Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites

Dehydroepiandrosterone ( DHEA) is known as an intermediate in the synthesis of mammalian steroids and a potent uncompetitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH), but not the enzyme from plants and lower eukaryotes. G6PDH catalyzes the first step of the pentose-phosphate pathway supplying cells with ribose 5-phosphate, a precursor of nucleic acid synthesis, and NADPH for biosynthetic processes and protection against oxidative stress. In this paper we demonstrate that also G6PDH of the protozoan parasite Trypanosoma brucei is uncompetitively inhibited by DHEA and epiandrosterone (EA), with K(i) values in the lower micromolar range. A viability assay confirmed the toxic effect of both steroids on cultured T. brucei bloodstream form cells. Additionally, RNAi mediated reduction of the G6PDH level in T. brucei bloodstream forms validated this enzyme as a drug target against Human African Trypanosomiasis. Together these findings show that inhibition of G6PDH by DHEA derivatives may lead to the development of a new class of anti-trypanosomatid compounds. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism

Interleukin-22 (IL-22) is a member of the interleukin-10 cytokine family, which is involved in anti-microbial defenses, tissue damage protection and repair, and acute phase responses. Its signaling mechanism involves the sequential binding of IL-22 to interleukin-22 receptor 1 (IL-22R1), and of this dimer to interleukin-10 receptor 2 (IL-10R2) extracellular domain. We report a 1.9 A crystal structure of the IL-22/IL-22R1 complex, revealing crucial interacting residues at the IL-22/IL-22R1 interface. Functional importance of key residues was confirmed by site-directed mutagenesis and functional studies. Based on the X-ray structure of the binary complex, we discuss a molecular basis of the IL-22/IL-22R1 recognition by IL-10R2.

Prosodic Morphology : Gender in Arabic Perfect Active and Passive 3rd Person Singular Verbs

Prosodic /template Morphology, that "draws heavily on the theoretical apparatus and formalisms of the generative phonology model known as autosegmental phonology" (Katamba, F. 1993: 154), is the best analysis that can handle Arabic morphology. Verbs in Arabic are represented on three independent tiers: root tier, the skeletal tier and the vocalic melody tier (Katamba, F. 1993). Vowel morphemes, which are represented by diacritics, are inserted within the consonant morphemes, which are represented by primary symbols, to form words. The morpheme tier hypothesis paves the way to understand the nonconcatenative Arabic morphology. This paper analyzes gender in perfect active and passive 3rd person singular verbs on the basis of PM. The focus of the analysis shall be drawn heavily on the most common Arabic verbs; triconsonantal verbs, with brief introduction of the less common verbs; quadriconsonantal perfect active and passive masculine and feminine 3rd person singular verbs. I shall, too, cast the light on some vowel changes that some verbs undergo when voice changes.

A Note on Proxy Variables and Instrument Variable Regression

This is a note about proxy variables and instruments for identification of structural parameters in regression models. We have experienced that in the econometric textbooks these two issues are treated separately, although in practice these two concepts are very often combined. Usually, proxy variables are inserted in instrument variable regressions with the motivation they are exogenous. Implicitly meaning they are exogenous in a reduced form model and not in a structural model. Actually if these variables are exogenous they should be redundant in the structural model, e.g. IQ as a proxy for ability. Valid proxies reduce unexplained variation and increases the efficiency of the estimator of the structural parameter of interest. This is especially important in situations when the instrument is weak. With a simple example we demonstrate what is required of a proxy and an instrument when they are combined. It turns out that when a researcher has a valid instrument the requirements on the proxy variable is weaker than if no such instrument exists

The Role of Motivational Strategies in the Upper Elementary Classroom : A systematic literature review about teacher strategies that promote self-confidence, motivation and a conducive learning environment

