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Guang-Yun Wang,1 Tie-Zheng Wang,1 Yuan-Yuan Zhang,1 Fang Li,1 Bo-Yang Yu,2 Jun-Ping Kou1 1State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of China; 2State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Resource and Development of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaCorrespondence: Jun-Ping KouState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaEmail junpingkou@cpu.edu.cnPurpose: Our previous studies have indicated that non-muscle myosin heavy chain IIA (NMMHC IIA) is involved in H2O2-induced neuronal apoptosis, which is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. However, the neuroprotective effect of NMMHC IIA inhibition with an adeno-associated virus (AAV) vector after transient middle cerebral artery occlusion (MCAO) and its role in caspases-3/ROCK1/MLC pathway remain blurred.Methods: Green fluorescent protein (GFP) and a small hairpin RNA targeting Myh9 (encoding NMMHC IIA) were cloned and packaged into the AAV9 vector. AAV-shMyh9 or control vector were injected into C57BL/6J mice four weeks prior to 60 min MCAO. Twenty-four hours after reperfusion, functional and histological analyses of the mice were performed.Results: In this study, AAV-shMyh9 was used to down-regulate NMMHC IIA expression in mice. We found that down-regulation of NMMHC IIA could improve neurological scores and his

During the early stage design of large-scale engineering systems, design teams are challenged to balance a complex set of considerations. The established structured approaches for optimizing complex system designs offer strategies for achieving optimal solutions, but in practice suboptimal system-level results are often reached due to factors such as satisficing, ill-defined problems, or other project constraints. Twelve subsystem and system-level practitioners at a large aerospace organization were interviewed to understand the ways in which they integrate subsystems in their own work. Responses showed subsystem team members often presented conservative, worst-case scenarios to other subsystems when negotiating a tradeoff as a way of hedging against their own future needs. This practice of biased information passing, referred to informally by the practitioners as adding "margins," is modeled in this paper with a series of optimization simulations. Three "bias" conditions were tested: no bias, a constant bias, and a bias which decreases with time. Results from the simulations show that biased information passing negatively affects both the number of iterations needed and the Pareto optimality of system-level solutions. Results are also compared to the interview responses and highlight several themes with respect to complex system design practice., University of Alabama in Huntsville. System Engineering Consortium, National Science Foundation (U.S.). Graduate Research Fellowship

Large-scale desalination plants are complex systems with many inter-disciplinary interactions and different levels of subsystem hierarchy. Advanced complex systems design tools have been shown to have a positive impact on design in aerospace and automotive, but have generally not been used in the design of water systems. This work presents a multi-disciplinary design optimization approach to desalination system design to minimize the total water production cost of a 30,000m3/day capacity reverse osmosis plant situated in the Middle East, with a focus on comparing monolithic with distributed optimization architectures. A hierarchical multi-disciplinary model is constructed to capture the entire system's functional components and subsystem interactions. Three different multi-disciplinary design optimization (MDO) architectures are then compared to find the optimal plant design that minimizes total water cost. The architectures include the monolithic architecture multidisciplinary feasible (MDF), individual disciplinary feasible (IDF) and the distributed architecture analytical target cascading (ATC). The results demonstrate that an MDF architecture was the most efficient for finding the optimal design, while a distributed MDO approach such as analytical target cascading is also a suitable approach for optimal design of desalination plants, but optimization performance may depend on initial conditions., King Fahd University of Petroleum & Minerals (Cneter fo Clean Water and Clean Energy at MIT and KFUPM under project number R13-CW-10)

Complex system design requires managing competing objectives between many subsystems. Previous field research has demonstrated that subsystem designers may use biased information passing as a negotiation tactic and thereby reach sub-optimal system-level results due to local optimization behavior. One strategy to combat the focus on local optimization is an incentive structure that promotes system-level optimization. This paper presents a new subsystem incentive structure based on Multi-disciplinary Optimization (MDO) techniques for improving robustness of the design process to such biased information passing strategies. Results from simulations of different utility functions for a test suite of multi-objective problems quantify the system robustness to biased information passing strategies. Results show that incentivizing subsystems with this new weighted structure may decrease the error resulting from biased information passing., University of Alabama in Huntsville. System Engineering Consortium, National Science Foundation (U.S.). Graduate Research Fellowship

The optimal maintenance scheduling of systems with degrading components is highly coupled with the design of the system and various uncertainties associated with the system, including the operating conditions, the interaction of different degradation profiles of various system components, and the ability to measure and predict degradation using prognostics and health management (PHM) technologies. Due to this complexity, designers need to understand the correlations and feedback between the design variables and lifecycle parameters to make optimal decisions. A framework is proposed for the high level integration of design, component degradation, and maintenance decisions. The framework includes constructing screening models for rapid design evaluation, defining a multi-objective robust optimization problem, and using sensitivity studies to compare trade-offs between different design and maintenance strategies. A case example of power plant condenser is used to illustrate the proposed framework and advise how designers can make informed comparisons between different design concepts and maintenance strategies under highly uncertain lifecycle conditions.

