ÖZGEÇMİŞ. İlkokul : Kazımkarabekir İlkokulu / Karaman (Mezuniyet: 1992) Ortaokul : Karaman Anadolu Lisesi / Antalya (Mezuniyet: 1996)

Transkript

1 ÖZGEÇMİŞ 1. Adı, Soyadı Yusuf ÖZKAY 2. Doğum Yeri ve Yılı Karaman 20 Mart Çalışmakta Olduğu Birim Anadolu Üniversitesi Eczacılık Fakültesi 4. Ayrıntılı Öğrenim Geçmişi İlkokul : Kazımkarabekir İlkokulu / Karaman (Mezuniyet: 1992) Ortaokul : Karaman Anadolu Lisesi / Antalya (Mezuniyet: 1996) Lise : Karaman Anadolu Lisesi / Antalya (Mezuniyet: 1999) Lisans : Anadolu Üniversitesi Eczacılık Fakültesi / Eskişehir (Mezuniyet: 2003) Yüksek Lisans: Anadolu Üniversitesi Sağlık Bilimleri Enstitüsü Farmasötik Kimya ABD / Eskişehir (Mezuniyet: 2005) Doktora : Anadolu Üniversitesi Sağlık Bilimleri Enstitüsü Farmasötik Kimya ABD / Eskişehir (Mezuniyet: 2009) 5. Akademik Ünvanlar ve Alınan Yıllar Araştırma Görevlisi : Öğretim Görevlisi Doktor : Yardımcı Doçent Doktor : Doçent Doktor : 2012-Devam Ediyor 6. Alanı ve Anabilim Dalı Sağlık Bilimleri Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Anabilim Dalı

2 7. Bugüne Kadar Bulunduğu Başlıca Görevler ve Tarihleri Anadolu Üniversitesi Eczacılık Fakültesi Dekan Yardımcılığı Diğer Faaliyetleri ve Sorumlulukları (Editör, Danışman Vb.) a) SCI tarafından taranan dergilerde yapılan hakemlikler [1] Bioorganic & Medicinal Chemistry ( ) [2] Medicinal Chemistry Research ( ) [3] European Journal of Medicinal Chemistry ( ) [4] Journal of Enzyme Inhibition and Medicinal Chemistry ( ) [5] Archiv der Pharmazie ( ) [6] Letters in Drug Design & Discovery ( ) [7] Turkish Journal of Chemistry ( ) b) SCI tarafından taranan dergilerde yapılan editörlükler [1] Turkish Journal of Biology (2012) c) Bilimsel araştırma projeleri [1] Bazı sübstitüe benzilidenanilin türevlerinin sentezlenmesi ve antiproliferatif etkilerinin araştırılması, Proje Yöneticisi: Prof. Dr. İlhan IŞIKDAĞ, Araştırmacı: Yusuf ÖZKAY, AUBAP (2007). [2] Bazı 2,2'-disübstitüe-1H,1H'-[5,5']-bis-benzimidazol türevleri ve 2,3,2',3'- tetrasübstitüe-[6,6']-bis-kinoksalin türevlerinin sentezleri, yapı aydınlatmaları ve antiproliferatif ve sitotoksik etkilerinin araştırması üzerine çalışmalar, Proje Yöneticisi: Prof. Dr. İlhan IŞIKDAĞ, Araştırmacı: Yusuf ÖZKAY AÜBAP (2009). [3] Bazı 2-sübstitüye-N-[4-(1-metil-4,5-difenil-1H-imidazol-2-il)fenil]asetamid türevlerinin sentezleri ve antikanser aktivitelerinin araştırılması üzerine çalışmalar", Proje Yöneticisi: Prof. Dr. İlhan IŞIKDAĞ, Araştırmacı: Yusuf ÖZKAY, AÜBAP (2010). [4] Bazı İmidazol Bileşiklerinin Sentezi ve Kantitatif Yapı Antimikrobiyel Aktivite İlişkilerinin İncelenmesi Proje Yöneticisi: Prof. Dr. Ümit UÇUCU, Araştırmacı: Yusuf ÖZKAY, AUBAP-1104S079 (2014).

