Exploring critical attributes during air traffic congestion with a fuzzy DEMATEL–ANP technique: a case study in Ninoy Aquino International Airport

Railway Engineering Science - The constant growth of air travel in the Philippines has brought about significant consequences to air traffic congestion. Given limited resources, major airports seek...     

Al-Tolerant Barley Mutant hvatr.g Shows the ATR-Regulated DNA Damage Response to Maleic Acid Hydrazide

ATR, a DNA damage signaling kinase, is required for cell cycle checkpoint regulation and detecting DNA damage caused by genotoxic factors including Al³⁺ ions. We analyzed the function of the HvATR gene in response to chemical clastogen-maleic acid hydrazide (MH). For this purpose, the Al-tolerant barley TILLING mutant hvatr.g was used. We described the effects of MH on the nuclear genome of hvatr.g mutant and its WT parent cv. “Sebastian”, showing that the genotoxic effect measured by TUNEL test and frequency of cells with micronuclei was much stronger in hvatr.g than in WT. MH caused a significant decrease in the mitotic activity of root cells in both genotypes, however this effect was significantly stronger in “Sebastian”. The impact of MH on the roots cell cycle, analyzed using flow cytometry, showed no differences between the mutant and WT.     

Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.     

Interrelated Mechanism by Which the Methide Quinone Celastrol,Obtained from the Roots of Tripterygium wilfordii,Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger

We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.     

Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Characterization of polar organic compounds in the organic film on indoor and outdoor glass windows

Organic films on an impervious surface (window glass) were sampled at paired indoor-outdoor sites in July 2000 and characterized for their paraffinic and polar organic compositions along an urban-rural transect. Four classes of polar compounds (C11-C31 aliphatic monocarboxylic, C6-C14 dicarboxylic, nine aromatic polycarboxylic, and five terpenoid acids) constituted between 81 and 95% (w/w) of the total organic fraction analyzed comprising n-alkanes (C10-C36), 46 PAH, 97 PCBs, and 18 OC pesticides. Concentrations of the polar compounds plus their precursors, n-alkanes, ranged from 8 to 124 microg m(-20 and were dominated by monocarboxylic acids (67-89%, w/w). On outdoor windows, n-alkanes, aromatic acids, and terpenoid acids decreased in concentration along the urban-rural transect. The carbon preference index values and the interpretations of individual compounds indicate that the main sources of n-alkanes were plant waxes followed by petrogenic sources; monocarboxylic and dicarboxylic acids were from plant waxes and animal fats. Results of principal component analysis showed closer correspondence between outdoor and indoor signatures than among locations. In outdoor films, these compounds are suggested to play an important role in mediating chemical fate in urban areas by air-film exchange and facilitating "wash-off" due to their surfactant-like properties. In indoor films, these compounds provide a medium for the accumulation of more toxic compounds.     

Evaluation of the interaction between sodium hypochlorite and several formulations containing chlorhexidine and its effect on the radicular dentin—SEM and push‐out bond strength analysis

The aim of the current study was to evaluate the presence of debris and smear layer after endodontic irrigation with different formulations of 2% chlorhexidine gluconate (CHX) and its effects on the push‐out bond strength of an epoxy‐based sealer on the radicular dentin. One hundred extracted human canines were prepared to F5 instrument and irrigated with 2.5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Fifty teeth were divided into five groups (n = 10), according to the final irrigation protocol with different 2% CHX formulations: G1 (control, no final rinse irrigation), G2 (CHX solution), G3 (CHX gel), G4 (Concepsis), and G5 (CHX Plus). In sequence, the specimens were submitted to scanning electron microscopy (SEM) analysis, in the cervical‐medium and medium‐apical segments, to evaluate the presence of debris and smear layer. The other 50 teeth were treated equally to a SEM study, but with the root canals filled with an epoxy‐based endodontic sealer and submitted to a push‐out bond strength test, in the cervical, middle, and apical thirds. G2, G3, G4, and G5 provided higher precipitation of the debris and smear layer than G1 (P < 0.05), but these groups were similar to each other (P > 0.05), in both segments. The values obtained in the push out test did not differ between groups, independent of the radicular third (P > 0.05). The CHXs formulations caused precipitation of the debris and smear layer on the radicular dentin, but these residues did not interfere in the push‐out bond strength of the epoxy‐based sealer. Microsc. Res. Tech. 77:17–22, 2014. © 2013 Wiley Periodicals, Inc.     

Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

The catabolism and structure of high‐density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A‐I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL‐apo A‐I was evaluated by exogenous radiolabelling with iodine‐131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol‐to‐phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [¹³¹I]‐apo A‐I in the proteinuric rabbits was faster (FCR = 0.036 h^?1) compared to control rabbits group (FCR = 0.026 h^?1, P < 0.05). Apo E increased and apo A‐I decreased in HDL, whereas PON‐1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase‐1 activity, and a rise in the fractional catabolic rate of the [¹³¹I]‐apo A‐I.