Academic literature on the topic 'Uibm'

A lack of adequate consideration of underwater image enhancement gives room for more research into the field. The global background light has not been adequately addressed amid the presence of backscattering. This paper presents a technique based on pixel differences between global and local patches in scene depth estimation. The pixel variance is based on green and red, green and blue, and red and blue channels besides the absolute mean intensity functions. The global background light is extracted based on a moving average of the impact of suspended light and the brightest pixels within the image color channels. We introduce the block-greedy algorithm in a novel Convolutional Neural Network (CNN) proposed to normalize different color channels’ attenuation ratios and select regions with the lowest variance. We address the discontinuity associated with underwater images by transforming both local and global pixel values. We minimize energy in the proposed CNN via a novel Markov random field to smooth edges and improve the final underwater image features. A comparison of the performance of the proposed technique against existing state-of-the-art algorithms using entropy, Underwater Color Image Quality Evaluation (UCIQE), Underwater Image Quality Measure (UIQM), Underwater Image Colorfulness Measure (UICM), and Underwater Image Sharpness Measure (UISM) indicate better performance of the proposed approach in terms of average and consistency. As it concerns to averagely, UICM has higher values in the technique than the reference methods, which explainsits higher color balance. The μ values of UCIQE, UISM, and UICM of the proposed method supersede those of the existing techniques. The proposed noted a percent improvement of 0.4%, 4.8%, 9.7%, 5.1% and 7.2% in entropy, UCIQE, UIQM, UICM and UISM respectively compared to the best existing techniques. Consequently, dehazed images have sharp, colorful, and clear features in most images when compared to those resulting from the existing state-of-the-art methods. Stable σ values explain the consistency in visual analysis in terms of sharpness of color and clarity of features in most of the proposed image results when compared with reference methods. Our own assessment shows that only weakness of the proposed technique is that it only applies to underwater images. Future research could seek to establish edge strengthening without color saturation enhancement.

Vaccine hesitancy as a great health risk is related to trust in healthcare providers’ recommendations and provider-parent interaction. The negative image of doctors and their motives may hinder open communication and trustful relationship. As the role of the internet as a source for health information and emotional support has become significant, social media discussions about health and medicine provide valuable opportunities to observe the formation of critical attitudes towards doctors and medicine. This article examines representations of medical specialists in an Estonian vaccine-critical public Facebook group. On the forum, doctors are depicted as dumb and blind believers who operate in a wrong paradigm and are not able to see the full and accurate picture of “real health”. According to the group rhetoric, doctors’ willingness to help parents and children is limited as they depend on a broader exploitive medical system or Big Pharma. As medical specialists are not trustworthy and do not take any responsibility, parents feel that they must closely control all the actions. The group members believe that it is better not tell the truth to doctors and, if necessary, to threaten them with law enforcement. Many of the forum posts are very emotional, illustrating the heavy burden parents perceive in taking vaccine-related decisions. The ridiculing of medical specialists has an empowering effect on patients to feel more in control. Forum posts emphasize common belonging and shared concerns. Therefore, social media is not only a stage for vaccine information but an active factor contributing to the circulation of meanings and enabling emotional support and community formation.

Massive Open Online Course (MOOC) was one of the initiatives of the Malaysia Ministry of Education to ensure the standard of our national education system was at par with the global education trends. This initiative was documented in Malaysian Education Blueprint 2015 -2025 (Higher Education, Shift No.9: Globalised Online Learning). Universiti Teknologi MARA (UiTM) was among the public universities in Malaysia that were seriously involved in MOOC development. Starting with one MOOC in 2014, four MOOCs in 2015, 16 MOOCs in 2016, UiTM embarked into developing 450 new MOOCs in 2017. To ensure UiTM MOOC had achieved the required standard and quality of Malaysian MOOC, an internal guideline for UiTM MOOC Development (i-Learn Centre, 2016) was constructed. The construction of the guideline was based on the standard provided by the Guidelines of Development and Delivery of Malaysian MOOC (KPT, 2017). Some additional elements required by the administrator of UiTM MOOC were also added. The study was interested to determine whether the MOOCs developed by UiTM lecturers complied with the standard of UiTM MOOC and ultimately the Malaysian MOOC. It was also interested to determine the readiness of UiTM MOOC for credit transfer. To do that, a UiTM MOOC Evaluation Checklist was introduced. The checklist consisted of 45 questions which were constructed based on the guideline on UiTM MOOC Development (i-Learn Centre, 2016) and the Guidelines for Credit Transfer for MOOC (MQA, 2016). The study evaluated two active UiTM MOOCs in terms of adherence to the standard of UiTM MOOC. The findings of the study highlighted areas to be improved and provided suggestions to increase readiness for MOOC credit transfer.

