Compositional evolution with mass transfer in closed systems

Evolution of compositions in time, space, temperature or other covariates is frequentin practice. For instance, the radioactive decomposition of a sample changes its composition with time. Some of the involved isotopes decompose into other isotopes of thesample, thus producing a transfer of mass from some components to other ones, butpreserving the total mass present in the system. This evolution is traditionally modelledas a system of ordinary di erential equations of the mass of each component. However,this kind of evolution can be decomposed into a compositional change, expressed interms of simplicial derivatives, and a mass evolution (constant in this example). A rst result is that the simplicial system of di erential equations is non-linear, despiteof some subcompositions behaving linearly.The goal is to study the characteristics of such simplicial systems of di erential equa-tions such as linearity and stability. This is performed extracting the compositional differential equations from the mass equations. Then, simplicial derivatives are expressedin coordinates of the simplex, thus reducing the problem to the standard theory ofsystems of di erential equations, including stability. The characterisation of stabilityof these non-linear systems relays on the linearisation of the system of di erential equations at the stationary point, if any. The eigenvelues of the linearised matrix and theassociated behaviour of the orbits are the main tools. For a three component system,these orbits can be plotted both in coordinates of the simplex or in a ternary diagram.A characterisation of processes with transfer of mass in closed systems in terms of stability is thus concluded. Two examples are presented for illustration, one of them is aradioactive decay

LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase.

Intracellular signals elicited by LDLs are likely to play a role in the pathogenesis associated with increased LDL blood levels. We have previously determined that LDL stimulation of human skin fibroblasts, used as a model system for adventitial fibroblasts, activates p38 mitogen-activated protein kinases (MAPKs), followed by IL-8 production and increased wound-healing capacity of the cells. The proximal events triggering these responses had not been characterized, however. Here we show that MAPK kinases MKK3 and MKK6, but not MKK4, are the upstream kinases responsible for the activation of the p38 MAPKs and stimulation of wound closure in response to LDLs. Phosphoinositide 3 kinases (PI3Ks) and Ras have been suggested to participate in lipoprotein-induced MAPK activation. However, specific PI3K inhibitors or expression of a dominant-negative form of Ras failed to blunt LDL-induced p38 MAPK activation. The classical LDL receptor does not participate in LDL signaling, but the contribution of other candidate lipoprotein receptors has not been investigated. Using cells derived from scavenger receptor class B type I (SR-BI) knockout mice or the BLT-1 SR-BI inhibitor, we now show that this receptor is required for LDLs to stimulate p38 MAPKs and to promote wound healing. Identification of MKK3/6 and SR-BI as cellular relays in LDL-mediated p38 activation further defines the signaling events that could participate in LDL-mediated pathophysiological responses.

