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Selective adaptation in networks of cortical neurons.

A key property of neural systems is their ability to adapt selectively to stimuli with different features. Using multisite electrical recordings from networks of cortical neurons developing ex vivo, we show that neurons adapt selectively to different stimuli invading the network. We focus on selective adaptation to frequent and rare stimuli; networks were stimulated at two sites with two different stimulus frequencies. When both stimuli were presented within the same period, neurons in the network attenuated their responsiveness to the more frequent input, whereas their responsiveness to the rarely delivered stimuli showed a marked average increase. The amplification of the response to rare stimuli required the presence of the other, more frequent stimulation source. By contrast, the decreased response to the frequent stimuli occurred regardless of the presence of the rare stimuli. Analysis of the response of single units suggests that both of these effects are caused by changes in synaptic transmission. By using synaptic blockers, we find that the increased responsiveness to the rarely stimulated site depends specifically on fast GABAergic transmission. Thus, excitatory synaptic depression, the inhibitory sub-network, and their balance play an active role in generating selective gain control. The observation that selective adaptation arises naturally in a network of cortical neurons developing ex vivo indicates that this is an inherent feature of spontaneously organizing cortical networks.

Action Potentials↗

Visualisation and navigation methods for typed protein-protein interaction networks.

Protein-protein interactions form large and complex networks. Their visualisation can aid biologists in gaining new insights about the processes in cells and is, therefore, very useful for building sophisticated research tools. Often standard force-directed graph drawing algorithms are used for the visualisation of these networks. However, currently available visual interfaces to biological databases only show general interactions and cannot cope well with more complex networks with different types of interactions. This paper presents a new approach to the visual analysis of protein-protein interaction networks. It uses a combination of circular and force-directed graph drawing algorithms to compute visual representations of protein networks depending on the type of the selected interaction. Smooth transitions between subsequent drawings enable users to explore different functional clusters in these networks without getting lost in the entire network. The visualisation system has been tested with data from the BRITE database.

Algorithms↗

Abductive network committees for improved classification of medical data.

OBJECTIVES: To introduce abductive network classifier committees as an ensemble method for improving classification accuracy in medical diagnosis. While neural networks allow many ways to introduce enough diversity among member models to improve performance when forming a committee, the self-organizing, automatic-stopping nature, and learning approach used by abductive networks are not very conducive for this purpose. We explore ways of over-coming this limitation and demonstrate improved classification on three standard medical datasets. METHODS: Two standard 2-class medical datasets (Pima Indians Diabetes and Heart Disease) and a 6-class dataset (Dermatology) were used to investigate ways of training abductive networks with adequate independence, as well as methods of combining their outputs to form a network that improves performance beyond that of single models. RESULTS: Two- or three-member committees of models trained on completely or partially different subsets of training data and using simple output combination methods achieve improvements between 2 and 5 percentage points in the classification accuracy over the best single model developed using the full training set. CONCLUSIONS: Varying model complexity alone gives abductive network models that are too correlated to ensure enough diversity for forming a useful committee. Diversity achieved through training member networks on independent subsets of the training data outweighs limitations of the smaller training set for each, resulting in net gain in committee performance. As such models train faster and can be trained in parallel, this can also speed up classifier development.

Data Collection↗

How to build your network.

Many sensational ideas have faded away into obscurity because they failed to reach the right people. A strong personal network, however, can launch a burgeoning plan into the limelight by delivering private information, access to diverse skill sets, and power. Most executives know that they need to learn about the best ideas and that, in turn, their best ideas must be heard by the rest of the world. But strong personal networks don't just happen around a watercooler or at reunions with old college friends. As Brian Uzzi and Shannon Dunlap explain, networks have to be carefully constructed through relatively high-stakes activities that bring you into contact with a diverse group of people. Most personal networks are highly clustered--that is, your friends are likely to be friends with one another as well. And, if you made those friends by introducing yourself to them, the chances are high that their experiences and perspectives echo your own. Because ideas generated within this type of network circulate among the same people with shared views, though, a potential winner can wither away and die if no one in the group has what it takes to bring that idea to fruition. But what if someone within that cluster knows someone else who belongs to a whole different group? That connection, formed by an information broker, can expose your idea to a new world, filled with fresh opportunities for success. Diversity makes the difference. Uzzi and Dunlap show you how to assess what kind of network you currently have, helping you to identify your super-connectors and demonstrating how you act as an information broker for others. They then explain how to diversify your contacts through shared activities and how to manage your new, more potent, network.

