486 results on '"Mital S"'
Search Results
2. Author Correction: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
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Xiao, Lanbo, Parolia, Abhijit, Qiao, Yuanyuan, Bawa, Pushpinder, Eyunni, Sanjana, Mannan, Rahul, Carson, Sandra E., Chang, Yu, Wang, Xiaoju, Zhang, Yuping, Vo, Josh N., Kregel, Steven, Simko, Stephanie A., Delekta, Andrew D., Jaber, Mustapha, Zheng, Heng, Apel, Ingrid J., McMurry, Lisa, Su, Fengyun, Wang, Rui, Zelenka-Wang, Sylvia, Sasmal, Sanjita, Khare, Leena, Mukherjee, Subhendu, Abbineni, Chandrasekhar, Aithal, Kiran, Bhakta, Mital S., Ghurye, Jay, Cao, Xuhong, Navone, Nora M., Nesvizhskii, Alexey I., Mehra, Rohit, Vaishampayan, Ulka, Blanchette, Marco, Wang, Yuzhuo, Samajdar, Susanta, Ramachandra, Murali, and Chinnaiyan, Arul M.
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- 2024
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3. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
- Author
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Xiao, Lanbo, Parolia, Abhijit, Qiao, Yuanyuan, Bawa, Pushpinder, Eyunni, Sanjana, Mannan, Rahul, Carson, Sandra E., Chang, Yu, Wang, Xiaoju, Zhang, Yuping, Vo, Josh N., Kregel, Steven, Simko, Stephanie A., Delekta, Andrew D., Jaber, Mustapha, Zheng, Heng, Apel, Ingrid J., McMurry, Lisa, Su, Fengyun, Wang, Rui, Zelenka-Wang, Sylvia, Sasmal, Sanjita, Khare, Leena, Mukherjee, Subhendu, Abbineni, Chandrasekhar, Aithal, Kiran, Bhakta, Mital S., Ghurye, Jay, Cao, Xuhong, Navone, Nora M., Nesvizhskii, Alexey I., Mehra, Rohit, Vaishampayan, Ulka, Blanchette, Marco, Wang, Yuzhuo, Samajdar, Susanta, Ramachandra, Murali, and Chinnaiyan, Arul M.
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- 2022
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- View/download PDF
4. A comparative study of trabeculectomy in cases of chronic simple glaucoma
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Mital S, Avasthi P, and Anand N
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Ophthalmology ,RE1-994 - Published
- 1979
5. Effects on the transcriptome upon deletion of a distal element cannot be predicted by the size of the H3K27Ac peak in human cells
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Tak, Yu Gyoung, Hung, Yuli, Yao, Lijing, Grimmer, Matthew R, Do, Albert, Bhakta, Mital S, O'Geen, Henriette, Segal, David J, and Farnham, Peggy J
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Biological Sciences ,Genetics ,Digestive Diseases ,Cancer ,Colo-Rectal Cancer ,Prevention ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Acetylation ,Cell Proliferation ,Colorectal Neoplasms ,Enhancer Elements ,Genetic ,Gene Expression Regulation ,Neoplastic ,Genome-Wide Association Study ,HCT116 Cells ,HEK293 Cells ,Histones ,Humans ,Papillomavirus E7 Proteins ,Polymorphism ,Single Nucleotide ,Protein Processing ,Post-Translational ,Sequence Deletion ,Transcriptome ,Environmental Sciences ,Information and Computing Sciences ,Developmental Biology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased risk for colorectal cancer (CRC). A molecular understanding of the functional consequences of this genetic variation is complicated because most GWAS SNPs are located in non-coding regions. We used epigenomic information to identify H3K27Ac peaks in HCT116 colon cancer cells that harbor SNPs associated with an increased risk for CRC. Employing CRISPR/Cas9 nucleases, we deleted a CRC risk-associated H3K27Ac peak from HCT116 cells and observed large-scale changes in gene expression, resulting in decreased expression of many nearby genes. As a comparison, we showed that deletion of a robust H3K27Ac peak not associated with CRC had minimal effects on the transcriptome. Interestingly, although there is no H3K27Ac peak in HEK293 cells in the E7 region, deletion of this region in HEK293 cells decreased expression of several of the same genes that were downregulated in HCT116 cells, including the MYC oncogene. Accordingly, deletion of E7 causes changes in cell culture assays in HCT116 and HEK293 cells. In summary, we show that effects on the transcriptome upon deletion of a distal regulatory element cannot be predicted by the size or presence of an H3K27Ac peak.
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- 2016
6. High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics
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Sept, Corriene E., primary, Tak, Y. Esther, additional, Cerda-Smith, Christian G., additional, Hutchinson, Haley M., additional, Goel, Viraat, additional, Blanchette, Marco, additional, Bhakta, Mital S., additional, Hansen, Anders S., additional, Joung, J. Keith, additional, Johnstone, Sarah, additional, Eyler, Christine E., additional, and Aryee, Martin J., additional
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- 2023
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7. A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture
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O'Geen, Henriette, Henry, Isabelle M, Bhakta, Mital S, Meckler, Joshua F, and Segal, David J
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Human Genome ,Animals ,Bacterial Proteins ,Base Sequence ,Binding Sites ,CRISPR-Associated Proteins ,Cell Line ,Clustered Regularly Interspaced Short Palindromic Repeats ,Genome-Wide Association Study ,INDEL Mutation ,Mice ,RNA ,Guide ,CRISPR-Cas Systems ,Streptococcus pyogenes ,Environmental Sciences ,Information and Computing Sciences ,Developmental Biology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided nucleases have gathered considerable excitement as a tool for genome engineering. However, questions remain about the specificity of target site recognition. Cleavage specificity is typically evaluated by low throughput assays (T7 endonuclease I assay, target amplification followed by high-throughput sequencing), which are limited to a subset of potential off-target sites. Here, we used ChIP-seq to examine genome-wide CRISPR binding specificity at gRNA-specific and gRNA-independent sites for two guide RNAs. RNA-guided Cas9 binding was highly specific to the target site while off-target binding occurred at much lower intensities. Cas9-bound regions were highly enriched in NGG sites, a sequence required for target site recognition by Streptococcus pyogenes Cas9. To determine the relationship between Cas9 binding and endonuclease activity, we applied targeted sequence capture, which allowed us to survey 1200 genomic loci simultaneously including potential off-target sites identified by ChIP-seq and by computational prediction. A high frequency of indels was observed at both target sites and one off-target site, while no cleavage activity could be detected at other ChIP-bound regions. Our results confirm the high-specificity of CRISPR endonucleases and demonstrate that sequence capture can be used as a high-throughput genome-wide approach to identify off-target activity.