Study of the proteolytic activity of the paracaspase MALT1 in T cell activation

Summary : Several signalling cascades are initiated through the triggering of the T cell receptor (TCR) by an antigenic peptide expressed at the surface of an antigen presenting cell. These pathways lead to morphological changes controlling T cell adhesiveness and migration to the site of infection, and to the activation of transcription factors that regulate key genes for the proper development of the immune response. Amongst them, the nuclear factor xB (NF-κB) is the subject of intense research since more than twenty years because deregulated NF-κB signalling in lymphocytes can lead to immunodeficiency, autoimmunity or lymphomas. Therefore, the understanding of the molecular mechanisms regulating NF-κB activation is important for the development of new therapeutics aimed at treating various diseases. In T lymphocytes, a complex composed of CARMAI, BCL10 and MALT1 relays signals from TCR proximal events to NF-κB activation. Gene translocations of the BCL10 or MALTI genes or oncogenic mutations affecting CARNA 1 result in constitutive NF-κB activation and are related to the development of certain forms of lymphomas. MALT1 contains acaspase-like domain, but it is unknown whether this domain is proteolytically active. In this study, we found that MALT1 has arginine-directed proteolytic activity. We showed that the proteolytic activity of MALT 1 is key to TCR-induced NF-κB activation and production of interleukin 2. We identified BCL 10 as a MALT 1 substrate, and we showed that its cleavage regulates T cell adhesion to the extracellular matrix protein fibronectin. Furthermore, we identified caspase 10 as another substrate of MALT1. caspase 10 is a close homologue of caspase 8 and is known to be involved in the induction of apoptosis upon Fast or TRAIL stimulation. We showed that caspase 10 is important for TCR-induced NF-κB activation and interleukin 2 production, identifying for the first time a non apoptotic function for caspase 10. These data provide evidence for previously uncharacterized roles of MALT 1 and BCL 10 in the regulation of T cell adhesion and of caspase 10 in the activation of lymphocytes, and allow a better understanding of the molecular mechanisms of T lymphocyte activation. Since the proteolytic activity of MALT1 is essential to T cell activation, it suggests that the targeting of this activity may be relevant for the development of immunomodulatory or anticancer drugs. Résumé : De nombreuses voies de signalisation sont initiées via la stimulation des récepteurs des cellules T (TCR) par un peptide antigénique exprimé à la surface d'une cellule présentatrice d'antigènes. Ces cascades de signalisation produisent des changements morphologiques qui contrôlent l'adhésion des cellules T et leur migration vers le site d'infection. Elles contrôlent également l'activation de facteurs de transcription qui régulent la transcription de gènes importants pour la réponse immunitaire. Parmi ces derniers, le facteur nucléaire KB (NF-κB) joue un rôle essentiel, puisqu'une régulation aberrante de son activité dans les lymphocytes peut causer des immunodéficiences, des maladies autoimmunes ou des lymphomes. C'est pour cela que la compréhension des mécanismes moléculaires qui contrôlent l'activation de NF-κB est donc importante pour le développement de nouvelles thérapies. Un complexe contenant les protéines CAIZMAI, BCL10 et MALT1 transmet, dans les lymphocytes T, le signal du TCR vers l'activation de NF-κB. Des translocations des gènes qui codent pour BCL10 et MALTI et des mutations affectant la fonction de CARNAI ont été liées au développement de certaines formes de lymphomes. MALTI contient un domaine qui ressemble au domaine catalytique présent dans les caspases, mais il n'est pas connu si ce domaine a une activité protéolytique. Dans cette étude, nous avons découvert que MALTI est une protéase qui a une spécificité pour les acides aminés basiques comme l'arginine. Nous montrons que l'activité protéolytique de MALTI est importante pour l'activation de NF-κB et la production d'interleukine 2 après stimulation du TCR. Nous avons observé que BCL10 est clivé par MALTI pendant l'activation des lymphocytes T, et que ce clivage est impliqué dans la régulation de l'adhésion des lymphocytes T à la fibronectin, une protéine de la matrice extracellulaire. De plus, nous avons identifié que la caspase 10, qui a une grande homologie avec la caspase 8 et qui jusqu'à maintenant est connue pour son rôle dans l'induction de la mort cellulaire en réponse à une stimulation par Fast ou par TRAIL, est également un substrat de MALT 1. En montrant que la caspase 10 est nécessaire à l' activation de NF-icB et à la production de l'interleukine 2 après stimulation du TCR, nous décrivons pour la première fois une fonction non apoptotique de la caspase 10. Ces résultats décrivent de nouveaux rôles pour MALT1 et BCL10 dans le contrôle de l'adhésion des lymphocytes T et de la caspase 10 pour l'activation des lymphocytes T. Puisque l'activité protéolytique de MALT1 est essentielle pour l'activation des lymphocytes T, nous suggérons que cibler cette activité protéolytique de MALT 1 pourrait amener de nouvelles possibilités de traitement de maladies où une activation aberrante des lymphocytes est impliquée.