Humans↗

Reconstruction of gene regulatory networks under the finite state linear model.

We study the Finite State Linear Model (FSLM) for modelling gene regulatory networks proposed by A. Brazma and T. Schlitt in [4]. The model incorporates biologically intuitive gene regulatory mechanism similar to that in Boolean networks, and can describe also the continuous changes in protein levels. We consider several theoretical properties of this model; in particular we show that the problem whether a particular gene will reach an active state is algorithmically unsolvable. This imposes some practical difficulties in simulation and reverse engineering of FSLM networks. Nevertheless, our simulation experiments show that sufficiently many of FSLM networks exhibit a regular behaviour and that the model is still quite adequate to describe biological reality. We also propose a comparatively efficient O(2(K)n(K+1)M(2K)m log m) time algorithm for reconstruction of FSLM networks from experimental data. Experiments on reconstruction of random networks are performed to estimate the running time of the algorithm in practice, as well as the number of measurements needed for successful network reconstruction.

Algorithms↗

Gene knockout experiments to quantify a G2/M genetic network simulation for mammary cancer susceptibility.

A G2/M genetic network simulation is trained with tumor incidence data from knockout experiments. The genetic network is implemented using a neural network; knockout genotypes are simulated by removing nodes in the neural network. Two analyses are used to interpret the resulting network weights. We use a novel approach of fixing the network topology that allows knockout TSG (tumor suppressor gene) data from multiple studies to overlap and indirectly inform one another. The trained simulation is validated by reproducing qualitative mammary cancer susceptibilities of ATM, BRCA1, and p53 TSGs. The work described is valuable because it allows TSG mammary cancer susceptibility to be quantified using genetic network topology and in vivo knockout data.

Animals↗

Size and effectiveness of informal helping networks: a panel study of older people in the community.

This paper examines the impact over time of changes in older people's health and functional capacity on the size and effectiveness of their informal helping networks. Theoretical perspectives on networks differ in their predictions regarding the impact of declines in health on network size. Previous empirical studies have not examined the effects of changes in health on the size of networks. We examine empirical evidence on the impact of health changes on informal helping networks with longitudinal data obtained from a probability sample of older people living in the community. Results suggest that networks respond to diminishing health by increasing the scope of assistance provided but neither increase nor decrease in size as a consequence. The results also suggest that declines in functioning can produce increases in needs which exceed the capacity of informal networks.

Activities of Daily Living↗

Health professionals' use of documents obtained through the Regional Medical Library Network.

The Pacific Southwest Regional Medical Library Service (PSRMLS) studied how health professionals use documents obtained through the regional medical library (RML) network and how various factors, such as delivery time, affected that use. A random sample of libraries in Region 7 of the RML network was selected to survey health professionals who had received documents through the interlibrary loan (ILL) network. The survey provided data about the purposes for which health professionals requested documents, how the immediacy of need for the items affected their usefulness, what effect the obtained information had on the health professionals' work, and whether the illustrations represented an important part of the information content of the items. Survey results provided a positive assessment of the ILL network. Results also verified the basic value of the materials provided to health professionals through ILL and identified some areas for consideration in future network development. Users of the documents indicated that the network works efficiently and effectively to provide timely and useful information needed by health professionals. Technological developments in electronic information transmission and imaging will further enhance network operation in the future.

Health Occupations↗

Type IV collagen lateral associations in the EHS tumor matrix. Comparison with amniotic and in vitro networks.

