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This paper presents an optimization method for the structural design of horizontal-axis wind turbine (HAWT) blades based on the particle swarm optimization algorithm (PSO) combined with the finite element method (FEM). The main goal is to create an optimization tool and to demonstrate the potential improvements that could be brought to the structural design of HAWT blades. A multi-criteria constrained optimization design model pursued with respect to minimum mass of the blade is developed. The number and the location of layers in the spar cap and the positions of the shear webs are employed as the design variables, while the strain limit, blade/tower clearance limit and vibration limit are taken into account as the constraint conditions. The optimization of the design of a commercial 1.5 MW HAWT blade is carried out by combining the above method and design model under ultimate (extreme) flap-wise load conditions. The optimization results are described and compared with the original design. It shows that the method used in this study is efficient and produces improved designs.

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

In the present study, several physiological responses of the red marine alga Porphyra haitanesis to elevated concentrations of copper (up to 50 μM) and zinc (up to 100 μM) were investigated. Our results showed that the effects of Cu2+ and Zn2+ on growth, photosynthetic pigments (chlorophylls and carotenoids), phycobiliprotein and metabolism (the fluorescence emission spectra and the activities of photosystemII) did not follow the same pattern. The relative growth rate was inhibited by different concentrations of Cu2+, and was slightly increased at lower concentrations (up to 10 μM) and inhibited at higher Zn2+concentrations. On the other hand, the phycoerythrin contents were slightly increased at relatively low concentrations (up to 1 μM Cu2+ or 20 μM Zn2+) and inhibited by high Cu2+ and Zn2+ concentrations. Moreover, photosynthesis and respiration showed an increase in the amount of oxygen exchange in response to relatively low Cu2+ (up to 1 μM) and Zn2+ concentrations (up to 10 μM), and a reduction to relatively high Cu2+ and Zn2+ concentrations. Oxygen evolution was more sensitive than oxygen uptake to Cu2+ and Zn2+. In addition, the photoreductive activities and fluorescence emission of photosystem II (PS II) were enhanced by lower concentrations of Cu2+ (up to 0.1 μM) and Zn2+ (up to 10 μM) and inhibited by higher concentrations. Furthermore, the intensity of chlorophyll a fluorescence and the active PSII reaction centers followed a similar pattern in response to elevated concentrations of Cu2+ and Zn2+. These results suggest that lower concentrations of Cu2+ and Zn2+ affected the metabolism of P. haitanesis, which was inhibited by higher concentrations of these metals.No presente estudo foram investigadas as respostas fisiológicas da alga vermelha Porphyra haitanesis às elevadas concentrações de cobre (acima de 50 μM) e de zinco (acima de 100 μM). Os resultados mostram que os efeitos de Cu2+ e Zn2+ sobre o crescimento, pigmentos fotossintéticos (clorofilas e carotenóides), ficobiliproteína e metabolismo (o espectro de emissão de fluorescência e as atividades do fotossistema) não seguem o mesmo padrão. A taxa de crescimento relativo foi inibida por diferentes concentrações de Cu2+ e, em presença de Zn2+, aumentou ligeiramente em baixas concentrações (abaixo de 10 μM) e foi inibida em altas concentrações. Por outro lado, os teores de ficoeritrina apresentaram leve aumento em concentrações relativamente baixas de Cu2+ e Zn2+ (até 1 μM Cu2+ e até 20 μM Zn2+, respectivamente) e foram inibidas por altas concentrações. Além disso, tanto a fotossíntese quanto a respiração mostraram aumento nas trocas de oxigênio em resposta às concentrações relativamente baixas de Cu2+ (até 1 μM) e de Zn2+ (até 10 μM), além da redução em concentrações relativamente altas desses metais. Adicionalmente, as atividades fotoredutoras e as emissões de fluorescência do fotossistema II (PSII) foram incrementadas em baixas concentrações de Cu2+ (até 0,1 μM) e de Zn2+ (até 10 μM) e inibidas por altas concentrações. Desta forma, a intensidade da fluorescência da clorofila-a e dos centros de reação ativa PSII seguiram um padrão semelhante em resposta às elevadas concentrações de Cu2+ e Zn2+. Esses resultados sugerem que baixas concentrações de Cu2+ e Zn2+ afetam o metabolismo de P. haitanesis, que se torna inibido por altas concentrações desses metais.

