroscience, a complex and increasingly more firmly established scientific discipline which comprises the totality of all sciences dealing with neuronal functions, including the close epistemic associations of APM and neuroimaging. This is the effective epistemic central idea determining the theory of the neuronal network which, in the form of a connectionist psychopathology, is intended to make possible a fundamentally new access to the comprehension of psychiatric forms of illness. In this respect it is evident, however, that the perception of the naturality of the mind as the fundamental thesis of APM and thus of connectionism cannot be followed through, since, up to now, neither from the phenomenality of the mind (especially the quality of senses, "Qualia") nor from intentionality of the mind (i. e. the ability to act intentionally, free from the constraint of the causality of nature and thus in self-responsible fashion) has proved it possible to reconstruct a generally accepted naturalist theory. Furthermore, it has not been possible to reformulate it in an exclusively physical, i. e. non-phenomenological concept and terminology which is, above all, free from the intentionality idiom. The consequence of this, however, is that a connectionist psychopathology can only represent a subpersonal, i. e., subhuman area and that in order to establish a personal psychopathology, naturalistic unreduced theories of experience-qualities and intentional acts of completeness are absolutely essential. The neuroscientific-connectionist paradigm of psychopathology must therefore - at least for the present - be supplement by the paradigm of a non-natural (e. g. phenomenological-hermeneutic) psychopathology. This result can only encourage the relinquishing of epistemically one-sided materialist and other monistic mind-brain theories of APM in favour of an epistemically open pragmatic interactionist dualism as the scientific position which best represents the current state of knowledge.

Humans↗
PubMed2004

Evolution of document networks.

How does a network of documents grow without centralized control? This question is becoming crucial as we try to explain the emergent scale-free topology of the World Wide Web and use link analysis to identify important information resources. Existing models of growing information networks have focused on the structure of links but neglected the content of nodes. Here I show that the current models fail to reproduce a critical characteristic of information networks, namely the distribution of textual similarity among linked documents. I propose a more realistic model that generates links by using both popularity and content. This model yields remarkably accurate predictions of both degree and similarity distributions in networks of web pages and scientific literature.

Databases, Bibliographic↗
PubMed2004

Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana.

Plant metabolism is a complex set of processes that produce a wide diversity of foods, woods, and medicines. With the genome sequences of Arabidopsis and rice in hands, postgenomics studies integrating all "omics" sciences can depict precise pictures of a whole-cellular process. Here, we present, to our knowledge, the first report of investigation for gene-to-metabolite networks regulating sulfur and nitrogen nutrition and secondary metabolism in Arabidopsis, with integration of metabolomics and transcriptomics. Transcriptome and metabolome analyses were carried out, respectively, with DNA macroarray and several chemical analytical methods, including ultra high-resolution Fourier transform-ion cyclotron MS. Mathematical analyses, including principal component analysis and batch-learning self-organizing map analysis of transcriptome and metabolome data suggested the presence of general responses to sulfur and nitrogen deficiencies. In addition, specific responses to either sulfur or nitrogen deficiency were observed in several metabolic pathways: in particular, the genes and metabolites involved in glucosinolate metabolism were shown to be coordinately modulated. Understanding such gene-to-metabolite networks in primary and secondary metabolism through integration of transcriptomics and metabolomics can lead to identification of gene function and subsequent improvement of production of useful compounds in plants.

Arabidopsis↗
PubMed2006

The impossible interview with the man of the neuron doctrine. Interview by Edward G Jones.

This paper follows the form of that by Mazzarello that precedes it (Mazzarello, 2006) and presents an imaginary interview with Santiago Ramón y Cajal in December 1906. A few days earlier Cajal had been awarded the Nobel Prize for Physiology or Medicine, an award that he shared equally with Professor Camillo Golgi. Golgi had been recognized for his work as a pioneer into investigations of the nervous system, primarily on account of his discovery of the "black reaction" of silver chromate impregnation of whole nerve cells and their processes. Cajal had been recognized for his implementation of that method and for laying with it the foundations of what was to become modern neuroanatomical science. Paradoxically, the two awardees had been led by their researches to diametrically opposed views of the organization of the nervous system. Golgi believed in a continuous network of axons that formed the basis of all the integrative properties of the nervous system, while Cajal had provided the information that led to the formulation of the neuron doctrine that saw the nervous system as being made up of chains of discontinuous cells joined by polarized functional contacts that we now call synapses. The paper takes the form of an interview with Professor Cajal in the Grand Hotel Stockholm. His responses to questions posed by the imaginary interviewer are all taken from Cajal's own writings.

