Manejo de lepidópteros-praga na cultura do milho com o evento Bt piramidado Cry1A.105 e Cry2Ab2

O objetivo deste trabalho foi avaliar a eficácia do evento piramidado (MON 89034), que expressa as proteínas Cry1A.105 e Cry2Ab2, no controle dos principais lepidópteros-praga da cultura do milho no Brasil, Spodoptera frugiperda, Helicoverpa spp. e Diatraea saccharalis. Os ensaios foram conduzidos em quatro regiões do país, com o híbrido DKB 390, submetido a seis tratamentos: híbrido com o evento piramidado, híbrido com o evento que expressa apenas a proteína Cry1A(b) (MON 810) e híbrido convencional (não Bt), todos com e sem manejo integrado de S. frugiperda. Para o evento piramidado, não foi necessário o controle químico em nenhum dos locais avaliados. Diferenças significativas foram observadas entre os tratamentos quanto aos danos e à presença de lagartas. Em geral, essas variáveis foram mais baixas no híbrido com o evento piramidado e mais altas no híbrido convencional, sem controle químico. Sob alta infestação, o controle químico reduziu os danos causados por S. frugiperda e D. saccharalis, tanto no evento que expressa apenas uma proteína, como no híbrido convencional. Com base nos danos causados pelos insetos, o evento piramidado Cry1A.105 e Cry2Ab2 é eficiente no controle dos principais lepidópteros-pragas do milho no Brasil.

Guideline adaptation: an approach to enhance efficiency in guideline development and improve utilisation.

BACKGROUND: Developing and updating high-quality guidelines requires substantial time and resources. To reduce duplication of effort and enhance efficiency, we developed a process for guideline adaptation and assessed initial perceptions of its feasibility and usefulness. METHODS: Based on preliminary developments and empirical studies, a series of meetings with guideline experts were organised to define a process for guideline adaptation (ADAPTE) and to develop a manual and a toolkit made available on a website (http://www.adapte.org). Potential users, guideline developers and implementers, were invited to register and to complete a questionnaire evaluating their perception about the proposed process. RESULTS: The ADAPTE process consists of three phases (set-up, adaptation, finalisation), 9 modules and 24 steps. The adaptation phase involves identifying specific clinical questions, searching for, retrieving and assessing available guidelines, and preparing the draft adapted guideline. Among 330 registered individuals (46 countries), 144 completed the questionnaire. A majority found the ADAPTE process clear (78%), comprehensive (69%) and feasible (60%), and the manual useful (79%). However, 21% found the ADAPTE process complex. 44% feared that they will not find appropriate and high-quality source guidelines. DISCUSSION: A comprehensive framework for guideline adaptation has been developed to meet the challenges of timely guideline development and implementation. The ADAPTE process generated important interest among guideline developers and implementers. The majority perceived the ADAPTE process to be feasible, useful and leading to improved methodological rigour and guideline quality. However, some de novo development might be needed if no high quality guideline exists for a given topic.

IFRS-standardienvaikutus osakkeiden hintatasoon

Euroopan Unionin hyväksymän IAS-asetuksen mukaan kaikkien julkisesti noteerattujen yritysten on siirryttävä käyttämään tilinpäätöksen laatimisessa IFRS-standardeja viimeistään vuodesta 2005 lähtien. Tämän tutkimuksen tavoitteena on selvittää onko IFRS-standardeihin siirtymisellä ollut vaikutusta osakkeiden hintatasoon Suomen Pörssissä noteerattujen metallitoimialan yritysten kohdalla. IFRS-standardien vaikutuksia osakkeiden epänormaaleihin tuottoihin tutkitaan ns. tapahtumatutkimuksen avulla. Tutkittava tapahtuma eli ns. event on hetki, jolloin yritys on ensimmäisen kerran julkaissut IFRSstandardien mukaista tilinpäätösinformaatiota. Valittujen tunnuslukujen (P/E-, P/B-, EV/EBIT- ja Grahamin tunnuslukujen) muutosten ja tapahtuman jälkeisten ylituottojen avulla puolestaan tutkitaan ovatko markkinat sopeutuneet muuttuneeseen tilinpäätösinformaatioon. Saatujen tutkimustulosten perusteella voidaantodeta, että etenkin liikearvopoistojen päättyminen sekä ns. eläkestandardi ovat vaikuttaneet yritysten tuloslaskelmiin. Taseen puolella suurimmat muutokset ovat aiheuttaneet rahoitusleasingiä ja tuotekehityksen aktivointia käsittelevät standardit. Tutkimuksen mukaan IFRS:n tuomat tase- ja tuloslaskelma muutokset ovat myös heijastuneet osakkeiden markkinahintoihin.

