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Raybuck, Ariel L.,Cho, Sung Hoon,Li, Jingxin,Rogers, Meredith C.,Lee, Keunwook,Williams, Christopher L.,Shlomchik, Mark,Thomas, James W.,Chen, Jin,Williams, John V.,Boothby, Mark R. American Association of Immunologists 2018 Journal of Immunology Vol. No.
<P>B lymphocytes migrate among varied microenvironmental niches during diversification, selection, and conversion to memory or Ab-secreting plasma cells. Aspects of the nutrient milieu differ within these lymphoid microenvironments and can influence signaling molecules such as the mechanistic target of rapamycin (mTOR). However, much remains to be elucidated as to the B cell–intrinsic functions of nutrient-sensing signal transducers that modulate B cell differentiation or Ab affinity. We now show that the amino acid–sensing mTOR complex 1 (mTORC1) is vital for induction of Bcl6—a key transcriptional regulator of the germinal center (GC) fate—in activated B lymphocytes. Accordingly, disruption of mTORC1 after B cell development and activation led to reduced populations of Ag-specific memory B cells as well as plasma cells and GC B cells. In addition, induction of the germ line transcript that guides activation-induced deaminase in selection of the IgG1 H chain region during class switching required mTORC1. Expression of the somatic mutator activation-induced deaminase was reduced by a lack of mTORC1 in B cells, whereas point mutation frequencies in Ag-specific GC-phenotype B cells were only halved. These effects culminated in a B cell–intrinsic defect that impacted an antiviral Ab response and drastically impaired generation of high-affinity IgG1. Collectively, these data establish that mTORC1 governs critical B cell–intrinsic mechanisms essential for establishment of GC differentiation and effective Ab production.</P>
GLOBULAR AND OPEN CLUSTERS OBSERVED BY SDSS/SEGUE: THE GIANT STARS
Morrison, Heather L.,Ma, Zhibo,Clem, James L.,An, Deokkeun,Connor, Thomas,Schechtman-Rook, Andrew,Casagrande, Luca,Rockosi, Constance,Yanny, Brian,Harding, Paul,Beers, Timothy C.,Johnson, Jennifer A. American Astronomical Society 2016 The Astronomical journal Vol.151 No.1
<P>We present griz observations for the clusters M92, M13 and NGC 6791 and gr photometry for M71, Be 29 and NGC 7789. In addition we present new membership identifications for all these clusters, which have been observed spectroscopically as calibrators for the Sloan Digital Sky Survey (SDSS)/SEGUE survey; this paper focuses in particular on the red giant branch stars in the clusters. In a number of cases, these giants were too bright to be observed in the normal SDSS survey operations, and we describe the procedure used to obtain spectra for these stars. For M71, we also present a new variable reddening map and a new fiducial for the gr giant branch. For NGC 7789, we derived a transformation from T-eff to g-r for giants of near solar abundance, using IRFM T-eff measures of stars with good ugriz. and 2MASS photometry and SEGUE spectra. The result of our analysis is a robust list of known cluster members with correctly dereddened and (if needed) transformed gr photometry for crucial calibration efforts for SDSS and SEGUE.</P>
^1H-NMR studies on d(GCTTAAGC)_2 and its complex with berenil
HU, Sungho,WEISZ, Klaus,JAMES, Thomas L.,SHAFER, Richard H. 충남대학교 생물공학연구소 1993 생물공학연구지 Vol.3 No.-
Two-dimensional (2D) ^1H-NMR spectroscopy has been used analyze the structure of d(GCTTAAGC)_2 and its interaction with berenil in solution. Nuclear Overhauser enhancement connectivities enabled sequential assignments of nearly all proton resonances in the self-complementary octamer duplex and demonstrated that the oligonucleotide is primarily in a B-type conformation. No major conformational changes were observed by the addition of berenil, but proton resonances of the two adenosine nucleotides shifted substantially. Intermolecular nuclear Overhauser effects between berenil and the DNA duplex revealed that the drug binds via the minor groove of d(GCTTAAGC)_2 in the A.T-base-pair region. At 18℃ the twofold symmetry of the duplex is preserved on berenil binding .However, strongly shifted proton resonances broadened significantly. A model is proposed for the berenil-d(GCTTAAGC)_2 complex involving fast exchange of berenil between two equivalent symmetry-related binding sites, which span the 5'-TAA-3' region and are asymmetrically disposed with respect to the dyad axis of the duplex. These results are compared with previous studies on the berenil-d(GCAATTGC)_2 complex.
