Publications by authors named "Guoming Zhu"

9 Publications

  • Page 1 of 1

Effect of Secondary Cold Reduction Rates on Microstructure, Texture and Earing Behavior of Double Reduction Tinplate.

Materials (Basel) 2021 Jul 20;14(14). Epub 2021 Jul 20.

School of Material Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.

In order to evaluate the effect of secondary cold reduction rate on the drawing performance of double reduction tinplate and explain the mechanism, a detailed investigation into the microstructural characterization, dissolved carbon atoms, texture characterization by an X-ray powder diffractometer (XRD) and electron backscatter diffraction (EBSD), and earing behavior were carried out with different secondary cold reduction rates of 15%, 20% and 25% for double reduction tinplate. The experimental results indicate that 15% secondary cold reduction rate could obtain a better drawing performance because there are no holes and cracks at the microstructure, and the content of dissolved carbon atom is relatively low; at the same time, it has a better texture distribution and low earing coefficient.
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http://dx.doi.org/10.3390/ma14144040DOI Listing
July 2021

LPV Modeling of a Flexible Wing Aircraft Using Modal Alignment and Adaptive Gridding Methods.

Aerosp Sci Technol 2017 Jul 10;66:92-102. Epub 2017 Mar 10.

Intelligent Systems Division, NASA Ames Research Center.

One of the earliest approaches in gain-scheduling control is the based approach, in which a set of local linear time-invariant models are obtained at various gridded points corresponding to the varying parameters within the flight envelop. In order to ensure smooth and effective Linear Parameter-Varying control, aligning all the flexible modes within each local model and maintaining small number of representative local models over the gridded parameter space are crucial. In addition, since the flexible structural models tend to have large dimensions, a tractable model reduction process is necessary. In this paper, the notion of -shifted [Formula: see text]- and [Formula: see text]-norm are introduced and used as a metric to measure the model mismatch. A new modal alignment algorithm is developed which utilizes the defined metric for aligning all the local models over the entire gridded parameter space. Furthermore, an Adaptive Grid Step Size Determination algorithm is developed to minimize the number of local models required to represent the gridded parameter space. For model reduction, we propose to utilize the concept of Composite Modal Cost Analysis, through which the collective contribution of each flexible mode is computed and ranked. Therefore, a reduced-order model is constructed by retaining only those modes with significant contribution. The NASA Generic Transport Model operating at various flight speeds is studied for verification purpose, and the analysis and simulation results demonstrate the effectiveness of the proposed modeling approach.
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http://dx.doi.org/10.1016/j.ast.2017.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713486PMC
July 2017

Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma.

J Med Chem 2017 10 16;60(20):8466-8481. Epub 2017 Oct 16.

Novartis Institutes for BioMedical Research, Inc. , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139-4133, United States.

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound 16 (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclinical efficacy and safety profile, the compound was advanced into clinical trials.
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http://dx.doi.org/10.1021/acs.jmedchem.7b00900DOI Listing
October 2017

Optimum Wing Shape Determination of Highly Flexible Morphing Aircraft for Improved Flight Performance.

J Aircr 2016 09 10;53(5):1305-1316. Epub 2016 Mar 10.

Michigan State University, East Lansing, MI 48824.

In this paper, optimum wing bending and torsion deformations are explored for a mission adaptive, highly flexible morphing aircraft. The complete highly flexible aircraft is modeled using a strain-based geometrically nonlinear beam formulation, coupled with unsteady aerodynamics and 6-dof rigid-body motions. Since there are no conventional discrete control surfaces for trimming the flexible aircraft, the design space for searching the optimum wing geometries is enlarged. To achieve high performance flight, the wing geometry is best tailored according to the specific flight mission needs. In this study, the steady level flight and the coordinated turn flight are considered, and the optimum wing deformations with the minimum drag at these flight conditions are searched by utilizing a modal-based optimization procedure, subject to the trim and other constraints. The numerical study verifies the feasibility of the modal-based optimization approach, and shows the resulting optimum wing configuration and its sensitivity under different flight profiles.
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http://dx.doi.org/10.2514/1.C033490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770154PMC
September 2016

R-HPDC Process with Forced Convection Mixing Device for Automotive Part of A380 Aluminum Alloy.

