Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease.

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.

Ego identity in adolescence: preliminary validation of a French short-form of the EIPQ

Following the seminal work on personal identity of Erikson, Marcia's identity status model has been one of the most enduring paradigms. The Ego Identity Process Questionnaire (EIPQ; Balistreri, Busch-Rossnagel, & Geissinger, 1995) is a widely used measure of identity status. The purpose of this study was to evaluate the factor structure and the reliability of a French version of the EIPQ. The hypothesized structures were not confirmed. In light of the failed attempts to validate the original version, an alternative short-form version of the EIPQ (EIPQ-SF), maintaining the integrity of the original model, was developed in one sample and cross-validated in another sample. Additionally, theoretically consistent associations between the EIPQ-SF dimensions and self-esteem confirmed convergent validity. Globally, the results indicated that the French short-version of the EIPQ might be a useful instrument for the assessment of the identity statuses in adolescence and emerging adulthood.

Shallow-transfer rule-based machine translation for Czech to Polish

This article describes the developmentof an Open Source shallow-transfer machine translation system from Czech to Polish in theApertium platform. It gives details ofthe methods and resources used in contructingthe system. Although the resulting system has quite a high error rate, it is still competitive with other systems.

Error probability in synchronous digital circuits due to power supply noise

This paper presents a probabilistic approach to model the problem of power supply voltage fluctuations. Error probability calculations are shown for some 90-nm technology digital circuits.The analysis here considered gives the timing violation error probability as a new design quality factor in front of conventional techniques that assume the full perfection of the circuit. The evaluation of the error bound can be useful for new design paradigms where retry and self-recoveringtechniques are being applied to the design of high performance processors. The method here described allows to evaluate the performance of these techniques by means of calculating the expected error probability in terms of power supply distribution quality.

Nouvelles armes thérapeutiques contre le mélanome de stade IV [New therapeutic weapons in stage IV melanoma].

The treatment of stage IV melanoma has been revolutionized over the last years with the development of immunotherapies that, for the first time, have shown a significant benefit in overall survival, as well as with extremely effective targeted therapies, that also led to improved survival. These results are the fruits of an important translational research effort that allowed a rational approach with a very fast clinical development. The treatment of metastatic melanoma is, therefore, an illustration of the new paradigms of modern molecular research in oncology. In this review, we will present the various agents that have made the proof of their clinical benefit, as well as the scientific discoveries that allowed their development. Some of the remaining questions will be touched upon with the ongoing clinical trials. Inclusion of patients in these studies remains the top priority to improve on the clinical care.

Strategies and tools for preventing neurotoxicity: to test, to predict and how to do it

A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National Research Council (NRC) of the US National Academies of Science, high-throughput in vitro tests will provide evidence for alterations in"toxicity pathways" as the best possible method of large scale toxicity prediction. The challenges to implement this proposal are enormous, and provide much room for debate. While many efforts address the technical aspects of implementing the vision, many questions around it need also to be addressed. Is the overall strategy the only one to be pursued? How can we move from current to future paradigms? Will we ever be able to reliably model for chronic and developmental neurotoxicity in vitro? This paper summarizes four presentations from a symposium held at the International Neurotoxicology Conference held in Xi"an, China, in June 2011. A. Li reviewed the current guidelines for neurotoxicity and developmental neurotoxicity testing, and discussed the major challenges existing to realize the NCR vision for toxicity testing. J. Llorens reviewed the biology of mammalian toxic avoidance in view of present knowledge on the physiology and molecular biology of the chemical senses, taste and smell. This background information supports the hypothesis that relating in vivo toxicity to chemical epitope descriptors that mimic the chemical encoding performed by the olfactory system may provide a way to the long term future of complete in silico toxicity prediction. S. Ceccatelli reviewed the implementation of rodent and human neural stem cells (NSCs) as models for in vitro toxicity testing that measures parameters such as cell proliferation, differentiation and migration. These appear to be sensitive endpoints that can identify substances with developmental neurotoxic potential. C. Sun ol reviewed the use of primary neuronal cultures in testing for neurotoxicity of environmental pollutants, including the study of the effects of persistent exposures and/or in differentiating cells, which allow recording of effects that can be extrapolated to human developmental neurotoxicity.