Structure-property relationships for a series of amorphous partially aliphatic polyimides
Eichstadt, Amy E.,Ward, Thomas C.,Bagwell, Melanie D.,Farr, Isaac V.,Dunson, Debra L.,McGrath, James E. Wiley Subscription Services, Inc., A Wiley Company 2002 Journal of polymer science. Part B, Polymer physic Vol.40 No.14
<P>High molecular weight, soluble, amorphous, partially aliphatic polyimides were successfully synthesized using an ester acid high-temperature solution imidization route, which allows one to control desired glass-transition (T<SUB>g</SUB>) and processing temperatures. This method involves the prereaction of aromatic dianhydrides with ethanol and a tertiary amine catalyst to form ester acids, followed by the addition of diamines. Subsequent thermal reaction forms fully cyclized polyimides. This reaction pathway eliminates the need for anhydrous solvents and overcomes the problem of salt formation commonly observed for nucleophilic, more-basic aliphatic amines when utilizing the traditional polyamic acid synthesis route. The molar ratio of aromatic-to-aliphatic diamines was varied to generate a series of copolyimides with the chosen dianhydride and tailor the physical properties for specific adhesive applications. This series of copolyimides was characterized by their molecular weight, T<SUB>g</SUB>, thermal stability, coefficient of thermal expansion, refractive index, and dielectric constant. Structure-property relationships were established. The γ and β sub-T<SUB>g</SUB> viscoelastic properties were researched to understand their molecular origins. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1503–1512, 2002</P>
Regional Structure of the Indian Summer Monsoon in Observations, Reanalysis, and Simulation
Cash, Benjamin A.,Kinter III, James L.,Adams, Jennifer,Altshuler, Eric,Huang, Bohua,Jin, Emilia K.,Manganello, Julia,Marx, Larry,Jung, Thomas American Meteorological Society 2015 Journal of climate Vol.28 No.5
Jacob, Chaim O,Zhu, Jiankun,Armstrong, Don L,Yan, Mei,Han, Jie,Zhou, Xin J,Thomas, James A,Reiff, Andreas,Myones, Barry L,Ojwang, Joshua O,Kaufman, Kenneth M,Klein-Gitelman, Marisa,McCurdy, Deborah,Wa National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.15
<P>A combined forward and reverse genetic approach was undertaken to test the candidacy of IRAK1 (interleukin-1 receptor associated kinase-1) as an X chromosome-encoded risk factor for systemic lupus erythematosus (SLE). In studying approximately 5,000 subjects and healthy controls, 5 SNPs spanning the IRAK1 gene showed disease association (P values reaching 10(-10), odds ratio >1.5) in both adult- and childhood-onset SLE, in 4 different ethnic groups, with a 4 SNP haplotype (GGGG) being strongly associated with the disease. The functional role of IRAK1 was next examined by using congenic mouse models bearing the disease loci: Sle1 or Sle3. IRAK1 deficiency abrogated all lupus-associated phenotypes, including IgM and IgG autoantibodies, lymphocytic activation, and renal disease in both models. In addition, the absence of IRAK1 reversed the dendritic cell 'hyperactivity' associated with Sle3. Collectively, the forward genetic studies in human SLE and the mechanistic studies in mouse models establish IRAK1 as a disease gene in lupus, capable of modulating at least 2 key checkpoints in disease development. This demonstration of an X chromosome gene as a disease susceptibility factor in human SLE raises the possibility that the gender difference in SLE may in part be attributed to sex chromosome genes.</P>
A new approach to deal with sensor errors in structural controls with MR damper
Han Wang,Luyu Li,Gangbing Song,James B. Dabney,Thomas L. Harman 국제구조공학회 2015 Smart Structures and Systems, An International Jou Vol.16 No.2
As commonly known, sensor errors and faulty signals may potentially lead structures in vibration to catastrophic failures. This paper presents a new approach to deal with sensor errors/faults in vibration control of structures by using the Fault detection and isolation (FDI) technique. To demonstrate the effectiveness of the approach, a space truss structure with semi-active devices such as Magneto-Rheological (MR) damper is used as an example. To address the problem, a Linear Matrix Inequality (LMI) based fixed-order H∞ FDI filter is introduced and designed. Modeling errors are treated as uncertainties in the FDI filter design to verify the robustness of the proposed FDI filter. Furthermore, an innovative Fuzzy Fault Tolerant Controller (FFTC) has been developed for this space truss structure model to preserve the pre-specified performance in the presence of sensor errors or faults. Simulation results have demonstrated that the proposed FDI filter is capable of detecting and isolating sensor errors/faults and actuator faults e.g., accelerometers and MR dampers, and the proposed FFTC can maintain the structural vibration suppression in faulty conditions.
Liu, Kai-Hsi,Lin, Hung-Yin,Thomas, James L.,Shih, Yuan-Pin,Yang, Zhuan-Yi,Chen, Jen-Tsung,Lee, Mei-Hwa The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.5
Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb<sub>1</sub> from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb<sub>1</sub> from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl<sub>2</sub> to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.
Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting
Costa, Francesco,Van Klaveren, David,Feres, Fausto,James, Stefan,Rä,ber, Lorenz,Pilgrim, Thomas,Hong, Myeong-Ki,Kim, Hyo-Soo,Colombo, Antonio,Steg, Philippe Gabriel,Bhatt, Deepak L.,Stone, Gregg W Elsevier Inc. 2019 Journal of the American College of Cardiology Vol.73 No.7
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized.</P> <P><B>Objectives</B></P> <P>This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.</P> <P><B>Methods</B></P> <P>Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.</P> <P><B>Results</B></P> <P>Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.</P> <P><B>Conclusions</B></P> <P>Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.</P> <P><B>Central Illustration</B></P> <P>[DISPLAY OMISSION]</P>