Design and synthesis of small molecules as tools for drug discovery and chemical biology: identification of new LDH-A inhibitors and development of fluorescent probes to investigate neurogenesis

The present work includes distinct research projects having as common platform the design and synthesis of biologically active small molecules, useful as tools both for drug discovery and chemical biology studies. The main project (Part I) focused on the identification of LDH-A inhibitors as hit candidates in the discovery of new anticancer agents. My work aimed to explore the chemical space around galloflavin (GF) by synthesizing a small library of analogs to perform structure-activity relationships (SAR) studies. GF, LDH-A inhibitor previously identified and synthesized by our group, was not investigated in terms of SAR because of its poor chemical tractability. In the present work, natural urolithin M6 (UM6) has been selected as simplified analog of GF. It is endowed with improved physicochemical properties and showed to reproduce GF’s biological behaviour. An efficient synthetic strategy has been developed to obtain UM6, which synthesis was not previously reported. This route gave an easy access to a series of structural analogs for SAR investigation. The second project (Part II), carried out at Oxford University under the supervision of Professor Angela Russell, aimed to use a chemical biology approach to develop a proneurogenic small molecule recently identified by the group (OX02672), into a fluorescent probe to assess its molecular interactions and localization in neural stem cells (NSCs). My work focused on the design and synthesis of alkyne-tagged derivatives of OX02672 for subsequent development into probes by “click” conjugation with azide-containing fluorophores. The third part includes a side-project (Part III), carried out in collaboration with group of Professor Maria Laura Bolognesi. It focused on the design and synthesis of multi-target-directed ligands (MTDLs) useful as potential hit candidates in the search for new drugs against Alzheimer’s disease (AD). Tacrine-resveratrol hybrid compounds have been designed and synthesized by using a fusing strategy

Explaining short text classification with diverse synthetic exemplars and counter-exemplars

We present xspells, a model-agnostic local approach for explaining the decisions of black box models in classification of short texts. The explanations provided consist of a set of exemplar sentences and a set of counter-exemplar sentences. The former are examples classified by the black box with the same label as the text to explain. The latter are examples classified with a different label (a form of counter-factuals). Both are close in meaning to the text to explain, and both are meaningful sentences – albeit they are synthetically generated. xspells generates neighbors of the text to explain in a latent space using Variational Autoencoders for encoding text and decoding latent instances. A decision tree is learned from randomly generated neighbors, and used to drive the selection of the exemplars and counter-exemplars. Moreover, diversity of counter-exemplars is modeled as an optimization problem, solved by a greedy algorithm with theoretical guarantee. We report experiments on three datasets showing that xspells outperforms the well-known lime method in terms of quality of explanations, fidelity, diversity, and usefulness, and that is comparable to it in terms of stability

The italian music superdiversity: Geography, emotion and language: one resource to find them, one resource to rule them all

Globalization can lead to a growing standardization of musical contents. Using a cross-service multi-level dataset we investigate the actual Italian music scene. The investigation highlights the musical Italian superdiversity both individually analyzing the geographical and lexical dimensions and combining them. Using different kinds of features over the geographical dimension leads to two similar, comparable and coherent results, confirming the strong and essential correlation between melodies and lyrics. The profiles identified are markedly distinct one from another with respect to sentiment, lexicon, and melodic features. Through a novel application of a sentiment spreading algorithm and songs’ melodic features, we are able to highlight discriminant characteristics that violate the standard regional political boundaries, reconfiguring them following the actual musical communicative practices

Gamma-spectrometric measurement of radioactivity in agricultural soils of the Lombardia region, northern Italy

Abstract This work is part of a wider monitoring project of the agricultural soils in Lombardia, which aims to build a database of topsoil properties and the potentially toxic elements, organic pollutants and gamma emitting radionuclides that the topsoils contain. A total of 156 agricultural soils were sampled according to the LUCAS (Land Use/Cover Area frame statistical Survey) standard procedure. The aim was to provide a baseline to document the conditions present at the time of sampling. The results of the project concerning soil radioactivity are presented here. The aim was to assess the content of 238U, 232Th, 137Cs and 40K by measuring soil samples by gamma spectrometry. 238U, 232Th and 40K activities range 24–231, 20–70, and 242–1434 Bq kg−1 respectively. The geographic distribution of 238U reflects the geophysical framework of the Lombardia region: the soils with high content of uranium are distributed for the most part in the South Alpine belt, where the presence of magmatic rocks is widespread. These soils show an higher activity of 238U than of 232Th. The 238U activities become lower than 232Th when soils are located in the plain, originating from basic sedimentary rocks. 137Cs activity ranges 0.4–86.8 kBq m−2. The lowest activity of 137Cs is in the plain, whereas the highest is in the North on soils kept as lawn or pasture. The 137Cs activity of some samples suggests the presence of accumulation processes that lead to 137Cs enriched soils. This is the first survey of gamma emitting radionuclides in Lombardia that is based on the LUCAS standard sampling. The results from this monitoring campaign are important for the human radiation exposure and provide the zero point, which will be useful for assessing future effects due to external factors such as human activities

