Ziel dieser Arbeit ist es, die Verwendung von Modellen in schriftlichen Erklärungen optischer Phänomene vor dem Hintergrund eines praxisorientierten Modellbegriffs zu analysieren. Dafür wird ausgehend von einer bereits existierenden Charakterisierung von Modellen ein praxisrelevanter Modellbegriff entwickelt und dargelegt, wie Erklärungen in Bezug auf diesen Begriff zu verstehen sind. Als wesentliches Merkmal von Modellen stellt sich dabei ihre Position als funktionale Vermittler zwischen Ausschnitten von Phänomenen und Theorien heraus. Sprachliche Erklärungen sind demnach sprachliche Darstellungen von Modellen. Zur Untersuchung der Schwierigkeiten Physiklernender in schriftlichen Erklärungen wird ein geeignetes Verfahren zur Analyse der Modellstruktur in den Erklärungen entwickelt. Als geeignete Darstellung dieser Struktur erweisen sich Concept Maps, die hier jedoch noch um eine Kategorienstruktur erweitert werden. Das Verfahren zum Erstellen von kategorienorientierten Concept Maps kann in einer Vorstudie als reliabel und valide gekennzeichnet werden. In einer qualitativen Untersuchung von 64 Erklärungen Physikstudierender und Experten zu Phänomenen der optischen Hebung wird das Verfahren angewendet. Dabei können verschiedene Schwierigkeiten präzise benannt werden. Studierende führen das Phänomen teilweise einzig auf den Begriff der Brechung von Licht zurück, ohne diesen Zusammenhang präzise darzulegen. In einigen Erklärungen werden Begriffe aus nicht relevanten optischen Konzepten eingebunden, es fehlen zentrale Elemente oder Erklärungen zerfallen in Fragmente. Vor allem die Schnittstelle zwischen Phänomen und Theorie zeigt sich besonders fehleranfällig. Kategorienorientierte Concept Maps eignen sich auch, um auf Basis der fehlerbehafteten Erklärungen Vorschläge für konstruktive Interventionen zu entwickeln, die zu einer fachlich angemessenen Erklärung führen. Die Ergebnisse belegen die Notwendigkeit und Fruchtbarkeit eines praxisorientierten Modellbegriffs. / Goal of this thesis is to analyze the use of models in written explanations of optics phenomena, based on a practice-orientated framework on models. Starting from an already existing framework, an authentic model conception will be developed and the notion ‘explanation’ will be integrated in the conception. The position of models as functional mediators between relevant aspects of phenomena and theory turns out to be their core characteristic. Written explanations are linguistic presentations of models. A procedure will be developed directly from the given description of models in order to visualize the structure of written explanations. The result is a modified network visualization based on concept maps with inherent categories. This visualization is called ‘categorized concept map’. In a preliminary study, the procedure can be described as reliable and valid. In a following qualitative investigation of 64 explanations of optics phenomena (‘apparent depth’) by means of light rays, given by university physics students and experts, categorized concept maps are used to identify difficulties in giving appropriate explanations. Students trace back the observed phenomena only to the term of ‘refraction’, instead of precisely describing the interrelation between ray optics and those phenomena. Furthermore, elements of other conceptions (waves, particles) appear in some of the explanations, whereas central elements of ray optics (i.e., the image concept) are missed. The cut point between theory and the real world turns out to be the most fragile part in students models. Categorized concept maps show their strength in making a variety of difficulties visible and also in subsequently giving the opportunity to develop an appropriate explanation. The results show both, the need and the fruitfulness of an authentic model conception.