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- 2015
8. Transcription activator like effector (TALE)-directed piggyBac transposition in human cells
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Owens, Jesse B, Mauro, Damiano, Stoytchev, Ilko, Bhakta, Mital S, Kim, Moon-Soo, Segal, David J, and Moisyadi, Stefan
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetic Testing ,Human Genome ,Gene Therapy ,Biotechnology ,Genetics ,Generic health relevance ,DNA Transposable Elements ,DNA-Binding Proteins ,Gene Targeting ,HEK293 Cells ,Humans ,Receptors ,CCR5 ,Recombinant Fusion Proteins ,Transposases ,Environmental Sciences ,Information and Computing Sciences ,Developmental Biology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
Insertional therapies have shown great potential for combating genetic disease and safer methods would undoubtedly broaden the variety of possible illness that can be treated. A major challenge that remains is reducing the risk of insertional mutagenesis due to random insertion by both viral and non-viral vectors. Targetable nucleases are capable of inducing double-stranded breaks to enhance homologous recombination for the introduction of transgenes at specific sequences. However, off-target DNA cleavages at unknown sites can lead to mutations that are difficult to detect. Alternatively, the piggyBac transposase is able perform all of the steps required for integration; therefore, cells confirmed to contain a single copy of a targeted transposon, for which its location is known, are likely to be devoid of aberrant genomic modifications. We aimed to retarget transposon insertions by comparing a series of novel hyperactive piggyBac constructs tethered to a custom transcription activator like effector DNA-binding domain designed to bind the first intron of the human CCR5 gene. Multiple targeting strategies were evaluated using combinations of both plasmid-DNA and transposase-protein relocalization to the target sequence. We demonstrated user-defined directed transposition to the CCR5 genomic safe harbor and isolated single-copy clones harboring targeted integrations.
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- 2013
9. Effect of age on refraction, intra-ocular pressure, facility of aqueous outflow and scleral rigidity
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Avasthi P, Ahmed Gower, Mital S, and Anand N
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Ophthalmology ,RE1-994 - Published
- 1979
10. Quantitative analysis of TALE–DNA interactions suggests polarity effects
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Meckler, Joshua F, Bhakta, Mital S, Kim, Moon-Soo, Ovadia, Robert, Habrian, Chris H, Zykovich, Artem, Yu, Abigail, Lockwood, Sarah H, Morbitzer, Robert, Elsäesser, Janett, Lahaye, Thomas, Segal, David J, and Baldwin, Enoch P
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Biochemistry and Cell Biology ,Biological Sciences ,Genetics ,DNA ,DNA-Binding Proteins ,Protein Binding ,Repetitive Sequences ,Amino Acid ,Trans-Activators ,Transcriptional Activation ,Environmental Sciences ,Information and Computing Sciences ,Developmental Biology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ≈ NN >> NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 10(3)-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches 'standard' RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5'-T. Another surprising observation was that base mismatches at the 5' end of the target site had more disruptive effects on affinity than those at the 3' end, particularly in designed TALEs. These results provide evidence that TALE-DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.
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- 2013
11. Dissecting the genetic architecture of coronary artery disease by genome engineering
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Segal, David J, Bhakta, Mital S, Das, Kumitaa, Sun, Chongxiu, Grace, Natalie M, Nolta, Jan A, Knowlton, Anne A, Rocke, David M, and Simon, Scott I
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- 2012
12. Structure of Aart, a designed six-finger zinc finger peptide, bound to DNA
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Segal, David J, Crotty, Justin W, Bhakta, Mital S, Barbas, Carlos F, and Horton, Nancy C
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zinc finger ,Aart ,structure ,peptide - Abstract
Cys2-His2 zinc fingers are one of the most common types of DNA-binding domains. Modifications to zinc-finger binding specificity have recently enabled custom DNA-binding proteins to be designed to a wide array of target sequences. We present here a 1.96 angstrom structure of Aart, a designed six-zinc finger protein, bound to a consensus DNA target site. This is the first structure of a designed protein with six fingers, and was intended to provide insights into the unusual affinity and specificity characteristics of this protein. Most protein-DNA contacts were found to be consistent with expectations, while others were unanticipated or insufficient to explain specificity. Several were unexpectedly mediated by glycerol, water molecules or amino acid-base stacking interactions. These results challenge some conventional concepts of recognition, particularly the finding that triplets containing 5'A, C, or T are typically not specified by direct interaction with the amino acid in position 6 of the recognition helix. (c) 2006 Elsevier Ltd. All rights reserved.
