Elevation of Tear MMP-9 Concentration as a Biomarker of Inflammation in Ocular Pathology by Antibody Microarray Immunodetection Assays

Matrix metalloproteinases are a family of enzymes fundamental in inflammatory processes. Between them, MMP-9 is up-regulated during inflammation; thus, its quantification in non-invasive fluids is a promising approach for inflammation identification. To this goal, a biomarker quantification test was developed for ocular inflammation detection using anti-MMP-9 antibody microarrays (AbMAs). After validation with eight healthy control tear samples characterized by ELISA, 20 samples were tested from individuals diagnosed with ocular inflammation due to: cataracts, glaucoma, meibomian gland dysfunction, allergy, or dry eye. Concentration values of tear MMP-9 were obtained for each sample, and 12 patients surpassed the pathological threshold (30 ng/mL). A significant elevation of MMP-9 concentration in the tears of glaucoma patients compared with healthy controls was observed. In order to evaluate the diagnostic ability, an ROC curve analysis was performed using our data, determining the optimal threshold for the test at 33.6 ng/mL of tear MMP-9. In addition, a confusion matrix was applied, estimating sensitivity at 60%, specificity at 88%, and accuracy at 68%. In conclusion, we demonstrated that the AbMAs system allows the quantification of MMP-9 in pathologies that involve inflammation of the ocular surface.     

Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620—Dipotassium Glycyrrhizinate Effect on Melanoma

Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC₅₀ = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC₅₀) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC₅₀-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10⁻⁶) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10⁻⁴). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation.     

SARS-CoV-2 Infection Dysregulates Cilia and Basal Cell Homeostasis in the Respiratory Epithelium of Hamsters

Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73⁺ and CK14⁺ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways.     

Large-scale phase retrieval

The coherent interaction between an electromagnetic field and a 3D weakly scattering medium results in a simple Fourier transform relationship between the objec...     

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.     

Solving a weak NP-complete problem in polynomial time by using mutual mobile membrane systems

Mutual mobile membrane systems represent a variant of mobile membrane systems in which endocytosis and exocytosis work whenever the involved membranes ??agree?? on the movement by using mutual complement objects placed in membranes. We provide a semi-uniform polynomial solution for a weak NP-complete problem (namely partition problem) by means of mutual mobile membrane systems.     

Self and mutual admittance of slot antennas on a dielectric half-space

In this paper, an efficient implementation of the spectral domain moment technique is presented for computing the self and mutual coupling between slot antennas on a dielectric half-space. It is demonstrated that by the proper selection of the weighting functions in the method of moments, the analytic evaluation or simplification of the transverse moment integrals is enabled. This results into a significant reduction of the required computational labor. The method is then utilized in order to provide design data for the self and mutual admittances between two slot antennas on a dielectric substrate lens in the case of fused quartz (∈ _r =3.80), crystal quartz (∈ _r =4.53), silicon (∈ _r =11.9) and GaAs (∈ _r =12.8). The presented technique and associated results are useful when designing twin slot quasi-optical receivers, imaging arrays, phased arrays or power-combining arrays of slot elements at millimeter-wave frequencies.     

Pre‐reservation of Resources and Controlled Loops for Contention Resolution in OBS Networks

A new scheme to alleviate contention in optical burst switching networks is proposed. It consists of preventively reserving resources in a node, to be used if resources are busy on the next hop node. The burst is sent back to the preceding node and then resent forward. Simulations are carried out to assess the feasibility of the proposed scheme. Its performance is compared with that of contention resolution based on deflection routing.     

Proactive defragmentation in elastic optical networks under dynamic load conditions

The main weakness of elastic optical networks (EON), under dynamic traffic conditions, stems from spectrum fragmentation. A lot of research efforts have been dedicated during recent years to spectrum defragmentation. In this work, a thorough study about proactive defragmentation is carried out. Effects of the different defragmentation parameters on the EON performance are analyzed, and appropriate values of the defragmentation period, which guarantee suitable network performance while keeping the network control complexity at reasonable values, are obtained by means of extensive simulations. Benefit obtained by applying different defragmentation strategies, in terms of increase in the supported load at a given bandwidth blocking probability, is also reported. Different traffic conditions and network topologies are simulated to assess the validity of the obtained results.