Distribution of neuronal and metabolic markers in the human auditory cortex

SUMMARY The human auditory cortex, located on the supratemporal plane of the temporal lobe, is divided in a primary auditory area and several non-primary areas surrounding it. These different areas show anatomical and functional differences. Many studies have focussed on auditory areas in non-human primates, using investigation techniques such as electrophysiological recordings, tracing of neural connections, or immunohistochemical and histochemical staining. Some of these studies have suggested parallel and hierarchical organization of the cortical auditory areas as well as subcortical auditory relays. In humans, only few studies have investigated these regions immunohistochemically, but activation and lesion studies speak in favour of parallel and hierarchical organization, very similar to that of non-human primates. Calcium-binding proteins and metabolic markers were used to investigate possible correlates of hierarchical and parallel organization in man. Calcium-binding proteins, parvalbumin, calretinin and calbindin, modulate the concentration of intracellular free calcium ions and were found in distinct subpopulations of GABAergic neurons in non-human primates species. In our study, their distribution showed several differences between auditory areas: the primary auditory area was darkly stained for both parvalbumin and calbindin, and their expression rapidly decreased while moving away from the primary area. This staining pattern suggests a hierarchical organization of the areas, in which the more darkly stained areas could correspond to an earlier integration level and the areas showing light staining may correspond to higher level integration areas. Parallel organization of primary and non-primary auditory areas was suggested by the complementarity, within a given area, between parvalbumin and calbindin expression across layers. To investigate the possible differences in the energetic metabolism of the cortical auditory areas, several metabolic markers were used: cytochrome oxidase and LDH1 were used as oxidative metabolism markers and LDH5 was used as glycolytic metabolism marker. The results obtained show a difference in the expression of enzymes involved in oxidative metabolism between areas. In the primary auditory area the oxidative metabolism markers were maximally expressed in layer IV. In contrast, higher order areas showed maximal staining in supragranular layers. The expression of LDH5 varied in patches, but did not differ between the different hierarchical auditory areas. The distribution of the two LDH enzymes isoforms also provides information about cellular aspects of metabolic organization, since neurons expressed the LDH1 isoform whereas astrocytes express primarily LDH5, but some astrocytes also contained the LDH1 isoform. This cellular distribution pattern supports the hypothesis of the existence of an astrocyte-neuron lactate shuttle, previously suggested in rodent studies, and in particular of lactate transfer from astrocytes, which produce lactate from the glucose obtained from the circulation, to neurons that use lactate as energy substrate. In conclusion, the hypothesis of parallel and hierarchical organization of the auditory areas can be supported by CaBPs, cytochrome oxidase and LDH1 distribution. Moreover, the two LDHs cellular distribution pattern support the hypothesis of an astrocyte-neuron lactate shuttle in human cortex.

Bacterial sensors: synthetic design and application principles

Bacterial reporters are live, genetically engineered cells with promising application in bioanalytics. They contain genetic circuitry to produce a cellular sensing element, which detects the target compound and relays the detection to specific synthesis of so-called reporter proteins (the presence or activity of which is easy to quantify). Bioassays with bacterial reporters are a useful complement to chemical analytics because they measure biological responses rather than total chemical concentrations. Simple bacterial reporter assays may also replace more costly chemical methods as a first line sample analysis technique. Recent promising developments integrate bacterial reporter cells with microsystems to produce bacterial biosensors. This lecture presents an in-depth treatment of the synthetic biological design principles of bacterial reporters, the engineering of which started as simple recombinant DNA puzzles, but has now become a more rational approach of choosing and combining sensing, controlling and reporting DNA 'parts'. Several examples of existing bacterial reporter designs and their genetic circuitry will be illustrated. Besides the design principles, the lecture also focuses on the application principles of bacterial reporter assays. A variety of assay formats will be illustrated, and principles of quantification will be dealt with. In addition to this discussion, substantial reference material is supplied in various Annexes.

