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A primer on molecular biology for imagers: III. Proteins: structure and function.

This article along with the first 2 in this series (4,12) completes the discussion on the key molecules and process inside the cell namely, DNA, RNA, and proteins. These 3 articles provide a very basic foundation for understanding molecular biology concepts and summarize some of the work of numerous scientists over the past century. We understand these processes far better now than we did in the past, but clearly this knowledge is by no means complete and a number of basic scientists are working hard to elucidate and understand the fundamental mechanisms that operate within a cell. Genes and gene products work with each other in complex, interconnected pathways, and in perfect harmony to make a functional cell, tissue, and an organism as a whole. There is a lot of cross-talk that happens between different proteins that interact with various other proteins, DNA, and RNA to establish pathways, networks, and molecular systems as a team working to perfection. The past 15 years have seen the rapid development of systems biology approaches. We live in an era that emphasizes multi-disciplinary, cross-functional teams to perform science rather than individual researchers working on the bench on a very specific problem. Global approaches have become more common and the amount of data generated must be managed by trained bioinformatics personnel and large computers. In our subsequent articles, we will discuss these global approaches and the areas of genomics, functional genomics, and proteomics that have revolutionized the way we perform science.

Molecular Biology↗

Models of the subthalamic nucleus. The importance of intranuclear connectivity.

A coherent set of models is presented that provide novel and testable predictions about the functional role of the subthalamic nucleus (STN) in the basal ganglia. The STN is emerging as an important target for novel therapeutic strategies for the alleviation of Parkinsonian type symptoms [Lancet 345 (1995) 91; Science 249 (1990) 1436]. Computational and mathematical models based on the properties of the STN and its interactions are reviewed. These models focus on core anatomical and physiological data that span many levels. By assessing models of anatomy, dynamic network models, and a detailed model of a recent pharmacological experiment, we can expose the primary modes of STN function and highlight their underlying properties. We show that the presence of functional interactions between STN projection neurons is critical in defining its behaviour and how it interacts with other basal ganglia nuclei. Pulses or switch-like activity patterns emerge in the models as a consequence of these local interactions. Furthermore, the models demonstrate that this behaviour can break down under abnormal conditions resulting in low frequency bursting oscillations. Such oscillations may play a role in symptoms of Parkinson's disease.

Action Potentials↗

Brainstem origins for cortical 'what' and 'where' pathways in the auditory system.

We have developed a data-driven conceptual framework that links two areas of science: the source-filter model of acoustics and cortical sensory processing streams. The source-filter model describes the mechanics behind speech production: the identity of the speaker is carried largely in the vocal cord source and the message is shaped by the ever-changing filters of the vocal tract. Sensory processing streams, popularly called 'what' and 'where' pathways, are well established in the visual system as a neural scheme for separately carrying different facets of visual objects, namely their identity and their position/motion, to the cortex. A similar functional organization has been postulated in the auditory system. Both speaker identity and the spoken message, which are simultaneously conveyed in the acoustic structure of speech, can be disentangled into discrete brainstem response components. We argue that these two response classes are early manifestations of auditory 'what' and 'where' streams in the cortex. This brainstem link forges a new understanding of the relationship between the acoustics of speech and cortical processing streams, unites two hitherto separate areas in science, and provides a model for future investigations of auditory function.

Animals↗

Force Parameters for On-line Tool Wear Estimation: A Neural Network Approach.

Reliable on-line tool conditioning monitoring is an essential feature of modern sophisticated and automated machine tools. Appropriate and timely decision for tool-change is urgently required in the machining systems. Ample researches have been carried out in this direction.Recently artificial neural networks (NN) are applied for this purpose in conjunction with suitable sensory systems. Its fast processing capability is well-suited for quick estimation of tool condition and corrective measure to be taken.The present work uses back-propagation type training and feed-forward testing procedures for the neural networks. Three models using different force parameters are tried to monitor tool wear on-line. The close estimation of the modeled output to the actual wear value demonstrates the possibility of successful tool wear monitoring. Copyright 1996 Elsevier Science Ltd.

Journal Article↗

Earning a Master's of Science in Nursing through distance education.

The increased availability of telecommunications technology has made possible the offering of degree programs via distance education. Such programs make courses and degrees more readily accessible to a wider range of students than has traditionally been the case. The University of Tennessee, Memphis, College of Nursing has undertaken to offer a Master's of Science in Nursing degree entirely by distance education. The challenges, successes, and technology of the program are discussed.

Computer Communication Networks↗

Transient oxygen clathrate-like hydrate and water networks induced by magnetic fields.

