Fragm. lat. I 69 - Psalterium (Ps 22,4 - 6; 23,5 - 9; 29,13 - 30,4; 30,10 - 12; 31,5 - 8; 32,1 - 7; 37,5 - 11; 37,13 - 18)

Vorbesitzer: Gustav Freytag

Fragm. lat. III 40 - Digesta (D.7.7.6 - 7.8.12), mit Glosse

Trägerband: 15/69; Vorbesitzer: Dominikanerkloster Frankfurt am Main

Macrocyclic systems containing 2,6,9-trioxabicyclo[3.3.1]-nona-3,7-dienes as chiral spacer groups: Synthesis, stereochemical features and preliminary complexation properties

Novel 2:2-macrocycles bearing bridged concave 2,6,9-trioxabicyclo[3.3.1]nona-3,7-dienes as chiral spacer units were obtained by cyclocondensation reaction of the chiral bisacid chloride and the corresponding diols, while use of methylene diamines instead of diols afforded 1:1 macrocycles only. Applying the same, but now template-assisted, experimental procedure to the reaction of the bisacid chloride with triethylene glycol brought about a significant increase in yield as well as a suitable simplification of the work-up during preparation and separation of the corresponding 1:1 as well as 2:2 macrocycles, when compared to results reported previously. HPLC separation on chiral columns revealed the presence of diastereoisomers [RR(S,S)- and RS-(meso)-forms] for all 2:2 macrocycles, which was further evidenced by the CD spectrum of one of those species as an example. Preliminary ESI-MS experiments indicated strong complexation abilities of the sulphur-containing ligand towards Ag(I), Cu(II) and Au(III) ions.

Flexible synthesis of enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes from propargylic and homopropargylic alcohols

A new approach to enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro [4.5] decanes is described and utilizes enantiomerically pure homopropargylic alcohols obtained from lithium acetylide opening of enantiomerically pure epoxides, which are, in turn, acquired by hydrolytic kinetic resolution of the corresponding racemic epoxides. Alkyne carboxylation and conversion to the Weinreb amide may be followed by triple-bond manipulation prior to reaction with a second alkynyllithium derived from a homo- or propargylic alcohol. In this way, the two ring components of the spiroacetal are individually constructed, with deprotection and cyclization affording the spiroacetal. The procedure is illustrated by acquisition of (2S,5R,7S) and (2R,5R,7S)-2-n-butyl-7-methyl-1,6-dioxaspiro[4.5]-decanes (1), (2S,6R,8S)-2-methyl-8-n-pentyl-1,7-dioxaspiro[5.5]undecane (2), and (2S,6R,8S)-2-methyl-8-n-propyl-1,7-dioxaspiro[5.5]undecane (3). The widely distributed insect component, (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (4), was acquired by linking two identical alkyne precursors via ethyl formate. In addition, [H-2(4)]-regioisomers, 10,10,11,11-[H-2(4)] and 4,4,5,5-[H-2(4)] of 3 and 4,4,5,5-[H-2(4)]-4, were acquired by triple-bond deuteration, using deuterium gas and Wilkinson's catalyst. This alkyne-based approach is, in principle, applicable to more complex spiroacetal systems not only by use of more elaborate alkynes but also by triple-bond functionalization during the general sequence.

PARA UMA PAZ SEM FIM : Um estudo, sócio-político e teológico, da tipologia messiânica nas perícopes de Isaías 7,10-17 e 8,23-9,6.

O ato de ungir, do qual se origina o termo messias, era um costume dos povos do Antigo Oriente Médio e foi assimilado por Israel. O Antigo Testamento, porém, reinterpretou esta unção. Ele atribuiu ao rei, num primeiro momento, o título de ungido, maxiah;. Nesta perspectiva, o rei Davi foi aquele que deu origem à mentalidade messiânica em Israel. E a respeito da teologia messiânica, o profeta Isaías tornou-se um dos seus expoentes. Ele se dirige à classe alta de Jerusalém e propõe um Ungido de Javé em substituição ao rei da casa de Davi. Isto porque, o messianismo também se tornou um movimento de resistência frente a não observância da justiça e do direito, que culmina com a ausência da paz. Nesse sentido, Isaías apresenta também uma nova percepção do messianismo, a saber, uma ruptura com a casa de Davi (7,17). Este messias não estava sob os critérios humanos de um bom rei, forte e guerreiro, mas sob a direção do Espírito de Javé. Por isso, ele poderá ser um messias criança (7,14; 9,5). Esta dissertação tem, portanto, a finalidade de percorrer o caminho do surgimento do ungido, ou do ato de se ungir, até a concepção isaiânica de messias. Esse desenvolvimento mostrará, ao final do trabalho, a tipologia messiânica apresentada pelo profeta Isaías, a partir das perícopes de 7,10-17 e 8,23-9,6.(AU)

