eLearning in the context of a one-year postgraduate course in macroscopy in pathology: benefits of a multifaceted and pluripotent concept

Performing Macroscopy in Pathology implies to plan and implement methods of selection, description and collection of biological material from human organs and tissues, actively contributing to the clinical pathology analysis by preparing macroscopic report and the collection and identification of fragments, according to the standardized protocols and recognizing the criteria internationally established for determining the prognosis. The Macroscopy in Pathology course is a full year program with theoretical and pratical components taught by Pathologists. It is divided by organ/system surgical pathology into weekly modules and includes a practical "hands-on" component in Pathology Departments. The students are 50 biomedical scientists aged from 22 to 50 years old from all across the country that want to acquire competences in macroscopy. A blended learning strategy was used in order to: give students the opportunity to attend from distance; support the contents, lessons and the interaction with colleagues and teachers; facilitate the formative/summative assessment.

Early programming of the oocyte epigenome temporally controls late prophase I transcription and chromatin remodelling

Oocytes are arrested for long periods of time in the prophase of the first meiotic division (prophase I). As chromosome condensation poses significant constraints to gene expression, the mechanisms regulating transcriptional activity in the prophase I-arrested oocyte are still not entirely understood. We hypothesized that gene expression during the prophase I arrest is primarily epigenetically regulated. Here we comprehensively define the Drosophila female germ line epigenome throughout oogenesis and show that the oocyte has a unique, dynamic and remarkably diversified epigenome characterized by the presence of both euchromatic and heterochromatic marks. We observed that the perturbation of the oocyte's epigenome in early oogenesis, through depletion of the dKDM5 histone demethylase, results in the temporal deregulation of meiotic transcription and affects female fertility. Taken together, our results indicate that the early programming of the oocyte epigenome primes meiotic chromatin for subsequent functions in late prophase I.

Event-Code Interaction Directed Test Cases

The Graphical User Interface (GUI) is an integral component of contemporary computer software. A stable and reliable GUI is necessary for correct functioning of software applications. Comprehensive verification of the GUI is a routine part of most software development life-cycles. The input space of a GUI is typically large, making exhaustive verification difficult. GUI defects are often revealed by exercising parts of the GUI that interact with each other. It is challenging for a verification method to drive the GUI into states that might contain defects. In recent years, model-based methods, that target specific GUI interactions, have been developed. These methods create a formal model of the GUI’s input space from specification of the GUI, visible GUI behaviors and static analysis of the GUI’s program-code. GUIs are typically dynamic in nature, whose user-visible state is guided by underlying program-code and dynamic program-state. This research extends existing model-based GUI testing techniques by modelling interactions between the visible GUI of a GUI-based software and its underlying program-code. The new model is able to, efficiently and effectively, test the GUI in ways that were not possible using existing methods. The thesis is this: Long, useful GUI testcases can be created by examining the interactions between the GUI, of a GUI-based application, and its program-code. To explore this thesis, a model-based GUI testing approach is formulated and evaluated. In this approach, program-code level interactions between GUI event handlers will be examined, modelled and deployed for constructing long GUI testcases. These testcases are able to drive the GUI into states that were not possible using existing models. Implementation and evaluation has been conducted using GUITAR, a fully-automated, open-source GUI testing framework.

Cone penetration testing to assess slope stability in the 1979 Nice landslide area (Ligurian Margin, SE France)

