메뉴 건너뛰기




Volumn 32, Issue 11, 2012, Pages 3591-3600

Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR;

EID: 84858047773     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.2908-11.2012     Document Type: Article
Times cited : (168)

References (57)
  • 1
    • 0034668801 scopus 로고    scopus 로고
    • Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats
    • Baker TL, Mitchell GS (2000) Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats. J Physiol 529:215-219.
    • (2000) J Physiol , vol.529 , pp. 215-219
    • Baker, T.L.1    Mitchell, G.S.2
  • 2
    • 0037101635 scopus 로고    scopus 로고
    • Phrenic long-term facilitation requires spinal serotonin receptor activation and protein synthesis
    • Baker-Herman TL, Mitchell GS (2002) Phrenic long-term facilitation requires spinal serotonin receptor activation and protein synthesis. J Neurosci 22:6239-6246.
    • (2002) J Neurosci , vol.22 , pp. 6239-6246
    • Baker-Herman, T.L.1    Mitchell, G.S.2
  • 4
    • 1442324486 scopus 로고    scopus 로고
    • Just one word: Plasticity
    • Blight AR (2004) Just one word: plasticity. Nat Neurosci 7:206-208.
    • (2004) Nat Neurosci , vol.7 , pp. 206-208
    • Blight, A.R.1
  • 5
    • 1642447131 scopus 로고    scopus 로고
    • Synaptic activity-independent persistent plasticity in endogenously active mammalian motoneurons
    • Bocchiaro CM, Feldman JL (2004) Synaptic activity-independent persistent plasticity in endogenously active mammalian motoneurons. Proc Natl Acad Sci U S A 101:4292-4295.
    • (2004) Proc Natl Acad Sci U S A , vol.101 , pp. 4292-4295
    • Bocchiaro, C.M.1    Feldman, J.L.2
  • 6
    • 72549109502 scopus 로고    scopus 로고
    • Strategies to restore motor functions after spinal cord injury
    • Boulenguez P, Vinay L (2009) Strategies to restore motor functions after spinal cord injury. Curr Opin Neurobiol 19:587-600.
    • (2009) Curr Opin Neurobiol , vol.19 , pp. 587-600
    • Boulenguez, P.1    Vinay, L.2
  • 7
    • 34047263255 scopus 로고    scopus 로고
    • Specific and artifactual labeling in the rat spinal cord and medulla after injection of monosynaptic retrograde tracers into the diaphragm
    • Boulenguez P, Gestreau C, Vinit S, Stamegna JC, Kastner A, Gauthier P (2007) Specific and artifactual labeling in the rat spinal cord and medulla after injection of monosynaptic retrograde tracers into the diaphragm. Neurosci Lett 417:206-211.
    • (2007) Neurosci Lett , vol.417 , pp. 206-211
    • Boulenguez, P.1    Gestreau, C.2    Vinit, S.3    Stamegna, J.C.4    Kastner, A.5    Gauthier, P.6
  • 8
    • 42749096670 scopus 로고    scopus 로고
    • Axonal growth therapeutics: Regeneration or sprouting or plasticity?
    • Cafferty WB, McGee AW, Strittmatter SM (2008) Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends Neurosci 31:215-220.
    • (2008) Trends Neurosci , vol.31 , pp. 215-220
    • Cafferty, W.B.1    McGee, A.W.2    Strittmatter, S.M.3
  • 10
    • 79957642986 scopus 로고    scopus 로고
    • Spinal vascular endothelial growth factor induces pireni motor facilitation via extracellular signalregulated kinase and Akt signaling
    • Dale-Nagle EA, Satriotomo I, Mitchell GS (2011) Spinal vascular endothelial growth factor induces pireni motor facilitation via extracellular signalregulated kinase and Akt signaling. J Neurosci 31:7682-7690.
    • (2011) J Neurosci , vol.31 , pp. 7682-7690
    • Dale-Nagle, E.A.1    Satriotomo, I.2    Mitchell, G.S.3
  • 11
    • 47849103782 scopus 로고    scopus 로고
    • Neuroinflammation and synaptic plasticity: Theoretical basis for a novel, immunecentered, therapeutic approach to neurological disorders
    • Di Filippo M, Sarchielli P, Picconi B, Calabresi P (2008) Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immunecentered, therapeutic approach to neurological disorders. Trends Pharm Sci 29:402-412.
