Optimal hybrid resonant current controller for microgrids connected to an unbalanced IEEE test distribution network.

Microgrids (MGs) based on renewable energies have emerged as a proficient strategy for tackling power quality issues in conventional distribution networks. Nonetheless, MG systems require a suitable control scheme to supply energy optimally towards the electrical grid. This paper presents an innovative framework for designing hybrid Proportional-Resonant (PR) controllers with Linear Quadratic Regulators (LQR), PR+LQR, which merge relevant properties of PR and LQR controllers. This method simultaneously determines the MG control parameters and the current unbalanced factor generated at the distribution network. We select the traditional IEEE 13-bus test feeder network and place two MGs at strategic locations to validate our approach. Moreover, we use the Grey Wolf Optimizer (GWO) to find control parameters through a reliable fitness function that leads to high-performance microgrids. Finally, we conceive several tests to assess the efficacy of GWO for tuning the hybrid controller and compare the resulting data across distinct realistic operation conditions representing power quality events. So, we choose four case studies considering different renewable energy penetration indexes and power factors and evaluate the effects of the MGs over the distribution grid. We also compare the proposed hybrid PR+LQR controller against closely-related alternatives from the literature and validate its robustness and stability through the disk margin approach and the Nyquist criterion. Our numerical simulations prove that hybrid controllers driven by GWO are highly reliable strategies, yielding an average unbalanced current reduction of 30.03%.

Can serum M30 levels be utilized as an activation marker in patients with ulcerative colitis?

SUMMARY OBJECTIVE: Ascertainment of disease activation is an important component of therapeutic decisions in ulcerative colitis patients and may present certain clinical challenges. The objective of this study was to determine serum levels of the M30 fragment of cytokeratin 18 and its utility as an activation marker in patients with ulcerative colitis, who are known to have increased apoptosis. METHODS: A total of 60 ulcerative colitis (30 active and 30 remission) patients aged over 18 years and 29 healthy individuals as controls were included in the study. M30, C-reactive protein, and mean platelet volume were evaluated in all participants and compared between ulcerative colitis patients and controls, as well as between those with active disease or remission. RESULTS: Although ulcerative colitis patients with active disease had higher M30 levels than those in remission, the difference was not statistically significant (p=0.085). The mean M30 levels tended to increase with increasing extent of involvement, although the differences were not significant (p=0.065). The comparison of C-reactive protein and mean platelet volume according to the site of involvement, however, showed significant differences (p=0.02 and 0.004, respectively). M30 did not show significant correlations with C-reactive protein, mean platelet volume, and Mayo Score (p=0.0834, 0.768, and 0.401, respectively). CONCLUSIONS: Our results suggest that, in contrast to C-reactive protein and mean platelet volume, M30 levels do not have a significant role as an activation marker in ulcerative colitis patients. Thus, we believe that M30 may not represent an appropriate marker to be used for this purpose.

Novel Multipotent Amantadine-M30D Hybrids with Highly Selective Butyrylcholinesterase Inhibition and Neuroprotective Effects as Effective Anti-Alzheimer's Agents.

As a contribution to the development of new dual/multifunctional drugs, a novel therapeutical scaffold merging key structural features from memantine and M30D was designed, synthesized, and explored for its AChE/BuChE inhibitory activity and neuroprotective effects. All synthetized hybrids were not able to inhibit AChE, but most of them exhibit inhibition with high selectivity toward butyrylcholinesterase (BuChE). Notably, among the tested compounds, amantadine/M30D hybrids with six, seven, nine, and twelve methylene groups in the spacer (5d, 5e, 5f, and 5g) not only highlighted having the best potency and selective butyrylcholinesterase inhibition greater than 83% but also, particularly 5e and 5d, elicited considerable neuroprotection when evaluated in pretreatment conditions, by reducing injury effects caused by glutamate with maximum protection reached about 47.82 ± 0.81% (5e) and 42 ± 2.20% (5d) in comparison with memantine (37.27 ± 2.69%). Likewise, we chose 5e as the hit compound, which in a glutamate excitotoxity coculture model prevented astroglia reactivity and neuronal death, as well as a 91% restoration of calcium levels and an increasing ATP level in both pre-/post-treatments of 61.48 ± 4.60 and 45.16 ± 10.55%, respectively. Regarding docking studies, a blockade of the NMDA channel pore by 5e would explain its neuroprotective response. Finally, the hit compound 5e exhibited in vitro blood-brain barrier (BBB) permeability and human plasma stability, as well as an optimal in silico neuropharmacokinetic profile. From a therapeutic perspective, merging key pharmacophoric features from memantine and M30D provides a new medicinal scaffold with dual-/multifunctional properties and human plasma stability for the future development of potential drugs for treating AD.