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- 2006
13. Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries
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Škorić-Milosavljević, D, Tadros, R, Bosada, FM, Tessadori, F, van Weerd, JH, Woudstra, OI, Tjong, FVY, Lahrouchi, N, Bajolle, F, Cordell, HJ, Agopian, AJ, Blue, GM, Barge-Schaapveld, DQCM, Gewillig, M, Preuss, C, Lodder, EM, Barnett, P, Ilgun, A, Beekman, L, van Duijvenboden, K, Bokenkamp, R, Müller-Nurasyid, M, Vliegen, HW, Konings, TC, van Melle, JP, van Dijk, APJ, van Kimmenade, RRJ, Roos-Hesselink, JW, Sieswerda, GT, Meijboom, F, Abdul-Khaliq, H, Berger, F, Dittrich, S, Hitz, M-P, Moosmann, J, Riede, F-T, Schubert, S, Galan, P, Lathrop, M, Munter, HM, Al-Chalabi, A, Shaw, CE, Shaw, PJ, Morrison, KE, Veldink, JH, van den Berg, LH, Evans, S, Nobrega, MA, Aneas, I, Radivojkov-Blagojević, M, Meitinger, T, Oechslin, E, Mondal, T, Bergin, L, Smythe, JF, Altamirano-Diaz, L, Lougheed, J, Bouma, BJ, Chaix, M-A, Kline, J, Bassett, AS, Andelfinger, G, van der Palen, RLF, Bouvagnet, P, Clur, S-AB, Breckpot, J, Kerstjens-Frederikse, WS, Winlaw, DS, Bauer, UMM, Mital, S, Goldmuntz, E, Keavney, B, Bonnet, D, Mulder, BJ, Tanck, MWT, Bakkers, J, Christoffels, VM, Boogerd, CJ, Postma, AV, Bezzina, CR, Hubrecht Institute for Developmental Biology and Stem Cell Research, Cardiology, Cardiovascular Centre (CVC), Medical Biology, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Human Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Cardiovascular Sciences, General Paediatrics, Paediatric Cardiology, APH - Aging & Later Life, APH - Personalized Medicine, Epidemiology and Data Science, APH - Methodology, Pediatric surgery, and Physiology
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Genome-wide association study ,Multifactorial Inheritance ,congenital, hereditary, and neonatal diseases and abnormalities ,Cardiac & Cardiovascular Systems ,Physiology ,Transposition of Great Vessels ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,ZIC3 MUTATIONS ,DE-NOVO ,Polymorphism, Single Nucleotide ,Wnt-5a Protein ,Article ,Mice ,OF-FUNCTION MUTATIONS ,Congenital Heart Disease ,Genome-wide Association Study ,Single Nucleotide Polymorphism ,Transposition Of Great Vessels ,Animals ,Humans ,MALFORMATIONS ,Myocytes, Cardiac ,GENOME-WIDE ASSOCIATION ,Transposition of great vessels ,Cells, Cultured ,Zebrafish ,Congenital heart disease ,WNT5A MUTATIONS ,Science & Technology ,HERITABILITY ,Wnt-5a protein ,Hematology ,DEFECTS ,Single nucleotide polymorphism ,CONGENITAL HEART-DISEASE ,Peripheral Vascular Disease ,Cardiovascular System & Cardiology ,HYPOPLASTIC LEFT-HEART ,T-Box Domain Proteins ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine - Abstract
Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 -10 , OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10 -5 ). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A , which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A . Genomic and functional data support a causal role of WNT5A at the locus.
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- 2022
14. Long-term passive wastewater surveillance of SARS-CoV-2 for seven university dormitories in comparison to municipal surveillance
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Jain, N., primary, Hamilton, D., additional, Mital, S., additional, Ilias, A., additional, Brinkmann, M., additional, and McPhedran, K., additional
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- 2022
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15. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
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Lanbo Xiao, Abhijit Parolia, Yuanyuan Qiao, Pushpinder Bawa, Sanjana Eyunni, Rahul Mannan, Sandra E. Carson, Yu Chang, Xiaoju Wang, Yuping Zhang, Josh N. Vo, Steven Kregel, Stephanie A. Simko, Andrew D. Delekta, Mustapha Jaber, Heng Zheng, Ingrid J. Apel, Lisa McMurry, Fengyun Su, Rui Wang, Sylvia Zelenka-Wang, Sanjita Sasmal, Leena Khare, Subhendu Mukherjee, Chandrasekhar Abbineni, Kiran Aithal, Mital S. Bhakta, Jay Ghurye, Xuhong Cao, Nora M. Navone, Alexey I. Nesvizhskii, Rohit Mehra, Ulka Vaishampayan, Marco Blanchette, Yuzhuo Wang, Susanta Samajdar, Murali Ramachandra, and Arul M. Chinnaiyan
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Hepatocyte Nuclear Factor 3-alpha ,Male ,cells ,genetic processes ,Genes, myc ,Chromatin remodelling ,macromolecular substances ,Article ,Targeted therapies ,Transcriptional Regulator ERG ,Nitriles ,Phenylthiohydantoin ,Animals ,Humans ,Adenosine Triphosphatases ,Multidisciplinary ,Prostate cancer ,DNA Helicases ,Nuclear Proteins ,Prostatic Neoplasms ,Oncogenes ,Xenograft Model Antitumor Assays ,enzymes and coenzymes (carbohydrates) ,Enhancer Elements, Genetic ,Receptors, Androgen ,Benzamides ,biological phenomena, cell phenomena, and immunity ,Transcription Factors - Abstract
The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1 and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+ forkhead box A1 (FOXA1)+ prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers., PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.
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- 2021
16. Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy
- Author
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Mathew, J., Zahavich, L., Lafreniere‐Roula, M., Wilson, J., George, K., Benson, L., Bowdin, S., and Mital, S.
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- 2018
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17. Clinical genetic testing in pediatric cardiomyopathy: Is bigger better?
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Ouellette, A.C., Mathew, J., Manickaraj, A.K., Manase, G., Zahavich, L., Wilson, J., George, K., Benson, L., Bowdin, S., and Mital, S.