    • (2008) Trends Pharm Sci , vol.29 , pp. 402-412
    • di Filippo, M.1    Sarchielli, P.2    Picconi, B.3    Calabresi, P.4
  • 14
    • 0037390475 scopus 로고    scopus 로고
    • Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia after cervical spinal cord injury
    • Fuller DD, Johnson SM, Olson EB Jr, Mitchell GS (2003) Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia after cervical spinal cord injury. J Neurosci 23:2993-3000.
    • (2003) J Neurosci , vol.23 , pp. 2993-3000
    • Fuller, D.D.1    Johnson, S.M.2    Olson Jr., E.B.3    Mitchell, G.S.4
  • 15
    • 33645808468 scopus 로고    scopus 로고
    • Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats
    • Fuller DD, Golder FJ, Olson EB Jr, Mitchell GS (2006) Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats. J Appl Physiol 100:800-806.
    • (2006) J Appl Physiol , vol.100 , pp. 800-806
    • Fuller, D.D.1    Golder, F.J.2    Olson Jr., E.B.3    Mitchell, G.S.4
  • 16
    • 15244344433 scopus 로고    scopus 로고
    • Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury
    • Golder FJ, Mitchell GS (2005) Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci 25:2925-2932.
    • (2005) J Neurosci , vol.25 , pp. 2925-2932
    • Golder, F.J.1    Mitchell, G.S.2
  • 17
    • 0035192159 scopus 로고    scopus 로고
    • Cervical spinal cord injury alters the pattern of breathing in anesthetized rats
    • Golder FJ, Reier PJ, Davenport PW, Bolser DC (2001a) Cervical spinal cord injury alters the pattern of breathing in anesthetized rats. J Appl Physiol 91:2451-2458.
    • (2001) J Appl Physiol , vol.91 , pp. 2451-2458
    • Golder, F.J.1    Reier, P.J.2    Davenport, P.W.3    Bolser, D.C.4
  • 18
    • 0035503406 scopus 로고    scopus 로고
    • Altered respiratory motor drive after spinal cord injury: Supraspinal and bilateral effects of a unilateral lesion
    • Golder FJ, Reier PJ, Bolser DC (2001b) Altered respiratory motor drive after spinal cord injury: supraspinal and bilateral effects of a unilateral lesion. J Neurosci 21:8680-8689.
    • (2001) J Neurosci , vol.21 , pp. 8680-8689
    • Golder, F.J.1    Reier, P.J.2    Bolser, D.C.3
  • 20
    • 0019475414 scopus 로고
    • The role of cervical afferent nerve fiber inhibition of the crossed phrenic phenomenon
    • Goshgarian HG (1981) The role of cervical afferent nerve fiber inhibition of the crossed phrenic phenomenon. Exp Neurol 72:211-225.
    • (1981) Exp Neurol , vol.72 , pp. 211-225
    • Goshgarian, H.G.1
  • 21
    • 0037310262 scopus 로고    scopus 로고
    • Plasticity in respiratory motor control-Invited review: The crossed phrenic phenomenon: A model for plasticity in the respiratory pathways following spinal cord injury
    • Goshgarian HG (2003) Plasticity in respiratory motor control-Invited review: the crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury. J Appl Physiol 94:795-810.
    • (2003) J Appl Physiol , vol.94 , pp. 795-810
    • Goshgarian, H.G.1
  • 22
    • 34848858683 scopus 로고    scopus 로고
    • Neurocognitive and behavioral morbidity in children with sleep disorders
    • Gozal D, Kheirandish-Gozal L (2007) Neurocognitive and behavioral morbidity in children with sleep disorders. Curr Opin Pulm Med 13:505-509.
    • (2007) Curr Opin Pulm Med , vol.13 , pp. 505-509
    • Gozal, D.1    Kheirandish-Gozal, L.2
  • 23
    • 0035313599 scopus 로고    scopus 로고
    • Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat
    • Gozal D, Daniel JM, Dohanich GP (2001) Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci 21:2442-2450.
    • (2001) J Neurosci , vol.21 , pp. 2442-2450
    • Gozal, D.1    Daniel, J.M.2    Dohanich, G.P.3
  • 24
    • 40749097184 scopus 로고    scopus 로고
    • Peripheral inflammation undermines the plasticity of the isolated spinal cord
    • Hook MA, Huie JR, Grau JW (2008) Peripheral inflammation undermines the plasticity of the isolated spinal cord. Behav Neurosci 122:233-249.