Platelet-derived growth factor (PDGF) isoforms, which bind to closely related a- and b-tyrosine kinase receptors, induce migration, proliferation, survival and differentiation of mesenchymal cells. They signal by the active receptor attracting Src homology 2 (SH2) domain containing proteins, which subsequently initiate a set of signaling pathways. The aim of this thesis was to elucidate regulatory mechanisms involved in PDGFRb signaling. In the first two projects we investigated the roles in downregulation of PDGFRb of two related adaptor proteins, i.e. ALG-2 interacting protein X (Alix) and His-domain containing protein tyrosine phosphatase (HD-PTP) functions of. We found that Alix and HD-PTP influence ubiquitination of PDGFRb following PDGF stimulation, by affecting the E3 ligase c-Cbl. Alix enhances complex formation between c-Cbl and PDGFRb, increases c-Cbl phosphorylation and decreases its stability. Interestingly, while both HD-PTP and Alix participate in degradation of PDGFRb, only Alix affects receptor internalization. Moreover, we demonstrated that absence of HD-PTP promotes cell proliferation. In conclusion, we suggest that both Alix and HD-PTP are important adaptor proteins in regulation of PDGFRb downregulation, although the observed differences between their actions suggest that Alix and HD-PTP exert their functions via different mechanisms. The third study explored the importance of tyrosine residue 857 in the activation loop of PDGFRb. We report that, in vitro the tyrosine residue 857 to phenylalanine (Y857F) mutant receptor kinase activity is diminished while in vivo it does not affect the phosphorylation of PDGFRb. The phosphorylation pattern of PDGFRb revealed that most sites in the Y857F mutant receptor were phosphorylated similarly as in the wild-type receptor. However, tyrosine residue 771 was found to be hyperphosphorylated in the Y857F mutant receptor. This may be due to defective phosphorylation and activation of SHP-2, since it has been shown to dephosphorylate the receptor at Y771. In addition, activation of the Erk1/2 and Akt pathways was defective downstream of the Y857F mutant receptor. Interestingly, the Y857F mutant receptor was able to mediate cell migration, but not proliferation. The last study investigated a role of the tyrosine kinase Fer in PDGF signaling. We showed that Fer interacted with and was activated by PDGFRb in a ligand-dependent manner. In cells depleted of Fer, receptor phosphorylation was decreased and phosphorylation of Stat3 was abolished, whereas Stat5, Erk1/2 and Akt were activated normally. Colony formation in soft agar was abolished in cells depleted of Fer, but no effect was seen on cell proliferation and migration. Since Stat3 has been shown to be involved in transformation, we speculate that phosphorylation of Stat3 in Fer-depleted cells, affects the ability of cells to form colonies.

Inhalt: Jahresrückblick 1999/2000 MoUSe - ein Werkzeug zur Verwaltung von URZ-Geschäftsvorgängen

Allt sedan traditionsprincipen i början av 1900-talet fick klart fäste i svensk rätt har olika syften angetts för, samt krav uppställts med principen. Syftet torde numera vara stävjandet av borgenärsbedrägliga transaktioner. Vad gäller uppställda krav för erhållandet av borgenärsskydd, synes domstolarna frångått att tillmäta faktisk besittningsövergång och publicitet avgörande betydelse. Även om rättsläget kan betecknas som oklart, torde det avgörande numera vara att en överlåtare avskurits från sin rådighet över den överlåtna egendomen i form av avskuren mottagande- och betalningslegitimation eller förhindrats från att fortsatt bruka egendomen. Om en övergång till avtalsprincipen skulle kunna vara till för- eller nackdel för borgenärskollektivet är inte entydigt eftersom det går att framhålla argument åt båda håll. I förevarande uppsats framhålls dock att det individualiseringskrav som föreslås uppställas för lösöreöverlåtelser vid en övergång till avtalsprincipen, möjligen skulle kunna föranleda ett ökat antal borgenärsbedrägliga transaktioner. Företagshypotekets ställning som säkerhet skulle vidare vid en övergång till avtalsprincipen kunna påverkas negativt, men däremot torde den gränsöverskridande handel som Sverige bedriver inte beröras i någon nämnvärd utsträckning. Uttalanden från representanter för våra nordiska grannländer vad gäller avtalsprincipens tillämpning i deras respektive rättsordningar, bör inte okritiskt godtas som argument för hur en övergång till avtalsprincipen i svensk rätt skulle kunna ta sig uttryck. Däremot föranleder traditionsprincipens redan förändrade innebörd att en eventuell övergång inte nödvändigtvis skulle innebära en omvälvande förändring av rättsläget. Det är först vid en övergång till avtalsprincipen som de utmätningsrättsliga  presumtionsreglerna anses kunna bli av betydelse vid tredje mäns äganderättsanspråk grundade på förvärv. Det torde uppställas höga krav på presumtionens brytande och ur den aspekten bör gäldenärens förmögenhet, vid en övergång till avtalsprincipen, inte minska markant till följd av tredjemansanspråk.

