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1

Hou, Kun, Hui Jiang, Md Rezaul Karim, Chao Zhong, Zhouwen Xu, Lin Liu, Minxin Guan, Jianzhong Shao, and Xiao Huang. "A Critical E-box in Barhl1 3′ Enhancer Is Essential for Auditory Hair Cell Differentiation." Cells 8, no. 5 (May 15, 2019): 458. http://dx.doi.org/10.3390/cells8050458.

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Barhl1, a mouse homologous gene of Drosophila BarH class homeobox genes, is highly expressed within the inner ear and crucial for the long-term maintenance of auditory hair cells that mediate hearing and balance, yet little is known about the molecular events underlying Barhl1 regulation and function in hair cells. In this study, through data mining and in vitro report assay, we firstly identified Barhl1 as a direct target gene of Atoh1 and one E-box (E3) in Barhl1 3’ enhancer is crucial for Atoh1-mediated Barhl1 activation. Then we generated a mouse embryonic stem cell (mESC) line carrying disruptions on this E3 site E-box (CAGCTG) using CRISPR/Cas9 technology and this E3 mutated mESC line is further subjected to an efficient stepwise hair cell differentiation strategy in vitro. Disruptions on this E3 site caused dramatic loss of Barhl1 expression and significantly reduced the number of induced hair cell-like cells, while no affections on the differentiation toward early primitive ectoderm-like cells and otic progenitors. Finally, through RNA-seq profiling and gene ontology (GO) enrichment analysis, we found that this E3 box was indispensable for Barhl1 expression to maintain hair cell development and normal functions. We also compared the transcriptional profiles of induced cells from CDS mutated and E3 mutated mESCs, respectively, and got very consistent results except the Barhl1 transcript itself. These observations indicated that Atoh1-mediated Barhl1 expression could have important roles during auditory hair cell development. In brief, our findings delineate the detail molecular mechanism of Barhl1 expression regulation in auditory hair cell differentiation.
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2

Chellappa, Ramesh, Shengguo Li, Sarah Pauley, Israt Jahan, Kangxin Jin, and Mengqing Xiang. "Barhl1 Regulatory Sequences Required for Cell-Specific Gene Expression and Autoregulation in the Inner Ear and Central Nervous System." Molecular and Cellular Biology 28, no. 6 (January 22, 2008): 1905–14. http://dx.doi.org/10.1128/mcb.01454-07.

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ABSTRACT The development of the nervous system requires the concerted actions of multiple transcription factors, yet the molecular events leading to their expression remain poorly understood. Barhl1, a mammalian homeodomain transcription factor of the BarH class, is expressed by developing inner ear hair cells, cerebellar granule cells, precerebellar neurons, and collicular neurons. Targeted gene inactivation has demonstrated a crucial role for Barhl1 in the survival and/or migration of these sensory cells and neurons. Here we report the regulatory sequences of Barhl1 necessary for directing its proper spatiotemporal expression pattern in the inner ear and central nervous system (CNS). Using a transgenic approach, we have found that high-level and cell-specific expression of Barhl1 within the inner ear and CNS depends on both its 5′ promoter and 3′ enhancer sequences. Further transcriptional, binding, and mutational analyses of the 5′ promoter have identified two homeoprotein binding motifs that can be occupied and activated by Barhl1. Moreover, proper Barhl1 expression in inner ear hair cells and cerebellar and precerebellar neurons requires the presence of Atoh1. Together, these data delineate useful Barhl1 regulatory sequences that direct strong and specific gene expression to inner ear hair cells and CNS sensory neurons, establish a role for autoregulation in the maintenance of Barhl1 expression, and identify Atoh1 as a key upstream regulator.
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3

Li, Shengguo, Sandy M. Price, Hugh Cahill, David K. Ryugo, Michael M. Shen, and Mengqing Xiang. "Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene." Development 129, no. 14 (July 15, 2002): 3523–32. http://dx.doi.org/10.1242/dev.129.14.3523.

