A numerical solution to fluid-structure interaction of membrane structures under wind action

Fang-jin Sun,Ming Gu 한국풍공학회 2014 Wind and Structures, An International Journal (WAS Vol.19 No.1

A numerical simultaneous solution involving a linear elastic model was applied to study the fluid-structure interaction (FSI) of membrane structures under wind actions, i.e., formulating the fluid-structure system with a single equation system and solving it simultaneously. The linear elastic model was applied to managing the data transfer at the fluid and structure interface. The monolithic equation of the FSI system was formulated by means of variational forms of equations for the fluid, structure and linear elastic model, and was solved by the Newton-Raphson method. Computation procedures of the proposed simultaneous solution are presented. It was applied to computation of flow around an elastic cylinder and a typical FSI problem to verify the validity and accuracy of the method. Then fluid-structure interaction analyses of a saddle membrane structure under wind actions for three typical cases were performed with the method. Wind pressure, wind-induced responses, displacement power spectra, aerodynamic damping and added mass of the membrane structure were computed and analyzed.

Preconditioning technique for a simultaneous solution to wind-membrane interaction

Fang-jin Sun,Ming Gu 한국풍공학회 2016 Wind and Structures, An International Journal (WAS Vol.22 No.3

A preconditioning technique is presented for a simultaneous solution to wind-membrane interaction. In the simultaneous equations, a linear elastic model was employed to deal with the fluid-structure data transfer at the interface. A Lagrange multiplier was introduced to impose the specified boundary conditions at the interface and strongly coupled simultaneous equations are derived after space and time discretization. An initial linear elastic model preconditioner and modified one were derived by treating the linearized elastic model equation as a saddle point problem, respectively. Accordingly, initial and modified fluid-structure interaction (FSI) preconditioner for the simultaneous equations were derived based on the initial and modified linear elastic model preconditioners, respectively. Wind-membrane interaction analysis by the proposed preconditioners, for two and three dimensional membranous structures respectively, was performed. Comparison was made between the performance of initial and modified preconditioners by comparing parameters such as iteration numbers, relative residuals and convergence in FSI computation. The results show that the proposed preconditioning technique greatly improves calculation accuracy and efficiency. The priority of the modified FSI preconditioner is verified. The proposed preconditioning technique provides an efficient solution procedure and paves the way for practical application of simultaneous solution for wind-structure interaction computation.

Preconditioning technique for a simultaneous solution to wind-membrane interaction

Sun, Fang-jin,Gu, Ming Techno-Press 2016 Wind and Structures, An International Journal (WAS Vol.22 No.3

A preconditioning technique is presented for a simultaneous solution to wind-membrane interaction. In the simultaneous equations, a linear elastic model was employed to deal with the fluid-structure data transfer at the interface. A Lagrange multiplier was introduced to impose the specified boundary conditions at the interface and strongly coupled simultaneous equations are derived after space and time discretization. An initial linear elastic model preconditioner and modified one were derived by treating the linearized elastic model equation as a saddle point problem, respectively. Accordingly, initial and modified fluid-structure interaction (FSI) preconditioner for the simultaneous equations were derived based on the initial and modified linear elastic model preconditioners, respectively. Wind-membrane interaction analysis by the proposed preconditioners, for two and three dimensional membranous structures respectively, was performed. Comparison was made between the performance of initial and modified preconditioners by comparing parameters such as iteration numbers, relative residuals and convergence in FSI computation. The results show that the proposed preconditioning technique greatly improves calculation accuracy and efficiency. The priority of the modified FSI preconditioner is verified. The proposed preconditioning technique provides an efficient solution procedure and paves the way for practical application of simultaneous solution for wind-structure interaction computation.