Workshop "Netz- und Service-Infrastrukturen" Darstellung wesentlicher technischer und inhaltlicher Aspekte eines einheitlichen Identitätsmanagements an der UB Chemnitz unter konkreter Beachtung des Lokalsystems LIBERO, das an allen wissenschaftlichen Bibliotheken Sachsens betrieben wird

Argumentieren ist zentraler Bestandteil naturwissenschaftlicher Erkenntnisgewinnung. Dennoch gibt es bisher nur wenige Arbeiten, die untersuchen, wie Lernende auf der Grundlage selbstständig durchgeführter Experimente für bzw. gegen eine eigene Hypothese argumentieren. Vor diesem Hintergrund untersucht diese Arbeit, welchen Einfluss personale Faktoren (u. a. das Fachwissen und das situationale Interesse) und die Art der Lernumgebung (Realexperiment vs. Computersimulation) darauf nehmen, welche Typen von Argumenten verwendet werden. Ferner wird in dieser Arbeit untersucht, inwiefern die Verwendung dieser Argumentkategorien den Lernerfolg beeinflusst. Auf der Basis von Interviewdaten konnten zunächst für die vorgebrachten Argumente beim Wechseln bzw. Beibehalten eigener Hypothesen beim Experimentieren zehn Kategorien identifiziert werden (u. a. „Intuition“, „Expertenwissen“, „Messunsicherheiten“ sowie „Daten als Evidenz“). Zur quantitativen Erfassung wurde dann für die vier o. g. Argumentkategorien ein Likert-skaliertes Instrument entwickelt. Die aufgeführten Fragestellungen wurden schließlich in einer randomisierten Studie mit 938 Schülerinnen und Schülern untersucht. Bei der Untersuchung des Einflusses personaler Faktoren zeigt sich u. a., dass Lernende in einer Argumentation umso eher Daten als Evidenz heranziehen, je höher das fachliche Vorwissen ist. Die Verwendung dieser Argumentkategorie erhöht wiederum die Wahrscheinlichkeit dafür, dass Lernende nach dem Experimentieren eine fachlich adäquate Hypothese aufstellen. Dies impliziert, dass der Umgang mit experimentellen Daten und Beobachtungen im Physikunterricht stärker als bisher berücksichtigt werden muss, z. B. durch eine explizitere Förderung von Fähigkeiten zum Umgang mit experimentellen Daten. Bis auf einen gut erklärbaren Unterschied können grundlegende Unterschiede beim Experimentieren zwischen Gruppen, die mit einem Real- bzw. Computerexperiment gearbeitet haben, nicht belegt werden. / Argumentation from data and evidence evaluation is widely seen as a scientific core practice. One approach to engage students in a meaningful argumentation practice is to provide lab work situations where they can construct hypotheses on the basis of their own prior knowledge and consequently evaluate these hypotheses in light of self-collected data. However, until recently, only little research has analyzed students' argumentation from data. Against this backdrop this research seeks to identify: a) the influences of personal factors (such as content knowledge and situational interest); b) the type of learning environment as a situational factor (real vs. virtual experiment) on the use of different categories of argument (such as Intuition, Appeal to Authority, Measurement Uncertainties (explicit) and Data as Evidence); c) the influence of argumentation on learning outcomes through experimentation in school labs. First, an interview-study was used to identify the different types of arguments used by students. Analyses focused on the nature of justification in argument and revealed ten different categories students use while arguing for or against hypotheses. As a next step, four out of ten categories were operationalized by means of a Likert-scaled instrument to assess the use of different types of argument in a valid and reliable manner. The findings from a randomized study among 938 secondary school students in a lab work setting indicate, among others, that content knowledge is positively related to the use of data as evidence. Again, the use of data as evidence increases the probability of stating a correct hypothesis after conducting the experiment. This implies that the ability to deal with data and measurement uncertainties should be better fostered in physics classes. Besides one explicable difference, no evidence was found, which supports the hypothesis that students' argumentation would differ while working with hands-on materials vs. computer simulations.