The macromolecular structural organization of the type IV collagen network in the extracellular matrix of the EHS tumor has been investigated using a stereoscopic freeze-dry Pt/C replication technique. This network, which can be specifically decorated with type IV collagen antibody, is formed in great part by the lateral joining of narrow filaments (2.7 nm average metal coated diameter) to form a complex three-dimensional irregular polygonal array of variable diameter branching strands. Globular domains, similar to the C-terminal globular domains of purified type IV dimers, can be identified in the network. In many regions of the network the filaments appear to twist around each other along the strand axis. The network is similar to that visualized in the human amnion as well as to a reconstituted network formed in vitro. These data strongly suggest that the laterally and end-domain-associated network is a widespread supramolecular architecture of type IV collagen in basement membranes.

Amnion↗

Control theory applied to neural networks illuminates synaptic basis of interictal epileptiform activity.

A brief historical account is presented of the formulation of two hypotheses that have been proposed to explain the mechanisms underlying the paroxysmal depolarizing shift (PDS) in experimental epilepsy. The two hypotheses are called the giant EPSP hypothesis and the endogenous burst hypothesis. The giant EPSP hypothesis states that the PDS (the intracellular correlate of the interictal discharge) is comprised of a larger-than-normal-strength excitatory synaptic input, whereas the endogenous burst hypothesis states that the PDS is an endogenous burst triggered by an excitatory postsynaptic potential of normal strength. Two sets of four experimentally testable predictions, which were derived from these two hypotheses for the PDS, are presented. These predictions describe the expected behavior of the PDS in response to changes in membrane potential and under conditions of voltage clamping. With the advent of single-electrode current- and voltage-clamp techniques and improved intracellular recording conditions, the testing of these predictions has become possible. Experiments are described in which each of the predictions from the two hypotheses were tested. The results strongly support the giant EPSP hypothesis and are not easily reconciled with the endogenous burst hypothesis. Because the PDS is a network-driven event, it is important to understand the properties of the neuronal network responsible for the genesis of the PDS. Others have proposed that there are three necessary conditions for epileptiform activity in any neuronal network: endogenous bursting, disinhibition, and recurrent excitatory synapses. Using control theory as a frame of reference, we argue that it is premature to raise these three phenomena to the level of general theoretical requirements for interictal activity. Insufficient quantitative information exists about the properties of neurons, synapses, and connectivity patterns in any cortical neuronal network to conclude that the three preposed requirements are necessary and sufficient general conditions for epileptiform activity. Because all of the key predictions of the giant EPSP hypothesis have now been experimentally verified, we conclude that the PDS is a large, network-driven EPSP. The current challenge to neurophysiologists is to describe is detail the properties of neurons and synapses in a cortical neuronal network and then to evaluate the relative contributions of network and individual neuronal properties to the expression of interictal epileptiform activity.

Animals↗

The national biomedical communications network as a developing structure.

The National Biomedical Communications Network has evolved both from a set of conceptual recommendations over the last twelve years and an accumulation of needs manifesting themselves in the requests of members of the medical community. With a short history of three years this network and its developing structure have exhibited most of the stresses of technology interfacing with customer groups, and of a structure attempting to build itself upon many existing fragmentary unconnected segments of a potentially viable resourcesharing capability. In addition to addressing these topics, the paper treats a design appropriate to any network devoted to information transfer in a special interest user community. It discusses fundamentals of network design, highlighting that network structure most appropriate to a national information network. Examples are given of cost analyses of information services and certain conjectures are offered concerning the roles of national networks.

Communication↗

Morphology of the interlacunar network in four sites of hyaline cartilage of neonatal, juvenile, and adult rats.

The honeycomb matrix and interlacunar network are described and compared in femoral head articular cartilage, proximal femoral physis, xiphoid, and tracheal cartilages from neonatal, juvenile, and adult rats. The honeycomb matrix is morphologically constant in all four sites of all age groups. The network is plentiful in cartilage of neonatal rats, reduced in juveniles, and rare in adults. In a given cartilage site, the network has a constant pattern and concentration gradient among rats of the same age. It is hypothesized that the network functions only during rapid cartilage growth and is not related to weight-bearing. The network is composed of element sheets averaging 0.5 micrometer in thickness, which connect adjacent chondrocytes. Ultrastructurally, the network is observed as the thickened, dense areas of the honeycomb matrix and as nonmembrane-bound channels of granular material. The network and chondrocyte capsules are morphologically and cytochemically similar.

