Regulated expression of mature human insulin in the liver of transgenic mice

AbstractTransgenic mice expressing either human proinsulin cDNA or mutated proinsulin cDNA in the liver were created. The human proinsulin cDNA was mutated to generate a protein cleavable by the ubiquitous prohormone convertase furin, thus leading to mature insulin peptide. All transgenic lines expressed human C-peptide in the blood, whose level varied according to nutritional conditions. High performance liquid chromatography fractionation of mouse serum revealed that mutant proinsulin was effectively processed into mature insulin in vivo. This transgenic mouse model provides a useful tool for further prospects of gene therapy of insulin-dependent diabetes mellitus

FOREST SYSTEMS, SOIL FAUNA, AND SOIL FEATURES: HOW FIELD MANAGEMENT CHANGE THIS RELATIONSHIP?

The objective of this study was to identify differences in land use systems and forest management on the diversity of soil fauna and Collembola eco-morphotypes, and their relationship with physical-chemical attributes of the soil. Sampling was carried out in Native Forest (NF), Araucaria Reforestation (AR) and Eucalyptus (ER). In all, 19 taxonomic groups were identified, of which Formicidae and Collembola were the most abundant, in addition to 21 morphotypes of springtail. For TSBF, AR presented the highest abundance and NF the highest values of wealth and diversity of groups. Potassium and magnesium contents, total porosity, pore volume, penetration resistance (Rpen), organic matter, and pH were the environmental variables that contributed to explain the distribution of the soil fauna. In pitfalls traps, ER showed the greatest abundance, NF the greatest richness and AR the greatest diversity. Rpen and soil moisture contributed to explain the distribution of soil fauna. NF provided greater abundance, diversity, and richness of Collembola eco-morphotypes and biopores, macropores, clay, manganese and copper levels affected the community structure. Different forest systems affect the structure of the soil community, showing improvement in biological indicators in the Native Forest areas, Araucaria, and Eucalyptus Reforestation, under the influence of physical and chemical attributes

French Experience of 2009 A/H1N1v Influenza in Pregnant Women

BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population

The SOPHIE search for northern extrasolar planets XIV. A temperate (Teq ~ 300 K) super-earth around the nearby star Gliese 411

Periodic radial velocity variations in the nearby M-dwarf star Gl 411 are reported, based on measurements with the SOPHIE spectrograph. Current data do not allow us to distinguish between a 12.95-day period and its one-day alias at 1.08 days, but favour the former slightly. The velocity variation has an amplitude of 1.6 m s−1, making this the lowest-amplitude signal detected with SOPHIE up to now. We have performed a detailed analysis of the significance of the signal and its origin, including extensive simulations with both uncorrelated and correlated noise, representing the signal induced by stellar activity. The signal is significantly detected, and the results from all tests point to its planetary origin. Additionally, the presence of an additional acceleration in the velocity time series is suggested by the current data. On the other hand, a previously reported signal with a period of 9.9 days, detected in HIRES velocities of this star, is not recovered in the SOPHIE data. An independent analysis of the HIRES dataset also fails to unveil the 9.9-day signal. If the 12.95-day period is the real one, the amplitude of the signal detected with SOPHIE implies the presence of a planet, called Gl 411 b, with a minimum mass of around three Earth masses, orbiting its star at a distance of 0.079 AU. The planet receives about 3.5 times the insolation received by Earth, which implies an equilibrium temperature between 256 and 350 K, and makes it too hot to be in the habitable zone. At a distance of only 2.5 pc, Gl 411 b, is the third closest low-mass planet detected to date. Its proximity to Earth will permit probing its atmosphere with a combination of high-contrast imaging and high-dispersion spectroscopy in the next decade

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Application of model weaving in model transformation in MDA.

Uma das principais atividades dos enfoques de desenvolvimento de software centrados em modelos, como por exemplo a Arquitetura Dirigida por Modelo (Model Driven Architecture - MDA), é o processo de transformação de modelos. Geralmente, um passo preliminar para a transformação dos modelos é o mapeamento dos elementos do meta-modelo fonte nos elementos do meta-modelo alvo. Este trabalho apresenta uma aplicação de uma técnica de mapeamento de modelos denominada tecelagem de modelos. Esta técnica permite ao usuário definir a semântica das ligações estabelecidas entre os elementos do meta-modelo fonte e os elementos do meta-modelo alvo. A semântica é definida através de tipos fortes associados às ligações. O presente trabalho analisa, através de dois experimentos, alguns aspectos da geração de modelos de transformação de modelos no arcabouço MDA, utilizando a técnica de tecelagem de modelos. A análise utiliza duas alternativas de especificação de transformação de modelos a título de comparação: a que usa somente uma linguagem de especificação de modelos de transformação e a que usa a técnica de tecelagem de modelos. Os aspectos analisados são: a reutilização de trechos de código escritos na linguagem de geração de especificações de transformação e a reutilização de decisões de projeto (design) no mapeamento entre dois meta-modelos distintos.One of the main activities of the model-centric approaches of software development, as for example the Model Driven Architecture (MDA), is the process of model transformation. Usually, a preliminary step for model transformation is the mapping of source metamodel elements into target metamodel elements. This work presents an application of a technique for model mapping called model weaving. This technique allows the user to define the semantics of the links binding source metamodel elements and target metamodel elements. The semantics is defined through types associated to links. The work analyzes, through two experiments, some aspects of the generation of models transformation in the MDA framework, using a technique known as model weaving. The analysis, for comparison purposes, uses two techniques of model transformation specification: one using only a specification language for model transformation specification and another using model weaving. The analyzed aspects are: the reuse of pieces of code written in the language that generates the transformation of specifications and the reuse of design decisions in the mapping between two distinct metamodels