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- 2018
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18. Use of the DICE (Dual Integrase Cassette Exchange) System
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Farruggio, Alfonso P., primary, Bhakta, Mital S., additional, and Calos, Michele P., additional
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- 2017
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19. Abstract 5469: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
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Xiao, Lanbo, primary, Parolia, Abhijit, additional, Qiao, Yuanyuan, additional, Pushpinder, Pushpinder Bawa, additional, Eyunni, Sanjana, additional, Mannan, Rahul, additional, Carson, Sandra E., additional, Chang, Yu, additional, Wang, Xiaoju, additional, Zhang, Yuping, additional, Vo, Josh, additional, Kregel, Steven, additional, Simko, Stephanie A., additional, Delekta, Andrew D., additional, Jaber, Mustapha, additional, Zheng, Heng, additional, Apel, Ingrid, additional, McMurry, Lisa, additional, Su, Fengyun, additional, Wang, Rui, additional, Wang, Sylvia, additional, Sasmal, Sanjita, additional, Satyam, Leena K., additional, Mukherjee, Subhendu, additional, AbbinenI, Chandrasekhar, additional, Aithal, Kiran, additional, Bhakta, Mital S., additional, Ghurye, Jay, additional, Cao, Xuhong, additional, Navone, Nora M., additional, Nesvizhskii, Alexey, additional, Mehra, Rohit, additional, Vaishampayan, Ulka, additional, Blanchette, Marco, additional, Wang, Yuzhuo, additional, Samajdar, Susanta, additional, Ramachandra, Murali, additional, and Chinnaiyan, Arul M., additional
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- 2022
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20. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
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Xiao, Lanbo, primary, Parolia, Abhijit, additional, Qiao, Yuanyuan, additional, Bawa, Pushpinder, additional, Eyunni, Sanjana, additional, Mannan, Rahul, additional, Carson, Sandra E., additional, Chang, Yu, additional, Wang, Xiaoju, additional, Zhang, Yuping, additional, Vo, Josh N., additional, Kregel, Steven, additional, Simko, Stephanie A., additional, Delekta, Andrew D., additional, Jaber, Mustapha, additional, Zheng, Heng, additional, Apel, Ingrid J., additional, McMurry, Lisa, additional, Su, Fengyun, additional, Wang, Rui, additional, Zelenka-Wang, Sylvia, additional, Sasmal, Sanjita, additional, Khare, Leena, additional, Mukherjee, Subhendu, additional, Abbineni, Chandrasekhar, additional, Aithal, Kiran, additional, Bhakta, Mital S., additional, Ghurye, Jay, additional, Cao, Xuhong, additional, Navone, Nora M., additional, Nesvizhskii, Alexey I., additional, Mehra, Rohit, additional, Vaishampayan, Ulka, additional, Blanchette, Marco, additional, Wang, Yuzhuo, additional, Samajdar, Susanta, additional, Ramachandra, Murali, additional, and Chinnaiyan, Arul M., additional
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- 2021
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21. Hypoxia inducible factor (HIF1A) is associated with increased right ventricular fibrosis by T1 mapping cardiac magnetic resonance in patients with repaired tetralogy of Fallot
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Vaikom House, A, primary, Chetan, D, additional, Grosse Wortmann, L, additional, and Mital, S, additional
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- 2021
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22. WHOLE GENOME SEQUENCING IDENTIFIES NOVEL CRYPTIC SPLICE SITE VARIANTS IN CHILDREN WITH CARDIOMYOPATHY
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Lesurf, R, primary, Persad, G, additional, and Mital, S, additional
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- 2021
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23. FUNCTIONAL VALIDATION OF NON-CODING REGULATORY VARIANTS ASSOCIATED WITH CHILDHOOD CARDIOMYOPATHY
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Said, A, primary, Lesurf, R, additional, Delfosse, K, additional, Oliveros, W, additional, Mattiolo, K, additional, Meng, G, additional, Mele, M, additional, Maass, P, additional, Ellis, J, additional, Scherer, S, additional, and Mital, S, additional
- Published
- 2021
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24. Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene
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Luyckx, I, Kumar, AA, Reyniers, E, Dekeyser, E, Vanderstraeten, K, Vandeweyer, G, Wunnemann, F, Preuss, C, Mazzella, JM, Goudot, G, Messas, E, Albuisson, J, Jeunemaitre, X, Eriksson, P, Mohamed, SA, Kempers, M, Salemink, S, Duijnhouwer, A, Andelfinger, G, Dietz, HC, Verstraeten, A (Aline), Van Laer, L, Loeys, BL, Zhurayev, R, Zerbino, D, Mital, S, Mertens, L, Franco-Cereceda, A, Verhagen, Judith, De Graaf - van de Laar, Ingrid, Wessels, Marja, Nemcikova, M, Krebsova, A, Clinical Genetics, MIBAVA Leducq Consortium, Goudot, Guillaume, University of Antwerp (UA), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], The Jackson Laboratory [Bar Harbor] (JAX), Centre de Réféfence des Maladies Vasculaires Rares [HEGP, APHP] (CRMVR), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Radboud University Medical Center [Nijmegen], Howard Hughes Medical Institute (HHMI), Johns Hopkins University School of Medicine [Baltimore], and MIBAVA Leducq Consortium: Rustam Zhurayev, Dmytro Zerbino, Seema Mital, Luc Mertens, Anders Franco-Cereceda, Judith M A Verhagen, Ingrid M B H van de Laar, Marja W Wessels, Michaela Nemcikova, Alice Krebsova
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Adult ,Heart Defects, Congenital ,Male ,Candidate gene ,DNA Copy Number Variations ,[SDV]Life Sciences [q-bio] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Population ,Heart Valve Diseases ,Genome-wide association study ,Disease ,complex mixtures ,Article ,03 medical and health sciences ,Aortic aneurysm ,All institutes and research themes of the Radboud University Medical Center ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Databases, Genetic ,parasitic diseases ,Genetics ,medicine ,Humans ,Copy-number variation ,education ,Biology ,Genetics (clinical) ,0303 health sciences ,education.field_of_study ,Aortic Aneurysm, Thoracic ,business.industry ,030305 genetics & heredity ,Middle Aged ,medicine.disease ,Phenotype ,digestive system diseases ,[SDV] Life Sciences [q-bio] ,Chemistry ,Aortic Valve ,Female ,Human medicine ,T-Box Domain Proteins ,business ,Genome-Wide Association Study ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
International audience; Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD), affecting 1-2% of the population. BAV is associated with thoracic aortic aneurysms (TAAs). Deleterious copy number variations (CNVs) were found previously in up to 10% of CHD cases. This study aimed at unravelling the contribution of deleterious deletions or duplications in 95 unrelated BAV/TAA patients. Seven unique or rare CNVs were validated, harbouring protein-coding genes with a role in the cardiovascular system. Based on the presence of overlapping CNVs in patients with cardiovascular phenotypes in the DECIPHER database, the identification of similar CNVs in whole-exome sequencing data of 67 BAV/TAA patients and suggested topological domain involvement from Hi-C data, supportive evidence was obtained for two genes (DGCR6 and TBX20) of the seven initially validated CNVs. A rare variant burden analysis using next-generation sequencing data from 637 BAV/TAA patients was performed for these two candidate genes. This revealed a suggestive genetic role for TBX20 in BAV/TAA aetiology, further reinforced by segregation of a rare TBX20 variant with the phenotype within a BAV/TAA family. To conclude, our results do not confirm a significant contribution for deleterious CNVs in BAV/TAA as only one potentially pathogenic CNV (1.05%) was identified. We cannot exclude the possibility that BAV/TAA is occasionally attributed to causal CNVs though, or that certain CNVs act as genetic risk factors by creating a sensitised background for BAV/TAA. Finally, accumulative evidence for TBX20 involvement in BAV/TAA aetiology underlines the importance of this transcription factor in cardiovascular disease.
