Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility

Zhao, Jian,Wu, Hui,Khosravi, Melanie,Cui, Huijuan,Qian, Xiaoxia,Kelly, Jennifer A.,Kaufman, Kenneth M.,Langefeld, Carl D.,Williams, Adrienne H.,Comeau, Mary E.,Ziegler, Julie T.,Marion, Miranda C.,Adl Public Library of Science 2011 PLoS genetics Vol.7 No.5

<▼1><P>Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the <I>CFH</I>-<I>CFHRs</I> region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic <I>CFH</I> SNP (rs6677604, in intron 11, <I>P</I><SUB>meta</SUB> = 6.6×10<SUP>−8</SUP>, OR = 1.18) and an intergenic SNP between <I>CFHR1</I> and <I>CFHR4</I> (rs16840639, <I>P</I><SUB>meta</SUB> = 2.9×10<SUP>−7</SUP>, OR = 1.17) rather than to previously identified disease-associated <I>CFH</I> exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ∼146 kb block extending from intron 9 of <I>CFH</I> to downstream of <I>CFHR1</I>. Within this block, the deletion of <I>CFHR3</I> and <I>CFHR1</I> (<I>CFHR3-1</I>Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of <I>CFHR3-1</I>Δ (<I>P</I><SUB>meta</SUB> = 3.2×10<SUP>−7</SUP>, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (<I>P</I><SUB>meta</SUB> = 3.5×10<SUP>−4</SUP>, OR = 1.14). These results suggested that the <I>CFHR3-1</I>Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of <I>CFH</I>, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.</P></▼1><▼2><P><B>Author Summary</B></P><P>Systemic lupus erythematosus (SLE) is a complex autoimmune disease, associated with increased complement activation. Previous studies have provided evidence for the presence of SLE susceptibility gene(s) in the chromosome 1q31-32 locus. Within 1q32, genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) may contribute to the development of SLE, because genetic variants of these genes impair complement regulation and predispose to various human diseases. In this study, we tested association of genetic variants in the region containing <I>CFH</I> and <I>CFHRs</I> with SLE. We identified genetic variants predisposing to SLE in European American, African American, and Asian populations, which might be attributed to the deletion of <I>CFHR3</I> and <I>CFHR1</I> genes but not previously identified disease-associated exonic variants of <I>CFH</I>. This study provides the first evidence for consistent association between <I>CFH/CFHRs</I> and SLE across multi-ancestral SLE datasets, providing new insights into the role of complement regulators in the pathogenesis of SLE.</P></▼2>

Emergence and Persistence of NS5A and NS3 Resistance-Associated Substitutions in HCV Genotype 1b Patients Treated with Daclatasvir and Asunaprevir

( F. Mcphee ),( D. Hernandez ),( N. Zhou ),( F. Yu ),( B. Kienzle ),( Y. Zhao ),( M. Linaberry ),( S. Noviello ),( M. L. Yu ),( S. H. Ahn ),( Y. Karino ),( K. Chayama ),( H. Kumada ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: A pooled analysis of emergent RAS was performed in HCV genotype (GT-)1b-infected patients receiving daclatasvir and asunaprevir (DCV+ASV) and the persistence of DCV- and ASV-resistant substitutions through ≥post-treatment Week (PTWK)192 was assessed to understand the RAS profile and help guide potential retreatment options. Methods: HCV GT-1b-infected patients without a sustained virologic response (SVR) and with HCV RNA ≥1000 IU/mL on or after DCV+ASV treatment were included from 5 Phase 2 and 3 studies. Baseline and post-baseline plasma samples were sequenced at a sensitivity cut-off ł20%. To determine the persistence of emergent RAS, samples at the end of study (up to PTWK48) and/or from a 3-year long-term follow-up rollover study were sequenced (sensitivity cut-off ≥20%, and ≥1% for select samples). Results: 152 DCV+ASV-treated patients without SVR met the resistance testing criteria: 89% (136/152) had NS5A and 95% (145/152) had NS3 sequences at both baseline and virologic failure (VF). NS5A and NS3 RAS emerged in 99% (134/136) and 89% (129/145), respectively, at VF (Table). Overall, 93% (142/152) of patients with VF had both NS5A and NS3 sequence data at failure, of which 77% (109/142) had RAS at L31, Y93 and D168. Emergent NS5A RAS persisted at PTWK96 (92%;24/26) and ≥PTWK192 (100;7/7compared with 22% (6/27) and 14% (1/7), respectively, for emergent NS3 RAS. Replacement of emergent NS5A and NS3 RAS observed at VF occurred in 8% (2/26) of NS5A and 74% (17/23) of NS3 sequences at PTWK96 and in 0% (0/7) of NS5A and 86% (6/7) of NS3 sequences at ≥PTWK192. Conclusions: NS5A and NS3 RAS emerged in most patients treated with DCV+ASV who experienced VF, and NS5A RAS persisted post-treatment. Therapy options for DCV+ASV treatment failures may depend on the timing of retreatment: an NS3 inhibitor-containing regimen may be possible if NS3 RAS are no longer observed, while regimens not impacted by the NS5A-L31+Y93 and NS3-D168 RAS combination would offer an immediate alternative.