Computer-based tools have great potential for facilitating the design of large-scale engineering systems. Interviews with veteran designers of desalination systems revealed that they tended to employ a trial-and-error approach to determine critical design parameters when using software design packages. A series of human experiments were conducted to observe the performance and behavior of test subjects during a series of simulated design processes involving seawater reverse osmosis (SWRO) plants. The subjects were mostly students with a spectrum of knowledge levels in desalination system design. The experiments showed that subjects who ranked top in performance behaved very differently from those who were bottom-ranked. The problem-solving profiles of the best performing subjects resembled a well-tuned simulated annealing optimization algorithm while the worst performing subjects used a pseudo random search strategy. This finding could be used to improve computerbased design tools by utilizing the synergy between strengths of humans and computers.

We introduce the modulation-doping strategy in bulk SiGe nanostructures to improve the thermoelectric power factor. By separating charge carriers from their parent atoms via embedding heavily doped nanoparticles inside an intrinsic host matrix, the ionized impurity scattering rate could be largely reduced, resulting in enhanced mobility. By band engineering, the carriers can spill over from nanoparticles into the host matrix, resulting in similar carrier concentrations, Fermi levels and consequently Seebeck coefficients as those of the uniform nanocomposites. In addition, nanoparticles with low thermal conductivities can further reduce the overall thermal conductivity of the sample. Combining the enhanced electrical conductivity, the reduced thermal conductivity and the unaffected Seebeck coefficient, we were able to enhance the thermoelectric properties of Si-rich Si[subscript 95]Ge[subscript 5]. And therefore were able to fabricate a low-cost sample with a competitive performance as those of the state of the art Si[subscript 80]Ge[subscript 20]., Solid-State Solar-Thermal Energy Conversion Center (United States. Department of Energy. Office of Basic Energy Sciences award number DESC0001299/DE-FG02-09ER46577)

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction bet

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction bet

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction bet

Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L. or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile to evaluate the antioxidant and anti-inflammatory activities of FAI and the transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was anaerobically incubated with human intestinal bacterial suspensions for 48 h at 37 degrees C. Liquid chromatography-hybridised with quadru-pole- time-of-flight mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total of 45 compounds were identified in FAI, eleven of which were metabolized by human intestinal bacteria. Nine major metabolites were identified as eriodictyol, naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin and diosmetin. The metabolic profile of FAI was elucidated on the basis of metabolite information. We found that the concentrations of acetic, propionic and butyric acids in FAI culture were all increased during fermentation relative to those of the control. Further bioactive evaluations showed that TFAI exhibited more potent antioxidant and anti-inflammatory abilities than FAI in vitro. Additionally, in vivo experiment confirmed that FAI significantly attenuated the blood endotoxin and TNF-alpha levels in the conventional rats compared to those of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a key role in the antioxidant and anti-inflammatory capacities of FAI.

Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L. or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile to evaluate the antioxidant and anti-inflammatory activities of FAI and the transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was anaerobically incubated with human intestinal bacterial suspensions for 48 h at 37 degrees C. Liquid chromatography-hybridised with quadru-pole- time-of-flight mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total of 45 compounds were identified in FAI, eleven of which were metabolized by human intestinal bacteria. Nine major metabolites were identified as eriodictyol, naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin and diosmetin. The metabolic profile of FAI was elucidated on the basis of metabolite information. We found that the concentrations of acetic, propionic and butyric acids in FAI culture were all increased during fermentation relative to those of the control. Further bioactive evaluations showed that TFAI exhibited more potent antioxidant and anti-inflammatory abilities than FAI in vitro. Additionally, in vivo experiment confirmed that FAI significantly attenuated the blood endotoxin and TNF-alpha levels in the conventional rats compared to those of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a key role in the antioxidant and anti-inflammatory capacities of FAI.

