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( 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.
Bilateral venous sinuses of Kelch
Mitchell Couldwell,Aimee Aysenne,Joe Iwanaga,Aaron S,Dumont,R,Shane Tubbs 대한해부학회 2021 Anatomy & Cell Biology Vol.54 No.3
Knowledge of the variant anatomy of the intradural venous sinuses is important to anatomists and clinicians alike. Herein, we report a cadaveric case of the rare venous sinus of Kelch, which some have believed is a remnant of the cranioorbital sinuses. To our knowledge, only one other cadaveric case has been reported in the extant medical literature. Clinically, knowledge of such a variant venous sinus can minimize misdiagnoses such as when anatomical variations are noted on imaging. Surgically, such an understanding can avoid intraoperative complications such as iatrogenic hemorrhage.
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>
Mitchell, David L.,Adams-Deutsch, Tristan,Olson, Mark H. Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.1
We examined survival and DNA damage in rainbow trout larvae (Oncorhynchus mykiss) resulting from a range of sublethal to lethal ultraviolet-B exposures in the presence and absence of photoreactivating radiation. We found that after low, sublethal UV-B exposures trout larvae are quite proficient at photoenzymatic repair but that this capacity decreases exponentially with the total incident UV-B dose. The relationship between the dose dependence of PER and trout development and vulnerability in fisheries and in the natural environment are discussed.
DO SECTOR RETURNS LEAD THE STOCK MARKET? THE INTERNATIONAL EVIDENCE
Mitchell Ratner,Ilhan Meric,Gulser Meric People&Global Business Association 2006 Global Business and Finance Review Vol.11 No.2
This paper investigates the lead/lag relationship between the returns of a country's stock market index and 10 primary sector index returns. The sample consists of the Group of Seven (G-7) industrialized countries from January 1974 through December 2003. This study documents a statistically significant lead/lag relationship between sector returns and the stock market index returns in all seven countries. No sector is consistently significant across countries. The results of this study support the gradual information diffusion hypothesis: information travels slowly between asset classes.
CORIUM COOLABILITY UNDER EX-VESSEL ACCIDENT CONDITIONS FOR LWRs
MITCHELL T. FARMER,DENNIS J. KILSDONK,ROBERT W. AESCHLIMANN 한국원자력학회 2009 Nuclear Engineering and Technology Vol.41 No.5
In the wake of the Three Mile Island accident, vigorous research efforts were initiated to acquire a basic knowledge of the progression and consequences of accidents that involve a substantial degree of core degradation and melting. The primary emphasis of this research was placed on containment integrity, with: i) hydrogen combustion-detonation, ii) steam explosion, iii) direct containment heating (DCH), and iv) melt attack on the BWR Mark-I containment shell identified as energetic processes that could lead to early containment failure (i.e., within the first 24 hours of the accident). Should the core melt fail the reactor vessel, then non-condensable gas production from Molten Core-Concrete Interaction (MCCI) was identified as a mechanism that could fail the containment by pressurization over the long term. One signification question that arose as part of this investigation was the effectiveness of water in terminating an MCCI by flooding the interacting masses from above, thereby quenching the molten core debris and rendering it permanently coolable. Successful quenching of the core melt would prevent basemat melt through, as well as continued containment pressurization by non-condensable gas production, and so the accident progression would be successfully terminated without release of radioactivity to the environment. Based on these potential merits, ex-vessel corium coolability has been the focus of extensive research over the last 20 years as a potential accident management strategy for current plants. In addition, outcomes from this research have impacted the accident management strategies for the Gen III+ LWR plant designs that are currently being deployed around the world. This paper provides: i) an historical overview of corium coolability research, ii) summarizes the current status of research in this area, and iii) highlights trends in severe accident management strategies that have evolved based on the findings from this work.