    • (2008) Behav Neurosci , vol.122 , pp. 233-249
    • Hook, M.A.1    Huie, J.R.2    Grau, J.W.3
  • 25
    • 0036976969 scopus 로고    scopus 로고
    • Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats
    • Kaegi S, Schwab ME, Dietz V, Fouad K (2002) Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats. Eur J Neurosci 16:249-258.
    • (2002) Eur J Neurosci , vol.16 , pp. 249-258
    • Kaegi, S.1    Schwab, M.E.2    Dietz, V.3    Fouad, K.4
  • 26
    • 59749086321 scopus 로고    scopus 로고
    • Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats
    • Kanagal SG, Muir GD (2009) Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats. Exp Neurol 216:193-206.
    • (2009) Exp Neurol , vol.216 , pp. 193-206
    • Kanagal, S.G.1    Muir, G.D.2
  • 27
    • 34247523363 scopus 로고    scopus 로고
    • Adaptive depression in synaptic transmission in the nucleus of the solitary tract after in vivo chronic intermittent hypoxia: Evidence for homeostatic plasticity
    • Kline DD, Ramirez-Navarro A, Kunze DL (2007) Adaptive depression in synaptic transmission in the nucleus of the solitary tract after in vivo chronic intermittent hypoxia: evidence for homeostatic plasticity. J Neurosci 27:4663-4673.
    • (2007) J Neurosci , vol.27 , pp. 4663-4673
    • Kline, D.D.1    Ramirez-Navarro, A.2    Kunze, D.L.3
  • 29
    • 0027991346 scopus 로고
    • Serotonin reveals ineffective spinal pathways to contralateral phrenic motoneurons in spinally hemisected rats
    • Ling L, Bach KB, Mitchell GS (1994) Serotonin reveals ineffective spinal pathways to contralateral phrenic motoneurons in spinally hemisected rats. Exp Brain Res 101:35-43.
    • (1994) Exp Brain Res , vol.101 , pp. 35-43
    • Ling, L.1    Bach, K.B.2    Mitchell, G.S.3
  • 30
    • 0035879152 scopus 로고    scopus 로고
    • Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing
    • Ling L, Fuller DD, Bach KB, Kinkead R, Olson EB Jr, Mitchell GS (2001) Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J Neurosci 21:5381-5388.
    • (2001) J Neurosci , vol.21 , pp. 5381-5388
    • Ling, L.1    Fuller, D.D.2    Bach, K.B.3    Kinkead, R.4    Olson Jr., E.B.5    Mitchell, G.S.6
  • 31
    • 33749368928 scopus 로고    scopus 로고
    • Serotonininduced in vitro long-term facilitation exhibits differential pattern sensitivity in cervical and thoracic inspiratory motor output
    • Lovett-Barr MR, Mitchell GS, Satriotomo I, Johnson SM (2006) Serotonininduced in vitro long-term facilitation exhibits differential pattern sensitivity in cervical and thoracic inspiratory motor output. Neuroscience 142:885-892.
    • (2006) Neuroscience , vol.142 , pp. 885-892
    • Lovett-Barr, M.R.1    Mitchell, G.S.2    Satriotomo, I.3    Johnson, S.M.4
  • 32
    • 70649112429 scopus 로고    scopus 로고
    • Episodic spinal serotonin receptor activation elicits long-lasting phrenic motor facilitation by an NADPH oxidase-dependent mechanism
    • MacFarlane PM, Mitchell GS (2009) Episodic spinal serotonin receptor activation elicits long-lasting phrenic motor facilitation by an NADPH oxidase-dependent mechanism. J Physiol 587:5469-5481.
    • (2009) J Physiol , vol.587 , pp. 5469-5481
    • Macfarlane, P.M.1    Mitchell, G.S.2
  • 34
    • 33846188463 scopus 로고    scopus 로고
    • Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea?
    • Mahamed S, Mitchell GS (2007) Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea? Exp Physiol 92:27-37.
    • (2007) Exp Physiol , vol.92 , pp. 27-37
    • Mahamed, S.1    Mitchell, G.S.2
  • 35
    • 68249115332 scopus 로고    scopus 로고
    • Retrograde labeling of phrenic motoneurons by intrapleural injection
    • Mantilla CB, Zhan WZ, Sieck GC (2009) Retrograde labeling of phrenic motoneurons by intrapleural injection. J Neurosci Methods 182:244-249.