Ultra-thin wearing course (UTWC) has been developed in pavement preventive maintenance for many years. However, how to prolong the service life of UTWC still requires further research. This study introduced AC-5 and SMA-5 asphalt mixtures, which can be induction heated. Steel fiber and steel slag were used in the mixtures as additives. Marshall Stability and induction heating property of mixtures were characterized. In addition, self-healing property of UTWC materials had been emphatically conducted. Adding steel fiber in mixtures led to higher Marshall Stability and lower flow value, while steel slag generally showed a negative effect. Induction heating property showed a positive relationship with the additives. Induction heating time was positively correlated to the healing ratio of the mixtures. Induction heating on the mixtures could recover the strength of mixtures to a certain degree. Mixtures with more steel fiber showed a higher healing ratio. Basalt-steel slag based mixtures showed better healing ratios than the basalt based mixtures. The healing ratios of mixtures illustrated a decreasing tendency as the healing cycle increased.

In this study, the aged asphalt binder and mixture were laboratory prepared through short-term ageing testing and long-term ageing testing. Firstly, the effect of rejuvenator on physical properties of aged asphalt binders was investigated. In addition, a series of laboratory tests were performed to evaluate the influence of ageing and rejuvenator content on the mechanical properties, durability and dynamic characteristics of asphalt mixtures. Physical test results of asphalt binder testified that rejuvenator used can efficiently recover the aged asphalt binder. However, the effect of ageing and rejuvenator content exhibits different trends depending on the physical property tests conducted. Moreover, artificially aged asphalt mixture with rejuvenator has better ability to resist moisture damage and ravelling. In addition, the ITSR value is more suitable to evaluate the moisture susceptibility for asphalt recycling. Although rejuvenator improves the thermal cracking resistance and fatigue property of aged asphalt mixture, rejuvenated mixture shows greater modulus and inferior ability to resist reflective cracking than the unaged mixture. Moreover, rejuvenated mixture shows less dependence on frequency at high temperature regions and stronger dependence at low temperature regions compared to unaged and long-term aged mixtures.

To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2.

Rotating bending fatigue tests were carried out by using the 7075-T7351 Al alloy with a microarc oxidation (MAO) coating (h = 10 μm) and with no coating. Tests were conducted in air and 5.0% NaCl aqueous solution conditions. The fatigue microscopic fracture behavior of the metals was investigated by using scanning electron microscope and three-dimensional digital microscope technologies. The empirical formulas between the stress intensity factor ΔK and the fatigue life Nf in the different conditions were obtained. In addition, the reason for data scattering in the fatigue lives of uncoated 7075-T7351 samples under the same stress amplitude in air was analyzed. Furthermore, the fatigue characteristic life of 7075-T7351 alloy was predicted by the three-parameter Weibull distribution model.

Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin’s principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose–response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on ‘more is better’. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.

Physiological management of migration-reproduction trade-offs in energy allocation often includes a package of adaptions referred to as the oogenesis-flight syndrome. In some species, this trade-off may be overestimated, because factors like flight behavior and environmental conditions may mitigate it. In this study, we examined the reproductive consequences induced by different flight scenarios in an economically-important Asian migrant insect, Cnaphalocrocis medinalis. We found that the influences of flight on reproduction are not absolutely positive or negative, but instead depend on the age at which the moth begins flight, flight duration, and how many consecutive nights they are flown. Adult flight on the 1st or 2nd night after emergence, flight for 6 h or 12 h nightly, and flight on the first two consecutive nights after emergence significantly accelerated onset of oviposition or enhanced synchrony of egg-laying. The latter can contribute to subsequent larval outbreaks. However, flight after the 3rd night, flight for 18 h at any age, or flight on more than 3 consecutive nights after adult emergence did not promote reproductive development, and in some scenarios even constrained adult reproduction. These results indicate that there is a migration/reproduction trade-off in C.medinalis, but that it is mitigated or eliminated by flight under appropriate conditions. The strategy of advanced and synchronized oviposition triggered by migratory flight of young females may be common in other migratory insect pests.

Enantioselective cyclopropanation of α-carbonyl sulfoxonium ylides (SY) has so far been limited to addition/ring closure reactions on electron-poor olefins. Herein, we report the iridium-catalyzed intramolecular cyclopropanation of SY in the presence of a chiral diene in up to 96% yield and 98% enantioselectivity. Moreover, density functional theory calculations suggest that the re face of the olefin preferably attacks an iridium carbene intermediate in an asynchronous concerted step that is independent of the geometry of the olefin.

Conductive asphalt concrete with high thermal conductivity has been proposed to improve the solar energy collection and snow melting efficiencies of asphalt solar collector (ASC). This paper aims to provide some insight into choosing the basic materials for preparation of conductive asphalt concrete, as well as determining the evolution of thermal characteristics affected by environmental factors. The thermal properties of conductive asphalt concrete were studied by the Thermal Constants Analyzer. Experimental results showed that aggregate and conductive filler have a significant effect on the thermal properties of asphalt concrete, while the effect of asphalt binder was not evident due to its low proportion. Utilization of mineral aggregate and conductive filler with higher thermal conductivity is an efficient method to prepare conductive asphalt concrete. Moreover, change in thermal properties of asphalt concrete under different temperature and moisture conditions should be taken into account to determine the actual thermal properties of asphalt concrete. There was no noticeable difference in thermal properties of asphalt concrete before and after aging. Furthermore, freezing–thawing cycles strongly affect the thermal properties of conductive asphalt concrete, due to volume expansion and bonding degradation.