Objective: This study was done to investigate the repeatability measurements in reading rate using the Universiti Teknologi MARA Malay related words (UiTM-Mrw) reading chart and Universiti Teknologi MARA Malay unrelated words (UiTM-Muw) reading chart. Methodology: Thirty normally sighted participants were randomly recruited through randomised sampling (mean age =21.5±1.1 years). Participants were instructed to read aloud, clearly and as quickly as possible at 2 different sessions using two different charts. The two charts were selected at random sequence. A minimum of 7 days interval was used to minimize the learning affect. The time taken to read each chart was recorded and any errors while reading was noted. Reading performance was quantified as reading rate in words per minute (wpm). Results: Comparison of reading rate between session 1 and session 2 was not significantly different (p=0.894, df=1, F=0.018) for UiTM-Mrw reading chart. The reading rate between session 1 and 2 also showed no significant difference (p=0.99, df=1, F=2.811) in UiTM-Muw reading chart. Intra-class correlation coefficient (ICC) showed a good consistency in repeatability for both UiTM-Mrw reading chart and UiTM-Muw reading chart with ICC values of 0.849 and 0.814 respectively. The Bland and Altman plot between measurement of reading rate in session 1 and session 2 showed a good agreement in UiTM-Mrw reading chart and UiTM-Muw reading chart. Conclusion: Both UiTM-Mrw reading chart and UiTM-Mur reading chart showed a good consistency and good agreement in repeated measurement of reading rate.Bangladesh Journal of Medical Science Vol.14(3) 2015 p.236-240

Covid-19 pandemic has hit the world at the end of 2019 and Malaysia is one of the affected countries. The Malaysian government has tried to minimize movement to reduce the spread of this virus. As we all know, the learning and training process is one of the areas affected. All institutions of higher learning and schools had to be closed for the benefit of all. UiTM has also issued operating guidelines during Covid-19. Institute of Leadership Development (ILD) UiTM is a training centre for staff that needs to be managed and given attention. Even in uncertain situations, training for staff needs to be continued. As a solution, ILD UiTM has adopted new practices to continue the functions of this centre. Online training was introduced to further enliven the training to staff. But there are challenges in reaching, adapting, and achieving effectiveness of online training.

The establishment of a Higher Learning Institution (HLI) has posed some positive impacts on the community and industry within its vicinity. Universiti Teknologi MARA (UiTM) Cawangan Perlis has been established for over 40 years. Therefore, with the concern about the effect of UiTM Cawangan Perlis on the local population, there has been some critical questions that have not been addressed. To what degree does the presence of UiTM Cawangan Perlis affect the industry within its vicinity? This study aims to investigate the growth of industrial development in Perlis due to the existence of this HLI. Data was collected using an online survey which was distributed to 198 respondents selected using systematic sampling from the list of active businesses registered with Kangar Municipal Council. Data collected was analysed and compared with the data collected in the same study carried out in 2007. The result of this study has revealed that UiTM Cawangan Perlis existence has contributed to both direct and indirect impact on the industrial growth, particularly in the revenue generation in the form of gross profit and the supply of highly qualified manpower. It is hoped that the result of this study could be used by UiTM to justify the return of the investment made by the government and strategize the plan for UiTM Cawangan Perlis development and sustainability in the future.

This letter compares the footprints on a spectral axis of the main unidentified infrared emission bands (UIBs) with the recombination lines of atomic hydrogen. The comparison shows striking correspondences, suggesting that atomic hydrogen may be involved in the production of UIBs.

Gli accordi di coesistenza sono strumenti molto diffusi per la composizione di controversie attuali o potenziali. Presentano tuttavia ancora molti interrogativi irrisolti. Il lavoro analizza alcune tematiche chiave che hanno interessato o che tuttora interessano gli accordi di coesistenza, considerando in primo luogo il punto di vista dell’ordinamento italiano, facendo anche ricorso alla comparazione con l’esperienza e le soluzioni offerte dagli ordinamenti di altri paesi. Viene in primo luogo analizzato il tema della validità degli accordi di coesistenza: un tempo considerati nulli, sono stati successivamente riconosciuti validi sia dalla dottrina che dalla giurisprudenza, con prospettazioni poi assecondate anche dal legislatore. Viene inoltre analizzato il contenuto tipico degli accordi di coesistenza, con una rassegna delle principali obbligazioni (limitazioni merceologiche, spartizioni territoriali, modifiche all’aspetto grafico o denominativo del segno, etc.), e sono individuati i profili critici sui quali più frequentemente le parti possono trovarsi successivamente a discutere. È infatti noto l’adagio secondo cui gli accordi di coesistenza sarebbero i sistemi più diffusi per risolvere controversie attuali, rinviando la lite a controversie future. Il lavoro approfondisce inoltre il tema della rilevanza degli accordi di coesistenza rispetto ai terzi, e i problemi che possono scaturire dalla qualificazione giuridica degli accordi di coesistenza quali i contratti aventi efficacia meramente obbligatoria, e quindi vincolanti solo per le parti che lo hanno sottoscritto. Infine, viene esaminato l’atteggiamento dell’EUIPO e dell’UIBM rispetto agli accordi di coesistenza, nello specifico nell’ambito delle procedure di opposizione. Nell’ordinamento italiano il tema è ancora pressoché inesplorato, e risulta solo un caso portato all’attenzione dell’UIBM che ha avuto esiti opposti nei due gradi di giudizio davanti alla Divisione di Opposizione e alla Commissione Ricorsi.
Trademark co-existence agreements are very popular tools to avoid/settle trademark disputes. However, many questions concerning these agreements remain unanswered. This thesis explores some of the most relevant issues from an Italian legal standpoint and the solutions offered by other countries. The thesis starts by analysing the issue of the validity of co-existence agreements (they were once considered void, were then accepted as valid by some courts and then finally also by the legislator). The thesis then analyses the typical content of co-existence agreements, with an overview of the main provisions (limitation to products and services, territorial divisions, modifications to the signs, etc.), with a focus on some wording that the parties may have further discussions on. Also examined is the relationship between co-existence agreements and third parties and the issues that can arise from the legal qualification of co-existence agreements as being binding only on the parties to it. The thesis closes with an analysis of the impact of co-existence agreements in opposition proceedings by examining the European and Italian trademark offices’ main caselaw.