A numerical solution to fluid-structure interaction of membrane structures under wind action

Sun, Fang-Jin,Gu, Ming Techno-Press 2014 Wind and Structures, An International Journal (WAS Vol.19 No.1

A numerical simultaneous solution involving a linear elastic model was applied to study the fluid-structure interaction (FSI) of membrane structures under wind actions, i.e., formulating the fluid-structure system with a single equation system and solving it simultaneously. The linear elastic model was applied to managing the data transfer at the fluid and structure interface. The monolithic equation of the FSI system was formulated by means of variational forms of equations for the fluid, structure and linear elastic model, and was solved by the Newton-Raphson method. Computation procedures of the proposed simultaneous solution are presented. It was applied to computation of flow around an elastic cylinder and a typical FSI problem to verify the validity and accuracy of the method. Then fluid-structure interaction analyses of a saddle membrane structure under wind actions for three typical cases were performed with the method. Wind pressure, wind-induced responses, displacement power spectra, aerodynamic damping and added mass of the membrane structure were computed and analyzed.

Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in <i>RAS</i> mutant cancers

Sun, Chaoyang,Fang, Yong,Yin, Jun,Chen, Jian,Ju, Zhenlin,Zhang, Dong,Chen, Xiaohua,Vellano, Christopher P.,Jeong, Kang Jin,Ng, Patrick Kwok-Shing,Eterovic, Agda Karina B.,Bhola, Neil H.,Lu, Yiling,Wes American Association for the Advancement of Scienc 2017 Science translational medicine Vol.9 No.392

<P>Mutant <I>RAS</I> has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple <I>RAS</I> mutant tumor models across tumor lineages where <I>RAS</I> mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of <I>BRCA1/2</I> and <I>p53</I> mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in <I>RAS</I> mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor–induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant <I>RAS</I> to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in <I>RAS</I> mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with <I>RAS</I> mutant tumors where there are few effective therapeutic options.</P>

Protein Kinases as Pharmacological Targets for the Reduction of Interleukin-1 Expression in Lipopolysaccaride-Activated Primary Glial Cell

Sun Hu-Nan,Fang Wan,Jin Mei-Hua,Han Ying-Hao,Kim Sun-Uk,Lee Sang-Han,Kim Nam-Soon,Kim Cheol-Hee,Lee Dong-Seok The Korean Society for Biomedical Laboratory Scien 2004 Journal of biomedical laboratory sciences Vol.10 No.4

Inflammatory factor such as Interleukin-1 play important roles in determining the fate of both acute and chronic neurological disorders. We investigated whether inhibitors of PKC or PTK can serve as pharmacological agents to reduce IL-I production and the mechanisms underlying their pharmacological effects in a mixed population of glia. Inhibitors of PKC such as H7, Go6976 and Ro31-8220 significantly reduced both the mRNA and protein levels of IL-1α and IL-β in lipopolysaccharide-activated primary glial cells. While the PTK inhibitor genistein also significantly reduced the production of these cytokines, it did not affect the expression of their mRNA. Taken together, inhibitors of PKC and PTK could serve as pharmacological agents to reduce IL-1 production. However, the mechanisms underlying their pharmacological effects are different. Our results provide evidence that inhibitors of protein kinases can serve as pharmacological agents to modulate IL-1 production in glial cell, and in turn, alleviate neuronal injury.

BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency

Sun, Chaoyang,Yin, Jun,Fang, Yong,Chen, Jian,Jeong, Kang Jin,Chen, Xiaohua,Vellano, Christopher P.,Ju, Zhenlin,Zhao, Wei,Zhang, Dong,Lu, Yiling,Meric-Bernstam, Funda,Yap, Timothy A.,Hattersley, Mauree Cell Press 2018 CANCER CELL Vol. No.

