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Mostrando recursos 1 - 20 de 106
1.
Activation Ratios For Reconstruction Of Signal Transduction Networks - Femenia, F. Javier; Stephanopoulos, Gregory
We have developed a novel framework that can be applied for the analysis of signal transduction networks, both to facilitate reconstruction of the network structure and quantitatively characterize the interaction between network components. This approach, termed activation ratio analysis, involves the ratio between active and inactive forms of signaling intermediates at steady state. The activation ratio of an intermediate is shown to depend linearly upon the concentration of the activating enzyme. The slope of the line is defined as the activation factor, and is determined by the kinetic parameters of activation and inactivation. When activation ratios for simple signaling systems...
2.
Association Behavior of Poly(methacrylic acid)-block-Poly(methyl methacrylate) in Aqueous Medium: Potentiometric and Laser Light Scattering Studies - Palaniswamy, R.; Wang, C; Tam, Michael K. C.; Gan, L.H.
Atom transfer radical polymerisation (ATRP) technique was used to synthesize poly(methacrylic acid-block-methyl methacrylate) (P(MAAâ??â??â??-b-MMAâ??â??)) copolymer in order to study the aggregation behavior in aqueous solution over the course of neutralization. A combination of static and dynamic light scattering (SLS, DLS) and potentiometric titration techniques were used to investigate the size and shape of the micelle at various degrees of neutralization. The hydrodynamic radius (Rh) determined from dynamic light scattering increases from ~26nm (for unneutralized) to ~42nm (for completely neutralized sample). Both potentiometric and laser light scattering studies indicate the formation of a core shell micelle. The weighted average molecular weights...
3.
Changes in the Overall Extent of Protein Glycosylation by Chinese Hamster Ovary Cells Over the Course of Batch Culture - Yuk, Inn Huam Yvonne.; Wang, Daniel I.C.
Glycosylation of recombinant proteins can change during the culture of animal cells. Since lipid-linked oligosaccharides (LLOs) are the carbohydrate donors in N-linked glycosylation, their availability is postulated to influence the extent of glycosylation. To test this hypothesis, relative LLO and glycosylation levels in Chinese hamster ovary (CHO) cells were monitored over the course of batch culture for corresponding changes. Radiolabelling studies reveal that throughout the length of culture, intracellular LLO levels remained within a 2-fold range and overall CHO protein glycosylation varied by less than 30%. The implications of these results and hypotheses to explain the findings are discussed.
4.
Computational Method for Drug Target Search and Application in Drug Discovery - Chen, Yuzong; Li, Zerong; Ung, C.Y.
Ligand-protein inverse docking has recently been introduced as a computer method for identification of potential protein targets of a drug. A protein structure database is searched to find proteins to which a drug can bind or weakly bind. Examples of potential applications of this method in facilitating drug discovery include: (1) identification of unknown and secondary therapeutic targets of a drug, (2) prediction of potential toxicity and side effect of an investigative drug, and (3) probing molecular mechanism of bioactive herbal compounds such as those extracted from plants used in traditional medicines. This method and recent results on its applications...
5.
Computer-Aided Drug Target Search - Chen, Yuzong; Li, Zerong; Ung, C.Y.
Identification of the unknown targets of drugs, investigative drugs and herbal ingredients is an important task in drug discovery. It can potentially help in several aspects including: (1) determination of unknown therapeutic mechanism of certain drugs and medicinal herbs, (2) prediction of drug toxicity and side effect, and (3) analysis of protein-mediated pharmacokinetic properties of drugs. Here, a computer-aided drug target search method and its validation studies are presented.
6.
Designer peptides to understand the mineralization of calcium salts - Ajikumar, Parayil Kumaran; Lakshminarayanan, Rajamani; Valiyaveettil, Suresh; Kini, R. Manjunatha
Recently, we reported the extraction, purification and amino acid sequence of ansocalcin, the major goose eggshell matrix protein. In vitro studies showed that ansocalcin induces spherical calcite crystal aggregates. We designed two peptides using the unique features of the sequence of ansocalcin and the role of these peptides in CaCO₃ crystallization was investigated. The peptides showed similar activities as compared to ansocalcin, but at a higher concentration. The full characterization of the peptides and a rational for the observed morphology for the calcite crystals are discussed in detail.
7.
Electrochemical Insertion/extraction of Lithium in Multiwall Carbon Nanotube/Sb and SnSbâ??.â?? Nanocomposites - Chen, Wei Xiang; Lee, Jim Yang; Liu, Zhaolin
Multiwall carbon nanotubes (CNTs) were synthesized by catalytic chemical vapor deposition of acetylene and used as templates to prepare CNT-Sb and CNT-SnSbâ??.â?? nanocomposites via the chemical reduction of SnClâ?? and SbClâ?? precursors. SEM and TEM imagings show that the Sb and SnSbâ??.â?? particles were uniformly dispersed in the CNT web and on the outside surface of CNTs. These CNT-metal composites are active anode materials for lithium ion batteries, showing improved cyclability compared to unsupported Sb and SnSb particles; and higher reversible specific capacities than CNTs. The improvement in cyclability may be attributed to the nanoscale dimensions of the metal particles...