Separation dynamics of hydrogen isotope gas in mesoporous and microporous adsorbent beds at 77 K: SBA-15 and zeolites 5A, Y, 10X

Chu, X.Z.,Cheng, Z.P.,Xiang, X.X.,Xu, J.M.,Zhao, Y.J.,Zhang, W.G.,Lv, J.S.,Zhou, Y.P.,Zhou, L.,Moon, D.K.,Lee, C.H. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.9

The separation of a hydrogen isotope mixture on porous materials was studied using equilibrium and breakthrough experiments. The adsorption equilibria of H<SUB>2</SUB> and D<SUB>2</SUB> on SBA-15 with mesopores and molecular sieves 5A, Y, and 10X with micropores were measured at 77 K using the volumetric method. The breakthrough experiments of a H<SUB>2</SUB> and D<SUB>2</SUB> mixture in each adsorbent bed were carried out at various conditions of flow rate and pressure. The equilibrium ratio of D<SUB>2</SUB> to H<SUB>2</SUB> on mesoporous molecular sieves was larger than the ratio on microporous molecular sieves (SBA-15 > 10X > Y > 5A), but the difference among the adsorbents decreased with increases in pressure. On the other hand, the order of breakthrough separation factor showed the opposite result (SBA-15 < 10X < Y < 5A). The breakthrough separation factors for zeolite 10X was approximately equal to the equilibrium ratio of D<SUB>2</SUB> to H<SUB>2</SUB> at the corresponding partial pressures, whereas zeolites 5A and Y showed higher breakthrough separation factors than their equilibrium ratios. In SBA-15, the separation factors from breakthrough results were even smaller than the corresponding equilibrium ratio. In the microporous adsorbent with a limited pore size (zeolite 5A in the study), the diffusion mechanism contributed to the separation of hydrogen isotope gases as one of key factors.

Low-Power Clock Tree Design for Pre-Bond Testing of 3-D Stacked ICs

Xin Zhao,Lewis, D L,Lee, Hsien-Hsin S,Sung Kyu Lim IEEE 2011 IEEE transactions on computer-aided design of inte Vol.30 No.5

<P>Pre-bond testing of 3-D stacked integrated circuits (ICs) involves testing each individual die before bonding. The overall yield of 3-D ICs improves with pre-bond testability because manufacturers can avoid stacking defective dies with good ones. However, pre-bond testability presents unique challenges to 3-D clock tree design. First, each die needs a complete 2-D clock tree to enable pre-bond test. Second, the entire 3-D stack needs a complete 3-D clock tree for post-bond test and operation. In the case of a two-die stack, a straightforward solution is to have two complete 2-D clock trees connected with a single through-silicon-via (TSV). We show that this solution suffers from long wirelength (WL) and high clock power consumption. Our algorithm improves on this solution, minimizes the overall WL and clock power consumption, and provides both pre-bond testability and post-bond operability with minimum skew and constrained slew. Compared with the single-TSV solution, SPICE simulation results show that our multi-TSV approach significantly reduces the clock power by up to 15.9% for two-die and 29.7% for four-die stacks. In addition, the WL is reduced by up to 24.4% and 42.0%.</P>