In the landslide-prone area near the Nice international airport, southeastern France, an interdisciplinary approach is applied to develop realistic lithological/geometrical profiles and geotechnical/strength sub-seafloor models. Such models are indispensable for slope stability assessments using limit equilibrium or finite element methods. Regression analyses, based on the undrained shear strength (su) of intact gassy sediments are used to generate a sub-seafloor strength model based on 37 short dynamic and eight long static piezocone penetration tests, and laboratory experiments on one Calypso piston and 10 gravity cores. Significant strength variations were detected when comparing measurements from the shelf and the shelf break, with a significant drop in su to 5.5 kPa being interpreted as a weak zone at a depth between 6.5 and 8.5 m below seafloor (mbsf). Here, a 10% reduction of the in situ total unit weight compared to the surrounding sediments is found to coincide with coarse-grained layers that turn into a weak zone and detachment plane for former and present-day gravitational, retrogressive slide events, as seen in 2D chirp profiles. The combination of high-resolution chirp profiles and comprehensive geotechnical information allows us to compute enhanced 2D finite element slope stability analysis with undrained sediment response compared to previous 2D numerical and 3D limit equilibrium assessments. Those models suggest that significant portions (detachment planes at 20 m or even 55 mbsf) of the Quaternary delta and slope apron deposits may be mobilized. Given that factors of safety are equal or less than 1 when further considering the effect of free gas, a high risk for a landslide event of considerable size off Nice international airport is identified

Hierarchical clustering with multiple-height branch-cut applied to short time-series gene expression data.

Rigid adherence to pre-specified thresholds and static graphical representations can lead to incorrect decisions on merging of clusters. As an alternative to existing automated or semi-automated methods, we developed a visual analytics approach for performing hierarchical clustering analysis of short time-series gene expression data. Dynamic sliders control parameters such as the similarity threshold at which clusters are merged and the level of relative intra-cluster distinctiveness, which can be used to identify "weak-edges" within clusters. An expert user can drill down to further explore the dendrogram and detect nested clusters and outliers. This is done by using the sliders and by pointing and clicking on the representation to cut the branches of the tree in multiple-heights. A prototype of this tool has been developed in collaboration with a small group of biologists for analysing their own datasets. Initial feedback on the tool has been positive.

The role of knowledge management and renewal in building innovation performance

Tämän työn tavoitteena oli selvittää tietojohtamisen eri käytäntöjen vaikutusta oppimiseen, uudistumiseen sekä yrityksen innovaatiokyvykkyyteen. Työssä on keskitytty erityisesti sellaisiin tietojohtamisen käytäntöihin, jotka edistävät oppimista ja uusiutumista yrityksissä. Työssä on käytetty tilastollisia menetelmiä, muun muassa faktorianalyysia, korrelaatioanalyysia sekä regressiota, analysoitaessa 259 suomalaisesta yrityksestä kerättyä kyselydataa niiden tietojohtamisen käytöntöihin ja aineettomaan pääomaan liittyen. Analyysi osoittaa, että useat tietojohtamisen käytännöt vaikuttavat positiivisesti yrityksen uudistumiseen ja sitä kautta innovaatiokyvykkyyteen. Henkilöstön kouluttaminen sekä parhaiden käytäntöjen kerääminen ja soveltaminen yrityksessä ovat positiivisesti yhteydessä innovaatiokyvykkyyteen. Henkilöstön kouluttamisella on merkittävin suora vaikutus innovaatiokyvykkyyteen ja tässä työssä on esitetty, että koulutuksen tarjoamisen suurin vaikutus on oppimismyönteisen kulttuurin kehittyminen yrityksiin sen sijaan, että koulutuksella pyrittäisiin vain parantamaan tehtäväkenttään liittyviä taitoja ja tietoja. Henkilöstön kouluttaminen, parhaat käytännöt sekä sosialisaatiossa tapahtuva tiedon vaihto ja suhteiden solmiminen vaikuttavat positiivisesti uudistumispääomaan. Työn tulosten perusteella uudistumispääomalla on merkittävä rooli innovaatioiden syntymisessä yrityksissä. Uudistumispääoma medioi koulutuksen, parhaiden käytäntöjen ja mahdollisesti myös sosialisaation vaikutusta innovaatiokyvykkyyteen ja on näin merkittävä osa innovaatioiden syntyä yrityksissä. Innovaatiokyvykkyyden osatekijöiden ymmärtäminen voi auttaa johtajia ja esimiehiä keskittämään huomionsa tiettyihin tietojohtamisen käytäntöihin edistääkseen innovaatioiden syntymistä yrityksessä sen sijaan, että he pyrkisivät vain vaikuttamaan innovaatioprosessiin.