Pituusleikkurin turvaväylät ja koneturvallisuus

Turvallisuuteen liittyvän ohjausjärjestelmän tehtävänä on siirtää ja käsitellä turvallisuuskriittistä tietoa. Esimerkiksi anturin (turvalaitteen) havaitessa vaaravyöhykkeelle pyrkivän ihmisen tulee ensimmäisenä tiedon välittyä ohjausjärjestelmään. Ohjausjärjestelmän on muodostettava saapuneen tiedon perusteella käsky tehonohjauselimille. Tehonohjauselimillä säädellään koneen käyttöenergian syöttöä ja sitä kautta on mahdollista pysäyttää koneen liike ennen mahdollisen vahingon sattumista. Perinteiset turvaratkaisut ovat perustuneet pakkotoimintaisiin releisiin ja kahdennuksiin. Tällämenetelmällä on toteutettu varmatoimintaisia turvaratkaisuja, joissa yksittäiset viat ovat paljastuneet. Nykyisin on kuitenkin yhä enemmän tarvetta integroida turvatoiminnot automaatiojärjestelmään ja toteuttaa turvaratkaisut hajautetuillajärjestelmillä. Hajautetut järjestelmät sisältävät osittain ohjelmoitavien järjestelmien etuja ja haittoja, mutta tuovat mukanaan myös uudenlaisia vikoja. Työn tarkoitus oli selvittää, millaisia rajoituksia koneturvallisuus asettaa paperiteollisuuden pituusleikkurien turvallisuuteen liittyville ohjausjärjestelmille, sekä selvittää turvallisuuteen liittyvien järjestelmien rakennetta ja ominaisuuksia. Tässä työssä tutkittiin AS-i, EsaLan ja ProfiSafe turvajärjestelmiä teknisten tietojen perusteella. Tutkitut järjestelmät ovat erilaisia ja soveltuvat tämän vuoksi hieman erilaisiin kohteisiin. Kaikilla näillä järjestelmillä on kuitenkin mahdollista toteuttaa pituusleikkurin turvaväyläjärjestelmässä riittävä turvallisuuden taso koneturvallisuuden näkökulmasta. Tämä edellyttää oikein tehtyä riskianalyysiä ja oikeita suunnittelumenetelmiä. Teknisten tietojen perusteella otettiin testattavaksi AS-i safety at workja EsaLan:in Compact järjestelmät, joille suoritettiin sähkömagneettiseen yhteensopivuuteen (EMC) ja toiminnallisuuteen liittyviä testejä.

Matkapuhelinverkon MAP-protokollatoteutus älyverkkopalveluiden ohjauspisteeseen

Työssä esitellään yleiseurooppalaisen GSM-matkapuhelinjärjestelmän verkkoelementtejä ja perehdytään niiden väliseen standardoituun merkinantoprotokollaan. Lisäksi tarkastellaan protokollan lyhytsanomien välitykseen liittyviä operaatioita ja niissä tapahtunutta kehitystä standardoinnin eri vaiheissa. Tavoitteena oli toteuttaa GSM-matkapuhelinverkon merkinantoprotokollaan perustuva ohjelma, jonka tehtävänä on välittää lyhytsanomia matkapuhelin- ja lyhytsanomakeskuksen välillä. Matkapuhelimeen päättyvän lyhytsanoman välitykseen liittyy lisäksi reititystiedon hakeminen vastaanottajan kotirekisteristä. Toteutuksessa on ohjelmointirajapinta, joka helpottaa matkapuhelinverkon uusien palvelusovellusten kehittämistä. Toteutus testattiin standardoituja testitapauksia soveltaen. Yhdenmukaisuustestauksessa käytettiin apuna merkinantoanalysaattoria. Testauksessa tarkastettiin, että protokolla toimii loogisesti oikein. Suorituskykyä ei ole voitu testata todellisessa testiympäristössä, mutta ohjelmallisesti toteutettujen simulaattoreiden avulla on saatu hyviä tuloksia.

Modernization of protection and control system of HV/MV substation in Russia

This work describes different possibilities of protection and control system improvement of primary distribution substation. The status of condition and main problems of power networks from reliability point of view in Russia are described. This work studies technologies used today in Russia for protection of distribution networks with their disadvantages. Majority of medium voltage networks (6-35 kV) has isolated network point. There is still no any protection available on the market which allows to estimate distance to fault in case of earth fault. The thesis analyses methods of earth fault distance calculation. On the basis of computer simulation the influence of various factors on calculation accuracy is studied. The practical implementation of the method presupposes usage of digital relay. Application of digital relay is accompanied by numerous opportunities which are described in this work. Also advantages of system implemented on the basis of IEC 61850 standard are examined. Finally, suitability of modern digital relays from GOST standard point of view is analyzed.

