LEADER 04481nam 22005415 450 001 9910298586003321 005 20200706175932.0 010 $a981-10-6547-0 024 7 $a10.1007/978-981-10-6547-7 035 $a(CKB)4100000000587613 035 $a(DE-He213)978-981-10-6547-7 035 $a(MiAaPQ)EBC5050085 035 $a(PPN)204531365 035 $a(EXLCZ)994100000000587613 100 $a20170919d2018 u| 0 101 0 $aeng 135 $aurnn|008mamaa 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aAdvancing Development of Synthetic Gene Regulators $eWith the Power of High-Throughput Sequencing in Chemical Biology /$fby Anandhakumar Chandran 205 $a1st ed. 2018. 210 1$aSingapore :$cSpringer Singapore :$cImprint: Springer,$d2018. 215 $a1 online resource (XV, 114 p. 49 illus., 44 illus. in color.) 225 1 $aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 311 $a981-10-6546-2 320 $aIncludes bibliographical references. 327 $aOverview of Next-Generation Sequencing Technologies and its application in Chemical Biology -- Next Generation Sequencing Studies Guide the Design of Pyrrole-Imidazole Polyamides with Improved Binding Specificity by the Addition of ?-alanine -- Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by Utilizing the Power of High-Throughput Sequencing -- Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing. 330 $aThis book focuses on an ?outside the box? notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)?N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence. . 410 0$aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 606 $aBiotechnology 606 $aGene therapy 606 $aBioorganic chemistry 606 $aBiotechnology$3https://scigraph.springernature.com/ontologies/product-market-codes/C12002 606 $aGene Therapy$3https://scigraph.springernature.com/ontologies/product-market-codes/B12020 606 $aBioorganic Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C19010 615 0$aBiotechnology. 615 0$aGene therapy. 615 0$aBioorganic chemistry. 615 14$aBiotechnology. 615 24$aGene Therapy. 615 24$aBioorganic Chemistry. 676 $a660.6 700 $aChandran$b Anandhakumar$4aut$4http://id.loc.gov/vocabulary/relators/aut$0768466 906 $aBOOK 912 $a9910298586003321 996 $aAdvancing Development of Synthetic Gene Regulators$91565444 997 $aUNINA LEADER 04144oam 2200553z 450 001 9910157823503321 005 20240102175554.0 010 $a0-19-181328-1 035 $a(CKB)3780000000081184 035 $a(SSID)ssj0001559784 035 $a(PQKBManifestationID)16190976 035 $a(PQKBTitleCode)TC0001559784 035 $a(PQKBWorkID)14824321 035 $a(PQKB)11618613 035 $a(StDuBDS)EDZ0001208091 035 $a(MiAaPQ)EBC4842327 035 $a(MiAaPQ)EBC7034862 035 $a(Au-PeEL)EBL7034862 035 $a(OCoLC)920859835 035 $a(EXLCZ)993780000000081184 100 $a20160829d2015 uy 0 101 0 $aeng 135 $aur||||||||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aWhat was tragedy? : theory and the early modern canon /$fBlair Hoxby 205 $aFirst edition. 210 1$aOxford :$cOxford University Press,$d2015. 215 $a1 online resource $cillustrations (black and white) 300 $aBibliographic Level Mode of Issuance: Monograph 311 0 $a0-19-874916-3 320 $aIncludes bibliographical references and index. 327 $aI. The philosophy of the tragic and the poetics of tragedy -- 1. Our tragic culture -- The early modern conception of tragedy -- The philosophy of the tragic -- Literary form, the philosophy of history, and the canon -- Tragedy born anew from the spirit of music? -- Decadence and primitivism -- The post-structural assault on tragic freedom -- Reassessing the legacy of idealism -- Approaching the world we have lost -- 2. An early modern poetics of tragedy -- Definitions -- The objects of tragic imitation -- Fables -- Manners -- Sentiments -- Diction -- The player's passions -- Spectacle -- The chorus -- Tragic pleasure -- II. The world we have lost -- 3. Simple pathetic tragedy -- Classical exemplars -- Recovery and invention: Trissino's Sofonisba (1515) -- A theoretical interlude -- Racine's Be?re?nice (1670) -- Milton's Samson Agonistes (1671) -- Simplicity and reformation -- Gluck's Alceste (1779) -- La Harpe's philocte?te (1781) -- From pathos to moral freedom -- 4. Operatic discoveries: The complex tragedy with a happy ending -- Did tragic heroes sing? -- Euripides and the operatic repertoire -- The Euripidean tragedy of anticipated woe -- Idomeneo and the tragedy of averted sacrifice -- 5. Counter-reformation tragedy: The laurel and the cypress -- Tragedy as spiritual exercise -- Jesuit defenses of counter-reformation tragedy -- Enlightened critiques and idealist defenses -- Final reckonings -- 6. History as tragedy, tragedy as design: Where Shakespeare and Dryden part company -- Antony and Cleopatra as a great occurence -- The art of portraiture -- Sublimity raised from the very elements of littleness -- Dryden's artificial order -- Portraiture and history painting -- Tides that swell and retire to seas -- Language -- The world well lost -- Tragedy and history. 330 8 $aModern critics have definite ideas about tragedy, maintaining that in a true tragedy fate must feel the resistance of the tragic hero's moral freedom before finally crushing him, thus generating our ambivalent sense of terrible waste coupled with spiritual consolation. Yet far from being a timeless truth, this account of tragedy only emerged in the wake of the French Revolution. This study demonstrates that this account of the tragic, which has been hegemonic from the early 19th century despite recent twists and turns of critical fashion, obscured an earlier poetics of tragedy that evolved from 1515 to 1795. 606 $aTragedy$xHistory and criticism 606 $aDrama$2HILCC 606 $aMusic, Dance, Drama & Film$2HILCC 608 $aCriticism, interpretation, etc.$2fast 615 0$aTragedy$xHistory and criticism. 615 7$aDrama 615 7$aMusic, Dance, Drama & Film 676 $a809.2512 700 $aHoxby$b Blair$f1966-$01175759 801 0$bPQKB 906 $aBOOK 912 $a9910157823503321 996 $aWhat was tragedy? : theory and the early modern canon$93657958 997 $aUNINA