993 resultados para G.1.6 Optimization


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This report contains information on the Appeal Activity in the Public Assistance Programs. Programs included are FIP (Iowa’s TANF program), Title IV-D (Child Support), Food Stamps (USDA Food Assistance Program), Title XIX (Medicaid), Title XX (Social Services Block Grant), Juvenile Parole, State Supplemental Assistance, Other, Food Stamp Fraud, FIP Fraud, RCA (Refugee Cash Assistance) Fraud, and a total for all the programs. This report is issued monthly.

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This report contains information on the Appeal Activity in the Public Assistance Programs. Programs included are FIP (Iowa’s TANF program), Title IV-D (Child Support), Food Stamps (USDA Food Assistance Program), Title XIX (Medicaid), Title XX (Social Services Block Grant), Juvenile Parole, State Supplemental Assistance, Other, Food Stamp Fraud, FIP Fraud, RCA (Refugee Cash Assistance) Fraud, and a total for all the programs. This report is issued monthly.

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This report contains information on the Appeal Activity in the Public Assistance Programs. Programs included are FIP (Iowa’s TANF program), Title IV-D (Child Support), Food Stamps (USDA Food Assistance Program), Title XIX (Medicaid), Title XX (Social Services Block Grant), Juvenile Parole, State Supplemental Assistance, Other, Food Stamp Fraud, FIP Fraud, RCA (Refugee Cash Assistance) Fraud, and a total for all the programs. This report is issued monthly.

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This report contains information on the Appeal Activity in the Public Assistance Programs. Programs included are FIP (Iowa’s TANF program), Title IV-D (Child Support), Food Stamps (USDA Food Assistance Program), Title XIX (Medicaid), Title XX (Social Services Block Grant), Juvenile Parole, State Supplemental Assistance, Other, Food Stamp Fraud, FIP Fraud, RCA (Refugee Cash Assistance) Fraud, and a total for all the programs. This report is issued monthly.

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Kilpailu - Välimiesoikeuden velvollisuus soveltaa omasta aloitteestaan 81 EY artiklaa (aiemmin 85 artiklaa) - 81 EY artiklan ordre public -luonne - Kansallisen tuomioistuimen velvollisuus kumota välitystuomio

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A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.

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A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.

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Syftet med avhandlingen var att analysera och kartlägga sångrepertoaren i den finlandssvenska skolans årskurs 1-6 i början av 2000-talet. Läroplansreformen 1994 gav skolorna valmöjligheter i samband med utformandet av skolvisa läroplaner. Härmed undersöktes hur denna reform inverkat på repertoarvalet och sångtraditionen. Utgående från mitt syfte ställdes två övergripande forskningsfrågor. Vilka sånger tillhör enligt lärare repertoaren i den finlandssvenska skolan? Vilka faktorer bidrar till att gestalta repertoaren? Undersökningsansatsen var kvalitativ och avhandlingen fick en deskriptiv karaktär. Tre teman - det utvecklingspsykologiska, läroplansteoretiska och social-psykologiska vägledde teoridelen. Lärarna uppskattar valfriheten samtidigt som en klar majoritet ställer sig positivt till en bestämd repertoar. När repertoaren ses ur ett lärarperspektiv visar det sig att traditionella finlandssvenska sånger placerar sig i toppen. Psalmer, sånger från Sverige och nya finlandssvenska tillskott har likaså en naturlig plats i repertoaren. Därtill finns utrymme för en varierande internationell repertoar och populärmusik. Sångerna som väljs har olika funktioner. De stöder elevens kännedom om den egna kulturen och andra kulturers uttryckssätt, stärker identiteten, utvecklar elevens musikaliska förmåga och blir en del av allmänbildningen. Lärarens personliga kompetens, självmedvetenhet och speciellt samarbetsförmåga är viktiga faktorer inför valsituationer. Läroplanen och läromedel är grundläggande styrmedel. Utöver dessa tillkommermassmediernas inflytande och möjligheten till fortbildning. Sångrepertoaren är omfattande och lärarens roll betydelsefull. Det traditionella i repertoaren lever kvar men utrymme ges också åt nya tillskott och multikulturella inslag. Idealet är en balans mellan det traditionella och moderna. En delvis bestämd repertoar kunde underlätta valsituationen och skapa en mer enhetlig finlandssvensk grundskola. Här framställs en förkortad, beskrivande version av avhandlingen inom ramen för studieprogrammet i pop och jazz vid yrkeshögskolan Stadia.

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A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.

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A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.