The aim of this literature review is to investigate which strategies teachers use to motivate pupils to communicate orally in English. The literature review also investigates how these teacher strategies affect pupils. The methodology used for this investigation is a systematic literature review. Various databases have been used when searching for literature. Scientific articles and theses have been searched for. They have also been read and analyzed before they have become a part of this review. The results indicate that some teachers feel insecure when speaking English. Therefore Swedish is spoken in many language classrooms. Teachers speaking in front of the class is the traditional way of teaching, and it does not seem to be a strategy who influences pupils positively. If teachers speak the target language among pupils they often get more motivated and focused pupils who feel comfortable speaking English. Young pupils are fast learners. By exposing them to the English language in early ages they receive great opportunities to learn a foreign language and strengthen their self-confidence. Drama, songs and rhymes are preferable strategies to use when teaching young learners. What position teachers decide to take in the classroom is also a significant element when teaching foreign languages.

Connecting Scientific Data to Scientific Experiments with Provenance

As scientific workflows and the data they operate on, grow in size and complexity, the task of defining how those workflows should execute (which resources to use, where the resources must be in readiness for processing etc.) becomes proportionally more difficult. While "workflow compilers", such as Pegasus, reduce this burden, a further problem arises: since specifying details of execution is now automatic, a workflow's results are harder to interpret, as they are partly due to specifics of execution. By automating steps between the experiment design and its results, we lose the connection between them, hindering interpretation of results. To reconnect the scientific data with the original experiment, we argue that scientists should have access to the full provenance of their data, including not only parameters, inputs and intermediary data, but also the abstract experiment, refined into a concrete execution by the "workflow compiler". In this paper, we describe preliminary work on adapting Pegasus to capture the process of workflow refinement in the PASOA provenance system.

Where did all these books come from? The Publishing Industry and American Intellectual Life

The American book publishing industry shapes the character of American intellectual life. While the newspaper and television industries have been accused of and investigated for bias and lowering America’s intellectual standards, book publishing has gone largely unexamined by scholars. The existing studies of the publishing industry have focused on finance, procedure and history. “There are few ‘theories’ of publishing – efforts to understand the ‘whys’ as well as the ‘hows.’ Few scholarly scientists have devoted significant scholarly attention to publishing” (Altbach and Hoshino, xiii). There are many possible reasons for this lacuna. First, there is a perception that books have always been around, that they are an “old” technology and therefore they don’t appear to have had as much of an impact on our society as television and other media (which were developed quickly and suddenly) seem to have had (Altbach and Hoshino, xiv). Also, despite books’ present and past popularity, television, radio, and now the internet reach more people more easily, and are therefore more topical points of study and observation. In studying the effects of mass media on everyday American life, television and the internet may be the most logical points of study. Regarding public intellectual life however, books play a much more important role. Public intellectual life has always been associated with independent thinkers publishing their work for the masses. For this reason, this I focus on trade publishing. Trade publishing produces fiction and non-fiction works for the general reading public, as opposed to technical manuals, textbooks, and other fiction and nonfiction books targeted to small and specific audiences. Although, quantitatively speaking, “the largest part of book publishing business is embodied in that great complex of companies and activities producing educational, business, scientific, technical, and reference books and materials,” (Tebbel 1987, 439) the trade industry publishes most of the books that most people read. It is the most public segment of the industry, and the most likely place to find public intellectualism. Trade publishing is not only the most public segment of the industry, but it is also the most susceptible to corruption and lowered intellectual standards. Unlike specialty publishing, which caters to a specific, known segment of society, trade publishers must compete with countless other publications, as well as with other forms of media, for the patronage of the general public. As John Tebbel (author of a widely referenced history of the publishing industry) puts it, “The textbook, scientific, or technical book is subjected to much more rigorous scrutiny by buyers and users, and in an intensively competitive market inferior products are quickly lost" (Tebbel 1987, xiv). Since the standards for trade publishing are not nearly as specific – trade books simply need to catch the attention of a significant number of readers, they don’t have to measure up to a given level of quality – the quality of trade books is much more variable. And yet, a successful trade publication can have a much greater impact on society than the most rigorously researched and edited textbook or scholarly study.