<div>The papain-like protease (PLP) domain of nonstructural protein 3 (nsp3) of the coronavirus (CoV) genome promotes viral replication by processing the CoV polyprotein (protease) and also antagonize innate immune responses by deubiquitinating (DUB) and deISGylating (deISG) host substrates. Selectively removing the DUB/deISG activities of PLP while keeping the protease activity intact is a potential strategy for designing a live attenuated virus. However, it is unclear in the literature the precise mechanism by which PLPs support CoV evasion of the innate immune system. Deciphering the substrate specificity of PLPs for host ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) can therefore help in the design of PLP mutants that selectively lack one activity for evaluating the DUB and deISG mechanism in CoV pathogenesis and replication. </div><div> In this dissertation, we investigate the structure and function of the single PLP (PLpro) from beta-CoVs, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), which are dangerous viral pathogens that emerged from a zoonotic source to cause infectious disease in the human population. Additionally, we translate the knowledge gained to the equivalent PLP2 from alpha-CoV porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV), which cause fatal disease in suckling piglets on industrial pork farms and household cats, respectively. The primary objective of this work is to rationally design PLP mutants across beta- and alpha-CoVs to help attenuate CoV infection, as no antiviral or vaccine exist for human CoVs and the efficacy of PEDV vaccines are an ongoing research topic. </div><div><br></div><div>In Chapter 1, different human, animal, and the bat origin CoV strains are introduced. The CoV life-cycle and virion structure are outlined, along with the replicase complex for viral replication. The multidomain nsp3 from alpha- and beta-CoV genomes are also described with a focus on the PLP domain and its proposed cleavage sites of the viral polyprotein. The discovery of the first viral protease DUB and the multiple activities of PLPs are defined, which includes a proposed model of how DUB versus deISG activities may act in the innate immune response. This leads into the therapeutic potential of PLP for an antiviral or live attenuated vaccine, which is followed by the introduction of live attenuated vaccines and the reverse genetics system. Next, proof of concept studies on PLP2 mutants are described and the introduction is concluded by stating the ultimate goal for the design of PLP mutants.</div><div><br></div><div>In Chapter 2, we hypothesize that the flanking ubiquitin-like (Ubl2) domain of MERS-CoV PLpro is not required for its enzymatic function. We characterize the specific activity, kinetics, substrate specificity, and inhibition of the PLpro enzyme with and without the Ubl2 domain and reveal that the Ubl2 domain does not significantly alter PLpro function. We determine the structure of the core PLpro, smallest catalytic unit to 1.9 Å resolution and observed no structural changes compared to the wild-type. Additionally, we demonstrate that a purported MERS-CoV PLpro inhibitor is nonselective in non-reducing conditions and should not be pursed for therapeutic use. We show that the core PLpro enzyme i.e. without the Ubl2 domain is a stable and robust construct for crystallization and is also thermally stable based on thermal melting studies with utility for structure-based drug design. </div><div><br></div><div>In Chapter 3, we shed light on the specificity of SARS-CoV PLpro towards Ub versus ISG15 by characterizing the specific activity and kinetic parameters of SARS-CoV PLpro mutants. In addition, the structure of SARS-CoV PLpro in complex with the