Transcriptome, carbohydrate, and phytohormone analysis of Petunia hybrida reveals a complex disturbance of plant functional integrity under mild chilling stress

Cultivation of chilling-tolerant ornamental crops at lower temperature could reduce the energy demands of heated greenhouses. To provide a better understanding of how sub-optimal temperatures (12 degrees C vs. 16 degrees C) affect growth of the sensitive Petunia hybrida cultivar 'SweetSunshine Williams', the transcriptome, carbohydrate metabolism, and phytohormone homeostasis were monitored in aerial plant parts over 4 weeks by use of a microarray, enzymatic assays and GC-MS/MS. The data revealed three consecutive phases of chilling response. The first days were marked by a strong accumulation of sugars, particularly in source leaves, preferential up-regulation of genes in the same tissue and down-regulation of several genes in the shoot apex, especially those involved in the abiotic stress response. The midterm phase featured a partial normalization of carbohydrate levels and gene expression. After 3 weeks of chilling exposure, a new stabilized balance was established. Reduced hexose levels in the shoot apex, reduced ratios of sugar levels between the apex and source leaves and a higher apical sucrose/hexose ratio, associated with decreased activity and expression of cell wall invertase, indicate that prolonged chilling induced sugar accumulation in source leaves at the expense of reduced sugar transport to and reduced sucrose utilization in the shoot. This was associated with reduced levels of indole-3-acetic acid and abscisic acid in the apex and high numbers of differentially, particularly up-regulated genes, especially in the source leaves, including those regulating histones, ethylene action, transcription factors, and a jasmonate-ZIM-domain protein. Transcripts of one Jumonji C domain containing protein and one expansin accumulated in source leaves throughout the chilling period. The results reveal a dynamic and complex disturbance of plant function in response to mild chilling, opening new perspectives for the comparative analysis of differently tolerant cultivars.

A study of ignorance: suffering and freedom in early Buddhist teachings and parallels in modern neuroscience

What might early Buddhist teachings offer neuroscience and how might neuroscience inform contemporary Buddhism? Both early Buddhist teachings and cognitive neuroscience suggest that the conditioning of our cognitive apparatus and brain plays a role in agency that may be either efficacious or non-efficacious. Both consider internal time to play a central role in the efficacy of agency. Buddhism offers an approach that promises to increase the efficacy of agency. This approach is found in five early Buddhist teachings that are re-interpreted here with a view to explaining how they might be understood as a dynamic basis for ‘participatory will’ in the context of existing free will debates and the neuroscientific work of Patrick Haggard (et al.). These perspectives offer Buddhism and neuroscience a basis for informing each other as the shared themes of: (1) cognition is dynamic and complex/aggregate based, (2) being dynamic, cognition lacks a fixed basis of efficacy, and (3) efficacy of cognition may be achieved by an understanding of the concept of dynamic: as harmony and efficiency and by means of Buddha-warranted processes that involve internal time.

Multi-Agent Simulation and Management Practices

Intelligent agents offer a new and exciting way of understanding the world of work. Agent-Based Simulation (ABS), one way of using intelligent agents, carries great potential for progressing our understanding of management practices and how they link to retail performance. We have developed simulation models based on research by a multi-disciplinary team of economists, work psychologists and computer scientists. We will discuss our experiences of implementing these concepts working with a well-known retail department store. There is no doubt that management practices are linked to the performance of an organisation (Reynolds et al., 2005; Wall & Wood, 2005). Best practices have been developed, but when it comes down to the actual application of these guidelines considerable ambiguity remains regarding their effectiveness within particular contexts (Siebers et al., forthcoming a). Most Operational Research (OR) methods can only be used as analysis tools once management practices have been implemented. Often they are not very useful for giving answers to speculative ‘what-if’ questions, particularly when one is interested in the development of the system over time rather than just the state of the system at a certain point in time. Simulation can be used to analyse the operation of dynamic and stochastic systems. ABS is particularly useful when complex interactions between system entities exist, such as autonomous decision making or negotiation. In an ABS model the researcher explicitly describes the decision process of simulated actors at the micro level. Structures emerge at the macro level as a result of the actions of the agents and their interactions with other agents and the environment. We will show how ABS experiments can deal with testing and optimising management practices such as training, empowerment or teamwork. Hence, questions such as “will staff setting their own break times improve performance?” can be investigated.

