Dissociation of CAK from Core TFIIH Reveals a Functional Link between XP-G/CS and the TFIIH Disassembly State

Transcription factor II H (TFIIH) is comprised of core TFIIH and Cdk-activating kinase (CAK) complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER). While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b) CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation

Human genome meeting 2016 : Houston, TX, USA. 28 February - 2 March 2016

: O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth weight and subsequent postnatal outcomes: findings from GUSTO, an Asian birth cohort X. Lin, I. Y. Lim, Y. Wu, A. L. Teh, L. Chen, I. M. Aris, S. E. Soh, M. T. Tint, J. L. MacIsaac, F. Yap, K. Kwek, S. M. Saw, M. S. Kobor, M. J. Meaney, K. M. Godfrey, Y. S. Chong, J. D. Holbrook, Y. S. Lee, P. D. Gluckman, N. Karnani, GUSTO study group O4 High-throughput identification of specific qt interval modulating enhancers at the SCN5A locus A. Kapoor, D. Lee, A. Chakravarti O5 Identification of extracellular matrix components inducing cancer cell migration in the supernatant of cultivated mesenchymal stem cells C. Maercker, F. Graf, M. Boutros O6 Single cell allele specific expression (ASE) IN T21 and common trisomies: a novel approach to understand DOWN syndrome and other aneuploidies G. Stamoulis, F. Santoni, P. Makrythanasis, A. Letourneau, M. Guipponi, N. Panousis, M. Garieri, P. Ribaux, E. Falconnet, C. Borel, S. E. Antonarakis O7 Role of microRNA in LCL to IPSC reprogramming S. Kumar, J. Curran, J. Blangero O8 Multiple enhancer variants disrupt gene regulatory network in Hirschsprung disease S. Chatterjee, A. Kapoor, J. Akiyama, D. Auer, C. Berrios, L. Pennacchio, A. Chakravarti O9 Metabolomic profiling for the diagnosis of neurometabolic disorders T. R. Donti, G. Cappuccio, M. Miller, P. Atwal, A. Kennedy, A. Cardon, C. Bacino, L. Emrick, J. Hertecant, F. Baumer, B. Porter, M. Bainbridge, P. Bonnen, B. Graham, R. Sutton, Q. Sun, S. Elsea O10 A novel causal methylation network approach to Alzheimer’s disease Z. Hu, P. Wang, Y. Zhu, J. Zhao, M. Xiong, David A Bennett O11 A microRNA signature identifies subtypes of triple-negative breast cancer and reveals MIR-342-3P as regulator of a lactate metabolic pathway A. Hidalgo-Miranda, S. Romero-Cordoba, S. Rodriguez-Cuevas, R. Rebollar-Vega, E. Tagliabue, M. Iorio, E. D’Ippolito, S. Baroni O12 Transcriptome analysis identifies genes, enhancer RNAs and repetitive elements that are recurrently deregulated across multiple cancer types B. Kaczkowski, Y. Tanaka, H. Kawaji, A. Sandelin, R. Andersson, M. Itoh, T. Lassmann, the FANTOM5 consortium, Y. Hayashizaki, P. Carninci, A. R. R. Forrest O13 Elevated mutation and widespread loss of constraint at regulatory and architectural binding sites across 11 tumour types C. A. Semple O14 Exome sequencing provides evidence of pathogenicity for genes implicated in colorectal cancer E. A. Rosenthal, B. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, A. Burt, P. Robertson, P. Beyers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. Dorschner, D. Nickerson, J. Smith, K. Patterson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. Jarvik, NHLBI GO Exome Sequencing Project O15 The tandem duplicator phenotype as a distinct genomic configuration in cancer F. Menghi, K. Inaki, X. Woo, P. Kumar, K. Grzeda, A. Malhotra, H. Kim, D. Ucar, P. Shreckengast, K. Karuturi, J. Keck, J. Chuang, E. T. Liu O16 Modeling genetic interactions associated with molecular subtypes of breast cancer B. Ji, A. Tyler, G. Ananda, G. Carter O17 Recurrent somatic mutation in the MYC associated factor X in brain tumors H. Nikbakht, M. Montagne, M. Zeinieh, A. Harutyunyan, M. Mcconechy, N. Jabado, P. Lavigne, J. Majewski O18 Predictive biomarkers to metastatic pancreatic cancer treatment J. B. Goldstein, M. Overman, G. Varadhachary, R. Shroff, R. Wolff, M. Javle, A. Futreal, D. Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. Puech, B. Bakall, R. Silva-Garcia, K. Rohrschneider, M. Leys, F. S. Shaya, E. Stone O29 PhenoDB and genematcher, solving unsolved whole exome sequencing data N. L. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, D. Valle, A. Hamosh O30 Baylor-Johns Hopkins Center for Mendelian genomics: a four year review S. N. Jhangiani, Z. Coban Akdemir, M. N. Bainbridge, W. Charng, W. Wiszniewski, T. Gambin, E. Karaca, Y. Bayram, M. K. Eldomery, J. Posey, H. Doddapaneni, J. Hu, V. R. Sutton, D. M. Muzny, E. A. Boerwinkle, D. Valle, J. R. Lupski, R. A. Gibbs O31 Using read overlap assembly to accurately identify structural genetic differences in an ashkenazi jewish trio S. Shekar, W. Salerno, A. English, A. Mangubat, J. Bruestle O32 Legal interoperability: a sine qua non for international data sharing A. Thorogood, B. M. Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. Weinshilboum, R. Gibbs O38 Melanoma reprogramming state correlates with response to CTLA-4 blockade in metastatic melanoma T. Karpinets, T. Calderone, K. Wani, X. Yu, C. Creasy, C. Haymaker, M. Forget, V. Nanda, J. Roszik, J. Wargo, L. Haydu, X. Song, A. Lazar, J. Gershenwald, M. Davies, C. Bernatchez, J. Zhang, A. Futreal, S. Woodman O39 Data-driven refinement of complex disease classification from integration of heterogeneous functional genomics data in GeneWeaver E. J. Chesler, T. Reynolds, J. A. Bubier, C. Phillips, M. A. Langston, E. J. Baker O40 A general statistic framework for genome-based disease risk prediction M. Xiong, L. Ma, N. Lin, C. Amos O41 Integrative large-scale causal network analysis of imaging and genomic data and its application in schizophrenia studies N. Lin, P. Wang, Y. Zhu, J. Zhao, V. Calhoun, M. Xiong O42 Big data and NGS data analysis: the cloud to the rescue O. Dobretsberger, M. Egger, F. Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. Gibbs O56 A diploid personal human genome model for better genomes from diverse sequence data K. C. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, X. Qin, O. A. Hampton, P. Larsen, C. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, A. Yoder, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs O57 Development of PacBio long range capture for detection of pathogenic structural variants Q. Meng, M. Bainbridge, M. Wang, H. Doddapaneni, Y. Han, D. Muzny, R. Gibbs O58 Rhesus macaques exhibit more non-synonymous variation but greater impact of purifying selection than humans R. A. Harris, M. Raveenedran, C. Xue, M. Dahdouli, L. Cox, G. Fan, B. Ferguson, J. Hovarth, Z. Johnson, S. Kanthaswamy, M. Kubisch, M. Platt, D. Smith, E. Vallender, R. Wiseman, X. Liu, J. Below, D. Muzny, R. Gibbs, F. Yu, J. Rogers O59 Assessing RNA structure disruption induced by single-nucleotide variation J. Lin, Y. Zhang, Z. Ouyang P1 A meta-analysis of genome-wide association studies of mitochondrial dna copy number A. Moore, Z. Wang, J. Hofmann, M. Purdue, R. Stolzenberg-Solomon, S. Weinstein, D. Albanes, C.-S. Liu, W.-L. Cheng, T.-T. Lin, Q. Lan, N. Rothman, S. Berndt P2 Missense polymorphic genetic combinations underlying down syndrome susceptibility E. S. Chen P4 The evaluation of alteration of ELAM-1 expression in the endometriosis patients H. Bahrami, A. Khoshzaban, S. Heidari Keshal P5 Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population K. K. R. Alharbi P6 Genome-associated personalized antithrombotical therapy for patients with high risk of thrombosis and bleeding M. Zhalbinova, A. Akilzhanova, S. Rakhimova, M. Bekbosynova, S. Myrzakhmetova P7 Frequency of Xmn1 polymorphism among sickle cell carrier cases in UAE population M. Matar P8 Differentiating inflammatory bowel diseases by using genomic data: dimension of the problem and network organization N. Mili, R. Molinari, Y. Ma, S. Guerrier P9 Vulnerability of genetic