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TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifier...
The first comprehensive study of medieval changelings and associated attitudes to the health and care of children in the period. The changeling - a monstrous creature swapped for a human child by malevolent powers - is an enduring image in the popular imagination; dubbing a child a changeling is traditionally understood as a way to justify the often-violent rejection of a disabled or ailing infant. Belief in the reality of changelings is famously attested in Stephen of Bourbon's disapproving thirteenth-century account of rites at the shrine of Saint Guinefort the Holy Greyhound, where sick children were brought to be cured. However, the focus on the St. Guinefort rituals has meant some schol...
This edited volume is the first to propose new readings of Italian and transnational female-authored texts through the lens of Trauma Studies. Illuminating a space that has so far been left in the shadows, Trauma Narratives in Italian and Transnational Women’s Writing provides new insights into how the trope of trauma shapes the narrative, temporal and linguistic dimension of these works. The various contributions delineate a landscape of female-authored Italian and transnational trauma narratives and their complex textual negotiation of suffering and pathos, from the twentieth century to the present day. These zones of trauma engender a new aesthetics and a new reading of history and cultural memory as an articulation of female creativity and resistance against a dominant cultural and social order.
There is growing interest in the field of melatonin research regarding its neurobiological mechanisms as well as its repercussions in clinical practice. Melatonin: Therapeutic Value and Neuroprotection explores melatonin’s neuroprotective effects and discusses the therapeutic potential of melatonin and melatonin agonists in treating neurodegenerative diseases and other ailments. Topics include: The basic aspects of melatonin’s physiology, including its production, bioavailability, and metabolism The functional importance of melatonin receptors and their role in mediating the therapeutic effectiveness of melatonin in cancer Melatonin’s effect on the regulation of blood pressure, sleep, ...
Despite being the leading paradigm in computer vision, deep neural networks are inherently limited by the visual and semantic information contained in their training set. In this thesis, we aim to design deep models operating with previously unseen visual domains and semantic concepts. We first describe different solutions for generalizing to new visual domains, applying variants of normalization layers to multiple challenging settings e.g. where new domain data is not available but arrives online or is described by metadata. In the second part, we incorporate new semantic concepts into pretrained deep models. We propose specific solutions for different problems such as multi-task/incremental learning and open-world recognition. Finally, we merge the two challenges: given images of multiple domains and categories, can we recognize unseen concepts in unseen domains? We propose an approach that is the first, promising step, towards solving this problem. Winner of the Competition “Prize for PhD Thesis 2020” arranged by Sapienza University Press.
The LIU program at CERN is of paramount importance at international level. The program foresees a significant upgrade of the LHC injector chain to increase the luminosity of the LHC beam by a factor of ten after 2024, when the HL-LHC era will start. This thesis deals with longitudinal beam dynamics studies for two LHC injectors (PSB and SPS), the main goal being the analysis of beam instabilities in the HL-LHC scenario.
Microtubules are essential cellular constituents of eukaryotes formed by tubulin subunits. This book is a collection of medicinal chemistry research projects that utilizes microtubules as drug targets for human diseases of global health impact. The main chapters (2 – 4) include an in-depth description of different synthetic and biological approaches to characterize the therapeutic potential of novel synthetic molecules for cancer, Alzheimer’s disease, and neglected tropical diseases. This book also includes three short chapters (5 – 7) of additional collaborative projects focused on varied drug discovery topics, including SAR studies of new lead compounds targeting carbonic anhydrase enzymes, FAAH and TRPV1, and novel bioisosteres of the carboxylic acid functional group.
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Some vols. include supplemental journals of "such proceedings of the sessions, as, during the time they were depending, were ordered to be kept secret, and respecting which the injunction of secrecy was afterwards taken off by the order of the House."
The Congressional Record is the official record of the proceedings and debates of the United States Congress. It is published daily when Congress is in session. The Congressional Record began publication in 1873. Debates for sessions prior to 1873 are recorded in The Debates and Proceedings in the Congress of the United States (1789-1824), the Register of Debates in Congress (1824-1837), and the Congressional Globe (1833-1873)