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The cochlea of the mammalian inner ear contains three rows of outer hair cells and a single row of inner hair cells. These hair cell receptors reside in the organ of Corti and function to transduce mechanical stimuli into electrical signals that mediate hearing. To date, the molecular mechanisms underlying the maintenance of these delicate sensory hair cells are unknown. We report that targeted disruption of Barhl1, a mouse homolog of the Drosophila BarH homeobox genes, results in severe to profound hearing loss, providing a unique model for the study of age-related human deafness disorders. Barhl1 is expressed in all sensory hair cells during inner ear development, 2 days after the onset of hair cell generation. Loss of Barhl1 function in mice results in age-related progressive degeneration of both outer and inner hair cells in the organ of Corti, following two reciprocal longitudinal gradients. Our data together indicate an essential role for Barhl1 in the long-term maintenance of cochlear hair cells, but not in the determination or differentiation of these cells.
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4

Lopes, Carmela, Anne-Lise Delezoide, Jean-Maurice Delabar, and Mohammed Rachidi. "BARHL1 homeogene, the human ortholog of the mouse Barhl1 involved in cerebellum development, shows regional and cellular specificities in restricted domains of developing human central nervous system." Biochemical and Biophysical Research Communications 339, no. 1 (January 2006): 296–304. http://dx.doi.org/10.1016/j.bbrc.2005.11.021.

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5

Dong, Hongyan, Carole L. Yauk, and Michael G. Wade. "Barhl1 is directly regulated by thyroid hormone in the developing cerebellum of mice." Biochemical and Biophysical Research Communications 415, no. 1 (November 2011): 157–62. http://dx.doi.org/10.1016/j.bbrc.2011.10.041.

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6

Pöschl, J., A. Lorenz, W. Hartmann, A. O. von Bueren, M. Kool, S. Li, A. Peraud, et al. "Expression of BARHL1 in medulloblastoma is associated with prolonged survival in mice and humans." Oncogene 30, no. 47 (May 23, 2011): 4721–30. http://dx.doi.org/10.1038/onc.2011.173.

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7

Sud, Richa, Chris M. Jones, Sandro Banfi, and Sally J. Dawson. "Transcriptional regulation by Barhl1 and Brn-3c in organ of corti derived cell lines." Molecular Brain Research 141, no. 2 (November 2005): 174–80. http://dx.doi.org/10.1016/j.molbrainres.2005.09.007.

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8

Barh, Debmalya, María García-Solano, Sandeep Tiwari, Antaripa Bhattacharya, Neha Jain, Daniel Torres-Moreno, Belén Ferri, et al. "BARHL1 Is Downregulated in Alzheimer’s Disease and May Regulate Cognitive Functions through ESR1 and Multiple Pathways." Genes 8, no. 10 (September 28, 2017): 245. http://dx.doi.org/10.3390/genes8100245.

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9

Li, S. "Barhl1 Regulates Migration and Survival of Cerebellar Granule Cells by Controlling Expression of the Neurotrophin-3 Gene." Journal of Neuroscience 24, no. 12 (March 24, 2004): 3104–14. http://dx.doi.org/10.1523/jneurosci.4444-03.2004.

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10

Li, Shengguo, and Mengqing Xiang. "Barhl1 is required for maintenance of a large population of neurons in the zonal layer of the superior colliculus." Developmental Dynamics 235, no. 8 (2006): 2260–65. http://dx.doi.org/10.1002/dvdy.20858.

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11

Bulfone, A. "Barhl1, a gene belonging to a new subfamily of mammalian homeobox genes, is expressed in migrating neurons of the CNS." Human Molecular Genetics 9, no. 9 (May 22, 2000): 1443–52. http://dx.doi.org/10.1093/hmg/9.9.1443.

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12

Rachidi, Mohammed, and Carmela Lopes. "Differential transcription of Barhl1 homeobox gene in restricted functional domains of the central nervous system suggests a role in brain patterning." International Journal of Developmental Neuroscience 24, no. 1 (December 27, 2005): 35–44. http://dx.doi.org/10.1016/j.ijdevneu.2005.11.015.

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13

Tu, Shu, and Jian Zuo. "Systematic single cell RNA sequencing analysis reveals unique transcriptional regulatory networks of Atoh1-mediated hair cell conversion in adult mouse cochleae." PLOS ONE 18, no. 12 (December 11, 2023): e0284685. http://dx.doi.org/10.1371/journal.pone.0284685.

