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Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin–Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies. [ABSTRACT FROM AUTHOR]

Featured Application: The methods described here can be applied in interferometric measurements of dynamic events that are challenging to analyze using conventional approaches incapable of evaluating a single interferogram with closed fringes. Frequency-guided sequential demodulation (FSD) is a technique used to recover the phase of closed fringe patterns when only a single interferogram is available. FSD is a sequential method that follows simple and intuitive processing steps for interferogram demodulation, guided by the frequency of the fringes. The objective of this work is to apply an optimizer block that feeds from the first stages of the FSD and make feedback in such a manner as to optimize the search for guided frequencies. This approach significantly reduces demodulation errors, especially when dealing with high-frequency fringe patterns. The results of using the FSD with and without optimizers are compared. The optimizers used are the Harmonic Search Optimization (HSO) as well as the Particle Swarm Optimization (PSO). Results show that FSD with PSO delivers better results compared with other methods here analyzed. [ABSTRACT FROM AUTHOR]

This paper shows a practice to raise the reliability of an electric power system by the installation of distributed generation, taking gasified biomass as fuel. To calculate the reliability index, a probabilistic load flow was used. This index is determined as the fault probability of the system. The resolution of this probabilistic load flow combines the method of cumulants and Gram–Charlier expansion. To achieve the reliability index, simulating a number of contingencies is required; the greater the number of simulated contingencies, the higher the accuracy of the index obtained. This probabilistic technique uses the random variables as starting information, so the two generators and loads are simulated as random variables. The generators of this distributed generation are biomass-fueled gas engines, commonly found in Spain. The simulations carried out on the IEEE 14-bus Test System, including three biomass generators, show that the inclusion of this type of generation improves the overall reliability indices of the electrical system. [ABSTRACT FROM AUTHOR]

Exposure to environmental noise is related to negative health effects. To prevent it, the city councils develop noise maps and action plans to identify, quantify, and decrease noise pollution. Smart cities are deploying wireless acoustic sensor networks that continuously gather the sound pressure level from many locations using acoustics nodes. These nodes provide very relevant updated information, both temporally and spatially, over the acoustic zones of the city. In this paper, the performance of several data clustering techniques is evaluated for discovering and analyzing different behavior patterns of the sound pressure level. A comparison of clustering techniques is carried out using noise data from two large cities, considering isolated and federated data. Experiments support that Hierarchical Agglomeration Clustering and K-means are the algorithms more appropriate to fit acoustics sound pressure level data. [ABSTRACT FROM AUTHOR]

The isothermal crystallization of poly(ethylene terephthalate) (PET) homopolymers with different molecular weight was studied in a wide temperature range (140-230 °C) using different experimental techniques. Three different morphological regions, labeled r1, r2 and r3, were distinguished as a function of crystallization temperature (Tc). In r1 (low Tc) crystallized samples were characterized by a low crystalline degree with a small spherulite texture containing thin crystals. In r2 (intermediate Tc) samples showed medium size spherulites composed of two distinct crystalline families (thin and thick crystals). In this temperature range, the crystallization exhibited a maximum value and it was associated with a high content of secondary crystals. In r3 (high Tc), samples presented considerable amorphous zones and regions consisting of oversized spherulites containing only thick crystals. Time-resolved wide-angle X-ray diffraction measurements, using synchrotron radiation, indicated a rapid evolution of the crystalline degree within the second region, incontrast with the quite slow evolution observed in the third region. On the other hand, by small-angle X-ray scattering (SAXS) and time-resolved SAXS experiment, it was found that the long period (L) as well as the lamellar thickness (lc) increase as a function of Tc, corroborating the formation of the thickest crystals in the third region. From all these observations, a morphological model was proposed for each region. [ABSTRACT FROM AUTHOR]

This work presents a comprehensive analysis of two cubic techniques for Power Flow (PF) studies. In this regard, the families of Weerakoon-like and Darvishi-like techniques are considered. Several theoretical findings are presented and posteriorly confirmed by multiple numerical results. Based on the obtained results, the Weerakoon's technique is considered more reliable than the Newton-Raphson and Darvishi's methods. As counterpart, it presents a high computational burden. Regarding this point, the Darvishi's technique has turned out to be quite efficient and fully competitive with the Newton's scheme. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) patients have an exacerbated risk of head and neck squamous cell carcinoma (HNSCC). Treatment is challenging as FA patients display enhanced toxicity to standard treatments, including radio/chemotherapy. Therefore, better therapies as well as new disease models are urgently needed. We have used CRISPR/Cas9 editing tools in order to interrupt the human FANCA gene by the generation of insertions/deletions (indels) in exon 4 in two cancer cell lines from sporadic HNSCC having no mutation in FA-genes: CAL27 and CAL33 cells. Our approach allowed efficient editing, subsequent purification of single-cell clones, and Sanger sequencing validation at the edited locus. Clones having frameshift indels in homozygosis did not express FANCA protein and were selected for further analysis. When compared with parental CAL27 and CAL33, FANCA-mutant cell clones displayed a FA-phenotype as they (i) are highly sensitive to DNA interstrand crosslink (ICL) agents such as mitomycin C (MMC) or cisplatin, (ii) do not monoubiquitinate FANCD2 upon MMC treatment and therefore (iii) do not form FANCD2 nuclear foci, and (iv) they display increased chromosome fragility and G2 arrest after diepoxybutane (DEB) treatment. These FANCA-mutant clones display similar growth rates as their parental cells. Interestingly, mutant cells acquire phenotypes associated with more aggressive disease, such as increased migration in wound healing assays. Therefore, CAL27 and CAL33 cells with FANCA mutations are phenocopies of FA-HNSCC cells. [ABSTRACT FROM AUTHOR]