Laminin as a Biomarker of Blood–Brain Barrier Disruption under Neuroinflammation: A Systematic Review

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood–brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (β and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.     

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.     

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.     

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.     

RF Power Amplifier Behavioral Modeling Based on Takenaka–Malmquist–Volterra Series

In this paper, a Takenaka–Malmquist–Volterra (TMV) model structure is employed to improve the approximations in the low-pass equivalent behavioral modeling of radio frequency (RF) power amplifiers (PAs). The Takenaka–Malmquist basis generalizes the orthonormal basis functions previously used in this context. In addition, it allows each nonlinearity order in the expanded Volterra model to be parameterized by multiple complex poles (dynamics). The state-space realizations for the TMV models are introduced. The pole sets for the TMV model and also for the previous Laguerre–Volterra (LV) and Kautz–Volterra (KV) models are obtained using a constrained nonlinear optimization approach. Based on experimental data measured on a GaN HEMT class AB RF PA excited by a WCDMA signal, it is observed that the TMV model reduces the normalized mean-square error and the adjacent channel error power ratio for the upper adjacent channel (upper ACEPR) by 1.6 dB when it is compared to the previous LV and KV models under the same computational complexity.     

A time Petri net-based method for embedded hard real-time software synthesis

Over the last few years, embedded software synthesis has drawn much attention. However, few works deal with software synthesis for hard real-time systems considering arbitrary inter-tasks precedence and exclusion relations. Code generation for meeting all timing and resource constraints is not a trivial task. Thus, this research area has several open issues, mainly related to generation of predictable-guaranteed scheduled code. The method proposed in this paper starts from a high-level specification, and automatically translates such specification into a time Petri net model; this model is adopted for finding a feasible static schedule meeting all constraints. If found, the approach generates a scheduled code, based on the found feasible schedule. Therefore, the user just enter the specification and receives, as result, the scheduled code. Thus, all intermediary phases are hidden from the users.     

Urban data and urban design: A data mining approach to architecture education

The configuration of urban projects using Information and Communication Technologies is an essential aspect in the education of future architects. Students must know the technologies that will facilitate their academic and professional development, as well as anticipating the needs of the citizens and the requirements of their designs. In this paper, a data mining approach was used to outline the strategic requirements for an urban design project in an architecture course using a Project-Based Learning strategy. Informal data related to an award-winning public space (Gillett Square in London, UK) was retrieved from two social networks (Flickr and Twitter), and from its official website. The analysis focused on semantic, temporal and spatial patterns, aspects generally overlooked in traditional approaches. Text-mining techniques were used to relate semantic and temporal data, focusing on seasonal and weekly (work-leisure) cycles, and the geographic patterns were extracted both from geotagged pictures and by geocoding user locations. The results showed that it is possible to obtain and extract valuable data and information in order to determine the different uses and architectural requirements of an urban space, but such data and information can be challenging to retrieve, structure, analyze and visualize. The main goal of the paper is to outline a strategy and present a visualization of the results, in a way designed to be attractive and informative for both students and professionals – even without a technical background – so the conducted analysis may be reproducible in other urban data contexts.     

A scanning electron microscopy study of diseased root surfaces conditioned with EDTA gel plus Cetavlon after scaling and root planing

In the present investigation, a scanning electron microscopy analysis was performed to evaluate the effects of the topical application of ethylenediaminetetraacetic acid (EDTA) gel associated with Cetavlon (EDTAC) in removing the smear layer and exposing collagen fibers following root surface instrumentation. Twenty-eight teeth from adult humans, single rooted and scheduled for extraction due to periodontal reasons, were selected. Each tooth was submitted to manual (scaling and root planing) instrumentation alone or combined with ultrasonic instruments, with or without etching using a 24% EDTAC gel. Following extraction, specimens were processed and examined under a scanning electron microscope. A comparative morphological semi-quantitative analysis was performed; the intensity of the smear layer and the decalcification of cementum and dentinal surfaces were graded in 12 sets using an arbitrary scale ranging from 1 (area covered by a smear layer) to 4 (no smear layer). Root debridement with hand instruments alone or combined with ultrasonic instruments resulted in a similar smear layer covering the root surfaces. The smear layer was successfully removed from the surfaces treated with EDTAC, which exhibited numerous exposed dentinal tubules and collagen fibers. This study supports the hypothesis that manual instrumentation alone or instrumentation combined with ultrasonic instrumentation is unable to remove the smear layer, whereas the subsequent topical application of EDTAC gel effectively removes the smear layer, uncovers dentinal openings and exposes collagen fibers.     

Multicast deflector

Technological evolution is leading telecommunications toward all-IP scenarios, where multiple services are transported as IP packets. Among these services is the broadcast of video. A possible mechanism for broadcasting multiple video channels over IP is to use IP multicast, and let each client decide about the reception of a channel. The secure IP multicast specified by the IETF MSEC working group is a candidate solution for securing these broadcast services. In this paper we propose a new solution for supporting the broadcast of multiple video channels which can be accessed only by authorized users; besides, when a video channel is not visualized in the last mile its transmission is temporarily suspended, so that the cable can be used for other services such as standard Internet access.