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Mammalian Systems Biotechnology Reveals Global Cellular Adaptations in a Recombinant CHO Cell Line
Yusufi, F.N.K.,Lakshmanan, M.,Ho, Y.S.,Loo, B.L.W.,Ariyaratne, P.,Yang, Y.,Ng, S.K.,Tan, T.R.M.,Yeo, H.C.,Lim, H.L.,Ng, S.W.,Hiu, A.P.,Chow, C.P.,Wan, C.,Chen, S.,Teo, G.,Song, G.,Chin, J.X.,Ruan, X. Cell Press 2017 Cell systems Vol.4 No.5
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipid species, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner.
Manh, T. V.,Phan, T. L.,Lee, B. W.,Liu, Chunli,Ho, T. A.,Thanh, T. D.,Vuong, N. M.,Yu, S. C. IEEE 2015 IEEE transactions on magnetics Vol.51 No.11
<P>Previous studies pointed out that ferromagnetism in Mn-doped ZnO was related to exchange interactions between Mn ions mediated by lattice defects. This means that it is possible to modify a Mn-doped ZnO paramagnet to a ferromagnet by creating lattice defects in it. The present work starts from a paramagnetic Zn0.98Mn0.02O sample prepared by solid-state reaction and then creates more defects upon mechanical milling. By changing the milling time (t(m)) from 0.5 to 20 h, we produced nanocrystalline (NC) samples with average crystallite sizes (d) ranging from 30 to 157 nm. The d decrease generated lattice strain and defects. This broadens and blurs the lines of Raman scattering and electron spin resonance (ESR) spectra. Interestingly, magnetization studies versus magnetic field revealed the samples with d <= 150 nm exhibiting room-temperature ferromagnetic (FM) order. The FM order became largest as d = 72 nm, corresponding to a saturation magnetization of M-s approximate to 0.006 emu/g. Apart from this d value, M-s would be gradually decreased. X-ray absorption fine structure (XAFS) spectra revealed a coexistence of Mn2+ and Mn3+ ions in the samples. Their concentration ratio was slightly changed with decreasing d, due to the slight shift of the absorption edge. With the features of Fourier-transformed XAFS and ESR spectra, we believe that ferromagnetism in the NC samples is related to oxygen vacancies residing on the surface of nanoparticles. Local lattice distortions can lead to zinc interstitials for the samples d < 72 nm, which decreases M-s.</P>
Ho, T. A.,Phan, M. H.,Phuc, N. X.,Lam, V. D.,Phan, T. L.,Yu, S. C. Springer Science + Business Media 2016 Journal of electronic materials Vol.45 No.5
<P>The Ti-substitution influence on the magnetic and magnetocaloric properties of La0.7Ba0.3Mn1-x Ti (x) O-3 (x = 0.05 and 0.1) was investigated. Based on Banerjee's criteria and Franco's universal curves, we proved the existence of a second-order magnetic phase transition in the samples. Using the modified Arrott plot method, we determined the critical parameters T (C) a parts per thousand 245 K, beta = 0.374 +/- A 0.013, gamma = 1.228 +/- A 0.045, and delta = 4.26 +/- A 0.03 for x = 0.05, and T (C) a parts per thousand 169 K, beta = 0.339 +/- A 0.001, gamma = 1.307 +/- A 0.003, and delta = 4.78 +/- A 0.02 for x = 0.1. With these critical values, the predictable scaling behavior of the M(H) data above and below T (C) proves that the calculated exponents are unambiguous and intrinsic. The values beta = 0.374 for x = 0.05 and beta = 0.339 for x = 0.1 suggest that the magnetic phase transition of the samples falls into the three-dimensional (3D) Heisenberg and 3D Ising universality classes, respectively, corresponding to short-range ferromagnetic (FM) order due to FM clusters in a wide temperature range even above T (C), as confirmed by electron spin resonance studies. In reference to the magnetocaloric effect around T (C), the magnetic entropy change reaches maximum values (|Delta S-max|) of about 4 and 3 J kg(-1) K-1 for x = 0.05 and 0.1, respectively, for a magnetic field change 50 kOe. Magnetic field dependencies of |Delta S-max| obey a power function |Delta S-max(H)| ae H (n) , where exponent values n = 0.59 and 0.61 for x = 0.05 and 0.1, respectively, were determined from the relation n = 1 + (beta-1)/(beta + gamma). The difference between the experimental n values and the theoretical value n = 2/3 of the mean field model is due to the presence of short-range FM order in the samples.</P>
