The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

The effects of cultural distance and international experience on CEO departure in cross border acquisitions

LAUREA MAGISTRALEIn meno di venti anni, il numero di acquisizioni cross-border, ossia acquisizioni tra imprese i cui rispettivi quartier generali hanno sede in diversi paesi, è più che triplicato. Questa tesi cerca di capire l’impatto che la distanza culturale e l’esperienza internazionale degli amministratori delegati hanno in queste acquisizioni e, in particolare, i loro effetti sulla decisione dell’impresa acquirente di mantenere o meno l'amministratore delegato dell’impresa acquisita. Abbiamo studiato 197 acquisizioni di piccole imprese operanti in settori ad alta tecnologia in cui le conoscenze tacite, le caratteristiche e le capacità del management e dei dirigenti sono un’importante fonte di vantaggio competitivo e in cui il fatto che l’amministratore delegato dell’impresa acquisita lasci il suo incarico può portare al fallimento dell’acquisizione. Basandoci sulla letteratura sul tema, discutiamo teoricamente e mostriamo empiricamente che, maggiore è la distanza culturale tra il paese dell’impresa acquirente e quello dell’impresa acquisita, più alta è la probabilità che l’amministratore delegato dell’impresa acquisita lasci il suo incarico, mentre l'esperienza internazionale di tali amministratori delegati è negativamente correlata alla loro partenza. In particolare, abbiamo diviso l'esperienza internazionale degli amministratori in generale e specifica al paese dell’acquirente (country-specific). L’esperienza generale è calcolata come la somma delle esperienze lavorative maturate in un paese straniero, mentre quella specifica è l'esperienza che l’amministratore delegato dell’impresa acquisita ha maturato in imprese il cui quartier generale ha sede nel paese dell'acquirente. Inoltre, la tesi discute e mostra che questi due tipi di esperienza internazionale possono indebolire l'effetto positivo della distanza culturale sulla probabilità che l’amministratore delegato dell’impresa acquisita lasci il suo incarico in seguito a una operazione di acquisizione cross-border.In less than twenty years, the number of cross-border acquisitions, i.e. acquisitions between firms whose respective headquarters are based in different countries, has more than tripled. This thesis tries to understand the impact of cultural distance and international experience of CEOs have in these acquisitions and, in particular, their effects on the decision of the acquiring company to whether maintain or not the CEO of the acquired one. We studied 197 acquisitions of small high tech firms in which the tacit knowledge, the characteristics and capabilities of management and managers are an important source of competitive advantage and where the departure of the CEO of the acquired company can lead to the failure of the acquisition. Based on the literature on the topic, we discuss theoretically and empirically show that the greater the cultural distance between the country of the acquiring and the acquired firm, the higher is the probability that the CEO of the acquired company leaves the company, while the international experience of these CEOs is negatively related to their departure. In particular, we have divided the international experience of the CEOs in general and specific to the buyer's country (country-specific). The general experience is computed as the sum of work experiences gained in a foreign country, while the specific is the experience that the CEO of the acquired company has gained in companies whose headquarters is based in the buyer's country. In addition, the thesis discusses and shows that these two types of international experience may weaken the positive effect of cultural distance on the probability that the CEO of the acquired company will leave his role following a cross-border acquisition

Graphene and other 2D layered hybrid nanomaterial-based films: Synthesis, properties, and applications

This Special Issue contains a series of reviews and research articles demonstrating actual perspectives and future trends of 2D-based materials for the generation of functional films, coatings, and hybrid interfaces with controlled morphology and structure

A complete hand-drawn sketch vectorization framework

Vectorizing hand-drawn sketches is a challenging task, which is of paramount importance for creating CAD vectorized versions for the fashion and creative workflows. This paper proposes a complete framework that automatically transforms noisy and complex hand-drawn sketches with different stroke types in a precise, reliable and highly-simplified vectorized model. The proposed framework includes a novel line extraction algorithm based on a multi-resolution application of Pearson's cross correlation and a new unbiased thinning algorithm that can get rid of scribbles and variable-width strokes to obtain clean 1-pixel lines. Other contributions include variants of pruning, merging and edge linking procedures to post-process the obtained paths. Finally, a modification of the original Schneider's vectorization algorithm is designed to obtain fewer control points in the resulting Bezier splines. All the proposed steps of the framework have been extensively tested and compared with state-of-the-art algorithms, showing (both qualitatively and quantitatively) its outperformance

Smart Tools for Smart Applications: New Insights into Inorganic Magnetic Systems and Materials

This Special Issue, consisting of four reviews and three research articles, presents some of the recent advances and future perspectives in the field of magnetic materials and systems, which are designed to meet some of our current challenge

Multifunctional Nanomaterials for Energy Applications

In the last few decades, global energy requirements have grown exponentially, and increased demand is expected in the upcoming decades [...