Proactive multipath routing with a predictive mechanism in software‐defined networks

With the growth of network traffic volume, link congestion cannot be avoided efficiently with conventional routing protocols. By utilizing the single shortest‐path routing algorithm from link state advertisement information, standard routing protocols lack of global awareness and are difficult to be modified in a traditional network environment. Recently, software‐defined network (SDN) provided innovative architecture for researchers to program their own network protocols. With SDN, we can divert heavy traffic to multiple paths in order to resolve link congestion. Furthermore, certain network traffics come in periodic fashion such as peak hours at working days so that we can leverage forecasting for resource management to improve its performance. In this paper, we propose a proactive multipath routing with a predictive mechanism (PMRP) to achieve high‐performance congestion resolution. PMRP has two main concepts: (a) a proactive mechanism where PMRP deploys M/M/1 queue and traffic statistics to simulate weighted delay for possible combinations of multipaths placement of all subnet pairs, and leverage genetic algorithm for accelerating selection of optimized solution, and (b) a predictive mechanism whereby PMRP uses exponential smoothing for demand traffic volumes and variance predictions. Experimental results show a 49% reduction in average delay as compared with single shortest routing, and a 16% reduction in average delay compared with utilization & topology‐aware multipath routing (UTAMP). With the predictive mechanism, PMRP can decrease an additional 20% average delay. Furthermore, PMRP reduces 93% of flow table usage on average as compared with UTAMP.     

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Solvent‐Assisted Low‐Temperature Crystallization of SnO2 Electron‐Transfer Layer for High‐Efficiency Planar Perovskite Solar Cells

A high‐quality polycrystalline SnO₂ electron‐transfer layer is synthesized through an in situ, low‐temperature, and unique butanol–water solvent‐assisted process. By choosing a mixture of butanol and water as a solvent, the crystallinity is enhanced and the crystallization temperature is lowered to 130 °C, making the process fully compatible with flexible plastic substrates. The best solar cells fabricated using these layers achieve an efficiency of 20.52% (average 19.02%) which is among the best in the class of planar n–i–p‐type perovskite (MAPbI₃) solar cells. The strongly reduced crystallization temperature of the materials allows their use on a flexible substrate, with a resulting device efficiency of 18%.     

Multistimuli‐Responsive Display Materials to Encrypt Differentiated Information in Bright and Dark Fields

Visually readable codes play a crucial role in anticounterfeiting measures. However, current coding approaches do not enable time‐dependent codes to be visually read, adjusted, and differentiated in bright and dark fields. Here, using a combined strategy of piezoelectric lattice selection, oxygen vacancy engineering, and activator doping, a lanthanide ion‐doped titanate is developed that integrates mechano‐, thermo‐, and photo‐responsive color change (>18 h for bright field), persistent luminescence (>6 h for dark field), and stimulus‐triggered multimodal luminescence. The feasibility of optical encoding, visual displaying, and stimulus‐responsive encrypting of time‐dependent, dual‐field information by using the developed material is demonstrated. In particular, the differentiated display of dual‐field modes is achieved by combining mechanostimulated abolition of only the persistent luminescence and thermo‐ and photostimulated reversal of both the color change and persistent luminescence. The results provide new insights for designing advanced materials and encryption technologies for photonic displays, information security, and intelligent anticounterfeiting.     

Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.Subject terms: Heart failure, Embryonic stem cells, Stem-cell differentiation     

Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.Subject terms: Chemotaxis, Bone, Ion channel signalling, Rheumatoid arthritis, Drug development     

Multistage homotopy perturbation method for nonlinear reaction networks

In this paper, we present the multistage homotopy perturbation method for finding the solution of the chemical kinetics with nonlinear reactions. We develop a general scheme for finding the analytic solution of chemical reaction networks and apply it to motivating chemical examples such as the enzyme kinetics model and the Brusselator model. We illustrate the numerical result for the models and show the accuracy of the method.     

A rapid and selective HPLC‐UV method for the quantitation of efavirenz in plasma from patients on concurrent HIV/AIDS and tuberculosis treatments

Owing to heterogeneity in therapeutic response, efavirenz is of research and clinical interest. There is a need to quantitate it using noncostly and selective methods. A method for efavirenz quantitation in plasma containing HIV and tuberculosis drugs was developed. Chromatographic separation was carried out using a C₁₈ column. The mobile phase consisted of 0.1% formic acid and acetonitrile, and was pumped at a flow rate of 0.3 mL/min. Efavirenz and ritonavir (internal standard) were monitored at 247 nm. Plasma proteins were precipitated by centrifugation. The analysis time was 6 min. The response was linear (r = 0.9997). The accuracy ranged between 98 and 115% (intraday) and between 99 and 117% (interday). The precision ranged from 1.670 to 4.087% (intraday) and from 3.447 to 13.347% (interday). Recovery ranged from 98 to 132%. Stability ranged between 99 and 123%. The selectivity was proven by analysis of drugs used for the management of HIV/AIDS and tuberculosis. Plasma sample analysis showed an efavirenz retention time of 5.57 min and a peak plasma concentration of 2.4 µg/mL occurring at 2 h. This method is rapid and selective, and thus suitable for monitoring efavirenz in patients with HIV/AIDS alone or co‐infected with tuberculosis in a less resourced setting. Copyright © 2013 John Wiley & Sons, Ltd.