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Regeneration of mammalian cochlear hair cells (HCs) by modulating molecular pathways or transcription factors is a promising approach to hearing restoration; however, immaturity of the regenerated HCs in vivo remains a major challenge. Here, we analyzed a single cell RNA sequencing (scRNA-seq) dataset during Atoh1-induced supporting cell (SC) to hair cell (HC) conversion in adult mouse cochleae (Yamashita et al. (2018)) using multiple high-throughput sequencing analytical tools (WGCNA, SCENIC, ARACNE, and VIPER). Instead of focusing on differentially expressed genes, we established independent expression modules and confirmed the existence of multiple conversion stages. Gene regulatory network (GRN) analysis uncovered previously unidentified key regulators, including Nhlh1, Lhx3, Barhl1 and Nfia, that guide converted HC differentiation. Comparison of the late-stage converted HCs with the scRNA-seq data from neonatal mouse cochleae (Kolla et al. (2020)) revealed that they closely resemble postnatal day 1 wild-type OHCs, in contrast to other developmental stages. Using ARACNE and VIPER, we discovered multiple key regulators likely to promote conversion to a more mature OHC-like state, including Zbtb20, Nfia, Zmiz1, Gm14418, Bhlhe40, Six2, Fosb and Klf9. Our findings provide insights into the regulation of HC regeneration in adult mammalian cochleae in vivo and demonstrate an approach for analyzing GRNs in large scRNA-seq datasets.
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14

Zhong, Chao, Zhenhuang Chen, Xiaocui Luo, Cuicui Wang, Hui Jiang, Jianzhong Shao, Minxin Guan, Liquan Huang, Xiao Huang, and Jinfu Wang. "Corrigendum to “Barhl1 is required for the differentiation of inner ear hair cell-like cells from mouse embryonic stem cells” [Int. J. Biochem. Cell Biol. 96 (2018) 79–89]." International Journal of Biochemistry & Cell Biology 97 (April 2018): 128–29. http://dx.doi.org/10.1016/j.biocel.2018.02.009.

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15

Scholten, Frits. "'A Thing of Beauty is a Joy Forever’." Rijksmuseum Bulletin 66, no. 3 (September 15, 2018): 254–69. http://dx.doi.org/10.52476/trb.9758.

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A somewhat neglected late fifteenth-century panel from the collection of the Amsterdam-Swiss surgeon and art collector Otto Lanz, which he cherished, is investigated here. This article argues persuasively that the panel is a devotional tabernacle, intended for private devotion, of a kind that often hung on the wall of a bedchamber in the late Middle Ages. The missing central image may have been a Virgin and Child or a Pietà. Lanz attributed the carving to the woodcarver Antonio di Neri Barili or Barile (1453-1516). Barile was the most important woodcarver in Siena, who worked for distinguished clients, among them the Piccolomini family, which was responsible for introducing the Roman all’antica style to Siena shortly after 1500. The tabernacle contains the family’s coat of arms and various motifs that correspond to documented work by Barili, and was carved in his characteristic crisp, open style. If this panel is indeed by Barili, it would be the smallest surviving object in its own right to come out of his workshop.
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16

Lum, G., and X. J. Min. "FunSecKB: the Fungal Secretome KnowledgeBase." Database 2011 (February 6, 2011): bar001. http://dx.doi.org/10.1093/database/bar001.

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17

Blankenberg, D., N. Coraor, G. Von Kuster, J. Taylor, and A. Nekrutenko. "Integrating diverse databases into an unified analysis framework: a Galaxy approach." Database 2011 (April 29, 2011): bar011. http://dx.doi.org/10.1093/database/bar011.

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18

Raju, R., L. Balakrishnan, V. Nanjappa, M. Bhattacharjee, D. Getnet, B. Muthusamy, J. Kurian Thomas, et al. "A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway." Database 2011 (July 8, 2011): bar021. http://dx.doi.org/10.1093/database/bar021.

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19

Haw, R. A., D. Croft, C. K. Yung, N. Ndegwa, P. D'Eustachio, H. Hermjakob, and L. D. Stein. "The Reactome BioMart." Database 2011 (October 19, 2011): bar031. http://dx.doi.org/10.1093/database/bar031.