Optimal two-sided tests for instrumental variables regression with heteroskedastic and autocorrelated errors

This paper considers two-sided tests for the parameter of an endogenous variable in an instrumental variable (IV) model with heteroskedastic and autocorrelated errors. We develop the nite-sample theory of weighted-average power (WAP) tests with normal errors and a known long-run variance. We introduce two weights which are invariant to orthogonal transformations of the instruments; e.g., changing the order in which the instruments appear. While tests using the MM1 weight can be severely biased, optimal tests based on the MM2 weight are naturally two-sided when errors are homoskedastic. We propose two boundary conditions that yield two-sided tests whether errors are homoskedastic or not. The locally unbiased (LU) condition is related to the power around the null hypothesis and is a weaker requirement than unbiasedness. The strongly unbiased (SU) condition is more restrictive than LU, but the associated WAP tests are easier to implement. Several tests are SU in nite samples or asymptotically, including tests robust to weak IV (such as the Anderson-Rubin, score, conditional quasi-likelihood ratio, and I. Andrews' (2015) PI-CLC tests) and two-sided tests which are optimal when the sample size is large and instruments are strong. We refer to the WAP-SU tests based on our weights as MM1-SU and MM2-SU tests. Dropping the restrictive assumptions of normality and known variance, the theory is shown to remain valid at the cost of asymptotic approximations. The MM2-SU test is optimal under the strong IV asymptotics, and outperforms other existing tests under the weak IV asymptotics.

Ética na pesquisa em Administração

Ethics on scientific research is approached and often discussed in several areas of knowledge connected to health. In the Administration area there are very few studies which approach the topic of ethics on research. The present paper tried to fill in this gap in the production of knowledge about the topic, investigating how the ethical principles found in the literature and in the codes of conduct are noticed and taken into account in Administration research activities developed by acting researchers in Administration Post Graduation Programs. Theoretically speaking, the study was based mainly on the approaches by Creswell (2007) and Bell and Bryman (2007), which discuss the research ethical principles. Methodologically speaking it was all about an exploratory kind of study, with qualitative research approach. Upon data collection, personal interviews were made aiming at its depth and focus groups were formed. The first stage had interviews with four experienced researchers who took part on a teaching and researching event and on the second stage we used the focus group technique. The focus groups were done in four college institutions along with the post graduation programs in Administration in the states of Rio Grande do Norte, Paraíba and Pernambuco, in Brazil. The results suggest the existence of general principles and parameters for the scientific research recommended in the literature and on official resolution. However, in the Administration area, there are only a few recommendations of good practices when it comes to submitting articles for scientific publications but we found no guidance with ethical principles and parameters which cover all the activities in the scientific research and which specifically meet the research particularities in Administration. The main ethical dilemma pointed by the researchers refers to ethical questions which arise at the time of data collection and on disclosing the results. Most researchers do not know the guidelines and the ethical norms on ethics about research that we have in our country neither do they send in their projects to the research ethics committee. When dilemma arises, they decide the ethical question based on their values and common sense. These elements confirm the thesis that the researcher s procedure in the research activities in Administration is predominantly signed by personal values or by common sense and less by ethical principles, whether by not knowing the normative instruments related to ethics or by disagreeing with any disciplining rules on ethical behavior in the research

Repercussões sociais da violência contra crianças e adolescentes: deliqüência

This research is responsible for the investigation and problematization of the violence production process in children and teenagers through deviant behaviour, especially the drug s use and traffic, given that the deviant behaviour named juvenile criminality is something built and that can t be disassociated from the social and institutional relations that are ideological and violent, as well as the construction of, social and individual, positive identities can become important instruments for the process of democratization and the effective juvenile citizenship. In relation to the teorical referential, the work was developed from readings beyond the social science camp, without getting far from it, searching for support in other scientific camps and making your bases on Manuel Castells formulations about the power of the identity, and on Nancy Fraser and Axel Honneth in relation to the recognition struggle. In the empiric field, the discourses and graphic representations from twenty four children and teenagers that attend a social project were privileged, and compared to those shown at the documentary and the book Falcão Meninos do Tráfico produced by MV Bill, in relation to the social profile and life trajectory. From the study subjects' perspective, the data suggest that the children and the teenagers conceive violence as a natural thing, either as victims or persecutors. However, the research shows that, despite the subjects of the two studied groups reveled in your discourses the influence of the violent relations in their daily lives, the subjects got recognition during the process of identity construction by the groups with which they maintained the sense of belonging, either it being the family, the community or the school, they were positively influenced and established a positive representation of themselves and didn t show any deviant and violent tendency or behaviour. Therefore, we demonstrate the role of the school for an education for peace, as well as the participation of the family, the community and the stimulation of the juvenile protagonism as transforming practices, capable of awaking the citizenship and avoiding the construction of people that reproduce deviant and violent behaviour

