ModelDB: an environment for running and storing computational models and their results applied to neuroscience.

Research groups within the Human Brain Project are developing technologies to help organize and make accessible the vast quantities of information being accumulated in the neurosciences. The goal of this work is to provide systems that enable this complex information from many diverse sources to be synthesized into a coherent theory of nervous system function. Our initial approach to this problem has been to create several small databases. While addressing the issues of each individual database, we are also considering how each might be incorporated into an integrated cluster of databases. In this paper, we describe a pilot project in which we construct a database of computational models of neuronal function. This database allows models to be created and run and their results reviewed through a World Wide Web interface. Because models encapsulate knowledge in a formal manner about how neuronal systems function, we also discuss how this database forms a natural center for our initial attempts at creating a cluster of related databases. General issues of database development in the context of the Web are also discussed.

Exploration and virtual experimentation in a local neuroscience database.

Work is currently being done by a number of groups to investigate the possibility of creating one or more neuroscience databases. These databases could provide: (1) a means for conveying complete descriptions of experiments; (2) a platform for virtual experiments; (3) and an interface where modeling and experimental results could be exchanged. This paper describes work towards creating a local database with these capabilities by creating a set of experimental neurophysiology software tools that are tied to a database of experiment descriptions via external scripting mechanisms. These tools provide a means of exploring results and data that can lead to insights into the data that suggest new avenues of research. Because the scriptability of the tools allows for automation of re-analysis of the data, virtual experiments for testing new hypotheses over large datasets becomes possible. Such virtual experiments are particularly relevant to computational neuroscience, as they allow hypotheses generated by models to be immediately tested without further collection of experimental data.

A new approach to optical imaging applied to rat barrel cortex.

Several groups have described using intrinsic optical imaging to form images of activity patterns in the cortex. Because the signal is small, the general approach has been to use expensive camera equipment with a high dynamic range to make these measurements. However, by using signal averaging to compensate for lower dynamic range, images can be obtained using equipment already available in many laboratories. This modified technique has been used for imaging activity in 'barrel' cortex of the rat. A map of the representation of a single whisker as determined by the imaging technique corresponded well with a similar map made using standard electrophysiology. A map of several whiskers was made by overlaying images of single-whisker representations. The details of the images differ from those previously described. Possible mechanisms for the signal are discussed.

EXP: a Macintosh program for automating data acquisition and analysis applied to neurophysiology.

EXP is a Macintosh program for doing quantitative neurophysiology. It supports signal design, simultaneous signal output and data collection, spike sorting, histogram production, and many other analysis features. The hierarchical structure used to design protocols provides a straightforward method for designing complex experiments. The degree of automation supported by the program makes it possible to perform large-scale experiments and to collect and analyze large quantities of data in a reasonable amount of time. It has been used successfully in a large number of experimental paradigms by several different researchers. EXP is one of several cooperative programs designed to help perform neurophysiological experiments. These programs can be used in tandem not only to collect and analyze data but to help interpret and present results as well. The programs contain mechanisms to encourage re-analysis or 'virtual experiments' on data collected previously by oneself or other researchers.

MAP: a Macintosh program for generating categorical maps applied to cortical mapping.

One technique for studying the cortex entails mapping the distribution of neuronal response properties across a cortical zone. In sensory cortex, 'receptive fields' are arranged in an orderly way such that they form a topographical representation, or 'map', of the sensory surface on the cortex. Detailed maps can be constructed by making many microelectrode penetrations across the cortex and measuring the receptive field at each site. A computer program called MAP was designed to aid in the efficient generation of these maps. MAP allows the user to mark penetration sites on digitized images of the cortical surface and to draw receptive fields on digitized images of the skin surface being studied. Penetration sites are then automatically assigned a category based on the location of the receptive field. MAP has significantly increased the speed of this experimental process. MAP contains a number of mechanisms designed to facilitate analysis. For example, it can automatically generate cortical maps based on receptive field locations. It can also show recorded neurophysiological data at each penetration site allowing the experimenter to visualize activity across the cortical zone. These features along with several others make MAP an effective tool for cortical mapping.

The inferior olivary complex of guinea pig: cytoarchitecture and cellular morphology.

The inferior olivary complex (I.O.C.) of the guinea pig can be divided into three primary subdivisions: the principal olive (PO), the medial accessory olive (MAO), and the dorsal accessory olive (DAO). In Nissl-stained preparations, the PO possessed darker staining cells than did the MAO and DAO and was the most densely populated with cells. All neuronal somata in the I.O.C. were oblique-spheroid in profile (mean size: coronal = 18.3 microns, parasagittal = 15.8 microns). Based on Golgi impregnations, it was apparent that inferior olive cells were of two unique radiate-cell types (I and II). Type I neurons had relatively diffuse, sparsely branched dendritic arbors, whereas type II cells had dendrites which were highly branched and massed about the cell body, at times creating complex spirals. Type II cells were further categorized into types IIa and IIb based on geometric variations of the type II dendritic arbors. Indices of branching and tortuosity, together with estimates of dendritic arbor volume, were quite helpful in distinguishing cell types. The cell types were differentially distributed across the subdivisions with type I neurons being encountered in the MAO while type II cells were found in all three subdivisions. Within the neuropil of the I.O.C., three different afferent axonal arbors were identified, as was the presence of dendrites from surrounding reticular formation cells. Neuronal aggregates creating a possible electrical syncytium within the I.O.C. are consistent with the dendroarchitectonics of the cells.

Threat and authoritarianism in the United States, 1978-1987.

Studies at both the individual and collective levels have implicated threat as an important factor in authoritarianism. As a follow-up to Sales's (1973) study relating behavioral indicators of authoritarianism to levels of social threat, the present research analyzed archival data from the United States for high-threat (1978-1982) and low-threat (1983-1987) periods. Societal measures of most attitude and behavioral components of the authoritarian syndrome significantly decreased between the high-threat and the low-threat periods. These results support the threat-authoritarianism relationship but also suggest a more complicated theoretical model that links perceived social conditions, arousal of authoritarian sentiments, dispositional authoritarianism, and the nature of political appeals--particularly those that engage authoritarian aggression.

Using personal and fictional documents to assess psychosocial development: a case study of Vera Brittain's generativity.

Adult diaries and novels written by the British feminist and pacifist Vera Brittain (1893-1970) were content analyzed for Eriksonian themes of identity, intimacy, and generativity. Brittain's concerns with identity and intimacy decreased over time, while her generative concerns increased, suggesting that she expressed the issue of generativity vs. stagnation in her mid-life diaries and fiction. The large number of identity themes relative to both intimacy and generativity provokes speculations about Brittain's personality, the characteristics of writers, the influence of gender, the impact of society, and the possibility that the crisis of identity vs. role confusion involves the last major structural change in personality development. This archival case study is consistent with Erikson's notion of a sequence of concerns with psychosocial issues, although directions for theoretical revision and elaboration are discussed.

Antecedents and contexts of generativity motivation at midlife.

A semiprojective measure of generativity motivation--the desire to contribute to the welfare of society--was developed and applied to a longitudinal sample of educated women. In support of previous theory that generativity represents a fusion of agency and communion, generativity at midlife was related to a combination of adolescent scores on achievement, affiliation, and power motivation. The measure was also related to independent indexes of generative wishes and Q-sort generativity. The importance of contextualizing generativity motivation is demonstrated: Generative women with careers found gratification through work, whereas generative women not working in careers experienced gratification through parenting. Generativity was also related to political consciousness. Finally, as young adults, generative women expressed gratitude toward mentors. The authors discuss theoretical implications for E. H. Erikson's (1950) concept of psychosocial generativity.

Realization of generativity in two samples of women at midlife.