Recently, careful experiments of oxygen-dissolved pure water treated by high magnetic fields showed indirectly the existence of magnetic field-affecting water (MFA water), which brought about a decrease in the contact angle of water on metals, an increase in the electrolytic potential of water, inhibition of metal corrosion, and changes in the crystal structure of calcium carbonate due to magnetic treatment. Here we report the infrared and Raman spectroscopic evidence indicating quasi-stable structures in the MFA water; oxygen clathrate-like hydrate and developed water networks, which were induced by magnetic interactions while a vacuum-distilled water, followed by oxygen exposure, crossed a steady magnetic field. The mechanism of MFA water formation and survival under thermal fluctuation is a challenging problem for the science community.

Letter↗

Dynamics of traffic flow with real-time traffic information.

We studied dynamics of traffic flow with real-time information provided. Provision of the real-time traffic information based on advancements in telecommunication technology is expected to facilitate the efficient utilization of available road capacity. This system has a potentiality of not only engineering for road usage but also the science of complexity series. In the system, the information plays a role of feedback connecting microscopic and macroscopic phenomena beyond the hierarchical structure of statistical physics. In this paper, we tried to clarify how the information works in a network of traffic flow from the perspective of statistical physics. The dynamical feature of the traffic flow is abstracted by a contrastive study between the nonequilibrium statistical physics and a computer simulation based on cellular automaton. We found that the information disrupts the local equilibrium of traffic flow by a characteristic dissipation process due to interaction between the information and individual vehicles. The dissipative structure was observed in the time evolution of traffic flow driven far from equilibrium as a consequence of the breakdown of the local-equilibrium hypothesis.

Journal Article↗

The state of the art of nanobioscience in Japan.

This paper reviews a part of the state of the art of nanobioscience in Japan. The importance of combination and integration of interdisciplinary principles is emphasized for the development of nanobioscience. Biomagnetics, biomechanics, nanomachining, self-replicating cell model, neuronal network, drug delivery system, and tissue engineering are discussed.

Biological Science Disciplines↗

International Training and Research in Central and Eastern Europe: The University of Iowa model.

In 1995, with support from the Fogarty International Center of the National Institutes of Health, The Center for International Rural and Environmental Health (CIREH) at The University of Iowa began developing the multi-level International Training and Research Program in Occupational and Environmental Health, focusing on countries in Central and Eastern Europe that were formerly under socialist control and have particular occupational and environmental health needs after decades of neglect and mismanagement. The purpose of the program is to prepare health science professionals to return to their home countries with new skills, added confidence, and leadership capabilities in public health to lead their colleagues and institutions in meeting the needs in their respective countries and establish active national and international networks and collaborations. By December 1998, 19 trainees had completed the five-month program and returned home to conduct workshops for others in their countries. Details of the program are presented.

Communism↗

Talkback telephone network. Techniques of providing library continuing education.

Four lectures on solving medical reference requests were given over a talkback telephone teleconference network which links 110 hospitals throughout the state. Participants in the course were librarians in nonurban public libraries, systems libraries, and small hospital libraries. Professional librarians as well as library personnel with little training took the course. Techniques were developed for providing continuing education over this telephone network to individuals located in remote areas. These techniques are described including analysis of their advantages and disadvantages.

Education, Continuing↗

[The PAL+ program, an incentive concerted action about malaria and associated infectious diseases, for developing countries].

The French Ministry in charge of Research has launched a multi-institutional incentive concerted action to assist Southern countries on malaria: the PAL+ program. PAL+ aims at bringing out: 1) conditions to promote novel preventive and therapeutic tools adapted to existing situations in the countries concerned; 2) a contribution to help research teams in Southern countries become competitive. PAL+ plans to strengthen cooperative relationships with developing countries (subsaharian Africa, South East Asia and South American countries). Research programs were oriented towards public health needs in malaria-endemic countries and thus mainly focused on: i) development of new antimalarial drugs and new therapeutical strategies: new targets and new leads for drugs, clinical assays for recognition of malaria and optimization of effective treatment or prophylactic drug dosage; ii) pathophysiology of severe malaria: mechanisms of immunity, biology and genome of host and parasite and research leading to vaccine trials; iii) basic and field research on mosquito genetics and biology which may lead to new prevention and control opportunities; iv) social studies on behaviours and habits around prevention and medication of malaria. The objective is to help Southern countries increase their capacity in clinical research, epidemiology, therapeutics, public health and social science (e.g. behaviours and habits accompanying medicine-taking). This means a true partnership and training adapted to specific needs and based on sound science. Research was therefore largely pursued in the laboratories of Southern countries and PAL+ supported the initiative in different ways by: i) providing easier opportunities for scientists from the North to collaborate with scientists from the South; ii) supporting networks of scientist collaborations. This was achieved by setting up a new type of relationships between scientists, based on a continuous dialogue and on bringing them together in small meetings on thematic discussions, the so-called Ateliers de PAL+. The Ateliers should play a major role in increasing the scientific capacity in developing countries. PAL+ program is a commitment to speed up better understanding of the disease by helping endemic countries contribute to research for their own benefit.