Det globala konsultföretaget CGI är leverantör för Sametingets nätverk. Behovet av en förbättrad övervakning på Sametingets nätverk efterfrågades av CGI. Genom att förnya och förbättra övervakningen säkerställs en snabbare felsökning och en högre tillgänglighet. Plattformen som skulle användas för att förverkliga målet heter CA Unified Infrastructure Management (CA UIM).   Eftersom slutprodukten skulle övervaka en skarp miljö så började arbetet med att upprätta en testmiljö där experiment kunde utföras. En liten del av arbetet bestod av att kartlägga det nätverk som skulle övervakas. Det huvudsakliga arbetet gick ut på att lära känna programvaran. UIM bygger på att prober utför insamling av data som sedan transporteras vidare till en gemensam databas för den specifika domänen. Databasen kan i sin tur leverera data till exempelvis dashboards på front-end sidan.  Följande prober har använts i vårt arbete: Net_Connect – Använder ICMP för att bekräfta en enhets tillgänglighet. Interface_Traffic - Övervakar nätverkstrafiken med SNMP-agenter. CDM - Ansvar för övervakningen av CPU, disk och minnesutnyttjande på servrar.   Efter att designen av våra dashboards var färdigställda och övervakningen fungerade så gick vi över till den skarpa miljön och upprättade samma koncept där. Arbetet presenteras sedan för CGI i Kiruna med positiva reaktioner.

Propiamente los resultados que de este trabajo de investigación se habían planteado como hipótesis, resultaron comprobables y es así como la relación que guardan las expectativas educativas y laborales de los alumnos de la UIEM, están en conexión con el propósito de dicha formación intercultural, ya que los alumnos guardan el fiel compromiso de seguir formándose bajo la línea intercultural que su marco social y académico le permitieron establecer, así como emplear en lo laboral dichos conocimientos para beneficio social y personal.
El presente trabajo tiene como propósito dar cuenta de las Expectativas Educativas y Laborales de los alumnos de la UIEM. Esto como resultado de un proceso de formación bajo el cual se desarrolla el alumno que tiene que ver con el ámbito social y cultural en el cual se ha formado desde nacimiento y que de cierta manera le aporta características particulares que lo identifican como perteneciente a un grupo cultural distinto a los demás.
Universidad Autónoma del Estado de México

La marque n’est plus seulement un signe distinctif, elle est devenue un actif incorporel dont la valeur peut dépasser largement celle de tous les autres actifs réunis d’une entreprise. Le secteur des services financiers tunisien a connu plusieurs opérations de fusions-acquisitions. Ces opérations ont donné l’occasion aux entreprises du secteur de changer de noms et de choisir entre un nouveau nom ou maintenir l’ancien ou préserver les noms des entreprises alliées (co-branding). Le but de ce travail est d’étudier l’impact de cette stratégie de co-branding sur l’attitude des consommateurs (aspect affectif, conatif mais surtout cognitif). La marque-entreprise a été considérée dans cette recherche comme étant une représentation sociale. Afin de comprendre l’effet de la stratégie de co-branding sur l’image de marque il s’agit dès lors d’évaluer l’évolution du noyau central et du système périphérique de cette représentation
The trademark is no longer considered as a distinctive sign, rather; it has become an intangible asset whose value can far exceed that of all other combined assets of a company. The Tunisian financial services sector has experienced several processes of mergers and acquisitions. These operations have provided an opportunity for companies in the sector to change names and to choose a new name, to maintain the old one or to keep the names of the allied companies (co-branding). The aim of this work is to study the impact of this strategy of co-branding on consumer attitudes (affective, conative and especially cognitive). The brand company in this research was considered as a social representation. In order to understand the impact of the strategy of co-branding on the brand image, it comes to assess the evolution of the central core and the peripheral system of this representation

