Hyperactivity and impaired response habituation in hyperdopaminergic mice

Abnormal dopaminergic transmission is implicated in schizophrenia, attention deficit hyperactivity disorder, and drug addiction. In an attempt to model aspects of these disorders, we have generated hyperdopaminergic mutant mice by reducing expression of the dopamine transporter (DAT) to 10% of wild-type levels (DAT knockdown). Fast-scan cyclic voltammetry and in vivo microdialysis revealed that released dopamine was cleared at a slow rate in knockdown mice, which resulted in a higher extracellular dopamine concentration. Unlike the DAT knockout mice, the DAT knockdown mice do not display a growth retardation phenotype. They have normal home cage activity but display hyperactivity and impaired response habituation in novel environments. In addition, we show that both the indirect dopamine receptor agonist amphetamine and the direct agonists apomorphine and quinpirole inhibit locomotor activity in the DAT knockdown mice, leading to the hypothesis that a shift in the balance between dopamine auto and heteroreceptor function may contribute to the therapeutic effect of psychostimulants in attention deficit hyperactivity disorder.

Circulation of core collection monographs in an academic medical library

Academic medical librarians responsible for monograph acquisition face a challenging task. From the plethora of medical monographs published each year, academic medical librarians must select those most useful to their patrons. Unfortunately, none of the selection tools available to medical librarians are specifically intended to assist academic librarians with medical monograph selection. The few short core collection lists that are available are intended for use in the small hospital or internal medicine department library. As these are the only selection tools available, however, many academic medical librarians spend considerable time reviewing these collection lists and place heavy emphasis on the acquisition of listed books. The study reported here was initiated to determine whether the circulation of listed books in an academic library justified the emphasis placed on the acquisition of these books. Circulation statistics for “listed” and “nonlisted” books in the hematology (WH) section of Indiana University School of Medicine's Ruth Lilly Medical Library were studied. The average circulation figures for listed books were nearly two times as high as the corresponding figures for the WH books in general. These data support the policies of those academic medical libraries that place a high priority on collection of listed books.

The challenge of contracting for technological information

Contracting to provide technological information (TI) is a significant challenge. TI is an unusual commodity in five ways. (i) TI is difficult to count and value; conventional indicators, such as patents and citations, hardly indicate value. TI is often sold at different prices to different parties. (ii) To value TI, it may be necessary to “give away the secret.” This danger, despite nondisclosure agreements, inhibits efforts to market TI. (iii) To prove its value, TI is often bundled into complete products, such as a computer chip or pharmaceutical product. Efficient exchange, by contrast, would involve merely the raw information. (iv) Sellers’ superior knowledge about TI’s value make buyers wary of overpaying. (v) Inefficient contracts are often designed to secure rents from TI. For example, licensing agreements charge more than marginal cost. These contracting difficulties affect the way TI is produced, encouraging self-reliance. This should be an advantage to large firms. However, small research and development firms spend more per employee than large firms, and nonprofit universities are major producers. Networks of organizational relationships, particularly between universities and industry, are critical in transmitting TI. Implicit barter—money for guidance—is common. Property rights for TI are hard to establish. Patents, quite suitable for better mousetraps, are inadequate for an era when we design better mice. Much TI is not patented, and what is patented sets fuzzy demarcations. New organizational forms are a promising approach to contracting difficulties for TI. Webs of relationships, formal and informal, involving universities, start-up firms, corporate giants, and venture capitalists play a major role in facilitating the production and spread of TI.

A synthetic random basic copolymer with promiscuous binding to class II major histocompatibility complex molecules inhibits T-cell proliferative responses to major and minor histocompatibility antigens in vitro and confers the capacity to prevent murine graft-versus-host disease in vivo.