Africa South of the Sahara↗

NLM Medical Library Resource Improvement Grant Program: an evaluation.

The Extramural Programs, NLM, undertook a staff study to evaluate the Medical Library Resource Improvement Grant Program in order to determine impact on hospital library development and to assess factors significant to regional medical library (RML) network development. Initiated in fiscal year 1971, the improvement grant program provides one-year, one-time grant awards of a maximum of $3,000 to assist in establishing a basic collection of books, journals, and other health science information resources for community hospitals and comparable health facilities. Applicants who received grant awards were compared to applicants who did not receive awards and to nonapplicants, using nine dependent variables, four independent variables, and responses to an RML questionnaire. Results show that the applicants who received awards outperformed the other groups, and that the improvement grant program has been successful in stimulating library development. As a result of this study, the improvement grant program will be modified to support consortium arrangements as well as individual institutions, and to extend the period of grant support to two years. Future grant support will be a maximum of $4,000 in the first year, and up to $3,000 with a provision of $1,000 in matching funds from the grantee in the second year.

Economics, Hospital↗

Bioinformatics for the genomic sciences and towards systems biology. Japanese activities in the post-genome era.

The knowledge gleaned from genome sequencing and post-genome analyses is having a very significant impact on a whole range of life sciences and their applications. 'Genome-wide analysis' is a good keyword to represent this tendency. Thanks to innovations in high-throughput measurement technologies and information technologies, genome-wide analysis is becoming available in a broad range of research fields from DNA sequences, gene and protein expressions, protein structures and interactions, to pathways or networks analysis. In fact, the number of research targets has increased by more than two orders in recent years and we should change drastically the attitude to research activities. The scope and speed of research activities are expanding and the field of bioinformatics is playing an important role. In parallel with the data-driven research approach that focuses on speedy handling and analyzing of the huge amount of data, a new approach is gradually gaining power. This is a 'model-driven research' approach, that incorporates biological modeling in its research framework. Computational simulations of biological processes play a pivotal role. By modeling and simulating, this approach aims at predicting and even designing the dynamic behaviors of complex biological systems, which is expected to make rapid progress in life science researches and lead to meaningful applications to various fields such as health care, food supply and improvement of environment. Genomic sciences are now advancing as great frontiers of research and applications in the 21st century. This article starts with surveying the general progress of bioinformatics (Section 1), and describes Japanese activities in bioinformatics (Section 2). In Section 3, I will introduce recent developments in Systems Biology which I think will become more important in the future.

Animals↗

On the inter-relations between artificial and physiological neural networks.

This paper discusses the inter-relations between findings on the physiological neural network (PNN) and artificial neural networks (ANN). It discusses the interaction of progress in both PNN and ANN for the purpose of borrowing from ANN's mathematical understandings to establish pointers for further explorations to better understand the PNN, and also for the reciprocal transferring of knowledge from PNN findings to improve ANN schemes. Such improvements in ANN are essential for better handling the needs of the information technology (IT) explosion in dealing with huge data bases and where data often defy analysis and are incomplete and fuzzy. On the other hand, principles and elements of ANN designs that appear to be important and successful can serve as guides for identifying them in the PNN, to be subsequently confirmed by bioanalytical tests. Hence progress in PNN is obviously essential for progress in ANN, as is progress in ANN helpful in PNN modeling, though its laboratory confirmation is still a far lengthier process. We discuss certain specific ANN schemes with respect to the above inter-relations with PNN. We feel that the progress in both PNN and ANN research provides a major link between the thrust in information technology developments and the thrust in biological science research, which are most probably the two major focus areas of research at the dawn of the 21st century.

Animals↗

Organization of face and object recognition in modular neural network models.