Orientador: José Maria Ferreira Jardim da Silveira
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Economia
Made available in DSpace on 2018-08-22T21:54:14Z (GMT). No. of bitstreams: 1 Oliveira_PauloRicardodaSilva_M.pdf: 1949080 bytes, checksum: 79c2935874a90f66b236b1b640335f4c (MD5) Previous issue date: 2012
Resumo: Tendo sua produção comercial iniciada em 1996, os alimentos geneticamente modificados (GM) têm gerado, desde então, uma série de polêmicas que envolvem não só fatores de ordem científica, mas também de ordem econômica, política e social. Este trabalho trata, especificamente, da inserção comercial da soja GM na agricultura e os decorrentes impactos ocorridos na cadeia global de comercialização. Através do Método das Parcelas Constantes (Constant Market Share- CMS), decompõem-se as alterações do market share dos países em efeitos distintos, possibilitando o isolamento do efeito da inovação tecnológica e sua adoção sobre os destinos e as quantidades da soja exportada pelos maiores produtores globais. O estudo revela que, a adoção tecnológica por parte dos produtores, ocorrida em períodos distintos para cada país, e a rejeição comercial por parte de alguns mercados podem explicar de forma consistente grande parte das alterações nas relações comerciais entre produtores e consumidores tradicionais, ocorridas a partir de 1996. Ao contrário do que parte da literatura vem enfatizando sobre o comércio de alimentos GM, as barreiras legais, isto é, as proibições e moratórias de facto não tiveram papel importante nos desdobramentos que sucederam o caso da soja GM. Ademais, o trabalho tece considerações a respeito das tendências mais atuais, analisando como os efeitos sofridos pelo comércio internacional de OGM foram se perpetuando a despeito de mudanças nos padrões de oferta do produto e persistem até dias atuais. Evidências levantadas neste trabalho contribuem para compreensão e, consequentemente, para a formulação de políticas que permeiem a difusão de tecnologias com rejeição de mercado
Abstract: Genetically modified food has been being commercially produced since 1996. There are a number of controversies surrounding GM food that involve not only scientific issues, but economic, political and social ones as well. This thesis primarily discusses the introduction of genetically modified (GM) seeds into agriculture and the impact they have on the modus operandi of the international trade of agricultural commodities. An adapted Constant Market Share is used. This method makes it possible to analyze the increase or decrease in the market share of a country in terms of distinct effects, making it possible to identify the effect of technology adoption, in terms of destination and quantity, on the largest soybean producer's worldwide. The central finding in this thesis is that the technology adopted by producers, which took place at different time periods for each country, and the market rejection in certain countries, consistently explain the changes in the soybean market, in terms of exporters and traditional importers after 1996. Contrary to certain studies on the topic, it is argued that bans and de facto moratoriums on GM-Food importation have played no important role in explaining the case of GM soybeans. Furthermore, the thesis examines more modern trends, analyzing how changes in the international trade of GMOs continued over the years despite recent alterations in the demand and supply pattern. Findings from this thesis contribute to better understanding the diffusion process of technologies with market rejection and consequently to the development of political policies
Mestrado
Desenvolvimento Economico, Espaço e Meio Ambiente
Mestre em Desenvolvimento Econômico

