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PubMed2002

Multi-objective cooperative coevolution of artificial neural networks (multi-objective cooperative networks).

In this paper we present a cooperative coevolutive model for the evolution of neural network topology and weights, called MOBNET. MOBNET evolves subcomponents that must be combined in order to form a network, instead of whole networks. The problem of assigning credit to the subcomponents is approached as a multi-objective optimization task. The subcomponents in a cooperative coevolutive model must fulfill different criteria to be useful, these criteria usually conflict with each other. The problem of evaluating the fitness on an individual based on many criteria that must be optimized together can be approached as a multi-criteria optimization problems, so the methods from multi-objective optimization offer the most natural way to solve the problem. In this work we show how using several objectives for every subcomponent and evaluating its fitness as a multi-objective optimization problem, the performance of the model is highly competitive. MOBNET is compared with several standard methods of classification and with other neural network models in solving four real-world problems, and it shows the best overall performance of all classification methods applied. It also produces smaller networks when compared to other models. The basic idea underlying MOBNET is extensible to a more general model of coevolutionary computation, as none of its features are exclusive of neural networks design. There are many applications of cooperative coevolution that could benefit from the multi-objective optimization approach proposed in this paper.

Biological Evolution↗
PubMedDate not supplied

Coincubation of tissue slices, a new way to study metabolic cooperation between organs: hepatorenal cooperation in the biotransformation of CGP 47 969 A.

INTRODUCTION: There is limited information on in vitro/ex vivo tools to be used for studying interorgan metabolic cooperation. We report here the use of the tissue slice technique for this purpose. METHODS: Rat liver and kidney slices were used to study metabolic cooperation for the metabolism of CGP 47 969, a potential anti-inflammatory compound which in vivo is extensively conjugated with glutathione and subsequently degraded via the mercapturic acid pathway. RESULTS: Upon incubation with liver slices, CGP 47 969 was extensively conjugated with GSH whilst degradation of the GSH conjugate was moderate. Upon incubation with kidney slices, conjugation of CGP 47 969 with GSH was moderate but degradation of the GSH conjugate was complete. Upon coincubation of CGP 47 969 with liver and kidney slices, both conjugation with GSH and its subsequent degradation were almost complete. Thus, coincubation of liver and kidney slices permitted the efficient in vitro reproduction of the complete biotransformation of CGP 47 969 via its GSH conjugate to the ultimate mercapturic acid metabolite in a one step procedure. DISCUSSION: This novel slice coincubation culture could serve as an in vitro model for interorgan cooperation in multistep metabolic processing.

Acetylcysteine↗
PubMed2005

Cooperativity and pseudo-cooperativity in the glutathione S-transferase from Plasmodium falciparum.

Binding and catalytic properties of glutathione S-transferase from Plasmodium falciparum (PfGST) have been studied by means of fluorescence, steady state and pre-steady state kinetic experiments, and docking simulations. This enzyme displays a peculiar reversible low-high affinity transition, never observed in other GSTs, which involves the G-site and shifts the apparent K(D) for glutathione (GSH) from 200 to 0.18 mM. The transition toward the high affinity conformation is triggered by the simultaneous binding of two GSH molecules to the dimeric enzyme, and it is manifested as an uncorrected homotropic behavior, termed "pseudo-cooperativity." The high affinity enzyme is able to activate GSH, lowering its pK(a) value from 9.0 to 7.0, a behavior similar to that found in all known GSTs. Using 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, this enzyme reveals a potential optimized mechanism for the GSH conjugation but a low catalytic efficiency mainly due to a very low affinity for this co-substrate. Conversely, PfGST efficiently binds one molecule of hemin/monomer. The binding is highly cooperative (n(H) = 1.8) and occurs only when GSH is bound to the enzyme. The thiolate of GSH plays a crucial role in the intersubunit communication because no cooperativity is observed when S-methylglutathione replaces GSH. Docking simulations suggest that hemin binds to a pocket leaning into both the G-site and the H-site. The iron is coordinated by the amidic nitrogen of Asn-115, and the two carboxylate groups are in electrostatic interaction with the epsilon-amino group of Lys-15. Kinetic and structural data suggest that PfGST evolved by optimizing its binding property with the parasitotoxic hemin rather than its catalytic efficiency toward toxic electrophilic compounds.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Is Ca(II) ion binding to prothrombin fragment 1 intrinsically cooperative, or is the cooperative binding accounted for by self-association?

