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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.
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>
Special Education Assessment in the United States : Issues in law and Policy
Mitchell L. Yell 국립특수교육원 2009 특수교육대상학생의 학업성취도 평가에 관한 국제적 동향 Vol. No.
학생의 사정은 최소 3개의 이유에서 특수교육에서 가장 중요한 단계일 수 있다. 첫째, 학생의 부모를 포함하여 사정에 대해 지식을 가지고 있는 인원으로 이루어진 팀이 한 학생에 대해 특수교육에 대한 적격성을 가지고 있다고 결정하지 않는다면, 그 학생은 특수교육 프로그램에 배치될 수 없다. 둘째, 특수교육 프로그램의 모든 측면(학업성취와 기능적 수행능력에 대한 현재 수준, 목표, 특수교육 서비스 등)은 학생의 사정 자료에 기초한다. 만약 사정 자료가 완벽하지 않거나 혹은 부정확하다면, IEP의 나머지 역시 쓸모없게 된다. 세 번째로 IDEIA는 학생이 학습하고 있는지를 결정하기 위하여 특수교육 프로그램 내에서 학생의 진전도를 지속적으로 사정하도록 요구하고 있다. 사정은 단순히 적격성을 결정하기 위해 의례적으로 따라야 하는 것이 아니다; 이보다는 의미있고 측정가능하도록 의도된 특수교육 프로그램을 개발하기 위함이다. IEP의 일차적인 목적은 (a) 학생의 독특한 교육적 요구에 기초한 개별화된 특수교육 프로그램을 개발하고, (b) 프로그램을 실시하고, (c) 그 프로그램이 제대로 작동하는지 혹은 그렇지 않다면 수정해야 하는지 알아보기 위함이다. 사실 무상의 적절한 공교육을 평가하는데 가장 중대한 결정 요인은 학생의 진전도이다. 따라서 사정절차는 각 학생의 FAPE를 위한 기초가 된다. 특수교육 관련자가 IDEA에 따른 그들의 사정 관련 의무를 이해하고, 최선을 다해 이러한 책임을 순행하려고 노력하는 것은 매우 중요하다. The assessment of a student is perhaps the most crucial step in the special education process for at least three reasons. First, a student cannot be placed in a special, education program unless a team of knowledgeable persons, including a student‘s parents, determine that he or she meets the eligibility criteria. Second, every aspect of a student’s special education program (e.g., present levels of academic achievement and functional performance, goals, special education services) is based on his or her assessment data. If the assessment data are not complete or are inappropriate, the rest of the IEP will be flawed. Third, the IDEIA requires continuous assessment of a student‘s progress in his or her special education program to determine if the student is learning. The assessment process is not just about following procedures to determine eligibility; rather it is about developing special education programs that lead to meaningful and measurable educational progress. The primary purpose of the IEP process is to (a) develop an individualized special education program based on a student‘s unique educational needs, (b) implement the program, and (c) see if it works and change it if it is not working. Indeed, it is a student’s progress that is the critical determinant of a free appropriate public education. The assessment process, therefore, is the basis of each student‘s FAPE. It is crucial that special education personnel understand their assessment duties under the IDEA and discharge these responsibilities to the best of their abilities.
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, W. J. 신라대학교 예술연구소 2002 예술연구 Vol.8 No.-
미술사의 주요한 임무가 시각 이미지에 관한 연구라고 한다면 말과 이미지의 문제는 시각적 재현과 언어와의 관계에 관심의 초점을 맞추고 있다고 할 수 있다. 좀 더 폭넓게 말하자면 말과 이미지는 문학사, 텍스트 연구, 언어학 그리고 주로 언어로 된 표현을 다루는 그 외의 학문 분야와 미술사와의 관계를 의미한다. 좀 더 일반적으로 말하자면 말과 이미지는 재현, 제시 presentation, 상징에 대한 인간 경험을 기본적으로 나누어 명명할 때 붙일 수 있는 일종의 간단한 명칭이다.