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      • SCISCIESCOPUS

        Efficient long-term amplification of hepatitis B virus isolates after infection of slow proliferating HepG2-NTCP cells

        ,nig, Alexander,Yang, Jaewon,Jo, Eunji,Park, Kyu Ho Paul,Kim, Hyun,Than, Thoa Thi,Song, Xiyong,Qi, Xiaoxuan,Dai, Xinghong,Park, Soonju,Shum, David,Ryu, Wang-Shick,Kim, Jung-Hee,Yoon, Seung Kew,P Elsevier 2019 Journal of hepatology Vol.71 No.2

        <P><B>Background & Aims</B></P> <P>As hepatitis B virus (HBV) spreads through the infected liver it is simultaneously secreted into the blood. HBV-susceptible <I>in vitro</I> infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens.</P> <P><B>Methods</B></P> <P>An HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny was selected. Secreted HBV progeny were characterized by native gel electrophoresis and electron microscopy. Comparative RNA-seq transcriptomics was performed to quantify the expression of host proviral and restriction factors. Viral spread routes were evaluated using HBV entry- or replication inhibitors, visualization of viral cell-to-cell spread in reporter cells, and nearest neighbor infection determination. Amplification kinetics of HBV genotypes B-D were analyzed.</P> <P><B>Results</B></P> <P>Infected HepG2-NTCPsec+ secreted high levels of large HBV surface protein-enveloped infectious HBV progeny with typical appearance under electron microscopy. RNA-seq transcriptomics revealed that HBV does not induce significant gene expression changes in HepG2-NTCPsec+, however, transcription factors favoring HBV amplification were more strongly expressed than in less permissive HepG2-NTCPsec−. Upon inoculation with HBV-containing patient sera, rates of infected cells increased from 10% initially to 70% by viral spread to adjacent cells, and viral progeny and antigens were efficiently secreted. HepG2-NTCPsec+ supported up to 1,300-fold net amplification of HBV genomes depending on the source of virus. Viral spread and amplification were abolished by entry and replication inhibitors; viral rebound was observed after inhibitor discontinuation.</P> <P><B>Conclusions</B></P> <P>The novel HepG2-NTCPsec+ cells efficiently support the complete HBV life cycle, long-term viral spread and amplification of HBV derived from patients or cell culture, resembling relevant features of HBV-infected patients.</P> <P><B>Lay summary</B></P> <P>Currently available laboratory systems are unable to reproduce the dynamics of hepatitis B virus (HBV) spread through the infected liver and release into the blood. We developed a slowly dividing liver-derived cell line which multiplies infectious viral particles upon inoculation with patient- or cell culture-derived HBV. This new infection model can improve therapy by measuring, in advance, the sensitivity of a patient’s HBV strain to specific antiviral drugs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cell culture system that mimicks complete HBV life cycle from entry to egress. </LI> <LI> Efficient <I>in vitro</I> infection with crude HBV patient sera. </LI> <LI> Up to 50- and 1,300-fold net amplification of patient- and cell culture-derived input HBV in the supernatant. </LI> <LI> Polyethylene glycol-independent HBV spread to adjacent cells, forming infected cell clusters. </LI> <LI> Evaluation of patient- and cell culture-derived HBV amplification w/wo antivirals over 8 weeks. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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      • Time resolved coherence-imaging spectrometer on WEGA stellarator

        Chung, Jinil,,nig, Ralf,Howard, John,Otte, Matthias,Klinger, Thomas Published jointly by The Institute of Physics and 2005 Plasma physics and controlled fusion Vol.47 No.6

