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Stabilizer operations are at the heart of quantum error correction and are typically implemented in software-controlled entangling gates and measurements of groups of qubits. Alternatively, qubits can be designed so that the Hamiltonian corresponds directly to a stabilizer for protecting quantum information. We demonstrate such a hardware implementation of stabilizers in a superconducting circuit composed of chains of π-periodic Josephson elements. With local on-chip flux and charge biasing, we observe a progressive softening of the energy band dispersion with respect to flux as the number of frustrated plaquette elements is increased, in close agreement with our numerical modeling.
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OBJECTIVE: Short sleep duration and sleep problems increase risks of overweight and weight gain. Few previous studies have examined sleep and weight repeatedly over development. This study examined the associations between yearly reports of sleep problems and weight status from ages 5 to 11. Although, previous studies have shown that inter-individual differences moderate the effect of short sleep duration on weight, it is not known whether inter-individual differences also moderate the effect of sleep problems on weight. We tested how the longitudinal associations between sleep problems and weight status were moderated by impulsivity and genetic variants in DRD2 and ANKK1. DESIGN: Seven-year longitudinal study. PARTICIPANTS: A total of 567 children from the Child Development Project for the analysis with impulsivity and 363 for the analysis with genetic variants. MEASUREMENTS AND RESULTS: Sleep problems and weight status were measured by mothers' reports yearly. Impulsivity was measured by teachers' reports yearly. Six single-nucleotide polymorphisms located in DRD2 and ANKK1 were genotyped. Data were analyzed using multilevel modeling. Higher average levels of sleep deprivation across years were associated with greater increases in overweight (P=0.0024). Sleep problems and overweight were associated at both within-person across time (P<0.0001) and between-person levels (P<0.0001). Impulsivity and two polymorphisms, rs1799978 and rs4245149 in DRD2, moderated the association between sleep problems and overweight; the association was stronger in children who were more impulsive (P=0.0022), in G allele carriers for rs1799978 (P=0.0007) and in A allele carriers for rs4245149 (P=0.0002). CONCLUSIONS: This study provided incremental evidence for the influence of sleep problems on weight. Findings of DRD2, ANKK1 and impulsivity are novel; they suggest that reward sensitivity and self-regulatory abilities might modulate the influences of sleep on weight gain. The analysis of polymorphisms was restricted to European Americans and hence the results might not generalize to other populations.
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Conducta Impulsiva , Sobrepeso/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/genética , Receptores de Dopamina D2/genética , Privación de Sueño/genética , Aumento de Peso , Alelos , Niño , Preescolar , Femenino , Genotipo , Humanos , Desequilibrio de Ligamiento , Estudios Longitudinales , Masculino , Actividad Motora , Sobrepeso/etiología , Sobrepeso/prevención & control , Privación de Sueño/complicaciones , Factores Socioeconómicos , Estados Unidos/epidemiología , Población BlancaRESUMEN
A longitudinal, prospective design was used to examine the roles of peer rejection in middle childhood and antisocial peer involvement in early adolescence in the development of adolescent externalizing behavior problems. Both early starter and late starter pathways were considered. Classroom sociometric interviews from ages 6 through 9 years, adolescent reports of peers' behavior at age 13 years, and parent, teacher, and adolescent self-reports of externalizing behavior problems from age 5 through 14 years were available for 400 adolescents. Results indicate that experiencing peer rejection in elementary school and greater involvement with antisocial peers in early adolescence are correlated but that these peer relationship experiences may represent two different pathways to adolescent externalizing behavior problems. Peer rejection experiences, but not involvement with antisocial peers. predict later externalizing behavior problems when controlling for stability in externalizing behavior. Externalizing problems were most common when rejection was experienced repeatedly. Early externalizing problems did not appear to moderate the relation between peer rejection and later problem behavior. Discussion highlights multiple pathways connecting externalizing behavior problems from early childhood through adolescence with peer relationship experiences in middle childhood and early adolescence.