variants to the risk of autism among Saudi children N. Elhawary, M. Tayeb, N. Bogari, N. Qotb P10 Chromatin profiles from ex vivo purified dopaminergic neurons establish a promising model to support studies of neurological function and dysfunction S. A. McClymont, P. W. Hook, L. A. Goff, A. McCallion P11 Utilization of a sensitized chemical mutagenesis screen to identify genetic modifiers of retinal dysplasia in homozygous Nr2e3rd7 mice Y. Kong, J. R. Charette, W. L. Hicks, J. K. Naggert, L. Zhao, P. M. Nishina P12 Ion torrent next generation sequencing of recessive polycystic kidney disease in Saudi patients B. M. Edrees, M. Athar, F. A. Al-Allaf, M. M. Taher, W. Khan, A. Bouazzaoui, N. A. Harbi, R. Safar, H. Al-Edressi, A. Anazi, N. Altayeb, M. A. Ahmed, K. Alansary, Z. Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. Zhang, A. Schuh, T. Stockley, S. Kamel-Reid P36 Accessing genomic evidence for clinical variants at NCBI S. Sherry, C. Xiao, D. Slotta, K. Rodarmer, M. Feolo, M. Kimelman, G. Godynskiy, C. O’Sullivan, E. Yaschenko P37 NGS-SWIFT: a cloud-based variant analysis framework using control-accessed sequencing data from DBGAP/SRA C. Xiao, E. Yaschenko, S. Sherry P38 Computational assessment of drug induced hepatotoxicity through gene expression profiling C. Rangel-Escareño, H. Rueda-Zarate P40 Flowr: robust and efficient pipelines using a simple language-agnostic approach;ultraseq; fast modular pipeline for somatic variation calling using flowr S. Seth, S. Amin, X. Song, X. Mao, H. Sun, R. G. Verhaak, A. Futreal, J. Zhang P41 Applying “Big data” technologies to the rapid analysis of heterogenous large cohort data S. J. Whiite, T. Chiang, A. English, J. Farek, Z. Kahn, W. Salerno, N. Veeraraghavan, E. Boerwinkle, R. Gibbs P42 FANTOM5 web resource for the large-scale genome-wide transcription start site activity profiles of wide-range of mammalian cells T. Kasukawa, M. Lizio, J. Harshbarger, S. Hisashi, J. Severin, A. Imad, S. Sahin, T. C. Freeman, K. Baillie, A. Sandelin, P. Carninci, A. R. R. Forrest, H. Kawaji, The FANTOM Consortium P43 Rapid and scalable typing of structural variants for disease cohorts W. Salerno, A. English, S. N. Shekar, A. Mangubat, J. Bruestle, E. Boerwinkle, R. A. Gibbs P44 Polymorphism of glutathione S-transferases and sulphotransferases genes in an Arab population A. H. Salem, M. Ali, A. Ibrahim, M. Ibrahim P46 Genetic divergence of CYP3A5*3 pharmacogenomic marker for native and admixed Mexican populations J. C. Fernandez-Lopez, V. Bonifaz-Peña, C. Rangel-Escareño, A. Hidalgo-Miranda, A. V. Contreras P47 Whole exome sequence meta-analysis of 13 white blood cell, red blood cell, and platelet traits L. Polfus, CHARGE and NHLBI Exome Sequence Project Working Groups P48 Association of adipoq gene with type 2 diabetes and related phenotypes in african american men and women: The jackson heart study S. Davis, R. Xu, S. Gebeab, P Riestra, A Gaye, R. Khan, J. Wilson, A. Bidulescu P49 Common variants in casr gene are associated with serum calcium levels in koreans S. H. Jung, N. Vinayagamoorthy, S. H. Yim, Y. J. Chung P50 Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions Y. Zhou, S. Xu P51 A Bayesian framework for generalized linear mixed models in genome-wide association studies X. Wang, V. Philip, G. Carter P52 Targeted sequencing approach for the identification of the genetic causes of hereditary hearing impairment A. A. Abuzenadah, M. Gari, R. Turki, A. Dallol P53 Identification of enhancer sequences by ATAC-seq open chromatin profiling A. Uyar, A. Kaygun, S. Zaman, E. Marquez, J. George, D. Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. Andreesen, E. Holler P61 Compound heterozygous mutation in the LDLR gene in Saudi patients suffering severe hypercholesterolemia F. Al-Allaf, A. Alashwal, Z. Abduljaleel, M. Taher, A. Bouazzaoui, H. Abalkhail, A. Al-Allaf, R. Bamardadh, M. Atha

