Immunomodulating Profile of Dental Mesenchymal Stromal Cells: A Comprehensive Overview

: Dental mesenchymal stromal cells (MSCs) are multipotent cells present in dental tissues, characterized by plastic adherence in culture and specific surface markers (CD105, CD73, CD90, STRO-1, CD106, and CD146), common to all other MSC subtypes. Dental pulp, periodontal ligament, apical papilla, human exfoliated deciduous teeth, alveolar bone, dental follicle, tooth germ, and gingiva are all different sources for isolation and expansion of MSCs. Dental MSCs have regenerative and immunomodulatory properties; they are scarcely immunogenic but actively modulate T cell reactivity. in vitro studies and animal models of autoimmune diseases have provided evidence for the suppressive effects of dental MSCs on peripheral blood mononuclear cell proliferation, clearance of apoptotic cells, and promotion of a shift in the Treg/Th17 cell ratio. Appropriately stimulated MSCs produce anti-inflammatory mediators, such as transforming growth factor-\u3b2 (TGF-\u3b2), prostaglandin E2, and interleukin (IL)-10. A particular mechanism through which MSCs exert their immunomodulatory action is via the production of extracellular vesicles containing such anti-inflammatory mediators. Recent studies demonstrated MSC-mediated inhibitory effects both on monocytes and activated macrophages, promoting their polarization to an anti-inflammatory M2-phenotype. A growing number of trials focusing on MSCs to treat autoimmune and inflammatory conditions are ongoing, but very few use dental tissue as a cellular source. Recent results suggest that dental MSCs are a promising therapeutic tool for immune-mediated disorders. However, the exact mechanisms responsible for dental MSC-mediated immunosuppression remain to be clarified, and impairment of dental MSCs immunosuppressive function in inflammatory conditions and aging must be assessed before considering autologous MSCs or their secreted vesicles for therapeutic purposes

Ado's Theorem

Questa tesi è dedicata allo studio della dimostrazione del Teorema di Ado per algebre di Lie di dimensione finita su un campo K algebricamente chiuso e di caratteristica 0. Il teorema afferma che per ogni algebra di Lie siffatta esiste una rappresentazione fedele e di dimensione finita. In altre parole, il Teorema di Ado ci consente di vedere ogni algebra di Lie di dimensione finita come una sottoalgebra di un’algebra di Lie fatta di endomorfismi (equivalentemente di matrici). Nel primo capitolo vengono dati risultati e definizioni basilari sulle algebre di Lie. Il secondo capitolo presenta l'algebra universale inviluppante di un'algebra di Lie e la dimostrazione del Teorema di Ado nei casi semisemplice e abeliano. Nel terzo capitolo viene dimostrato il teorema per algebre nilpotenti e vengono illustrate ulteriori proprietà delle algebre di Lie di questo tipo, mentre nel quarto capitolo si dimostra il teorema nel caso di algebre risolubili. Infine, nel quinto capitolo viene data la dimostrazione per una qualsiasi algebra di Lie di dimensione finita su K, usando la decomposizione di Levi

Nuclear shape instability caused by lamin A deregulation promotes invasiveness in pediatric bone sarcomas: from nucleo-cytoskeleton dynamics to novel therapeutic opportunities

Osteosarcoma (OS) and Ewing sarcoma (EWS) are the two most frequent primary bone tumors, in which metastases remain the most relevant adverse prognostic factor. Lamin A is the main constituent of the nuclear lamina, with a fundamental role in maintaining the connection between nucleus and cytoskeleton (through LINC complex proteins interactions), and its alterations can be implicated in tumor progression. We investigated how nucleo-cytoskeleton dynamics is influenced by lamin A modulation in OS and EWS, demonstrating that both these cancer models had low levels of lamin A, which are linked to a significantly more marked nuclear misshaping. In our in vitro studies, reduced levels of lamin A promoted migratory abilities in these tumors. Moreover, these findings were corroborated by gene expression analyses on EWS patient samples, showing that LMNA levels were significantly lower in metastatic lesions compared to primary tumors and that patients with low LMNA had a significant worse overall survival. We also found that LMNA expression significantly impaired EWS metastases formation in vivo. We demonstrated that low lamin A expression was linked to a severe mislocalization of LINC complex proteins, thus disrupting nucleo-cytoskeleton interactions, with a corresponding gain in malignant properties, which resulted in increased invasiveness. Lamin A overexpression or its accumulation by a statin-based pharmacological treatment allowed us to reconstitute a functional nucleo-cytoskeleton interplay, which resulted in significant downmodulation of ROCK2 and YAP, two crucial drivers of EWS aggressiveness. Our study demonstrated that lamin A is a favorable mediator of nuclear shape stability in bone sarcomas, and its modulation rescues LINC complex protein localization and regulates mechano-signaling pathways, thus promoting a less aggressive cancer phenotype. We also identified statins, already employed in clinical practice, as a tool capable to increase lamin A levels, and to reconstitute functional nucleo-cytoskeletal dynamics, resulting in reduced cellular migration