Introduction to Multi-Agent Simulation

When designing systems that are complex, dynamic and stochastic in nature, simulation is generally recognised as one of the best design support technologies, and a valuable aid in the strategic and tactical decision making process. A simulation model consists of a set of rules that define how a system changes over time, given its current state. Unlike analytical models, a simulation model is not solved but is run and the changes of system states can be observed at any point in time. This provides an insight into system dynamics rather than just predicting the output of a system based on specific inputs. Simulation is not a decision making tool but a decision support tool, allowing better informed decisions to be made. Due to the complexity of the real world, a simulation model can only be an approximation of the target system. The essence of the art of simulation modelling is abstraction and simplification. Only those characteristics that are important for the study and analysis of the target system should be included in the simulation model. The purpose of simulation is either to better understand the operation of a target system, or to make predictions about a target system’s performance. It can be viewed as an artificial white-room which allows one to gain insight but also to test new theories and practices without disrupting the daily routine of the focal organisation. What you can expect to gain from a simulation study is very well summarised by FIRMA (2000). His idea is that if the theory that has been framed about the target system holds, and if this theory has been adequately translated into a computer model this would allow you to answer some of the following questions: · Which kind of behaviour can be expected under arbitrarily given parameter combinations and initial conditions? · Which kind of behaviour will a given target system display in the future? · Which state will the target system reach in the future? The required accuracy of the simulation model very much depends on the type of question one is trying to answer. In order to be able to respond to the first question the simulation model needs to be an explanatory model. This requires less data accuracy. In comparison, the simulation model required to answer the latter two questions has to be predictive in nature and therefore needs highly accurate input data to achieve credible outputs. These predictions involve showing trends, rather than giving precise and absolute predictions of the target system performance. The numerical results of a simulation experiment on their own are most often not very useful and need to be rigorously analysed with statistical methods. These results then need to be considered in the context of the real system and interpreted in a qualitative way to make meaningful recommendations or compile best practice guidelines. One needs a good working knowledge about the behaviour of the real system to be able to fully exploit the understanding gained from simulation experiments. The goal of this chapter is to brace the newcomer to the topic of what we think is a valuable asset to the toolset of analysts and decision makers. We will give you a summary of information we have gathered from the literature and of the experiences that we have made first hand during the last five years, whilst obtaining a better understanding of this exciting technology. We hope that this will help you to avoid some pitfalls that we have unwittingly encountered. Section 2 is an introduction to the different types of simulation used in Operational Research and Management Science with a clear focus on agent-based simulation. In Section 3 we outline the theoretical background of multi-agent systems and their elements to prepare you for Section 4 where we discuss how to develop a multi-agent simulation model. Section 5 outlines a simple example of a multi-agent system. Section 6 provides a collection of resources for further studies and finally in Section 7 we will conclude the chapter with a short summary.

Desenvolvimento de magnetizador para tratamento magnético da água

Dissertação (mestrado)—Universidade de Brasília, Faculdade Gama, Programa de Pós-Graduação em Engenharia Biomédica, 2015.