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Conducta del Adolescente/psicología , Trastorno de Personalidad Antisocial/psicología , Trastornos de la Conducta Infantil/psicología , Grupo Paritario , Rechazo en Psicología , Adolescente , Niño , Trastornos de la Conducta Infantil/diagnóstico , Preescolar , Femenino , Humanos , Relaciones Interpersonales , MasculinoRESUMEN
The early childhood antecedents and behavior-problem correlates of monitoring and psychological control were examined in this prospective, longitudinal, multi-informant study. Parenting data were collected during home visit interviews with 440 mothers and their 13-year-old children. Behavior problems (anxiety/depression and delinquent behavior) were assessed via mother, teacher, and/or adolescent reports at ages 8 through 10 years and again at ages 13 through 14. Home-interview data collected at age 5 years were used to measure antecedent parenting (harsh/reactive, positive/proactive), family background (e.g., socioeconomic status), and mother-rated child behavior problems. Consistent with expectation, monitoring was anteceded by a proactive parenting style and by advantageous family-ecological characteristics, and psychological control was anteceded by harsh parenting and by mothers' earlier reports of child externalizing problems. Consistent with prior research, monitoring was associated with fewer delinquent behavior problems. Links between psychological control and adjustment were more complex: High levels of psychological control were associated with more delinquent problems for girls and for teens who were low in preadolescent delinquent problems, and with more anxiety/depression for girls and for teens who were high in preadolescent anxiety/depression.
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Conducta del Adolescente/psicología , Relaciones Madre-Hijo , Responsabilidad Parental/psicología , Ajuste Social , Adolescente , Ansiedad/psicología , Niño , Depresión/psicología , Femenino , Humanos , Control Interno-Externo , Delincuencia Juvenil/psicología , Estudios Longitudinales , Masculino , Estudios ProspectivosRESUMEN
To explore an approach for death receptor targeting in cancer, we developed murine mAbs to human death receptor 4 (DR4). The mAb 4H6 (IgG1) competed with Apo2L/TNF-related apoptosis-inducing ligand (DR4's ligand) for binding to DR4, whereas mAb 4G7 (IgG2a) did not. In vitro, both mAbs showed minimal intrinsic apoptosis-inducing activity, but each triggered potent apoptosis upon cross-linking. In a colon tumor nude mouse model in vivo, mAb 4H6 treatment without addition of exogenous linkers induced apoptosis in tumor cells and caused complete tumor regression, whereas mAb 4G7 partially inhibited tumor growth. An IgG2a isotype switch variant of mAb 4H6 was much less effective in vivo than the parent IgG1-4H6, despite similar binding affinities to DR4. The same conclusion was obtained by comparing other IgG1 and IgG2 mAbs to DR4 for their anti-tumor activities in vivo. Thus, the isotype of anti-DR4 mAb may be more important than DR4 binding affinity for tumor elimination in vivo. Anti-DR4 mAbs of the IgG1 isotype may provide a useful tool for investigating the therapeutic potential of death receptor targeting in cancer.
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Anticuerpos Monoclonales/fisiología , Antineoplásicos/farmacología , Inhibidores de Crecimiento/fisiología , Inmunoglobulina G/fisiología , Isotipos de Inmunoglobulinas/fisiología , Neoplasias Experimentales/patología , Neoplasias Experimentales/prevención & control , Receptores del Factor de Necrosis Tumoral/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Apoptosis/inmunología , Sitios de Unión de Anticuerpos , Modelos Animales de Enfermedad , Inhibidores de Crecimiento/administración & dosificación , Humanos , Inmunoglobulina G/administración & dosificación , Isotipos de Inmunoglobulinas/administración & dosificación , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF , Trasplante Heterólogo , Células Tumorales Cultivadas/trasplanteRESUMEN
Spatiotemporal regulation of protein kinase A (PKA) activity involves the manipulation of compartmentalized cAMP pools. Now we demonstrate that the muscle-selective A-kinase anchoring protein, mAKAP, maintains a cAMP signaling module, including PKA and the rolipram-inhibited cAMP-specific phosphodiesterase (PDE4D3) in heart tissues. Functional analyses indicate that tonic PDE4D3 activity reduces the activity of the anchored PKA holoenzyme, whereas kinase activation stimulates mAKAP-associated phosphodiesterase activity. Disruption of PKA- mAKAP interaction prevents this enhancement of PDE4D3 activity, suggesting that the proximity of both enzymes in the mAKAP signaling complex forms a negative feedback loop to restore basal cAMP levels.
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3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Proteínas Musculares/metabolismo , Miocardio/metabolismo , Animales , Células Cultivadas , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Retroalimentación , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/metabolismo , Modelos Biológicos , Miocardio/citología , Unión Proteica , Ratas , Transducción de SeñalRESUMEN
The correlation between boys' social cognitions and their aggressive behavior toward peers was examined as being actor driven, partner driven, or dyadic relationship driven. Eleven groups of 6 familiar boys each (N = 165 dyads) met for 5 consecutive days to participate in play sessions and social-cognitive interviews. With a variance partitioning procedure, boys' social-cognitive processes were found to vary reliably across their dyadic relationships. Furthermore, mixed models regression analyses indicated that hostile attributional biases toward a particular peer were related to directly observed reactive aggression toward that peer even after controlling for actor and partner effects, suggesting that these phenomena are dyadic or relationship oriented. On the other hand, the relation between outcome expectancies for aggression and the display of proactive aggression appeared to be more actor driven and partner driven that dyadic.