Tramas da (ir)racionalidade contemporânea para a composição do mito-tecno-lógico

The plot myth-techno-logic, contemporary, was developed starting from the dualism myth-reason. In this study, we deepened the alluded dualism taking as reference the historical contexts of the Renaissance and of the Enlightenment, emphasizing the discussion of the economical rationalization as conductive thread of the western development, in which we identified the game of the rational and of the irrational, for assure the superiority of the reason. In the context of that game, we analyzed the implications of the modernization, for the education, in function of the instrumental rationality, responsible for the environment of adaptation of the technological instruments to the scenery of the contemporary modernization. The new context is constituted by points of union and of ruptures among the technique, the science and the myth. Through our analysis, we noticed that the basic needs for the contemporary society were linked to the changes in the production means, for which the machine determine the rhythm of the work and the quality of the product. However, the changes in the productive processes promoted the appearance of the commercial marks that, as we see it, they represented the synthesis of the perfect harmony of the myth, of the technique, of the science and of the technology, in the conduction of the economical rationalization to the contemporary modernization. Thus, the contemporary modernization it arrives us for the economical rationalization, developed with the support of the technician-scientific knowledge and communicated by the articulations of the myth-techno-logical

Avaliação do programa escola ativa como política pública para escolas do campo com turmas multisseriadas: a experiência em jardim do seridó/rn (1998-2009)

This work aims at developing an evaluation of the implementation of the Program Escola Ativa as a public policy for rural schools with combined grade classrooms in Jardim do Seridó RN (1998 2009) focusing on the following dimensions: school s physical environment, training, follow up, and didactic usage of the methodology. In order to develop this research we refer to the literature that analyzes the cycle of policies (FREY, 2000). In this approach, evaluation represents an important step in the process of analyzing the implementation of public policies, as a way of measuring up their performance, as well as a guide for realignments and redefinitions (PRESSMAN; WILDAVSKY, 1998). In order to accomplish this function, the evaluator of policies must be acquainted with scientific concepts and methods that consist of describing, interpreting and analyzing the policies in the governmental sphere (MENY; THOENIG, 1992; LIMA JÚNIOR, 1978). In this perspective, we intend to investigate whether in its proposition of minimizing the blanks in the Brazilian educational system, the implementation of the Program would be contributing to the improvement of the political-pedagogical practices in the rural schools with combined grade classrooms in Jardim do Seridó RN. In order to do this research, we have developed a theoretical-methodological matrix made of analysis dimensions, variables, indicators and instruments, such as literary revision, documental analysis, semi-structured interviews with four teachers and three supervisors that work and/or have worked in Escola Ativa in that town in the period comprised among 1998 2009, besides notes taken from field observation and photographs from four rural schools with combined grade classrooms. With this research we have identified that the Program, at a national level, has gone through different phases in its implementation process, for the town was not ready to fully take the responsibilities of the autonomous expansion, in 2002. From that period on, the execution of Escola Ativa has suffered several discontinuities, such as the lack of professional training and supervising. It is also noted that the methodology contributes to the dynamization of the didactic-pedagogical activities and promotes the cooperation and autonomy of the students in the organization and the applicability of the components of the curriculum, especially of Governo Estudantil and Cantinhos de Aprendizagem. Although the directions of the Program (BRASIL, 2005) point out that Escola Ativa has among its principles social transformation, we identified that, isolated, the initiative is not capable of promoting the changes that the rural schools need, namely investments in the physical, material, pedagogical and technological infra-structure, besides the estimation and a career plan for the teachers. In a general draft of the results of this research, we realized that some aspects presented about the peculiarities of Escola Ativa in Jardim do Seridó as a governmental Program, reinforce the need for the public policies to be evaluated, in order to confront critic and operationally the planning with the practice, revising action, whenever necessary

