Controlled dynamic generation of standard 1,6-hexamethylene diisocyanate aerosols

A procedure for the dynamic generation of 1,6-hexamethylene diisocyanate (HDI) aerosol atmospheres of 70 micrograms m-3 (0.01 ppm) to 1.75 mg m-3 (0.25 ppm), based on the precise control of the evaporation of pure liquid HDI and subsequent dilution with air, was developed. The apparatus consisted of a home-made glass nebulizer coupled with a separation stage to exclude non-respirable droplets (greater than 10 microns). The aerosol concentrations were achieved by passing air through the nebulizer at 1.5-4.5 l. min-1 to generate dynamically 0.01-0.25 ppm of diisocyanate in an experimental chamber of 8.55 m3. The distribution of the liquid aerosol was established with an optical counter and the diisocyanate concentration was determined from samples collected in impingers by a high-pressure liquid chromatographic method. The atmospheres generated were suitable for the evaluation both of sampling procedures full scale, and of analytical methods: at 140 micrograms m-3 (0.02 ppm) they remained stable for 15-min provocation tests in clinical asthma, as verified by breath-zone sampling of exposed patients.

Kni 1/6 -25

Kirje Kajaani 1.6.1925

Assistentti Seppo Laakso 1/6 1970

Kirje 1.6.1970

Helsinki 1.6.1925

Kirje

Euroopan yhteisöjen tuomioistuimen tuomio 1.6.1999 asiassa C-126/97 (Eco Swiss China Time)

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

1-6-19, Colombes, le général Pershing félicite les vainqueurs des éliminatoires [championnats d'athlétisme de l'armée américaine] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54200

1-6-19, le général Pershing remettant les récompenses [aux vainqueurs des éliminatoires des championnats d'athlétisme de l'armée américaine] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54207

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

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.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

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.

Optisen 1.6 GHz signaalin monistin

Tässä diplomityössä suunnitellaan CERN:in (Conseil Europëen pour la Recherche Nuclëaire) Compact Muon Solenoid –nimiseen hiukkasilmaisinjärjestelmään laite, joka monistaa 1.6 Gbit/s nopeudella saapuvia optisia signaaleja useaan eri kohteeseen. Aluksi suunnitellaan ja rakennetaan testauslaite, jonka avulla tutkitaan eri komponenttien soveltuvuutta laitteistoon. Lisäksi testauslaitteella haetaan laserohjaimille ja vastaanottimille sopivia säätöarvoja. Testauslaitteesta saatujen kokemusten perusteella suunnitellaan ja rakennetaan signaalinmonistinlaitteisto, johon tuodaan useita satoja erillisiä signaaleja. Jokainen näistä signaaleista monistetaan joko kahdeksi tai neljäksi lähteväksi signaaliksi. Lopuksi testauslaitteella tutkitaan signaalinmonistinlaitteiston toimintaa ja luotettavuutta.

Poikkitieteellinen väitöskirja intiaaninuorten elämästä : lectio praecursoria 1.6.2007 Helsingin yliopistossa

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