La fabrique des urbanistes : une identité professionnelle controversée ?

Ce texte de débat s'intéresse à l'identité professionnelle des urbanistes à un moment singulier de l'histoire de la discipline, celui de l'avènement d'une nouvelle professionnalité dans le champ de la pratique. Les auteurs cherchent à comprendre, dans un contexte caractérisé par 1) une mutation des institutions et outils de la production urbaine ; 2) une refondation des cursus susceptibles de conduire au titre d'urbaniste, comment les acteurs historiques de la profession s'organisent pour défendre une conception de la pratique professionnelle conforme à leur cursus de formation - singulièrement axée sur le projet, considéré notamment comme un art de la représentation graphique. La discussion porte sur la République et canton de Genève en Suisse, laboratoire d'une flexibilisation de l'urbanisme, dont l'Institut d'architecture a récemment été fermé, laissant le champ aux spécialistes des sciences sociales de l'aménagement en matière de formation des professionnels de la fabrique des territoires urbains. Les auteurs montrent comment un discours sur la déprofessionnalisation a été créé, principalement par des acteurs individuels et peu relayés par les associations professionnelles, qui vise à protéger la licence (au sens d'Everett Hughes) octroyée aux architectes-urbanistes de faire la ville. Les auteurs mobilisent un matériau recueilli dans le cadre de deux enquêtes, dont l'une en cours, consacrées pour la première aux transformations de métiers de l'urbanisme et, pour la seconde, aux nouvelles filières de formation aux métiers de la fabrique des territoires.

El piano francès dels segles XX i XXI : una breu investigació per al disseny d'un repertori de concert

Aquest projecte pretén estudiar les aportacions de Messiaen, Dutilleux i Boulez en l’escriptura pianística, analitzant-ne la transcendència en el terreny interpretatiu actual. Per tal d’assolir aquest objectiu, es repassa quina ha sigut l’evolució de la tècnica pianística francesa, s’estudia el material i les circumstàncies que originen els respectius catàlegs per a piano i es realitza una comparativa del repertori estudiat en els principals conservatoris superiors de Barcelona, París, Sant Petersburg i Moscou. Aquest anàlisi permet determinar que el conservatori de París potencia les obres de nova creació, mentre que als de Barcelona, Sant Petersburg i Moscou encara s’opta per un estudi convergent al cànon. Com a conseqüència, els autors esmentats es consideren objecte d’estudi essencial a París, mentre que a Barcelona i les urbs russes encara no s’han establert en el pla d’estudis.

e-Business and collaboration: A case study of pulp supply chain

This thesis studies how the case company could digitalize its supply chain and what kind of advantages this would create in the light of supply chain efficiency. The case company manufactures several pulp products that are used for paper, fabrics and packaging products by customers worldwide. The paper and pulp industry has been paying more and more attention to increasing supply chain efficiency with new operating and service models made possible by today’s information technology. The main focus of this study is on the supply chain between the case company and its key customers and the goal is to find ways to make the operations between them as efficient as possible. The study relays heavily on collaboration techniques and digitalization technologies. In addition to a theoretical framework, the study includes several empirical studies that offer real-life examples of how these theories and technologies are applied in operating environments similar to the case company. A plan with strategic and operational levels is created according to the findings of the previous sections to support the case company’s future operations. The plan is based on an RFID-supported collaboration model that aims to advance information sharing between the supply chain partners. The time for an RFID-investment is sought to be very optimal and the benefits of such system to be noteworthy, but challenging to measure in monetary terms.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.