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction bet

Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L. or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile to evaluate the antioxidant and anti-inflammatory activities of FAI and the transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was anaerobically incubated with human intestinal bacterial suspensions for 48 h at 37 degrees C. Liquid chromatography-hybridised with quadru-pole- time-of-flight mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total of 45 compounds were identified in FAI, eleven of which were metabolized by human intestinal bacteria. Nine major metabolites were identified as eriodictyol, naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin and diosmetin. The metabolic profile of FAI was elucidated on the basis of metabolite information. We found that the concentrations of acetic, propionic and butyric acids in FAI culture were all increased during fermentation relative to those of the control. Further bioactive evaluations showed that TFAI exhibited more potent antioxidant and anti-inflammatory abilities than FAI in vitro. Additionally, in vivo experiment confirmed that FAI significantly attenuated the blood endotoxin and TNF-alpha levels in the conventional rats compared to those of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a key role in the antioxidant and anti-inflammatory capacities of FAI.

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and alpha-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction bet

The early stage design of large-scale engineering systems challenges design teams to balance a complex set of considerations. Established structured approaches for optimizing complex system designs offer strategies for achieving optimal solutions, but in practice sub-optimal system-level results are often reached due to factors such as satisficing, ill-defined problems or other project constraints. Twelve sub-system and system-level practitioners at a large aerospace organization were interviewed to understand the ways in which they integrate sub-systems. Responses showed sub-system team members often presented conservative, worst-case scenarios to other sub-systems when negotiating a trade-off as a way of hedging their own future needs. This practice of biased information passing, referred to informally by the practitioners as adding “margins,” is modeled with a series of optimization simulations. Three “bias” conditions were tested: no bias, a constant bias and a bias which decreases with time. Results from the simulations show that biased information passing negatively affects both the number of iterations needed to reach and the Pareto optimality of system-level solutions. Results are also compared to the interview responses and highlight several themes with respect to complex system design practice., National Science Foundation (U.S.). Graduate Research Fellowship Program

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2015., Cataloged from PDF version of thesis., Includes bibliographical references (pages 153-160)., The goal of this thesis is to better understand the design practice employed by the desalination industry from a systems-level viewpoint and offer recommendations to improve the process of design. A human-centered design research approach is used, in which industry practitioners were interviewed about the design strategies they employ for industrial desalination systems. A common theme from the interviews is that long term performance of desalination systems needs to be emphasized during the design process. Based on this observation, a novel design framework is proposed that incorporates health monitoring and maintenance in the design stage. The proposed framework is shown to make the design process more effective and can result in more optimal design over the lifecycle of a plant. The interviews also suggest open questions about how designers use computational tools for the design of desalination system. An investigation of how designers respond to the complexity of desalination parameter design problems was conducted. The behavior of designers during a series of simulated design processes involving seawater reverse osmosis (SWRO) plants was observed. The experiments revealed that desalination knowledge seemed to lead to better performance, but the results also showed that subjects with limited desalination knowledge could perform worse than subjects with no desalination knowledge. It was also observed that human designers had difficulties understanding the sensitivity of coupled variables, which can lead to poor performance on parameter design problems. Additionally, the top-performance-ranked subjects were observed to behavior very differently from the bottom-ranked. The problem-solving profiles of best performing subjects resembled a well-tuned simulated annealing algorithm while the worst performing subjects used a pseudo random search strategy., by Bo Yang Yu., Ph. D.

Psorothatins A-C (1-3), three antibacterial prenylated acylphloroglucinol derivatives, were isolated from the native American plant Psorothamnus fremontii. They feature an unusual alpha,beta-epoxyketone functionality and a beta-hydroxy-alpha,beta-unsaturated ketone structural moiety. The latter forms a pseudo-six-membered heterocyclic ring due to strong intramolecular hydrogen bonding, as indicated by the long-range proton-carbon correlations in the NMR experiments. Psorothatin C (3) was the most active compound against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, with IC50 values in the range 1.4-8.8 mu g/mL. The first total synthesis of 3 described herein permits future access to structural analogues with potentially improved antibacterial activities.

This paper proposes a method that dynamically improves a statistical model of system degradation by incorporating uncertainty. The method is illustrated by a case example of fouling, or degradation, in a heat exchanger in a cogeneration desalination plant. The goal of the proposed method is to select the best model from several representative condenser fouling models including linear, falling rate, and asymptotic fouling, and to validate and improve model parameters over the duration of operation. Maximum likelihood estimation (MLE) was applied to obtain a stochastic distribution of condenser fouling. Akaike’s Information Criterion (AIC) and the Bayesian Information Criterion (BIC) were then computed at time intervals to assess the accuracy of the MLE results. The degradation model was further evaluated by estimating future prognoses and then cross-validating with real world fouling data. The results show the accuracy of a prognosis can be improved substantially by continuously updating fouling model parameters. The proposed method is a step toward facilitating prognosis of engineering systems in the early design stages by improving the prediction of future component degradation., Center for Clean Water and Clean Energy at MIT and KFUPM, Natural Sciences and Engineering Research Council of Canada