An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure.

Amyloid beta (Aß) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer's disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aß peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aß experiments, as it allows to explore the binding mechanism between metal ions and Aß oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aß peptides. Aß oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aß binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aß. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aß dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation.

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study

ABSTRACT BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

M30/M65 ratio predicts the outcome of paclitaxel chemotherapy for NSCLC.

PURPOSE: Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC. METHODS: The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed. RESULT: We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01). CONCLUSION: Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC.

Role of apoptosis in erosive and reticular oral lichen planus exhibiting variable epithelial thickness

Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical types. Reticular and erosive forms are the most common. Although the cause of OLP remains speculative, many findings suggest auto-immune involvement, mediated by T lymphocytes against the basal keratinocytes. Inflammation, mechanical trauma or toxic agents can affect the epithelial homeostasia. Increased apoptosis may cause a decrease in epithelial thickness reflecting in the activity of the lesion. The objective of this study was to evaluate the occurrence of apoptosis and epithelial thickness in reticular and erosive forms of OLP. 15 samples of OLP each type (reticular and erosive) plus 10 of healthy mucosa were collected and processed. After morphometry, the apoptotic index and epitelial thickness were obtained. TUNEL and M30 CytoDEATH immunohistochemical assay were used to validate the morphologic criteria used. Apoptosis in the erosive OLP was significantly more intense than in the reticular type and both forms of OLP presented more apoptosis than the healthy oral mucosa. Healthy oral mucosa was thicker than both OLP forms and thicker in OLP reticular form than in the erosive one. The clinical differences between reticular and erosive forms of OLP are related to variations in epithelial thickness and in intensity of apoptosis.

O líquen plano oral (LPO) é uma doença inflamatória crônica com diferentes tipos clínicos. As mais comuns são as formas reticular e erosiva. Embora a causa do LPO permaneça no campo especulativo, muitos achados sugerem tratar-se de uma doença auto-imune, mediada por linfócitos T que têm como alvo os ceratinócitos basais. Inflamação, trauma mecânico ou agentes tóxicos podem afetar a homeostasia epitelial. O aumento da apoptose pode levar a uma diminuição da espessura epitelial e isto refletir na atividade da doença. O objetivo deste estudo foi avaliar a ocorrência de apoptose e a espessura epitelial nas formas reticular e erosiva de LPO. 15 amostras de LPO de cada tipo reticular e erosivo, além de 10 amostras de mucosa saudável foram coletadas e processadas. Depois da morfometria, o índice apoptótico (IA) e a espessura do epitélio foram obtidas. Reação de TUNEL e imunohistoquímica do M30 CytoDeath foram usadas para validação dos critérios morfológicos. A apoptose no LPO erosivo foi significativamente maior que no tipo reticular e ambas as formas de LPO apresentaram mais apoptose que a mucosa oral normal. A mucosa oral normal foi mais espessa que ambas as formas de LPO, sendo que, a forma reticular foi mais espessa que o tipo erosivo. As diferenças clínicas entre as formas reticular e erosiva de LPO têm relação com as variações na espessura epitelial e na intensidade da apoptose.