    • (2009) J Neurosci Methods , vol.182 , pp. 244-249
    • Mantilla, C.B.1    Zhan, W.Z.2    Sieck, G.C.3
  • 36
    • 0037214068 scopus 로고    scopus 로고
    • Neuroplasticity in respiratory motor control
    • Mitchell GS, Johnson SM (2003) Neuroplasticity in respiratory motor control. J Appl Physiol 94:358-374.
    • (2003) J Appl Physiol , vol.94 , pp. 358-374
    • Mitchell, G.S.1    Johnson, S.M.2
  • 38
    • 34147176469 scopus 로고    scopus 로고
    • Dorsolateral cervical spinal injury differentially affects forelimb and hindlimb action in rats
    • Muir GD, Webb AA, Kanagal S, Taylor L (2007) Dorsolateral cervical spinal injury differentially affects forelimb and hindlimb action in rats. Eur J Neurosci 25:1501-1510.
    • (2007) Eur J Neurosci , vol.25 , pp. 1501-1510
    • Muir, G.D.1    Webb, A.A.2    Kanagal, S.3    Taylor, L.4
  • 39
    • 0035126856 scopus 로고    scopus 로고
    • Alkylxanthine-induced recovery of respiratory function following cervical spinal cord injury in adult rats
    • Nantwi KD, Goshgarian HG (2001) Alkylxanthine-induced recovery of respiratory function following cervical spinal cord injury in adult rats. Exp Neurol 168:123-134.
    • (2001) Exp Neurol , vol.168 , pp. 123-134
    • Nantwi, K.D.1    Goshgarian, H.G.2
  • 41
    • 45149086674 scopus 로고    scopus 로고
    • Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia
    • Pawar A, Peng YJ, Jacono FJ, Prabhakar NR (2008) Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia. J Appl Physiol 104:1287-1294.
    • (2008) J Appl Physiol , vol.104 , pp. 1287-1294
    • Pawar, A.1    Peng, Y.J.2    Jacono, F.J.3    Prabhakar, N.R.4
  • 43
    • 0035702405 scopus 로고    scopus 로고
    • Chronic intermittent hypoxia enhances carotid body chemoreceptor response to low oxygen
    • Peng Y, Kline DD, Dick TE, Prabhakar NR (2001) Chronic intermittent hypoxia enhances carotid body chemoreceptor response to low oxygen. Adv Exp Med Biol 499:33-38.
    • (2001) Adv Exp Med Biol , vol.499 , pp. 33-38
    • Peng, Y.1    Kline, D.D.2    Dick, T.E.3    Prabhakar, N.R.4
  • 44
    • 16244423295 scopus 로고    scopus 로고
    • Treadmill training ameliorates dopamine loss but not behavioral deficits in hemi-parkinsonian rats
    • Poulton NP, Muir GD (2005) Treadmill training ameliorates dopamine loss but not behavioral deficits in hemi-parkinsonian rats. Exp Neurol 193:181-197.
    • (2005) Exp Neurol , vol.193 , pp. 181-197
    • Poulton, N.P.1    Muir, G.D.2
  • 45
    • 2542432073 scopus 로고    scopus 로고
    • Oxidative stress in the systemic and cellular responses to intermittent hypoxia
    • Prabhakar NR, Kumar GK (2004) Oxidative stress in the systemic and cellular responses to intermittent hypoxia. Biol Chem 385:217-221.
    • (2004) Biol Chem , vol.385 , pp. 217-221
    • Prabhakar, N.R.1    Kumar, G.K.2
  • 46
    • 20344369336 scopus 로고    scopus 로고
    • Cardiovascular alterations by chronic intermittent hypoxia: Importance of carotid body chemoreflexes
    • Prabhakar NR, Peng YJ, Jacono FJ, Kumar GK, Dick TE (2005) Cardiovascular alterations by chronic intermittent hypoxia: importance of carotid body chemoreflexes. Clin Exp Pharmacol Physiol 32:447-449.
    • (2005) Clin Exp Pharmacol Physiol , vol.32 , pp. 447-449
    • Prabhakar, N.R.1    Peng, Y.J.2    Jacono, F.J.3    Kumar, G.K.4    Dick, T.E.5
  • 47
    • 0035319602 scopus 로고    scopus 로고
    • Plasticity of motor systems after incomplete spinal cord injury
    • Raineteau O, Schwab ME (2001) Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2:263-273.