        <P>Imaging sensor technologies such as charge coupled devices and complementary metal-oxide-semiconductor have made remarkable progress in recent years. Fast imaging systems based on these new technologies are now being routinely employed for advanced fusion diagnostics. Since two-dimensional imaging considerably improves the investigation of three-dimensional structural physics, we have installed and operated the first high-speed two-dimensional coherence imaging camera system for the study of ion temperatures and flow velocities in the WEGA stellarator based on the Doppler broadening of 468.6 nm He II line emission. The coherence imaging camera was able to image the complete plasma poloidal cross-section over a toroidal region spanning 10°. The camera was used for basic plasma studies, including electron cyclotron resonance heating (ECRH) power step experiments. The ion temperature of helium plasmas in WEGA is found to be 1.5–2.0 eV at maximum (26 kW) ECRH power. The plasma rotates in the <I>E</I> × <I>B</I> direction with speeds between 500 and 1000 m s<SUP>−1</SUP>, increasing at higher ECRH power. It was confirmed that the flow direction reverses with the direction of the magnetic field. The observed ion temperatures and flows were cross checked against a multi-channel Echelle spectrometer and satisfactory agreement obtained.</P>

      • Association of <i>SNCA</i> variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease

        Chung, Sun Ju,,nig, Inke R.,Lohmann, Katja,Hinrichs, Frauke,Kim, Juyeon,Ryu, Ho-Sung,Lee, Hyo Jeong,Kim, Kiju,Lee, Jeong Hoon,Jung, Kee Wook,Kim, Mi Jung,Kim, Mi-Jung,Kim, Young Jin,Yun, Sung-Ch Elsevier 2019 Parkinsonism & related disorders Vol.61 No.-

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between <I>SNCA</I> variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals.</P> <P><B>Methods</B></P> <P>The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the <I>SNCA</I> gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped.</P> <P><B>Results</B></P> <P>In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70–20.97, <I>P</I> = 0.01). In an interaction analysis, SNP rs11931074–PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58–33.88, <I>P</I> = 0.01). Longer <I>SNCA</I> REP1 alleles were not associated with positive α-Syn immunostaining in the ENS.</P> <P><B>Conclusion</B></P> <P>This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with <I>SNCA</I> variants in patients with PD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Determining factors for alpha-synuclein (α-Syn) deposition in the enteric nervous system (ENS) of humans are still unclear. </LI> <LI> <I>SNCA</I> rs11931074 (G allele) is associated with α-Syn immunostaining in the ENS in patients with Parkinson's disease (PD). </LI> <LI> α-Syn deposition in the ENS may be associated with <I>SNCA</I> variants in patients with PD. </LI> </UL> </P>

      • THE CORE ELEMENTS OF STORY: INTRODUCING THEORIES AND METHODS OF NARRATOLOGY AND LINGUISTIC FOR THE CONCEPT OF STORYTELLING IN MARKETING AND MANAGEMENT ON THE EXAMPLE OF CREATING VALUES

        Klaus-Peter Wiedmann,Jan C. L. K?nig 글로벌지식마케팅경영학회 2014 Global Marketing Conference Vol.2014 No.7

        Storytelling is a genuine field of interest of narratology and the philologies. While it becomes important to both managers and researchers, these origins in analysing and discussing seem to be underrated in contemporary approaches. This paper seeks to close this gap by introducing theories from the humanities regarding qualitative methods for a conceptual frame that covers the core elements of storytelling and the possibilities of transmitting certain issues on the purpose of specific effect. For values are a typical issue in brand management, we offer an example of a qualitative approach towards values in storytelling. Finally, we offer an outlook on a following consecutive research combining both qualitative and quantitative methods.

      • Absolute binding free energy calculations of CBClip host-guest systems in the SAMPL5 blind challenge

        Lee, Juyong,Tofoleanu, Florentina,Pickard IV, Frank C.,,nig, Gerhard,Huang, Jing,Damjanović,, Ana,Baek, Minkyung,Seok, Chaok,Brooks, Bernard R. Springer-Verlag 2017 Journal of computer-aided molecular design Vol.31 No.1