There is strong evidence that face processing in the brain is localized. The double dissociation between prosopagnosia, a face recognition deficit occurring after brain damage, and visual object agnosia, difficulty recognizing other kinds of complex objects, indicates that face and non-face object recognition may be served by partially independent neural mechanisms. In this paper, we use computational models to show how the face processing specialization apparently underlying prosopagnosia and visual object agnosia could be attributed to (1) a relatively simple competitive selection mechanism that, during development, devotes neural resources to the tasks they are best at performing, (2) the developing infant's need to perform subordinate classification (identification) of faces early on, and (3) the infant's low visual acuity at birth. Inspired by de Schonen, Mancini and Liegeois' arguments (1998) [de Schonen, S., Mancini, J., Liegeois, F. (1998). About functional cortical specialization: the development of face recognition. In: F. Simon & G. Butterworth, The development of sensory, motor, and cognitive capacities in early infancy (pp. 103-116). Hove, UK: Psychology Press] that factors like these could bias the visual system to develop a processing subsystem particularly useful for face recognition, and Jacobs and Kosslyn's experiments (1994) [Jacobs, R. A., & Kosslyn, S. M. (1994). Encoding shape and spatial relations-the role of receptive field size in coordination complementary representations. Cognitive Science, 18(3), 361-368] in the mixtures of experts (ME) modeling paradigm, we provide a preliminary computational demonstration of how this theory accounts for the double dissociation between face and object processing. We present two feed-forward computational models of visual processing. In both models, the selection mechanism is a gating network that mediates a competition between modules attempting to classify input stimuli. In Model I, when the modules are simple unbiased classifiers, the competition is sufficient to achieve enough of a specialization that damaging one module impairs the model's face recognition more than its object recognition, and damaging the other module impairs the model's object recognition more than its face recognition. However, the model is not completely satisfactory because it requires a search of parameter space. With Model II, we explore biases that lead to more consistent specialization. We bias the modules by providing one with low spatial frequency information and the other with high spatial frequency information. In this case, when the model's task is subordinate classification of faces and superordinate classification of objects, the low spatial frequency network shows an even stronger specialization for faces. No other combination of tasks and inputs shows this strong specialization. We take these results as support for the idea that something resembling a face processing "module" could arise as a natural consequence of the infant's developmental environment without being innately specified.

Journal Article↗

Monograph support provided by the National Library of Medicine and its regional medical libraries in the medical behavioral sciences.

The National Library of Medicine's (NLM) monographic resources in the medical behavioral sciences (MBS) were examined to assess NLM's ability to support the needs of researchers writing in this area. A sample of 239 representative monographs derived from citations in MBS-related articles published in 61 journals in 1981 were evaluated. These monographs were limited to works published between 1978 and 1981, inclusive. The subject distribution of the sample included fourteen of the twenty-one main classes in the LC classification, although BF (psychology), H (social sciences), and R (medicine) constituted 80.3% of the sample. The study revealed that NLM held 48.5% of the sample. The holdings of ten research medical libraries, including six of the seven regional medical libraries, were also evaluated in order to gauge NLM's ability to support that element of the medical library network. The holding rates of these libraries ranged widely (9.6% to 36%), although NLM was found to have far more extensive holdings overall, and when assessed against classes BF, H, and R. Overall, NLM could have supplied from 28.8% to 44.5% of the monographs not held by the medical libraries. In only a few cases were the ten medical libraries able to provide access to monographs not held by NLM. The findings of the study indicate that, regardless of NLM's indication of support to the MBS area, the holdings of more general research and academic libraries are essential to support the monograph needs of MBS researchers.

Behavioral Sciences↗

Rational design of vaccines against enveloped RNA viruses.

The enveloped RNA viruses are responsible for many important infectious diseases both in the UK and worldwide. The most familiar of these would probably be influenza, measles, mumps, rubella, rabies, dengue and yellow fever. Conventional vaccines against all of the most widespread diseases have been available for several years, although with widely varying degrees of safety and efficacy. Although vaccines against diseases such as measles, rubella, and yellow fever have been fairly successful, all vaccines against diseases caused by this group of viruses still have several drawbacks and are in need of improvement for a variety of reasons. During the past decade our knowledge in several diverse areas of the biological sciences has expanded to the extent that it can now be combined and serious attempts made to design and engineer biological molecules with immunogenic potential. First, significant advances have been made in elucidating the mechanisms operating in the immune defence network and in determining the structure of both immunogenic molecules and the components of the immune system with which they interact. Second, the development of recombinant DNA technology has enabled biological molecules to be synthesized under conditions not restricted by the characteristics of their parent organism. Such molecules can then be altered in such a way as to improve their efficiency and their level of production. It is the purpose of this paper to outline the problems associated with the production of vaccines against enveloped RNA viruses and to discuss how recent advances in knowledge and techniques can help to overcome these problems.

Antigen-Presenting Cells↗

An Efficient EM-based Training Algorithm for Feedforward Neural Networks.

A fast training algorithm is developed for two-layer feedforward neural networks based on a probabilistic model for hidden representations and the EM algorithm. The algorithm decomposes training the original two-layer networks into training a set of single neurons. The individual neurons are then trained via a linear weighted regression algorithm. Significant improvement on training speed has been made using this algorithm for several bench-mark problems. Copyright 1997 Elsevier Science Ltd. All Rights Reserved.

Journal Article↗