Enhancing the Therapeutic Potential of Mesenchymal Stromal Cell-Based Therapies with an Anti-Fibrotic Agent for the Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) affects 1 in 10 members of the general population, placing these patients at an increasingly high risk of kidney failure. Despite the significant burden of CKD on various healthcare systems, there are no effective cures that reverse or even halt its progression. In recent years, human bone-marrow-derived mesenchymal stromal cells (BM-MSCs) have been recognised as a novel therapy for CKDs, owing to their well-established immunomodulatory and tissue-reparative properties in preclinical settings, and their promising safety profile that has been demonstrated in patients with CKDs from several clinical trials. However, renal fibrosis (scarring), a hallmark of CKD, has been shown to impair the viability and functionality of BM-MSCs post-transplantation. This has suggested that BM-MSCs might require a pre-treatment or adjunct therapy that can enhance the viability and therapeutic efficacy of these stromal cells in chronic disease settings. To address this, recent studies that have combined BM-MSCs with the anti-fibrotic drug serelaxin (RLX), have demonstrated the enhanced therapeutic potential of this combination therapy in normotensive and hypertensive preclinical models of CKD. In this review, a critical appraisal of the preclinical data available on the anti-fibrotic and renoprotective actions of BM-MSCs or RLX alone and when combined, as a treatment option for normotensive vs. hypertensive CKD, is discussed.     

Leptin Signaling in Obesity and Colorectal Cancer

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.     

Description and composition of bio-inspired design patterns: a complete overview

In the last decade, bio-inspired self-organising mechanisms have been applied to different domains, achieving results beyond traditional approaches. However, researchers usually use these mechanisms in an ad-hoc manner. In this way, their interpretation, definition, boundary (i.e. when one mechanism stops, and when another starts), and implementation typically vary in the existing literature, thus preventing these mechanisms from being applied clearly and systematically to solve recurrent problems. To ease engineering of artificial bio-inspired systems, this paper describes a catalogue of bio-inspired mechanisms in terms of modular and reusable design patterns organised into different layers. This catalogue uniformly frames and classifies a variety of different patterns. Additionally, this paper places the design patterns inside existing self-organising methodologies and hints for selecting and using a design pattern.     

Comparison of the Determination of Eight Cholesterol Oxides in Dry�CCured Shoulder by GC�CFID, GC�CMS, and GC Tandem Mass Spectrometry

The analysis of eight cholesterol oxidation products: 7α–hydroxycholesterol, 7β–hydroxycholesterol, α–epoxycholesterol, β–epoxycholesterol, 20α–hydroxycholesterol, cholestanetriol, 25–hydroxycholesterol, and 7–ketocholesterol in dry–cured shoulder was carried out. The extraction of lipids was performed by using the Bligh and Dyer method (1959). Interferences were removed by solid-phase extraction (SPE) in two steps with silica and aminipropylsilica SPE columns. The separation of the eight cholesterol oxidation products was done by gas chromatography, and the detection was performed by flame ionization detection (FID) and mass spectrometry (MS). The results obtained from the use of both systems of detection were compared. The results showed that gas chromatography-mass spectrometry (GC–MS) was the most suitable technique to obtain reliable quantitative data, and significant differences (p < 0.05) between FID and MS determining 7α–hydroxycholesterol, 20α–hydroxycholesterol, and 25–hydroxycholesterol were observed. For the determination of cholesterol oxidation products, it was necessary to apply gas chromatography-tandem mass spectrometry to increase the sensitivity and to avoid interference from other compounds.     