Traumatismes précoces et réponses de stress, leur association aves la santé mentale, l'attachement et l'ocytocine

Lorsqu'un individu est confronté à une situation stressante, une des réponses les plus saillantes est l'activation de l'axe HPA, caractérisée par le déclenchement d'un taux élevé de glucocorticoïdes dans le sang. De manière générale, cette réponse hormonale est adaptative et elle a pour but la mobilisation des ressources physiques et cognitives de l'individu pour une action spécifique (Axelrod & Reisine, 1984; Chrousos & Gold, 1992; N. M. Kaplan, 1988; McEwen, 2004). Cependant, lorsque une personne est confrontée très tôt dans son développement, et de manière répétée, à des situations de stress, cette réponse physiologique peut s'altérer, devenir inadaptée (Anand, 1993; Bremner et al., 1995; Meaney et al., 1996; Mirescu, Peters, & Gould, 2004; Plotsky & Meaney, 1993; Sapolsky, 2000) et être associée à des troubles cognitifs (McEwen & Sapolsky, 1995) et émotionnels (McEwen, 2000). A l'âge adulte, le résultat de ces altérations psychoneuroendocriniennes se traduit au cours de l'activation de l'axe HPA et elles sont visibles lors de situations de stress moins intenses (Graham, Heim, Goodman, Miller, & Nemeroff, 1999; Mirescu et al., 2004; Stam, Bruijnzeel, & Wiegant, 2000; A. Taylor, Fisk, & Glover, 2000). La dysregulation de l'axe HPA semble représenter un facteur de vulnérabilité lié à des dysfonctionnements psychiques et physiologiques chez les adultes (Heim, Ehlert, & Hellhammer, 2000; Heim & Nemeroff, 1999; Heim, Newport, Mletzko, Miller, & Hemeroff, 2008). Cependant, des facteurs de protection peuvent influencer à leur tour ces vulnérabilités. La littérature, basée sur des études translationnelles (animaux, humains), converge vers le postulat selon lequel la dimension relationnelle apportée par l'environnement est fondamentale dans le développement des vulnérabilités physiologiques et psychiques du sujet. Dans ce sens, les relations d'attachement ont été particulièrement étudiées. A l'âge adulte, par exemple, la qualité des représentations d'attachement semble influencer directement l'expression de gènes impliqués dans les réponses hormonales de stress (Biagini, Pich, Carani, Marrama, & Agnati, 1998; Caldji, Diorio, & Meaney, 2000; Dallman, 2000; De Kloet, Rosenfeld, Van Eekelen, Sutanto, & Levine, 1988; Rincon-Cortes & Sullivan, 2014; Romeo, Tang, & Sullivan, 2009; van Oers, de Kloet, Whelan, & Levine, 1998), illustrant ainsi une perspective épigénétique. Traumatismes précoces et réponses de stress, leur association avec la santé mentale, l'attachement et l'ocytocine Deux objectifs principaux définissent ce travail de doctorat. Le premier est de comprendre comment un événement à portée traumatique, qui a eu lieu pendant la période périnatale, l'enfance ou l'adolescence, peut s'inscrire au niveau physiologique (axe hypotalamico- hypophysaire-surrénalien - axe HPA), au niveau psychopathologique ou encore au niveau de la régulation émotionnelle au cours de l'âge adulte. A ce propos, nous avons évalué les réponses physiologiques (telles que le Cortisol, l'ACTH et l'ocytocine), la présence de psychopathologies (relatives à l'axe I du DSM-IV) et les réponses émotionnelles (telles que la perception au stress) au cours d'une situation de stress de nature psychosociale, induite en laboratoire. Le deuxième objectif de ce travail est de savoir si les représentations d'attachement peuvent médiatiser ces effets, chez des individus exposés à différents événements à portée traumatique. Dans ce but, trois populations ont été considérées. La première est relative à des jeunes adultes nés grands prématurés ; la deuxième, concerne des femmes adultes ayant vécu un ou plusieurs abus sexuels au cours de leur enfance ou de leur adolescence et enfin la troisième est constituée de personnes adultes qui ont survécu à une maladie grave (cancer) pendant leur enfance ou leur adolescence. Enfin, ces trois populations sont comparées à des groupes contrôle. La prise en considération de différents types de traumatismes a permis de relever : premièrement, qu'un événement à portée traumatique de nature différente, peut influencer de manière semblable les structures neuronales, par exemple l'hypocortisolémie ; deuxièmement, qu'un dysfonctionnement de l'axe HPA n'aboutit pas nécessairement à la présence de signes de souffrance mentale ; enfin, des effets protecteurs ont été mis en évidence. Ces facteurs sont sous-tendus, d'un point de vue psychologique, par les représentations d'attachement et, d'un point de vue physiologique, par la sécrétion d'ocytocjne périphérique. Traumatismes précoces et réponses de stress, leur association avec la santé mentale, l'attachement et l'ocytocine -- When an individual is faced by a stressful situation, one of the most notable responses is the activation of the HPA axis, which is characterized by a heightened level of glucocortisoids in the blood. In general, this is an adaptive hormonal response which prepares the individual both physically and cognitively for a specific action (Axelrod & Reisine, 1984; Chrousos & Gold, 1992; N. M. Kaplan, 1988; McEwen, 2004). However, should a person be confronted to stressful situations very early and repeatedly in their development, this physiologic response may be altered and become maladapted (Anand, 1993; Bremner et al., 1995; Meaney et al., 1996; Mirescu et al., 2004; Plotsky & Meaney, 1993; Sapolsky, 2000) which can be associated to emotional (McEwen, 2000) and cognitive disorders(McEwen & Sapolsky, 1995). Throughout adulthood, the result of these psychoneuroendocrine alterations affects the activation of the HPA axis and are noticeable during less intense stressful situations (Graham et al., 1999; Mirescu et al., 2004; Stam et al., 2000; A. Taylor et al., 2000). HPA axis dysregulation appears to represent a factor of vulnerability linked to psychological and physical disorders in adults (Heim, Ehlert, et al., 2000; Heim & Nemeroff, 1999; Heim, Newport, et al., 2008). Nonetheless, these vulnerabilities may be influenced by further protection factors. The literature, based on translational studies (animals and humans), suggests that relationships formed in the context of the individual's environment are fundamental in the development of their physiological and psychological vulnerabilities. Thus, attachment relationships have been particularly studied. In adulthood, for example, the quality of attachment representations appear to influence directly the expression of genes involved in the hormonal responses to stress (Biagini et al., 1998; Caldji et al., 2000; Dallman, 2000; De Kloet et al., 1988; Rincon-Cortes & Sullivan, 2014; Romeo et al., 2009; van Oers et al., 1998). With the goal to study these dimensions, two principal objectives define these doctoral study. The first is to understand how an event considered to be traumatic, which took place during early infancy, infancy, or adolescence, could influence physiology (HPA axis), psychopathology or emotional regulation during adulthood. Therefore we have evaluated the presence of psychopathologies (relative to axis I of the DSM), physiological responses (such as Cortisol, ACTH and oxytocin) and emotional responses (such as perception of stress) throughout a psychosocial stress situation, conducted in a laboratory setting. The second objective of this study is to understand if attachment representations can mediate these effects, in individuals exposed to three different types of traumatic events. Therefore, three populations have been considered. The first is young adults who were born prematurely; the second concerns adult women who have suffered sexual abuse, on one or more occasions, during their childhood or adolescence; finally the third group is constituted of people who have survived a grave childhood illness. These populations were all compared to control groups. The consideration of different types of traumatic events has demonstrated, firstly, that different events which are considered to be traumatic can similarly influence neuronal structures, for example hypocortisolism. Secondly, that an HPA axis disorder does not necessarily lead to the presence of mental signs of distress, as is the case for those born very prematurely. Finally, protective effects were demonstrated, distinctively from a psychological point of view, by attachment representations and furthermore by peripheral oxytocin secretion from a physiological perspective.

Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells.

Recently, a handful of intergenic long noncoding RNAs (lncRNAs) have been shown to compete with mRNAs for binding to miRNAs and to contribute to development and disease. Beyond these reports, little is yet known of the extent and functional consequences of miRNA-mediated regulation of mRNA levels by lncRNAs. To gain further insight into lncRNA-mRNA miRNA-mediated crosstalk, we reanalyzed transcriptome-wide changes induced by the targeted knockdown of over 100 lncRNA transcripts in mouse embryonic stem cells (mESCs). We predicted that, on average, almost one-fifth of the transcript level changes induced by lncRNAs are dependent on miRNAs that are highly abundant in mESCs. We validated these findings experimentally by temporally profiling transcriptome-wide changes in gene expression following the loss of miRNA biogenesis in mESCs. Following the depletion of miRNAs, we found that >50% of lncRNAs and their miRNA-dependent mRNA targets were up-regulated coordinately, consistent with their interaction being miRNA-mediated. These lncRNAs are preferentially located in the cytoplasm, and the response elements for miRNAs they share with their targets have been preserved in mammals by purifying selection. Lastly, miRNA-dependent mRNA targets of each lncRNA tended to share common biological functions. Post-transcriptional miRNA-mediated crosstalk between lncRNAs and mRNA, in mESCs, is thus surprisingly prevalent, conserved in mammals, and likely to contribute to critical developmental processes.