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- 2019
25. Abstract 5469: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
- Author
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Lanbo Xiao, Abhijit Parolia, Yuanyuan Qiao, Pushpinder Bawa Pushpinder, Sanjana Eyunni, Rahul Mannan, Sandra E. Carson, Yu Chang, Xiaoju Wang, Yuping Zhang, Josh Vo, Steven Kregel, Stephanie A. Simko, Andrew D. Delekta, Mustapha Jaber, Heng Zheng, Ingrid Apel, Lisa McMurry, Fengyun Su, Rui Wang, Sylvia Wang, Sanjita Sasmal, Leena K. Satyam, Subhendu Mukherjee, Chandrasekhar AbbinenI, Kiran Aithal, Mital S. Bhakta, Jay Ghurye, Xuhong Cao, Nora M. Navone, Alexey Nesvizhskii, Rohit Mehra, Ulka Vaishampayan, Marco Blanchette, Yuzhuo Wang, Susanta Samajdar, Murali Ramachandra, and Arul M. Chinnaiyan
- Subjects
Cancer Research ,Oncology - Abstract
The switch/sucrose non-fermentable (SWI/SNF) complex plays a crucial role in chromatin remodeling and is recurrently altered in over 20% of human cancers. Here, we developed a proteolysis targeting chimera (PROTAC) degrader of ATPase subunits of the SWI/SNF complex, SMARCA2 and SMARCA4. Intriguingly, we found androgen receptor (AR)/forkhead box A1 (FOXA1)-positive prostate cancer to be exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to benign prostate as well as other cancer cell lines, including those with inactivating SMARCA4 mutations. Mechanistically, SWI/SNF inhibition rapidly compacts the cis-regulatory elements that are bound and activated by transcription factors that drive cancer proliferation, namely AR, FOXA1, ERG, and MYC. This ensues in chromatin untethering of these oncogenic drivers, chemical decommissioning of their core enhancer circuitry, and attenuation of downstream gene programs. Furthermore, we found SWI/SNF inhibition to disrupt super-enhancer and promoter DNA looping interactions that wire supra-physiologic expression of the AR, FOXA1, and MYC oncogenes, thereby tempering their expression in cancer cells. Monotherapy with the SMARCA2/4 degrader induced potent inhibition of tumor growth in cell line-derived xenograft models of prostate cancer and remarkably synergized with AR antagonists, inducing disease remission in models of castration-resistant prostate cancer. We also found the combinatorial treatment to significantly inhibit the growth of enzalutamide resistant disease using in vitro as well as patient-derived xenograft models. Notably, no major toxicities were seen in mice upon prolonged treatment with the SMARCA2/4 degrader, including no indications of thrombocytopenia, gastrointestinal goblet cell depletion, or germ cell degeneration. Taken together, these results suggest that impeding enhancer accessibility through SWI/SNF ATPase inactivation represents a novel therapeutic approach in enhancer addicted human cancers. Citation Format: Lanbo Xiao, Abhijit Parolia, Yuanyuan Qiao, Pushpinder Bawa Pushpinder, Sanjana Eyunni, Rahul Mannan, Sandra E. Carson, Yu Chang, Xiaoju Wang, Yuping Zhang, Josh Vo, Steven Kregel, Stephanie A. Simko, Andrew D. Delekta, Mustapha Jaber, Heng Zheng, Ingrid Apel, Lisa McMurry, Fengyun Su, Rui Wang, Sylvia Wang, Sanjita Sasmal, Leena K. Satyam, Subhendu Mukherjee, Chandrasekhar AbbinenI, Kiran Aithal, Mital S. Bhakta, Jay Ghurye, Xuhong Cao, Nora M. Navone, Alexey Nesvizhskii, Rohit Mehra, Ulka Vaishampayan, Marco Blanchette, Yuzhuo Wang, Susanta Samajdar, Murali Ramachandra, Arul M. Chinnaiyan. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5469.
- Published
- 2022
26. Sudden Cardiac Death and ICD Use in Rasopathy-Associated Hypertrophic Cardiomyopathy
- Author
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Lynch, A., primary, Ahuja, S., additional, Miron, A., additional, Nakano, S., additional, Howard, T., additional, Villa, C., additional, Armstrong, K., additional, Kaufman, B., additional, Gardin, L., additional, Whitehill, R., additional, Parent, J., additional, Godown, J., additional, Henderson, H., additional, Aziz, P., additional, Colan, S., additional, Seshadri, B., additional, Kantor, P., additional, Russell, M., additional, Lal, A., additional, Butts, R., additional, Richmond, M., additional, Conway, J., additional, Weintraub, R., additional, Rossano, J., additional, and Mital, S., additional
- Published
- 2021
- Full Text
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27. Twenty-Year Experience With Heart Transplantation for Infants and Children With Restrictive Cardiomyopathy: 1986–2006
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Bograd, A.J., Mital, S., Schwarzenberger, J.C., Mosca, R.S., Quaegebeur, J.M., Addonizio, L.J., Hsu, D.T., Lamour, J.M., and Chen, J.M.
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- 2008
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28. Hypertrophy signaling during peripartum cardiac remodeling
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Gonzalez, A.M.D., Osorio, J.C., Manlhiot, C., Gruber, D., Homma, S., and Mital, S.