Hyperelasticity of three-dimensional carbon nanotube sponge controlled by the stiffness of covalent junctions

Zhao, W.,Shan, C.,Elias, A.L.,Rajukumar, L.P.,O'Brien, D.J.,Terrones, M.,Wei, B.,Suhr, J.,Lu, X.L. Pergamon Press ; Elsevier Science Ltd 2015 Carbon Vol.95 No.-

To expand the applications of carbon nanotubes (CNTs) at macroscale, a heteroatom doping technique has been employed to fabricate isotropic 3-D CNT architectures by inducing elbow-like covalent junctions into multiwalled CNTs. As the junctions modify the topology of each CNT by favoring the stable bends in CNTs, junction stiffness and the consequence of junction-related morphology changes in sponge's hyperelasticity remain largely elusive. In this study, two types of 3-D multiwalled CNT sponges were fabricated by inducing boron-doped or nitrogen-doped covalent junctions into CNTs. Hyperelastic properties of the sponges were experimentally quantified as the functions of CNT morphology. A novel microstructure informed continuum constitutive law was developed specifically for such isotropic CNT sponges with junctions. Analyzing the experimental data with the new theory demonstrated that, for the first time, the effective modulus of boron-doped junctions (~100 GPa) is higher than that of nitrogen-doped junctions (~20 GPa), and the junction stiffness is a key factor in regulating the hyperelastic compressive modulus of the material. Theoretical analysis further revealed that increased number of junctions and shorter segments on each individual CNT chain would result in stronger hyperelastic 3-D CNT networks. This study has established a fundamental knowledge base to provide guidance for the future design and fabrication of 3-D CNT macrostructures.

Complete genome sequence of rice virus A, a new member of the family Tombusviridae

Zhao, F.,Baek, D.,Igori, D.,Bae, J. Y.,Kim, S. M.,Ra, J. E.,Park, K.,Lee, B. C.,Moon, J. S. Springer Science + Business Media 2017 Archives of virology Vol.162 No.10

Full-Color Mesophase Silicate Thin Film Phosphors Incorporated with Rare Earth Ions and Photosensitizers

Zhao, D.,Seo, S.-J.,Bae, B.-S. WILEY-VCH Verlag 2007 Advanced Materials Vol.19 No.21

<B>Graphic Abstract</B> <P>Full-color mesophase silicate thin film phosphors incorporated with rare earth ions and photosensitizers exhibit multicolor photoluminescence that covere the whole visible range under UV excitation. The multiple colors can be finely tuned by varying the relative concentrations of the RE trivalent ions and photosensitizers. The mesophase silica thin films have promising applications in display field. <img src='wiley_img/09359648-2007-19-21-ADMA200602562-content.gif' alt='wiley_img/09359648-2007-19-21-ADMA200602562-content'> </P>

A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury

Zhao, Bixiao,Lu, Qiongshi,Cheng, Yuwei,Belcher, Justin M.,Siew, Edward D.,Leaf, David E.,Body, Simon C.,Fox, Amanda A.,Waikar, Sushrut S.,Collard, Charles D. American Thoracic Society 2017 American journal of respiratory and critical care Vol.195 No.4

A 30-V transmitter front-end IC for ultrasound medical imaging applications

Zhao, D.,Cha, H.K. Elsevier 2013 Microelectronics journal Vol.44 No.3

A transmitter front-end IC for ultrasound medical imaging applications is implemented using 30-V 0.18-μm Bipolar/CMOS/DMOS process. The proposed ultrasound transmitter front-end, consisting of voltage level-shifters and an output driver, achieves high integration and maintains good reliability while generating a 33ns output pulse signal in order to drive a large capacitive load, which represents the equivalent capacitance of the capacitive micromachined ultrasound transducer device. The proposed high-frequency transmitter achieves a delay of less than 20ns at 30 Vp-p output voltage while successfully driving a capacitive load of 44 pF and consumes an area of 0.34mm<SUP>2</SUP>.

A Durable Alternative for Proton-Exchange Membranes: Sulfonated Poly(Benzoxazole Thioether Sulfone)s

Zhao, D.,Li, J.,Song, M. K.,Yi, B.,Zhang, H.,Liu, M. Wiley 2011 Advanced energy materials Vol.1 No.2