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20

Guberman, J. M., J. Ai, O. Arnaiz, J. Baran, A. Blake, R. Baldock, C. Chelala, et al. "BioMart Central Portal: an open database network for the biological community." Database 2011 (September 18, 2011): bar041. http://dx.doi.org/10.1093/database/bar041.

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21

Jung, S., N. Menda, S. Redmond, R. M. Buels, M. Friesen, Y. Bendana, L. A. Sanderson, et al. "The Chado Natural Diversity module: a new generic database schema for large-scale phenotyping and genotyping data." Database 2011 (November 26, 2011): bar051. http://dx.doi.org/10.1093/database/bar051.

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22

Brose, Michelle. "Barely Breathing." Narrative Inquiry in Bioethics 10, no. 3 (2020): 202–5. http://dx.doi.org/10.1353/nib.2020.0057.

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23

Chesser, T., M. F. Gargan, and K. M. Willett. "'Barfly' injuries." BMJ 305, no. 6853 (September 5, 1992): 583. http://dx.doi.org/10.1136/bmj.305.6853.583-b.

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24

Compton, Tony. "Barely literate." New Scientist 210, no. 2808 (April 2011): 31. http://dx.doi.org/10.1016/s0262-4079(11)60863-4.

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25

Maynard, Jake. "Barely Runnable." Appalachian Heritage 46, no. 2 (2018): 48–59. http://dx.doi.org/10.1353/aph.2018.0004.

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26

Coylewright, Megan, and Alexander M. Kowal. "Barely Contained." American Journal of Medicine 122, no. 6 (June 2009): 525–27. http://dx.doi.org/10.1016/j.amjmed.2009.03.007.

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27

Anderson, D. "Barely the Moon." Iowa Journal of Literary Studies 10, no. 1 (1989): 124. http://dx.doi.org/10.17077/0743-2747.1312.

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28

Peters, Tom. "Prometheus barely unbound." Academy of Management Perspectives 4, no. 4 (April 1990): 70–84. http://dx.doi.org/10.5465/ame.1990.4277211.

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29

Fingerhut, L. A. "The Barell matrix." Injury Prevention 8, no. 3 (September 1, 2002): 259. http://dx.doi.org/10.1136/ip.8.3.259.

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30

Magriel, Nicolas. "The Barhat Tree." Asian Music 28, no. 2 (1997): 109. http://dx.doi.org/10.2307/834476.

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31

Sampson, Fred. "Managing, just barely." Interactions 14, no. 1 (January 2007): 10–11. http://dx.doi.org/10.1145/1189976.1189986.

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32

Goodall, Christopher. "Managing, but barely coping." Nursing Standard 8, no. 5 (October 20, 1993): 51. http://dx.doi.org/10.7748/ns.8.5.51.s63.

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33

Holsti, Kal J., Jack Snyder, and Robert Jervis. "Barely Coping with Complexity." Mershon International Studies Review 38, no. 2 (October 1994): 285. http://dx.doi.org/10.2307/222726.

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34

Black, Donald D. "The Barkly West Declaration." Baptist Quarterly 34, no. 1 (January 1991): 43–45. http://dx.doi.org/10.1080/0005576x.1991.11751855.

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35

SENNETT, EDWARD J. "Fred C. Barald, MD." Radiology 181, no. 2 (November 1991): 609. http://dx.doi.org/10.1148/radiology.181.2.609-a.

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36

Christie, Christina A. "Interview With Eric Barela." American Journal of Evaluation 29, no. 4 (December 2008): 534–46. http://dx.doi.org/10.1177/1098214008328409.

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37

Currie, J. R. "Impossible Reconciliations (Barely Heard)." Music and Letters 88, no. 1 (October 25, 2006): 121–33. http://dx.doi.org/10.1093/ml/gcl075.

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38

Vinik, A. I. "Barely Scratching the Surface." Diabetes Care 33, no. 1 (December 29, 2009): 210–12. http://dx.doi.org/10.2337/dc09-2035.