3 [5] Bazı Kinoksalin Türevlerinin Sentezi ve Kantitatif Yapı Antimikrobiyel Aktivite İlişkilerinin İncelenmesi Proje Yöneticisi: Prof. Dr. İlhan IŞIKDAĞ, Araştırmacı: Yusuf ÖZKAY AÜBAP-1104S080 (2014). [6] Benzimidazol Yapısı Taşıyan Moklobemid Analogu Yeni Bileşiklerin Sentezlenmesi ve Sıçanların Depresyon Parametreleri ile Beyin Monoamin Düzeyleri Üzerine Etkilerinin İncelenmesi Proje Yöneticisi: Yard. Doç. Dr. Nafiz Öncü CAN, Araştırmacı: Yusuf ÖZKAY AÜBAP-1105S101. (Devam ediyor). [7] Bazı N-(4-Sübstitüefenil)-2-Hetoroarilsulfanil Asetamid Türevlerinin Sentezleri ve Kolinesteraz Enzimleri Üzerine Etkinliklerinin İncelenmesi, Proje Yöneticisi: Doç. Dr. Yusuf ÖZKAY, Üniversitesi Araştırma Fonu Projesi No: 1205S88. (Devam ediyor). [8] Kolinesteraz İnhibitörleri Olarak Bazı Yeni Piperidin/Piperazin- Ditiyokarbamat Türevlerinin Sentezlenmesi ve İnvitro Enzim Aktivitelerinin Araştırılması Proje Yöneticisi: Prof. Dr. Ümit UÇUCU, Araştırmacı: Yusuf ÖZKAY, AUBAP-1104S079 (Devam Ediyor). 9. Kazandığı ödüller Novartis Bilim Ödülü; Farmasötik ve medisinal kimya ilaç tasarım ve geliştirme araştırma ödülleri üçüncülük ödülü (14 Nisan 2011). 10. Yurtiçi ve yurtdışında üyesi olduğu kuruluşlar Türk Farmasötik ve Medisinal Kimya Derneği Anadolu Üniversitesi Eczacılık Fakültesi Mezunlar Derneği 11. Yayın Listesi a) Uluslararası Makaleleri (Social Sciences Citation Index, Science Citation Index veya Arts and Humanities Citation Index tarafından taranan dergiler) [1] (SCI) Özkay, Y., İncesu, Z.S., Işıkdağ, İ., Yeşilkaya, M. Antiproliferative effects of some N-benzylideneanilines.Cell Biochemistry and Function.26, (2008) [2] (SCI) Alanyalı, F.S., Arıcı, M., Artagan, Ö., Işıkdağ, İ., Özkay, Y., Mutagenicity of bisbenzimidazole derivatives. Z.Naturforsch.65c,10-14., (2010) [3] (SCI) Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ, İ. Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety, European Journal of Medicinal Chemistry 45, (2010)

4 [4] (SCI) Özkay, Y., Işıkdağ, İ., İncesu, Z., Akalın, G. Synthesis of 2-substituted- N-[4-(1-methyl-4,5-diphenyl-1H-imidazole-2-yl)phenyl]acetamide derivatives and evaluation of their anticancer activity, European Journal of Medicinal Chemistry 45, (2010) [5] (SCI) Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ, İ. Synthesis and antimicrobial activity investigation of some novel benzimidazole hydrazides, Asian Journal of Chemistry 23, (2011) [6] (SCI ) Özkay-Demir,Ü., Özkay.,Y., Can,Ö.D., Synthesis and analgesic effects of 2-(2-carboxyphenylsulfanyl)-N-(4- substitutedphenyl)acetamide derivatives. Medicinal Chemistry Research, 20, , (2011) [7] (SCI) Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ, İ., Antimicrobial Activity of a New Combination System of Benzimidazole and Various Azoles, Archiv der Pharmazie, 344(4): (2011) [8] (SCI) Turan-Zıtounı,G., Özkay, Y., Özdemır, A., Kaplancıklı,Z.A., Altıntop, M.D. Synthesis of Some Benzothiazole Based Piperazine-Dithiocarbamate Derivatives and Evaluation of Their Anticancer Activities, Letters in Drug Discovery & Design 8, (2011) [9] (SCI) Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ, İ. Antimicrobial Activity of a New Series of Benzimidazole Derivatives, Archives of Pharmacal Research 34, (2011) [10] (SCI) Işıkdağ, İ., Özkay, Y., İncesu, Z., Akalın, G., Anticancer Activity of Some Bisbenzimidazoles Z.Naturforsch.65c, (2011) [11] (SCI) Özkay-Demir,Ü., Can,Ö.D., Özkay, Y., Öztürk,Y., Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocininduced cognitive deficits. Pharmacological Reports, 64, (2012) [12] (SCI) Yurttaş L., Özkay Y., Kaplancıklı Z.A, Synthesis of New Thiazole- Piperazine Compounds As Acetylcholinesterase Inhibitors, Journal of Enzyme Inhibition and Medicinal Chemistry, 28, (2013) [13] (SCI) Özkay,Y.,İncesu,Z.S., Önder, N.İ.,Tunalı, Y., Karaca, H., Işıkdağ, İ., Uçucu, Ü., Antimicrobial and anticancer effects of some 2-substitutedsulfanyl)-N- (5-methyl-isoxazol-3-yl acetamide derivatives, Medicinal Chemistry Research, 22, (2013) [14] (SCI) Yurttaş L., Özkay Y., Kaplancıklı Z.A., Tunalı Y., Karaca H.,"Synthesis and antimicrobial activity of some new hydrazone-bridged thiazole-pyrrole