Materials (Basel) 2014 Apr 15;7(4):3084-3105. Epub 2014 Apr 15.

School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.

The continuing quest for cost-effective and complex shaped aluminum castings with fewer defects for applications in the automotive industries has aroused the interest in rheological high pressure die casting (R-HPDC). A new machine, forced convection mixing (FCM) device, based on the mechanical stirring and convection mixing theory for the preparation of semisolid slurry in convenience and functionality was proposed to produce the automotive shock absorber part by R-HPDC process. The effect of barrel temperature and rotational speed of the device on the grain size and morphology of semi-solid slurry were extensively studied. In addition, flow behavior and temperature field of the melt in the FCM process was investigated combining computational fluid dynamics simulation. The results indicate that the microstructure and pore defects at different locations of R-HPDC casting have been greatly improved. The vigorous fluid convection in FCM process has changed the temperature field and composition distribution of conventional solidification. Appropriately increasing the rotational speed can lead to a uniform temperature filed sooner. The lower barrel temperature leads to a larger uniform degree of supercooling of the melt that benefits the promotion of nucleation rate. Both of them contribute to the decrease of the grain size and the roundness of grain morphology.
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http://dx.doi.org/10.3390/ma7043084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453376PMC
April 2014

miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3.

Cancer Lett 2012 Oct 30;323(1):41-47. Epub 2012 Mar 30.

Department of Surgery, Korea University Anam Hospital, South Korea.

The phosphatase of regenerating liver-3 (PRL-3) gene is associated with metastasis in gastric cancer, and is believed to play a causative role by promoting tumor cell motility, invasion, and metastasis, but little is known of the mechanisms involved. We previously reported that PRL-3 expression is significantly higher in the tissues of primary gastric carcinomas with peritoneal metastasis. In the present study, we found that two microRNAs (miRNAs), miR-495 and miR-551a, predicted to target PRL-3, are downregulated in gastric carcinoma samples. The validation of this interaction between those two miRNAs and PRL-3 was confirmed by western blotting and quantitative real-time PCR (qPCR) in GC cell lines transfected with miR-495 and miR-551a mimics. Furthermore, the migration and invasion of GC cells were significantly inhibited by transfection with miR-495 or -551a mimics, and the mRNA and protein levels of PRL-3 were reduced in cells overexpressing miR-495 or -551a. Collectively, our findings suggest that miR-495 and miR-551a both act as tumor suppressors by targeting the PRL-3 oncogene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miRNA mimics in GC gene therapy.
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http://dx.doi.org/10.1016/j.canlet.2012.03.029DOI Listing
October 2012

Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8.

Mol Pharmacol 2007 Aug;72(2):327-40

Laboratory for Molecular Pharmacology, Department of Pharmacology, The Panum Institute, Copenhagen University, Blegdamsvej 2, 2200 Copenhagen, Denmark.