This study investigated the influence of layered double hydroxides (LDHs) on the fatigue properties of asphalt mixture. In this paper, different aging levels (thin film oven test (TFOT) and ultraviolet radiation aging (UV aging for short)) of bitumen modified with various mass ratios of the LDHs were investigated. The TFOT and UV aging process were used to simulate short-term field thermal-oxidative aging and long-term field light UV aging of bitumen, respectively. The influences of LDHs on the fatigue properties of LDHs were evaluated by dynamic shear rheometer (DSR) and indirect tensile fatigue test. Results indicated that the introduction of LDHs could change the fatigue properties of bitumen under a stress control mode. The mixture with modified bitumen showed better fatigue resistance than the mixture with base bitumen. The results illustrated that the LDHs would be alternative modifiers used in the bitumen to improve the lifetime of asphalt pavements.

BACKGROUND: Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients' treatment, but couldn't provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application. METHODS: A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed. RESULTS: Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P = 0.02) and progression free survival (PFS) (P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P = 0.21), 2-year PFS (P = 0.10), overall response rate (ORR) (P = 0.76) and partial response (PR) (P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest. CONCLUSIONS: Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients.

A case study of catalytic carbon-carbon σ-bond homolysis is presented. The coordination of a redox-active Lewis acid catalyst reduces the bond-dissociation free energies of adjacent carbon-carbon σ-bonds, and this complexation-induced bond-weakening is used to effect reversible carbon-carbon bond homolysis. Stereochemical isomerization of 1,2-disubstituted cyclopropanes was investigated as a model reaction with a ruthenium (III/II) redox couple adopted for bond weakening. Results from our mechanistic investigation into the stereospecificity of the isomerization reaction are consistent with selective complexation-induced carbon-carbon bond homolysis. The ΔG‡ of catalyzed and uncatalyzed reactions were estimated to be 14.4 and 40.0 kcal/mol, respectively with the computational method, (U)PBE0-D3/def2-TZVPP-SMD(toluene)//(U)B3LYP-D3/def2-SVP. We report this work as the first catalytic example where the complexation-induced bond-weakening effect is quantified through transition state analysis.

This paper presents an in-plane sandwich nano-g microelectromechanical systems (MEMS) accelerometer. The proof-mass fabrication is based on silicon etching through technology using inductive coupled plasma (ICP) etching. The capacitive detection system, which employs the area-changing sensing method, combines elementary capacitive pickup electrodes with periodic-sensing-array transducers. In order to achieve a large dynamic range with an ultrahigh resolution, the capacitive detection system employs two periodic-sensing-array transducers. Each of them can provide numbers for the signal period in the entire operating range. The suspended proof-mass is encapsulated between two glass caps, which results in a three dimensional structure. The measured resonant frequency and quality factor (Q) are 13.2 Hz and 47, respectively. The calibration response of a ±0.7 g input acceleration is presented, and the accelerometer system presents a sensitivity of 122 V/g and a noise floor of 30 ng/√Hz (at 1 Hz, and 1 atm). The bias stability for a period of 10 h is 30 μg. The device has endured a shock up to ±2.6 g, and the full scale output appears to be approximately ±1.4 g presently. This work presents a new opportunity for highly sensitive MEMS fabrication to enable future high-precision measurement applications, such as for gravity measurements.

The effects of corrosive media on rotating bending fatigue lives (the cyclic numbers from 104 to 108) of different aluminum alloys were investigated, which involved the corrosion fatigue lives of five kinds of aluminum alloys in air, at 3.5 wt. % and 5.0 wt. % NaCl aqueous solutions. Experimental results indicate that corrosive media have different harmful influences on fatigue lives of different aluminum alloys, in which the differences of corrosion fatigue lives depend strongly on the plastic property (such as the elongation parameter) of aluminum alloys and whether to exist with and without fracture mode II. The other various influence factors (such as the dropping corrosive liquid rate, the loading style, and the nondimensionalization of strength) of corrosion fatigue lives in three media were also discussed in detail by using the typical cases. Furthermore, fracture morphologies and characteristics of samples, which showed the different fatigue cracking behaviors of aluminum alloys in three media, were investigated by scanning electron microscopy (SEM) in this paper.