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      • SCIESCOPUSKCI등재
      • SCIESCOPUSKCI등재
      • HBV : No Detectable Tenofovir Resistance with Tenofovir Disoproxil Fumarate (TDF) or Emtricitabine+TDF (FTC/TDF) through 96 Weeks in Lamivudine Resistance CHB Patients

        ( Edward Gane ),( Amoreena C Corsa ),( Yang Liu ),( Ben C Mitchell2 ),( John F Flaherty ),( Michael D Miller ),( Kathryn M Kitrinos ),( Scott Fung ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

        Background/Aim: To evaluate amino acid changes within HBV pol/RT after 96 weeks of treatment with TDF or FTC/ TDF and determine their potential association with TDF resistance. Methods: In Study GS-US-174-0121, 280 patients receiving lamivudine (LAM) with detectable LAM-resistance mutations in HBV pol/RT (LAM-R: rtM204V/I±rtL180M) were randomized 1:1 to receive blinded treatment with TDF or FTC/TDF for 96 weeks. Virologic breakthrough (VB) was defined as confirmed HBV DNA >1 log10 increase from nadir or HBV DNA ≥400 copies/mL (69 IU/mL) after <400 copies/mL. Resistance genotyping by HBV pol/RT sequencing was attempted for all patients at baseline and if viremic (HBV DNA ≥400 copies/ mL) at Week 96/study discontinuation. Results: Overall, 18 patients (9 TDF, 9 FTC/TDF) were viremic viremic at Week 96/last visit. The mean baseline HBV DNA was significantly higher for viremic patients (8.04 log10 copies/mL) compared to patients who did not qualify for genotyping (6.39 log10 copies/mL). In the TDF arm, 3 patients had conserved site changes/reversions (1 with VB), 1 had unique polymorphic site changes, 2 had no change, and 3 were unable to be genotyped. In the FTC/TDF arm, 2 patients had conserved site changes/reversions, 1 had unique polymorphic site changes, 4 had no change, and 2 were unable to be genotyped. No phenotypic resistance to TDF was observed. Four of eight (50%) patients had LAM-R reversions (rtV/I204M±rtM180L) on TDF while 1/8 (12.5%) patients on FTC/TDF had LAM-R reversions. Thirteen patients (4.6%) with prior entecavir (ETV) exposure and 25 patients (8.9%) with baseline ETV-R were enrolled; neither had an impact on viral kinetics. Conclusions: No TDF resistance has been detected through 96 weeks of treatment with either TDF or FTC/TDF in LAM-R patients. The presence of ETV-R or ETV exposure did not impact viral kinetics through 96 weeks. Resistance surveillance in this population will continue through Year 5.

      • KCI등재

        Are the Distribution of Einstein Crossing Times of Galactic Microlensing Events Bimodal?

        Mitchell F. Struble,Thulsi Wickramasinghe 한국우주과학회 2012 Journal of Astronomy and Space Sciences Vol.29 No.2

        The observed distribution of a blending-corrected sample of Einstein ring crossing times, tE, for microlensing events toward the galactic bulge/bar are analyzed. An inspection of the distribution of crossing times suggests that it may be bimodal, indicating that two populations of lenses could be responsible for observed microlensing events. Given the possibility that microlensing in this direction can be due to the two most common classes of stars, main-sequence and white dwarf, we analyze and show via Monte Carlo simulations that the observed bimodality of tE can be derived from their accepted mass functions, and the density distributions of both stellar populations in the galactic disk and bulge/bar, with a transverse velocity distribution that is consistent with the density distribution. Kolmogorov-Smirnov (KS) one sample tests shows that a white dwarf population of about 25% of all stars in the galaxy agrees well with the observed bimodality with a KS significance level greater than 97%. This is an expanded and updated version of a previous investigation (Wickramasinghe, Neusima, & Struble, in Mao 2008). A power-point version of the talk, with introductory figures, is found at: https://sites.google.com/site/rhkochconference/agenda-1/program.

      • KCI등재

        The Domestic Origins of the Second Korean War: New Evidence from Communist Bloc Archives

        ( Mitchell Lerner ) 서울대학교 규장각한국학연구원 2018 Seoul journal of Korean studies Vol.31 No.1

        In the late 1960s, the Korean Peninsula suddenly exploded with a violence not seen since the end of the Korean War, driven by a sudden wave of North Korea aggression that culminated in January 1968 with the attempted assassination of Park Chung Hee and the capture of the USS Pueblo. For decades, scholars have struggled to understand this crisis, as they lacked access to materials that could open a window into DPRK policy. Only now, with the recent release of new materials collected from the archives of the Communist bloc nations, can we begin to understand the critical events of the Second Korean War and the larger environment that surrounded it. This paper integrates the most recent materials from former Communist bloc states to revisit our understanding of this dangerous situation, and to suggest that it was driven above all else by domestic political and economic circumstances inside North Korea.

