68 research outputs found
MyoD-Induced Trans-Differentiation: A Paradigm for Dissecting the Molecular Mechanisms of Cell Commitment, Differentiation and Reprogramming
No full textThe discovery of the skeletal muscle-specific transcription factor MyoD represents a milestone in the field of transcriptional regulation during differentiation and cell-fate reprogramming. MyoD was the first tissue-specific factor found capable of converting non-muscle somatic cells into skeletal muscle cells. A unique feature of MyoD, with respect to other lineage-specific factors able to drive trans-differentiation processes, is its ability to dramatically change the cell fate even when expressed alone. The present review will outline the molecular strategies by which MyoD reprograms the transcriptional regulation of the cell of origin during the myogenic conversion, focusing on the activation and coordination of a complex network of co-factors and epigenetic mechanisms. Some molecular roadblocks, found to restrain MyoD-dependent trans-differentiation, and the possible ways for overcoming these barriers, will also be discussed. Indeed, they are of critical importance not only to expand our knowledge of basic muscle biology but also to improve the generation skeletal muscle cells for translational research
m6A RNA methylation and beyond - the epigenetic machinery and potential treatment options
No full textm6A is emerging as one of the most important RNA modifications because of its involvement in pathological and physiological events. Here, we provide an overview of this epitranscriptomic modification, beginning with a description of the molecular players involved and continuing with a focus on the role of m6A in the maintenance of stemness, induction of the epithelial to mesenchymal transition (EMT), and tumor progression. Finally, we discuss the state of the art regarding the design and validation of inhibitors of m6A writers or erasers to provide a background for future investigations and for the development of specific therapeutics
Next RNA Therapeutics: The Mine of Non-Coding
No full textThe growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond the Central Dogma of Biology, it is clearly known that not all RNAs code for protein products, and they exert a broader repertoire of biological functions. As described in this review, ncRNAs participate in gene expression regulation both at transcriptional and post-transcriptional levels and represent critical elements driving and controlling pathophysiological processes in multicellular organisms. For this reason, in recent years, a great boost was given to ncRNA-based strategies with potential therapeutic abilities, and nowadays, the use of RNA molecules is experimentally validated and actually exploited in clinics to counteract several diseases. In this review, we summarize the principal classes of therapeutic ncRNA molecules that are potentially implied in disease onset and progression, which are already used in clinics or under clinical trials, highlighting the advantages and the need for a targeted therapeutic strategy design. Furthermore, we discuss the benefits and the limits of RNA therapeutics and the ongoing development of delivery strategies to limit the off-target effects and to increase the translational application
Gunnar Garbo as journalist
No full textGunnar Garbo er mest kjent som stortingspolitiker og leder av partiet Venstre under splittelsen av partiet under EF-kampen i 1972. Han levde et liv i offentligheten helt til han døde 92 år gammel i 2016. Artikkelen er basert på nærlesning av avisene han arbeidet i hans 12 år som journalist og avisredaktør. Forfatteren har også hatt tilgang til private brev, dagbøker og notater som er i familiens eie. Forskningsspørsmålet som søkes besvart er: Hva kjennetegnet Garbo som journalist og pressemann? Han kom fra eksil i Stockholm i 1945 og fikk jobb Bergens Tidende (BT). Det var starten på tolv år i journalistikken. Først ni år som journalist i BT, deretter tre år som redaktør i Nidaros i Trondheim. Her ble han helt til han ble valgt inn som stortingsrepresentant for Venstre i 1957. Han hadde skrivegleden med seg fra barnsben av og var inspirert av faren Ingvald som ble skutt av de tyske okkupantene. En linje i hele hans virke som journalist og redaktør var motstand mot krig og opprustning og interesse for internasjonale forhold og utenrikspolitikk. Det er en grunnleggende tese i denne artikkelen at farens skjebne preget hele hans liv og ble et viktig premiss for hans karriere som journalist og politiker der det internasjonale engasjementet står helt sentralt.
