Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

Microscopic simulation of electronic noise in semiconductormaterials and devices

We present a microscopic interpretation of electronic noise in semiconductor materials and two-terminal devices. The theory is based on Monte Carlo simulations of the carrier motion self-consistently coupled with a Poisson solver. Current and voltage noise operations are applied and their respective representations discussed. As application we consider the cases of homogeneous materials, resistors, n⁺nn ⁺ structures, and Schottky-barrier diodes. Phenomena associated with coupling between fluctuations in carrier velocity and self-consistent electric field are quantitatively investigated for the first time. At increasing applied fields hot-carrier effects are found to be of relevant importance in all the cases considered here. As a general result, noise spectroscopy is found to be a source of valuable information to investigate and characterize transport properties of semiconductor materials and devices     

Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin

Human peripheral blood monocytes were examined for migration across an endothelial cell monolayer in an in vitro vessel wall construct. Few monocytes invaded in the absence of a chemotactic gradient, despite significant adhesion to the endothelial monolayer. However, the addition of zymosan-activated human plasma to the lower compartment, to create a chemotactic gradient across the vessel wall, resulted in significantly enhanced monocyte migration. Pretreatment of the monocytes with monoclonal antibodies to thrombospondin (TSP) dramatically inhibited monocyte diapedesis into the vessel wall. The same treatment inhibited monocyte adhesion to endothelial cells in two-dimensional monolayer cultures as well as in vessel wall constructs (no chemotactic gradient). Of interest, however, the monoclonal antibodies had no inhibitory effect on monocyte migration into collagen gels devoid of endothelial cells in response to the same chemotactic gradient, suggesting the importance of TSP in monocyte-endothelial cell interactions. Monoclonal antibodies to fibronectin and normal mouse immunoglobulin G did not inhibit migration in this model of a vessel wall. Furthermore, monoclonal antibodies to TSP showed no inhibition of human peripheral blood neutrophil migration. Previous studies have shown that monocytes synthesize TSP and express this moiety on their surface. The present data suggest that monocytes may utilize TSP to interact with endothelial cells lining the vessel wall during diapedesis.     

A Multicriteria Decision Support Methodology for Annual Rehabilitation Programs of Water Networks

Abstract:   This article provides an overview of a multicriteria decision support methodology for annual rehabilitation programs of water networks. A first set of criteria is formulated for the purpose of comparing and ranking rehabilitation projects. Each proposed criterion is a measure of a particular impact of the condition of a pipe. The ELECTRE TRI method is implemented for defining rehabilitation priorities . Two reference profiles are used to define the limits of three categories associated with three increasing priority levels. With these two reference profiles, applying the ELECTRE TRI method to an asset stock ( a set of pipes that are candidates for rehabilitation ) means assigning each pipe to one of six possible priority groups. A second set of criteria, based on the concept of efficiency, is proposed for comparing alternative rehabilitation programs ( subsets of the asset stock ).     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Update on the pharmacology of Spirulina (Arthrospira), an unconventional food

Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.     

Ceramic Microtubes from Preceramic Polymers

A novel process for the production of ceramic microtubes involving the microextrusion of preceramic polymers was studied. Microtubes with a wide range of inner and outer diameters and several centimeters long were produced from two silicone resins. A coextrusion approach was also used to extend the forming capability of the technique. The addition of carbon black resulted in electrically conductive silicon oxycarbide (SiOC) ceramic microtubes. SiOC microtubes possessed a high bending strength, ranging from ∼30–1100 MPa.     

An incentive mechanism for message relaying in unstructured peer-to-peer systems

Distributed message relaying is an important function of a peer-to-peer system to discover service providers. Existing search protocols in unstructured peer-to-peer systems create huge burden on communications, cause long response time, or result in unreliable performance. Moreover, with self-interested peers, these systems are vulnerable to the free-riding problem. In this paper we present an incentive mechanism that not only mitigates the free-riding problem, but also achieves good system efficiency in message relaying for peer discovery. In this mechanism promised rewards are passed along the message propagation process. A peer is rewarded if a service provider is found via a relaying path that includes this peer. The mechanism allows peers to rationally trade-off communication efficiency and reliability while maintaining information locality. We provide some analytic insights to the symmetric Nash equilibrium strategies of this game, and an approximate approach to calculate this equilibrium. Experiments show that this incentive mechanism brings a system utility generally higher than breadth-first search and random walks, based on both the estimated utility from our approximate equilibrium and the utility generated from learning in the incentive mechanism.     

3D Knitting for Pneumatic Soft Robotics

Soft robots adapt passively to complex environments due to their inherent compliance, allowing them to interact safely with fragile or irregular objects and traverse uneven terrain. The vast tunability and ubiquity of textiles has enabled new soft robotic capabilities, especially in the field of wearable robots, but existing textile processing techniques (e.g., cut-and-sew, thermal bonding) are limited in terms of rapid, additive, accessible, and waste-free manufacturing. While 3D knitting has the potential to address these limitations, an incomplete understanding of the impact of structure and material on knit-scale mechanical properties and macro-scale device performance has precluded the widespread adoption of knitted robots. In this work, the roles of knit structure and yarn material properties on textile mechanics spanning three regimes–unfolding, geometric rearrangement, and yarn stretching–are elucidated and shown to be tailorable across unique knit architectures and yarn materials. Based on this understanding, 3D knit soft actuators for extension, contraction, and bending are constructed. Combining these actuation primitives enables the monolithic fabrication of entire soft grippers and robots in a single-step additive manufacturing procedure suitable for a variety of applications. This approach represents a first step in seamlessly “printing” conformal, low-cost, customizable textile-based soft robots on-demand.