IMANUEL E ESPÍRITO DE IAHWEH: Leitura e releitura do messianismo em Isaías (7,10-17; 8,23-9,6; 11,1-9)

O objeto de pesquisa desta dissertação são as perícopes de Isaías 7,10-17;8,23-9,6 e 11,1-9. Nelas encontra-se o cerne do pensamento messiânico de Isaías. É importante salientar que o messianismo isaiano parte da concepção de um messias que vem para governar a partir do direito e da justiça, e, assim, estabelecer a paz. O messianismo apresentado por este profeta não parte das esferas de poder da corte, mas dos pequenos e frágeis da sociedade, dotados do espírito de Javé. Há que se destacar que a profecia de Isaías é um divisor de águas no que concerne à teologia messiânica no Reino do Sul, especialmente nos profetas depois dele. Em Isaías, encontra-se a ruptura com as classes dominantes e com um messianismo bélico. A proposta deste profeta aponta para um messias frágil, mas que é movido pelo sopro, pelo movimento de Javé em suas ações. E assim, Isaías abre as portas para compreensão de um messias pobre, como retrata Zacarias, um messias servo, apresentado pelo Dêutero-Isaías, ou quem sabe um messias pastor, como proposto por Miquéias e Ezequiel e bem recebido pelas tradições do primeiro século (Jo 10,10). O messias em Isaías tem nomes e adjetivos : Imanuel, menino, raiz de Jessé, mas não tem rosto, não tem localização geográfica, não se enquadra em nenhum tipo messiânico desde o davidismo de Jerusalém. Este messias pode ser encontrado em qualquer época com qualquer rosto, por isso a importante releitura messiânica apresentada em textos do cristianismo nascente. Muitos deles inspirados na profecia isaiana do 8º. século a.C.

Studies on the neurotoxicity of 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) in SH-SY5Y cells

We have studied the hypothesis that 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) is neurotoxic. Salsolinol induced a significant time and dose related inhibition of 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazoyl blue (MTT) reduction, and increased lactate dehydrogenase release (LDH) release from human SH-SY5Y neuroblastoma cells, at concentrations within the range of 1-methyl-4-phenylpyridinium (MPP+) cytotoxicity, in vitro. Cytotoxicity was not inhibited by the addition of antioxidants, monoamine oxidase inhibitors or imipramine. In confluent monolayers, salsolinol stimulated catecholamine uptake with EC50 values of 17 muM and 11 muM, for noradrenaline and dopamine, respectively. Conversely, at concentrations above 100 muM, salsolinol inhibited the uptake of noradrenaline and dopamine, with IC50 values of 411 muM and 379 muM, respectively. The inhibition of catecholamine uptake corresponded to the increase displacement of [3H]nisoxetine from the uptake 1 site by salsolinol, as the Ki (353 muM) for displacement was similar to the IC50 (411 and 379 muM) for uptake. Salsolinol stimulated catecholamine uptake does not involve the uptake recognition site, or elevation of cAMP, cGMP, or inhibition of protein kinase C. Salsolinol also inhibited both carbachol (1 mM) and K+ (100 mM, Na+ adjusted) evoked released of noradrenaline from SH-SY5Y cells, with IC50 values of 500 muM and 120 muM, respectively. In conclusion, salsolinol appears to be cytotoxic to SH-SY5Y cells, via a mechanism that does not require uptake 1, bioactivation by monoamine oxidase, or membrane based free radical damage. The effects of salsolinol on catecholamine uptake, and the mechanism of toxicity require further investigation.

25-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages

Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not I?B degradation or tumour necrosis factor- release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling.

The nitric oxide-donating pravastatin derivative, NCX 6550 [(1S-[1α(βS*, δS*), 2α, 6α, 8β-(R*), 8aα]]-1,2,6,7,8,8a-hexahydro-β, δ, 6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphtalene-heptanoic acid 4-(nitrooxy)butyl ester)], reduces splenocyte adhesion and reactive oxygen species generation in normal and atherosclerotic mice

