Tuberculosis (TB) is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb), one of the most dangerous aerobic bacteria. The need for long-term treatments and the increase in drug resistance mechanisms make it necessary to urgently develop new strategies to combat this potentially lethal pathogen. beta-Lactam Antibiotics (BLA) are the most widely used and safest antibiotics in the clinic and include several classes such as penicillins, cephalosporins and carbapenems. However, historically these agents have not been used to treat TB. There are two mechanisms of resistance to BLA in Mtb: the cell envelope rich in lipoglycans which acts as a barrier for the penetration of many drugs, including BLA, and the expression of BlaC, a specific beta-lactamase enzyme capable of hydrolyze and inactivate the BLA. Recent studies have shown that the combination of meropenem (a beta-lactam carbapenem), amoxicillin (a beta-lactam penicillin) and clavulanate (a beta-Lactamase inhibitor) markedly reduced the Mtb load in the patient’s sputum after two weeks, therefore giving new hope to the use of BLA to tackle the tuberculosis epidemic. This proposal aims to develop new compounds that behave as BLA adjuvant for anti-Mtb treatment with a dual mechanism of action. We will design and synthesize novel Boronic Acid Transition State Inhibitors (BATSIs) as inhibitors of BlaC, the beta-lactamase expressed in Mtb, and investigate whether they can be derivatized to become disrupting agents of Mtb’s unique outer “capsule” made of lipoglycans, to promote better penetration of drugs into the cell. This project will also investigate the possibility of improving the penetration of molecules into the necrotic granuloma formed in vivo as part of the disease process, by developing a lipid-based prodrug strategy. To achieve these specific objectives, the project will be divided into three main work packages, involving a combination of biological, chemical, and analytical expertise.

BlackHoleWeather aims to unify the astrophysics of black-hole (BH) feeding and feedback within cosmic structures, in one comprehensive theory that leverages novel high-performance simulations, fundamental gas physics, and timely multiwavelength observations. Most of the ordinary matter in the Universe is in the form of a tenuous gas which fills galaxies, groups, and clusters of galaxies (circumgalactic, intragroup, and intracluster medium). Such cosmic atmospheres are shaped by complex thermo-hydrodynamical processes - akin to Earth weather - with the central BH acting as cosmic thermostat over scales of 9 orders of magnitude. We have entered a Golden Age of multiphase gas detections continuously discovering ionized filaments (optical/UV), neutral gas (IR/21cm), and molecular clouds (radio) which condense out of the hot X-ray halos or that are ejected via BH feedback. We will tackle key challenges of modern astrophysics: what is the origin and evolution of the macro precipitation; how the multiphase rain (or chaotic cold accretion) is fed down through the BH horizon; how matter/energy is re-ejected back by the BH and deposited via multiphase outflows, jets and radiation; what is the role of dust, turbulence, stars, and cosmic rays; and how the self-regulated BH feeding-feedback loop shapes galaxies throughout cosmic time. Bridging BH feeding and feedback via ab-initio, multi-scale (mpc to Mpc), and first-principle physics (magnetohydrodynamics, transport, chemistry, cosmology) is ambitious, yet it is a zero-to-one leap that current astrophysics must undertake, and whose public datasets will provide invaluable legacy for many astronomical communities. BlackHoleWeather is a frontier yet feasible project, exploiting the timely convergence of our groundbreaking massively-parallel GPU code (GAMER2) and our ongoing multifrequency observing programs (e.g., Chandra, XMM, HST, ALMA, MUSE, JWST, SOFIA, MeerKAT).