    • (2001) Nat Rev Neurosci , vol.2 , pp. 263-273
    • Raineteau, O.1    Schwab, M.E.2
  • 48
    • 0033812170 scopus 로고    scopus 로고
    • Progress in spinal cord research: A refined strategy for the international spinal research trust
    • Ramer MS, Harper GP, Bradbury EJ (2000) Progress in spinal cord research: a refined strategy for the international spinal research trust. Spinal Cord 38:449-472.
    • (2000) Spinal Cord , vol.38 , pp. 449-472
    • Ramer, M.S.1    Harper, G.P.2    Bradbury, E.J.3
  • 49
    • 7444220066 scopus 로고    scopus 로고
    • Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia
    • Rey S, Del Rio R, Alcayaga J, Iturriaga R (2004) Chronic intermittent hypoxia enhances cat chemosensory and ventilatory responses to hypoxia. J Physiol 560:577-586.
    • (2004) J Physiol , vol.560 , pp. 577-586
    • Rey, S.1    del Rio, R.2    Alcayaga, J.3    Iturriaga, R.4
  • 50
    • 60649085826 scopus 로고    scopus 로고
    • Obstructive sleep apnea and pulmonary hypertension
    • Sajkov D, McEvoy RD (2009) Obstructive sleep apnea and pulmonary hypertension. Prog Cardiovasc Dis 51:363-370.
    • (2009) Prog Cardiovasc Dis , vol.51 , pp. 363-370
    • Sajkov, D.1    McEvoy, R.D.2
  • 51
    • 84856361151 scopus 로고    scopus 로고
    • Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury
    • Trumbower RD, Jayaraman A, Mitchell GS, Rymer WZ (2012) Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair 26:163-172.
    • (2012) Neurorehabil Neural Repair , vol.26 , pp. 163-172
    • Trumbower, R.D.1    Jayaraman, A.2    Mitchell, G.S.3    Rymer, W.Z.4
  • 52
    • 72049104808 scopus 로고    scopus 로고
    • Intermittent hypoxia induces functional recovery following cervical spinal injury
    • Vinit S, Lovett-Barr MR, Mitchell GS (2009) Intermittent hypoxia induces functional recovery following cervical spinal injury. Respir Physiol Neurobiol 169:210-217.
    • (2009) Respir Physiol Neurobiol , vol.169 , pp. 210-217
    • Vinit, S.1    Lovett-Barr, M.R.2    Mitchell, G.S.3
  • 53
    • 79954961324 scopus 로고    scopus 로고
    • Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia
    • Vinit S, Windelborn JA, Mitchell GS (2011) Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia. Respir Physiol Neurobiol 176:130-135.
    • (2011) Respir Physiol Neurobiol , vol.176 , pp. 130-135
    • Vinit, S.1    Windelborn, J.A.2    Mitchell, G.S.3
  • 54
    • 0043235662 scopus 로고    scopus 로고
    • Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat
    • Webb AA, Muir GD (2003) Unilateral dorsal column and rubrospinal tract injuries affect overground locomotion in the unrestrained rat. Eur J Neurosci 18:412-422.
    • (2003) Eur J Neurosci , vol.18 , pp. 412-422
    • Webb, A.A.1    Muir, G.D.2
  • 55
    • 64249165170 scopus 로고    scopus 로고
    • Preconditioning with daily acute intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation in Brown Norway rats
    • Wilkerson JE, Mitchell GS (2009) Preconditioning with daily acute intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation in Brown Norway rats. Exp Neurol 217:116-123.
    • (2009) Exp Neurol , vol.217 , pp. 116-123
    • Wilkerson, J.E.1    Mitchell, G.S.2
  • 56
    • 2942668297 scopus 로고    scopus 로고
    • Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea
    • Xu W, Chi L, Row BW, Xu R, Ke Y, Xu B, Luo C, Kheirandish L, Gozal D, Liu R (2004) Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. Neuroscience 12:313-323.
    • (2004) Neuroscience , vol.12 , pp. 313-323
    • Xu, W.1    Chi, L.2    Row, B.W.3    Xu, R.4    Ke, Y.5    Xu, B.6    Luo, C.7    Kheirandish, L.8    Gozal, D.9    Liu, R.10
  • 57
    • 33746602312 scopus 로고    scopus 로고
    • Effects of intermittent hypoxia on pulmonary haemodynamics
    • Zieliński J (2005) Effects of intermittent hypoxia on pulmonary haemodynamics. Pneumonol Alergol Pol 73:86-93.
    • (2005) Pneumonol Alergol Pol , vol.73 , pp. 86-93
    • Zieliński, J.1


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.