La circolazione internazionale dei minori stranieri non accompaganti

Al giorno d’oggi i fenomeni migratori sono divenuti parte assai rilevante della vita di tutti i giorni e quindi hanno assunto, necessariamente, anche rilevanza giuridica. Con la presente dissertazione ci si propone di analizzare una porzione del fenomeno migratorio di non scarsa rilevanza giuridica e sociale, cioè la circolazione dei minori stranieri non accompagnati. Si è voluto andare ad analizzare la tutela giuridica che viene assicurata a questa particolare categoria di soggetti, i quali, in ragione della loro vulnerabilità, necessitano di un grado di protezione più elevato rispetto ai migranti adulti, tutela che, purtroppo, nella pratica non viene sempre assicurata. Nel tentativo di comprendere e di fare chiarezza sulla normativa concernente il problema si è analizzato in primo luogo quanto previsto dalle fonti internazionali (una su tutte la Convenzione di New York del 1989) sulla tutela dei minori e sui loro diritti fondamentali; si è proseguito analizzando la normativa regionale, cioè quanto prescritto sia dal Consiglio d’ Europa sia dall’Unione Europea in particolare il Regolamento Dublino ((UE) N. 604/2013) e la Direttive sulle regole per l’accoglienza (2013/33/UE) e si è concluso con un’analisi della normativa nazionale in tema di accoglienza e di tutela dei minori non accompagnati. Nello studiare le prescrizioni si è riscontrata una scarsa quantità di norme specificatamente indirizzata alla tutela dei minori stranieri non accompagnati e, sebbene sia possibile estendere in via interpretativa le prescrizioni generiche in materia di tutela minorile, sarebbe opportuno che si formulassero, almeno a livello nazionale, delle soluzioni “a misura di minore non accompagnato”, data la particolare vulnerabilità di questi soggetti