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Agresión/psicología , Cognición , Percepción Social , Análisis de Varianza , Niño , Humanos , Masculino , Modelos Psicológicos , North Carolina , Grupo Paritario , Juego e Implementos de Juego , Análisis de RegresiónRESUMEN
Public policy in the United States has historically considered youth violence as a moral problem to be punished after the fact, but growing scientific evidence supports a public health perspective on violent behavior as an interaction between cultural forces and failures in development. Prevention science has provided a bridge between an understanding of how chronic violence develops and how prevention programs can interrupt that development. Articles in this journal supplement provide yet another bridge between efficacious university-based programs and effective community-based programs. It is suggested that yet one more bridge will need to be constructed in future research between community-based programs that are known to be effective and community-wide implementation of prevention efforts at full scale. This last bridge integrates the science of children's development, the science of prevention, and the science of public policy.
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Desarrollo de Programa , Política Pública , Violencia/prevención & control , Niño , Desarrollo Infantil , Preescolar , Diversidad Cultural , Humanos , Estados UnidosRESUMEN
In a sample of 578 children assessed in kindergarten through the eighth grade, we used growth modeling to determine the basic developmental trajectories of mother-reported and teacher-reported externalizing and internalizing behaviors for three physical maltreatment groups of children-early-harmed (prior to age 5 years), later-harmed (age 5 years and over), and nonharmed--controlling for SES and gender. Results demonstrated that the earlier children experienced harsh physical treatment by significant adults, the more likely they were to experience adjustment problems in early adolescence. Over multiple domains, early physical maltreatment was related to more negative sequelae than the same type of maltreatment occurring at later periods. In addition, the fitted growth models revealed that the early-harmed group exhibited someswhat higher initial levels of teacher-reported externalizing problems in kindergarten and significantly different rates of change in these problem behaviors than other children, as reported by mothers over the 9 years of this study. The early-harmed children were also seen by teachers, in kindergarten, as exhibiting higher levels of internalizing behaviors. The later-harmed children were seen by their teachers as increasing their externalizing problem behaviors more rapidly over the 9 years than did the early- or nonharmed children. These findings indicate that the timing of maltreatment is a salient factor in examining the developmental effects of physical harm.
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Maltrato a los Niños/psicología , Control Interno-Externo , Determinación de la Personalidad , Desarrollo de la Personalidad , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Masculino , Factores de RiesgoRESUMEN
Direct and indirect precursors to parents' harsh discipline responses to hypothetical vignettes about child misbehavior were studied with data from 978 parents (59% mothers; 82% European American and 16% African American) of 585 kindergarten-aged children. SEM analyses showed that parents' beliefs about spanking and child aggression and family stress mediated a negative relation between socioeconomic status and discipline. In turn, perception of the child and cognitive-emotional processes (hostile attributions, emotional upset, worry about child's future, available alternative disciplinary strategies, and available preventive strategies) mediated the effect of stress on discipline. Similar relations between ethnicity and discipline were found (African Americans reported harsher discipline), especially among low-income parents. Societally based experiences may lead some parents to rely on accessible and coherent goals in their discipline, whereas others are more reactive.
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Negro o Afroamericano/psicología , Control Interno-Externo , Responsabilidad Parental/psicología , Socialización , Factores Socioeconómicos , Estrés Psicológico/complicaciones , Población Blanca/psicología , Niño , Preescolar , Femenino , Humanos , Masculino , Valores SocialesRESUMEN
A molecular explanation for the specificity of the cAMP-dependent protein kinase (PKA) can be provided by its compartmentalization through association with A-kinase-anchoring proteins (AKAPs). Structural and functional studies have led to the development of an anchoring model proposing that AKAPs contain a common PKA binding domain and a unique subcellular targeting domain. The discovery that AKAPs can bind other signaling enzymes led to the addition of a third property, that of scaffolding molecule. Recent research has now expanded the role of AKAPs to members of multiunit complexes containing both upstream activators and downstream targets.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras/fisiología , Modelos Neurológicos , Neuronas/fisiología , Transducción de Señal , Proteínas de Anclaje a la Quinasa A , Animales , Proteínas Portadoras/genética , Membrana Celular/fisiología , HumanosRESUMEN
In a sample of 405 children assessed in kindergarten through the seventh grade, we determined the basic developmental trajectories of mother-reported and teacher-reported externalizing and internalizing behaviors using cross-domain latent growth modeling techniques. We also investigated the effects of race, socioeconomic level, gender, and sociometric peer-rejection status in kindergarten on these trajectories. The results indicated that, on average, the development of these behaviors was different depending upon the source of the data. We found evidence of the codevelopment of externalizing and internalizing behaviors within and across reporters. In addition, we found that African-American children had lower levels of externalizing behavior in kindergarten as reported by mothers than did European-American children but they had greater increases in these behaviors when reported by teachers. Children from homes with lower SES levels had higher initial levels of externalizing behaviors and teacher-reported internalizing behaviors. Males showed greater increases in teacher-reported externalizing behavior over time than did the females. Rejected children had trajectories of mother-reported externalizing and internalizing behavior that began at higher levels and either remained stable or increased more rapidly than did the trajectories for non-rejected children which decreased over time.