      • SCISCIESCOPUS

        Src family kinase tyrosine phosphorylates Toll-like receptor 4 to dissociate MyD88 and Mal/Tirap, suppressing LPS-induced inflammatory responses

        Mitchell, Jonathon,Kim, Su Jin,Seelmann, Alexandra,Veit, Brendan,Shepard, Brooke,Im, Eunok,Rhee, Sang Hoon Elsevier 2018 Biochemical pharmacology Vol.147 No.-

        <P><B>Abstract</B></P> <P>Src family kinases (SFKs) are a family of protein tyrosine kinases containing nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK activation is a major immediate signaling event in LPS/Toll-like receptor 4 (TLR4) signaling, its precise role has remained elusive due to various contradictory results obtained from a certain SFK member-deficient mice or cells. The observed inconsistencies may be due to the compensation or redundancy by other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to induce temporal and precise SFK activation in living cells, thereby limiting the chance of cellular adaption to a SFK-deficient condition.</P> <P>Using the rescuing approach, we demonstrate that restoring SFK activity not only induces tyrosine phosphorylation of TLR4, but also inhibits LPS-induced NFκB and JNK1/2 activation and consequently suppresses LPS-induced cytokine production. TLR4 normally recruits TIR domain-containing adaptors in response to LPS, however, temporally restored SFK activation disrupts the LPS-induced association of MyD88 and Mal/Tirap with TLR4. Additionally, using kinase-dead SFK-Lyn (Y397/508F) and constitutively active SFK-Lyn (Y508F), we found that the kinase-dead SFK inhibits TLR4 tyrosine phosphorylation with reduced binding affinity to TLR4, while the kinase-active SFK strongly binds to TLR4 and promotes TLR4 tyrosine phosphorylation, suggesting that SFK kinase activity is required for TLR4 tyrosine phosphorylation and TLR4-SFK interaction.</P> <P>Together, our results demonstrate that SFK activation induces TLR4 tyrosine phosphorylation, consequently dissociating MyD88 and Mal/Tirap from TLR4 and inhibiting LPS-induced inflammatory responses, suggesting a negative feedback loop regulated by SFK-induced tyrosine phosphorylation in TLR4.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SSCISCOPUSKCI등재

        Drifting apart? The U,S, -ROK alliance at risk

        ( Mitchell B Reiss ) 한국국방연구원 2009 The Korean Journal of Defense Analysis Vol.21 No.1

        Given the success of the U.S.-ROK alliance over the past five and half decades, it is far easier to envision that it will remain undisturbed than to imagine major change, let alone the end of the alliance. Yet past history is no guarantee of future success. Major shifts in American foreign policy, new transnational challenges and a changing political, economic, and security environment in Northeast Asia, call into question whether the alliance will last another 10 years, let alone another half century. By the start of the twenty-first century, the United States had increasingly conceptualized the alliance in regional or even global terms, whereas the ROK military, despite some impressive blue-water naval assets, was still wedded to the mission of peninsular defense. Ideally, the United States would like the ROK to join with U.S. forces in addressing regional and global contingencies, in addition to fulfilling its primary missions to deter and, if necessary, defeat North Korea. Yet America`s reorientation of its forces on the Korean peninsula and the ROK`s military transformation were driven more by domestic political concerns than by jointly shared security imperatives. As a result, larger questions about the future of the alliance went begging. With both partners transitioning to new force structures, these measures portended an alliance that was drifting apart, not a maturing alliance that was becoming a more equal and cohesive partnership. Questions remain unanswered, or even unasked, about whether the two partners agree on the strategic environment in the region and the respective roles both should play. Although there have been discussions on the ````future of the alliance,```` these have focused on U.S. base realignment and other details, not on the future security environment in the region and its larger strategic implications. It is these offshore missions, not North Korea, where threat assessments will likely diverge and where alliance disagreements will arise in the future. In short, the two parties have yet to confront the full implications of the military and defense decisions of the past few years, often undertaken unilaterally and attuned more to domestic audiences than to strategic realities. The ability to paper over a lack of common purpose and shared vision may be useful as a temporary placeholder, but it will not provide an adequate foundation for the future viability of the alliance. The good news is that consensus exists in both countries that the alliance needs to be preserved; the bad news is that charting the way ahead is neither easy nor obvious. The risk is that without the development of a clear and common vision of a shared future with defined and mutually agreed-upon roles, the United States and South Korea will gradually drift apart, along with a partnership that has proved so successful over the past half century.

      • Strain analysis of protein structures and low dimensionality of mechanical allosteric couplings

        Mitchell, Michael R.,Tlusty, Tsvi,Leibler, Stanislas National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.40

        <P>In many proteins, especially allosteric proteins that communicate regulatory states from allosteric to active sites, structural deformations are functionally important. To understand these deformations, dynamical experiments are ideal but challenging. Using static structural information, although more limited than dynamical analysis, is much more accessible. Underused for protein analysis, strain is the natural quantity for studying local deformations. We calculate strain tensor fields for proteins deformed by ligands or thermal fluctuations using crystal and NMR structure ensembles. Strains-primarily shears-show deformations around binding sites. These deformations can be induced solely by ligand binding at distant allosteric sites. Shears reveal quasi-2D paths of mechanical coupling between allosteric and active sites that may constitute a widespread mechanism of allostery. We argue that strain-particularly shear-is the most appropriate quantity for analysis of local protein deformations. This analysis can reveal mechanical and biological properties of many proteins.</P>

      • KCI등재

        Dynamic Pose Tracking Accuracy Improvement via Fusing HTC Vive Trackers and Inertia Measurement Units

        Mitchell Weber,Roman Hartl,Michael F. Zäh,Jihyun Lee 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.24 No.9

        Virtual reality tracking devices are being investigated for application to motion tracking of robots, human bodies, indoor drones, mobile systems, etc., but most studies so far have been limited to performance analysis of commercialized tracking devices in static conditions. This paper investigated methods for improving the measurement accuracy of dynamic positioning and orientation of the HTC tracker. The signals from the photodiodes in the tracker were extracted and fused together, as well as with external Inertial Measurement Units (IMUs) signals using the Extended Kalman Filter (EKF) and the Unscented Kalman Filter (UKF). Multiple base stations, trackers and IMUs were applied to evaluate the measurement accuracy. Multiple paths were used to test different dynamic operating conditions. The results show that the proposed tracking system can improve accuracy by up to several mm by using the UKF as opposed to the EKF algorithm, increasing the number of base stations, increasing the number of trackers and fusing IMUs.

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