C.N.M. Ho,H. Breuninger,S. Pettersson,G. Escobar,F. Canales 전력전자학회 2011 ICPE(ISPE)논문집 Vol.2011 No.5
A performance comparison of an interleaved boost converter (IBC) using Si and SiC diodes for PV energy conversion systems is presented in this paper. Performance attributes under investigation include the device behavior, thermal requirement, system efficiency and power density. The interleaved boost converter is designed for sustaining the dc link voltage in the energy conversion system. Due to the absence of reverse recovery current in SiC Schottky diodes, low switching loss is generated in the diodes and the switches. This benefit causes higher system efficiency and lower cooling system design requirement. As a benefit, the volume and weight of the heatsink can be further reduced. Furthermore, behaviors of semiconductors and steady-state characteristics of IBC are discussed in the paper. The validity of the analyses is confirmed experimentally by using a 2.5 ㎾ IBC prototype with wide power and input voltage operating range.
Practical Implementation of an Interleaved Boost Converter using SiC Diodes for PV Applications
C.N.M. Ho,H. Breuninger,S. Pettersson,G. Escobar,L. Serpa,A. Coccia 전력전자학회 2011 ICPE(ISPE)논문집 Vol.2011 No.5
The implementation of an interleaved boost converter using SiC diodes for PV applications is presented in this paper. The converter consists of two switching cells sharing the PV panel output current. Their switching patterns are synchronized with 180 degree phase shift. Each switching cell has a SiC Schottky diode and a CoolMOS switching device. The SiC diodes provide zero reverse recovery current ideally, which reduces the commutation losses of the switches. Such advantage from the SiC diodes can make the converter system achieve higher efficiency and higher power density by reducing the requirement of the cooling system. This paper presents also an optimization study of the size and efficiency of the interleaved boost converter. Based on 1) the steady-state characteristic of the topology, 2) the static and dynamic characteristics of the switching cells, 3) the loss model of the magnetic components and 4) the cooling system design, the paper provides a set of design criteria, procedures and experimental results for a 2.5 ㎾ interleaved boost converter using SiC diodes prototype.
Infrared spectroscopy and nano-imaging of the insulator-to-metal transition in vanadium dioxide
Qazilbash, M. M.,Brehm, M.,Andreev, G. O.,Frenzel, A.,Ho, P.-C.,Chae, Byung-Gyu,Kim, Bong-Jun,Yun, Sun Jin,Kim, Hyun-Tak,Balatsky, A. V.,Shpyrko, O. G.,Maple, M. B.,Keilmann, F.,Basov, D. N. American Physical Society 2009 Physical review. B, Condensed matter and materials Vol.79 No.7
Ma, R. C. W.,Hu, C.,Tam, C. H.,Zhang, R.,Kwan, P.,Leung, T. F.,Thomas, G. N.,Go, M. J.,Hara, K.,Sim, X.,Ho, J. S. K.,Wang, C.,Li, H.,Lu, L.,Wang, Y.,Li, J. W.,Wang, Y.,Lam, V. K. L.,Wang, J.,Yu, W.,Ki Springer-Verlag 2013 Diabetologia Vol.56 No.6
<P><B>Aims/hypothesis</B></P><P>Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.</P><P><B>Methods</B></P><P>We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.</P><P><B>Results</B></P><P>We identified <I>CDKN2A/B</I> and four novel type 2 diabetes association signals with <I>p</I> < 1 × 10<SUP>−5</SUP> from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (<I>p</I><SUB>meta</SUB> = 2.6 × 10<SUP>−8</SUP>; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (<I>p</I><SUB>meta</SUB> = 2.3 × 10<SUP>−10</SUP>) and a population of European descent (<I>p</I> = 8.6 × 10<SUP>−3</SUP>). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.</P><P><B>Conclusions/interpretation</B></P><P>Our study identifies rs10229583 near <I>PAX4</I> as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-013-2874-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>