Graft-versus-host disease (GVHD) is a T-cell-mediated disease of transplanted donor T cells recognizing host alloantigens. Data presented in this report show, to our knowledge, for the first time that a synthetic copolymer of the amino acids L-Glu, L-Lys, L-Ala, and L-Tyr (molecular ratio, 1.9:6.0:4.7:1.0; Mr, 6000-8500) [corrected], termed GLAT, with promiscuous binding to multiple major histocompatibility complex class II alleles is capable of preventing lethal GVHD in the B10.D2 --> BALB/c model (both H-2d) across minor histocompatibility barriers. Administration of GLAT over a limited time after transplant significantly reduced the incidence, onset, and severity of disease. GLAT also improved long-term survival from lethal GVHD: 14/25 (56%) of experimental mice survived > 140 days after transplant compared to 2/26 of saline-treated or to 1/10 of hen egg lysozyme-treated control mice (P < 0.01). Long-term survivors were documented to be fully chimeric by PCR analysis of a polymorphic microsatellite region in the interleukin 1beta gene. In vitro, GLAT inhibited the mixed lymphocyte culture in a dose-dependent fashion across a variety of major barriers tested. Furthermore, GLAT inhibited the response of nylon wool-enriched T cells to syngeneic antigen-presenting cells presenting minor histocompatibility antigens. Prepulsing of the antigen-presenting cells with GLAT reduced the proliferative response, suggesting that GLAT inhibits antigen presentation.

Conformations and folding of lysozyme ions in vacuo.

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.

Evidence for incorporation of intact dietary pyrimidine (but not purine) nucleosides into hepatic RNA.

The absorption and metabolism of dietary nucleic acids have received less attention than those of other organic nutrients, largely because of methodological difficulties. We supplemented the rations of poultry and mice with the edible alga Spirulina platensis, which had been uniformly labeled with 13C by hydroponic culture in 13CO2. The rations were ingested by a hen for 4 wk and by four mice for 6 days; two mice were fed a normal diet and two were fed a nucleic acid-deficient diet. The animals were killed and nucleosides were isolated from hepatic RNA. The isotopic enrichment of all mass isotopomers of the nucleosides was analyzed by selected ion monitoring of the negative chemical ionization mass spectrum and the labeling pattern was deconvoluted by reference to the enrichment pattern of the tracer material. We found a distinct difference in the 13C enrichment pattern between pyrimidine and purine nucleosides; the isotopic enrichment of uniformly labeled [M + 9] isotopomers of pyrimidines exceeded that of purines [M + 10] by > 2 orders of magnitude in the avian nucleic acids and by 7- and 14-fold in the murine nucleic acids. The purines were more enriched in lower mass isotopomers, those less than [M + 3], than the pyrimidines. Our results suggest that large quantities of dietary pyrimidine nucleosides and almost no dietary purine nucleosides are incorporated into hepatic nucleic acids without hydrolytic removal of the ribose moiety. In addition, our results support a potential nutritional role for nucleosides and suggest that pyrimidines are conditionally essential organic nutrients.

Kinetic traps in lysozyme folding.

Folding of lysozyme from hen egg white was investigated by using interrupted refolding experiments. This method makes use of a high energy barrier between the native state and transient folding intermediates, and, in contrast to conventional optical techniques, it enables one to specifically monitor the amount of native molecules during protein folding. The results show that under strongly native conditions lysozyme can refold on parallel pathways. The major part of the lysozyme molecules (86%) refold on a slow kinetic pathway with well-populated partially folded states. Additionally, 14% of the molecules fold faster. The rate constant of formation of native molecules on the fast pathway corresponds well to the rate constant expected for folding to occur by a two-state process without any detectable intermediates. The results suggest that formation of the native state for the major fraction of lysozyme molecules is retarded compared with the direct folding process. Partially structured intermediates that transiently populate seem to be kinetically trapped in a conformation that can only slowly reach the native structure.

Expression of endogenous peptide-major histocompatibility complex class II complexes derived from invariant chain-antigen fusion proteins.

CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently presented as peptide-MHC class II complexes when they are expressed as fusion proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusion proteins were associated intracellularly with MHC molecules. Most efficient expression of endogenous peptide-MHC complex was obtained with fusion proteins that contained the endosomal targeting signal within the N-terminal cytoplasmic Ii residues but did not require the luminal residues of Ii that are known to bind MHC molecules. These results suggest that signals within the Ii can allow endogenously synthesized proteins to efficiently enter the MHC class II presentation pathway. They also suggest a strategy for identifying unknown antigens presented by MHC class II molecules.