Exploitation du potentiel sismique des étoiles naines blanches

Le but de cette thèse est d’explorer le potentiel sismique des étoiles naines blanches pulsantes, et en particulier celles à atmosphères riches en hydrogène, les étoiles ZZ Ceti. La technique d’astérosismologie exploite l’information contenue dans les modes normaux de vibration qui peuvent être excités lors de phases particulières de l’évolution d’une étoile. Ces modes modulent le flux émergent de l’étoile pulsante et se manifestent principalement en termes de variations lumineuses multi-périodiques. L’astérosismologie consiste donc à examiner la luminosité d’étoiles pulsantes en fonction du temps, afin d’en extraire les périodes, les amplitudes apparentes, ainsi que les phases relatives des modes de pulsation détectés, en utilisant des méthodes standards de traitement de signal, telles que des techniques de Fourier. L’étape suivante consiste à comparer les périodes de pulsation observées avec des périodes générées par un modèle stellaire en cherchant l’accord optimal avec un modèle physique reconstituant le plus fidèlement possible l’étoile pulsante. Afin d’assurer une recherche optimale dans l’espace des paramètres, il est nécessaire d’avoir de bons modèles physiques, un algorithme d’optimisation de comparaison de périodes efficace, et une puissance de calcul considérable. Les périodes des modes de pulsation de modèles stellaires de naines blanches peuvent être généralement calculées de manière précise et fiable sur la base de la théorie linéaire des pulsations stellaires dans sa version adiabatique. Afin de définir dans son ensemble un modèle statique de naine blanche propre à l’analyse astérosismologique, il est nécessaire de spécifier la gravité de surface, la température effective, ainsi que différents paramètres décrivant la disposition en couche de l’enveloppe. En utilisant parallèlement les informations obtenues de manière indépendante (température effective et gravité de surface) par la méthode spectroscopique, il devient possible de vérifier la validité de la solution obtenue et de restreindre de manière remarquable l’espace des paramètres. L’exercice astérosismologique, s’il est réussi, mène donc à la détermination précise des paramètres de la structure globale de l’étoile pulsante et fournit de l’information unique sur sa structure interne et l’état de sa phase évolutive. On présente dans cette thèse l’analyse complète réussie, de l’extraction des fréquences à la solution sismique, de quatre étoiles naines blanches pulsantes. Il a été possible de déterminer les paramètres structuraux de ces étoiles et de les comparer remarquablement à toutes les contraintes indépendantes disponibles dans la littérature, mais aussi d’inférer sur la dynamique interne et de reconstruire le profil de rotation interne. Dans un premier temps, on analyse le duo d’étoiles ZZ Ceti, GD 165 et Ross 548, afin de comprendre les différences entre leurs propriétés de pulsation, malgré le fait qu’elles soient des étoiles similaires en tout point, spectroscopiquement parlant. L’analyse sismique révèle des structures internes différentes, et dévoile la sensibilité de certains modes de pulsation à la composition interne du noyau de l’étoile. Afin de palier à cette sensibilité, nouvellement découverte, et de rivaliser avec les données de qualité exceptionnelle que nous fournissent les missions spatiales Kepler et Kepler2, on développe une nouvelle paramétrisation des profils chimiques dans le coeur, et on valide la robustesse de notre technique et de nos modèles par de nombreux tests. Avec en main la nouvelle paramétrisation du noyau, on décroche enfin le ”Saint Graal” de l’astérosismologie, en étant capable de reproduire pour la première fois les périodes observées à la précision des observations, dans le cas de l’étude sismique des étoiles KIC 08626021 et de GD 1212.

