SIENA AND ITALIAN LYMPHOLOGY: FROM MASCAGNI TO COMPARINI....TO TOSATTI. A TRANSLATIONAL OVERVIEW FROM THE ORIGINS UNTIL TODAY, FROM SIENA TO GENOA, IN ITALY

n/

The DarkSide experiment

DarkSide is a dark matter direct search experiment at Laboratori Nazionali del Gran Sasso (LNGS). DarkSide is based on the detection of rare nuclear recoils possibly induced by hypothetical dark matter particles, which are supposed to be neutral, massive (m>10GeV) and weakly interactive (WIMP). The dark matter detector is a two-phase time projection chamber (TPC) filled with ultra-pure liquid argon. The TPC is placed inside a muon and a neutron active vetoes to suppress the background. Using argon as active target has many advantages, the key features are the strong discriminant power between nuclear and electron recoils, the spatial reconstruction and easy scalability to multi-tons size. At the moment DarkSide-50 is filled with ultra-pure argon, extracted from underground sources, and from April 2015 it is taking data in its final configuration. When combined with the preceding search with an atmospheric argon target, it is possible to set a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 2.0×10−44 cm2 for a WIMP mass of 100GeV/c2. The next phase of the experiment, DarkSide-20k, will be the construction of a new detector with an active mass of ∼ 20 tons

Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells

Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with β1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling.Fil: Sampayo, Rocío Guadalupe. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Toscani, Andrés Martin. Universidad Nacional de Luján; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rubashkin, Matthew G.. University of California; Estados UnidosFil: Thi, Kate. Lawrence Berkeley National Laboratory; Estados UnidosFil: Masullo, Luciano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Violi, Ianina Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Lakins, Jonathon N.. University of California; Estados UnidosFil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Hines, William C.. Lawrence Berkeley National Laboratory; Estados UnidosFil: Coluccio Leskow, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Luján; ArgentinaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Chialvo, Dante Renato. Universidad de Buenos Aires; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro Internacional de Estudios Avanzados; ArgentinaFil: Bissell, Mina J.. Lawrence Berkeley National Laboratory; Estados UnidosFil: Weaver, Valerie M.. University of California; Estados UnidosFil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

Engineered swift equilibration of a Brownian particle

A fundamental and intrinsic property of any device or natural system is its relaxation time relax, which is the time it takes to return to equilibrium after the sudden change of a control parameter [1]. Reducing $tau$ relax , is frequently necessary, and is often obtained by a complex feedback process. To overcome the limitations of such an approach, alternative methods based on driving have been recently demonstrated [2, 3], for isolated quantum and classical systems [4--9]. Their extension to open systems in contact with a thermostat is a stumbling block for applications. Here, we design a protocol,named Engineered Swift Equilibration (ESE), that shortcuts time-consuming relaxations, and we apply it to a Brownian particle trapped in an optical potential whose properties can be controlled in time. We implement the process experimentally, showing that it allows the system to reach equilibrium times faster than the natural equilibration rate. We also estimate the increase of the dissipated energy needed to get such a time reduction. The method paves the way for applications in micro and nano devices, where the reduction of operation time represents as substantial a challenge as miniaturization [10]. The concepts of equilibrium and of transformations from an equilibrium state to another, are cornerstones of thermodynamics. A textbook illustration is provided by the expansion of a gas, starting at equilibrium and expanding to reach a new equilibrium in a larger vessel. This operation can be performed either very slowly by a piston, without dissipating energy into the environment, or alternatively quickly, letting the piston freely move to reach the new volume

INVESTIGATING THE SEISMIC RESPONSE OF URM WALLS WITH IRREGULAR OPENING LAYOUT THROUGH DIFFERENT MODELING APPROACHES

The façade and internal walls of unreinforced masonry (URM) buildings often present an irregular opening layout, due to architectural reasons or modifications to the structure, which make the expected seismic damage pattern less predictable a priori. Therefore, the discretization of the walls in structural components is not standardized, conversely to cases with a regular opening layout for which the available modeling methods are corroborated by seismic damage surveys reporting recurrent failure patterns. The structural component discretization is a relevant step for the code-conforming seismic assessment, typically based on comparing the internal forces and drifts of each component to strength criteria and drift thresholds. Therefore, the lack of well-established approaches can significantly influence the assessment. The issue is even more evident when the structural components must be identified a priori in the modeling stage, namely for equivalent frame models. The applicability of available methods for discretization of URM walls with irregular opening layout has been already investigated in literature, but a conclusive judgment requires further studies. In this context, this paper presents an overview of the preliminary results addressing the numerical modeling of this type of walls within the framework of the DPC-ReLUIS 2022-2024 project (Subtask 10.3), funded by the Italian Department of Civil Protection. The Subtask aims to propose consensus-based recommendations for researchers and practitioners which can contribute to harmonize the use of different modeling approaches. Seven research groups are involved in the research, adopting different modeling approaches and computer codes, but similar assumptions and the same analysis method (pushover) are used. The benchmark URM structure illustrated in the paper is a two-story wall from which four configurations with increasing irregularity of opening layout were derived. The results of four modeling approached are presented. Three of them reproduce the mechanical response of masonry at the material scale by means of FE models implemented in OpenSees, DIANA and Abaqus software, while the remaining approach describes the mechanical response of masonry at the macro-element scale in 3DMacro software. Results were compared in terms of capacity curves, predicted failure mechanisms and evolution of internal forces in piers. The adoption of consistent assumptions among the different approaches led to an overall agreement of predictions at both wall and pier scales, particularly in terms of damage pattern with higher concentration of damage at the ground story. Despite that, differences on the pushover curves have been highlighted. They are mainly due to some deviations of the internal forces in squat piers deriving from a complex load flow in these elements