The recent suggestion that the apparent cooperativity seen in the binding of Ca(II) ions to prothrombin fragment 1 is due to protein aggregation is evaluated. Since (1) we find that the Ca(II) ion binding is not dependent upon protein concentration, (2) the analytical expression for the equilibrium constant of the aggregation model is unrealistically large when evaluated at realistic Ca(II) ion concentrations, and (3) a very simple allosteric cooperative binding model (Monod) can be shown to fit the experimental data, we conclude that the aggregation explanation for the apparent cooperativity in the Ca(II) ion binding by prothrombin fragment 1 is not correct.

Animals↗
PubMed2003

HNF-1alpha and endodermal transcription factors cooperatively activate Fabpl: MODY3 mutations abrogate cooperativity.

Hepatocyte nuclear factor (HNF)-1alpha plays a central role in intestinal and hepatic gene regulation and is required for hepatic expression of the liver fatty acid binding protein gene (Fabpl). An Fabpl transgene was directly activated through cognate sites by HNF-1alpha and HNF-1beta, as well as five other endodermal factors: CDX-1, C/EBPbeta, GATA-4, FoxA2, and HNF-4alpha. HNF-1alpha activated the Fabpl transgene by as much as 60-fold greater in the presence of the other five endodermal factors than in their absence, accounting for up to one-half the total transgene activation by the group of six factors. This degree of synergistic interaction suggests that multifactor cooperativity is a critical determinant of endodermal gene activation by HNF-1alpha. Mutations in HNF-1alpha that result in maturity onset diabetes of the young (MODY3) provide evidence for the in vivo significance of these synergistic interactions. An R131Q HNF-1alpha MODY3 mutant exhibits complete loss of synergistic activation in concert with the other endodermal transcription factors despite wild-type transactivation ability in their absence. Furthermore, whereas wild-type HNF-1alpha exhibited pairwise cooperative synergy with each of the other five factors, the R131Q mutant could synergize only with GATA-4 and C/EBPbeta. Selective loss of synergy with other endodermal transcription factors accompanied by retention of native transactivation ability in an HNF-1alpha MODY mutant suggests in vivo significance for cooperative synergy.

Animals↗
PubMed1990

[The importance of cooperation in primary health care. Utilization of physicians' services and home nursing services during different degrees of cooperation].

A study carried out in the county of Vestfold in the spring of 1989 clearly showed how cooperation between doctor and nurse influenced the level and quality of care provided by doctors to patients nursed at home. Good cooperation coincided with high quality health services, and ensured rational use of resources in relation to the patients' needs. The study showed that the quality and frequency of cooperation between doctor and nurse are of utmost importance for the service given to the patients.

Community Health Nursing↗
PubMed1982

[The interpersonal attitude change in the cooperative situation: the cooperation of the seeing with the blind].

This study was conducted to examine the change of interpersonal attitudes of the seeing and the blind through the cooperative task. Subjects were 14 pairs of the seeing and the blind. The seeing were college students and high school students whose ages were from 17 to 24. The blind were students of blind schools whose ages were from 17 to 27. Each pair cooperated in a task of matching 40 category names (tree, color, etc.) written in usual letters with 40 object names (pine, red, etc.) written in braille. The main results were as follows: (1) Before the task the attitudes of the seeing to their "partners" and to "the blind" were more negative than those of the blind to their "partners" and to "the seeing". (2) The attitudes of the seeing to their "partners" and to "the blind" were more positive after the task than before.

Adolescent↗
PubMed1988

Evaluation of pathology review of malignant lymphomas and Hodgkin's disease in cooperative clinical trials. The Eastern Cooperative Oncology Group experience.

