Real life decision-making frequently involves some level of affect, and research has demonstrated that individuals decide differently when outcomes are more or less rich with feeling. This difference in choice has previously been attributed to probability insensitivity in the presence of affect. In a series of three studies, we explored this possibility, while also testing alternative explanations, namely, that differences exist because of outcome characteristics such as comparability or precision. Individuals made choices between affect-rich side effects and affect-poor monetary lotteries in either a strictly numeric format, or with the addition of an icon array. Across the three studies we found little evidence that the icon array was beneficial, casting doubt on the previous explanation that differences in affect-rich and affect-poor choice are due to probability insensitivity. Contrary to our predictions, we did not find evidence that differences in choice could be attributed to outcome comparability, as there continued to be decrements in affect-rich choice, despite making affect-rich outcomes more comparable. As predicted, when precision in each affective context was better equated by describing monetary outcomes in less precise terms, the difference in affect-rich and affect-poor choice disappeared. It appears that it is difficult to choose well when outcomes are vague, which we suggest is potentially the result of a challenge integrating probability and outcome information. This research is a first step in providing a viable explanation for the “affect gap” and contributes to our understanding of how and why affect-rich and affect-poor choice may differ.

Orientador: Maricilda Palandi de Mello / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T17:10:17Z (GMT). No. of bitstreams: 1 Petroli_ReginaldoJose_M.pdf: 2303670 bytes, checksum: 1836c8a6df94a76ee177d830781dc293 (MD5) Previous issue date: 2010 / Resumo: Considera-se que insensibilidade androgênica seja a causa mais freqüente dos distúrbios da diferenciação do sexo em pacientes com cariótipo 46,XY. Trata-se de uma anomalia recessiva ligada ao cromossomo X, que pode se manifestar de forma branda, parcial ou completa, com um amplo espectro de variação fenotípica. O gene do receptor de andrógenos (AR) está localizado no cromossomo X, na região Xq11-12, sendo organizado em oito exons separados por introns de até 26 kb. Sua região codificante apresenta aproximadamente 2.757 pares de bases traduzindo uma proteína de 919 aminoácidos, cujo peso molecular é de aproximadamente 110 kDa. A proteína AR apresenta três domínios funcionais: domínio de regulação transcricional (amino-terminal), domínio de ligação ao DNA que contém dois dedos de zinco (zinc finger) e domínio de ligação ao esteróide (carboxi-terminal). O domínio amino-terminal possui repetições dos aminoácidos glutamina e glicina cujos números podem variar dentro da população normal. O domínio de ligação ao esteróide (carboxi-terminal), apresenta o maior número de mutações, cerca de 55% das descritas neste gene. Entre o domínio de ligação ao DNA e o domínio de ligação ao esteróide encontra-se a região hinge que contém um sinal responsável pela localização nuclear necessária para a translocação do complexo andrógeno/receptor do citoplasma para o núcleo da célula. Pacientes com cariótipo 46,XY e diagnóstico de insensibilidade androgênica geralmente apresentam fenótipo feminino ou ambigüidade genital, porém a produção de testosterona é normal. Nestes pacientes a investigação de mutações no gene do receptor de andrógeno é indicada para a identificação da alteração molecular relacionada à doença. Desta maneira, o presente estudo teve como objetivo a caracterização das alterações moleculares do gene AR, através da análise de seus oito exons e junções exons-introns por reação da cadeia da polimerase (PCR) seguida de sequenciamento dos fragmentos amplificados. Das 47 famílias que compõem a casuística deste trabalho, 14 apresentaram mutações no gene, sendo uma relacionada ao fenótipo brando da insensibilidade androgênica (p.P694S), sete relacionadas ao fenótipo parcial da insensibilidade androgênica (p.Q58L, p.A596T, p.S597R, p.M742V, p.Q798E, p.L830F e p.A896V) e seis relacionadas ao fenótipo completo da insensibilidade androgênica (p.R774H, p.P766S, p.C806F, p.R832Term, p.R855H e p.V866M). Uma paciente apresentou duas alterações, ambas no exon 6 deste gene. Quatro mutações estão sendo descritas pela primeira vez neste trabalho em pacientes com insensibilidade androgênica / Abstract: The androgen insensitivity syndrome (AIS) is considered the most frequent disorders of sex differentiation in patients with 46,XY karyotype. It is a recessive X linked disorder, which manifests as mild, partial or complete forms, with a broad spectrum of phenotypic variation. The androgen receptor gene (AR) is located on the X chromosome within Xq11-12 region. It is organized in eight exons separated by introns up to 26 kb in length. Its coding region comprises approximately 2,757 base pairs translating a protein of 919 amino acids, whose molecular weight is approximately 110 kDa. The AR protein has three functional domains: the transcriptional regulatory domain, the DNA binding domain which contains two zinc fingers and the steroid binding domain in the carboxy-terminal region. The amino-terminal domain presents repeats of glutamine and glycine whose numbers of residues vary within the normal population. The steroid-binding domain presents the highest number of mutations, around 55% of the mutations described in this gene are located in this region. Between the DNA-binding domain and the steroid-binding domain there is a hinge region that contains a signal responsible for nuclear localization required for translocation of the complex androgen/receptor from the cytoplasm to the cell nucleus. Patients with 46,XY karyotype and androgen insensitivity diagnosis usually have female or ambiguous genitalia, but normal testosterone production. In these patients the investigation of androgen receptor gene mutations is indicated to identify the molecular changes related with AIS. Therefore, the aim of this study was to characterize molecular alterations in the AR gene, by analysis of the eight exons and introns-exons junctions by polymerase chain reaction (PCR) followed by sequencing the amplified fragments. Fourteen out of 46 families comprised in this study had mutations identified. One mutation corresponded to the mild phenotype of androgen insensitivity (p.P694S), seven were related to the partial androgen insensitivity phenotype (p.Q58L, p.A596T, P. S597R, p.M742V, p.Q798E, p.L830F and p.A896V), and six were associated to the complete androgen insensitivity phenotype (p.R774H, p.P766S, p.C806F, p.R832Term, p.R855H and p.V866M). One patient presented two mutations, both located in exon 6 of the gene. Four mutations were described for the first time in this research in patients with androgen insensitivity / Mestrado / Genetica Animal e Evolução / Mestre em Genética e Biologia Molecular

Orientadores: Maricilda Palandi de Mello, Fernanda Caroline Soardi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T03:55:23Z (GMT). No. of bitstreams: 1 Petroli_ReginaldoJose_D.pdf: 6228632 bytes, checksum: e6e99d402e3d99ccab57c84290065e84 (MD5) Previous issue date: 2014 / Resumo: O receptor de andrógenos (AR) é um fator de transcrição pertencente à superfamília de receptores nucleares e é ativado por fosforilação e dimerização sob a ligação ao hormônio. Várias funções são atribuídas a este receptor, sendo a principal delas o desenvolvimento e manutenção das características sexuais masculinas, atua na regulação da expressão gênica e diferenciação celular em tecidos alvos. O presente trabalho teve por objetivo principal a análise do efeito das mutações p.Pro695Ser, p.Ser759Tre, p.Leu768Val., p.Cis806Fen+p.Gln798Glu, p.Leu830Fen, p.Ile898Fen e p.Pro904Arg sobre a função do AR. As mutações acima citadas, localizadas no domínio de ligação ao hormônio, foram identificadas por sequenciamento direto do gene do AR de pacientes 46,XY com diferentes graus da Síndrome da Insensibilidade Androgênica (AIS). Mutações nesse domínio geralmente rompem a ligação aos andrógenos naturais, porém há algumas que não afetam essa ligação, mas interferem na interação entre os domínios amino e carboxi-terminal (N/C terminal), importante para a estabilização receptor-ligante. Assim, ambas funções foram investigadas. Para se avaliar a capacidade de transativação das proteínas AR mutantes, foi realizada a técnica de mutagênese sítio dirigida no cDNA completo, seguida de transfecção e expressão em células e mamíferos e, análise de transativação induzida por concentrações crescentes de 5?