Multiscale clutch models for cell mechanics

Integrin-based cell adhesion is a key mechanism in fundamental biological processes such as cell migration and wound healing, and in diseases like osteoporosis and cancer. For example, during migration, cells form adhesion complexes as they move, exerting tractions on the extracellular matrix (ECM), which enable the formation of protrusions. So far experimental research has demonstrated the role of ligand spacing and substrate rigidity in adhesion dynamics. Moreover, some mathematical models have provided fundamental understanding in cell adhesion. Specifically, the Clutch Model has been very successful in explaining how cells can sense force and consequently, how they respond to substrate rigidity. To exploit its potential, we have used it to address single cell durotaxis, the migration of a cell due to a stiffness gradient in the substrate. We provide a mechanistic rationale of durotaxis by integrating continuum models of cell migration with the stochastic clutch model. We show that a gradient in the ECM stiffness activates an asymmetric intracellular retrograde flow during the initial cell spreading. The competition between this flow and the polymerization velocity at the cell membrane, creates a polarized state that establishes cell migration directionality. Our theoretical framework confirms previous experimental observations and rationalizes why some cell types follow positive stiffness gradients, while others move toward softer region.Unfortunately, current clutch models also present some limitations. Adhesion complexes present a number of different adaptor proteins, and are able to link the actomyosin cortex in the interior of the cell to the ECM. The study of their composition and function has shown that the integrin-talin-actin chain serves as a mechanosensor and mechanotransducer of the external and internal forces. Current models simplify the composition and organization of the adhesion complex and use a phenomenological approach to reproduce cell scale variables. However, they fail in modelling the sub-scale molecular behaviour. These simplifications have limited our mechanistic understanding of cell adhesion. Therefore, we propose a multiscale clutch model that, from the physical and biological laws of the cell components, reproduces the mechanics of an adhesion complex as well as the dynamics of the subcellular molecules. Because the ligands distance is fundamental for cell adhesion mechanics, we include a space-dependent ligand distribution and compute the displacement of the substrate point-wise thanks to Green’s functions. We also implement a detailed description of the talin rod. Given the importance of the recruitment of adaptor proteins in an adhesion complex, we implement the presence of vinculin binding sites (VBSs) and actin binding sites (ABSs) in the talin rod. Our results reproduce previous cell scale variables, but also reproduce the behavior of single adhesion molecules within the adhesion complex. Moreover, our results suggest that cell traction is mostly dependent on the complex adhesion size rather than ligand density. Our computational framework also allows us to easily manipulate VBSs and ABSs and analyze the effect of their depletion in cell adhesion mechanics. Our computational results reproduce experimental data of mouse embryonic fibroblasts, both with full-length talin and with different combinations of talin domains depletion, showing how the traction force changes with respect to the talin configuration. We believe that our detailed multi-scale model represents an important step forward in the understanding of cell adhesion, which can be further extended to account for other adhesion molecules and, e.g., for the study of adhesion maturation. The multi-scale durotaxis model can be also used in a wider biological context, to engineer better biomimetic tissue constructs or to propose strategies for arresting tumor invasion.La adhesión celular basada en integrinas es un mecanismo clave en procesos biológicos fundamentales como la migración celular y la cicatrización de heridas, y en enfermedades como el cáncer. Por ejemplo, durante la migración, las células forman complejos de adhesión a medida que se mueven, ejerciendo tracciones sobre la matriz extracelular (ECM). Hasta ahora, la investigación experimental ha demostrado el papel del espaciado entre ligandos y la rigidez del sustrato en la dinámica de adhesión. Además, algunos modelos matemáticos han proporcionado una comprensión fundamental de la adhesión celular. Específicamente, el modelo de embrague ha tenido mucho éxito al explicar cómo las células pueden sentir la fuerza y cómo responden a la rigidez del sustrato. Para explotar su potencial, lo hemos utilizado para abordar la durotaxis, la migración de una célula debido a un gradiente de rigidez en el sustrato. Proporcionamos una justificación mecánica de la durotaxis mediante la integración de modelos continuos de migración celular con el modelo de embrague estocástico. Mostramos que un gradiente en la rigidez de la ECM activa un flujo retrógrado intracelular asimétrico durante la propagación celular inicial. La competencia entre este flujo y la velocidad de polimerización en la membrana celular crea un estado polarizado que establece la direccionalidad de la migración celular. Nuestro marco teórico explica por qué algunos tipos de células siguen gradientes de rigidez positivos, mientras que otros se mueven hacia regiones más blandas. Desafortunadamente, los modelos de embrague actuales también presentan algunas limitaciones. Los complejos de adhesión presentan varias proteínas adaptadoras diferentes y pueden unir la corteza de actomiosina en el interior de la célula con la ECM. El estudio de su composición y función ha demostrado que la cadena integrina-talina-actina sirve como mecanosensor y mecanotransductor de las fuerzas. Los modelos actuales simplifican la composición y organización del complejo de adhesión y utilizan un enfoque fenomenológico para reproducir variables de escala celular. Sin embargo, fallan en modelar el comportamiento molecular a subescala. Estas simplificaciones han limitado nuestra comprensión mecánica de la adhesión celular. Por ello, proponemos un modelo de embrague multiescala que, a partir de las leyes físicas de los componentes celulares, reproduce la mecánica de un complejo de adhesión así como la dinámica de las moléculas subcelulares. Debido a que la distancia de los ligandos es fundamental para la mecánica de adhesión celular, incluimos una distribución de ligandos dependiente del espacio y calculamos el desplazamiento del sustrato por puntos gracias a las funciones de Green. También implementamos una descripción detallada de la talin. Dada la importancia del reclutamiento de proteínas adaptadoras en un complejo de adhesión, implementamos la presencia de sitios de unión de vinculina (VBS) y sitios de unión de actina (ABS) en la talina. Nuestros resultados reproducen variables de escala celular anteriores, y reproducen el comportamiento de moléculas de adhesión individuales dentro del complejo de adhesión. Nuestro marco computacional también nos permite manipular fácilmente VBS y ABS y analizar el efecto de su agotamiento en la mecánica de adhesión celular. Nuestros resultados computacionales reproducen datos experimentales de fibroblastos embrionarios de ratón, tanto con talin de longitud completa como con diferentes combinaciones de agotamiento de dominios de talin. Creemos que nuestro modelo detallado de múltiples escalas representa un importante paso adelante en la comprensión de la adhesión celular, que puede ampliarse aún más para tener en cuenta la maduración de las adherencias. El modelo de durotaxis multiescala también se puede utilizar en un contexto biológico más amplio, para diseñar mejores construcciones biomiméticas o para proponer estrategias para detener la invasión tumoral.Postprint (published version

Managing Risks in SMEs: A Literature Review and Research Agenda

In times of crisis, companies need to carefully monitor current expenses and forecast potential costs, which could be caused by risky actions. Risk is inherent in all business functions and in every kind of activity. Knowing how to identify risks, attribute a value and a priority scale, design actions and mechanisms to minimize risks, and continuously monitor them, are essential to guarantee companies’ survival and create sustainable value. This is especially true for small- and medium-sized businesses that are most exposed to the harmful effects of the risks, due to limited resources and structural features. The objective of this study is to analyze available literature on the subject of risk management for small- and medium-sized enterprises from 1999 to 2009. The analysis derives interesting characteristics from the scientific studies, highlighting gaps and guidelines for future research