        <P>Herein, we report the absolute binding free energy calculations of CBClip complexes in the SAMPL5 blind challenge. Initial conformations of CBClip complexes were obtained using docking and molecular dynamics simulations. Free energy calculations were performed using thermodynamic integration (TI) with soft-core potentials and Bennett's acceptance ratio (BAR) method based on a serial insertion scheme. We compared the results obtained with TI simulations with soft-core potentials and Hamiltonian replica exchange simulations with the serial insertion method combined with the BAR method. The results show that the difference between the two methods can be mainly attributed to the van der Waals free energies, suggesting that either the simulations used for TI or the simulations used for BAR, or both are not fully converged and the two sets of simulations may have sampled difference phase space regions. The penalty scores of force field parameters of the 10 guest molecules provided by CHARMM Generalized Force Field can be an indicator of the accuracy of binding free energy calculations. Among our submissions, the combination of docking and TI performed best, which yielded the root mean square deviation of 2.94 kcal/mol and an average unsigned error of 3.41 kcal/mol for the ten guest molecules. These values were best overall among all participants. However, our submissions had little correlation with experiments.</P>

      • KCI등재

        The legends of tomorrow: A semiotic approach towards a brand myth of luxury heritage

        Jan C. L. König,Klaus-Peter Wiedmann,Nadine Hennigs,Janina Haase 한국마케팅과학회 2016 마케팅과학연구 Vol.26 No.2

        The art of positioning luxury brands within a frame of heritage myths has become increasingly important for marketing and management recently, for communicating luxury values from the perspective of a unique brand is a major task to distinguish companies and products within the field of luxury and to gain a strong individual identity. However, the complexity of signs within shop designs is a semiotic phenomenon that is still rather focused on by the humanities, while its effective adaption for luxury fashion brands regarding heritage and value communication is still poorly understood and has not been explored so far. The most important value of our study is to present and analyse luxury sign chains in a traditional London gentleman’s bespoke shop with a semiotic approach. The analysis, based on Roland Barthes’ philosophy, leads to results which indicate remarkable implications for luxury brand management as well as to the suggestion to apply linguistic approaches more often for future research in luxury fashion, brand management, and marketing semiotics.

      • ONCE UPON A TIME THERE WAS A FASHION BRAND–DRIVING LUXURY VALUE PERCEPTION AND CONSUMER BEHAVIOUR VIA STORYTELLING

        Janina Haase,Nadine Hennigs,Jan C. L. König,Klaus-Peter Wiedmann 글로벌지식마케팅경영학회 2015 Global Fashion Management Conference Vol.2015 No.06

        Storytelling has become increasingly of interest for marketing and management in the last years and promises both aesthetic design and effecting consumers’ perception of fashion brands positively. Nevertheless, the complexity of story design, still being rather focussed by the humanities, and its effective adaption for luxury fashion brands regarding value perception and related behavioural consequences are still poorly understood and have not been explored so far. We seek to fill this research gap. In our study, we chose a luxury brand’s existing story and applied story concepts of narratology to rearrange plot, characters, and style first. In a second step, we examined the effect of applying the story concepts by testing the perception of three different groups (no story, original story, and rearranged story). Using PLS path modelling, we proved our hypotheses empirically. Our examination suggests that an application of narrative concepts for creating fashion brand stories has a measurable impact on consumer’s reception and behavioural outcome. On the one hand, this involves dimensions of luxury value, such as financial, functional, individual, and social consumer perceptions as well as an overall likability perception of the brand. On the other hand, this perception obviously impacts consumption habits regarding luxury fashion as much as it is related to recommendation behaviour, willingness to pay a premium price, and purchase intentions. Our findings strongly advice to consult established theories, concepts, and models of the humanities for storytelling in marketing and management. While measuring specific elements already proves their applicability, it will be a major task for theoretical and qualitative research to discuss existing material for the demands of marketing and management as well as (fashion) brands. Even for professionals in brand management, our study advices to have a closer look on traditional storytelling concepts to create effective campaigns. The particular value of our study is to present and empirically verify design elements of storytelling with respect to theoretical narrative approaches, which may have specific impact on certain luxury values and their causal effects on luxury fashion consumption. Our results reflect remarkable implications for luxury brand management as well as future research in luxury fashion, brand management, and marketing storytelling. A luxury company may stimulate purchase behaviour with a storytelling campaign. Nevertheless our study proved that a rather appropriate design, respecting research approaches of narratology, is able to increase the impact on consumers’ perception and behavioural outcome.

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