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Heart enlargement -- Physiological aspects ,Pregnancy -- Physiological aspects ,Nitric oxide -- Properties ,Protein kinases -- Properties ,Biological sciences - Abstract
Molecular signaling pathways that regulate peripartum cardiac remodeling are not well understood. Our objectives were to study the role of mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) in mediating pregnancy and postpartum (PP) cardiac remodeling. Methods: Adult female Sprague-Dawley rats were divided into nonpregnant (n = 5), 18 days pregnant (n = 5), 0 days PP (n = 7), and 14 days PP (n = 8). Rats underwent echocardiography under sedation to measure left ventricle (LV) size and function, and Western blots were performed to measure myocardial protein expression of MAPKs (p38, JNK, ERK), Akt, and eNOS. Results: 1) During pregnancy, there was an increase in LV mass (0.62 [+ or -] 0.03 to 1.1 [+ or -] 0.04 g, P < 0.001), mass/volume ratio (0.7 [+ or -] 0.02 to 1.28 [+ or -] 0.02 g/ml, P < 0.0001), and ejection fraction (EF) (64 [+ or -] 3 to 74 [+ or -] 2%). Whereas LV mass and mass/volume ratio returned to prepregnancy values in the PP period, EF remained below normal range (53 [+ or -] 3%, P < 0.05). 2) The expression of anti-hypertrophic factors (p38, JNK, Akt) decreased during pregnancy and normalized PP, except JNK, which increased to higher than normal levels, eNOS also increased to higher than baseline levels PP. 3) Activation of p38 and JNK was directly correlated with lower LV mass/volume ratio (r = -0.81 and -0.71, respectively; P < 0.05). Conclusion: Pregnancy is associated with physiological cardiac hypertrophy. There is rapid reversal of hypertrophy in the PP period while recovery of cardiac function is delayed, possibly related to PP upregulation of JNK. A dysregulation of MAPK signaling may be an important determinant of PP cardiac dysfunction. pregnancy; cardiac hypertrophy; nitric oxide; mitogen-activated protein kinases
- Published
- 2007
29. DNA-Mediated Gene Therapy in a Mouse Model of Limb Girdle Muscular Dystrophy 2B
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Michele P. Calos, Haley du Bois, Christophe Pichavant, Mital S. Bhakta, and Julia Ma
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0301 basic medicine ,lcsh:QH426-470 ,muscle ,Hindlimb ,Gene delivery ,Article ,Dysferlin ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,follistatin ,lcsh:QH573-671 ,Molecular Biology ,biology ,lcsh:Cytology ,Skeletal muscle ,Anatomy ,medicine.disease ,Molecular biology ,gene therapy ,dysferlin ,lcsh:Genetics ,030104 developmental biology ,medicine.anatomical_structure ,Naked DNA ,Knockout mouse ,biology.protein ,naked DNA ,limb girdle muscular dystrophy 2B ,Molecular Medicine ,030217 neurology & neurosurgery ,Limb-girdle muscular dystrophy ,Follistatin - Abstract
Mutations in the gene for dysferlin cause a degenerative disorder of skeletal muscle known as limb girdle muscular dystrophy 2B. To achieve gene delivery of plasmids encoding dysferlin to hind limb muscles of dysferlin knockout mice, we used a vascular injection method that perfused naked plasmid DNA into all major muscle groups of the hind limb. We monitored delivery by luciferase live imaging and western blot, confirming strong dysferlin expression that persisted over the 3-month time course of the experiment. Co-delivery of the follistatin gene, which may promote muscle growth, was monitored by ELISA. Immunohistochemistry documented the presence of dysferlin in muscle fibers in treated limbs, and PCR confirmed the presence of plasmid DNA. Because dysferlin is involved in repair of the sarcolemmal membrane, dysferlin loss leads to fragile sarcolemmal membranes that can be detected by permeability to Evan’s blue dye. We showed that after gene therapy with a plasmid encoding both dysferlin and follistatin, statistically significant reduction in Evan’s blue dye permeability was present in hamstring muscles. These results suggest that vascular delivery of plasmids carrying these therapeutic genes may lead to simple and effective approaches for improving the clinical condition of limb girdle muscular dystrophy 2B.
- Published
- 2017
30. The Generation of Zinc Finger Proteins by Modular Assembly
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Bhakta, Mital S., primary and Segal, David J., additional
- Published
- 2010
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31. Purification and characterization of alkaline protease from a newly isolated haloalkaliphilic Bacillus sp.
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Patel, Rajesh K., Dodia, Mital S., Joshi, Rupal H., and Singh, Satya P.
- Published
- 2006
- Full Text
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32. WALL THICKNESS NORMALIZATION IN PEDIATRIC HYPERTROPHIC CARDIOMYOPATHY: CHARACTERIZING PREDICTORS AND PATIENT OUTCOMES
- Author
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Lynch, A., primary, Ashkanase, J., additional, Arathoon, K., additional, Jeewa, A., additional, Mital, S., additional, and Jean-St-Michel, E., additional
- Published
- 2019
- Full Text
- View/download PDF
33. Spot test analysis of pesticides: Detection of carbaryl and mancozeb in water
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Rathore, H. S., Sharma, R., and Mital, S.
- Published
- 1997
- Full Text
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34. Probabilistic Aeroelastic Analysis of Turbomachinery Components
- Author
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Reddy, T. S. R, Mital, S. K, and Stefko, G. L
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Structural Mechanics - Abstract
A probabilistic approach is described for aeroelastic analysis of turbomachinery blade rows. Blade rows with subsonic flow and blade rows with supersonic flow with subsonic leading edge are considered. To demonstrate the probabilistic approach, the flutter frequency, damping and forced response of a blade row representing a compressor geometry is considered. The analysis accounts for uncertainties in structural and aerodynamic design variables. The results are presented in the form of probabilistic density function (PDF) and sensitivity factors. For subsonic flow cascade, comparisons are also made with different probabilistic distributions, probabilistic methods, and Monte-Carlo simulation. The approach shows that the probabilistic approach provides a more realistic and systematic way to assess the effect of uncertainties in design variables on the aeroelastic instabilities and response.