Gunnar Garbo is best known as a Norwegian parliamentarian and leader of the Liberal Party during the party’s split during the EEC referendum campaign in 1972. He lived a life in the public eye until he died at the age of 92 in 2016. The article is based on close reading of the newspapers he worked for during his 12 years as a journalist and newspaper editor. The author has also had access to private letters, diaries and notes that are in his family’s possession. The research question that is sought to answer is: What characterised Garbo as a journalist and editor? Garbo returned from exile in Stockholm in 1945 and got a job at Bergens Tidende (BT) where he stayed for nine years, followed by three years as an editor of Nidaros in Trondheim. He remained in this position until he was elected as a parliamentary representative for the Liberal Party in 1957. From childhood he enjoyed writing and was inspired by his father, Ingvald, who was shot by the German occupiers during the Second World War. His career as a journalist and editor was marked by his opposition to war and armaments and his interest in international affairs and foreign policy.publishedVersio
Sistemi di trasmissione ibridi per applicazioni off-highway: le macchine elettriche, la loro alimentazione e il loro controllo. Analisi dei vantaggi competitivi ottenibili attraverso schemi e soluzioni innovative
No full textHybridization and electrification of mobile working machinery are becoming promising areas of research and development for the off-highway industry. In this context, numerical modeling plays a fundamental role in predicting the performance of the vehicle transmission system and in optimizing its operation. A good design of the mechanical and electrical components of a hybrid transmission can be achieved only through an integrated approach.
Regarding the hybrid electric traction, by means of the Ph.D. with high level training apprenticeship contract, I proceeded to the identification and analysis of some schemes in order to develop innovative solutions for the off-highway industry.
I dealt with innovative solutions focusing on the modeling of industrial hybrid electric transmissions and agricultural electric powersplit transmissions. I chose to use AMESim as 1D multi-domain dynamic simulation tool. The results showed that an industrial vehicle equipped with an electric-hydrodynamic hybrid transmission, demonstrates 8% lower fuel consumption than a conventional vehicle. A representative working cycle defined by the author on the basis of the company experience and the data collected in literature was proposed as basis for comparison. Within the agricultural transmissions the electric variator has proved to be more competitive even better than conventional hydrostatic variator for power-split applications.
I went into detail about the design of electrical machines and their related power and control technologies adopted for off-highway hybrid transmission considering also their integration into the mechanical system. This activity, aimed at the design of an electric drive for an industrial application, has allowed me to develop a model of electric motor, taking into account iron and copper losses, to be integrated in the simulation model of the complete vehicle. In this way, the electromagnetic and thermal design aspects were examined, identifying the parameters of optimization and the trade-offs that play a role in the design of a permanent magnet synchronous electric machine and in the development of the control algorithms.
Having identified and quantified the benefits of hybrid solutions compared to conventional designs, thanks to the skills that I have acquired during the training period inside the company, my research has focused on the development of a preliminary design for a hybrid transmission, addressing also constructive aspects: from mechanical design to manufacturing and assembly. This concept will be tested in the research and development department of the company upon completion of the detailed design
Greta Garbo como forma fílmica: cinesias de uma atriz-autora no cinema hollywoodiano
No full textGreta Garbo, considered as the symbol of the star system until the end of the 1940s, played as a professional film actress in over 30 movies, from the pre-sound synchronic cinema to the post-sound synchronic cinema, an integral part of the complex Fordist-Taylorist Hollywood model. Nevertheless, the Garbo myth became an operating model for acting – a class of actors and actresses. Thus, through the methodology of bibliographic review, we seek to identify the the actorial operative kinesias that led her to consolidate herself in the cinematographic canon, in two instances: acting and extrafilmic. To this end, we articulate the notion of kinesias – anthropological movements that are not always ascendant in liminal environments – to actor studies, especially to Patrick McGilligan’s theory of the actor-auteur. Through a critical analysis of bibliographic review, we found that Greta Garbo amalgamated all the notorious and current acting precepts in their temporary context (fascination, dramatic action, photogenic, movie diva, rosticity, embody film and embodiment in acting, verisimilitude, star system through the bias of the persona mister), becoming an actress-author: dictating the forms of films and interfering in the direction of Hollywood power. The industry bounced back, and Garbo never won an Oscar in her acting career.Greta Garbo, considered as the symbol of the star system until the end of the 1940s, played as a professional film actress in over 30 movies, from the pre-sound synchronic cinema to the post-sound synchronic cinema, an integral part of the complex Fordist-Taylorist Hollywood model. Nevertheless, the Garbo myth became an operating model for acting – a class of actors and actresses. Thus, through the methodology of bibliographic review, we seek to identify the the actorial operative kinesias that led her to consolidate herself in the cinematographic canon, in two instances: acting and extrafilmic. To this end, we articulate the notion of kinesias – anthropological movements that are not always ascendant in liminal environments – to actor studies, especially to Patrick McGilligan’s theory of the actor-auteur. Through a critical analysis of bibliographic review, we found that Greta Garbo amalgamated all the notorious and current acting precepts in their temporary context (fascination, dramatic action, photogenic, movie diva, rosticity, embody film and embodiment in acting, verisimilitude, star system through the bias of the persona mister), becoming an actress-author: dictating the forms of films and interfering in the direction of Hollywood power. The industry bounced back, and Garbo never won an Oscar in her acting career.Greta Garbo, considered as the symbol of the star system until the end of the 1940s, played as a professional film actress in over 30 movies, from the pre-sound synchronic cinema to the post-sound synchronic cinema, an integral part of the complex Fordist-Taylorist Hollywood model. Nevertheless, the Garbo myth became an operating model for acting – a class of actors and actresses. Thus, through the methodology of bibliographic review, we seek to identify the the actorial operative kinesias that led her to consolidate herself in the cinematographic canon, in two instances: acting and extrafilmic. To this end, we articulate the notion of kinesias – anthropological movements that are not always ascendant in liminal environments – to actor studies, especially to Patrick McGilligan’s theory of the actor-auteur. Through a critical analysis of bibliographic review, we found that Greta Garbo amalgamated all the notorious and current acting precepts in their temporary context (fascination, dramatic action, photogenic, movie diva, rosticity, embody film and embodiment in acting, verisimilitude, star system through the bias of the persona mister), becoming an actress-author: dictating the forms of films and interfering in the direction of Hollywood power. The industry bounced back, and Garbo never won an Oscar in her acting career.Greta Garbo, considerada como símbolo do sistema de estrelas até o final da década de 1940, atuou como atriz profissional em mais de 30 filmes, desde o cinema pré-sonoro até o cinema pós-sonoro, sendo parte integrante do complexo modelo hollywoodiano Fordista-Taylorista. No entanto, o mito de Garbo se tornou um modelo operacional para atuação entre a atorialidade – a classe de atores e atrizes. Assim, por meio da metodologia de revisão bibliográfica, buscamos identificar as cinesias operacionais da atuação que a levaram a se consolidar no cânone cinematográfico, em duas instâncias: a atuação em si e o contexto extracinematográfico. Para isso, articulamos a noção de cinesias –movimentos antropológicos que nem sempre são ascendentes em ambientes liminares – aos estudos de atores, especialmente à teoria de ator-autor de Patrick McGilligan. Por meio de uma análise crítica da revisão bibliográfica, descobrimos que Greta Garbo amalgamou todos os preceitos atuação em seu contexto temporário (fascinação, ação dramática, fotogenia, diva do cinema, rosticidade, encarnação do filme e incorporação na atuação, verossimilhança, star system por meio do viés da persona misteriosa), tornando-se uma atriz-autora: ditando as formas dos filmes e interferindo na direção do poder em Hollywood. A indústria revidou, e Garbo nunca ganhou um Oscar em sua carreira de atriz
Improving Irony and Stereotype Spreaders Detection using Data Augmentation and Convolutional Neural Network
No full textIn this paper we describe a deep learning model based on a Data Augmentation (DA) layer followed by a Convolutional Neural Network (CNN). The proposed model was developed by our team for the Profiling Irony and Stereotype Spreaders (ISSs) task proposed by the PAN 2022 organizers. As a first step, to classify an author as ISS or not (nISS), we developed a DA layer that expands each sample in the dataset provided. Using this augmented dataset we trained the CNN. Then, to submit our predictions, we apply our DA layer on the samples within the unlabeled test set too. Finally we fed our trained CNN with the augmented test set to generate our final predictions. To develop and test our model we used a 5-fold cross validation on the labelled training set. The proposed model reaches a maximum accuracy of 0.92 and an average accuracy of 0.89 over the five folds. Meanwhile, on the provided test set the proposed model reaches an accuracy of 0.9278
Selenium-Containing Agents Acting on Cancer—A New Hope?