8.
Engineering Mammalian Cells for Improved Recombinant Protein Production - Wong, Niki S.C.; Tan, Hong-Kiat; Wang, Daniel I.C.; Yap, Miranda G.S.
The production of recombinant glycoproteins from mammalian cell cultures requires robust processes that can achieve high protein yield while ensuring the efficacy of these proteins as human therapeutics. We describe two approaches currently being developed in our group to genetically engineer cell lines with desirable characteristics for recombinant protein production. To enhance the degree of sialylation in the glycoprotein product, we propose to increase intracellular sialic acid availability by overexpressing the CMP-sialic acid transporters. We are also interested in engineering mammalian cells that can proliferate at reduced cultivation temperatures. Low temperature cultivation of mammalian cells has been shown to enhance...
9.
Enhancing Production of Recombinant Proteins from Mammalian Cells - Wong, Victor V.T.; Wong, Niki S.C.; Tan, Hong-Kiat; Wang, Daniel I.C.; Yap, Miranda G.S.
The bio-manufacturing of recombinant proteins from mammalian cell cultures requires robust processes that can maximize protein yield while ensuring the efficacy of these proteins as human therapeutics. Recognizing that the challenge of improving protein yield and quality can be met through various approaches, this paper presents three strategies currently being developed in our group. A method for rapidly selecting subpopulations of cells with high production characteristics is proposed. This method combines the efficiency of green fluorescent protein/fluorescence-activated cell sorting (GFP/FACS)â??based screening with homologous recombination to generate and select high-producing subclones. Next, the development of chemically defined, protein-free media for enhancing...
10.
Glucose-Sensitive Nanoparticles for Controlled Insulin Delivery - Zion, Todd C.; Tsang, Henry H.; Ying, Jackie Y.
A novel reverse microemulsion (RM) mediated synthesis of glucose-responsive nanoparticles was developed for controlled insulin delivery. Nanoparticles were constructed using a model system comprised of dextran, poly(α-1,6 glucose), physically crosslinked with the tetrafunctional glucose-binding protein, Con A. A rapid-screening technique was used to quantify RM phase behavior in the presence of dextran, Con A and insulin. The extent of the RM existence region diminishes with increasing dextran and Con A concentrations and with increasing dextran molecular weight. Crosslinking efficiency between Con A and fluorescein isothiocyanate dextran (FITC-Dex) was found to depend on the total concentration of Con A as well...
11.
Glycosylation by Chinese Hamster Ovary Cells in Dolichol Phosphate-Supplemented Cultures - Yuk, Inn Huam Yvonne.; Wang, Daniel I.C.
N-linked glycosylation often imparts important properties to protein therapeutics. An essential step in this intracellular process is the transfer of oligosaccharide from dolichol monophosphate (Dol-P) to a potential glycosylation site. Variability in the success rate of this reaction affects the extent of protein glycosylation. The critical role of Dol-P suggests that its availability may influence the extent of glycosylation by limiting the pool of lipid-linked oligosaccharides (LLOs), the glycosyl donor. To test this hypothesis, the impact of Dol-P supplementation on protein glycosylation in Chinese hamster ovary (CHO) cells was investigated. Although exogenous Dol-P was incorporated by CHO cells and processed...
12.
Increasing The Odds Of Hit Iidentification By Screening Against Receptor Homologs - Chen, Yuzong; Cai, Congzhong; Li, Zerong; Han, Lianyi; Wang, Jifeng
Increasing the odds of hit identification in screening is of significance for drug discovery. The odds for finding a hit are closely related either to the diversity of libraries or to the availability of focused libraries. There are no truly diverse libraries and it is difficult to design focused libraries without sufficient information. Hence it is helpful to consider alternative approaches that can enhance the odds using existing libraries. Multiple members of a protein family have been considered collectively in inhibitor design, on the basis of the correlation between protein families and ligands derived from specific compound classes. Such a...
13.
A New Class of Photoresponsive Surfactants - Shang, Tiangang; Wang, Elizabeth A.; Smith, Kenneth A.; Hatton, T. Alan
Recently, surface tension has been shown to be important in emerging high technologies, such as in pumping and control of flow in microfluidic devices, in microchemical analysis of complex fluids, and in rapid DNA screening, etc. Advances in these new technologies will depend strongly on the availability of flexible methods for controlling surface tension. Photo-control using a photoresponsive surfactant is a potentially attractive route to accomplishing many of the tasks required in these processes. Photoresponsive surfactants typically incorporate an azobenzene group as the functional unit which experiences reversible trans-to-cis photoisomerization under different irradiation conditions. The photoisomerization usually causes a change...
14.