O português de herança em território fronteiriço: a LH em Olivença como arma para preservação de um grupo minoritário

Esta pesquisa tem como objetivo investigar a língua portuguesa nativa e de herança sobreviventes em território fronteiriço de língua oficial espanhola. Como locus de pesquisa selecionamos Olivença, uma cidade da Espanha em que a língua portuguesa se faz em situações específicas de uso. A relevância desta pesquisa traduz-se no fato de que espaços fronteiriços mantêm sobrepostas em espaços geográficos contíguos algumas realidades que se sobrepõem: a realidade da oficialidade linguística e a realidade do sentimento de pertença sociolinguística. Nesta tese, partimos da identificação, em trabalho de campo, da presença da língua portuguesa no território atualmente espanhol (mas historicamente português) e na constatação de que há uma flutuação de identificação-identidade linguística. No espaço geográfico em que fizemos incursão científica, duas cidades sobrepõem-se historicamente e duas geografias políticas, por outro lado, avizinham-se e roçam-se continuamente. Ao tomar contato com essa cidade, hipotetizamos que o sentimento de pertença linguística estaria presente entre os falantes mais velhos, que manteriam a herança de traços lusitanos em sua comunicação, mesmo ao falar o espanhol. A justificativa é que, logo de chegada, já avistáramos recintos comerciais com nomes portugueses e, contrariamente, não ouvíamos o som lusitano nas ruas. Sabemos que o domínio espanhol numa cidade outrora portuguesa tenderia a apagar vestígios portugueses. No entanto, em grupos íntimos pressupúnhamos o português como língua corrente. Durante o trabalho de campo, identificamos fortes valores culturais sendo empunhados como armas de resistência entre descendentes de portugueses, fazendo correr numa velocidade acentuada a reorganização dos valores lusitanos em redutos da cidade espanhola. Essa força e essa velocidade pareciam ser as molas propulsoras de uma mudança linguística muito sorrateira, que impactava o sentimento de unidade de um segmento social da comunidade sociolinguística. Isso nos inspirou a dar um passo investigativo seguinte em direção aos mais jovens, que tinham o espanhol como língua materna, mas tinham o português como língua de herança. À pergunta central sobre a força do português como língua de herança buscamos respostas por meio de duas outras questões mais indiretas feitas aos sujeitos entrevistados: será que os mais jovens percebiam-se como portugueses? será que os elementos culturais lusitanos presentes nas ruas eram reconhecidos como vinculados à língua de herança? Foi assim que passamos a recolher pistas sobre os traços de resiliência do português como língua incrustada na região espanhola de Olivença.

Análise de incertezas do modelo de teores associado aos investimentos de pesquisa de longo prazo

Os empreendimentos de mineração comumente demandam grande quantidade de investimentos financeiros e, na maioria das vezes, longos períodos de implantação, o que os torna altamente sujeitos a diversas fontes de incertezas. Tais incertezas comumente tendem a diminuir conforme a evolução do projeto. O objetivo deste estudo é correlacionar as incertezas associadas ao modelo de teores de cobre do depósito Sequeirinho com o volume de investimentos realizados ao longo de distintas fases da pesquisa geológica. Este depósito insere-se no contexto do Complexo de Mineração Sossego, localizado no município de Canaã dos Carajás (PA). Primeiramente, foram realizadas 100 simulações para cada domínio litológico em cada campanha de sondagem (pré-1998, 1999, 2000, 2002 e 2003) a partir do método de simulação sequencial gaussiana condicionada aos dados amostrais, totalizando 1.400 possíveis cenários. Para a avaliação das incertezas foram calculados três índices: variância condicional, coeficiente de variação condicional e intervalo interquartil. Por fim, a avaliação dos investimentos foi elaborada a partir dos custos estimados para o desenvolvimento de sondagens e análises químicas. Desde a campanha pré-1998, houve uma tendência de os teores médios do depósito aproximarem-se dos prováveis valores reais observados nas fases finais da pesquisa. No ano de 2000 ocorreu o maior investimento (cerca de 28 milhões de Reais) e a redução das incertezas atingiu o patamar de 15%. Os investimentos desenvolvidos em sondagens posteriores à campanha de 2000 foram da ordem de 9 milhões de Reais (cerca de 12 mil metros de sondagem), porém, não foram constatadas reduções significativas das incertezas. Este investimento seria melhor aproveitado caso fosse redirecionado a novas áreas de prospecção. Além do montante financeiro necessário para a redução das incertezas, foco deste estudo, as variações na interpretação geológica e a locação dos furos de sondagem são variáveis importantes na análise de incertezas associadas aos investimentos em pesquisa geológica.