Aging↗

The social networks of seriously mentally ill persons receiving case management services.

Social network characteristics, or the patterning of one's social ties, are an important indicator of social support for persons with serious mental illness. Yet relatively few studies have been done on the particular network characteristics of clients receiving case management services in community settings. An understanding of the range of potential and actual social network contacts for persons with serious mental illness is important for targeting interventions to enhance their community supports. In this study, 125 clients of two urban community treatment teams were surveyed by case managers to determine their overall social network size, personal or support network size, and participation in any of 11 network clusters. Results of the study are presented with implications for the social functioning of persons with serious mental illness and suggestions for case manager interventions toward network expansion.

Adult↗

[A field assessment of a community 'rehabilitation class' for home handicapped persons--focusing on participant social network].

The purpose of this study is to evaluate a community 'Rehabilitation class' for its effectiveness. A function of the 'Rehabilitation class' is the expansion of a participant's social network, and the following hypothesis was formulated: the reciprocal relationships of participant and class or staff members bring about psychological effectiveness and a change of their awareness, resulting in the expansion of social networks. Actual class activity, psychological aspects and social networks of twenty-six participants and twenty care takers, who responded to a questionnaire survey, were examined with respect to the above hypothesis. Those reporting having changed were compared to those reporting no change. The results were as follows: (1) Class activity was directed at developing relationships among participants, and while most of them were changed positively, it appeared that staff members were not sufficiently involved. (2) There were 23 participants in the 'changed' group. Most of their care takers and family were changed positively. Eleven reported receiving significant emotional support from other 'Rehabilitation class' members, and therefore their social networks appeared to have expanded generally. (3) The 'non changed' group consisted of 3 participants whose social networks did not appear to have expanded. (4) Social networks outside the home were not expanded for all participants, probably due to their reported receiving little social support from others outside family members, and because they had few social roles outside the home. Based on the above results, it is concluded that effective classes involve participants individually, and encourage the independent activity of participants, and that it is necessary to have networking with other organizations in community, and the 'Rehabilitation class' should be provided to smaller local regions.

Aged↗

Quantitative analysis of network architecture, and microhemodynamics in arteriolar vessel trees of the ventilated rabbit lung.

An experimental model has been developed for morphometric and microhemodynamic analysis of discrete arteriolar networks in the ventilated lung. We implanted a transparent window into the right thoracic wall of anesthetized rabbits. Autologous red blood cells were labeled with FITC in vitro. Using a fluorescence video microscopic technique the vessels of superficial arteriolar networks were mapped and classified hierarchically. Networks were investigated under zone 2 conditions (alveolar > left atrial pressure) during continuous monitoring of macrohemodynamics. We comprehensively measured segment length, diameter (D) and branching pattern in the whole network. Microhemodynamic parameters (red blood cell flux (Frbc), red blood cell velocity (Vrbc) and microhematocrit (H mu) were determined in terminal branches. As a result of network analysis the branching rules were found to be similar to those found by cast techniques in human and cat lungs. In terminal arterioles D (21 +/- 4 microns), Frbc (1472 +/- 662 cells/s), Vrbc (863 +/- 250 microns/s) and H mu (0.28 +/- 0.067) were heterogeneously distributed. Geometric, as well as microhemodynamic parameters fitted best to a lognormal distribution. This study represents an example of in vivo analysis of discrete microvascular networks. The measurements in hierarchically equivalent segments of pulmonary arteriolar vessel trees have been shown to be appropriate for estimation of topological, geometrical and microhemodynamic heterogeneity in pulmonary arteriolar networks.

Animals↗

Kinesin localizes to the trans-Golgi network regardless of microtubule organization.