No full textSelenium-containing agents are more and more considered as an innovative potential treatment option for cancer. Light is shed not only on the considerable advancements made in understanding the complex biology and chemistry related to selenium-containing small molecules but also on Se-nanoparticles. Numerous Se-containing agents have been widely investigated in recent years in cancer therapy in relation to tumour development and dissemination, drug delivery, multidrug resistance (MDR) and immune system-related (anti)cancer effects. Despite numerous efforts, Se-agents apart from selenocysteine and selenomethionine have not yet reached clinical trials for cancer therapy. The purpose of this review is to provide a concise critical overview of the current state of the art in the development of highly potent target-specific Se-containing agents
The star as a disruptive force: Greta Garbo and its reception in Spain in the twenties and thirties
No full textEste trabajo estudia de qué manera se construyó la imagen de Greta Garbo en el contexto específico de la
España de los años veinte y treinta, periodo en el cual la prensa cinematográfica conoce un gran impulso con
la aparición de revistas como Popular Film o La Pantalla. La recepción de Garbo se pone en relación con los
debates en torno a la cinematografía nacional, marcados por un rechazo de la españolada y de los estereotipos
femeninos hollywoodienses que convocaban el espectro de Carmen y que Garbo trató de superar por
su negación a interpretar papeles de vampiresa. Se observa así que, a finales de los años veinte, su figura fue
acogida de forma muy positiva y algunos intelectuales la consagraron como «estrella-autora». Se analizan
luego los cambios surgidos a partir de los años treinta, cuando la proclamación de la Segunda República
supuso una mejora de la condición femenina, despertando una crisis de masculinidad que se plasmó en la
cultura cinematográfica y que llevó a unos críticos a reivindicar la superioridad del «director», presentado
como auténtico guardián del genio creador a expensas de la estrella, en adelante combatida y denigrada con
el fin de reafirmar el estatuto de la creación artística como propiedad masculina. Se estudia, en último lugar,
la influencia de Greta Garbo en el público femenino español, lo cual permite entender mejor lo antes descritoThis article studies how Greta Garbo’s star image was built in the specific context of Spain in the twenties
and thirties, a period in which film journals enjoyed a boost in this country thanks to the arrival of magazines
such as Popular Film or La pantalla. Garbo’s reception is connected with the debates on national cinema,
characterized by the rejection of the «españolada» and Hollywood female stereotypes such as vamps that
brought the spectre of Carmen back, stereotypes Garbo had tried to overcome through her rejection of playing
such roles. In the late twenties, her image was positively regarded and some intellectuals described her
as a «star-author». Then I analyse the changes occurred in the thirties, when the proclamation of the Second
Republic meant an improvement of women’s status that triggered a crisis of masculinity. Such crisis can be
traced in cinematographic culture as some journalists claimed the director’s «superiority», now presented as
the authentic custodian of creative genius to the detriment of stars, which were henceforth attacked and denigrated
with the aim of reasserting the status of the artistic creation as a male prerogative. Finally, this paper
focuses on the influence of Greta Garbo on Spanish female spectatorship, which helps to better understand what has been previously describe
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