The quality of a written text is often described in figurative terms, such as clearness and smoothness. The explicit description of what makes a text clear and smoothly flowing is a challenging task, probably because the readers’ perception of a text is influenced by multiple variables, related to the way information is structured, and how the writer employs the lexical and morphosyntactic resources of a language. The difficulty in translating the readers’ perceptions of a text in measurable descriptors leads to challenges in literacy education. For instance, how can educators explain what makes a text clear and smoothly flowing? What are the crucial aspect to focus on when giving feedback or conducting formative assessment? Answering these questions is of fundamental importance, given that writing literacy may have a considerable impact on employability, social participation and lifelong learning. This project aims to explore the relationship between the holistic evaluation of texts, carried out by expert evaluators, and their linguistic characteristics, to understand to what extent it is possible to identify objective and measurable properties that distinguish texts perceived as well written, compared to those with less positive ratings. For this purpose, we will establish a corpus of argumentative and narrative texts, written by university students, who are L1, L2 (or L3) speakers of Italian, a language that has received little attention so far in international research on writing. The methods of analysis involve the use of linguistic indices identified by previous research, which focus on the lexical and morphosyntactic complexity of the texts, and their integration with new indices, based on the Basel model of text analysis. This model contributes to a deeper understanding of the architecture of a text, by analysing how information is structured and hierarchized, and how textual units are connected on different semantic-pragmatic levels.

In its latest action plan on digital education, the European Union underlined the ambition of ensuring that all citizens are prepared to live and work in the digital age. However, the current COVID-19 pandemic, with its widespread closure of schools and universities, has thrown into sharp relief how the introduction of digital technology fundamentally reshapes the organisation of education. Within a few months, it became evident that schooling without school or studying without campus prompts the influx of new, private actors on an unprecedented scale. This project focuses on such digital reorganisation of education, cut off from the classroom. In particular, I propose to investigate how the conversion towards digital learning platforms participates in a worldwide disruption of pedagogical valuation processes. While existing research has so far favoured questions of power and inequalities, the disruptive capacity of these learning platforms to radically redefine what education values as worth learning has hardly been studied. To fill this gap, MORPHOGENESIS proposes (1) to build a framework that formulates an ensemble of concepts with theoretical insights from three related (sub)disciplines (sociology of education, organisation studies and the study of regionalisation and globalisation processes). With the help of Luhmannian systems theory, the coherent formulation of such framework will make it possible to analyse how, through such digital platforms, the reorganisation and the differentiation of global education go hand in hand; (2) to develop an extended case ethnography of the start-up scene in New York, where this so-called EdTech is currently being imagined, coded and executed into the platforms that explicitly aspire to disrupt contemporary education. Together, the conceptual framework and methodology will enable a better grasp of the metamorphosis that education is currently undergoing and the unprecedented role that online learning platforms play within it.

The encompassing objective of BookSHUK (“book” and “shuk,” in Hebrew “market”) is to provide the first historical and transnational analysis and digital visualization of the scholarly and trade networks related to the market of Jewish manuscripts and early printed books from the beginning of the twentieth century to the aftermath of WWII and the foundation of the State of Israel. Although the last decades have seen a rich harvest of studies on a multitude of aspects concerning the history of the Jewish book from the Middle Ages to the Holocaust, in-depth research on the market in the twentieth century has been largely neglected. BookSHUK aims to assess the international and interconnected nature of networks involving market actors (such as antiquarians, booksellers, private dealers, auction houses, collectors, scholars, librarians) between Europe, Mandatory Palestine (then Israel), and the United States also reflecting on the impact that major historical events such as WWI and WWII had on the trade. Through archival research on selected cases of study concerning sellers, customers, and objects across Europe, Israel, and the United States, the project intends to: a) identify the sellers and their business networks; b) unravel the role of auction houses in the international trade of Jewish manuscripts and early printed books; c) reconstruct the interests and taste that drove customers – both privates and librarians acting on behalf of libraries – to purchase specimens or collections for their private and/or institutional libraries; d) trace back relations among sellers and customers while providing geographical, chronological, and data visualizations of their connections thanks to digital tools, thus contributing to a more inclusive intellectual and cultural history. The three-year MSCA-GF will bring me to the University of Pennsylvania, the University of Modena and Reggio Emilia, and, during a secondment, to the University of Amsterdam.