NIR-Sensitive Au-Auâ??S Nanoparticles for Drug Delivery - Ren, L.; Chow, Gan-Moog
Near IR (NIR) sensitive Au-Auâ??S nanoparticles were prepared by mixing HAuClâ?? and Naâ??S in aqueous solutions. An anti-tumor drug, cis-platin, was adsorbed onto Au-Auâ??S nanoparticle surface via the 11-mercaptoundecanoic acid layers. The results showed that the degree of adsorption of cis-platin onto Au-Auâ??S nanoparticles was controlled by the pH value of solution, and the drug release was sensitive to NIR irradiation. The cis-platin loaded Au-Auâ??S nanoparticles can be potentially applied as NIR activated drug delivery carrier.
15.
Quantitative linkage of physiology and gene expression through empirical model construction: an investigation of diabetes - Misra, J.; Alevizos, I.; Bullen, J.; Blueher, S.; Mantzoros, C.; Stephanopoulos, Gregory
A methodology for the construction of predictive empirical models of physiological characteristics from microarray data is presented. The method, applied here to the study of the development of diabetes and insulin resistance, can be further expanded to other cases and to also include a variety of other data, such as protein expression, or metabolic flux data. The importance of several of the genes identified by the modeling methodology can be verified by comparison with results from prior literature. This implies potentially significant roles in diabetes for several of the uncharacterized genes discovered during the modeling procedure.
16.
Quantification and signaling of alternatively spliced GFRα2 isoforms - Too, Heng-Phon; Fung, Winnie Kar Yee
Neurturin (NTN) belongs to the glial cell-line derived neurotrophic factor (GDNF) family of growth factors. Both NTN and GDNF have been shown to potently prevent the degeneration of dopaminergic neuron in vitro and in vivo. The GDNF family receptor alpha 2 (GFRα-2) is the preferred receptor for NTN. In addition to the known full-length isoform (GFRα-2a), we have previously reported the isolation of two novel alternatively spliced isoforms (GFRα-2b and GFRα-2c). The expression levels of these isoforms have yet to be quantified and the functional properties determined. In this report, we have developed a real time polymerase chain reaction (PCR)...
17.
Rheological and Thermodynamic Properties of PEO-PPE-PEO and PAA-g-PEO-PPO-PEO System - Tian, Y.; Dai, S.; Tam, Michael K. C.; Bromberg, Lev; Hatton, T. Alan
Rheological and thermodynamic properties of Pluronic F127 copolymer and Pluronic-g-PAA have been studied as a function of temperature and concentration. A combination of rheometry and DSC was employed to examine the gelation behavior of F127 and F127-g-PAA. The viscosity of F127 is extremely sensitive to temperature when the polymer concentration exceeds 10 wt%. But significant increase of viscosity has been observed for 1.0 wt%F127-PAA aqueous solution as a function of temperature. This could be due to the PAA grafts, acting as cross-links attached to the F127 backbone.
18.
Self-Assembled Coatings for Controlling Biomolecular Adsorption on Surfaces - Seong, Jiehyun; Lee, Seok-Won; Jun, Shinae; Choi, Hyun-Goo; Laibinis, Paul E.
We have investigated a series of molecular and polymeric approaches for generating adherent thin films that impart anti-fouling characteristics to oxide surfaces. These films incorporate oligo- or poly(ethylene glycol) moieties that are expressed in high density in the near-surface region. In our molecular approach, oligo(ethylene glycol)-terminated n-alkyl-trichlorosilanes, RO(CH₂CH₂O)₃(CH₂)₁₁SiCl₃, have been designed so to spontaneously adsorb onto oxide surfaces and produce densely packed films. Another strategy uses a surface initiated polymerization to generate reactive anchored polymer chains that are then chemically modified to incorporate oligo(ethylene glycol) units. Lastly, a comb copolymer comprising a poly(acrylic acid) backbone and different grafting ratios of...
19.
Smart Microgel Studies. Interaction of Polyether-Modified Poly(Acrylic Acid) Microgels with Anticancer Drugs - Bromberg, Lev; Hatton, T. Alan
Studies of submillimeter gels composed of covalently cross-linked poly(acrylic acid)-g-poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic-PAA) networks are reviewed in light of potential applications of the microgels as drug carriers in oral delivery. The microgels are capable of volumetric transitions in response to environmental stimulae such as pH and temperature. It is shown that the type of Pluronic used in the microgel synthesis changes the structure of the resulting microgels, with the more hydrophobic Pluronic imparting porosity. Microgels based on Pluronic L92 (L92-PAA-EGDMA) possess higher ion-exchange capacity than microgels based on Pluronic F127 (F127-PAA-EGDMA), albeit the former are more hydrophobic. Analogously, more...
20.
Stability of Granular Materials under Vertical Vibrations - Deng, Rensheng; Wang, Chi-Hwa
The influence of periodic vibrations on the granular flow of materials is of great interests to scientists and engineers due to both theoretical and practical reasons. In this paper, the stability of a vertically vibrated granular layer is examined by linear stability analysis. This includes two major steps, firstly, the base state at various values of mass holdup (Mt) and energy input (Qt) is calculated and secondly, small perturbations are introduced to verify the stability of the base state by solving the resultant eigenvalue problem derived from the linearized governing equations and corresponding boundary conditions. Results from the base state...
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