-diidrotestosterona (DHT) utilizando-se um gene repórter. A análise das interações N/C-terminal para cada AR mutante foi realizada pela técnica de duplo-híbrido em células de mamíferos. A mutação p.Pro695Ser apresentou atividades de transativação de 85% e 82% nos ensaios transativação com o cDNA completo e no duplo-híbrido, respectivamente, em valores de DHT fisiológicos (cerca de 1 nM). As atividades atingiram valores normais em concentrações elevadas de DHT indicando um baixo efeito sobre a atividade gonadal. No entanto, em concentrações de DHT inferiores a atividade de transativação decai para menos de 50% nos dois experimentos, podendo afetar as funções do AR em tecidos não gonadais. Esta mutação foi considerada "branda" e corresponde perfeitamente ao fenótipo masculino do paciente que se apresentava com ginecomastia, mas com fertilidade preservada. Com 1 nM de hormônio, as mutações p.Ser759Tre, p.Leu830Fen, p.Ile898Fen apresentaram atividade de transativação superior a 20%, havendo um aumento de resposta com concentrações crescentes. No entanto, o comportamento de cada uma no experimento de interação N/C diferiu sendo que a p.Ile898Fen não apresentou atividade em nenhuma concentração de ligante; as p.Ser759Tre e p.Leu830Fen responderam positivamente ao aumento da concentração de DHT atingindo 50% e 250% da atividade trancricional do receptor selvagem, respectivamente. Esses resultados indicam um fenótipo parcial de AIS (PAIS) para os portadores das mutações p.Ser759Tre e p.Leu830Fen. Nesses casos verificou-se uma boa correlação dos achados funcionais com os fenótipos dos pacientes que apresentavam graus variados de PAIS. Já para a mutação p.Ile898Fen o fenótipo esperado baseando-se nos resultados funcionais seria o de AIS na forma completa (CAIS), porém os pacientes portadores desta mutação apresentavam graus variados de ambiguidade genital compatíveis com o fenótipo PAIS. Isto indica que outros fatores devem estar influenciando a manifestação fenotípica nesse caso. A mutação p.Leu768Val apresentou atividade transcricional nula em 1 nM de DHT nos dois experimentos, um perfil típico do fenótipo CAIS apresentado pelo portador desta mutação. As mutações p.Gln798Glu e p.Cis806Fen estudadas separadamente apresentaram respostas à indução de DHT semelhantes às de mutações "brandas" e PAIS, respectivamente. No entanto, quando estudadas em conjunto, a atividade de transativação com 1 nM foi inferior a 10%, aumentando com o aumento da concentração de ligante, comportamento compatível com mutações mais graves resultando no fenótipo CAIS observado nesse caso. Por último, a mutação p.Pro904Arg, embora tenha reduzido a atividade trancricional para cerca de 20% da selvagem no experimento com o cDNA completo, no experimento com duplo híbrido a atividade foi nula indicando uma ação mais grave compatível com a forma CAIS observada. A análise funcional do AR aqui realizada pode elucidar alguns mecanismos moleculares associados a cada mutação, bem como pode fornecer subsídios para a resposta ao tratamento com DHT em cada caso em particular / Abstract: The androgen receptor (AR) is a transcription factor that belongs to the superfamily of nuclear receptors activated by phosphorylation and dimerization by hormone binding. Several functions are attributed for AR, like male sex development, regulation of gene expression and cell differentiation in target tissues. The aim of this study was to analyze the effect of mutations p.Pro695Ser, p.Ser759Tre, p.Leu768Val, p.Cys806Phe+ p.Gln798Glu, p.Leu830Phe, p.Ile898Phe and p.Pro904Arg upon AR transactivation activity. All mutations studied here are located in the hormone-binding domain and were identified in patients with different degrees of androgen insensitivity syndrome (AIS) by AR gene sequencing. Mutations in this domain can result in the impairment of androgen ligation, but there are cases that it does not affect the binding but interfere with the interaction between the amino and carboxi-terminal domains (N/C terminal), important step for receptor-binding stabilization. Thus, both functions have been studied in this work. To evaluate the ability of AR transactivation of mutant proteins, the site-directed mutagenesis