Investigating the seismic response of URM walls with irregular opening layout through different modeling approaches

TThe façade and internal walls of unreinforced masonry (URM) buildings often present an irregular opening layout, due to architectural reasons or modifications to the structure, which make the expected seismic damage pattern less predictable a priori. Therefore, the discretization of the walls in structural components is not standardized, conversely to cases with a regular opening layout for which the available modeling methods are corroborated by seismic damage surveys reporting recurrent failure patterns. The structural component discretization is a relevant step for the code-conforming seismic assessment, typically based on comparing the internal forces and drifts of each component to strength criteria and drift thresholds. Therefore, the lack of well-established approaches can significantly influence the assessment. The issue is even more evident when the structural components must be identified a priori in the modeling stage, namely for equivalent frame models. The applicability of available methods for discretization of URM walls with irregular opening layout has been already investigated in literature, but a conclusive judgment requires further studies. In this context, this paper presents an overview of the preliminary results addressing the numerical modeling of this type of walls within the framework of the DPC-ReLUIS 2022-2024 project (Subtask 10.3), funded by the Italian Department of Civil Protection. The Subtask aims to propose consensus-based recommendations for researchers and practitioners which can contribute to harmonize the use of different modeling approaches. Seven research groups are involved in the research, adopting different modeling approaches and computer codes, but similar assumptions and the same analysis method (pushover) are used. The benchmark URM structure illustrated in the paper is a two-story wall from which four configurations with increasing irregularity of opening layout were derived. The results of four modeling approached are presented. Three of them reproduce the mechanical response of masonry at the material scale by means of FE models implemented in OpenSees, DIANA and Abaqus software, while the remaining approach describes the mechanical response of masonry at the macro-element scale in 3DMacro software. Results were compared in terms of capacity curves, predicted failure mechanisms and evolution of internal forces in piers. The adoption of consistent assumptions among the different approaches led to an overall agreement of predictions at both wall and pier scales, particularly in terms of damage pattern with higher concentration of damage at the ground story. Despite that, differences on the pushover curves have been highlighted. They are mainly due to some deviations of the internal forces in squat piers deriving from a complex load flow in these elements.DPC - Dipartimento della Protezione Civile, Presidenza del Consiglio dei Ministri(LA/P/0112/2020

Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion

BACKGROUND: Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. METHODOLOGY/PRINCIPAL FINDINGS: In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane. CONCLUSIONS/SIGNIFICANCE: These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions

Integrin-Linked Kinase Overexpression and Its Oncogenic Role in Promoting Tumorigenicity of Hepatocellular Carcinoma

Background: Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers. Aberrant expression of ILK influenced a wide range of signaling pathways and cellular functions. Although ILK has been well characterized in many malignancies, its role in hepatocellular carcinoma (HCC) is still largely unknown. Methodology/Principal Findings: Quantitative PCR analysis was used to examine ILK mRNA expression in HCC clinical samples. It was shown that ILK was overexpressed in 36.9% (21/57) of HCC tissues when compared to the corresponding non-tumorous livers. The overall ILK expression level was significantly higher in tumorous tissues (P = 0.004), with a significant stepwise increase in expression level along tumor progression from tumor stage I to IV (P = 0.045). ILK knockdown stable clones were established in two HCC cell lines, BEL7402 and HLE, and were subjected to different functional assays. Knockdown of ILK significantly suppressed HCC cell growth, motility and invasion in vitro and inhibited tumorigenicity in vivo. Western blot analysis revealed a reduced phosphorylated-Akt (pAkt) at Serine-473 expression in ILK knockdown stable clones when compared to control clones. Conclusion/Significance: This study provides evidence about the clinical relevance of ILK in hepatocarcinogenesis. ILK was found to be progressively elevated along HCC progression. Here our findings also provide the first validation about the oncogenic capacity of ILK in vivo by suppressing its expression in HCC cells. The oncogenic role of ILK is implicated to be mediated by Akt pathway. © 2011 Chan et al.published_or_final_versio

Epithelial Membrane Protein-2 Promotes Endometrial Tumor Formation through Activation of FAK and Src

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling