An application of 'building blocks of competitive advantage' approach to the U.S. careal market leaders

In the strategic management field, the study of building and sustaining competitive advantage for businesses has been one of the most important research areas. Although there are various attempts to explain the processes of building and sustaining competitive advantage, it has continued to be a poorly defined and operationalized construct. This paper focuses on the application of a strategic analytical approach, “Building Blocks of Competitive Advantages”, to analyze and compare the sources of competitive advantage for two market leaders in the U.S. breakfast cereal industry, Kellogg’s and General Mills. Various literature were reviewed in order to gain an understanding of the industry, and the roles played by these companies. As expected, Kellogg’s and General Mills have similar sources of competitive advantage, however, these companies have shown different ways of developing competitive advantage. This study was carried out in an attempt to stimulate efforts and provide direction on the conceptual development of the sources for competitive advantage

An application of ‘Building Blocks of Competitive Advantage’ Approach to The U.S. Cereal Market Leaders

In the strategic management field, the study of building and sustaining competitive advantage for businesses has been one of the most important research areas. Although there are various attempts to explain the processes of building and sustaining competitive advantage, it has continued to be a poorly defined and operationalized construct. This paper focuses on the application of a strategic analytical approach, “Building Blocks of Competitive Advantages”, to analyze and compare the sources of competitive advantage for two market leaders in the U.S. breakfast cereal industry, Kellogg’s and General Mills. Various literature were reviewed in order to gain an understanding of the industry, and the roles played by these companies. As expected, Kellogg’s and General Mills have similar sources of competitive advantage, however, these companies have shown different ways of developing competitive advantage. This study was carried out in an attempt to stimulate efforts and provide direction on the conceptual development of the sources for competitive advantage

Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2′-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2′-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures

AN APPLICATION OF ‘BUILDING BLOCKS OF COMPETITIVE ADVANTAGE’ APPROACH TO THE U.S. CEREAL MARKET LEADERS

In the strategic management field, the study of building and sustaining competitive advantage for businesses has been one of the most important research areas. Although there are various attempts to explain the processes of building and sustaining competitive advantage, it has continued to be a poorly defined and operationalized construct. This paper focuses on the application of a strategic analytical approach, “Building Blocks of Competitive Advantages”, to analyze and compare the sources of competitive advantage for two market leaders in the U.S. breakfast cereal industry, Kellogg’s and General Mills. Various literature were reviewed in order to gain an understanding of the industry, and the roles played by these companies. As expected, Kellogg’s and General Mills have similar sources of competitive advantage, however, these companies have shown different ways of developing competitive advantage. This study was carried out in an attempt to stimulate efforts and provide direction on the conceptual development of the sources for competitive advantage

CMOS image sensor with nanostructure

Department of Electrical Engineeringclos

Impacts of secondary aerosol formation and long range transport on severe haze during the winter of 2017 in the Seoul metropolitan area

Severe haze episodes occur frequently in the Seoul Metropolitan Area (SMA) and throughout East Asian countries, especially during the winter and early spring. We investigated the sources and chemistry of particulate matter (PM) during three winter haze episodes in Seoul that occurred between January 1st and February 10th in 2017 using a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) and positive matrix factorization (PMF) analysis. The average concentration of sub-micrometer aerosol (PM1 = NR-PM1 (+) black carbon (BC)) was 32.6 mu g/m(3), which was composed of 42% organics, 27% nitrate, 11% sulfate, 13% ammonium and 4% BC by mass. Six distinct sources of organic aerosol (OA) were identified: vehicle emitted hydrocarbon-like OA ( HOA), cooking OA (COA), biomass burning OA (BBOA), and 3 different types of secondary OA (SOA) with varying degrees of oxidation and temporal trends. The nitrate mass fraction increased during the three haze episodes, with nitrate accounting for 27-33% of PM1 mass. Enhanced nitrate concentrations and higher nitrate oxidation ratios (NOR), despite lower enhancement in relative humidity (RH) than the low PM loading period, suggest that regional transport of nitrate contributed to the nitrate mass during the haze periods. Lower HOA and COA concentrations during the high PM loading periods further confirm that local emissions or stagnant meteorological conditions were not the main reason for the severe haze. Residence time analysis (RTA), concentration field analysis (CFA), and column-CFA results from FLEXPART also showed that the measurement period was accompanied by atmospheric transport of nitrate, sulfate, and ammonium from eastern China. Nevertheless, we found that NO2, a precursor of nitrate, was predominantly from local emissions. These findings suggest that nitrate in Seoul is not only locally formed, but also transported from upwind areas. (C) 2018 Published by Elsevier B.V.N

Bioimaging of Nucleolin Aptamer-Containing 5-(N-benzylcarboxyamide)-2 `-deoxyuridine More Capable of Specific Binding to Targets in Cancer Cells

Chemically modified nucleotides have been developed and applied into SELEX procedure to find a novel type of aptamers to fit with targets of interest. In this study, we directly performed chemical modification of 5-(N-benzylcarboxyamide)-2`-deoxyuridine (called 5-BzdU) in the AS1411 aptamer, which binds to the nucleolin protein expressed in cancer cells. Forty-seven compounds of AS1411-containing Cy3-labeled 5-BzdU (called Cy3-(5-BzdU)-modified-AS1411) were synthesized by randomly substituting thymidines one to twelve in AS1411 with Cy3-labeled 5-BzdU. Both statistically quantified fluorescence measurements and confocal imaging analysis demonstrated at least three potential compounds of interest: number 12, 29 and 41 that significantly increased the targeting affinity to cancer cells but no significant activity from normal healthy cells. These results suggest that the position and number of substituents in AS1411 are critical parameters to improve the aptamer function. In this study, we demonstrated that chemical modification of the existing aptamers enhanced the binding and targeting affinity to targets of interest without additional SELEX procedures.This work was supported by National R&D Program for Cancer Control ofMinistry of Health &Welfare (0820320), National Research Foundation of Korea (no. 20090084640), POSCO Strategy R&D program (40003503.01), and a grant of the Korea Healthcare technology R&D Project, Ministry for Health,Welfare & Family Affairs, South Korea (A085136).Ko MH, 2009, SMALL, V5, P1207, DOI 10.1002/smll.200801580Rudge JS, 2007, P NATL ACAD SCI USA, V104, P18363, DOI 10.1073/pnas.0708865104Mhawech-Fauceglia P, 2007, HISTOPATHOLOGY, V50, P472, DOI 10.1111/j.1365-2559.2007.02635.xHEIL JR, 2007Anikeeva N, 2006, P NATL ACAD SCI USA, V103, P16846, DOI 10.1073/pnas.0607771103Choi KH, 2006, MOL CANCER THER, V5, P2428, DOI 10.1158/1535-7163.MCT-05-0204Pas J, 2006, INT J BIOCHEM CELL B, V38, P1594, DOI 10.1016/j.biocel.2006.03.017Zhang Z, 2005, CYTOTHERAPY, V7, P186, DOI 10.1080/14653240510027091Burmeister PE, 2005, CHEM BIOL, V12, P25, DOI 10.1016/j.chembiol.2004.10.017Kato Y, 2005, NUCLEIC ACIDS RES, V33, P2942, DOI 10.1093/nar/gki578Dwarakanath S, 2004, BIOCHEM BIOPH RES CO, V325, P739, DOI 10.1016/j.bbrc.2004.10.099Vaught JD, 2004, J AM CHEM SOC, V126, P11231, DOI 10.1021/ja049009hHerbst RS, 2004, INT J RADIAT ONCOL, V59, P21, DOI 10.1016/j.ijrobp.2003.11.041Christian S, 2003, J CELL BIOL, V163, P871, DOI 10.1083/jcb.200304132Lato SM, 2002, NUCLEIC ACIDS RES, V30, P1401Micklefield J, 2001, CURR MED CHEM, V8, P1157Bardeesy N, 1998, NUCLEIC ACIDS RES, V26, P1784Eaton BE, 1997, BIOORGAN MED CHEM, V5, P1087Eaton BE, 1997, CURR OPIN CHEM BIOL, V1, P10Crooke ST, 1996, ANNU REV PHARMACOL, V36, P107ELLINGTON AD, 1990, NATURE, V346, P818TUERK C, 1990, SCIENCE, V249, P505

In vitro Derby Imaging of Cancer Biomarkers Using Quantum Dots

Semiconductor quantum dots (QDs), which have broad absorption with narrow. emission spectra, are useful for multiplex imaging. Here, fluorescence derby imaging using dual color QDs conjugated by the AS1411 aptamer (targeting nucleolin) and the arginine-glycine-aspartic acid (targeting the integrin alpha(v)beta(3)) in cancer cells is reported. Simultaneous fluorescence imaging of cellular distribution of nucleolin and integrin alpha(v)beta(3) using QDs enables easy monitoring of separate targets in the cancer cells and the normal healthy cells. These results suggest the feasibility of a concurrent visualization of QD-based multiple cancer biomarkers using small molecules such as aptamer or peptide ligands.This work was supported by the Nano Bio Regenomics Project of Korean Science and Engineering Foundation, Innovation Cluster for Advanced Medical Imaging Technology, KOSEF MOST (2008- 03767 and M20M04000039-08M0400-03910) and the National R&D Program for Cancer Control of Ministry of Health&Welfare (0820320).Rudge JS, 2007, P NATL ACAD SCI USA, V104, P18363, DOI 10.1073/pnas.0708865104Bagalkot V, 2007, NANO LETT, V7, P3065, DOI 10.1021/nl071546nKobayashi H, 2007, NANO LETT, V7, P1711, DOI 10.1021/nl0707003Hama Y, 2007, BREAST CANCER RES TR, V103, P23, DOI 10.1007/s10549-006-9347-0Mhawech-Fauceglia P, 2007, HISTOPATHOLOGY, V50, P472, DOI 10.1111/j.1365-2559.2007.02635.xTada H, 2007, CANCER RES, V67, P1138, DOI 10.1158/0008-5472.CAN-06-1185Laudadio J, 2007, EXPERT REV MOL DIAGN, V7, P53, DOI 10.1586/14737159.7.1.53Anikeeva N, 2006, P NATL ACAD SCI USA, V103, P16846, DOI 10.1073/pnas.0607771103Girvan AC, 2006, MOL CANCER THER, V5, P1790, DOI 10.1158/1535-7163.MCT-05-0361Cai WB, 2006, NANO LETT, V6, P669, DOI 10.1021/nl052405tZhang XZ, 2006, J NUCL MED, V47, P113Pas J, 2006, INT J BIOCHEM CELL B, V38, P1594, DOI 10.1016/j.biocel.2006.03.017Hoffman RM, 2005, NAT REV CANCER, V5, P796, DOI 10.1038/nrc1717Zhang Z, 2005, CYTOTHERAPY, V7, P186, DOI 10.1080/14653240510027091Dwarakanath S, 2004, BIOCHEM BIOPH RES CO, V325, P739, DOI 10.1016/j.bbrc.2004.10.099Gao XH, 2004, NAT BIOTECHNOL, V22, P969, DOI 10.1038/nbt994Herbst RS, 2004, INT J RADIAT ONCOL, V59, P21, DOI 10.1016/j.ijrobp.2003.11.041Legrand D, 2004, EUR J BIOCHEM, V271, P303, DOI 10.1046/j.1432-1033.2003.03929.xChristian S, 2003, J CELL BIOL, V163, P871, DOI 10.1083/jcb.200304132Kerbel R, 2002, NAT REV CANCER, V2, P727, DOI 10.1038/nrc905Akerman ME, 2002, P NATL ACAD SCI USA, V99, P12617, DOI 10.1073/pnas.152463399Xu KL, 2002, CELL MOTIL CYTOSKEL, V53, P39, DOI 10.1002/cm.10060Pecheur I, 2002, FASEB J, V16, P1266, DOI 10.1096/fj.01-0911fjeXiong JP, 2002, SCIENCE, V296, P151Xiong JP, 2001, SCIENCE, V294, P339, DOI 10.1126/science.1064535Zwick E, 2001, ENDOCR-RELAT CANCER, V8, P161Bates PJ, 1999, J BIOL CHEM, V274, P26369SHEU JR, 1994, PEPTIDES, V15, P1391LEITINGER N, 1993, J CELL BIOCHEM, V52, P1532

A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer

The recent advances in molecular imaging techniques, using cancer-targeting nanoparticle probes, provide noninvasive tracking information on cancer cells in living subjects. Here, we report a multimodal cancer-targeted imaging system capable of concurrent fluorescence imaging, radionuclide imaging, and MRI in vivo. Methods: A cobalt-ferrite nanoparticle surrounded by fluorescent rhodamine (designated MF) within a silica shell matrix was synthesized with the AS1411 aptamer (MF-AS1411) that targets nucleolin (a cellular membrane protein highly expressed in cancer) using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC). This purified MF-AS1411 particle was bound with 2-(p-isothio-cyanatobenzyl)-1,4,7-triazacyclonane1,4,7-triacetic acid (p-SCN-bn-NOTA) chelating agent and further labeled with (67)Ga-citrate (MFR-AS1411). The shape and size distribution of MFR-AS1411 were characterized by transmission electron microscope (TEM). The cellular distribution of the nucleolin protein using the MFR-AS1411 nanoparticle was detected by fluorescence confocal microscopy. Phantom MR images were obtained as the concentration of MFR-AS1411 increased, using a 1.5-T MRI scanner. In vivo (67)Ga radionuclide imaging and MRI were performed using a gamma-camera and a 1.5-T MR imager, respectively. Results: TEM imaging revealed MF and MFR-AS1411 to be spheric and well dispersed. The purified MFR-AS1411 nanoparticle showed specific fluorescence signals in nucleolin-expressing C6 cells, compared with MFR-AS1411 mutant (MFR-AS1411mt)-treated C6 cells. The rhodamine fluorescence intensity and (67)Ga activity of MFR-AS1411 were enhanced in a dose-dependent manner as the concentration of MFR-AS1411 was increased. The (67)Ga radionuclide was detected in both thighs of the mice injected with MFR-AS1411, whereas the MFR-AS1411 mutant (MFR-AS1411mt) administration revealed rapid clearance via the bloodstream, demonstrating that MFR-AS1411 specifically targeted cancer cells. Bioluminescence images in the C6 cells, stably expressing the luciferase gene, illustrated the in vivo distribution. T2-weighted MR images of the same mice injected with MFR-AS1411 showed dark T2 signals inside the tumor region, compared with the MRI signal of the tumor region injected with MFR-AS1411mt particles. Conclusion: We developed a nanoparticle-based cancer-specific imaging probe using the AS1411 aptamer in vivo and in vitro. This multimodal targeting imaging strategy, using a cancer-specific AS1411 aptamer, can be used as a versatile imaging tool for specific cancer diagnosis.Lee HY, 2008, J NUCL MED, V49, P1371, DOI 10.2967/jnumed.108.051243Jeong JM, 2008, J NUCL MED, V49, P830, DOI 10.2967/jnumed.107.047423Soundararajan S, 2008, CANCER RES, V68, P2358, DOI 10.1158/0008-5472.CAN-07-5723Cai WB, 2008, NAT PROTOC, V3, P89, DOI 10.1038/nprot.2007.478Love Z, 2007, J NUCL MED, V48, P2011, DOI 10.2967/jnumed.107.043166Bagalkot V, 2007, NANO LETT, V7, P3065, DOI 10.1021/nl071546nAntunes P, 2007, EUR J NUCL MED MOL I, V34, P982, DOI 10.1007/s00259-006-0317-xLiu YY, 2007, INT J CANCER, V120, P2527, DOI 10.1002/ijc.22709Wang W, 2007, BIOCONJUGATE CHEM, V18, P397, DOI 10.1021/bc0602679SURI SS, 2007, J OCCUP MED TOXICOL, V2, P16Sharrna P, 2006, ADV COLLOID INTERFAC, V123, P471, DOI 10.1016/j.cis.2006.05.026Girvan AC, 2006, MOL CANCER THER, V5, P1790, DOI 10.1158/1535-7163.MCT-05-0361Leary SP, 2006, NEUROSURGERY, V58, P805, DOI 10.1227/01.NEU.0000216793.45952.EDChu TC, 2006, BIOSENS BIOELECTRON, V21, P1859, DOI 10.1016/j.bios.2005.12.015Hicke BJ, 2006, J NUCL MED, V47, P668So MK, 2006, NAT BIOTECHNOL, V24, P339, DOI 10.1038/nbt1188Yoon TJ, 2006, SMALL, V2, P209, DOI 10.1002/smll.200500360Kim JS, 2006, TOXICOL SCI, V89, P338, DOI 10.1093/toxsci/kfj027Doubrovin M, 2004, BIOCONJUGATE CHEM, V15, P1376, DOI 10.1021/bc0498572Ray P, 2004, CANCER RES, V64, P1323Hovanessian AG, 2000, EXP CELL RES, V261, P312Ginisty H, 1999, J CELL SCI, V112, P761DERENZINI M, 1995, LAB INVEST, V73, P4973

PET imaging of HER2 expression with an 18F-fluoride labeled aptamer.

BACKGROUND/PURPOSE:Aptamers are oligonucleotide or peptide molecules that bind to a target molecule with high affinity and specificity. The present study aimed to evaluate the target specificity and applicability for in vivo molecular imaging of an aptamer labeled with a radioisotope. METHODS:The human epidermal growth factor receptor 2 (HER2/ErbB2) aptamer was radiolabeled with 18F-fluoride. HER2-positive tumor cell uptake of the aptamer was evaluated in comparison to negative controls by flow cytometry and confocal microscopy. Using 18F-labeled HER2-specific aptamer positron emission tomography (PET), in vivo molecular images of BT474 tumor-bearing mice were taken at 60, 90 and 120 minutes after injection. RESULTS:In flow cytometric analysis, HER2 aptamer showed strong binding to HER2-positive BT474 cells, while binding to HER2-negative MDA-MB231 cells was quite low. Likewise, in confocal microscopic images, the aptamer was bound to HER2-positive breast cancer cells, with minimal binding to HER2-negative cells. In vivo PET molecular imaging of BT474 tumor-bearing mice revealed significant higher uptake of the 18F-labeled HER2 specific aptamer into the tumor compared to the that of HER2-negative cell tumor(p = 0.033). HER2 aptamer was able to preferentially bind to HER2-positive breast cancer cells both in vitro and in vivo, by recognizing HER2 structure on the surface of these cells. CONCLUSION:The 18F-labeled aptamer enabled appropriate visualization of HER2 expression by human breast cancer cells. The results suggest that a radiolabeled HER2 aptamer could potentially be applied in the development of treatment strategies or in targeted therapy against HER2-positive breast cancer cells