Risk of extreme events in the configuration of priority systems

This paper presents a reliability-based framework for the configuration of priority systems that control the risks of extreme transaction latencies. Modeling of priority systems can be computationally complex and lack robustness with respect to the feasible variations of such systems. The analyses tend to be ad hoc and overly particular to the application at hand. Furthermore, modeling of priority systems has focused on assessment of the average latencies, rather than on the potential for extremes of latency. The developed framework includes (i) a compact notation useful for modeling of priority systems, (ii) assessment of the risk of extreme latencies, and (iii) multiobjective analysis for the tuning of system parameters. An acceptable balance is sought among multiple risks of extreme transaction latencies. The framework is demonstrated in the configuration of an e-business server to minimize the lost transactions, e.g. ‘purchase’ requests for which a customer needs to wait longer than 8 s.     

Specificity of a UDP‐GalNAc Pyranose–Furanose Mutase: A Potential Therapeutic Target for Campylobacter jejuni Infections

Pyranose–furanose mutases are essential enzymes in the life cycle of a number of microorganisms, but are absent in mammalian systems, and hence represent novel targets for drug development. To date, all such mutases show preferential recognition of a single substrate (e.g., UDP‐Gal). We report here the detailed structural characterization of the first bifunctional pyranose–furanose mutase, which recognizes both UDP‐Gal and UDP‐GalNAc. The enzyme under investigation (cjUNGM) is involved in the biosynthesis of capsular polysaccharides (CPSs) in Campylobacter jejuni 11168. These CPSs are known virulence factors that are required for adhesion and invasion of human epithelial cells. Using a combination of UV/visible spectroscopy, X‐ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics and CORCEMA‐ST calculations, we have characterized the binding of the enzyme to both UDP‐Galp and UDP‐GalpNAc, and compared these interactions with those of a homologous monofunctional mutase enzyme from E. coli (ecUGM). These studies reveal that two arginines in cjUNGM, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to a GalfNAc‐containing CPS. In ecUGM, these arginines are replaced with histidine and lysine, respectively, and this results in an enzyme that is selective for UDP‐Gal. We propose that these changes in amino acids allow C. jejuni 11168 to produce suitable quantities of the sugar nucleotide substrate required for the assembly of a CPS containing GalfNAc, which is essential for viability.     

Design of polymeric nanoparticles and its applications as drug delivery systems for acne treatment

Objective: The aim of this study was to evaluate a formulation made of poly(lactide-co-glycolide) (PLGA) nanoparticles containing azelaic acid for potential acne treatment.

Methods: Azelaic acid-loaded PLGA nanoparticles were prepared by spontaneous emulsification processes using poloxamer 188 as stabilizer. Several manufacturing parameters such as stirring rate, concentration of stabilizer and different recovery methods were investigated. Nanoparticles were evaluated in terms of size, zeta potential, encapsulation efficiency, release kinetics and permeation kinetics in vitro. Furthermore, in vitro toxicological studies were performed in Saccharomyces cerevisiae model.

Results: The results showed that by adjusting some formulation conditions it was possible to obtain nanoparticles with high loading and a controlled drug release. Freeze-dried recovery altered the nanoparticles structure by enhancing porous structures and mannitol was required to control the mean particle size. The centrifugation recovery was found to be the best approach to nanoparticles recovery. Similar toxicity profiles were observed for both drug-free and azelaic acid-loaded nanoparticles, with concentration-dependent decreases in cell viability.

Conclusion: These results indicate a potential formulation for controlled release delivery of azelaic acid to the follicular unit.     

Influence of Interfacial LSMO Nanoparticles/Layer on the Vortex Pinning Properties of YBCO Thin Film

YBa₂Cu₃O_7?δ (YBCO) thin films have been deposited on bare and La_0.67Sr_0.33MnO₃ (LSMO) modified single crystal SrTiO₃ (STO) substrates. The effect of randomly distributed ferromagnetic LSMO nanoparticles and a complete LSMO layer, present at STO/YBCO interface, on the superconducting properties of YBCO thin films has been investigated by temperature dependent magnetization studies. The YBCO thin film on LSMO nanoparticles decorated STO substrate shows significant improvement in the critical current density and pinning force density as compared to the YBCO thin film deposited on bare STO substrate and this improvement is more significant at higher applied magnetic field. However, the LSMO/YBCO bilayer showed the improved flux pinning properties only up to a magnetic field of 1.5 T above which it deteriorates. In the case of LSMO/YBCO bilayer, the underlying LSMO layer gives rise to magnetic inhomogeneities due to domain structure, which leads to improved flux pinning properties limited to lower field. However, in the case of LSMO nanoparticles decorated substrate, the presence of LSMO nanoparticles at YBCO/STO interface seems to introduce magnetic inhomogeneities as well as structural defects, which might be acting as correlated pinning sites leading to improved flux pinning properties of the YBCO thin film over a wide range of applied magnetic field.     

Probabilistic cumulative damage model to estimate fatigue life

This paper introduces a numerical model to estimate fatigue life under step‐stress conditions, using the Weibull and lognormal distributions. The maximum likelihood method was used to estimate the free parameters of the distributions. The model was fitted to an experimental data on fatigue life in the specimens of steel SAE 8620, by using evolutionary computation to optimize the likelihood function. Results are reported on the values of the parameters and their confidence interval. Also, a validation of the model is discussed using analysis of residuals.     

Measurement of residual stress in EFG ribbons using a phase-shifting IR photoelastic method

This paper reports on the measurement of residual stress in EFG silicon ribbons for solar cell applications using the phase-shifting infrared (IR) photoelastic method. The samples analysed were wafers cut from EFG octagons with 100 mm face width and from EFG 125 mm face-width octagon under development. Experimental results show that the distribution of residual stress in both types of samples is similar, within measurement uncertainties. The average residual stress in the samples is about 8 MPa. Maximum stresses of around 30 MPa are associated with twin and grain boundaries. Significant variations of stress along the growth direction, possibly related to buckling, were also measured.     

Adaptive response: modelling and experimental studies

Adaptive response (AR) is a term that has been generally accepted to describe the ability of a low 'priming' radiation dose to decrease the cell response to a subsequent higher 'challenging' dose. The main proposed mechanisms to explain AR are: increased efficiency of DNA repair and induction of antioxidant enzymes. A model that considers a modulation of the efficiency of DNA repair activity and of the level of antioxidant enzymes, starting from the framework of a lethal-potentially lethal (LPL) model is proposed. The LPL model has been extended with the inclusion of the dynamic variables representing the efficiency of repair, the levels of radiation induced radicals and of antioxidant enzymes. The model used here is able to describe the protective effect of a priming dose. Moreover, in agreement with the data in the literature, the simulations show that the AR happens in given priming dose and priming dose-rate ranges only, and requires at least 4 h to develop. In order to get more insights into the role of cell-cell communication as factors affecting the AR, experimental studies were planned using sparse or confluent AG1522 cell monolayer. The results obtained after gamma irradiation suggest that cell density is a crucial factor for observing an AR.     

New Perspectives on the Sustainable Employment of Chestnut Shells as Active Ingredient against Oral Mucositis: A First Screening

Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC₅₀ = 4.47 μg/mL) and ROO^• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC₅₀ (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM.     

Staphylococcus aureus Exfoliative Toxin E,Oligomeric State and Flip of P186: Implications for Its Action Mechanism

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.