Anatomy↗
PubMed1997

Recognition of 3'-processing sites of human mRNA precursors.

We have developed a computer program POLYAH and an algorithm for the identification of 3'-processing sites of human mRNA precursors. The algorithm is based on a linear discriminant function (LDF) trained to discriminate real poly(A) signal regions from the other regions of human genes possessing the AATAAA sequence which is most likely non-functional. As the parameters of LDF, various significant contextual characteristics of sequences surrounding AATAAA signals were used. An accuracy of method has been estimated on a set of 131 poly(A) regions and 1466 regions of human genes having the AATAAA sequence. When the threshold was set to predict 86% of poly(A) regions correctly, specificity of 51% and correlation coefficient of 0.62 had been achieved. The precision of this approach is better than for the other methods and has been tested on a larger data set. POLYAH can be used through World Wide Web (at Gene-Finder Home page: URL http:@dot.imgen.bcm.tmc.edu:9331/gene-finder/ gf.html) or by sending files with uncharacterized human sequences to the University of Houston or Weizmann Institute of Science e-mail servers.

Algorithms↗
PubMed2003

Fast HPLC with a silica-based monolithic ODS column.

Fast high-performance liquid chromatography is becoming routine in laboratories that require high throughput or for combinatorial libraries. Reduced analysis time is commonly achieved by using shorter columns and higher flow rates. Shorter columns require smaller particles in order to maintain efficiency. However, smaller particles increase backpressure, which limits both column length and higher flow rates for typical LC pumps. This disadvantage has been addressed by the emergence of monolithic liquid chromatographic columns (1). Unlike particle-base columns, monolithic columns consist of a continuous rod-shaped porous network with a bimodal pore distribution. In this study, a commercially available 50- x 4.6-mm silica-based octadecyl silane monolithic column (Chromolith SpeedROD RP18e, EM Science, Gibbstown, NJ) was used to separate a seven-component test mixture with a wide range of polarity. The primary goals of this investigation were: (a) to study the chemistry (selectivity) of the new silica-based monolithic columns and (b) to study their run-to-run and column-to-column performance (retention times and peak areas). The selectivity (alpha factor) is a ratio of partition coefficients and, if comparable for a variety of solutes, would mean that methods could be readily transferred between particulate and monolithic columns.

Journal Article↗
PubMed2004

Genes, longevity, and technology: meeting report from the 2nd conference on functional genomics of aging in Crete.

Whole-genome sequences are now available, and methods have evolved for targeting, in parallel, each gene in a genome, offering for the first time the opportunity to study the entire dynamic network of genes involved in aging. At a recent conference in Hersonissos, Crete, around 200 internationally renowned experts gathered to discuss techniques and emerging results as the science of aging undergoes a shift toward systems biology.

Aging↗
PubMedDate not supplied

Healthcare professional education: a unique role for hospices.

We sought to describe the educational experiences that hospices currently provide for students in health professions by using a national cross-sectional, Web-based survey of the National Hospice and Palliative Care Organization (NHPCO) and the Population-based Palliative Care Research Network (PoPCRN) hospice sites. Of the 75 responding sites, 71 (95 percent) participated in the education of health profession students, most commonly providing education for bachelor of science in nursing students (73 percent), associate's degree nursing students (61 percent), master's-level social work or counseling students (61 percent), registered nursing students (59 percent), medical students (58 percent), and medical residents (57 percent). Significant staff time was devoted to educating these students (averaging 11 to 30 hours/week), but less than 3 percent received any financial compensation. Therefore, we conclude that hospices provide a significant amount of uncompensated education. This conclusion provides a unique opportunity for hospices to collaborate with healthcare educational institutions and to influence the work force of the future.

Cross-Sectional Studies↗
PubMed2005

[Design and creation of cytomedicine for application to cell therapy].