A multi-scale clutch model for adhesion complex mechanics

Cell-matrix adhesion is a central mechanical function to a large number of phenomena in physiology and disease, including morphogenesis, wound healing, and tumor cell invasion. Today, how single cells respond to different extracellular cues has been comprehensively studied. However, how the mechanical behavior of the main individual molecules that form an adhesion complex cooperatively responds to force within the adhesion complex is still poorly understood. This is a key aspect of cell adhesion because how these cell adhesion molecules respond to force determines not only cell adhesion behavior but, ultimately, cell function. To answer this question, we develop a multi-scale computational model for adhesion complexes mechanics. We extend the classical clutch hypothesis to model individual adhesion chains made of a contractile actin network, a talin rod, and an integrin molecule that binds at individual adhesion sites on the extracellular matrix. We explore several scenarios of integrins dynamics and analyze the effects of diverse extracellular matrices on the behavior of the adhesion molecules and on the whole adhesion complex. Our results describe how every single component of the adhesion chain mechanically responds to the contractile actomyosin force and show how they control the traction forces exerted by the cell on the extracellular space. Importantly, our computational results agree with previous experimental data at the molecular and cellular levels. Our multi-scale clutch model presents a step forward not only to further understand adhesion complexes mechanics but also to impact, e.g., the engineering of biomimetic materials, tissue repairment, or strategies to arrest tumor progression.We acknowledge funding from the Spanish Ministry of Science and Innovation (Grant PID2019-11094GB-100 funded by MCIN/ AEI /10.13039/501100011033 to P.S.), the European Commission (H2020-FETPROACT-01-2016- 731957 to C.V. and P.S), the Generalitat de Catalunya (2017-SGR-1278 to P.S. and FI AGAUR 2018 for C.V. salary). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer ReviewedPostprint (published version

Determinants and Catalysts in Intrafirm Technology Transfer: Learning From Case Studies

The sharing of technological knowledge between firms or within the same firm is becoming essential to develop innovations. Although previous studies have investigated the determinants of technology transfer(TT), they have not pointed out the existence of catalysts, i.e. determinants that assume a more crucial role than others in making transfer effective, and which compensate for the weaknesses in other determinants. In this paper, from the analysis of transfer processes within three manufacturing multinationals, three catalysts have emerged: leadership by the top management, anticipated profitability from the adoption of the new technology, and the professionalism of centralized research and development staff

Product market regulation and innovation efficiency

We study the role of upstream product market regulation (PMR) in innovation efficiency. By estimating a knowledge production function on OECD industries through a stochastic frontier analysis, we find that service regulation reduces R&D efficiency in the manufacturing sector. These results are robust to controlling for the institutional setting of the technology, the labour and the financial market, and to various forms of heterogeneity. The marginal impact of PMR is higher in less regulated economies indicating that large improvements in R&D efficiency cannot be obtained at the earlier stages of deregulation. Potential efficiency gains for late reformers are however sizeable

On-surface coupling reactions on calcium carbonate

Le couplage covalent sur surface métallique en UHV (Ultra High Vacuum) est une technique émergente permettant de synthétiser des structures moléculaires impossibles à obtenir par la chimie en solution (nanorubans de graphène, polymères 2D par exemple). Aujourd'hui, le plus grand défi reste le développement de ces réactions sur des surfaces isolantes pour différentes applications comme, par exemple, l'électronique moléculaire. En particulier, le couplage de dérivés d'acides benzoïques, greffés sur les surfaces de carbonate de calcium en UHV par des groupes carboxyliques, a été démontré récemment pour la première fois. Lors de ces travaux, nous avons dans un premier temps synthétisé des molécules précurseurs de réactions de couplage (homo-couplage d'éthyne, photopolymérisation, polycondensation et réaction d'Ullmann) sur des surfaces de carbonate de calcium en UHV. Par la suite, nous avons mené cette étude à l'échelle macroscopique (semi-préparatoire), par greffage de molécules sur des microparticules de carbonate de calcium, puis activation de la réaction, et enfin dissolution du substrat afin d'extraire le produit final. Les microparticules ont été obtenues par broyage de produit commercial ainsi que par spray pyrolyse et complètement caractérisées par FTIR, ATG/DTG, DRX, MEB et BET. Les réactions de couplage ont été activées par deux méthodes sans solvant: par broyage dans une broyeuse planétaire ou par traitement thermique sous vide. Alors qu'en UHV le couplage de l'acide 4-iodobenzoïque donne l'acide biphenyldicarboxylique, en mécanochimie nous avons obtenu l'acide benzoïque et par activation thermique l'éther dibenzoïque.Covalent coupling on metallic surfaces in UHV (Ultra High Vacuum) conditions is a new method for preparing molecular structures otherwise impossible to achieve in solution (graphene nanoribbons, 2D polymers for instance). The major challenge is now to extend these reactions from metallic to insulating surfaces, for future applications as, for instance, in molecular electronics. In particular, the coupling reaction of benzoic acid derivatives, grafted on calcite via carboxylic groups, has been demonstrated for the first time in UHV conditions. In the first part of this work, we synthesized precursor molecules for specific reactions (homocoupling of ethynes, photopolymerization, polycondensation and Ullmann reaction) on calcium carbonate in UHV conditions. In the second part of this work we extended this investigation up to the macroscale level (semi-preparative) by grafting molecules on calcium carbonate microparticles, followed by reaction activation and finally by dissolution of the substrate in order to recover the coupling products. The calcium carbonate microparticles were prepared by grinding commercial product or by spray pyrolysis and were fully characterized by FTIR, TG/DTG, XRD, SEM and BET techniques. Then, after grafting of organic reactant, the reactions were activated with two different solvent-free methods: by grinding in a planetary milling machine or by heating the samples in a furnace under vacuum. Whereas in UHV conditions, 4-iodobenzoic acid affords biphenyldicarboxylic acid, mechanochemical condition gives benzoic acid and thermal activation the dibenzoic acid ether