The Streptococcus mutans GlnR protein exhibits an increased affinity for the glnRA operon promoter when bound to GlnK

The control of nitrogen metabolism in pathogenic Gram-positive bacteria has been studied in a variety of species and is involved with the expression of virulence factors. To date, no data have been reported regarding nitrogen metabolism in the odontopathogenic species Streptococcus mutans. GlnR, which controls nitrogen assimilation in the related bacterial species, Bacillus subtilis, was assessed in S. mutans for its DNA and protein binding activity. Electrophoretic mobility shift assay of the S. mutans GlnR protein indicated that GlnR binds to promoter regions of the glnRA and amtB-glnK operons. Cross-linking and pull-down assays demonstrated that GlnR interacts with GlnK, a signal transduction protein that coordinates the regulation of nitrogen metabolism. Upon formation of this stable complex, GlnK enhances the affinity of GlnR for the glnRA operon promoter. These results support an involvement of GlnR in transcriptional regulation of nitrogen metabolism-related genes and indicate that GlnK relays information regarding ammonium availability to GlnR.

Invoice process analysis and development. Case: Power and automation technology company

This master’s thesis studies the case company’s current purchase invoice process and the challenges that are related to it. Like most of other master’s thesis this study consists of both theoretical- and empirical parts. The purpose of this work is to combine theoretical and empirical parts together so that the theoretical part brings value to the empirical case study. The case company’s main business is frequency converters for both low voltage AC & DC drives and medium voltage AC Drives which are used across all industries and applications. The main focus of this study is on the current invoice process modelling. When modelling the existing process with discipline and care, current challenges can be understood better. Empirical study relays heavily on interviews and existing, yet fragmented, data. This, along with own calculations and analysis, creates the foundation for the empirical part of this master’s thesis.

Modulation de l'activité de structures cérébrales sous-corticales par optogénétique

L’optogénétique est une technique prometteuse pour la modulation de l’activité neuronale. Par l’insertion d’une opsine microbienne dans la membrane plasmique de neurones et par son activation photonique, il devient possible de réguler l’activité neuronale avec une grande résolution temporelle et spatiale. Beaucoup de travaux ont été faits pour caractériser et synthétiser de nouvelles opsines. Ainsi, plusieurs variétés d’opsines sont désormais disponibles, chacune présentant des cinétiques et sensibilités à des longueurs d’onde différentes. En effet, il existe des constructions optogénétiques permettant de moduler à la hausse ou à la baisse l’activité neuronale, telles la channelrhodopsine-2 (ChR2) ou la halorhodopsine (NpHR), respectivement. Les promesses de cette technologie incluent le potentiel de stimuler une région restreinte du cerveau, et ce, de façon réversible. Toutefois, peu d’applications en ce sens ont été réalisées, cette technique étant limitée par l’absorption et la diffusion de la lumière dans les tissus. Ce mémoire présente la conception d’une fibre optique illuminant à un angle de 90° à sa sortie, capable de guider la lumière à des structures bien précises dans le système nerveux central. Nous avons conduit des tests in vivo dans le système visuel de souris transgéniques exprimant la ChR2 dans l’ensemble du système nerveux central. Dans le système visuel, les signaux rétiniens sont conduits au corps genouillé latéral (CGL) avant d’être relayés au cortex visuel primaire (V1). Pour valider la capacité de mon montage optogénétique à stimuler spécifiquement une sous-population de neurones, nous avons tiré profit de l’organisation rétinotopique existant dans le système visuel. En stimulant optogénétiquement le CGL et en tournant la fibre optique sur elle-même à l’aide d’un moteur, il devient possible de stimuler séquentiellement différentes portions de cette structure thalamique et conséquemment, différentes représentations du champ visuel. L’activation des projections thalamiques sera enregistrée au niveau de l’aire V1 à l’aide de l’imagerie optique intrinsèque, une technique qui permet d’imager les variations de la concentration d’oxygène et du volume sanguin dans le tissu neuronal, sur une grande surface corticale. Comme l’organisation rétinotopique est maintenue au niveau de l’aire V1, l’espace activé au niveau du cortex révèlera l’étendue spatiale de notre stimulation optogénétique du CGL. Les expériences in vivo démontrèrent qu’en déplaçant la fibre optique dans le CGL, il nous était possible de stimuler différents sous- ensembles de neurones dans cette structure thalamique. En conclusion, cette étude montre notre capacité à développer un système à base de fibre optique capable de stimuler optogénétiquement une population de neurone avec une grande précision spatiale.