Location of Repository

Expression of corticotrophin-releasing hormone receptor subtypes in human myometrium and cloning of the promoter region for the CRH receptors type 2

By Jing Chen

Abstract

Corticotrophin releasing hormone (CRH) and CRH receptor (CRH-R) appear to play a number of important roles in human pregnancy. The purpose of the first part of my project was to clone and sequence CRH-R subtypes from human myometrial biopsies. In order to understand the molecular mechanisms that direct the expression of the CRH-R gene, the objective of the second part of my research project was to clone and characterise the promoter region of the human CRH-R2 gene.\ud \ud Our results demonstrated the presence of multiple CRH-R mRNAs in the human myometrium. Six subtypes of the CRH receptor, 1a, 1b, 1c, 2a, 2b, and 2g, were found in the pregnant human myometrium, whereas only three subtypes, 1a, 1b, and 2b were found in the nonpregnant myometrium. Multiple CRH-R mRNAs have been identified in human myometrium with differential expression pattern during pregnancy, which argues for multiple roles for CRH and/or related peptides in myometrial function and suggests distinct functional roles for each receptor during pregnancy. These findings suggest that CRH and its receptor play an important modulatory role in myometrial function.\ud \ud The genomic organisation of human CRH-R2 alternative exons has been determined in the project. The coding region of the gene spans over 18kb. The genomic orders of the alternative exons are CRH-R2b-2g-2a. The 5'-flanking region of the human CRH-R2 gene was cloned by the genomic walking method. Using 5'RACE, the transcription start sites were mapped. The results suggest that there may be a single promoter regulating the expression of all (2a, 2b and 2g) subtypes. The CRH-R2 5'-flanking sequence has many characteristics of the housekeeping gene promoter. Therefore, we speculated that the strong and housekeeping gene-like activity of the CRH-2R gene promoter may contribute to the ubiquitous expression of the CRH-R2 gene. For functional analysis, 5'-flanking sequences up to-1393 bp were fused to the Chloramphenicol acetyltransferase (CAT) gene and tested using a HEK-293 cell line by transfection CAT assays. The results confirmed that the DNA region indicated demonstrated strong basal promoter activity