5 derivatives", Journal of Enzyme Inhibition and Medicinal Chemistry 28, (2013) [15] (SCI) Yurttaş L., Özkay Y., Karaca H., Tunalı Y., Kaplancıklı Z.A., "Synthesis and Antimicrobial Evaluation of Some 2,5-Disubstituted Benzimidazole Derivatives " Letters in Drug Design & Discovery, 10, (2013) [16] (SCI) Demir Özkay, Ü. Yurttaş, L. Özkay, Y. Üçel, U.İ. Can, Ö.D. Öztürk, Y. "Synthesis of new 1-phenyl-2-(4-substituted-piperazin-1-yl)- propanol derivatives and evaluation of their antidepressant-like effects", Archives of Pharmacal Research, 36, (2013) [17] (SCI) Altıntop M.D., Gurkan-Alp A.S., Özkay Y., Kaplancıklı Z.A. Synthesis and Biological Evaluation of a Series of Dithiocarbamates as New Cholinesterase Inhibitors. Archiv der Pharmazie 346, (2013) [18] (SCI) Yurttaş, L., Özkay, Y., Akalin-Çiftçi, G., Ulusoylar-Yildirim, Ş. Synthesis and anticancer activity evaluation of N-[4-(2-methylthiazol-4-yl) phenyl]acetamide derivatives containing (benz)azole moiety. Journal of Enzyme Inhibition and Medicinal Chemistry 28, (2014) [19] (SCI) Yurttaş L., Özkay Y., Demirci F., Göger G., Ulusoylar-Yıldırım Ş., Abu Mohsen U., Öztürk Ö., Kaplancıklı Z.A. Synthesis, anticandidal activity, and cytotoxicity of some thiazole derivatives with dithiocarbamate side chains. Turkish Journal of Chemistry (DOI: /kim ) (2014) [20] Mohsen, U.A., Kaplancikli, Z.A., Özkay, Y., Yurttaş, L. Synthesis and Evaluation of Anti-acetylcholinesterase Activity of Some Benzothiazole Based New Piperazine-dithiocarbamate Derivatives. Drug Research (DOI: /s ) (2014) [21] Abu Mohsen, U., Yurttaş, L., Acar, U., Özkay, Y., Kaplacikli, Z.A., Karaca Gencer, H., Cantürk, Z. Synthesis and Biological Evaluation of Some New Amide Moiety Bearing Quinoxaline Derivatives as Antimicrobial Agents. Drug Research (DOI: /s ) (2014) b) Ulusal Makaleleri [1] Işıkdağ, İ., İncesu, Z., Gülnaz, D., Özkay, Y., Cytotoxic effects of some perimidine derivatives on F2408 and 5RP7 cell lines. FABAD J. Pharm. Sci., 33: (2008) [2] Işıkdağ, İ., Özkay, Y., İncesu, Z., Synthesis and anticancer activity of some bisquinoxaline derivatives. Turk. J. Pharm. Sci., 8: (2011)