Most nonpeptide antagonists for CC-chemokine receptors share a common pharmacophore with a centrally located, positively charged amine that interacts with the highly conserved glutamic acid (Glu) located in position 6 of transmembrane helix VII (VII:06). We present a novel CCR8 nonpeptide agonist, 8-[3-(2-methoxyphenoxy)benzyl]-1-phenethyl-1,3,8-triaza-spiro[4.5]decan-4-one (LMD-009), that also contains a centrally located, positively charged amine. LMD-009 selectively stimulated CCR8 among the 20 identified human chemokine receptors. It mediated chemotaxis, inositol phosphate accumulation, and calcium release with high potencies (EC50 from 11 to 87 nM) and with efficacies similar to that of the endogenous agonist CCL1, and it competed for 125I-CCL1 binding with an affinity of 66 nM. A series of 29 mutations targeting 25 amino acids broadly distributed in the minor and major ligand-binding pockets of CCR8 uncovered that the binding of LMD-009 and of four analogs [2-(1-(3-(2-methoxyphenoxy)benzyl)-4-hydroxypiperidin-4-yl)benzoic acid (LMD-584), N-ethyl-2-4-methoxybenzenesulfonamide (LMD-902), N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-2-phenyl-4-(pyrrolidin-1yl)butanamide (LMD-268), and N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-1,2,3,4-tetrahydro-2-oxoquinoline-4-carboxamide (LMD-174)] included several key-residues for nonpeptide antagonists targeting CCR1, -2, and -5. It is noteworthy that a decrease in potency of nearly 1000-fold was observed for all five compounds for the Ala substitution of the anchor-point GluVII:06 (Glu(286)) and a gain-of-function of 19-fold was observed for LMD-009 (but not the four other analogs) for the Ala substitution of PheVI:16 (Phe(254)). These structural hallmarks were particularly important in the generation of a model of the molecular mechanism of action for LMD-009. In conclusion, we present the first molecular mapping of the interaction of a nonpeptide agonist with a chemokine receptor and show that the binding pocket of LMD-009 and of analogs overlaps considerably with the binding pockets of CC-chemokine receptor nonpeptide antagonists in general.
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http://dx.doi.org/10.1124/mol.106.035543DOI Listing
August 2007

Recurrence of the D100N mutation in a Chinese family with brachydactyly type A1: evidence for a mutational hot spot in the Indian hedgehog gene.

Am J Med Genet A 2007 Jun;143A(11):1246-8

Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, Shandong University School of Medicine, Jinan, and Department of Orthopaedics, Hospital of Weihai Economic and Technical Development Zone, China.

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http://dx.doi.org/10.1002/ajmg.a.31728DOI Listing
June 2007

A system for the enhancement of adenovirus mediated gene transfer to uro-epithelium.

J Urol 2002 Aug;168(2):813-8

Department of Urology, Children's Hospital and Harvard Medical School and Renal Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.

Purpose: Recombinant adenovirus has been used widely as an in vivo gene transfer vector, although its transfection efficiency in bladder tissue is limited. Several studies have indicated that the bladder surface glycosaminoglycan (GAG) layer functions as a nonspecific anti-adherence factor and possibly as a first line anti-infection defense mechanism. We determined whether recombinant adenovirus mediated gene transfer could be enhanced in intact bladders by HCl pretreatment and by alterations in the GAG layer.

Materials And Methods: In vitro viral transfection efficiencies with and without the GAG analog pentosan polysulfate (Sigma Chemical Co., St. Louis, Missouri) were determined in bladder muscle and urothelial cells. Immunocytochemical studies and Western blot analysis were performed to determine whether urothelial cells possessed the Coxsackievirus and adenovirus receptor. Rat bladders were intravesically pretreated with HCl at various concentrations and for various periods. After 60 mM. HCl pretreatment for 10 minutes 2 x 109 pfu of recombinant adenovirus carrying the Escherichia coli LacZ gene were intravesically instilled into the bladders.

Results: Adenoviral infection of urothelial cells was significantly reduced in the presence of pentosan polysulfate in vitro. Coxsackievirus and adenovirus receptor expression was detected in urothelial cells in vivo and in vitro. Bladders pretreated with HCl resulted in an alteration of the bladder GAG layers. After intravesical gene instillation reporter gene analyses using X-5-bromo-4-chloro-3-inodolyl beta-D-galactopyranoside (Sigma Chemical Co.) showed approximately 80% urothelial cell transfection efficiency in bladders pretreated with HCl. However, less than 10% of the urothelial cells expressed the transfected gene in control HCl untreated bladders.

Conclusions: Primary urothelial cells and bladder carcinoma cells can be efficiently transfected using an adenoviral vector with similar infectivity. In vitro viral infection shows that the efficiency of adenoviral transfection is significantly reduced in the presence of pentosan polysulfate, a GAG analog. Adenoviral mediated gene transfer to bladder urothelium is enhanced by HCl pretreatment.
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August 2002
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