Topics: QP, QH426
OAI identifier: oai:wrap.warwick.ac.uk:3084

Suggested articles

Preview

Citations

  1. (1999). 7TM receptors: the splicing on the cake. Trends Pharmacol. doi
  2. (1982). A catalogue of splice junction sequences. doi
  3. (1987). A cellular protein, activating transcription factor, activates transcription of multiple EIA-inducible adenovirus early promoters. doi
  4. (1988). A constitutive promoter directs expression of the nerve growth factor receptor gene.
  5. (1986). A cyclic AMP - and phorbol ester-inducible DNA element. doi
  6. (1990). A developmentally regulated trans-acting factor recognizes dissimilar GC-rich elements controlling a class of cAMP-inducible Dictyostelium genes. Genes Dev. doi
  7. (1989). A molecular basis for bidirectional communication between the immune and neuroendocrine system. doi
  8. (1993). A mutation-induced activated state of the 02-adrenergic receptor. Extending the ternary complex model.
  9. (1991). A new cationic liposome reagent mediating nearly quantitative transfection of animal cells.
  10. (1997). A new functional isoforms of the human CRF2 receptor for corticotropin-releasing factor. doi
  11. (1995). A new type of human calcitonin receptor isoform generated by alternative splicing. doi
  12. (1999). A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes. doi
  13. (1995). A placental clock controlling the length of human pregnancy. doi
  14. (1995). A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle. doi
  15. (1991). A structural taxonomy of DNA binding domains. doi
  16. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. doi
  17. (1994). A variant of the human corticotropin-releasing factor (CRF) receptor: cloning, expression and pharmacology. doi
  18. (1991). Activation of junB by PKC and PKA signal transduction through a novel cis-acting element. doi
  19. (1999). Activation of protein kinase C by oxytocin inhibits the biological activity of the human myometrial corticotropinreleasing hormone receptor at term. doi
  20. (1991). AG protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. doi
  21. (1981). Amino acid composition and sequence analysis of sauvagion, a new active peptide from the skin of Phyllomedusa sauvagei. doi
  22. (1988). Analysis of the cAMP dependent protein kinase system using molecular genetic approaches. doi
  23. (1991). Analysis of the DNA-binding and activation properties of the human transcription factor AP-2. doi
  24. (1996). bZip proteins. doi
  25. (1990). cAMP-dependent transcription of the human CYP21B (P-450C21) gene requires a cis-regulatory element distinct from the consensus cAMP-regulatory element.
  26. (1981). Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and ß-endorphin. doi
  27. (1987). Characterization of corticotronpin releasing factor receptor-mediated adenylate cyclase activity in the rat central nervous system. Synpse doi
  28. (1986). Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoterregulatory region. II. Identification of cAMP and glucocorticoid regulatory domains.
  29. (1995). Characterization of the rat vasoactive intestinal polypeptide receptor gene 5'region. doi
  30. (1983). Chemical and biological characterization of corticotropin- releasing factor. Recent Prog. doi
  31. (1995). Cloning and characterization of a functionally distinct corticopin releasing factor receptor subtype from rat brain. doi
  32. (1999). Cloning and characterization of a short variant of the corticotronpin-releasing factor receptor subtype from rat amygdala. doi
  33. (1994). Cloning and characterization of an abundant subtype of the human calcitonin receptor.
  34. (1991). Cloning and characterization of the cDNA for human and rat corticotropinreleasing factor-binding proteins. doi
  35. (1996). Cloning and characterization of the human corticotropinreleasing factor-2 receptor complementary deoxyribonucleic acid. doi
  36. (1996). Cloning and characterization of the signal transduction of four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor. Evidence for dual coupling to adenylate cyclase and phospholipase doi
  37. (1996). Cloning and charaterization of human urocortin. doi
  38. (1988). Cloning and expression of AP-2, a cell-type-specific transcription factor that activates inducible enhancer elements. doi
  39. (1993). Cloning and functional expression of a rat brain corticotropin-releasing factor (CRF) receptor. doi
  40. (1988). Cloning and sequence analysis of cDNA for corticotropin releasing factor precursor from the teleost fish Catastomus commersoni. doi
  41. (1994). Cloning PCR products. In: PCR Technology: Current Innovation. Ist eds,
  42. (1982). Comparison of the biologic actions of corticotrophin-releasing factor and sauvagin. doi
  43. (1982). Complete amino acid sequence of urotensin-1, a hypotensive and corticotronpin releasing neuropeptide from Catostomus. doi
  44. (1996). Core promoters and transcriptional control. Trends Genet. doi
  45. (1998). Corticotrophin releasing hormone, receptor regulation and the stress response. doi
  46. (1997). Corticotrophin-releasing factor and endocrine responses to stress: CEF receptors, binding protein, and related peptides. Experimental Biology and Medicine. doi
  47. (1986). Corticotropin-releasing factor binding to the anterior pituitary receptor is modulated by divalent cations and guanyl nucleotides. doi
  48. (1983). Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study.
  49. (1996). Corticotropin-releasing factor receptor: from molecular biology to drug design. Trends in Pharmacol Sci. doi