Adaptive system supervising the response control for smart structures

The chapter will be dedicated in incorporating smart devices to enhance the seismic resilience of the civil engineering structures. The chapter would specifically deal with designing a computationally efficient and adaptive control algorithm with magnetorheological (MR) dampers as control devices, based on response optimization of the structure subjected to seismic excitation. This control strategy also requires fewer structural feedbacks than traditional control systems, making the whole application simple and cost-efficient. Moreover, the whole dynamic range of the MR damper is employed in increasing the compliance of structural control. The performance of the response-based adaptive (RBA) control with single and multiple objective optimizations is contrasted with H2/LQG (where LQG is linear quadratic Gaussian regulator) algorithm. Next, the experimental verification of the RBA control strategy with an MR damper installed on the ground floor is conducted on a five-story framed structure. Details of the shake table, experimental setup, transducers, control hardware, etc., are deliberated. Also, the design, fabrication, and details of the novel power amplifier circuit, which provides the required control current to the MR damper based on control voltage have been discussed. Finally, the proposed semi-active control strategy is compared with passive control strategies (passive-ON and passive-OFF)

Intelligent controller optimizing structural performance and control devices

This chapter is dedicated to exploring the bearing of a control system governing the input current to the control device on the position and number of devices incorporated into a structure. The device placements and controller parameters are derived using a combinatorial optimization technique as the number and location of control devices are also important for effective structural performance against dynamic forces. Because it is impractical to install dampers on every section, optimizing this parameter is an important task. This study aims to develop an embedded controller that looks to integrate the control device alignment strategy with adaptive semi-active controller. Single control objectives are selected for integrated control strategies and correspondingly compared with traditional genetic-based algorithms using a H2/LQG algorithm with clipped optimal controller, to ascertain the effectiveness of the controllers. Next, experimental verification of integrated control strategy for multiple magnetorheological (MR) damper-controlled structures is conducted on a shake table. The optimal position of MR dampers and corresponding control gains obtained during mathematical simulation is assigned to the structure and the controller. The structure is subjected to scaled ground excitations and tested for different configurations of 1, 2, and 3 MR dampers with optimal control gains assigned based on proposed control strategies. Furthermore, the application of the proposed integrated controller on a benchmark structure has been discussed

Investigation of proposed integrated control strategies based on performance and positioning of MR dampers on shaking table

Most of the studies in the field of structural control are focused on maximizing the performance of control devices without taking into consideration the complex dynamic response of the structure, computational efficiency, performance flexibility, and feedback reliability. Also, the location algorithm of energy dissipation should be concatenated with the control strategy, for effective structural control of multi-story structures. Moreover, in recent years, non-contact measurements using digital image correlation techniques have been adopted and implemented for the monitoring of civil engineering structures. However, its application is restricted to reinforced cement concrete members, involving a lower frequency spectrum, small displacements, and a lower image capture rate. In this study two response-based-adaptive control strategies based on inter-story drift and acceleration response reduction objectives respectively have been proposed. The control strategies are then integrated with the device location algorithm to establish the optimum configuration/location of magnetorheological dampers in addition to the design parameters of the controls system. The performance of proposed strategies is numerically compared with the benchmark Genetic algorithm using the Clipped optimal controller. The corresponding results indicated that proposed control strategies performed better for high-intensity ground motion and satisfactorily for low-intensity records. Next, the shake table results validated the performance of response-based-adaptive control strategies with device allocation algorithm in alleviating the peak and RMS response of the structure. The response of the structure was also attenuated and distributed among the modes of the structure, as indicated by the fast Fourier transform response of the structure