Protein kinase CK2 is an anti-apoptotic, constitutively active and ubiquitous Ser/Thr protein kinase. CK2 phosphorylates hundreds of substrates, characterized by the presence of acidic residues near the Ser/Thr target; its minimal consensus sequence is the motif S/TXXE/D/pS,pY,pT, where X is any amino acid and E/D/pX are acidic residues or previously phosphorylated ones. CK2 stabilizes anti-apoptotic signalling pathways and therefore is regarded as a pro-survival kinase. It is highly expressed in cancer where it sustains abnormal cell growth and survival. Therefore, CK2 represents a promising drug target against which several inhibitory compounds have been developed so far. However, there are now compelling evidences for a critical function of CK2 in neurons and a role in neurodegeneration has been suggested, but never studied in detail. Interestingly, we noticed that the CK2 consensus is superimposable to a sequence inside the ubiquitin interacting motif (UIM) of the neuronal-specific chaperone HSJ1. HSJ1 has a neuroprotective role and controls the folding, misfolding, aggregation and degradation of protein clients, thus maintaining their homeostasis (proteostasis). Consistently, functional mutations in its gene have been associated to neurodegenerative disease (NDs). The project presented in this thesis is based on the working hypothesis that phosphorylation of residues conforming to the CK2 consensus on HSJ1 could affect its functions. HSJ1 belongs to the DNAJ protein family. It is preferentially expressed in neuronal tissues and contains an N-terminal J domain and two UIM domains near the C-terminus. It is codified by the DNAJB2 gene and alternatively spliced to produce two isoforms: HSJ1a and HSJ1b. The former is mainly located in the nuclear and cytosolic compartments, the latter is anchored to the cytosolic face of the endoplasmic reticulum. HSJ1b participates in the endoplasmic reticulum-associated protein degradation (ERAD) system as a folding controller of membrane-associated proteins. HSJ1a cooperates with Hsp70 in binding and delivering ubiquitylated proteins to proteasomal degradation. In particular, it suppresses the deposition of aggregation-prone proteins such as SOD1 (Superoxide Dismutase 1) in amiotrophic lateral sclerosis, polyglutamine expanded huntingtin in Huntington’s disease, ataxin-3 in spinocerebellar ataxias, and promotes the refolding of a Parkin mutant in Parkinson’s disease. Genetic studies have provided further evidences for a role of HSJ1 in neuronal survival, as mutations in DNAJB2 cause distal hereditary motor neuropathy and Charcot-Marie-Tooth type 2. Nevertheless, the biochemical mechanisms by which HSJ1 acts in these pathologies are only partially understood. The results we obtained suggest that CK2 is a prominent HSJ1 phosphorylating kinase. As mentioned above, HSJ1 UIMs display canonical CK2 consensus sites. Therefore, we first performed in vitro phosphorylation experiments on HSJ1a. We expressed the protein in HEK-293T cells and confirmed the phosphorylation of HSJ1 by means of cell loading with [32P]phosphate, followed by the immunoprecipitation of the chaperone. In this assay, the HSJ1 phosphorylation was assessed by autoradiography of the immunoprecipitated protein and the CK2-dependendece by demonstrating its sensitivity to the CK2 inhibitor CX-4945. A mass spectrometry analysis revealed that Ser247, Ser250 and Ser264 are phosphorylated and are inside the second UIM. Then, we produced Serine-to-Alanine mutants of each CK2 target-residue, both in prokaryotic and eukaryotic expression vectors. We performed in vitro kinase assays on recombinant purified proteins or upon their expression in HEK-293T cells and subsequent immunoprecipitation. Collectively, the data demonstrated that Ser250 is the main phospho-site on HSJ1. The Ser264 only marginally contributes to the overall HSJ1 phosphorylation and Ser247 is a hierarchical site. In fact, Ser247 does not fulfil the CK2 minimal consensus sequence, because it does not have an acidic residue in +3 position. However, once Ser250 is phosphorylated the residue becomes acidic and fits the consensus sequence. This implies that a hierarchical phosphorylation can occur in HSJ1, where the previous phosphorylation of Ser250 primes Ser247 for subsequent phosphorylation. Then, we successfully designed and developed a strategy for the production of phospho-specific antibodies against the main Ser247/Ser250 phospho-sites. The signal of he purified antibodies strongly reduced in response to cell treatments with different CK2 specific inhibitors. They were also useful to confirm the phosphorylation of both HSJ1 isoforms, a and b, in cells. We then aimed at investigating the effects of HSJ1a phosphorylation on its functions and in particular on the binding to its ubiquitylated clients. To this purpose, we exploited the transfection of phospho-null and phospho-mimetic mutants into HEK-293T cells. The analysis of the ubiquitylated proteins co-immunoprecipitated with WT or mutated HSJ1a followed. Results showed that HSJ1a is able to bind more ubiquitylated clients when the phosphorylation at its CK2 sites is prevented. Moreover, we also found that these not-phosphorylated forms have enhanced activities in delivering the reporter luciferase protein to proteasomal degradation. We concluded that the phosphorylation of HSJ1a by CK2 impairs its chaperone function. With this study, we disclosed an unanticipated HSJ1/CK2 connection with important implications for the molecular mechanisms of neurodegeneration and hopefully for the development of associated therapies. The HSJ1 co-chaperone function is critical in preventing neurodegeneration and is enhanced by the dephosphorylation of the sites targeted by CK2; therefore, treatments with CK2 inhibitors could be explored in the future as novel therapeutic compounds in NDs. Since we observed that UIMs residues are evolutionary conserved in other proteins and superimposable to the CK2 consensus, with this work we suggest that other UIM-containing proteins could be phosphorylated. Indeed, we already showed that the UIM-containing proteasome subunit S5a is phosphorylated by CK2. Therefore, the CK2/HSJ1 connection could be a paradigmatic example of a broader regulation mechanism able to influence the processing of ubiquitylated proteins. Related Projects Protein kinase CK2 appeared to be a prominent druggable target after the discovery of its deregulated activity in cancer. Cancer cells were demonstrated to be more sensitive to the inhibition of CK2 than their healthy counterparts. This observation promotes the design and testing of several inhibitory molecules some of which are currently patented and/or in clinical trials. However, the use of inhibitors was also of invaluable support in helping understanding the role of CK2 in other pathologies. From the work described in the main project, is now evident that CK2 inhibitors should be indeed considered in a therapeutic perspective for neurodegeneration. Despite the wide use and availability of CK2 inhibitory compounds, the characterization of their mechanism of action and tolerability are still under intensive investigations. Most inhibitors have been designed as competitors for the ATP-binding pocket on protein kinases. However, different strategies have been explored in order to increase the therapeutic efficacy. We designed, developed and characterized two alternative inhibition strategies. A first project concerned the analysis of a chimeric molecule named CK2-MCP, designed to specifically target the consensus recognized by CK2 in its substrates. We showed that CK2-MCP is able to double-hit both substrates and the kinase itself. A second project concerned a different kind of ’double-hit’ strategy addressed by a compound named TDB. It was designed to multitarget both CK2 and Pim-1, another kinase implied in cancer onset and progression. We compared TDB and CX-4945 in term of their ability to inhibit the CK2 activity and to reduce cancer cells viability. Our results, in different treatments times and protocols, revealed that TDB displays a higher persistence of the inhibitory effect on CK2. This peculiarity produced a more pronounced toxicity for cancer cells, despite the superiority of CX-4945 efficacy in vitro. We suggest that the optimization of the cellular persistence of the CK2-inhibitor complex is a crucial aspect that should be considered during the optimization of inhibitory compounds.
La proteinchinasi CK2 è una serina/treonina chinasi espressa ubiquitariamente in tutti i tessuti dove svolge un importante ruolo anti-apoptotico. Questo enzima fosoforila una molteplicità di substrati coinvolti nella proliferazione e sopravvivenza cellulari ed accomunati dalla presenza di un “sito consenso”. Questo sito presenta un residuo di serina (S) o treonina (T) inserito in un intorno di amminoacidi acidi che definiscono il motivo minimo S/TXXE/pS/pY/pT: X rappresenta un generico amminoacido mentre E/D/pX sono residui acidi o fosforilati in precedenza. Elevati livelli di espressione di CK2 sono stati riscontrati in neoplasie dove il suo ruolo anti-apoptotico promuove la proliferazione e l’invasione delle cellule cancerose. Di conseguenza, l’enzima è considerato un importante bersaglio, contro cui sono stati sviluppati negli anni diversi inibitori in grado di ridurne l’attività. Tuttavia, vi sono ormai evidenze del coinvolgimento di CK2 nello sviluppo e funzione neuronali; inoltre, è stato suggerito, ma non studiato nel dettaglio, che il ruolo di CK2 nei neuroni possa avere ripercussioni nella progressione e sviluppo di malattie neurodegenerative. Abbiamo notato che uno dei “sito consenso” riconosciti da CK2 nei suoi substrati, coincide con una sequenza all’interno di un motivo in grado di legare l’ubiquitina (UIM) della proteina HSJ1. HSJ1, espressa prevalentemente in cellule neuronali, agisce da “chaperone molecolare”: controlla l’assemblaggio (folding), disassemblaggio, aggregazione e degradazione delle proteine che riconosce mediante i suoi domini UIM, mantenendo i loro livelli in equilibrio dinamico (proteostasi). Ne consegue che HSJ1 esercita un ruolo neuroprotettore. Infatti, sono state identificate alcune mutazioni a carico del suo gene DNAJB2, ed associate all’insorgenza di alcune malattie neurodegenerative. Inoltre, alcune di queste mutazioni sono in grado di compromettere la funzione neuroprotettiva di HSJ1. Il progetto di questa tesi si pone come obiettivo di dimostrare che la fosforilazione di alcuni residui di HSJ1 da parte di CK2 è in grado di influenzarne la funzione. HSJ1 è una proteina appartenente alla famiglia detta DNAJ cui membri sono accomunati dalla presenza del dominio proteico detto “dominio J”. HSJ1, come detto prima, contiene anche due domini UIM localizzati al C-terminale. Il genoma umano codifica un unico trascritto, poi processato per produrre due isoforme: HSJ1a, espressa nel citosol, ed HSJ1b, ancorata alla faccia esterna del reticolo endoplasmatico. Entrambe le isoforme cooperano con la proteina Hsp70 nel legare e dirigere proteine ubiquitilate al proteasoma per essere degradate. In particolare, HSJ1a promuove la degradazione di proteine prone all’aggregazione. Infatti, il non corretto folding proteico può causarne la deposizione come aggregati intracellulari tossici, detti amiloidi, e considerati come un sintomo indicativo nella diagnosi di molte malattie neurodegenerative. Ad esempio, HSJ1a è tra i mediatori della degradazione della proteina SOD1 (superossido dismutasi 1) coinvolta nella sclerosi laterale amiotrofica, di proteine con tratti poliglutamminici espansi ed associati alla malattia di Huntington, ed infine della proteina ataxina-3, considerata agente eziologico nelle atassie spinocerebellari. Inoltre, HSJ1a coadiuva il folding della proteina parkina coinvolta nell’insorgenza di alcune forme del morbo di Parkinson. Studi di associazione genetica hanno anche dimostrato che alcune mutazioni nel gene DNAJB2 causano neuropatie motorie ereditarie e la malattia di Charcot Marie Tooth - tipo 2. Tuttavia i meccanismi molecolari mediante cui HSJ1 agisce sono stati compresi solo parzialmente. I risultati che abbiamo ottenuto dimostrano che HSJ1 è fosforilata da CK2. Come detto in precedenza, HSJ1 presenta alcuni residui amminoacidici all’interno del suo dominio UIM che sono potenzialmente fosforilabili da CK2. Abbiamo quindi svolto un’analisi in spettrometria di massa della proteina fosforilata che ci ha permesso di identificare i siti riconosciuti da CK2 che sono: i residui di serina alle posizione 247, 250 e 264. Successivamente, abbiamo espresso HSJ1 in cellule mediante vettori di espressioni eucariotici. Questi esperimenti erano atti a dimostrare che HSJ1 è fosforilata anche in cellule da CK2. Infatti, trattamenti in cui l’attività dell’enzima è stata ridotta mediante l’uso dell’inibitore CX-4945, hanno dimostrato che HSJ1 è substrato di CK2. Inoltre, abbiamo operato singole sostituzioni amminoacidiche a carico dei residui serinici riconosciuti dall’enzima che sono stati mutati in residui alaninici. Ciò ha confermato ulteriormente i siti da noi identificati su HSJ1 come fosforilati da CK2, sia in vitro che in cellule. Collettivamente, i dati raccolti confermano che il sito principale di fosforilazione è la serina alla posizione 250. Il residuo alla posizione 264 contribuisce solo marginalmente. La serina 247 invece è definita come un sito gerarchico. Infatti, l’intorno amminoacidico del residuo alla posizione 247 non soddisfa i requisiti minimi per essere definito “sito consenso” per CK2. Ciò può avvenire solo una volta che la serina 250 è fosforilata. Di conseguenza, la serina 247 potrà essere riconosciuta da CK2 grazie al residuo acidico in posizione +3, in questo caso rappresentato dalla serina 250 fosforilata in precedenza. Abbiamo poi ideato e sviluppato una strategia che ci ha permesso di produrre anticorpi in grado di riconoscere in maniera specifica le serine alla posizione 247 e 250, solo nel caso esse siano fosforilate da CK2. Questo strumento è stato utilizzato per confermare che entrambe le isoforme di HSJ1, a e b, sono fosforilate in cellule. Inoltre, abbiamo potuto verificare che la fosforilazione di HSJ1a è sensibile all’inibizione esercitata da un ampio pannello di inibitori specifici di CK2. Abbiamo poi analizzato se la fosforilazione di HSJ1 possa avere un impatto sulla sua funzione di legare proteine ubiquitinate da convogliare al proteasoma per la degradazione. Abbiamo quindi espresso HSJ1 in cellule, nella sua forma originale o mutata nei siti di fosforilazione. Mediante la co-precipitazione della proteina, a cui permangono legati i partner ubiquitilati, abbiamo potuto dimostrare che la fosforilazione dei siti-chiave da noi identificati causa una minor funzionalità del dominio UIM di HSJ1. Al contrario, la prevenzione della fosforilazione aumenta la capacità del dominio UIM di legare proteine ubiquitilate e di trasportarle al proteasoma, come abbiamo verificato nei riguardi della proteina luciferasi. Abbiamo potuto così concludere che la fosforilazione di HSJ1 da parte di CK2 contrasta la sua funzione di “chaperone molecolare”. Questo studio ci ha consentito di dimostrare una nuova connessione tra HSJ1 e CK2, in grado di aiutarci a comprendere meglio i meccanismi molecolari che sottendono l’insorgenza e lo sviluppo delle malattie neurodegenerative. Vi sono inoltre importanti risvolti terapeutici, dal momento che l’uso di inibitori di CK2 potrebbe essere proposto per aumentare la funzionalità di HSJ1. Infine, abbiamo notato che alcuni residui amminoacidici all’interno del motivo UIM sono evolutivamente conservati e coincidono con la “sequenza consenso” minima richiesta per la fosforilazione da parte di CK2. Pertanto consideriamo altamente probabile che altre proteine contenenti domini UIM possano essere substrati di CK2, come dimostriamo in questa tesi anche per la proteina S5a, una subunità del proteasoma. Pertanto, HSJ1 vuole porsi come esempio paradigmatico di una possibile più ampia regolazione da parte di CK2 in grado di influenzare questa via di segnale mediata dall’ubiquitina. Progetti complementari Dalla scoperta del coinvolgimento della proteinchinasi CK2 nel cancro, le cellule neoplastiche si sono rivelate essere più sensibili all’inibizione della sua attività, rispetto alle cellule sane. Questo ha favorito lo sviluppo di molti inibitori alcuni dei quali sono al momento brevettati e/o in trials clinici. Tuttavia, come suggerito dal lavoro principale di questa tesi, queste molecole si sono rivelate utili strumenti per meglio comprendere il ruolo di CK2 in altre patologie (i.e. nelle malattie neurodegenerative) e potrebbero essere presi in considerazione per il loro trattamento. Nonostante l’uso diffuso di inibitori di CK2, la comprensione del loro meccanismo d’azione e tollerabilità non sono stati ancora del tutto chiariti. Molti degli inibitori sviluppati fino ad ora sono ATP-competitivi, quindi in grado di legarsi alla tasca per i nucleotidi in CK2. Tuttavia, si stanno prendendo in considerazione strategie differenti per cercare di aumentarne l’efficacia terapeutica. In progetti complementari all’argomento principale di questa tesi, abbiamo analizzato due strategie di inibizione alternative. La prima ha riguardato lo sviluppo di una molecola chimerica chiamata CK2-MCP. Questa è in grado di legare per complementarietà il “sito consenso” di CK2 nei suoi substrati, impedendo all’enzima di accedervi per fosforilarli. Abbiamo però dimostrato che questa classe di composti è in grado di legare sia i substrati di CK2, come atteso, che l’enzima stesso. Nel secondo progetto complementare, abbiamo invece preso in considerazione un altro tipo di strategia duale, mediante l’uso di un inibitore sviluppato recentemente, detto TDB. Questo composto è in grado di inibire sia CK2 che Pim-1, un’altra proteinchinasi implicata nello sviluppo tumorale. Abbiamo comparato i composti CX-4945 e TDB per la loro capacità di inibire CK2 e di ridurre la vitalità delle cellule cancerose. Differenti tempi e condizioni di trattamento hanno dimostrato la più alta persistenza dell’inibizione di CK2 esercitata dal TDB in cellule, nonostante la superiorità del CX-4945 in vitro. La maggior durata dell’inibizione di CK2, indipendentemente dal fatto che il TDB inibisca anche Pim-1, sembra essere responsabile dei maggiori effetti citotossici indotti dal TDB nelle cellule tumorali. Questo suggerisce che l’ottimizzazione di inibitori di CK2 in cellule debba tenere conto anche di questo parametro.