ML4JIT - a framework for research on machine learning in JIT compilers.

Determinar o melhor conjunto de otimizações para serem aplicadas a um programa tem sido o foco de pesquisas em otimização de compilação por décadas. Em geral, o conjunto de otimizações é definido manualmente pelos desenvolvedores do compilador e aplicado a todos os programas. Técnicas de aprendizado de máquina supervisionado têm sido usadas para o desenvolvimento de heurísticas de otimização de código. Elas pretendem determinar o melhor conjunto de otimizações com o mínimo de interferência humana. Este trabalho apresenta o ML4JIT, um arcabouço para pesquisa com aprendizado de máquina em compiladores JIT para a linguagem Java. O arcabouço permite que sejam realizadas pesquisas para encontrar uma melhor sintonia das otimizações específica para cada método de um programa. Experimentos foram realizados para a validação do arcabouço com o objetivo de verificar se com seu uso houve uma redução no tempo de compilação dos métodos e também no tempo de execução do programa.Determining the best set of optimizations to be applied in a program has been the focus of research on compile optimization for decades. In general, the set of optimization is manually defined by compiler developers and apply to all programs. Supervised machine learning techniques have been used for the development of code optimization heuristics. They intend to determine the best set of optimization with minimal human intervention. This work presents the ML4JIT, a framework for research with machine learning in JIT compilers for Java language. The framework allows research to be performed to better tune the optimizations specific to each method of a program. Experiments were performed for the validation of the framework with the objective of verifying if its use had a reduction in the compilation time of the methods and also in the execution time of the program

Deconstructing the myth of development aid by assessing farmer organizations’ capacity to innovate in open environments

International audienceIn West Africa, farmer organizations (FOs) collaborate with diverse foreign development aid organizations in order to develop innovative digital extension services. However, the results do not often come up to hopes and expectations. Previous studies on open innovation (OI) show that organizations require specific capacities to innovate successfully in collaborative environments. However, none addressed the case of FOs in developing countries. In this article, we thus assess FO's capacity to innovate in collaborative situations, building upon two perspectives: the OI theory to characterize partnering modalities and the capacity-based approach of innovation management. We assumed that in a development context where FOs' capabilities are considered as globally weak, collaboration setups might influence their capacity to innovate. We developed and tested an analytical grid of the capacities to innovate, linking internal organizational features with inter-organizational collaborative practices. We compared two case studies in Burkina Faso, reflecting two contrasted partnering situations with similar objectives. We found out that FOs' capacity to innovate was weak in both cases and that their partnership with NGOs prevented them to mobilize and develop essential capabilities to innovate. Our results give new insights into digital-based innovation processes in the service sector. The focus usually made on technological rather than organizational aspects rather prevented FOs from developing relevant and sustainable digital tools for extension. This study highlights the importance of taking into account organizational capacity development issues back to back with technology development when implementing collaborative innovation projects in developing countries

Construction(s) et contradictions des données de recherche en SHS

International audienceIn the last decade, political injunctions to curate and share research data have increased significantly. A survey conducted in 2017 in Rennes 2, a french Humanities and Social Sciences university, enabled us to question the habits and representations of the researchers in this matter, but also the term of "data" itself. Contrary to the idea that data are given, which is implicit in the french word "données", the notion of "data" is far from being self-evident and actually proves to be complex and multifaceted. This article aims at showing that a triple redefinition and construction of research data is at stake in the discourses of researchers and institutional stakeholders: it operates at epistemological, intellectual and political levels. These concepts of data conflict with existing practices in the field.La structuration et le partage des données s'imposent depuis cinq ans au monde de la recherche, à travers des injonctions politiques (de Horizon 2020 au Plan national pour la science ouverte). L'analyse de l'enquête menée en 2017 auprès des chercheurs de l'université Rennes 2 sur leurs pratiques, représentations et attentes en matière de données conduit à interroger le terme lui-même. Variable et complexe, contrairement à ce que suggère le mot « donnée », la notion ne va pas de soi. L'article s'efforcera de montrer qu'elle fait l'objet d'une triple construction, épistémologique, intellectuelle et politique, dans les discours des chercheurs et des acteurs institutionnels, en tension avec les pratiques constatées sur le terrain

McDonald’s : key success factors in France, India and the United States

International and European Busines