assay was performed on full-length cDNA, followed by transfection and expression in mammalian cells. The analysis of transactivation of a reporter gene with different dihydrotestosterone (DHT) concentrations was performed. The analysis of N/C-terminal interactions for each mutant AR was performed by two- hybrid mammalian assay. The mutation p.Pro695Ser reveled transactivation activities of 85% and 82% in transactivation assays with the full-length cDNA and two hybrid assay, respectively, at DHT physiological values (approximately 1 nM). The activities reached normal values at high DHT concentrations, indicating a low effect on gonadal activity. However, in low DHT concentrations, the transactivation activity decays to less than 50% in both experiments, which may affect AR functions in non-gonadal tissues. This mutation was considered "mild" and corresponds perfectly to the male phenotype of the patient who presented with gynecomastia, but with preserved fertility. With 1 nM hormone, the p.Ser759Tre, p.Leu830Phe, p.Ile898Phe mutations showed transactivation activity higher than 20%, the response increased with higher DHT concentrations. However, in N/C interaction assays, those mutations showed different results. The p.Ile898Phe revealed a complete disruption in N/C interaction at all hormone concentrations; the p.Ser759Tre and p.Leu830Phe showed positive response with the increasing in DHT concentrations and reached 50% and 250% of the transcriptional activity of wild type, respectively. Such results indicate a partial AIS phenotype (PAIS) as functional effect for p.Ser759Tre and p.Leu830Phe. In these cases there was a positive correlation with the phenotypes of patients that presented different degrees of PAIS. For the p.Ile898Phe, the expected phenotype based on functional analysis would be the complete form of AIS (CAIS), but the patients with this mutation had variable degrees of genital ambiguity consistent to PAIS. This indicates that other factors must influence the phenotypic manifestation. The p.Leu768Val revealed a complete disruption at 1 nM DHT in both experiments, typical of CAIS. The p.Gln798Glu and p.Cys806Phe mutations studied separately revealed responses to the induction of DHT similar to Mild and Partial phenotypes, respectively. However, when analyzed together, the transactivation activity of 1 nM was lower than 10%, increasing in high ligand concentration, which is consistent to CAIS phenotype. Finally, p.Pro904Arg, although showed residual transcriptional activity around 20% of the wild type in the experiment with the full-length cDNA, it abolished the transcriptional activity when N/C terminal interaction was tested indicating a CAIS phenotype, as observed in the patient. Functional analysis of the AR performed here could elucidate some molecular mechanisms associated with each mutation, and may provide a basis for response to treatment with DHT in each particular case / Doutorado / Genetica Animal e Evolução / Doutor em Genetica e Biologia Molecular

Computer designers rely upon near-cycle-accurate microarchitectural simulation to explore the design space of new systems. Unfortunately, such simulators are becoming increasingly slow as systems become more complex. Hybrid simulators which offload some of the simulation work onto FPGAs can increase the speed; however, such simulators must be automatically synthesized or the time to design them becomes prohibitive. Furthermore, FPGA implementations of simulators may require multiple FPGA clock cycles to implement behavior that takes place within one simulated clock cycle, making correct arbitrary composition of simulator components impossible and limiting the amount of hardware concurrency which can be achieved. Latency-Insensitive Bounded Dataflow Networks (LI-BDNs) have been suggested as a means to permit composition of simulator components in FPGAs. However, previous work has required that LI-BDNs be created manually. This paper introduces techniques for automated synthesis of LI-BDNs from the processes of a System-C microarchitectural model. We demonstrate that LI-BDNs can be successfully synthesized. We also introduce a technique for reducing the overhead of LI-BDNs when the latency-insensitive property is unnecessary, resulting in up to a 60% reduction in FPGA resource requirements.