Madurez sintáctica: influencia de las TIC en sus índices y estudio comparativo entre las generaciones pre y post-internet

There is a growing concern about the poor quality of the writing of children and teenagers because of the continuous and constant exposure to the new technologies. Increasingly parents complain that their children spend too much time with their phones, tablets, computers, video games, etc. There is also an increase in the number of teachers who complain about their students’ writing skills. Some of the most prominent criticisms are loss of vocabulary, simplified syntax and the poor spelling of the compositions. To verify if these criticisms are motivated or not by the use of information and communication technologies (ICT) is what moved us to initiate this doctoral dissertation entitled “The influence of ICT on ratings of syntactic maturity: a comparative study between pre- and post-internet generations”. We aim to know if a daily and constant exposure to the ICT can affect the syntactic maturity rates of children and teenagers. We also want to find out if there are differences between the levels of syntactic maturity of today’s students and those of the 1990s, when there were no ICT and internet. In order to do this, we have carried out a quantitative analysis taking as a reference previous studies by generativist researchers in the Anglo-Saxon and Hispanic world and we have used the same units of measure (T-unit and clause). We collected a corpus of 382 essays, half argumentative and half descriptive, from 191 individuals. We have analyzed them according to ten dependent variables or syntactic maturity rates and other independent variables (Hours in internet, Course, Sex, Location, Type of school) by applying techniques of descriptive and inferential statistics...

The Effects of Father Absence Due to Divorce: A Systems Interpretation.

In American society, the incidence of divorce continues to rise. In 1974, the estimate was that 40% of all new marriages would end in divorce. When children are involved, the mother usually regains custody. Although the number of children of divorce living with their fathers is increasing, it is still a small percent. In addition, the rate of remarriages is lower when children are involved (Hetherington.et al.,1977). Consequently, a large number of children are being raised in father-absent homes, and indications are that the numbers are increasing. A recent Denver Post article predicted that 50% of all children now being born will spend some of their childhood in a single-parent home. In terms of frequency, the father-absent family is becoming quite common, even "normal," yet it often continues to be considered a "broken" home and, when compared to the two-parent family, an inadequate structure in which to raise healthy children. Since father-absent families are so common these days, this opinion is in need of review.This paper will present a review of the father absence research in three areas: sex role development, cognitive development and personality development. The role of moderator variables will be discussed. And, finally,an open systems model will be proposed as a vehicle to better understand the effects of father absence and as a guide for future research.

Atribuição de causalidade ao desempenho acadêmico e autoestima de estudantes de Ciências Contábeis

A percepção sobre as causas dos acontecimentos faz parte da vida cotidiana. Atribui-se causas aos eventos na busca de entendimento que permita prever, controlar e alterar resultados futuros. Questões como \"Por que não passei na prova?\" e \"Porque fui o primeiro colocado no vestibular?\" conduzem à percepção de uma causa explicativa, seja para o fracasso ou para o sucesso. A Teoria da Atribuição Causal tem sido examinada para compreender e explicar como as pessoas interpretam os determinantes de seu sucesso ou fracasso em situações de desempenho. As causas percebidas estarão relacionadas à percepção de cada indivíduo sobre o evento, o que não implica causalidade real, dado que a ação será efetivada de acordo com a percepção de cada indivíduo sobre o evento. A abordagem teórica utilizada nessa pesquisa foi a Teoria da Atribuição Causal, proposta por Bernard Weiner, no contexto educacional, com foco nas atribuições causais para sucesso e fracasso acadêmicos. Neste cenário, o objetivo principal da pesquisa foi identificar as causas percebidas como explicativas do desempenho acadêmico de estudantes do curso de Ciências Contábeis. Buscou-se também obter evidências e subsidiar a discussão sobre a relação entre o sucesso e o fracasso acadêmico, a modalidade de ensino, a autoestima e o perfil do estudante. Os dados foram coletados por meio de um questionário aplicado aos estudantes de Ciências Contábeis de duas Universidades Federais que oferecem o curso em duas modalidades de ensino (presencial e a distância) e 738 respostas válidas foram obtidas para análise. O questionário foi estruturado em três blocos (I - desempenho e causas percebidas, II - mensuração da autoestima e III - perfil do estudante). Os resultados apresentaram um perfil com idade média dos estudantes de 27,4 anos (34,27 na modalidade EaD e 24,87 na modalidade Presencial). A maioria dos estudantes (83%) exercia atividade remunerada (90% na EaD e 80% na presencial) e as mulheres representaram a maioria dos respondentes (62% na modalidade EaD e 58% na modalidade presencial). As causas internas, especificamente o esforço e a capacidade, foram mais indicadas como explicativas do sucesso acadêmico e as causas externas, especificamente a dificuldade da tarefa, a flexibilidade de horário e a influência negativa do professor, foram as mais indicadas como explicativas do fracasso acadêmico. Como os resultados apontam que os estudantes indicaram com frequência a própria capacidade para explicar o sucesso, pode-se admitir manifestação da tendência autoservidora, que contribui para a manutenção da autoestima, diante da influência positiva na motivação. Entre as causas do sucesso, a capacidade associou-se a um nível mais elevado de autoestima e a causa sorte associou-se a um nível mais baixo de autoestima. Entre as causas do fracasso, a dificuldade da tarefa associou-se ao nível mais baixo de autoestima. Uma análise geral permite observar que os estudantes dedicam pouco tempo aos estudos, atribuem sucesso principalmente a si mesmos e o fracasso a terceiros, e apresentam uma elevada autoestima associada principalmente ao sucesso atribuído à capacidade. Em futuras pesquisas, recomenda-se estudos pilotos, com objetivo de definir outras atribuições causais para elaboração de novos instrumentos de coleta de dados, por meio de abordagem metodológica qualitativa, que possam ampliar os achados e contribuir com a literatura.