Data-parallel computation in parallel and distributed environments

The past few decades have seen a considerable increase in the number of parallel and distributed systems. With the development of more complex applications, the need for more powerful systems has emerged and various parallel and distributed environments have been designed and implemented. Each of the environments, including hardware and software, has unique strengths and weaknesses. There is no single parallel environment that can be identified as the best environment for all applications with respect to hardware and software properties. The main goal of this thesis is to provide a novel way of performing data-parallel computation in parallel and distributed environments by utilizing the best characteristics of difference aspects of parallel computing. For the purpose of this thesis, three aspects of parallel computing were identified and studied. First, three parallel environments (shared memory, distributed memory, and a network of workstations) are evaluated to quantify theirsuitability for different parallel applications. Due to the parallel and distributed nature of the environments, networks connecting the processors in these environments were investigated with respect to their performance characteristics. Second, scheduling algorithms are studied in order to make them more efficient and effective. A concept of application-specific information scheduling is introduced. The application- specific information is data about the workload extractedfrom an application, which is provided to a scheduling algorithm. Three scheduling algorithms are enhanced to utilize the application-specific information to further refine their scheduling properties. A more accurate description of the workload is especially important in cases where the workunits are heterogeneous and the parallel environment is heterogeneous and/or non-dedicated. The results obtained show that the additional information regarding the workload has a positive impact on the performance of applications. Third, a programming paradigm for networks of symmetric multiprocessor (SMP) workstations is introduced. The MPIT programming paradigm incorporates the Message Passing Interface (MPI) with threads to provide a methodology to write parallel applications that efficiently utilize the available resources and minimize the overhead. The MPIT allows for communication and computation to overlap by deploying a dedicated thread for communication. Furthermore, the programming paradigm implements an application-specific scheduling algorithm. The scheduling algorithm is executed by the communication thread. Thus, the scheduling does not affect the execution of the parallel application. Performance results achieved from the MPIT show that considerable improvements over conventional MPI applications are achieved.

Building a usable and accessible semantic web interaction platform

Semantic Web applications take off is being slower than expected, at least with respect to “real-world” applications and users. One of the main reasons for this lack of adoption is that most Semantic Web user interfaces are still immature from the usability and accessibility points of view. This is due to the novelty of these technologies, but this also motivates the exploration of alternative interaction paradigms, different from the “traditional” Web or Desktop applications ones. Our proposal is realized in the Rhizomer platform, which explores the possibilities of the object–action interaction paradigm at the Web scale. This paradigm is well suited for heterogeneous resource spaces such as those common in the Semantic Web. Resources, described by metadata, correspond to the objects in the paradigm. Semantic web services, which are dynamically associated to these objects, correspond to the actions. The platform is being put into practice in the context of a research project in order to build an open application for media distribution based on Semantic Web technologies. Moreover, its usability and accessibility have been evaluated in this real setting and compared to similar systems.

Imaging of prolonged BOLD response in the somatosensory cortex of the rat.

Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation. Copyright © 2015 John Wiley & Sons, Ltd.

Genetic consequences of population expansions and contractions in the common hippopotamus (Hippopotamus amphibius) since the Late Pleistocene.

Over the past two decades, an increasing amount of phylogeographic work has substantially improved our understanding of African biogeography, in particular the role played by Pleistocene pluvial-drought cycles on terrestrial vertebrates. However, still little is known on the evolutionary history of semi-aquatic animals, which faced tremendous challenges imposed by unpredictable availability of water resources. In this study, we investigate the Late Pleistocene history of the common hippopotamus (Hippopotamus amphibius), using mitochondrial and nuclear DNA sequence variation and range-wide sampling. We documented a global demographic and spatial expansion approximately 0.1-0.3 Myr ago, most likely associated with an episode of massive drainage overflow. These events presumably enabled a historical continent-wide gene flow among hippopotamus populations, and hence, no clear continental-scale genetic structuring remains. Nevertheless, present-day hippopotamus populations are genetically disconnected, probably as a result of the mid-Holocene aridification and contemporary anthropogenic pressures. This unique pattern contrasts with the biogeographic paradigms established for savannah-adapted ungulate mammals and should be further investigated in other water-associated taxa. Our study has important consequences for the conservation of the hippo, an emblematic but threatened species that requires specific protection to curtail its long-term decline.

Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm

Background Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech. Methods In the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe. Results The LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset. Conclusions The simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.

Bases cerebrales de la atención sostenida y la memoria de trabajo: un estudio de resonancia magnética funcional basado en el Continuous Performance Test

Introducción. Uno de los paradigmas más utilizados en el estudio de la atención es el Continuous Performance Test (CPT). La versión de pares idénticos (CPT-IP) se ha utilizado ampliamente para evaluar los déficits de atención en los trastornos del neurodesarrollo, neurológicos y psiquiátricos. Sin embargo, la localización de la activación cerebral de las redes atencionales varía significativamente según el diseño de resonancia magnética funcional (RMf) usado. Objetivo. Diseñar una tarea para evaluar la atención sostenida y la memoria de trabajo mediante RMf para proporcionar datos de investigación relacionados con la localización y el papel de estas funciones. Sujetos y métodos. El estudio contó con la participación de 40 estudiantes, todos ellos diestros (50%, mujeres; rango: 18-25 años). La tarea de CPT-IP se diseñó como una tarea de bloques, en la que se combinaban los períodos CPT-IP con los de reposo. Resultados. La tarea de CPT-IP utilizada activa una red formada por regiones frontales, parietales y occipitales, y éstas se relacionan con funciones ejecutivas y atencionales. Conclusiones. La tarea de CPT-IP utilizada en nuestro trabajo proporciona datos normativos en adultos sanos para el estudio del sustrato neural de la atención sostenida y la memoria de trabajo. Estos datos podrían ser útiles para evaluar trastornos que cursan con déficits en memoria de trabajo y en atención sostenida.