No description available.

Introduction: A subgroup of severe asthmatics (SA) remain uncontrolled with persistent airway eosinophilia despite high dose glucocorticosteroids (GCS) termed “steroid insensitivity.” A significant proportion of this subgroup get recurrent airway infections. Phosphoinositide-3 kinase (PI3K) pathway may contribute to both GCS insensitivity and further susceptibility to recurrent infections. Objectives: The effect of GCS and PI3K antagonism was evaluated on GCS induced eosinophil apoptosis as a mechanism of GCS insensitivity in healthy, mild to moderate and severe asthmatics. Furthermore, we investigated the relationship between PI3K activation, histone deacetylase (HDAC) and macrophage receptor with collagenous structure (MARCO) expression in SA±recurrent bacterial bronchitis. Methods: Blood eosinophils, isolated from healthy subjects (HS) and asthmatics, were incubated with increasing concentrations of dexamethasone (0.1, 1 and 10 uM) and a pan-PI3K antagonist (LY294002 at 1 and 2 uM). Cell viability was assessed using PrestoBlue cell viability assay, Trypan Blue exclusion test and PE-Annexin-V/7-AAD apoptosis detection (flow cytometry). Furthermore, PI3K activity, MARCO and HDAC levels were measured in macrophages isolated from healthy subjects and SA (±history of recurrent bacterial bronchitis). In a subgroup, sputa were examined for in situ PI3K activity and gene expression of PI3K isoforms by digital PCR. Results: In HS, a time-dependent increase in eosinophil apoptotic% was observed (1.9% at baseline, 25.7% at 16h and 31% at 24h) (p=0.06, p=0.005 respectively). Dexamethasone 10uM increased it to 40.1% at 16h (p=0.03). Dexamethasone induced eosinophil apoptosis was less in severe asthmatics (34.2%) vs. to mild-to-moderate asthmatics (46.7%) (p=0.05) suggesting steroid insensitivity. This was not reversed by co-incubation with LY294002 2uM (39.9% vs. 53.3%) (p=0.04) (Fig. 1B). Asthmatics with recurrent lung infections had higher blood PI3K activity (demonstrated as inverse of biotinylated-PIP3, p=0.02), MARCO expression (p=0.01), and trend for lower HDAC expression (p=0.067) vs. healthy donors. PI3KCD (encoding catalytic 𝛿 isoform) gene expression relative to HPRT1 (housekeeping gene) was increased in SA-infection group (p=0.03). A higher number of asthmatics with recurrent lung infections were on oral corticosteroids (p=0.015) and replacement immunoglobulins (p=0.016). Conclusions: Evaluating dexamethasone-induced apoptosis in blood eosinophil can assess GCS sensitivity ex vivo. Severe asthmatics demonstrate GCS insensitivity, which was not reversed by a pan-PI3K antagonist. PI3K activity is increased in SA with a previous history of recurrent lung infections, which is associated with a decrease in HDAC and MARCO expression. Targeting PI3K pathway, specifically the 𝛿 isoform, may be a potential therapeutic target in SA with mixed-granulocytic bronchitis. / Thesis / Master of Science in Medical Sciences (MSMS) / Eosinophils are a type of blood cell that is responsible for causing asthma symptoms and flare-ups. Steroids (in both inhaled and oral forms) decrease eosinophils and so are the main treatment for asthma. But a group of asthmatics continues to have symptoms and eosinophils in their lung secretions even with maximum dose of steroids. Some of these asthmatics also get repeated bacterial lung infections. In blood samples, we studied one of the proteins (phosphoinositide-3 kinase, PI3K), which may be responsible for poor response to steroids and repeated infections. We looked at the effect of