  50. (1995). Corticotropin-releasing factor receptor: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. doi
  51. (1993). Corticotropin-releasing factor-binding protein: A putative peripheral and central modulator of the CRF family of neuropeptides. doi
  52. (1994). Corticotropin-releasing hormone and beta-endorphin in labour. doi
  53. (1993). Corticotropin-releasing hormone binding protein (CRH-BP): plasma levels decrease during the third trimester of normal human pregnancy. doi
  54. (1992). Corticotropin-releasing hormone in humans. doi
  55. (1994). Corticotropin-releasing hormone increases prostaglandin F2a activity on human myometrium in vitro. doi
  56. (1994). Corticotropin-releasing hormone-induced vasodilatation in the human fetal placental circulation. doi
  57. (1985). Corticotropinreleasing factor, sauvagine and urotensin 1: effects on blood flow.
  58. (1998). Cortitropin-releasing hormone receptor subtype 1 is significantly up-regulated at the time of labour in the human myometrium. doi
  59. (1986). CpG-rich island and the function of DNA methylation. doi
  60. (1991). CREM gene: use of alternative DNA binding domains generates multiple antagonists of cAMP-induced transcription. doi
  61. (1995). CRF20C and CRF20 receptor mRNAs are differentially distributed between the rat central nervous system and peripheral tissues. doi
  62. (1991). Cross-family dimerization of transcription factors Fos/Jun and ATF/CRE alters DNA binding specificity. doi
  63. (1988). Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins. doi
  64. (1987). Cyclic AMP regulation of the human glycoprotein hormone alpha-subunit gene is mediated by an 18-base-pair element. doi
  65. Cyclic AMP-responsive DNA -binding protein: structure based on a cloned placental cDNA. doi
  66. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis. doi
  67. (1993). Differential signal transduction by five splice variants of the PACAP receptor. doi
  68. (1989). Differentiationinduced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. doi
  69. (1994). Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. doi
  70. (1995). Distribution of mRNAs encoding two distints CRF receptors in brain and pituitary of rat and mouse. 77th Annual Meeting of the Endocrine Society.
  71. (1983). DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. doi
  72. (1977). DNA sequencing with chainterminating inhibitors.
  73. (1992). Efficient large-scale sequencing of the escherichia coli genome: implementation of transponson-and PCR-based strategy for the analysis of order ? phage clones. doi
  74. (1998). Enhanceosome and transcriptional synergy. doi
  75. (1988). Enhancer sequences and the regulation of gene transcription. doi
  76. (1987). Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta. doi
  77. (1991). Exon amplification: A strategy to isolate mammalian genes based on RNA splicing. doi
  78. (1995). Exposure to an antisense oligonucleotide decreases corticotropin-releasing factor receptor binding in rat pituitary cultures. doi
  79. (1993). Expression cloning of a human corticotropin-releasing factor receptor. doi
  80. (1995). Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction. doi
  81. (1995). Functionally different isoforms of the human calcitonin receptor result from alternative splicing of the gene transcript. doi
  82. (1988). Genetic applications of an inverse polymerase chain reaction.
  83. (1997). Genomic organization of the rat pituitary adenylate cyclase-activating polypetide receptor gene. doi
  84. (1995). Helix-loop-helix. Protein profile.
  85. (1989). Heterogeneity between brain and pituitary corticotropin-releasing factor receptor is due to differential glycosylation. doi
  86. (1998). Hormone response units: one plus one equals more than two.
  87. (1994). Human corticotropin-releasing hormone receptor gene (CRHR) is located on the long arm of chromosome 17(17g12-qter). Chromosome Res. doi
  88. (1998). Human CRH receptor: differences in subtype expression between pregnant and non-pregnant myometrium. doi
  89. (1998). Human genome, chromosomes, and genes. doi
  90. (1955). Humoral hypothalamic control of anterior pituitary: a study with combined tissue cultures. doi
  91. (1992). Identification and characterization of the GC-rich and cyclic adenosin 3'S'-monophosphate (cAMP)-inducible promoter of the type IIB cAMP-dependent protein kinase regulatory subunit gene. doi
  92. (1986). Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. doi
  93. (1995). Identification of a novel murine receptor for corticotropin releasing hormone expressed in heart. doi
  94. (1987). Identification of a region in the human vasoactive intestinal polypeptide gene responsible for regulation by cyclic AMP.
  95. (1995). Identification of a second corticotropinreleasing factor receptor gene and characterization of a cDNA expressed in heart. doi
  96. (1993). Identification of a seven trans-membrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. doi
  97. (1995). Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormonereleasing hormone receptor in human pituitary adenomas. doi
  98. (1995). Identification of multiple human calcitonin receptor isoforms: Heterologous expression and pharmacological characterization. doi
  99. Identification of two corticotropin-releasing factor receptors from Xenopus laevis with 195 high ligand selectivity: unusual pharmacology of the type 1 receptor. doi
  100. (1983). Identification of two distinct regulatory regions adjacent to the human n-interferon gene. doi