On the basis of E. H. Erikson's (1950/1963) theory of midlife development, a measure of generativity realization was constructed with items from J. Block's (1961/1978) California Adult Q-Set (CAQ). Convergent and discriminant validity for the new CAQ measure were established through a survey of 2 samples of educated women at about 43 years of age (N = 208). These 2 samples, 1 from a study of Mills College graduates and the other from a study of Radcliffe College graduates, were also used to examine the personality, attitudinal, and life outcome correlates of generativity at midlife. Results indicated that generative women have prosocial personality characteristics, express generative attitudes through their work, are invested in the parenting process, and exhibit an expanded radius of care. In general, results conceptually replicated in the Mills and Radcliffe samples.

Serologic and structural comparisons of rabbit IgA allotypes.

Serologic and structural comparisons of the rabbit IgA-g allotypes revealed that 1) the IgA-g allotypes have multiple allotypic determinant sites, 2) the g74, g76 and g77 allotypic specificities have several allotypic determinants in common whereas g75 molecules do not appear to have allotypic determinants in common with g74, g76 and g77 molecules, 3) the partial amino acid sequence of alpha chain from g75 and g76 Fc2alpha fragments differ by at least one amino acid residue, and 4) the g74 alpha-chains may have the "extra" intradomain disulfide bond in the Calpha2 domain whereas the g75 and g76 alpha chains lack this disulfide bond. Thus, multiple mutational events must have occurred during the evolution of g74, g75 and g77 genes.

[Problems in early oncological pathology]. / Problemy rannei onkologicheskoi patologii.

The concept of early oncological pathology is elucidated, to which prelesion and the onset (tumors) are referred. The problem is considered first, as a sum of functional and morphological changes in the organism, organ, in tissue and cell, which naturally precede the development of a malignant tumor and the resultant initial morphological manifestations of it; second, the problem of early oncological pathology should be concerned with the possibilities of to-day to diagnose the onset of the lesion. Practically, of special importance is studying of the diagnosis and treatment of a microscopic malignant tumor and a minute tumor seen visually. The principles of a microscopic malignant tumor and a minute tumor seen visually. The principles of recognition, treatment and recording of incipient cancer are discussed, the programme is suggested for further investigations in this major field of oncology.

[Oncological patients in the stage-IV clinical group]. / Ob onkologicheskikh bol'nykh IV klinicheskoi gruppy.

The report deals with basement of development of palliative and psychotherapeutic measures aimed at relieving the condition of patients with tumors at stage IV who cannot be cured by special antitumor procedures. Such measures are of considerable practical importance. They are intended to ensure the biological, psychological and social adaptation of incurable patients to the terminal course of malignant disease. Some approaches to the solution of the problem are outlined.

[Pathogenetic bases of oncologic risk]. / Patogeneticheskoe obosnovanie onkologicheskogo riska.

Modern concepts on the etiology and pathogenesis of malignant tumors are reported, two basic links being distinguished-genetic factors and environmental factors--modifying ones. The specific weight of both factors in the etiology and pathogenesis of different oncological affections is varied. Based on the analysis of the modern concepts of the origin and development of a tumor the authors have elaborated a working scheme of selection of oncological risk groups among the population. The modifying factors being of primary importance for tumor growth are grouped by the authors into exogenous and endogenous ones. It is suggested to judge the degree of their manifestation in different individuals by the duration of their effect. The working scheme concerned may provide a logical basis for assessment of risk groups in various oncological lesions, but it needs some further verification in clinical practice.

[Development of combined methods of treatment of malignant tumors]. / Razvitie kombinirovannykh metodov lecheniia zlokachestvennykh opukholei.

The term "combination treatment" should implicate various methods of treatment for malignant tumors scheduled beforehand. The combination treatment of malignant tumors is aimed at improving the immediate and late results. This is gained by means of reducing the biological activity of a tumor, both the effect of summation and potentiation of the action of different therapeutic measures being observed. The choice of methods and their sequence is determined by the prognosis factors, which incude the histological tumor structure, anatomical type of growth, the degree of its proliferation both within the range of proximate and remote zones of metastases spread, the general patient's state. At this stage it is difficult to elaborate the methods of combination treatment. The difficulties are conditioned by a variety of forms of many solid tumors, methodical difficulties and complexity of estimating an efficacy of different variants of treatment. Accumulating of knowledge should determine the a range of lesions subject to the combination treatment.