steroids on eosinophils extracted from blood samples of healthy people, asthmatics with mild disease and asthmatics with severe disease. We also measured PI3K levels and related proteins in blood and sputum samples from healthy people, asthmatics who get repeated bacterial lung infections (more than two in the previous two years) and asthmatics without recurrent lung infections. We found that eosinophils obtained from asthmatics with severe disease were harder to kill with steroids. But, this was not reversed with a PI3K blocking agent. We also found that asthmatics with a previous history of repeated bacterial lung infections had a higher PI3K level. High PI3K activity was associated with a decrease in two other proteins – histone deacetylase (HDAC) and macrophage receptor with collagenous structure (MARCO). Decrease in HDAC can result in a lower response to steroids, which may result in an increase in eosinophils in the lungs. Lower levels of MARCO can cause a patient to have higher sensitivity to recurrent bacterial infections. Overall, this may lead to a dangerous cycle where repeated lung infection will lead to high PI3K activity, which will cause worse asthma control and more infections. More studies are needed to evaluate drugs that block PI3K, which may be helpful in asthmatics who are less responsive to steroids and also get repeated infections.

In this paper, we present a new compact hydraulic linear actuator. The concept is developed to change the rolling piston diameter of an active air spring during usage. By doing so, the air spring can actively apply pressure and tension forces. The actuator is designed for small movements at high forces. It is insensitive to side forces, which are introduced by the bellows rolling on the rolling piston of the air spring. A diaphragm sealing is used to minimize friction. Hence a precise adjustment of small displacements at high dynamics is possible and the system is completely leakage-free. We describe the design and development of this actuator and show first measurement results from preliminary tests to show its functionality.

A study was conducted to examine if people’s sensitivity to the magnitude to which somebody helps depends on how the help is framed. To test this, participants read vignettes about moral agents whose help had one of three different magnitudes: a base level, a medium level (the base level times 5) and a high level (the base level times 10). The moral agents’ help was also framed in one of three ways. They either helped victims, volunteered a number of hours, or donated an amount to charity. To measure the sensitivity, participants rated how likeable they found the agent. It turned out that if the help was framed as helping victims, the participants were not at all sensitive to the different magnitudes of help. That is, an agent was not liked more if they helped a high or medium number of victims than if they helped a low number; neither were they liked more if they helped a high number than if they helped a medium number. However, in the two other types of framing, participants were more sensitive. When help was framed as volunteering a number of hours, participants liked an agent more if they volunteered a medium or high number of hours than if they only volunteered a low number of hours. But they did not like a participant more if they volunteered a high number of hours than if they volunteered a medium number of hours. The same exact pattern was found when framing help as donating to charity. A possible explanation for the result is given in the discussion.