6 [3] Kutlu, M., Öztaş, E., Aydoğan, G., Işıkdağ, İ., Özkay, Y., Bazı 9-sübstitüe fenantren türevlerinin mutajenik aktivitelerinin Ames / Salmonella / mikrozom testi ile araştırılması. Anadolu Univ. J. Sci. Techno. C; Life Sci. Biotechno., 1: (2011) [4] Özkay, Y., Yurttaş, L., Mohsen, U.A., Sever B., Hussein, W., Öztürk, Ö., Sağlık, B.N., Acar, U., Erdoğan, Ö.N., Pekbağ, A., Kaplancıklı, ZA., Study on thiazolylhydrazone derivatives as acetylcholinesterase inhibitors. MÜSBED 4: (2014) c) Uluslararası Konferans bildiriler [1] Işıkdağ, İ., Özkay, Y., Uçucu, Ü., Microwave supported synthesis of some novel 2,3,6-trisubstituted quinoxaline derivatives. 13th Belgian Organic Synthesis Symposium, BOOS/XIII, KU Leuven, Belgium,, 15/07/2012 [2] Uçucu, Ü., Özkay, Y., Işıkdağ, İ., Microwave supported synthesis of some imidazole derivatives and the effect of catalysts on N-substition of imidazole, 13th Belgian Organic Synthesis Symposium, BOOS/XIII, KU Leuven, Belgium,, 15/07/2012 [3] Özkay, Y., Yurttaş, L., Akalın, G., Ulusoylar-Yıldırım, Ş., Synthesis of New Tiazole Derivatives As Anticancer Agents,10th International Symposium on Pharmaceutical Science (ISOPS-10), Ankara-TURKEY, 26/06/2012 [4] Yurttaş, L., Özkay, Y., Kaplancıkl, Z.A.,,Synthesis of New Thiazole-Piperazine Compounds as Acetylcholinesterase Inhibitors, 10th International Symposium on Pharmaceutical Science (ISOPS-10), Ankara-TURKEY,, 26/06/2012 [5] Yurttaş, L., Özkay, Y., Kaplancıklı, Z.A., Tunalı, Y., Karaca, H., Synthesis and antimicrobial activity of some new hydrazine-bridged pyrrole-thiazole derivaties, 15th Hellenic Symposium on Medicinal Chemistry, Athens-Grece, 25/05/2012 [6] Özkay, Y., Yurttaş, L., Tunalı, Y., Karaca, H., Synthesis of novel imidazole derivaties as antifungal agents. 15th Hellenic Symposium on Medicinal Chemistry, Athens-Grece, 25/05/2012 [7] Demir-Özkay, Ü., Devrim, C.O., Özkay, Y., Acetylcholinesterase Inhibitory Effects of Some Benzothiazole-Piperazine Derivatives Eur. J. of Pharm.Sci., Suppl. 1, 173 (2011), Bled, Slovenya,, 29/09/2011 [8] Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ, Antimicrobial effect of some new 2,5-disübstituted benzimidazoles, Eur. J. of Pharm.Sci.,44,Suppl. 1, 174 (2011), Bled, Solenya,, 29/09/2011