C-terminal domain of ISG15 is determined and compared with the Ub-bound structure. Based on the structure and kinetic results, the altered specificities of SARS-CoV PLpro mutants Arg167Glu, Met209Ala, and Gln233Glu are compared with the wild-type. Arg167Glu mutant exhibits DUB hyperactivity and is expected to adopt a more favorable interaction with the Arg42 of Ub. At the same time, ARG167GLU contains a shorter side-chain that hinders interaction with the unique Trp123 of ISG15 for deISG activity compared to the wild-type. These results aid in the development of SARS-CoV PLpro mutants that have directed shifts in substrate specificity for Ub versus ISG15. </div><div><br></div><div>In Chapter 4, the process and antiviral activity of ISGylation is reviewed and how viruses can modulate host-derived versus virus-derived machineries to counteract ISGylation for viral infection. MERS-CoV PLpro is cross-reactive for Ub, but less is known about its specificity towards ISG15. In this study, we determine the structure of MERS-CoV PLpro bound with ISG15 to 2.3 Å resolution and reveal a small hydrophobic pocket of ISG15 that consists of P130 and W123, which differs from Ub hydrophobic patch. We design and determine the kinetic parameters for 13 PLpro mutants and reveal that MERS-CoV PLpro only has a single ubiquitin recognition (SUb1) site. Kinetic studies show that removing the charge of the R1649 greatly enhances DUB/protease activity while mutating in an Arg near R42 of Ub or ISG15 hydrophobic region is detrimental to both DUB/deISG activities. Kinetic experiments and probe-reactivity assays showed that Val1691Arg, Val1691Lys, and His1652Arg mutants are drastically reduced DUB/deISG activities compared to the wild-type. Overall, MERS-CoV PLpro mutants with alter kinetic profiles will be useful for discovery tools and DUB/deISG deficient mutants are great candidates for removing host cell antagonism activity by PLpro for live attenuated vaccines.</div><div><br></div><div>In Chapter 5, the goal is to translate the knowledge gained in Chapters 2-4 on beta-CoVs PLpro and evaluate the substrate specificity of alpha-CoVs FIPV and PEDV PLP2 for mutagenesis experiments. First, we design and purify the core PLP2 enzymes for kinetics. PLP2s are efficient DUBs that prefer Ub to ISG15 in vitro, and this preference is conserved in beta-CoV MHV PLP2 as well as alpha-CoV NL63 PLP2. We determine the structure of alpha-CoV PEDV PLP2 to 1.95 Å resolution and reveal the unique Zn-finger coordinating Cys3-His arrangement of the alpha-CoV genus that differs from past beta-CoV PLP crystal structures. To determine residues of the SUb1 site, we generate a homology model of FIPV PLP2 and overlay our PLP2 structures with MERS-CoV PLpro bound with Ub. In addition, we create electrostatic surface maps across coronaviral PLP subfamilies to evaluate the charge distribution of the SUb1 for the rational design of several FIPV and PEDV PLP2 mutants. We evaluate the turnover of PLP mutants for FRET-based substrates and reveal that His101ArgFIPV and Asn101ArgPEDV are drastically reduced in Ub-AMC activity while their peptide activities are within 2-fold of the wild-type. These mutants show delayed reactivity for Ub probes and no longer cleave Ub-chains displaying isopeptide bonds compared to the wild-type. Results from this study reveal a hot spot in both alpha- and beta-CoVs that can be used to selectively remove DUB activity of PLPs for generating a DUB deficient PLP enzyme. </div><div><br></div><div>In this dissertation, we investigate the substrate specificity of PLPs across alpha- and beta-CoVs and develop a fingerprint for Ub and also shed light on ISG15 recognition. Specifically, hot spots were identified in the SUb1 site of different PLPs, which