[Data analysis of newly registered stomach cancer patients]. / Analiz dannykh o pervichno zaregistrirovannykh bol'nykh rakom zheludka.

Since 1969 to 1973 20 711 patients with gastric cancer were primarily registered, 35.6% of them were persons over 70 years of age. There is a certain tendency to increasing of the morbidity rate with age among aged persons. 30.7% of patients were considered to be incurable, surgery was denied due to age and concomitant diseases in 20.0%, 17.2% of patients refused the operation, 32.1% of patients were treated. Resectability makes 23.1% with a marked tendency to fall with age.

[Clinical aspects and treatment results in stage T1N0M0 lung cancer]. / Klinika i rezul'taty lecheniia raka legkogo v stadii T1N0M0.

Late results of surgical treatment for lung cancer in stage TINOMO have been studied. A 5-year survival was 83.3%, 10-year survival--67%. Primary multiplicity of malignant tumors was revealed in 16% of observations. Peripheral cancer has more frequently arisen against the background of scars, central- on the background of proliferation and metaplasia of bronchial epithelium. Roentgenological methods for recognizing small size tumors proved to be effective in peripheral cancer, repeat cytological assays of the sputum--in central one. Lobectomy is considered to be the operation of choice in this stage of cancer. The diagnosis of cancer established in stage T1N0M0 should be considered as being timely, but it requires further improvement in the organization of active recognition of such patients.

[Early oncological pathology of the stomach]. / Ranniaia onkologicheskaia patologiia zheludka.

The paper reports the results of a study of 586 gastrobioptical and cytological preparations obtained in the course of endoscopic examination of 223 patients with gastritis, polyps and gastric ulcers and resected material from 46 patients who had small-size malignant tumors of the stomach (up to 1 cm in dia). Gastrobiopsy revealed dysplasia-like changes in the epithelium in 33% of cases of chronic gastric diseases. Dysplasia in the mucosa surrounding tumor was identified in all cancer patients. Three degrees of dysplasia of gland epithelium--mild, moderate and severe--were distinguished, each allowing further division into two classes. It is suggested that patients with dysplasia of gastric mucosa epithelium, identified by gastrobiopsy, should be referred to a group at high risk and followed up closely.

[Combined (surgical and drug) therapy of lung cancer]. / Kombinirovannoe (khirurgicheskoe i lekarstvennoe) lechenie bol'nykh rakom legkogo.

The paper deals with an evaluation of the immediate and end results as well as the rates of lung tumor progression in the course of surgical and combined therapy including different schedules of long-term administration of preparation CCNU. Combined therapy was shown to be followed by a longer remission and survival, as compared with cancer patients in control. The said effect was particularly pronounced is cases of squamous-cell carcinoma and in patients treated with levomycetin.

The viability of cells obtained using the Reamer-Irrigator-Aspirator system and in bone graft from the iliac crest.

We hypothesised that cells obtained via a Reamer-Irrigator-Aspirator (RIA) system retain substantial osteogenic potential and are at least equivalent to graft harvested from the iliac crest. Graft was harvested using the RIA in 25 patients (mean age 37.6 years (18 to 68)) and from the iliac crest in 21 patients (mean age 44.6 years (24 to 78)), after which ≥ 1 g of bony particulate graft material was processed from each. Initial cell viability was assessed using Trypan blue exclusion, and initial fluorescence-activated cell sorting (FACS) analysis for cell lineage was performed. After culturing the cells, repeat FACS analysis for cell lineage was performed and enzyme-linked immunosorbent assay (ELISA) for osteocalcin, and Alizarin red staining to determine osteogenic potential. Cells obtained via RIA or from the iliac crest were viable and matured into mesenchymal stem cells, as shown by staining for the specific mesenchymal antigens CD90 and CD105. For samples from both RIA and the iliac crest there was a statistically significant increase in bone production (both p < 0.001), as demonstrated by osteocalcin production after induction. Medullary autograft cells harvested using RIA are viable and osteogenic. Cell viability and osteogenic potential were similar between bone grafts obtained from both the RIA system and the iliac crest.