  101. (1989). Immunoreactive corticotropinreleasing hormone, adrenocorticotropin and cortisol in human plasma during pregnancy and delivery and postpartum. doi
  102. (1989). Improved double stranded sequencing using the linear polymerase chain reaction. doi
  103. (1983). In vitro and in vivo ACTHreleasing activity of ovine CRF, sauvagine and urotensin-1. doi
  104. (1970). Induction of labour with prostaglandin E2. doi
  105. (1988). Interaction of a common cellular transcription factor, ATF, with regulatory elements in both Elaand cyclic AMP-inducible promoters. doi
  106. (1989). Isolation and identification of a diuretic hormone from the tobacco hornworm, Manduca sexta. doi
  107. (1991). Isolation and identification of a new diuretic peptide from the tobacco hornworm, Manduca sexta. doi
  108. (1994). Isolation, characterization, and chromosomal localization of the porcine calcitonin receptor gene. Identification of two variants of the receptor generated by alternative splicing.
  109. (1995). Ligand requirements of the human corticotropin releasing factor-binding protein. doi
  110. (1991). Ligation-mediated PCR: applications to genomic footprinting. doi
  111. (1989). Local stimulation of prostaglandin production by corticotropin-releasing hormone in human fetal membranes and placenta. doi
  112. (1995). Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression.
  113. (1997). Localization of the human CRF2 receptor to 7p21-p15 by radiation hybrid mapping and FISH analysis. doi
  114. (1995). MATIND and MATINSPECTOR- new fast and versatile tools for detection of consensus matches in nucleotide sequence data. doi
  115. (1990). Mechanism of transcriptional activation by Spl: evidence for coactivators. doi
  116. (1987). Mechanisms of action of CRF and other regulators of ACTH release in pituitary corticotrophins. Ann New York Acad Sei. doi
  117. (1998). Mechanisms of hormone action. doi
  118. (1995). Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids. doi
  119. (1991). Molecular cloning and expression of a cDNA encoding the secretin receptor.
  120. (1992). Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. doi
  121. (1995). Molecular cloning and functional expression of a third isoform of the human calcition receptor and partial characterization of the calcitonin receptor gene. doi
  122. (1996). Molecular cloning of a type A chicken corticotropin-releasing factor receptor with high affinity for urotensin I. doi
  123. (1989). Molecular Cloning: A Laboratory manual. 2nd edn, Edted by doi
  124. (1998). Molecular identification and analysis of a novel human corticotropin-releasing factor receptor: The CRF2y receptor. doi
  125. (1989). Multiple sequence elements in the c-fos promoter mediate induction by cAMP. doi
  126. (1997). Multiple steroidogenic factor 1 binding elements in the human steroidogenic acute regulatory protein gene 5'-flanking region are required for maximal promoter activity and cyclic AMP responsiveness. doi
  127. (1993). Nephrogenic diabetes insipidus. A vasopressin receptor unable to stimulate adenylyl cyclase. doi
  128. (1948). Neural control of the pituitary gland. doi
  129. (1991). NF-1 proteins from brain interact with the proenkephalin cAMP inducible enhancer. doi
  130. (1991). Novel cyclic adenosine 3', 5'-monophosphate response element in the human chorionic gonadotropin ß-subunit gene. doi
  131. (1991). Oligodoxynucleotide ligation to sscDNAs: A new tool for cloning 5'ends of mRNA and for constructing cDNA libraries by in vitro amplification. doi
  132. (1994). One armed PCR (OA-PCR): amplification of genomic DNA from a single primer domain. doi
  133. (1989). One-sided polymerase chain reaction: the amplification of cDNA. doi
  134. (1982). Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labour. doi
  135. (1982). Oxytocin, prostaglandins, and contractility of the human uterus at term pregnancy. Act Obstet Gynaecol Scandinav. doi
  136. (1995). Parathyroid hormone/parathyroidhormone-related peptide receptor gene transcripts are expressed from tissue-specific and ubiquitous promoters. doi
  137. (1987). Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. doi
  138. (1990). Physiological and behavioral responses to corticotrophin releasing factor administration: is CRF a mediator of anxiety of stress responses? Brain Res. doi
  139. (1995). Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Frontiers Neuroendocrinol. doi
  140. (1995). Placental corticotropin-releasing hormone: there by accident or design? doi
  141. (1987). Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. doi
  142. (1989). Polymerase chain reaction with single-side specificity: analysis of T cell receptor 8 chain. doi
  143. (1987). Positive and negative regulation of transcription in vitro: enhancer binding protein AP-2 is inhibited by SV40 T antigen. doi
  144. Possible placental origin of ACTH in normal human pregnancy. doi
  145. (1993). Primary structure and functional expression of mouse pituitary and human brain corticotropin-releasing factor receptors. doi
  146. (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. doi
  147. (1995). Proopioomelanocortin, corticotropin-releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin. doi
  148. (1988). Proteins bound at adjacent DNA elements act synerhistically to regulate human proenkephalin cAMP inducible transcription.
  149. (1991). Random-primed cDNA synthesis facilitates the isolation of multiple 5'-cDNA ends by RACE. doi