recognize R42 and hydrophobic Ile44 of Ub. Position 97-98 of PLPs can be used to remove DUB activity by substituting an Arg, but usually effect protease function. Substituting an Arg at position 101 and 136 of coronaviral PLPs serve as the best strategy to remove DUB function while not hindering active site functionality. The DUB/deISG deficient mutants described will be useful for inhibiting the ability of PLPs to function in the innate immune response. Ultimately, this work provides a guide for identifying attenuating mutants in existing CoVs for live attenuated vaccines and also a blueprint for engineering PLPs from new emerging CoVs. </div>

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-29T21:40:50Z No. of bitstreams: 1 CarlosAlbertoNunesMachado_TESE.pdf: 4383936 bytes, checksum: f242b77bd956f24ec3818296ce30b852 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-01T19:53:18Z (GMT) No. of bitstreams: 1 CarlosAlbertoNunesMachado_TESE.pdf: 4383936 bytes, checksum: f242b77bd956f24ec3818296ce30b852 (MD5) / Made available in DSpace on 2016-03-01T19:53:18Z (GMT). No. of bitstreams: 1 CarlosAlbertoNunesMachado_TESE.pdf: 4383936 bytes, checksum: f242b77bd956f24ec3818296ce30b852 (MD5) Previous issue date: 2015-01-29 / A computa??o ub?qua ? um paradigma no qual dispositivos com capacidade de processamento e comunica??o s?o embutidos nos elementos comuns de nossas vidas (casas, carros, m?quinas fotogr?ficas, telefones, escolas, museus, etc), provendo servi?os com um alto grau de mobilidade e transpar?ncia. O desenvolvimento de sistemas ub?quos ? uma tarefa complexa, uma vez que envolve v?rias ?reas da computa??o, como Engenharia de Software, Intelig?ncia Artificial e Sistemas Distribu?dos. Essa tarefa torna-se ainda mais complexa pela aus?ncia de uma arquitetura de refer?ncia para guiar o desenvolvimento de tais sistemas. Arquiteturas de refer?ncia t?m sido usadas para fornecer uma base comum e dar diretrizes para a constru??o de arquiteturas de softwares para diferentes classes de sistemas. Por outro lado, as linguagens de descri??o arquitetural (ADLs) fornecem uma sintaxe para representa??o estrutural dos elementos arquiteturais, suas restri??es e intera??es, permitindo-se expressar modelo arquitetural de sistemas. Atualmente n?o h?, na literatura, ADLs baseadas em arquiteturas de refer?ncia para o dom?nio de computa??o ub?qua. De forma a permitir a modelagem arquitetural de aplica??es ub?quas, esse trabalho tem como objetivo principal especificar UbiACME, uma linguagem de descri??o arquitetural para aplica??es ub?quas, bem como disponibilizar a ferramenta UbiACME Studio, que permitir? arquitetos de software realizar modelagens usando UbiACME. Para esse fim, inicialmente realizamos uma revis?o sistem?tica, de forma a investigar na literatura relacionada com sistemas ub?quos, os elementos comuns a esses sistemas que devem ser considerados no projeto de UbiACME. Al?m disso, com base na revis?o sistem?tica, definimos uma arquitetura de refer?ncia para sistemas ub?quos, RA-Ubi, que ? a base para a defini??o dos elementos necess?rios para a modelagem arquitetural e, portanto, fornece subs?dios para a defini??o dos elementos de UbiACME. Por fim, de forma a validar a linguagem e a ferramenta, apresentamos um experimento controlado onde arquitetos modelam uma aplica??o ub?qua usando UbiACME Studio e comparam com a modelagem da mesma aplica??o em SySML.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-20T21:14:31Z No. of bitstreams: 1 HugoBarrosCamboim_DISSERT.pdf: 2235324 bytes, checksum: ebcb1e19c35ba48ea27d27d8fce0b644 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-23T20:04:37Z (GMT) No. of bitstreams: 1 HugoBarrosCamboim_DISSERT.pdf: 2235324 bytes, checksum: ebcb1e19c35ba48ea27d27d8fce0b644 (MD5) / Made available in DSpace on 2017-02-23T20:04:37Z (GMT). No. of bitstreams: 1 HugoBarrosCamboim_DISSERT.pdf: 2235324 bytes, checksum: ebcb1e19c35ba48ea27d27d8fce0b644 (MD5) Previous issue date: 2015-12-17 / Vigil?ncia Inteligente desempenha um papel fundamental na assist?ncia tecnol?gica em cen?rios de seguran?a p?blica atrav?s de seu potencial em detectar objetos e eventos em tempo real. Essa tecnologia tem atra?do aten??o especial no campo de seguran?a p?blica, particularmente em ambientes veiculares pela habilidade em assistir cen?rios de miss?o cr?tica atrav?s de detec??o autom?tica por v?deo em tempo real(ex. assaltos, sequestros, atos de viol?ncia, etc.). Consequentemente, ? poss?vel permitir que autoridades realizem uma compensa??o entre reativa e pr?-ativa na tomada de a??es, buscando manter sistemas de alertas customizados, realizando um planejamento mais eficiente, e prover melhor qualidade de vida ? sociedade. Al?m disso, a associa??o de recursos de Computa??o em Nuvem ? suscept?vel de proporcionar perspectivas avan?adas para aplica??es de Vigil?ncia Inteligente, em termos de aprovisionamento refor?ado: (i) processamento, para permitir implanta??o de t?cnicas de computa??o inteligente para melhorar a precis?o; (ii) armazenamento, para adotar uma grande variedade de templates; (iii) e, acesso ub?quo para que qualquer dispositivo permane?a conectado em qualquer lugar. A investiga??o realizada neste trabalho ? focada na abordagem de Vigil?ncia Inteligente baseada em Computa??o em Nuvem conduzida para permitir execu??o de aplica??es m?veis baseadas em eventos no dom?nio de seguran?a p?blica. O objetivo ? permitir que aplica??es m?veis otimizadas, as quais explorando um esquema baseado em eventos, possam prover perspectivas de baixo consumo de recursos(energia, CPU e rede) em compra??o ? abordagem reativa cl?ssica. Uma avalia??o ? feita atrav?s de um conjunto de experimentos realizados em um testbed real, os quais demonstram que o trabalho proposto supera o esquema de computa??o m?vel cl?ssico. / Smart video surveillance plays a key role in offering technological assistance in public safety scenarios, due to its potential to allow events and objects to be automatically detected in realtime. The Smart video surveillance technology has attracted special attention in the field of public safety, particularly in vehicular environments by the ability in assisting mission critical scenarios through real-time video processing based automatic detections (e.g., assaults, kidnaps, acts of violence etc.). Hence, it is possible to enable a tradeoff to be made between reactive and pro-active authorities when taking action, seeking to keep customized alert systems, carry out more efficient planning, and thus provide society with a better quality of life. Moreover, the association to Cloud Computing capabilities, is likely to provide advanced perspectives to smart surveillance applications, in terms to provisioning enhanced: (i) processing, to allow for deploying smart computing techniques for improved accuracy; (ii) storage, to adopt a wide variety of templates; (iii), and ubiquitous access, to keep connected everywhere and to any device. The investigation carried in this work focus in deploying a smart surveillance driven cloud-enabled approach to allow for event-based mobile applications in the public safety field. The objective is to allow optimized mobile applications, by which exploiting event-based scheme to provide to low resource consumption (energy, CPU and network usage) perspectives in comparison to the classic reactive approach. The evaluation is carried out in a set of experiments over a real testbed, which demonstrates that the proposal outperforms the classical mobile computing scheme.