Knowledge of the mechanisms of intracellular membrane trafficking is critical for understanding cell function. Here, the microtubule motor kinesin is localized to the Sertoli cell trans-Golgi network with the SUK4 kinesin monoclonal antibody. Using immunoelectron and immunofluorescence microscopy, kinesin was shown to localize to the trans-Golgi network in primary Sertoli cell cultures. Kinesin immunostaining was not observed in brefeldin A-induced trans-Golgi network-derived membrane tubules and remained associated with trans-Golgi network remnants. Despite dramatic differences in microtubule organization between Sertoli cells in vivo and in vitro, kinesin immunostaining was consistently associated with the trans-Golgi network. In cryosections of control testis and testis treated with colchicine to disrupt microtubules, kinesin immunostaining was juxtaposed with immunostaining for a Golgi cisternal protein; however, brefeldin A exposure partitioned the kinesin immunostaining from the Golgi cisternal protein, indicating that kinesin was associated with the trans-Golgi network of Sertoli cells in vivo. These results are discussed in relation to known Golgi-associated microtubule-dependent transport events in other cell types and suggest that kinesin functions locally at the Sertoli cell trans-Golgi network.

Animals↗

The role of informal and formal social support networks for patients with cancer.

PURPOSE: In this study, the authors examined the role of informal and formal social support networks in mitigating barriers to cancer treatment among whites, blacks, and Hispanics, based on a representative sample of cancer patients in Texas. DESCRIPTION OF STUDY: The sample frame for this study was obtained from the University of Texas M. D. Anderson Cancer Center's Texas Community Oncology Network, a consortium of cancer treatment facilities in Texas. Of the 910 patients who were contacted, 593 (65%) responded to the survey. RESULTS: The results show the value of social support networks in assisting cancer patients with continuing treatment. An important finding indicated that health professionals do not provide information regarding social support groups to patients with cancer at the time of diagnosis. Fewer than half of the respondents were asked whether they would be interested in joining a formal social support group. Individuals of all racial/ethnic groups reported that the formal support groups provided emotional assistance. Minorities were more apt to report that the formal support groups helped with continuing treatment. In addition, informal social support networks, such as extended families and civic clubs, were seen as more helpful for blacks and Hispanics as compared with whites. CLINICAL IMPLICATIONS: The need for formal and informal networks is indicated by the results of this study, which show that networks, such as relationships with family, friends, and relatives, play an important role in assisting patients in coping with their cancer. These networks are part of the patient's total treatment experience and must be acknowledged by healthcare professionals. A large number of patients are not asked to join social support groups, suggesting a need for training healthcare professionals to provide information regarding the potential benefits of support groups for cancer patients.

Adolescent↗

[Living arrangements and social networks of elders. A selection of findings from a NESTOR-Study].

This article presents an overview of the design and results of the NESTOR survey 'Living Arrangements and Social Networks of Older Adults', an empirical study, started in 1992, among a representative sample of 4495 people, aged 55-89, selected from the population registers of 11 municipalities in the Netherlands. Questions were asked about living arrangements, the composition and functions of social networks, and important transitions in the marital, parental and occupational careers. The results indicated a wide diversity in living arrangements and social networks, a diversity which is particularly visible among the young old. They not only have larger networks, but are also more likely to live alone, to be divorced and to participate in shared housing arrangements. The networks vary considerably in size, from 0 to more than 40 important relationships. The decrease in network size with age appears to be directly related to specific life events such as widowhood, physical handicaps, residential moves etc. About 2/3 of the relationships are family relationships: parents, children (in law), grandchildren (in law), brothers and sisters (in law), uncles and aunts. Older people tend to be in touch at least once a month with the majority of close family members. The intensity of supportive exchanges (giving and receiving instrumental and emotional support in the twelve relationships with the highest levels of contact) is moderate, however mostly in balance. Only the very old receive somewhat more instrumental support and give considerably less than the 'young-old'. We studied the shift in balance between giving and receiving over a period of 12 months among a small proportion of the sample, checking a central hypothesis of exchange theory. In some cases a new balance evolves. In others the relationship continues to exist for a number of reasons, despite the imbalance. Early life experiences appear to be important for later life outcomes. Those who experienced the divorce of their parents before the age of 15 or those whose parents lived apart permanently (e.g. unmarried mothers) have a smaller social network and feel more lonely. Marital history has an impact on patterns of informal and formal care. E.g., those respondents without a partner who have children are less likely to use formal care than those who are childless. Among divorced elderly the use of formal care not only varies between men and women but also differs according to the marriage in which the children are born, first or second marriage. Occupational history is strongly related to the income level of older women living alone.

Aged↗