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Agresión , Trastornos de la Conducta Infantil/psicología , Relaciones Interpersonales , Desarrollo de la Personalidad , Negro o Afroamericano/psicología , Preescolar , Femenino , Humanos , Masculino , Modelos Psicológicos , Grupo Paritario , Factores Sexuales , Deseabilidad Social , Factores Socioeconómicos , Población Blanca/psicologíaRESUMEN
This article reports on a study of 64 female substance abusers in residential treatment for chemical dependency. This study was conducted with the purpose of describing the associations between: (a) demographic characteristics, (b) presence and severity of addiction, (c) depression, and (d) self-esteem. All participants were drawn from inpatient females, and were administered questionnaires that included the following instruments: (a) Screening/Intake Assessment, (b) the Michigan Alcohol Screening Test, (c) the Addiction Presence and Severity Index, (d) the Provision of Social Relations Scale, (e) the Rosenberg Self-Esteem Scale, and (f) the Costello-Comrey Depression Scale. Multivariate analyses revealed that levels of self-esteem were related to detoxification status and social support. Depression levels were associated with social support, and severity of addiction was more pronounced for White clients than Black clients in this study. Implications for program development are discussed.
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Trastornos Relacionados con Sustancias/terapia , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Autoimagen , Apoyo SocialRESUMEN
Espouses developmental psychopathology as a framework for training our future leaders due to its emphasis on an ecological, transactional lifespan perspective, as well as interdisciplinary bridging and policy focus. This perspective, used as a framework for questioning and thinking about the complex interplay of psychological and social phenomena, provides a method for closing the gaps in training future psychologists as it allows for the development of niche expertise under an umbrella of the broader, ecological perspective. In an increasingly complex world of shrinking mental health dollars and growing severity of mental health problems for families and youth, clinical psychologists are needed more than ever to solve social problems. The current training paradigms in clinical child psychology programs need redirection and clarification for future psychologists to contribute meaningfully to science, practice, and policy. This article provides background in the history and influence of the developmental psychopathology perspective, as well as future implications for doctoral training programs in clinical psychology.
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Discapacidades del Desarrollo/terapia , Psicología Infantil/educación , Psicología Clínica/educación , Adolescente , Adulto , Niño , Preescolar , Curriculum/tendencias , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/psicología , Terapia Familiar/educación , Predicción , Humanos , Lactante , Psicopatología , Problemas Sociales/tendenciasRESUMEN
During pregnancy in the rat, there is a change in the ability of chlorophenylthio (CPT)-cAMP to inhibit myometrial phosphatidylinositide turnover. This is accompanied by a change in the association of proteins with a plasma membrane A kinase anchoring protein (AKAP). Both CPT-cAMP and isoproterenol inhibited oxytocin-stimulated phosphatidylinositide turnover on days 12 through 20 of gestation, whereas neither agent had an effect on day 21. Accompanying this change was a dramatic decrease in the concentration and activity of cAMP-dependent protein kinase [protein kinase A (PKA)] and an increase in the concentration of protein phosphatase 2B (PP2B) in plasma membranes from day 21 compared with day 19 pregnant rats. In contrast, both PKA and PP2B concentrations and activities increased in total myometrial homogenates. Both PKA and PP2B coimmunoprecipitated with an antibody against the 150-kDa AKAP found in rat myometrial plasma membranes. More PKA was associated with AKAP150 on day 19 than on day 21, while the reverse was true for PP2B. Disruption of PKA/AKAP association in day 19 pregnant rat myometrial cells with the specific interaction inhibitor peptide S-Ht31 resulted in the loss of the cAMP-inhibitory effect on phosphatidylinositide turnover. PP2B activity in myometrial homogenates dephosphorylated PLCbeta3, a PKA substrate targeted in the inhibition of Galphaq-stimulated phosphatidylinositide turnover. The dramatic loss of the cAMP-inhibitory effect on day 21 of pregnancy may alter the balance between uterine contraction and relaxation near parturition. The changes in the relative concentrations of PKA and PP2B associated with AKAP150 are consistent with a functional role for AKAP150 scaffolding in the alteration of cellular signaling.