Dual career in European-funded projects: a critical analysis and review

ABSTRACT This study aimed to review the projects financed between 2014 and 2022 under the ERASMUS+ programme of the European Commission to examine the past and present implementation of the dual career (DC) of elite sportspersons and to highlight potential gaps to guide future project proposals. Findings showed a relevant focus of the financed projects on the micro and multi-dimensional aspects of DC of athletes as the main target group, implementing training courses/programmes in different settings, and partnerships mostly composed by educational institutions and NGOs. In the future, sports bodies should engage more in partnerships, whereas DC of employee-sportspersons as athletes and sports staff should be implemented, with a strong focus on the project’s long-term impact and sustainability

Ediciones críticas de literatura argentina del siglo XIX

This research aims to recover authors and texts from the nineteenth and early twentieth century. Theoretical framework: microhistory, cultural studies, sociology of Literature, gender studies, “genres of the self”, travel writings, the genetic poetics. From the Archive “Eduarda Mansilla”, material from and about the author has been digitalized; from the edition of the critical Anthology of brief narrative of writers, approximations based on cognitive poetics, gender stereotypes, motifs and literary topics and the anthropological discourse have been made about rescued authors; from the critical edition of the story of captivity among the ranqueles of Santiago Avendaño 60 % of the manuscripts of the Zeballos Archive have been transcript, survey of information gaps; survey of distance points and differences presented by the manuscript in relation to existing edition, and drafting of the preliminary study have been made; and the critical edition of the narrative work of Josefina Pelliza de Sagasta, publication of Margarita, original novel (1875) including introductory study on the author, overview of literature during this period and analysis of the novel from the theory of melodrama.Esta investigación se propone recuperar autores y textos del siglo XIX y principios del siglo XX. Aparato crítico: microhistoria, estudios culturales, sociología de la literatura, estudios de género, “géneros del yo”, escrituras del viaje, crítica genética. Hasta el momento, del Archivo “Eduarda Mansilla”, se ha digitalizado material de y sobre la autora; de la edición de la Antología crítica de narrativa breve de escritoras se han realizado aproximaciones basadas en la poética cognitiva, en estereotipos de género, en motivos y tópicos literarios, en el discurso antropológico, sobre autoras rescatadas; de la edición crítica del relato de cautiverio entre los ranqueles de Santiago Avendaño se ha transcripto el 60 % de los manuscritos del Archivo Zeballos, se han relevado vacíos de información, de puntos de distancia y diferencias del manuscrito con las ediciones existentes y redacción del estudio preliminar; y de la edición crítica de la obra narrativa y lírica de J. Pelliza de Sagasta, la publicación de Margarita, novela original (1875), con estudio introductorio sobre la autora, panorama de la literatura durante ese período y análisis de la novela desde la teoría del melodrama

Nkx2-5+Islet1+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Participate in Restoring Stromal Network Integrity

SummarySecondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5+Islet1+ lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity

¿“Pájinas insulsas e imperfectas”?: Edición crítica del Diario de viaje a Oriente (1850−1851) y otras crónicas del viaje oriental, de Lucio V. Mansilla

La edición crítica del Diario de viaje a Oriente 1850-1851 y otras crónicas del viaje oriental, de Lucio V. Mansilla, no involucró solamente la descripción general de los dos manuscritos encontrados, sino el examen riguroso del material, el análisis de las variantes textuales surgidas de la comparación entre uno y otro que evidencian la intención del autor de mejorar la primera versión, la comparación con la literatura de viaje posterior del propio Mansilla, su ubicación dentro del contexto histórico, cultural y biográfico, y la restauración de ambos textos decimonónicos para lectores del siglo XXI. Además, los manuscritos constituyen una invalorable fuente de datos para el estudio del español bonaerense de mediados del siglo XIX.The critical editing of Diario de viaje a Oriente (1850−1851), y otras crónicas del viaje oriental, by Lucio V. Mansilla, did not only involve the general description of the two recently found manuscripts, but also the thorough examination of the material, the analysis of the textual variations arisen in their comparison —which evidence the author ́s intention to improve the first version—, their comparison with travel literature written later by Mansilla himself, their situation in the historical, cultural and biographical context, and the restoration of both nineteenth century texts for readers in the twenty first century. Moreover, both manuscripts are a highly valuable source of information for research focused on the Spanish spoken in Buenos Aires in mid nineteenth century.Fil: Lojo Calatrava, Maria Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad del Salvador. Facultad de Filosofía, Historia y Letras; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Literatura Argentina "Ricardo Rojas"; ArgentinaFil: Guidotti, Marina Liliana. Universidad del Salvador. Facultad de Filosofía, Historia y Letras; ArgentinaFil: Pérez Gras, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Literatura Argentina "Ricardo Rojas"; Argentina. Universidad del Salvador. Facultad de Filosofía, Historia y Letras; Argentin

Mujeres que reseñan a mujeres en revista Sur (1931-1992). El caso de la literatura infantil

Despite the extensive bibliography on Sur, this Argentine journal still offers new fields of investigation, many of them of special interest for Women's studies. In this case, we will look into those reviews written by women about women, and we will pay special attention to those dedicated to a genre that has been significant in the career of many Latin American female writers: Children's Literature.A pesar de la extensa bibliografía existente sobre Sur, esta revista argentina aún ofrece nuevos campos de análisis, muchos de ellos de especial interés para los estudios sobre mujeres. En este caso, se consideran las reseñas allí publicadas por mujeres sobre mujeres y se presta especial atención a aquellas dedicadas a un género que ha sido significativo en la trayectoria de muchas escritoras latinoamericanas: la literatura infantil