FAM49 - A novel regulator of the protrusive behaviour and motility of cells

Most eukaryotic cell motility relies on plasma membrane protrusions, which depend on the actin cytoskeleton and its tight regulation. The SCAR/WAVE complex, a pentameric assembly comprising SCAR/WAVE, Nap1, CYFIP/Pir121, Abi and HSPC300, is a key driver of actin-based protrusions such as pseudopods. SCAR/WAVE is thought to activate the Arp2/3 complex, a crucial actin nucleator, after being itself activated by upstream signals such as active Rac1. Despite recent progress on the study of the SCAR/WAVE complex, its regulation is still incompletely understood, with Nap1’s role being particularly enigmatic. Upon screening for potential Nap1 binding partners in the social amoeba Dictyostelium discoideum – a well established model organism in the study of the actin cytoskeleton and cell motility – we found FAM49, a ~36 kDa protein of unknown function which is highly conserved in Metazoa (animals) and evolutionarily closer species such as D. discoideum. Interestingly, D. discoideum’s FAM49 and its homologs contain a DUF1394 domain, which is also predicted in CYFIP/Pir121 proteins and most likely involved in their direct binding to active Rac1, which in turn contributes to SCAR/WAVE’s activation. FAM49’s unknown role, apparent high degree of conservation and potential connections to SCAR/WAVE and Rac1 persuaded us to start investigating its function and biological relevance in D. discoideum, leading to the work presented in this thesis. Several pieces of our data collectively support a function for FAM49 in modulating the protrusive behaviour, and ultimately motility, of D. discoideum cells, as well as a regulatory link between FAM49 and Rac1. FAM49’s involvement in protrusion regulation was first hinted at by our observation that GFP-tagged FAM49 is enriched in pseudopods. The possibility of a link with Rac1 was then strengthened by two additional observations: first, pseudopodial GFP-FAM49 is substantially co-enriched with active Rac, both showing fairly comparable spatio-temporal accumulation dynamics; second, when dominant-active (G12V) Rac1 is expressed in cells, it triggers the recruitment and persistent accumulation of GFP-FAM49 at the plasma membrane, where both become highly co-enriched. We subsequently determined that fam49 KO cells differ from wild-type cells in the way they protrude and move, as assessed in under-agarose chemotaxis assays. In particular, our data indicate that fam49 KO cells tend to display a lower degree of global protrusive activity, their protrusions extend more slowly and are less discrete, and the cells end up moving at lower speeds and with higher directional persistence. This phenotype was substantially rescued by FAM49 re-expression. While re-expressing FAM49 in fam49 KO cells we generated putative FAM49 overexpressor cells; compared to wild-type cells, they displayed atypically thin pseudopods and what seemed to be an excessively dynamic, and perhaps less coordinated, protrusive behaviour. Additional data in our study suggest that pseudopods made by fam49 KO cells are still driven by SCAR/WAVE, which is clearly not being replaced by WASP (as is now known to be the case in D. discoideum cells lacking a functional SCAR/WAVE complex). Nonetheless, the peculiar dynamics of those pseudopods imply that SCAR/WAVE’s activity is regulated differently when FAM49 is lost, though it remains to be determined how. This thesis is the first report of a dedicated study on FAM49 and lays the foundation for future research on it.

An identification procedure of multi-input Wiener models for the distortion analysis of nonlinear circuits

In this contribution, a system identification procedure of a two-input Wiener model suitable for the analysis of the disturbance behavior of integrated nonlinear circuits is presented. The identified block model is comprised of two linear dynamic and one static nonlinear block, which are determined using an parameterized approach. In order to characterize the linear blocks, an correlation analysis using a white noise input in combination with a model reduction scheme is adopted. After having characterized the linear blocks, from the output spectrum under single tone excitation at each input a linear set of equations will be set up, whose solution gives the coefficients of the nonlinear block. By this data based black box approach, the distortion behavior of a nonlinear circuit under the influence of an interfering signal at an arbitrary input port can be determined. Such an interfering signal can be, for example, an electromagnetic interference signal which conductively couples into the port of consideration. © 2011 Author(s).

The Kinome of Pacific Oyster Crassostrea gigas, Its Expression during Development and in Response to Environmental Factors

Oysters play an important role in estuarine and coastal marine habitats, where the majority of humans live. In these ecosystems, environmental degradation is substantial, and oysters must cope with highly dynamic and stressful environmental constraints during their lives in the intertidal zone. The availability of the genome sequence of the Pacific oyster Crassostrea gigas represents a unique opportunity for a comprehensive assessment of the signal transduction pathways that the species has developed to deal with this unique habitat. We performed an in silico analysis to identify, annotate and classify protein kinases in C. gigas, according to their kinase domain taxonomy classification, and compared with kinome already described in other animal species. The C. gigas kinome consists of 371 protein kinases, making it closely related to the sea urchin kinome, which has 353 protein kinases. The absence of gene redundancy in some groups of the C. gigas kinome may simplify functional studies of protein kinases. Through data mining of transcriptomes in C. gigas, we identified part of the kinome which may be central during development and may play a role in response to various environmental factors. Overall, this work contributes to a better understanding of key sensing pathways that may be central for adaptation to a highly dynamic marine environment.