En dégradant la majorité des protéines cellulaires, le protéasome se positionne comme un régulateur clé du protéome, vis-à-vis duquel la plupart des tumeurs présentent une forte addiction en raison du débalancement protéique qui les caractérise. Quoique son inhibition se soit avérée être une bonne stratégie anticancer, elle est demeurée limitée aux cancers sanguins. Malheureusement, leur traitement devient tôt ou tard compromis par la résistance cellulaire. Raison pour laquelle l'élucidation du mécanisme de mort en jeu pourrait permettre de mieux cerner cette résistance, ce qui constituerait les fondements pour un traitement plus efficace. L'un des événements les plus spectaculaires et les plus précoces à se manifester dans le cadre de ce traitement, est la déubiquitination massive de l'histone H2A sur la lysine (K) 119. Une corrélation positive plutôt paradoxale entre cet événement, qui est associé à l'expression génique, et la sensibilité cellulaire à l'inhibition du protéasome, a été remarquée. Cela a mené à s'intéresser à sa signification biologique. Des cellules cancéreuses et primaires ont servi de systèmes d'étude protéomique par immunobuvardage et par immunofluorescence, pour analyser l'état de la chromatine et la distribution spatio-temporelle des histones durant l'inhibition du protéasome. Des inhibiteurs chimiques, des ARN interférents et des vecteurs d'expression ont été utilisés à cette fin. Un impressionnant phénomène survenant à la suite de l'inhibition du protéasome a été révélé. En effet, une baisse drastique du niveau d'histones sur la chromatine s'opère simultanément à la déubiquitination de H2A-ub (K119). Le protéasome étant inhibé, celles-ci, et possiblement les histones synthétisées en phase S, subiraient une translocation irréversible dans les nucléoles, et ce avant le déclenchement de l'apoptose. Ce phénomène est reproduit par divers inhibiteurs du protéasome et par siRNA, et il survient autant dans des cellules cancéreuses que primaires, mais pas dans les cellules résistantes, qui ne démontrent d'ailleurs pas de déubiquitination de H2A-ub (K119). Par ailleurs, il a été montré que la surexpression d'histones exogènes mène à leur translocation nucléolaire, et que la combinaison de l'inhibition du protéasome à cette surexpression pourrait être léthale. Quoique majoritairement préliminaires, les résultats révèleraient un surprenant mécanisme de régulation post-traductionnelle des histones endogènes, qui seraient séquestrées dans les nucléoles lorsqu'elles ne sont pas incorporées à la chromatine. En effet, l'inhibition du protéasome occasionne une importante perturbation de la chromatine pendant plusieurs heures. En raison de la cytotoxicité intrinsèque des histones libres et de leur abondance dans les cellules, celles-ci pourraient bien être à l'origine de la mort induite par l'inhibition du protéasome. Enfin, en sa qualité de senseur majeur de stress, le nucléole pourrait bien être le point de départ de la signalisation menant à la mort. / By degrading most of cellular proteins, the proteasome is positioned as a key regulator of the proteome, against which most tumors have a strong addiction, due to the protein imbalance that characterizes them. Although its inhibition has been shown to be a good anticancer strategy, it is still limited to blood cancers. Unfortunately, their treatment sooner or later becomes compromised by cellular resistance. This is why the elucidation of the mechanism of death involved could allow a better understanding of this resistance, which would in turn constitute the basis for a more effective treatment One of the most spectacular and early events to manifest during this treatment is the massive deubiquitylation of histone H2A on lysine (K) 119. A rather paradoxical positive correlation between this event, which is associated with gene expression, and cellular sensitivity to proteasome inhibition, has been noticed. This led to an interest in its biological significance. Cancer and primary cells have been used as systems for proteomic study by immunoblot and immunofluorescence, to analyze chromatin status and the spatio-temporal distribution of histones during proteasome inhibition. Chemical inhibitors, interfering RNAs and expression vectors have been used for this purpose. An impressive phenomenon occurring during the proteasome inhibition has been revealed. Indeed, a drastic drop in histones level on chromatin occurs simultaneously with the deubiquitylation of H2A-ub (K119). The proteasome being inhibited, these, and possibly histones synthesized in S phase, would undergo an irreversible translocation in the nucleoli before the onset of apoptosis. This phenomenon is replicated by various proteasome inhibitors and siRNA, and occurs in both cancer and primary cells, but not in resistant cells, which do not demonstrate deubiquitination of H2A-ub (K119). Furthermore, overexpression of exogenous histones has been shown to lead to their nucleolar translocation, and it is thought that the combination of proteasome inhibition with this overexpression could be lethal. Although mostly preliminary, the results would reveal a surprising mechanism of post-translational regulation of endogenous histones, which would be sequestered in nucleoli when not incorporated into chromatin. Indeed, inhibition of the proteasome causes a significant disruption of the chromatin for several hours. Due to the intrinsic cytotoxicity of free histones and to their great cellular abundance, these may well be the cause of the death induced by proteasome inhibition. Finally, as a major stress sensor, the nucleolus could be the starting point of the death signaling.