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      • SCIESCOPUSKCI등재

        Molecular Breeding of Genes, Pathways and Genomes by DNA Shuffing

        Stemmer, Willem P.C. The Korean Society for Biotechnology and Bioengine 2002 Biotechnology and Bioprocess Engineering Vol.7 No.3

        Existing methods for optimization of sequences by random mutagenesis generate libraries with a small number of mostly deleterious mutations, resulting in libraries containing a large fraction of non-functional clones that explore only a small part of sequence space. Large numbers of clones need to be screened to find the rare mutants with improvements. Library display formats are useful to screen very large libraries but impose screening limitations that limit the value of this approach for most commercial applications. By contrast, in both classical breeding and in DNA shuffling, natural diversity is permutated by homologous recombination, generating libraries of very high quality, from which improved clones can be identified with a small number of complex screens. Given that this small number of screens can be performed under the conditions of actual use of the product, commercially relevant improvements can be reliably obtained.

      • KCI등재후보

        Molecular Breeding of Genes, Pathways and Genomes by DNA Shuffling

        Willem P. C. Stemmer 한국생물공학회 2002 Biotechnology and Bioprocess Engineering Vol.7 No.3

        Existing methods for optimization of sequences by random mutagenesis generate libraries with a small number of mostly deleterious mutations, resulting in libraries containing a large of clones need to be screened to find the rare mutants with improvements. Library display formats are useful to screen very large libraries but impose screning limitations that limit the value of this approach for most comercial applications. By contrast, in both classical breeding and in DNA shuffling, natural diversity is permutated by homologous recombination, generating libraries of very high quality, from which improved clones can be identified with a small number of complex screens. Given that this small number of screens can be performed under the conditions of actual use of the product, commercially relevant improvements can be reliably obtained.

      • SCISCIESCOPUS
      • Treatment of orthotopic malignant peripheral nerve sheath tumors with oncolytic herpes simplex virus

        Antoszczyk, Slawomir,Spyra, Melanie,Mautner, Victor Felix,Kurtz, Andreas,Stemmer-Rachamimov, Anat O.,Martuza, Robert L.,Rabkin, Samuel D. Oxford University Press 2014 Neuro-oncology Vol.16 No.8

        <P><B>Backgrounds</B></P><P>Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive and often lethal sarcoma that frequently develops in patients with neurofibromatosis type 1 (NF1). We developed new preclinical MPNST models and tested the efficacy of oncolytic herpes simplex viruses (oHSVs), a promising cancer therapeutic that selectively replicates in and kills cancer cells.</P><P><B>Methods</B></P><P>Mouse NF1<SUP>−</SUP> MPNST cell lines and human NF1<SUP>−</SUP> MPNST stemlike cells (MSLCs) were implanted into the sciatic nerves of immunocompetent and athymic mice, respectively. Tumor growth was followed by external measurement and sciatic nerve deficit using a hind-limb scoring system. Oncolytic HSV G47Δ as well as “armed” G47Δ expressing platelet factor 4 (PF4) or interleukin (IL)-12 were injected intratumorally into established sciatic nerve tumors.</P><P><B>Results</B></P><P>Mouse MPNST cell lines formed tumors with varying growth kinetics. A single intratumoral injection of G47Δ in sciatic nerve tumors derived from human S462 MSLCs in athymic mice or mouse M2 (37-3-18-4) cells in immunocompetent mice significantly inhibited tumor growth and prolonged survival. Local IL-12 expression significantly improved the efficacy of G47Δ in syngeneic mice, while PF4 expression prolonged survival. Injection of G47Δ directly into the sciatic nerve of athymic mice resulted in only mild symptoms that did not differ from phosphate buffered saline control.</P><P><B>Conclusions</B></P><P>Two new orthotopic MPNST models are described, including in syngeneic mice, expanding the options for preclinical testing. Oncolytic HSV G47Δ exhibited robust efficacy in both immunodeficient and immunocompetent MPNST models while maintaining safety. Interleukin-12 expression improved efficacy. These studies support the clinical translation of G47Δ for patients with MPNST.</P>

      • SCISCIESCOPUS

        Emergence of room-temperature ferroelectricity at reduced dimensions

        Lee, D.,Lu, H.,Gu, Y.,Choi, S.-Y.,Li, S.-D.,Ryu, S.,Paudel, T. R.,Song, K.,Mikheev, E.,Lee, S.,Stemmer, S.,Tenne, D. A.,Oh, S. H.,Tsymbal, E. Y.,Wu, X.,Chen, L.-Q.,Gruverman, A.,Eom, C. B. American Association for the Advancement of Scienc 2015 Science Vol.349 No.6254

        <P><B>Thinning films induces ferroelectricity</B></P><P>Thin ferroelectric films are needed in computers and medical devices. However, traditional ferroelectric films typically become less and less polarized the thinner the films become. Instead of using a good ferroelectric and making it thinner, Lee <I>et al.</I> started with SrTiO<SUP>3</SUP>, which in its bulk form is not ferroelectric. This material does have naturally occurring nanosized polarized regions. and when the thickness of the SrTiO<SUB>3</SUB> films reaches the typical size of these regions, the whole film aligns and becomes ferroelectric.</P><P><I>Science</I>, this issue p. 1314</P><P>The enhancement of the functional properties of materials at reduced dimensions is crucial for continuous advancements in nanoelectronic applications. Here, we report that the scale reduction leads to the emergence of an important functional property, ferroelectricity, challenging the long-standing notion that ferroelectricity is inevitably suppressed at the scale of a few nanometers. A combination of theoretical calculations, electrical measurements, and structural analyses provides evidence of room-temperature ferroelectricity in strain-free epitaxial nanometer-thick films of otherwise nonferroelectric strontium titanate (SrTiO<SUB>3</SUB>). We show that electrically induced alignment of naturally existing polar nanoregions is responsible for the appearance of a stable net ferroelectric polarization in these films. This finding can be useful for the development of low-dimensional material systems with enhanced functional properties relevant to emerging nanoelectronic devices.</P>

      • 나노구조물 첨가를 이용한 고온에서의 고체 열전도도 감소

        김우철(Woochul Kim),김강민(Kangmin Kim),박준영(Junyoung Park),Suzanne L. Singer,Arun Majumdar,Dmitri Klenov,Arthur C. Gossard,Susanne Stemmer,Joshua M. O. Zide 대한기계학회 2008 대한기계학회 춘추학술대회 Vol.2008 No.5

        Thermal conductivity of a crystalline solid at high temperature is dominated by the Umklapp process because the number of high frequency phonons increases as with temperature. It is challenging to reduce the thermal conductivity of crystalline solids at high temperature although it is widely known that by increasing the atomic defect concentration, thermal conductivity of crystalline solids can be reduced at low temperature. By increasing the concentration of ErAs nanoparticles in In0.53Ga0.47 As up to 6 atomic percent, we demonstrate a thermal conductivity reduction by almost a factor of three below that of In0.53Ga0.47 As at high temperature. A theoretical model suggests that the mean free path of the low frequency phonons is suppressed by increasing the ErAs nanoparticle concentration.

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