Kilpailukyvyn kehittäminen yritystenvälisen yhteistyön avulla. Case: Etelä-Karjalan metsäteollisuus ja pk-sektori

Tutkimuksen tarkastelukohteena oli yritystenvälinen yhteistyö ja yritysten kilpailukyvyn kehittäminen Etelä-Karjalan maakunnassa tämän yhteistyön avulla. Tutkimuksessa hyödynnettiin konstruktiivista ja käsiteanalyyttista tutkimusotetta. Päätavoitteena oli selvittää kuinka Etelä-Karjalassa toimivan suuren metsäteollisuuden alihankintojen paikallisuusastetta voitaisiin lisätä tulevaisuudessa. Keskeisinä alatavoitteina tutkimuksessa oli selvittää alueen suuren metsäteollisuuden merkitystä alueen muille toimialoille sekä tutkia mitä yritystenvälisiä yhteistyömuotoja on käytössä tällä hetkellä Etelä-Karjalan maakunnassa. Tutkielma jakaantui teoreettiseen ja empiiriseen osaan. Teoriaosassa muodostettiin viitekehys yritystenvälisen yhteistyön ymmärtämiseksi ja erilaisten yritystenvälisten yhteistyömuotojen jaottelemiseksi. Työn empiirisessä osassa tätä viitekehystä hyödynnettiin kysely- ja haastattelututkimuksen pohjana. Tutkimustulosten joukossa korostui yritystenvälisen yhteistyön merkitys alueen suuryritysten alihankintojen paikallisuusasteen lisäämisessä. Lisäksi yritystenvälisen yhteistyön nähtiin lisäävän yritysten kilpailukykyä varsin laaja-alaisesti tutkimuspopulaation joukossa. Erityisen hyödyllisiksi yritykset näkivät yhteistyömuodot, joissa toiminta perustui pitkäjänteisyyteen ja yhteisen hyödyn tavoitteluun.

Visiosta toimivaksi yritysverkostoksi –verkostoitumisprosessin tutkiminen ja tulevaisuuden toimintamallin rakentaminen Case: Imatran Seudun Koivukeskus

Tutkimuksen tarkoitus oli tutkia, miten case-verkosto Imatran Seudun Koivukeskus on syntynyt ja luoda sille sopiva tulevaisuuden toimintamalli. Tutkimuksessa hyödynnettiin käsiteanalyyttista ja konstruktiivista tutkimusotetta. Tutkimuksen tavoitteita olivat keskeisten käsitteiden määrittely; onnistuneiden ja epäonnistuneiden verkostoitumisesimerkkien kuvaaminen ja analysointi; case-verkoston esittely; case-verkoston historiallinen analyysi, sen toimintamallin tutkiminen ja vertaaminen esimerkkitapauksiin sekä case-verkoston tulevaisuuden kehitysnäkymien analysointi ja sille sopivan toimintamallin muodostaminen. Tutkielma koostui teoreettisesta osasta ja empiirisestä osasta. Teoriaosio käsitteli verkostoitumisen teoriaa. Tämä osio ja suoritetut teemahaastattelut loivat pohjan empiiriselle osuudelle ja toimintamallin muodostamiselle case-yritykselle. Tutkimuksen perusteella kriittisimmiksi case-verkoston tulevaisuuden toimintamallin osa-alueiksi osoittautuivat raaka-aineen saatavuus sekä avoimuus ja tiedonkulku verkostossa. Näiden lisäksi toimintamallissa tulee painottaa alihankinnan ja jatkojalostuksen lisäämistä, tutkimus- ja kehitystoimintaa sekä kuivaustoiminnan osaamistason kehittämistä.

'Freakish Fat', 'Wretched Black': Female abject beings in contemporary Colombian media and culture

This paper explores the construction of female abject beings in Colombian contemporary media and culture comparing a character in the 2010 telenovela Chepe Fortuna named Venezuela, and the cultural representation of Piedad Córdoba. I argue that the construction of these two characters as abject beings is coherent with the dominant discourse of Alvaro Uribe's national project, which relied on a strong nationalist rhetoric based on binary oppositions of the type "we/other." In this context both Chepe Fortuna's Venezuela and Piedad Córdoba are constructed as "other." While Venezuela's abjection is partly effected on the basis of her being fat and black, Córdoba's is on the basis of her being a left-wing politician, and mediated through her being a black female. These two instances evidence an approach to femaleness that goes hand-in-hand with particular understandings of female subjectivity within current post-feminist paradigms.