7 [9] Uçucu, Ü., Özkay, Y., Işıkdağ, İ., Tunalı, Y., Karaca, H., Cantürk, Z.,Synthesis and antimicrobial activity of new imidazole derivatives, International Sympozium on advences in Synthetic and Medicinal Chemistry, ASMC 11 St. Petersburg, Russia, 21/08/2011 [10] Işıkdağ, İ., Özkay, Y., İncesu, Z., Synthesis and anticancer activity of novel antraquinone derivatives,international Sympozium on advences in Synthetic and Medicinal Chemistry, ASMC 11 St. Petersburg, Russia, 21/08/2011 [11] Özkay, Y., Can, Ö.D., Özkay-Demir, Ü., Yurttaş, L., Analgesic and Antiinflamatory Activity of Some Thiazole Derivatives, Internatinal Symposium on Drug Researh&Development "from chemistry to medicine" DRD 2011 Antalya- Türkiye, 27/05/2011 [12] Özkay, Ü.D., Özkay, Y., Öztürk,Y., Işıkdağ, İ., The effects of some benzotiazole/piperazine derivatives on learninig and memory parameters of streptozotocin model of alzheimer's disease in active avoidance test, Internatinal Symposium on Drug Researh&Development "from chemistry to medicine" DRD 2011 Antalya-Türkiye, 27/05/2011 [13] Özkay,Y., İncesu, Z., Önder, N.İ., Işıkdağ, İ., Anticancer activity of some isoxazole derivatives, Internatinal Symposium on Drug Researh&Development "from chemistry to medicine" DRD 2011 Antalya-Türkiye, 27/05/2011 [14] Işıkdağ, İ., Özkay, Y., İncesu, Z., Akalın, G., Synthesis and antiproliferative effects of some bis-benzimidazole derivatives, International Sympozium on Synthetic and Medicinal Chemistry, ASMC 09 Kiev, Ukranie, 23/08/2009 [15] Özata, A., Özkay, Y., Işıkdağ,İ., Başoğlan, Ö., Alanyalı, F., Mutagnic activity of two novel multisubstituted imidazole derivatives, International Sympozium on Synthetic and Medicinal Chemistry, ASMC 09 Kiev, Ukranie,, 23/08/2009 [16] Özdemir, A., Turan-Zitouni, G., Kaplancıklı, Z.A., Özkay, Y., Altıntop, M.D., Revial, G., Yazar, S., Synthesis of some substituted carbamodithioic acid esters and their anticancer proporties, 45th International Conference on Medicinal Chemistry, University of Orleans-France, 01/07/2009 [17] Demir-Özkay, Ü.,Can, Ö.D, Özkay, Y., Öztürk, Y., Işıkdağ, İ., Effects of some benzothiazole/piperazine derivatives on learninig and memory parameters of rat in plus maze test. 45th International Conference on Medicinal Chemistry, University of Orleans-France, 01/07/2009

8 [18] Özkay, Y., Işıkdağ, İ., İncesu, Z., Akalın, G., Cytotoxic and anticancer activity of some newly synthesized imidazole derivatives,45th International Conference on Medicinal Chemistry, University of Orleans-France, 01/07/2009 [19] Özkay, Y., Tunalı, Y., Karaca, H., Işıkdağ. İ., Antimicrobial activities of some newly synthesized benzimidazole derivatives bearing hydrazone moiety, 8th International Symposium on Pharmaceutical Sciences. Ankara Univ. Pharm. Faculty. Ankara-Turkey, 23/06/2009 [20] Özkay, Y., Tunalı, Y., Özarda, M.G., Işıkdağ. İ., Antimicrobial activities of some novel 1,2,5,6-tetrasubstituted benzimidazole derivatives, 8th International Symposium on Pharmaceutical Sciences. Ankara Univ. Pharm. Faculty. Ankara- Turkey, 23/06/2009 [21] Özkay, Y., İncesu, Z., Akalın, G., Işıkdağ, İ., Anticancer activities of some novel 1,2,4,5-tetrasubstituted imidazole derivatives, 8th International Symposium on Pharmaceutical Sciences. Ankara Univ. Pharm. Faculty. Ankara-Turkey, 23/06/2009 [22] Demir-Özkay, Ü., Can, Ö.D., Özkay, Y., Işıkdağ. İ., Öztürk, Y., Synthesis and analgesic activity of some bisthiazole derivatives, 8th International Symposium on Pharmaceutical Sciences. Ankara Univ. Pharm. Faculty. Ankara-TURKEY, 23/06/2009 [23] Özkay, Y., Işıkdağ, İ., İncesu, Z.,Synthesis and anti cancer activity of some dithicarbamate based bisthiazoles. 22nd Federation of Asian Pharmaceutical Associations Congress, Singapore, 10/11/2008 [24] Işıkdağ, İ., Demir, Ü., Devrim, C.O., Özkay, Y., Öztürk,Y, Sythesis and analgesic activity of some benzimidazole derivatives, International symposium on drug research & development "From chemistry to medicine", Hacattepe Univercity, Lara-Antalya-Türkiye, 17/05/2007 [25] Işıkdağ, İ., Özkay, Y., İncesu, Z., Studies on the synthesis and antiproliferative activity investigation of 2,2'-(3-methoxyphenyl) and 2,2'-(3-hydroxyphentl)- 1H,1H'-[5,5']-bis-benzimidazoles, International symposium on drug research & development "From chemistry to medicine", Hacattepe Univercity, Lara-Antalya- Türkiye, 17/05/2007 [26] Demir, Ü., Devrim, C.O., Ozkay, Y., Benkli, K., Işıkdağ, İ., Öztürk, Y., Analgesic and sedative activity of 2-(2-hydroxynapthalen-1-yl)5,6-dichloro-1(H)- benzimidazole(hndcb), The 15th wold congress of pharmacology,beijing, China, 03/07/2006