A residual-based a posteriori error estimator for a fully-mixed formulation of the Stokes–Darcy coupled problem

In this paper we develop an a posteriori error analysis of a new fully mixed finite element method for the coupling of fluid flow with porous media flow in 2D. Flows are governed by the Stokes and Darcy equations, respectively, and the corresponding transmission conditions are given by mass conservation, balance of normal forces, and the Beavers–Joseph–Saffman law. We consider dual-mixed formulations in both media, which yields the pseudostress and the velocity in the fluid, together with the velocity and the pressure in the porous medium, and the traces of the porous media pressure and the fluid velocity on the interface, as the resulting unknowns. The set of feasible finite element subspaces includes Raviart–Thomas elements of lowest order and piecewise constants for the velocities and pressures, respectively, in both domains, together with continuous piecewise linear elements for the traces. We derive a reliable and efficient residual-based a posteriori error estimator for the coupled problem. The proof of reliability makes use of the global inf–sup condition, Helmholtz decompositions in both media, and local approximation properties of the Clément interpolant and Raviart–Thomas operator. On the other hand, inverse inequalities, the localization technique based on element-bubble and edge-bubble functions, and known results from previous works, are the main tools for proving the efficiency of the estimator. Finally, some numerical results confirming the theoretical properties of this estimator, and illustrating the capability of the corresponding adaptive algorithm to localize the singularities of the solution, are reported.     

Electrical and Thermal Properties of Twin-Screw Extruded Multiwalled Carbon Nanotube/Epoxy Composites

This paper presents the experimental results of dispersing multiwalled carbon nanotubes (MWNTs) into epoxy (space grade structural adhesive) nanocomposites using co-rotating twin screw extrusion process. Two sets of specimens were prepared; set 1 with ultrasonication for predispersing MWNT before extrusion and set 2 direct dispersion of MWNT in the extruder. MWNT was loaded up to 8 vol.% in both the sets. The specimens were characterized for room temperature volume and surface resistivities as per ASTM D257 using Keithley Model 6517 and for thermal conductivity in the temperature range ?50 to 150 °C as per ASTM E 1530 using Thermal Conductivity Instrument (TCI) 2022 SX211. The volume resistivity of sets 1 and 2 decreased to an extent of 10¹¹ and 10⁹ respectively. The surface resistivity drop was of the order of 10⁹ for both the sets. These drops corresponded to the maximum MWNT loading of 8 vol.%. Electrical conductivity values of the specimens were fitted into the Power Law Model to evaluate the critical exponent. Both sets 1 and 2 showed increase in thermal conductivity with increase in temperature in the testing range. Thermal conductivity increased with increase in filler loading and the maximum increase was 60% at 150 °C in case of 8 vol.% MWNT nanocomposites for set 1. The corresponding value for the set 2 was 25%. Thermal conductivity values were predicted using Lewis Nielson model. DSC of the specimens showed increase in glass transition temperature with increase in filler loading. The dispersion of the nanofillers was studied using SEM and the surface morphology using AFM.     

CMOS harmonic upconverter with power management of $$2{\bf nd}$$ harmonic for wideband short-range communications

The design and simulation of a 2nd harmonic based upconverter is introduced. With the proposed upconverter, it is possible to reach a good noise figure with power and area reduction. The design of the circuit was made with the UMC \(0.18\,\upmu \hbox {m}\) Mixed Mode/RF CMOS technology. However, the design methodology can be extended to a different CMOS process. According to the performance exhibited by the purposed mixer, it may be useful in wideband short-range communication technologies, such as certified wireless USB.     

Distributed Approach to Control and Manage Context-based Multi-virtual Networks

Using the flexibility of Wireless Mesh Networks (WMNs) and network virtualization, we define a novel architecture that provides personalized access for users by splitting a WMN into several adaptable Virtual Networks (VNs). Each VN is configured to meet specific levels of user context demands (context can span from security, mobility or service requirements). Users are grouped according to similarity of their context, and associated to VNs matching their context. To break the traditional centralized solutions for WMN and virtualization control, this paper defines an overall framework to distribute the control responsibilities along the architectural entities, which can then cooperate to autonomously discover, select, create, extend or remove VNs on-demand according to user and WMN dynamics. We also propose an analytical model to evaluate several performance aspects of the distributed VN control when compared to centralized or decentralized solutions, validating the model against a simulation study.