This thesis is a case study that investigates the attitudes and behaviours of learners of a Preparatory English distance learning course (BEL 100 e-PJJ) offered at the Universiti Teknologi MARA (UiTM), Malaysia, and whether those attitudes and behaviours are influenced by their prior educational experiences and whether cultural factors may also have influence in the attitudes and behaviours of these learners. The research adopts a mixed-method case study design combining quantitative and qualitative approaches to the data collection and analysis. Thematic analysis has been adopted as a tool to analyse the interview data qualitatively. The thematic analyses constructed thematic networks which Attride-Stirling (2001) stressed served as an organizing principle and an illustrative tool in interpreting the analysed interview data. Another major source of data collected for this study was the asynchronous forum discussion transcripts. To match the needs of this study, several categories and examples of Henri’s (1992) framework combined with elements from Garrison, Anderson and Archer (2000) CoI model and Hofstede’s (1991) cultural values tool were adapted in analysing the asynchronous forum discussion transcripts. This was to identify the factors which contributed to the attitude and behaviour of the BEL 100 e-PJJ learners. This study has highlighted that the process of learning and teaching of the UiTM Malay/Bumiputera learners depend on the support and training given to the distance learners and facilitators. Learners’ attitudes, behaviours, facilitators’ intervention and purposeful tasks were found to be important in supporting active participation and effective interaction within the course.