9 [27] Ozkay, Y., Demir, Ü., Devrim, C.O., Öztürk, Y., Işıkdağ, İ., Central nervous system activity of 2-(naphthalen-1-il)-4,5-dimethyl-(1H)-imidazole(NDI), The 15th wold congress of pharmacology,beijing, China, 03/07/2006 [28] Akalın, G.,Özkay, Y.,İncesu, Z., Işıkdağ, İ., Antitumor and calcium mobilisation activities of 1,4-bis(heteroaryl substituted)benzene(bhb),the 15th wold congress of pharmacology,beijing, China, 03/07/2006 [29] Akalın, G., Özkay, Y., İncesu, Z., Işıkdağ, İ., Antitumor and calcium mobilisation activities of 1,4-bis-(4,5-difuran-2-yl-imidazol-2yl)-benzene (BDFIB)on U20S cells, 8th International Symposium on Pharmaceutical Chemistry. Ankara Univ. Pharm. Faculty. Ankara-TURKEY, 15/06/2006 [30] Can, Ö. D., Özkay, Y., Demir, Ü., Işıkdağ, İ., Öztürk, Y., Central nerveous system activity of 2-(3,5-dimetoxy-4-hydroxyphenyl)-5,6-dichloro-(1H)- benzimidazole (DPCB), 8th International Symposium on Pharmaceutical Chemistry. Ankara Univ. Pharm. Faculty. Ankara-TURKEY, 15/06/2006 [31] Özkay, Y., Işıkdağ, İ., İncesu, Z. S., Study on the synthesis of some 2- (substitutedphenyl) or 2-(substitutedphenyl)-5-substituted-1H-antra[1,2-d]- imidazole-6,11-dione derivatives and their cytotoxic and antiproliferative effects,international Symposium on medicinal chemistry research and development. Hacettepe University MCRD Kuşadası-TURKEY, 28/09/2005 [32] Özkay, Y., İncesu, Z.S., Işıkdağ, İ., The studies on the synthesis of some mono substituted benzylideneaniline derivatives and their cytotoxic and antiproliferative effects,international Symposium on medicinal chemistry research and development. Hacettepe University MCRD Kuşadası-TURKEY, 28/09/2005 [33] Özkay, Y., İncesu, Z.S., Işıkdağ, İ., The studies on the synthesis of some disubstituted benzylideneaniline derivatives and their cytotoxic and antiproliferative effects,international Symposium on medicinal chemistry research and development. Hacettepe University MCRD Kuşadası-TURKEY, 28/09/2005 [34] Kutlu, M., Aydoğan, G., Özkay, Y., Özata, A., Işıkdağ, İ., Synthesis and investigation of mutagenic activities of some substituted benzylideneaniline derivatives (I). 19th Europien Workshop on Drug Metabolism. Antalya-Turkey, 03/10/2004 [35] Kutlu, M., Aydoğan, G., Özkay, Y., Işıkdağ, İ., Özata, A., Synthesis and investigation of mutagenic activities of some substituted benzylideneaniline

10 derivatives (II). 19th Europien Workshop on Drug Metabolism. Antalya-Turkey, 03/10/2004 [36] Kutlu, M., Aydoğan, G., Özkay, Y., Işıkdağ, İ., Synthesis and investigation of mutagenic activities of some 9-substituted phenanthrene derivatives. 19th Europien Workshop on Drug Metabolism. Antalya-Turkey, 03/10/2004