Context-based energy disaggregation in smart homes

In this paper, we address the problem of energy conservation and optimization in residential environments by providing users with useful information to solicit a change in consumption behavior. Taking care to highly limit the costs of installation and management, our work proposes a Non-Intrusive Load Monitoring (NILM) approach, which consists of disaggregating the whole-house power consumption into the individual portions associated to each device. State of the art NILM algorithms need monitoring data sampled at high frequency, thus requiring high costs for data collection and management. In this paper, we propose an NILM approach that relaxes the requirements on monitoring data since it uses total active power measurements gathered at low frequency (about 1 Hz). The proposed approach is based on the use of Factorial Hidden Markov Models (FHMM) in conjunction with context information related to the user presence in the house and the hourly utilization of appliances. Through a set of tests, we investigated how the use of these additional context-awareness features could improve disaggregation results with respect to the basic FHMM algorithm. The tests have been performed by using Tracebase, an open dataset made of data gathered from real home environments

Context-based energy disaggregation in smart homes

In this paper, we address the problem of energy conservation and optimization in residential environments by providing users with useful information to solicit a change in consumption behavior. Taking care to highly limit the costs of installation and management, our work proposes a Non-Intrusive Load Monitoring (NILM) approach, which consists of disaggregating the whole-house power consumption into the individual portions associated to each device. State of the art NILM algorithms need monitoring data sampled at high frequency, thus requiring high costs for data collection and management. In this paper, we propose an NILM approach that relaxes the requirements on monitoring data since it uses total active power measurements gathered at low frequency (about 1 Hz). The proposed approach is based on the use of Factorial Hidden Markov Models (FHMM) in conjunction with context information related to the user presence in the house and the hourly utilization of appliances. Through a set of tests, we investigated how the use of these additional context-awareness features could improve disaggregation results with respect to the basic FHMM algorithm. The tests have been performed by using Tracebase, an open dataset made of data gathered from real home environments

Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL

Fracture strength and ribbond fibers : in vitro analysis of mod restorations

Ribbond fibers are supposed to be a reinforcing material in restoration of compromised teeth. This study aims to compare MOD restorations with and without Ribbond Fiber in terms of fracture strength under axial loading; to identify the minimum depth of M

Novelty Detection with Autoencoders for System Health Monitoring in Industrial Environments

Predictive Maintenance (PdM) is the newest strategy for maintenance management in industrial contexts. It aims to predict the occurrence of a failure to minimize unexpected downtimes and maximize the useful life of components. In data-driven approaches, PdM makes use of Machine Learning (ML) algorithms to extract relevant features from signals, identify and classify possible faults (diagnostics), and predict the components’ remaining useful life (prognostics). The major challenge lies in the high complexity of industrial plants, where both operational conditions change over time and a large number of unknown modes occur. A solution to this problem is offered by novelty detection, where a representation of the machinery normal operating state is learned and compared with online measurements to identify new operating conditions. In this paper, a systematic study of autoencoder-based methods for novelty detection is conducted. We introduce an architecture template, which includes a classification layer to detect and separate the operative conditions, and a localizer for identifying the most influencing signals. Four implementations, with different deep learning models, are described and used to evaluate the approach on data collected from a test rig. The evaluation shows the effectiveness of the architecture and that the autoencoders outperform the current baselines

Surgical approach to multifocal hepatocellular carcinoma with portal vein thrombosis and arterioportal shunt leading to portal hypertension and bleeding: a case report

It is reported the case of a 69 years man who presented to the Emergency Room because of pain and abdominal distension from ascites. After admission and paracentesis placement, he developed a digestive hemorrhage due to oesophageal varices from portal ipertension secondary to the formation of a portal shunt concomitant with a multifocal HepatoCellular Carcinoma (HCC) with portal vein thrombosis (PVT). The patient underwent endoscopic varices ligation, twice transarterial embolization (TAE) of arterial branches feeding the shunt and subsequent left hepatectomy. During the postoperative course he developed mild and transient signs of liver failure and was discharged in postoperative day 16. He is alive and disease free 8 months after surgery

Capsular polysaccharide induction of apoptosis by intrinsic and extrinsic mechanisms

A purified microbial capsular polysaccharide of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces Fas ligand (FasL) upregulation on macrophages and, as a consequence, apoptosis of lymphocytes. The mechanisms that lead to lymphocyte apoptosis in both in vitro and in vivo systems were investigated by cytofluorimetric analysis and Western blotting experiments. Caspase 8 cleaves caspase 3 in two different pathways: directly as well as indirectly by activation of Bcl-2 interacting domain, which initiates caspase 9 cleavage. Therefore, the caspase 8 and caspase 9 pathways cooperate in an amplification loop for efficient cell death, and noteworthily we provide evidence that they are both activated in one single cell. Furthermore, both activation of GXM-mediated caspase 8 and apoptosis were also found in in vivo systems in an experimental model of murine candidiasis. Collectively, our data show that GXM-induced apoptosis involves, in a single cell, a cross-talk between extrinsic and intrinsic pathways. Such a finding offers opportunities for the therapeutic usage of this polysaccharide in appropriate clinical settings for taming T-cell responses