Although central expert pathology review for quality assurance in cooperative clinical trials involving malignant lymphomas and Hodgkin's disease was put in place by the NCI two decades ago, its impact upon patient eligibility for given treatment protocols has never been assessed. We reviewed diagnoses from contributing pathologists, the Eastern Cooperative Oncology Group (ECOG) review pathologists and the Pathology Panel for Lymphoma Clinical Studies in 2019 cases from 14 ECOG protocols. Although we found high rates of disagreements in diagnoses, the vast majority of these represented differences which did not impact on protocol eligibility. A total of 221 cases (10.9%) were excluded from protocols, representing a range of 2.8 to 36.7% of cases per protocol. Eighty-six percent of the exclusions resulted from the initial review by the ECOG hematopathologists. Our data indicate that while central pathology review is mandatory for quality assurance in malignant lymphoma (ML) and Hodgkin's disease (HD) protocols, a two-tier review mechanism is not necessary for adequate quality control.

Clinical Trials as Topic↗
PubMed1993

Additive, cooperative and anti-cooperative effects between identity nucleotides of a tRNA.

We have investigated the functional relationship between nucleotides in yeast tRNAAsp that are important for aspartylation by yeast aspartyl-tRNA synthetase. Transcripts of tRNAAsp with two or more mutations at identity positions G73, G34, U35, C36 and base pair G10-U25 have been prepared and the steady-state kinetics of their aspartylation were measured. Multiple mutations affect the catalytic activities of the synthetase mainly at the level of the catalytic constant, kcat. Kinetic data were expressed as free energy variation at transition state of these multiple mutants and comparison of experimental values with those calculated from results on single mutants defined three types of relationships between the identity nucleotides of this tRNA. Nucleotides located far apart in the three-dimensional structure of the tRNA act cooperatively whereas nucleotides of the anticodon triplet act either additively or anti-cooperatively. These results are related to the specific interactions of functional groups on identity nucleotides with amino acids in the protein as revealed by the crystal structure of the tRNAAsp/aspartyl-tRNA synthetase complex. These relationships between identity nucleotides may play an important role in the biological function of tRNAs.

Acylation↗
PubMed2003

Transitions between cooperative and non-cooperative responding in the 'Pigeon's Dilemma'

Two pigeons played Iterated Prisoner's Dilemma (IPD) against a simulated opponent pre-programmed to play 'Tit-For-Tat' (TFT) and 'Random' (RND) strategies. Each pigeon received differential amounts of access to food following choices of either 'cooperate' or 'defect' on a trial. After 1000 trials against TFT and 500 trials against RND, results indicated that choice allocation was optimal when the birds played against RND but was sub-optimal when the birds played against TFT. In order to determine why the pigeons responded suboptimally against TFT, a trial-by-trial analysis of the data was conducted. The analysis revealed that once a pigeon had received the 'Sucker's' payoff (S), it was more likely to defect and receive the 'Temptation' payoff (T) than to cooperate and receive the 'Reward' (R) payoff. Local reinforcement contingencies appear to determine suboptimal responding against TFT in the iterated Pigeon's Dilemma.

Journal Article↗
PubMed2005

Asymmetric distribution of cooperativity in the binding cascade of normal human hemoglobin. 1. Cooperative and noncooperative oxygen binding in Zn-substituted hemoglobin.

The complete binding cascade of human hemoglobin consists of eight partially ligated intermediates and 16 binding constants. Each intermediate binding constant can be evaluated via dimer-tetramer assembly when ligand configurations within the tetramer are fixed through the use of hemesite analogs. The Zn/Fe analog, in which the nonbinding Zn2+ heme substitutes for deoxy Fe2+ heme, also permits direct measurement of O2 binding to the remaining Fe2+ hemesites within the symmetrically ligated Hb tetramers. Measurement of O2 binding over a range of Zn/Fe Hb concentrations to both alpha-subunits (species 23) or to both beta-subunits (species 24) shows noncooperative binding and incomplete saturation of the available Fe2+ hemesites. In contrast, the asymmetrically ligated Zn/FeO2 species 21, in which both oxygens are bound to one of the dimers within the tetramer, exhibits positive cooperativity and >90% ligation under atmospheric conditions. These properties are confirmed in the present study by measurement of the rate constant for tetramer dissociation to free dimer. The binding constants thus derived for these partially ligated intermediates are consistent with the stoichiometric constants measured for native hemoglobin by standard O2 binding techniques, providing additional evidence that Zn2+-heme substitution provides an excellent deoxy hemoglobin analog. There is no evidence that Zn-substitution stabilizes a low-affinity form of the tetramer, as previously suggested. These characterizations demonstrate distinct, nonadditive physical properties of the doubly ligated tetrameric species, yielding an asymmetric distribution of cooperativity within the cascade of O2 binding by human hemoglobin.

Allosteric Regulation↗
PubMed1976

Cooperative interactions of tetrahydrofolate with purified pig kidney serine transhydroxymethylase and loss of this cooperativity in L1210 tumors and in tissues of mice bearing these tumors.

Serine transhydroxymethylase (5,10-methylenetetrahydrofolate: glycine hydroxymethyl transferase, EC 2.1.2.1) purified 200-fold from pig kidneys showed cooperative interactions with tetrahydrofolate with a Hill coefficient (n value) of 3.9 and a substrate concentration at 50% of maximum velocity, the S(0.5) value, of 0.5 mM. The enzyme in mouse liver and kidney homogenates also showed cooperative interactions with tetrahydrofolate. However, the enzyme obtained from L1210 solid tumors of mice, and from livers and kidneys of mice inoculated with L1210 cells exhibited hyperbolic saturation kinetics and gave a Michaelis constant, Km, value of 0.5 mM for tetrahydrofolate. The interaction of serine with the enzyme from pig kidney, from tissues of normal or tumor-bearing mice, or from L1210 tumors was hyperbolic with a Km of 0.9 mM. The specific activities of the enzyme in the L1210 tumor and in mouse liver were 10-fold higher than in pig or mouse kidney. There was no significant change in the levels of the enzyme in mouse liver and kidney on inoculation with L1210 cells. These results suggest that a tumor can bring about biochemical changes in tissues that are distal to the tumor.

Allosteric Regulation↗
PubMed1976

Cooperation across the histocompatibility barrier: H2d T cells primed to antigen in an H-2d environment can cooperate with H-2k B cells.

H-2d spleen cells derived from either tetraparental or semiallogeneic radiation bone marrow chimeras can be primed to antigen within H-2d recipients to generate helper T cells capable of cooperating in a secondary response with equal efficiency with H-2d or H-2k B cells. Thus it would seem that the cooperative act between T and B cells does not require that the T cell interacts with its target B cells by either cell interaction genes or via an altered self mechanism involving both antigen and the target B-cell I-region products. This does not preclude a requirement for associative recognition or altered self in the interaction of helper T cells with accessory cells.

Animals↗
PubMed1995

The multicentre trial philosophy in stress echocardiography: lessons learned from the EPIC study. EPIC-EDIC Study Project. Echo Persantine International Cooperative Study. Echo-Dobutamine International Cooperative Study.

The scientific assessment of diagnostic tests should not be based upon a small series of results published by the best academic institutions, but ought to require large scale, multicentre validation founded on grass roots institutions with real doctors, real patients and real problems. To this purpose, an international network of stress echo laboratories has been organized, and within a few years has collected data from thousands of studies using pharmacological stress echocardiography, performed with either dipyridamole (EPIC: Echo Persantine International Cooperative Study) or dobutamine (EDIC: Echo Dobutamine International Cooperative Study) stresses. In a widely deregulated field, all network laboratories have agreed: to pass a quality control examination on stress echo reading before entering the study; to adopt an identical drug infusion protocol; to code similarly the LV segments; and to adopt a common scoring system for wall motion analysis. A minimum amount of historical, clinical, and-when available-stress electrocardiographic, angiographic and follow-up data have been collected on each patient, and disseminated in the various centres, facilitating the creation of an international stress echo language that will help, not only the production of high quality scientific data, but also the build up of a common stress echo lab, with a standardized way of making the studies, unifying the methods and terminology, and archiving data. To date, we have 50 echo laboratories from 15 nations across four continents (Europe, America, Asia and Africa) actively involved in this project. These data will ultimately fill the gap between the academic theory of journals and the pragmatic experience of daily life in a busy echocardiographic laboratory.

Echocardiography↗
PubMed1995

Cooperative conversations. The effect of cooperative learning on conversational interaction.

An ongoing challenge for educators of deaf and hard-of-hearing students is to find opportunities for students to use their language skills in a functional way, that is, through conversation. This study was initiated to determine whether cooperative learning is a viable means of encouraging mainstreamed hard-of-hearing students to engage in conversational interaction with their hearing peers and teachers. A single-subject design utilizing three mainstreamed hard-of-hearing subjects attending middle school was used to examine this question. Results of the study indicated that cooperative learning positively influenced the conversational turns, initiations, moves, and mean length of turn in these hard-of-hearing subjects.

Adolescent↗
PubMed1985

Medicare and Medicaid programs, health care financing research and demonstration cooperative agreements and grants and availability of funds for cooperative agreements and grants--HCFA. General notice.

This notice announces the availability of HCFA funds for certain priority research and demonstration cooperative agreements and grants for the Federal fiscal year 1985. HCFA makes funds available for activities that will help to resolve major health care financing issues or to develop innovative methods for the administration of Medicare and Medicaid. This notice contains information about the subject areas for cooperative agreements and grants that will be given priority; project requirements; application procedures and other pertinent information. It also cancels the February 4, 1985 closing date for HCFA waiver-only applications that was announced on November 9, 1983.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1988

Rat liver glycine methyltransferase. Cooperative binding of S-adenosylmethionine and loss of cooperativity by removal of a short NH2-terminal segment.

Rat liver glycine methyltransferase, a homotetramer, exhibits sigmoidal rate behavior with respect to S-adenosylmethionine (Ogawa, H., and Fujioka, M. (1982) J. Biol. Chem. 257, 3447-3452). The binding experiment shows that the sigmoidicity observed in initial velocity kinetics is explained by the cooperative binding of S-adenosylmethionine to the catalytic sites residing on each subunit. Limited proteolysis of glycine methyltransferase with trypsin in the presence of S-adenosylmethionine yields an enzyme lacking the NH2-terminal 8 residues. The proteolytically modified enzyme retains a tetrameric structure. The truncated enzyme shows no cooperativity with respect to S-adenosylmethionine binding and kinetics. It has values of Vmax and Km for glycine identical to those of the native enzyme, but a 3-fold lower [S]0.5 value for S-adenosylmethionine. The proteolytic modification is without effect on the circular dichroism and fluorescence spectra. Furthermore, the protein fluorescence of the modified enzyme is quenched upon addition of S-adenosylmethionine to the same extent as observed with the native enzyme. These results suggest that a short NH2-terminal segment, which lies outside the active site, is important for communication between subunits.

Animals↗
PubMedDate not supplied

[Model for tobacco mosaic virus assembly in vitro: specific dislocation by cooperative single-letter purine recognition and non-cooperative RNA "locking" between subunit layers].

A model of the molecular mechanism of tobacco mosaic virus (TMV) assembly in vitro is proposed. The model is based on the assumption that on interaction of TMV RNA chain with a double protein disk two different types of structural alterations occur in the protein subunits: "dislocating alterations" leading to screw dislocation of the disk into a helix fragment and "locking alterations" leading to locking of the RNA chain between the subunits layers. During initiation of TMV assembly the dislocating alterations occur cooperatively in all subunits of the disk as a result of specific interaction of purines (guanines) in the middle (horizontal) position of every trinucleotide unit with the 32--39 loop of the TMV protein molecule. Locking alterations are induced non-cooperatively by phosphate groups and lateral (vertical) bases of trinucleotide units. The sequence of events during TMV assembly in vitro and the role of topological factors in this process are discussed.

Models, Biological↗