Made available in DSpace on 2016-07-27T14:20:40Z (GMT). No. of bitstreams: 1 Sandra de Araujo Alvares.pdf: 390271 bytes, checksum: 072ed3480ff08e5c3fd6a96ef43ac8b7 (MD5) Previous issue date: 2006-03-27 / Various aspects are pointed out as possible influences on human sensibility to performance on reinforcement schedules. This study evaluates some of these aspects by submitting participants to a the task of touching a circle that appeared on a computed screen, according to a Fixed Ratio (FR) or a Low-rate Differential Reinforcement (LDR) reinforcement schedule. Each schedule was effective for three minutes and the change between them was neither signaled nor instructed. Correct responses produced points that could be exchanged for money. Experiment 1 verified if the arrangement of aversive consequences (loss of points) to behaviors inconsistent with the schedule would result in an increase in behavioral sensibility to this schedule. Six subjects were submitted to four experimental phases: A (FR 18), B (LDR 6 sec.), C (FR 18) and D (LDR 6 sec. + punishment). The results suggest that aspects pertaining to the strengthening of ongoing contingencies here represented by the insertion of punishment in phase D should be considered relevant in the discussion about behavioral sensibility/insensibility. Experiment 2 verified if the previous exposure to one condition that favors the contact with the ongoing schedule would be sufficient to establish adequate responding in a latter phase with clear signs of discrimination of the ongoing phase. Four participants ere submitted to the following phases: A (RF 18), B (LDR 6 sec.), C (FR 18), D (LDR 6 sec + punishment), E (FR 18) and F (LDR 6 sec.). Results show that the sensitive performances affected during phase D were sustained during phase F, showing that punishment not only generated sensitive performance patterns in relation to the programmed schedules, but also in maintaining such patterns in latter similar situations. / Vários são os aspectos apontados como passíveis de influenciarem a sensibilidade de desempenhos humanos a esquemas de reforçamento. A fim de avaliar alguns desses aspectos, o presente estudo submeteu participantes à tarefa de tocar um círculo central que aparecia na tela do computador de acordo com um esquema de RF (Razão Fixa) ou DRL (Reforçamento Diferencial de Baixas Taxas). Cada esquema vigorava por três minutos; a troca entre eles não era sinalizada e nem instruída. Respostas corretas produziam pontos trocáveis por dinheiro. O Experimento 1 teve por objetivo verificar se o arranjo de conseqüências aversivas (perda de pontos) para comportamentos inconsistentes com o esquema em vigor resultaria em aumento da sensibilidade comportamental a tal esquema. Para tanto, seis participantes foram submetidos a quatro fases experimentais: A (RF 18), B (DRL 6 seg.), C (RF 18) e D (DRL 6 seg. + punição). Os resultados sugeriram que aspectos relacionados a um fortalecimento das contingências em vigor representado no presente experimento pela inserção da punição na fase D devem ser considerados como relevantes em uma discussão sobre sensibilidade/insensibilidade comportamental. O Experimento 2 objetivou verificar se a exposição prévia a uma condição que favorecesse o contato com o esquema em vigor seria suficiente para estabelecer responder adequado em uma fase posterior, com sinais claros de discriminação do esquema em vigor. Quatro participantes foram submetidos às seguintes fases experimentais: A (RF 18), B (DRL 6 seg.), C (RF 18), D (DRL 6 seg. + punição), E (RF 18) e F (DRL 6 seg.). Os resultados evidenciaram que os desempenhos sensíveis atingidos durante a fase D, mantiveram-se durante a fase F, demonstrando os efeitos da punição não só em gerar ou intensificar padrões sensíveis de desempenho aos esquemas programados, como também, em manter tais padrões em situações posteriores e similares.

There are many situations in which human performances appear insensitive to changing contingencies of reinforcement when compared to nonhuman operant performances. Explanations of these discrepancies have appealed to rule-governance and have provided some evidence that instructions produce these differences by restricting response alternatives as well as functioning as discriminative stimuli for other contingencies. In order to further evaluate these potential functions, a canonical study on rule-governance was systematically replicated. Five undergraduate participants were tasked with earning blocks by pressing a button during LED-signaled, fixed-ratio 7 and differential-reinforcement-of-low-rate 5-s schedules of reinforcement. Phase 1 of the experiment switched between these two schedules, with the schedule alternating every 1 minute. Phase 2 added instructions to "Go Fast" and "Go Slow" to the LEDs and programmed the lit LED to switch 30 seconds into each 1-minute session. Phase 3 removed the instructions from the LEDs and returned to the procedures of phase 1, with only one LED lit during each 1-minute session. Results showed that instructions influence the response rates as well as stimulus control over those rates. Results also showed that all participants ignored instructions conflicting with the reinforceable rate by the end of Phase 2. These findings indicate that instances of insensitivity may result from instructions restricting response alternatives and their stimulus control, as opposed to instructions signaling a second contingency. These findings are discussed in terms of the nature of instructional stimulus control, its relation to the operant unit of analysis, and alternative interpretations of other instances of insensitivity.