- Published
- 2004
35. Telescoping Mechanics: A New Paradigm for Composite Behavior Simulation
- Author
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Chamis, C. C, Murthy, P. L. N, Gotsis, P. K, and Mital. S. K
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Structural Mechanics - Abstract
This report reviews the application of telescoping mechanics to composites using recursive laminate theory. The elemental scale is the fiber-matrix slice, the behavior of which propagates to laminate. The results from using applications for typical, hybrid, and smart composites and composite-enhanced reinforced concrete structures illustrate the versatility and generality of telescoping scale mechanics. Comparisons with approximate, single-cell, and two- and three-dimensional finite-element methods demonstrate the accuracy and computational effectiveness of telescoping scale mechanics for predicting complex composite behavior.
- Published
- 2004
36. A Novel Tool to Quantify Immune Suppression after Pediatric Transplantation: Flow Cytometric Activation Assays
- Author
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Penner, R.E., primary, Ionescu, L., additional, Mital, S., additional, Foster, B., additional, Birk, P., additional, Phan, V., additional, Blydt-Hansen, T., additional, Allen, U., additional, Hamiwka, L., additional, Morgan, C., additional, and Urschel, S., additional
- Published
- 2019
- Full Text
- View/download PDF
37. Pediatric Hypertrophic Cardiomyopathy: Survival and Prognostic Indicators in the Current Era
- Author
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Ashkanase, J., primary, Jeewa, A., additional, Arathoon, K., additional, Cui, E., additional, Dillon, K., additional, Mital, S., additional, and Jean-St-Michel, E., additional
- Published
- 2019
- Full Text
- View/download PDF
38. Outcomes in Pediatric Hypertrophic Cardiomyopathy Patients with Reduced Systolic Ventricular Function
- Author
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Ashkanase, J., primary, Jeewa, A., additional, Arathoon, K., additional, Cui, E., additional, Dillon, K., additional, Mital, S., additional, and Jean-St-Michel, E., additional
- Published
- 2019
- Full Text
- View/download PDF
39. GENOMIC ARCHITECTURE OF TETRALOGY OF FALLOT AND GENOMIC PREDICTORS OF ADVERSE RIGHT VENTRICULAR REMODELLING
- Author
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Chaix, M., primary, Akinrinade, O., additional, Yao, R., additional, Lafreniere-Roula, M., additional, Van der Laan, R., additional, Tran, G., additional, Sung, W., additional, Thiruvahindrapuram, B., additional, Altamirano Diaz, L., additional, Mondal, T., additional, Lougheed, J., additional, Smythe, J., additional, Gordon, E., additional, Bergin, L., additional, Oechslin, E., additional, van Arsdell, G., additional, Manlhiot, C., additional, Scherer, S., additional, Bezzina, C., additional, and Mital, S., additional
- Published
- 2018
- Full Text
- View/download PDF
40. Meso-Mechanics and Meso-Structures: A Matter of Scale
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Chamis, Christos C, Gotsis, P. K, and Mital, S. K
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Composite Materials - Abstract
Meso-mechanics and meso-structures are described in terms of the scales at which they are observed and formulated. Select composite examples are presented to illustrate that meso-mechanics and/or meso-structures are meaningful only when they refer to a specific scale in a hierarchical scale observation/simulation. These examples include different types of composite unit cells, woven fabric unit cells, and progressive fracture as a composite enhanced infrastructure made from reinforced concrete. The results from the select examples indicate that meso-mechanics and meso-structures are elusive terms and depend mainly on the investigators' knowledge and available information.
- Published
- 1998
41. ICAN - Second-Generation Integrated Composite Analyzer
- Author
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Murthy, P. L. N and Mital, S. K
- Subjects
Materials - Abstract
Integrated Composite Analyzer (ICAN) computer program provides for comprehensive linear analyses of multilayered matrix/fiber composite materials. Includes micromechanical design features to predict ply-level hygral, thermal, and mechanical properties. Laminate-analysis features included to account for interply layer effects. ICAN integrates these with additional features to provide capability for comprehensive analyses of composites structures. Modified version includes prediction of damping in polymer-matrix composites, ICAN/DAMP (LEW-15966, LEW-16073). Two machine versions of ICAN are available; the Amdahl version and the PC version. The Amdahl version (LEW-15832) is written in FORTRAN 77. The IBM PC version (LEW-15592) also written in FORTRAN 77.
- Published
- 1995
42. Program For Analysis Of Metal-Matrix Composites
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Murthy, P. L. N and Mital, S. K
- Subjects
Materials - Abstract
METCAN (METal matrix Composite ANalyzer) is computer program used to simulate computationally nonlinear behavior of high-temperature metal-matrix composite structural components in specific applications, providing comprehensive analyses of thermal and mechanical performances. Written in FORTRAN 77.
- Published
- 1994
43. Integrated Composite Analyzer (ICAN/PC)
- Author
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Murthy, P. L. N and Mital, S. K
- Subjects
Materials - Abstract
Integrated Composites Analyzer (ICAN/PC) computer program designed to carry out comprehensive linear analysis of multilayered continuous-fiber polymer matrix composites. Performs micromechanics, macromechanics, and laminate analyses, taking account of hygrothermal responses of fiber composites. Written in FORTRAN 77.
- Published
- 1994
44. Use of the DICE (Dual Integrase Cassette Exchange) System
- Author
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Alfonso P, Farruggio, Mital S, Bhakta, and Michele P, Calos
- Subjects
Recombination, Genetic ,Integrases ,Green Fluorescent Proteins ,Induced Pluripotent Stem Cells ,Transfection ,Polymerase Chain Reaction ,Cell Line ,Clone Cells ,Luminescent Proteins ,Viral Proteins ,Genes, Reporter ,Genetic Loci ,Transcription Activator-Like Effector Nucleases ,Gene Targeting ,Humans ,Bacteriophages ,Plasmids - Abstract
When constructing transgenic cell lines via plasmid DNA integration, precise targeting to a desired genomic location is advantageous. It is also often advantageous to remove the bacterial backbone, since bacterial elements can lead to the epigenetic silencing of neighboring DNA. The least cumbersome method to remove the plasmid backbone is recombinase-mediated cassette exchange (RMCE). RMCE is accomplished by arranging recombinase sites in the genome and in a donor plasmid such that a recombinase can both integrate the donor plasmid and excise its bacterial backbone. When a single recombinase is used for RMCE, recombination between undesired pairings of the sites can lead to a significant number of unwanted cell lines. To reduce the frequency with which these side products occur, several variants of RMCE that increase desired outcomes have been developed. Nevertheless, an important feature lacking from these improved RMCE methods is that none have fully utilized the recombinases that have been demonstrated to be the most robust and stringent at performing genomic integration in plants and animals, i.e., the phiC31 and Bxb1 phage integrases. To address this need, we have developed an RMCE protocol using these two serine integrases that we call dual integrase cassette exchange (DICE). Our DICE system provides a means to achieve high-precision DNA integration at a desired location and is especially well suited for repeated recombination into the same locus. In this chapter, we provide our most current protocols for using DICE in feeder-free human-induced pluripotent stem cells .