Il presente studio analizza le strategie e le tecniche della comunicazione politica adottate dai leader politici e sindacali per comunicare il temi del lavoro nel contesto italiano. Il framework teorico è ottenuto da una rivisitazione della teoria del framing in chiave neoretorica. Attraverso questa prospettiva la tesi analizza due casi di studio: la comunicazione politica dell’ultima riforma del mercato del lavoro italiano, conosciuta con il nome di Jobs Act,e il caso della comunicazione durante la negoziazione avvenuta attorno al cosiddetto Caso Fiat Pomigliano, nel 2010. Lo studio si occupa inoltre del caso della contrattazione nel settore dell’auto in America svoltasi tra l'estate e l'autunno del 2015. Nelle conclusioni lo studio ipotizza che per la comunicazione dei temi del lavoro, la strategia polemica frequente in comunicazione politica non sia efficace nel costruire un consenso duraturo.
This study analyzes the strategies and techniques of political communication adopted by politicians and union leaders to communicate labor and work in Italy. The theoretical framework is obtained by revisiting the framing theory from the perspective of the new rhetoric. The thesis provides the analysis of two case studies: the political communication of the last reform of the Italian labor market, known as the Jobs Act, and the public communication during the negotiation that took place around the so-called “Fiat Pomigliano” case in 2010. The study also analyzes collective bargaining in the US automotive sector during autumn 2015. The findings suggest that in communicating labor and work, the controversial strategy adopted in political communication may not be considered effective in building a lasting consensus.