Magnetic properties and magnetocaloric effect in Fe90-x Sn x Zr10 alloy ribbons
Phan, T. L.,Dan, N. H.,Thanh, T. D.,Mai, N. T.,Ho, T. A.,Yu, S. C.,Le, Anh-Tuan,Phan, M. H. Korean Physical Society 2015 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.66 No.8
<P>This work points out the possibility of tuning the magnetocaloric (MC) effect in Fe90-x Sn (x) Zr-10 alloy ribbons in the temperature range from 235 to 315 K by changing the Sn-doping content (x). Under an applied field change from 0 to 50 kOe, the maximum magnetic-entropy changes around the ferromagnetic-paramagnetic phase transition are about 3.6, 4.1 and 3.3 J kg(-1)center dot K-1 for x = 0, 2 and 4, respectively, which correspond to relative cooling powers of 280 similar to 410 J center dot kg(-1). Studying the magnetic properties of the alloy ribbons based on Banerjee's criteria and assessing the magneticordering parameter n = dLn|Delta S (m) |/dLnH (where Delta S (m) and H are the magnetic-entropy change and the magnetic field, respectively) reveals that the alloys undergo a second-order phase transition and exhibit a short-range ferromagnetic order. The nature of these phenomena is further analyzed by means of the results obtained from the analyses of the crystal structure, the Curie-Weiss law, and the Griffith phase.</P>
Phan, The-Long,Ho, T.A.,Thang, P.D.,Tran, Q.T.,Thanh, T.D.,Phuc, N.X.,Phan, M.H.,Huy, B.T.,Yu, S.C. Elsevier 2014 JOURNAL OF ALLOYS AND COMPOUNDS Vol.615 No.-
<P><B>Abstract</B></P> <P>We have determined the values of critical exponents of two polycrystalline samples (Nd<SUB>1−</SUB> <I> <SUB>x</SUB> </I>Y<I> <SUB>x</SUB> </I>)<SUB>0.7</SUB>Sr<SUB>0.3</SUB>MnO<SUB>3</SUB> (<I>x </I>=0 and 0.07) from the magnetization data versus temperature and magnetic field, <I>M</I>(<I>H</I>, <I>T</I>), to learn about their magnetic and magnetocaloric (MC) properties. The results reveal the samples exhibiting the crossover of first-order and second-order phase transitions, where the exponent values <I>β </I>=0.271 and <I>γ </I>=0.922 for <I>x </I>=0, and <I>β </I>=0.234–0.236 and <I>γ </I>=1.044–1.063 for <I>x </I>=0.07 determined by using modified Arrott plots and static-scaling hypothesis are close to those expected for the tricritical mean-field theory (<I>β </I>=0.25 and <I>γ </I>=1.0). Particularly, the <I>T</I> <SUB>C</SUB> of <I>x </I>=0 and 0.07 can be any value in the temperature ranges of 240–255K and 170–278K, respectively, depending on the magnitude of applied magnetic field and determination techniques. Around the <I>T</I> <SUB>C</SUB>, studying the MC effect of the samples has revealed a large magnetic-entropy change (Δ<I>S</I> <SUB>m</SUB>) up to ∼8J/kgK for the applied field interval Δ<I>H </I>=50kOe, corresponding to refrigerant capacity values of 200–245J/kg. These phenomena are related to the crossover nature and the persisting of FM/anti-FM interactions even above the <I>T</I> <SUB>C</SUB>, as further confirmed by electron-spin-resonance data, Curie–Weiss law-based analyses, and an exponential parameter characteristic of magnetic order <I>n </I>=dLn|Δ<I>S</I> <SUB>m</SUB>|/dLn<I>H</I>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Tricritical point in Y-doped Nd<SUB>0.7</SUB>Sr<SUB>0.3</SUB>MnO<SUB>3</SUB> manganites. </LI> <LI> A large magnetic-entropy change. </LI> <LI> Magnetic inhomogeneity and phase separation. </LI> </UL> </P>