Validação de instrumentos para avaliação do conhecimento e da habilidade acerca da sondagem vesical de demora

That study had the aim to validate an instrument to evaluate the knowledge about the Urinary Catheterization (UC) in males. Cross-sectional, descriptive, quantitative and methodological study, accomplished in Universidade Federal do Rio Grande do Norte (UFRN), Universidade do Estado do Rio Grande do Norte (UERN) and a private university from Rio Grande do Norte. Sample of 27 judges selected from the inclusion criteria: registered nurses, discipline of semiology and/or semiotics teachers, with at least 1 year of experience in the disciplines, to work at UFRN, UERN or in private university and agree to participate voluntarily with the signing of the Consent Form. Study developed in three stages: a) elaboration of twos instruments based on the scientific literature, resulting in a structured observation script type checklist consisting of 36 items and a knowledge questionnaire with 12 questions; b) submission of instruments to judges from June to September 2012, which should evaluate each item in "adequate," "adequate with changes" and "inappropriate", and make an overall evaluation of each instrument based on 10 requirements; c) and validation with a verification of the agreement level among the judges, through the application of Kappa Index (K) and Content Validity Index (CVI). It was used the consensus level higher than 0.60 (good) for Kappa Index and higher than 0.70 for CVI. The research project had favorable opinion from the Ethics in Research/HUOL (CAAE n. 0002.0.294.000-10). After being coded and tabulated, the data were analyzed using descriptive statistics. Of the 27 judges who evaluated the instrument, 77.8% are female, with a mean age of 36.6 (± 9.0) years, 63.0% worked in UFRN, 74.1% had master degree and 63.0% worked exclusively on teaching. The experience time mean in teaching was 7.9 (± 8.0) years and in the disciplines of semiology and/or semiotics in nursing was 5.5 (± 6.7) years. In judgment of the checklist and knowledge questionnaire, no step/question was considered inappropriate, since all achieved level of agreement within the established values. All the checklist steps obtained good to excellent K (between 0.60 and 1.00). Of the 36 items, 25 had excellent K (0.75 ≤ K <1.00) and excellent total K (K = 0.83). Regarding the IVC, all steps reached levels above 0.70 (between 0.74 and 1.00) and CVI total was 0.90. All questionnaire questions evaluated separately (K from 0.60 to 0.93 and CVI from 0.74 to 0.96) and generally (K from 0.79 to 1.00 and CVI from 0.89 to 1.00) had evaluation levels of content validity within the established values. The instruments were reformulated based on the agreement levels between judges and international guidelines, dissertations and scientific articles. Both instruments proved to be valid regarding to their content, allowing a clear and objective evaluation of knowledge and skills about UC, both nursing students as well as other students and health professionals, since the use of valid measures seeking the reduction of the risk of the results distorted

International conferences on environmental mutagens in human populations - Opportunities, accomplishments and challenges

A major mission for organizing the series of International Conferences on Environmental Mutagens in Human Populations is to bring science and scientists to the sites where the field of environmental health is in developmental stages and environmental health is a serious concern. The mission has been fulfilled in each of the previous conferences that were held in Egypt, Czech Republic, Thailand and Brazil. These conferences have led to significant enhancement of regional scientific expertise from the acquisition of scientific knowledge and from the generation of sustainable collaborative programs. (C) 2003 Elsevier B.V. All rights reserved.

Hyperalgesic and edematogenic effects of peptides isolated from the venoms of honeybee (Apis mellifera) and neotropical social wasps (Polybia paulista and Protonectarina sylveirae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)