- Published
- 2017
45. Three Novel Immune-deficient Mouse Models of Muscular Dystrophy
- Author
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Haley du Bois, Christopher R. R. Bjornson, Todd Gallagher, Tawny L. Neal, Michele P. Calos, Mital S. Bhakta, and Christophe Pichavant
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Immune system ,Immunology ,Deficient mouse ,medicine ,Medicine (miscellaneous) ,Muscular dystrophy ,Biology ,medicine.disease - Published
- 2017
46. Computational simulation of matrix micro-slip bands in SiC/Ti-15 composite
- Author
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Mital, S. K, Lee, H.-J, Murthy, P. L. N, and Chamis, C. C
- Subjects
Composite Materials - Abstract
Computational simulation procedures are used to identify the key deformation mechanisms for (0)(sub 8) and (90)(sub 8) SiC/Ti-15 metal matrix composites. The computational simulation procedures employed consist of a three-dimensional finite-element analysis and a micromechanics based computer code METCAN. The interphase properties used in the analysis have been calibrated using the METCAN computer code with the (90)(sub 8) experimental stress-strain curve. Results of simulation show that although shear stresses are sufficiently high to cause the formation of some slip bands in the matrix concentrated mostly near the fibers, the nonlinearity in the composite stress-strain curve in the case of (90)(sub 8) composite is dominated by interfacial damage, such as microcracks and debonding rather than microplasticity. The stress-strain curve for (0)(sub 8) composite is largely controlled by the fibers and shows only slight nonlinearity at higher strain levels that could be the result of matrix microplasticity.
- Published
- 1992
47. FRI0634 Cost savings of using hla-b*27 tag snp genotyping to determine hla-b*27 status in a canadian population
- Author
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Mital, S., primary, O'Rielly, D., additional, Nguyen, H. V., additional, and Rahman, P., additional
- Published
- 2018
- Full Text
- View/download PDF
48. Metal matrix composites microfracture - Computational simulation
- Author
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Mital, S. K, Caruso, J. J, and Chamis, C. C
- Subjects
Composite Materials - Abstract
Fiber/matrix fracture and fiber-matrix interface debonding in a metal matrix composite (MMC) are computationally simulated. These simulations are part of a research activity to develop computational methods for microfracture, microfracture propagation and fracture toughness of the metal matrix composites. The three-dimensional finite element model used in the simulation consists of a group of nine unidirectional fibers in three by three unit cell array of SiC/Ti15 metal matrix composite with a fiber volume ration of 0.35. This computational procedure is used to predict the fracture process and establish the hierarchy of fracture modes based on strain energy release rate. It is also used to predict stress redistribution to surrounding matrix-fibers due to initial and progressive fracture of fiber/matrix and due to debonding of fiber-matrix interface. Microfracture results for various loading cases such as longitudinal, transverse, shear and bending are presented and discussed. Step-by-step procedures are outlined to evaluate composite microfracture for a given composite system.
- Published
- 1990
- Full Text
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49. Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy
- Author
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Mathew, J., primary, Zahavich, L., additional, Lafreniere-Roula, M., additional, Wilson, J., additional, George, K., additional, Benson, L., additional, Bowdin, S., additional, and Mital, S., additional
- Published
- 2017
- Full Text
- View/download PDF
50. Transcription activator like effector (TALE)-directed piggyBac transposition in human cells
- Author
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Ilko Stoytchev, Mital S. Bhakta, David J. Segal, Damiano Mauro, Jesse B. Owens, Stefan Moisyadi, and Moon-Soo Kim
- Subjects
Transposable element ,Receptors, CCR5 ,Recombinant Fusion Proteins ,Transposases ,Biology ,medicine.disease_cause ,DNA-binding protein ,Insertional mutagenesis ,03 medical and health sciences ,0302 clinical medicine ,Information and Computing Sciences ,Receptors ,Genetics ,medicine ,Humans ,Transposase ,030304 developmental biology ,0303 health sciences ,Mutation ,Effector ,Gene targeting ,Biological Sciences ,DNA-Binding Proteins ,HEK293 Cells ,Synthetic Biology and Chemistry ,Gene Targeting ,DNA Transposable Elements ,Homologous recombination ,CCR5 ,Environmental Sciences ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Insertional therapies have shown great potential for combating genetic disease and safer methods would undoubtedly broaden the variety of possible illness that can be treated. A major challenge that remains is reducing the risk of insertional mutagenesis due to random insertion by both viral and non-viral vectors. Targetable nucleases are capable of inducing double-stranded breaks to enhance homologous recombination for the introduction of transgenes at specific sequences. However, off-target DNA cleavages at unknown sites can lead to mutations that are difficult to detect. Alternatively, the piggyBac transposase is able perform all of the steps required for integration; therefore, cells confirmed to contain a single copy of a targeted transposon, for which its location is known, are likely to be devoid of aberrant genomic modifications. We aimed to retarget transposon insertions by comparing a series of novel hyperactive piggyBac constructs tethered to a custom transcription activator like effector DNA-binding domain designed to bind the first intron of the human CCR5 gene. Multiple targeting strategies were evaluated using combinations of both plasmid-DNA and transposase-protein relocalization to the target sequence. We demonstrated user-defined directed transposition to the CCR5 genomic safe harbor and isolated single-copy clones harboring targeted integrations.
- Published
- 2013
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