Abstract Ubiquitous applications, especially in harsh environments and with strict safety requirements, make Fault Detection and Diagnosis (FDD) in hydraulic actuators an imperative concern for the industry. Model-based FDD uses estimation strategies, including observers and filters as estimation tools. In these methods, observability is a limiting factor in information extraction and parameter estimation for most applications such as in fluid power systems. To address the observability problem, adaptive strategies like Interactive Multiple Model (IMM) estimation have proven to be effective. In this paper a computationally efficient form of IMM referred to as the Updated IMM (UIMM) is used and applied to an Electro-Hydrostatic Actuator (EHA) for FDD. The UIMM is suited to fault conditions that are irreversible, meaning that if a fault happens it will persist in the system. In essence the UIMM follows through a progression of models that in line with the progression of the fault condition in lieu of having all models being considered at the same time (as is the case for IMM). Hence, UIMM significantly reduces the number of models running in parallel and at the same time. This has two major advantages which are higher computational efficiency and avoiding combinatorial explosion. The state and parameters estimation strategies that is used in conjunction with UIMM is the Variable Boundary Layer Smooth Variable Structure Filter (VBL-SVSF). The VBL SVSF is a robust optimal estimation strategy that is more stable than the Kalman Filter in relation to system and modeling uncertainties. The UIMM method is validated by simulation of fault conditions on an EHA.

Les déchets renferment de grandes quantités d’énergie aussi bien directe qu’indirecte. Les déchets ménagers incinérés chaque année en Suisse représentent une valeur énergétique de quelque 60 pétajoules. L’énergie qui en est directement tirée couvre environ 4 % des besoins en énergie finale. Le plus gros potentiel en matière de gestion des déchets réside cependant dans le recyclage des matériaux, afin de leur donner une seconde vie et d’éviter ainsi indirectement la production énergivore de matières premières Pour optimiser la contribution de la gestion des déchets à la transition énergétique, il s’agit dans un premier temps d’améliorer la transparence et la documentation des flux de matières et d’argent et, sur cette base, de hiérarchiser l’impact énergétique des diverses solutions de valorisation et d’élimination. Les catégories de déchets identifiées comme ayant le plus grand potentiel d’amélioration sont le papier, le carton ainsi que le plastique. En ce qui concerne le papier et le carton, les énormes quantités traitées promettent des résultats significatifs. À l’exception des bouteilles en PET, le tri sélectif des plastiques usagés demeure encore peu développé. Un potentiel d’optimisation notable a également été identifié au niveau de l’efficacité énergétique des usines d’incinération. Pour permettre une utilisation plus efficace de la chaleur générée par les usines d’incinération d’ordures ménagère (UIOM), les consommateurs de vapeur et d’énergie thermique doivent toutefois être implantés à proximité. Un facteur décisif pour progresser vers une gestion des déchets plus efficace sur le plan énergétique est la collaboration entre les nombreux acteurs du secteur à l’échelle fédérale. Ceux-ci doivent d’une part mieux s’organiser tout au long de la chaîne de création de valeur et d’autre part tirer profit de la marge de manœuvre que procure la souplesse du fédéralisme pour tester différentes approches.