Relación entre el número de horas de cuidado informal y el estado de salud mental de las personas cuidadoras

Fundamento: La salud mental de las personas cuidadoras se ve perjudicada por las tareas de cuidado. Son necesarios estudios que especifiquen la influencia de diversas variables en la asociación entre cuidado informal y salud mental. El objetivo del trabajo es analizar los efectos del tiempo dedicado al cuidado informal en la salud mental por sexo según el tipo de personas dependientes. Métodos: Los datos que se utilizaron fueron los de la Encuesta Nacional de Salud 2006, cuya muestra estaba compuesta por 29.478 participantes. Variables: salud mental (GHQ-12), tiempo de cuidado, edad, clase social y apoyo funcional (Duke-UNC). Se realizó análisis de regresión logística para determinar la probabilidad de contar con mala salud mental según horas de cuidado, ajustado por edad, clase social y apoyo funcional. Resultados: Las mujeres presentan peor salud mental a partir de 97 horas semanales en el cuidado a menores (OR=1,372), de 25 horas en el cuidado a personas mayores de 74 años (OR=1,602 entre 25 y 48 horas; OR=1,467 49-96h; OR=1,874 97-168h) y cuando dedican alguna hora al cuidado de personas adultas con discapacidad (OR=1,996 0-24h; OR=2,507 25-48h; OR=3,016 49-96h; OR=1,651 97-168h). Los varones muestran deterioro de la salud psicológica cuando dedican un elevado número de horas al cuidado de personas mayores de 74 años (OR=2,810 97168h.) y personas con discapacidad (OR=3,411 97-168h.) y cuando dedican de 0 a 24h al cuidado de menores (OR=1,595). Conclusiones: El efecto del número de horas de cuidado en la salud mental de las personas cuidadoras está influido por el tipo de persona dependiente y por el sexo de la persona cuidadora.

Simultaneous synthesis of heat exchanger networks with pressure recovery: optimal integration between heat and work

The optimal integration between heat and work may significantly reduce the energy demand and consequently the process cost. This paper introduces a new mathematical model for the simultaneous synthesis of heat exchanger networks (HENs) in which the pressure levels of the process streams can be adjusted to enhance the heat integration. A superstructure is proposed for the HEN design with pressure recovery, developed via generalized disjunctive programming (GDP) and mixed-integer nonlinear programming (MINLP) formulation. The process conditions (stream temperature and pressure) must be optimized. Furthermore, the approach allows for coupling of the turbines and compressors and selection of the turbines and valves to minimize the total annualized cost, which consists of the operational and capital expenses. The model is tested for its applicability in three case studies, including a cryogenic application. The results indicate that the energy integration reduces the quantity of utilities required, thus decreasing the overall cost.