In-plane measurements using a novel streamed digital image correlation for shake table test of steel structures controlled with MR dampers

The major problems related to structural control and monitoring systems are the challenges involved with the installation of traditional transducers, the number of transducers required to obtain the desired structural responses, and the computation effort and time required to analyze, process, and post-process the recorded signals. Non-contact measurements employing digital image correlation (DIC) techniques have become popular in control engineering in recent years. However, it can only be used on certain types of members with a narrow frequency range, minor deflections, and a slower image frame rate. This study aims at determining a in-plane measurement of a five-story steel frame controlled with magnetorheological dampers (MR) on a shaking table using the streamed DIC technique employing a template matching algorithm. The MR dampers (Passive-ON and Passive-OFF) are involved in varying the characteristic of the structural response and therefore assess the accuracy and flexibility of the proposed DIC technique. A high level of precision was achieved for all response quantities for each image. The measurements of acceleration, displacement, velocity, inter-story drift of the floors, and column base strains of the structure subjected to high-intensity bi-directional ground motions are obtained and compared with results obtained from traditional transducers. The shaking table results specified the efficiency and precision of the proposed DIC system in monitoring the structural responses compared to the noisy transducer responses, which emphasized the potential of using this technique for monitoring, control, and reconnaissance of a wide range of structures during and after extreme events

Configuration assessment of MR dampers for structural control using performance-based passive control strategies

The use of structural control devices to minimize structural response to seismic/dynamic excitations has attracted increased attention in recent years. The use of magnetorheological (MR) dampers as a control device have captured the attention of researchers in this field due to its flexibility, adaptability, easy control, and low power requirement compared to other control devices. However, little attention has been paid to the effect of configuration and number of dampers installed in a structure on responses reduction. This study assesses the control of a five-story structure using one and two MR dampers at different stories to determine the optimal damper positions and configurations based on performance indices. This paper also addresses the fail-safe current value to be applied to the MR damper at each floor in the event of feedback or control failure. The model is mathematically simulated in SIMULINK/MATLAB environment. Linear control strategies for current at 0 A, 0.5 A, 1 A, 1.5 A, 2 A, and 2.5 A are implemented for MR dampers, and the response of the structure to these control strategies for different configurations of dampers is compared with the uncontrolled structure. Based on the performance indices, it was concluded that the dampers should be positioned starting from the ground floor, then the 2nd floor followed by 1st and rest of the floors sequentially. The failsafe value of current for MR dampers located in lower floors (G+1) should be kept at a higher value compared to dampers at top floors for effective passive control of multi-story structures

A critical review on control strategies for structural vibration control

In recent years, the application of structural control strategies to attenuate the dynamic response of civil engineering structures subjected to human-induced and environmental loads has once again received much attention. The hardware involved in providing effective control, the stochastic nature of the dynamic excitation, the number of distinct variables required to determine the dissipating forces, and the nature of the control approach are a few of the parameters involved in determining the efficacy of structural control systems. However, the primary parameter to determine the overall performance of a smart adaptive structure is the implementation of a control algorithm that would conveniently counteract the external known and/or unknown excitation by providing additional force input through control devices. The control algorithm to be adopted should be robust, multi-purpose, and simple to design and implement. Moreover, the control algorithm should provide the flexibility in selecting performance objectives for a holistically effective response reduction. This paper focuses on providing a comprehensive review of control algorithms implemented in structural control engineering. This article first provides an overview of the fundamental concepts pertaining to the vibration control of structures subjected to dynamic excitations. Next, an exhaustive review of different types of control algorithms that feed the input signal to active-type control devices is conducted. Thereafter, important benchmark applications in the field of structural control in civil engineering are presented. Finally, conclusions are presented on the advantages and drawbacks of each control strategy and recommendations are presented for further research in this area