<P><B>Summary</B></P> <P>Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in <I>BRCA1</I>, <I>BRCA2</I>, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of <I>BRCA1/2</I>, <I>TP53</I>, <I>RAS</I>, or <I>BRAF</I> mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple <I>in vivo</I> models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BRD4 inhibition decreases homologous recombination competency by decreasing CtIP </LI> <LI> PARP and BRD4 inhibitors demonstrate synergy in multiple cancer lineages </LI> <LI> CtIP rescues DNA end resection and HR defect caused by BRD4 inhibition </LI> <LI> BRD4 inhibition resensitizes cells with acquired PARPi resistance to PARPi </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis and biological evaluation of fluoro-substituted 3,4-dihydroquinazoline derivatives for cytotoxic and analgesic effects

Kim, Jin Han,Jeong, Hui Rak,Jung, Da Woon,Yoon, Hong Bin,Kim, Sun Young,Kim, Hyoung Ja,Lee, Kyung-Tae,Gadotti, Vinicius M.,Huang, Junting,Zhang, Fang-Xiong,Zamponi, Gerald W.,Lee, Jae Yeol Pergamon 2017 Bioorganic & medicinal chemistry Vol.25 No.17

<P><B>Abstract</B></P> <P>As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Ca<SUB>v</SUB>3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound <B>8h</B> (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Ca<SUB>v</SUB>3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC<SUB>50</SUB> =5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S. Furthermore, <B>8h</B> showed approximately a 2-fold increase in liver metabolic stability in rat and human species compared to KYS05090S. Based on these overall results, <B>8h</B> (KCP10068F) may therefore represent a good backup compound for KYS05090S for further biological investigations as novel cytotoxic agent. In addition, compound <B>8g</B> (KCP10067F) was found to partially protect from inflammatory pain via a blockade of Ca<SUB>v</SUB>3.2 channels.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

The Value of Infectious Biomarkers for Prediction of Complication after Pancreatic Surgery

( Yuan Fang ),( Gang Jin ),( Xubao Liu ),( Yajin Chen ),( Bei Sun ),( Zhongtao Zhang ),( Wenchuan Wu ),( Wenhui Lou ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: To assess the predictive value of biomarkers for early complication after pancreatic surgery. Methods: 950 cases were recruited from 6 centers in China. Procalcitonin,C-reactive protein and WBC were measured on 1st, 3rd and 5th postoperative day . Chi-square test was for the complication risk factors. One-way ANOVA was for the comparison between the biomarkers in these 4 days. ROC curves was for the complication predictive value. Results: 1) 502 with and 448 without complication, pancreatic fistula (380,40%) had the highest morbidity, while the level A B C fistula were 278,90 and 12. 2) In the non-complication subgroup, the mean baseline,POD1, POD3 and POD 5 of PCT were 0.1, 0.81, 0.93, 0.57ug/L (P=0.118); CRP were 8.39, 70.81,99.59, 49.49mg/L (P=0.000). In the complication subgroup, the mean baseline,POD1, POD3 and POD 5 of PCT were 0.09, 0.93, 0.77, 0.37(P=0.000), CRP were 9.30, 79.70, 153.01, 85.83. (P=0.000) 3) There were significant differences in the subgroups classified by occurrence of infectious complication, abdominal infection and sepsis in POD3 and POD 5 of PCT, and significant difference by occurrence of complication, pancreatic fistula in POD3 and POD 5 of CRP, WBC and neutrophil%. 5) The AUC of POD3 and POD 5 of PCT were 0.8, 0.7, 0.6 (P=0.000) to predict sepsis, abdominal infection and infectious complication. AUC of POD3 and POD5 of CRP and WBC were 0.7,0.6 (P=0.000)to predict complication and pancreatic fistula. Conclusions: PCT is better to predict infectious complication, abdominal infection and sepsis while CRP, WBC and Neutrophil % are better to predict complication and pancreatic fistula.

Genetic Characterization of Two Putative Toxin-Antitoxin Systems on Cryptic Plasmids from Bacillus thuringiensis Strain YBT-1520

( Xiao Jin Liu ),( Shu Fang Zhu ),( Wei Xing Ye ),( Li Fang Ruan ),( Zi Niu Yu ),( Chang Ming Zhao ),( Ming Sun ) 한국미생물 · 생명공학회 2008 Journal of microbiology and biotechnology Vol.18 No.10