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Proteínas Portadoras/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/farmacología , Miometrio/metabolismo , Preñez/metabolismo , Animales , Calcineurina/metabolismo , Membrana Celular/metabolismo , Femenino , Edad Gestacional , Miometrio/efectos de los fármacos , Fosfatidilinositoles/metabolismo , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
The importance of the localization of protein kinase A (PKA) to the plasma membrane for cAMP-mediated inhibition of phosphatidylinositide turnover was tested in an immortalized pregnant human myometrial (PHM1-41) cell line, and the putative A kinase anchoring protein (AKAP) involved was identified. Preincubation in PHM1-41 cells with chlorophenylthio-cAMP (CPT-cAMP), forskolin, or relaxin inhibited the ability of oxytocin to stimulate phosphatidylinositide turnover. The addition of a peptide that specifically disrupts interactions of PKA RII subunits with AKAPs (S-Ht31) reversed the effects of these agents, whereas a control peptide was ineffective. The pharmacology of S-Ht31 on this particular membrane event was further characterized. A 10-min incubation with S-Ht31 at a concentration of 1 microM completely reversed the inhibitory effect of relaxin on phosphatidylinositide turnover. S-Ht31 inhibited cAMP-stimulated PKA activity in PHM1-41 cell plasma membranes and decreased the concentration of PKA. Overlay analysis detected a single AKAP of approximately 86 kDa associated with the plasma membrane of PHM1-41 cells, suggesting that the association of PKA with this AKAP is important for the cAMP inhibitory mechanism. The mol wt of this AKAP was similar to that of an AKAP associated with the plasma membrane in the human brain, AKAP79. Antibodies against AKAP79 recognized a band at 86 kDa in purified plasma membranes from the PHM1-41 cells, indicating similar determinants in these proteins. These data suggest that PKA is anchored to the myometrial plasma membrane through association with an AKAP similar to AKAP79, and that this anchoring is required for the cAMP-mediated inhibition of phosphatidylinositide turnover in PHM1-41 cells.
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Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras/metabolismo , Membrana Celular/enzimología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/farmacología , Miometrio/enzimología , Fosfatidilinositoles/metabolismo , Proteínas de Anclaje a la Quinasa A , Animales , Western Blotting , Línea Celular Transformada , AMP Cíclico/análogos & derivados , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular , Peso Molecular , Oxitocina/farmacología , Péptidos/farmacología , Embarazo , Ratas , Tionucleótidos/farmacologíaRESUMEN
In an 8-year prospective study of 173 girls and their families, the authors tested predictions from J. Belsky, L. Steinberg, and P. Draper's (1991) evolutionary model of individual differences in pubertal timing. This model suggests that more negative-coercive (or less positive-harmonious) family relationships in early childhood provoke earlier reproductive development in adolescence. Consistent with the model, fathers' presence in the home, more time spent by fathers in child care, greater supportiveness in the parental dyad, more father-daughter affection, and more mother-daughter affection, as assessed prior to kindergarten, each predicted later pubertal timing by daughters in 7th grade. The positive dimension of family relationships, rather than the negative dimension, accounted for these relations. In total, the quality of fathers' investment in the family emerged as the most important feature of the proximal family environment relative to daughters' pubertal timing.
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Relaciones Familiares , Familia/psicología , Pubertad/fisiología , Adolescente , Factores de Edad , Niño , Femenino , Humanos , Estudios Longitudinales , Relaciones Padres-Hijo , Estudios Prospectivos , Factores de TiempoRESUMEN
Observations of aggressive interactions in boys' laboratory play groups were used to evaluate the relative importance of relational and individual factors in accounting for aggressive acts. A classroom peer-rating method for identifying mutually aggressive dyads was validated in 11 5-session play groups, composed of 2 mutually aggressive boys and 4 randomly selected male classmates from 11 predominately African American 3rd-grade classrooms. When the social relations model was used, relationship effects accounted for equally as much of the variance in total aggression and proactive aggression as either actor or target effects. Mutually aggressive dyads displayed twice as much total aggression as randomly selected dyads. Members of mutually aggressive dyads attributed greater hostile intentions toward each other than did randomly selected dyads, which may serve to explain their greater aggression toward each other. The importance of studying relational factors, including social histories and social-cognitive processes, is discussed.