Statins possess anti-inflammatory effects that may contribute to their ability to slow atherogenesis, whereas nitric oxide (NO) also influences inflammatory cell adhesion. This study aimed to determine whether a novel NO-donating pravastatin derivative, NCX 6550 [(1S-[1∝(ßS*,dS*),2∝,6a∝,8ß-(R*),8a∝]]-1,2,6,7,8,8a-hexahydro-ß,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid 4-(nitrooxy)butyl ester)], has greater anti-inflammatory properties compared with pravastatin in normal and atherosclerotic apolipoprotein E receptor knockout (ApoE-/-) mice. C57BL/6 and ApoE-/- mice were administered pravastatin (40 mg/kg), NCX 6550 (48.5 mg/kg), or vehicle orally for 5 days. Ex vivo studies assessed splenocyte adhesion to arterial segments and splenocyte reactive oxygen species (ROS) generation. NCX 6550 significantly reduced splenocyte adhesion to artery segments in both C57BL/6 (8.8 ± 1.9% versus 16.6 ± 6.7% adhesion; P < 0.05) and ApoE-/- mice (9.3 ± 2.9% versus 23.4 ± 4.6% adhesion; P < 0.05) concomitant with an inhibition of endothelial intercellular adhesion molecule-1 expression. NCX 6550 also significantly reduced phorbol 12-myristate 13-acetate-induced ROS production that was enhanced in isolated ApoE-/- splenocytes. Conversely, pravastatin had no significant effects on adhesion in normal or ApoE-/- mice but reduced the enhanced ROS production from ApoE-/- splenocytes. In separate groups of ApoE-/- mice, NCX 6550 significantly enhanced endothelium-dependent relaxation to carbachol in aortic segments precon-tracted with phenylephrine (-logEC50, 6.37 ± 0.37) compared with both vehicle-treated (-logEC50, 5.81 ± 0.15; P < 0.001) and pravastatin-treated (-logEC50, 5.57 ± 0.45; P < 0.05) mice. NCX 6550 also significantly reduced plasma monocyte chemoattractant protein-1 levels (648.8 pg/ml) compared with both vehicle (1191.1 pg/ml; P < 0.001) and pravastatin (847 ± 71.0 pg/ml; P < 0.05) treatment. These data show that NCX 6550 exerts superior anti-inflammatory actions compared with pravastatin, possibly through NO-related mechanisms.

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2′,4′-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives

We thank European Commission (project “PET BRAIN: Mapping the brain with PET radiolabeled cannabinoid CB1 ligands”; FP7-People-2009-IAPP; Grant Agreement N.25142).

"Jag tänkte bara 15 + 7 –6" : En empiriskstudie omelevers tolkning av likhetstecknetoch sambandet mellan addition och subtraktion

Syftet med denna studie är att undersöka elevers förståelseav likhetstecknet och sambandet mellan addition och subtraktioni årskurs 3 samt deras klassläraresuppfattning av den egna matematikundervisningen, som behandlar addition, subtraktion och likhetstecknet.Studiens syfte besvaras genom följande frågeställningar: Vad kan specifikt utformade matematikuppgifter ge för information om elevers förståelse av likhetstecknet och sambandet mellan addition och subtraktioni årskurs 3?samtVad tänker en lärare om de resultat som framkommit av elevernas matematikuppgifter? Den empiriska undersökningen har genomförts med en kvantitativ metod, i form av en enkät där elever i årskurs 3 fått lösa speciellt utformade matematikuppgifter och en kvalitativ metod, i form av semi-struktureradintervju med elevernas lärare. Det resultat som framkommit i undersökningen har analyserats med hjälp av en innehållsanalys. Resultatet visar att alla elever intehar kunskapom att likhetstecknet indikerar ekvivalens mellan höger sida och vänster sida om likhetstecknet, men en majoritetav eleverna har den förståelsen. Det var inte väntat från lärarens sida att fyra eleverhelthade missförstått likhetstecknetsbetydelse. Läraren är medveten om att likhetstecknet kan vara svårt attförstå, men hade förväntat att alla elever skulle klara av att lösa minst matematikuppgifterna med delägsta talen.Resultatet visar även att nio av sexton elever har förstått sambandet mellan addition och subtraktion.Läraren menar att det sambandet återkommer under hela lågstadiet och därför hade förväntat sig att fler elever sett sambandet. Men samtidigt anser läraren att det är positivt att lite mer än halva gruppen har förstått sambandet mellan addition och subtraktion. Slutligen visar resultatet av studien att missförståelse av likhetstecknet har inverkan på elevers resultat vid uppgifter med öppna utsagor, men inte vid uppgifter där talen på vänster sida om likhetstecknet är likamed ett tal på höger sida om likhetstecknet.

Using Action Research to Develop My Solution-Focused Practice in Collaboration with Year 6 And 7 Pupils When Discussing Their Behavioural Self-Regulation at School

This action research study aimed to develop the researcher's use of solutionfocused techniques when working with Year 6 and 7 pupils’ self-regulation. A systematic literature review highlighted an evidence base that demonstrated the efficacy of solution-focused methods when working with this population. The researcher’s intention was to add to the body of Educational Psychology practice-based evidence in this area. The researcher recruited eight participants from primary and secondary school provisions. Solution-focused techniques were systematically trialled in partnership with the pupils and were modified through an action research cycle. Semistructured interviewing provided participants the opportunity to critically evaluate the researcher’s solution-focused practice. Thematic Analysis was used to assess feedback in order to adapt the delivery of solution-focused techniques. Developments to practice explored within this study included modifications to the use of the six core components of Solution Focused Brief Therapy. Adaptations have the potential to inform the use of these solution-focused approaches with other educational practitioners.