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39

Shampo, Marc A., and Robert A. Kyle. "Charles Barkla—Nobel Laureate." Mayo Clinic Proceedings 68, no. 12 (December 1993): 1176. http://dx.doi.org/10.1016/s0025-6196(12)60068-8.

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40

Anagnostopoulou, Vlasia, Susmit Biswas, Heba Saadeldeen, Alan Savage, Ricardo Bianchini, Tao Yang, Diana Franklin, and Frederic T. Chong. "Barely alive memory servers." ACM Journal on Emerging Technologies in Computing Systems 8, no. 4 (October 2012): 1–20. http://dx.doi.org/10.1145/2367736.2367742.

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41

Membrey, Conducted by Jill. "Interview with Peter Barham." Physics Education 35, no. 2 (February 24, 2000): 139–42. http://dx.doi.org/10.1088/0031-9120/35/2/312.

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42

Ophir, Adi. "A Barely Visible Protagonist." differences 26, no. 2 (September 2015): 106–20. http://dx.doi.org/10.1215/10407391-3146009.

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43

Hogg, D. W. "A Barely Tested Hypothesis." Science 286, no. 5445 (November 26, 1999): 1679b—1679. http://dx.doi.org/10.1126/science.286.5445.1679b.

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44

Stephens, Richard. "On barely continuous functions." International Journal of Mathematics and Mathematical Sciences 11, no. 4 (1988): 695–99. http://dx.doi.org/10.1155/s0161171288000845.

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The term barely continuous is a topological generalization of Baire-1according toF. Gerlits of the Mathematical Institute of the Hungarian Academy of Sciences, and thus worthy of further study. This paper compares barely continuous functions and continuous functions on an elementary level. Knowing how the continuity of the identity function between topologies on a given set yields the lattice structure for those topologies, the barely continuity of the identity function between topologies on a given set is investigated and used to add to the structure of that lattice. Included are certain sublattices generated by the barely continuity of the identity function between those topologies. Much attention is given to topologies on finite sets.
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45

Kuzucuoğlu, M. "Barely transitive permutation groups." Archiv der Mathematik 55, no. 6 (December 1990): 521–32. http://dx.doi.org/10.1007/bf01191686.

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46

Loudon, Michael F. "The 'Barely Veiled Warning'." JAMA: The Journal of the American Medical Association 259, no. 7 (February 19, 1988): 1019. http://dx.doi.org/10.1001/jama.1988.03720070023027.

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47

Loudon, M. F. "The 'barely veiled warning'." JAMA: The Journal of the American Medical Association 259, no. 7 (February 19, 1988): 1019–20. http://dx.doi.org/10.1001/jama.259.7.1019.

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48

Yamana, Shoji. "Sense of Guilt Barely Dodged:." International Journal of Human Culture Studies 2016, no. 26 (2016): 551–71. http://dx.doi.org/10.9748/hcs.2016.551.

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49

Singh Patel, Anand. "FOLK ARTS OF BARELA TRIBE." International Journal of Research -GRANTHAALAYAH 7, no. 11 (November 30, 2019): 165–71. http://dx.doi.org/10.29121/granthaalayah.v7.i11.2019.3730.

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Tribal traditional arts are associated with some rituals and festivals. The arts prevalent in the folk, which involve deep process and growth of rituals, are folk arts that should be made as demonstrators. The display has full potential. They should try to give a demonstrative look. आदिवासी पारम्परिक कलाएँ किसी न किसी अनुष्ठान और पर्व.उत्सव से जुड़ी रहती है।लोक में प्रचलित कलाएँ जिनमें अनुष्ठान की गहरी प्रक्रिया और वृद्धि निहित होती है ऐसी लोक कलाएँ जो प्रदर्शनकारी के रूप में बनायी जानी चाहिए।ऐसी विधाएँ जिनमें अनुष्ठान बहुत कम हैं जिनमें प्रदर्शन की पूरी क्षमता है। उन्हें ही प्रदर्शनकारी रूप देने का प्रयास करना चाहिए।
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50

Downey, Rod, Geoffrey Laforte, and Steffen Lempp. "A set with barely degree." Journal of Symbolic Logic 64, no. 4 (December 1999): 1700–1718. http://dx.doi.org/10.2307/2586807.

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