Helena Valentí, fúria i traducció

La filòloga i novel·lista Helena Valentí i Petit (Barcelona, 1940-1990) s’exilià de ben jove a Anglaterra, on buscà en la traducció el mitjà de vida. Entre altres autors i autores, traslladà al castellà William Blake, Marilyn French, Nicholas Guild, Najib Mahfuz, Harold Robbins, Bernice Rubens, Roger T. Taylor i Doris Lessing, de la qual traduí El quadern daurat. De retorn a Catalunya, el 1974, decidí compaginar la traducció amb la narrativa pròpia. Girà a la llengua catalana Al far i Una cambra pròpia de l’anglesa Virginia Woolf i La garden party i altres contes i Un home casat i altres crueltats de la neozelandesa Katherine Mansfield. En els anys vuitanta traslladà El factor humà de Graham Greene i Jo, Claudi de Robert Graves, i féu una breu incursió en la narrativa per a joves. Viatges indiscrets de Lisa St. Aubin, un recull de contes d’autores del segle XX, fou l’última traducció.

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

BACKGROUND: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. METHODS: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. RESULTS: All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. CONCLUSIONS: Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 μg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 μg/mL (25·8-56·3) in the low-dose group, and 5·2 μg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 μg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 μg/mL (19·3-28·6) in the low-dose group, and 3·2 μg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.

Detecting Detection: International Perspectives on the Uses of a Plot

One of the problems with books which are relatively general in nature is that many of the individual contributions tend to be so narrow and specialised that only the author has any knowledge of (or interest in) the issues under discussion. At first sight this appears to be the case with Detecting Detection. Fortunately, however, first impressions are deceiving. Although the essays in the volume deal with writers as diverse and disparate as the Catalano-Spanish writer Juan Marse, the Bulgarian-French philosopher Julia Kristeva and the once-vaunted giant of English literature,Graham Greene, among numerous others, there is much to be enjoyed and learnt, even if some of the works under discussion are unfamiliar to the crime fiction reader and/or scholar to whom the book initially appears to be directed.

Knapsack sets for cryptography

The basic goal of this study is to extend old and propose new ways to generate knapsack sets suitable for use in public key cryptography. The knapsack problem and its cryptographic use are reviewed in the introductory chapter. Terminology is based on common cryptographic vocabulary. For example, solving the knapsack problem (which is here a subset sum problem) is termed decipherment. Chapter 1 also reviews the most famous knapsack cryptosystem, the Merkle Hellman system. It is based on a superincreasing knapsack and uses modular multiplication as a trapdoor transformation. The insecurity caused by these two properties exemplifies the two general categories of attacks against knapsack systems. These categories provide the motivation for Chapters 2 and 4. Chapter 2 discusses the density of a knapsack and the dangers of having a low density. Chapter 3 interrupts for a while the more abstract treatment by showing examples of small injective knapsacks and extrapolating conjectures on some characteristics of knapsacks of larger size, especially their density and number. The most common trapdoor technique, modular multiplication, is likely to cause insecurity, but as argued in Chapter 4, it is difficult to find any other simple trapdoor techniques. This discussion also provides a basis for the introduction of various categories of non injectivity in Chapter 5. Besides general ideas of non injectivity of knapsack systems, Chapter 5 introduces and evaluates several ways to construct such systems, most notably the "exceptional blocks" in superincreasing knapsacks and the usage of "too small" a modulus in the modular multiplication as a trapdoor technique. The author believes that non injectivity is the most promising direction for development of knapsack cryptosystema. Chapter 6 modifies two well known knapsack schemes, the Merkle Hellman multiplicative trapdoor knapsack and the Graham Shamir knapsack. The main interest is in aspects other than non injectivity, although that is also exploited. In the end of the chapter, constructions proposed by Desmedt et. al. are presented to serve as a comparison for the developments of the subsequent three chapters. Chapter 7 provides a general framework for the iterative construction of injective knapsacks from smaller knapsacks, together with a simple example, the "three elements" system. In Chapters 8 and 9 the general framework is put into practice in two different ways. Modularly injective small knapsacks are used in Chapter 9 to construct a large knapsack, which is called the congruential knapsack. The addends of a subset sum can be found by decrementing the sum iteratively by using each of the small knapsacks and their moduli in turn. The construction is also generalized to the non injective case, which can lead to especially good results in the density, without complicating the deciphering process too much. Chapter 9 presents three related ways to realize the general framework of Chapter 7. The main idea is to join iteratively small knapsacks, each element of which would satisfy the superincreasing condition. As a whole, none of these systems need become superincreasing, though the development of density is not better than that. The new knapsack systems are injective but they can be deciphered with the same searching method as the non injective knapsacks with the "exceptional blocks" in Chapter 5. The final Chapter 10 first reviews the Chor Rivest knapsack system, which has withstood all cryptanalytic attacks. A couple of modifications to the use of this system are presented in order to further increase the security or make the construction easier. The latter goal is attempted by reducing the size of the Chor Rivest knapsack embedded in the modified system. '