  150. (1992). Rapid isolation of flanking genomic DNA using Biotin-RAGE, a variation of single-sided polymerase chain reaction. doi
  151. (1988). Rapid production of fulllength cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. doi
  152. (1992). Receptor effector coupling by G proteins: implications for normal and abnormal signal transduction. doi
  153. (1982). Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
  154. (1984). Relationship between internalization and calcitonin-induced receptor loss in T47D cells. doi
  155. (1995). Revolutions in rapid amplification of cDNA ends: new strategies for polymerase chain reaction cloning of full-length cDNA end. doi
  156. (1992). Role for cyclic adenosine monophosphate in the synergistic interaction between oxytocin and corticotropinreleasing factor in isolated human gestational myometrium. doi
  157. (1992). Roles of TATA and initiator elements in determining the start site location and direction of RNA polymerase II transcription.
  158. (1977). Screening lambda GT recombinant clones by hybridization to single plaques in situ. doi
  159. (1992). Sequence alignment of the G-protein coupled receptor superfamily. doi
  160. (1998). Sequence and activity of parthyroid hormone/parathyroidhormone-related peptide receptor promoter region in the human osteoblast-like cells. doi
  161. (1995). Signalling properties of mouse and human corticotropin-releasing factor (CRF) receptors: decreased coupling efficiency of human type II CRF receptor. doi
  162. (1993). Steroid and related receptors. doi
  163. (1993). Steroidogenic factor 1, an orphan nuclear receptor, regulates the expression of the rat aromatase gene in gonadal tissues. doi
  164. (1995). Stress-induced genetic expression of a selective corticotropin-releasing factor receptor subtype within the rat ovaries: An effect dependent on the ovulatory cycle. doi
  165. (1991). Structure and function of signal transducing GTP-binding proteins. doi
  166. (1998). Structure and regulation of the human growth hormone-releasing hormone receptor gene. doi
  167. (1995). Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene. doi
  168. (1991). Structures of regulatory regions in the human cytochrome p-450scc (desmolase) gene. doi
  169. (1989). The "initiator" as a transcription control element. doi
  170. (1993). The activation and activity control of AP-1 doi
  171. (1996). The biological activity of the corticotropin-releasing hormone receptor-adenylate cyclase complex in human myometrium is reduced at the end of pregnancy. doi
  172. (1991). The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase
  173. (1996). The deletion of 14 amino acids in the seventh transmembrane domain of a naturally occurring calcitionin receptor isoform alters ligand binding and selectively abolishes coupling to phospholipase doi
  174. (1982). The distribution of corticotropin-releasing factor-like immunoreactive neurons in rat brain. doi
  175. (1998). The genomic organization of the human corticopin-releasing factor type-1 receptor. doi
  176. (1996). The genomic structure of the rat corticotropin-releasing factor receptor. A member of the class II G proptein -coupled receptors. doi
  177. (1994). The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization. doi
  178. (1994). The human myometrial CRH receptor: G Proteins and second messengers. doi
  179. (1998). The human placenta and fetal membranes express the corticotropin-releasing hormone receptor la (CRH-Rl(x) and the CRH-C variant receptor. doi
  180. (1999). The human secretin receptor gene: genomic organization and promoter characterization. doi
  181. (1993). The identification of a human myometrial corticotropin-releasing hormone 198 receptor that increases in a affinity during pregnancy. doi
  182. (1995). The myometrium expresses multiple isoforms of the corticotropin-releasing hormone receptor. doi
  183. (1996). The orphan nuclear receptor steroidogenic factor-1 regulates the cyclic adenosine 3', 5'-monophosphate-mediated transcriptional activation of rat cytochrome P450c 17 (17 alpha-hydroxylase/c 17-20 lyase). doi
  184. (1994). The rat, mouse and human genes encoding the receptor for parathyroid hormone and parathyroid hormone-related peptide are highly homologous. doi
  185. (1992). The regulation of transcription by phosphorylation. doi
  186. (1998). The sequence of Homo sapiens PAC clone RP5-1143H19. Unpublished GenBank accession No.
  187. (1987). Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. doi
  188. (1995). Transcription factors responsive to cAMP. doi
  189. (1997). Transcription factors. doi
  190. (1997). Transcriptional regulation by the Sp family proteins. doi
  191. (1990). Transcriptional regulation of the bovine CYP17 (P-450 (17) Alpha) gene. Identification of two cAMP regulatory regions lacks the consensus cAMP-responsive element (CRE).
  192. (1993). Understanding the homeodomain.
  193. (1991). Unregulated expression of c-jun or c-fos proteins but not jun D inhibits oestrogen receptor activity in human breast cancer derived cells.
  194. (1996). Urocortin interaction with corticotropin-releasing factor (CRF) binding protein: A novel mechanism for elevating "free" CRF levels in human brain. doi
  195. (1995). Urocortin, a mammalian neuro-peptide related to fish urotensin I and to corticotropin- releasing factor. doi
  196. (1983). Very short repeats and coordinate induction of genes. doi
  197. (1995). Wholegenome random sequencing and assembly of haemophilus influenzaerd.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.