Cells, which are the basic unit of life, are the most intelligent particles on earth. Recent advances in life science research encourage the development of cell therapy utilizing specialized functions of highly differentiated cells, the self-renewal and differentiation abilities of stem cells, and signal networks among various types of cells. Although cell therapy including ex vivo gene therapy, cellular immunotherapy, and regenerative therapy is expected to become the next generation of medical care for intractable disorders, the establishment of technology to prepare cells as medical supplies, namely, cytomedicine, is essential for the assurance of efficacy and safety in cell therapy. This review introduces our approach to the design and creation of cytomedicine for application to cell therapy against diabetes mellitus and cancer.

Animals↗
PubMed2003

Two-dimensional gap analysis: a tool for efficient conservation planning and biodiversity policy implementation.

The maintenance of biodiversity by securing representative and well-connected habitat networks in managed landscapes requires a wise combination of protection, management, and restoration of habitats at several scales. We suggest that the integration of natural and social sciences in the form of "Two-dimensional gap analysis" is an efficient tool for the implementation of biodiversity policies. The tool links biologically relevant "horizontal" ecological issues with "vertical" issues related to institutions and other societal issues. Using forest biodiversity as an example, we illustrate how one can combine ecological and institutional aspects of biodiversity conservation, thus facilitating environmentally sustainable regional development. In particular, we use regional gap analysis for identification of focal forest types, habitat modelling for ascertaining the functional connectivity of "green infrastructures", as tools for the horizontal gap analysis. For the vertical dimension we suggest how the social sciences can be used for assessing the success in the implementation of biodiversity policies in real landscapes by identifying institutional obstacles while implementing policies. We argue that this interdisciplinary approach could be applied in a whole range of other environments including other terrestrial biota and aquatic ecosystems where functional habitat connectivity, nonlinear response to habitat loss and a multitude of economic and social interests co-occur in the same landscape.

Conservation of Natural Resources↗
PubMed2005

Biomarker World Congress 2005.

This report covers some of the many excellent talks, and a selected number of posters, that were presented at this conference. It includes several emerging issues in biomarker development and the question of how biomarker science can drive targeted drug discovery and development and form a scientific basis for personalized medicine. Although relatively small, the meeting provided a good opportunity for business networking, particularly for those involved in the development and regulation of medical diagnostics and biopharmaceuticals.

Animals↗
PubMed1981

[Experience with the organization of drug information in Hungary (author's transl)].

Medicinal therapy is changing more dynamically than all other fields of medicine. New therapeutic techniques, new drugs and combinations of drugs are in such a rapid succession that the knowledge required in modern therapeutic approaches can be imparted in time to physicians and pharmacists only by means of an adequate information system. In 1958, the Ministry of Health (consulting pharmacists) started the National Organization of Drug Information and charged the National Pharmaceutical Institute with its direction and further development. In the past 22 years this Organization established by its activity a co-operation between pharmacists and physicians which functions so well that now it cannot be dispensed with in everyday work. 50 specially qualified pharmacists are members of the Central Organization of Drug Information. An analysis of the therapeutic methods and of the supply of drugs testified to the positive activity of this Organization and to the need for its further development. In the framework of the health departments of the counties and of the pharmaceutical centres, there exists a so-called network of drug information, the activities of which are guided by members of the National Pharmaceutical Institute. The ever extending network of drug information is of incontestable value to the public health service, the medicinal therapy and to the correct information about drugs from the viewpoints of science and ethnics.

Drug Information Services↗
PubMedDate not supplied

Supercomputers open window of opportunity for nursing.

A window of opportunity was opened for nurse researchers with the High Performance Computing and Communications (HPCC) initiative in President Bush's 1992 fiscal-year budget. Nursing research moved into the high-performance computing environment through the University of Nevada Las Vegas/Cray Project for Nursing and Health Data Research (PNHDR). USing the CRAY YMP 2/216 supercomputer, the PNHDR established the validity of a supercomputer platform for nursing research. In addition, the research has identified a paradigm shift in statistical analysis, delineated actual and potential barriers to nursing research in a supercomputing environment, conceptualized a new branch of nursing science called Nurmetrics, and discovered new avenue for nursing research utilizing supercomputing tools.

Computer Communication Networks↗