Análise térmica de esparfloxacino

Sparfloxacin, a third-generation fluoroquinolone, is a potent antibacterial agent against a wide range of Gram-positive and Gram-negative organisms, for example Streptococcus pneumonias, Staphylococcus aureus (including methicillin-resistant strains), Legionella spp., Mycoplasma spp., Chlamydia spp. and Mycobacterium spp. This compound has been submitted to thermal analysis and the results are presented here. The DSC curve of sparfloxacin has an endothermic peak that indicates a melting point at 276.5 °C. The DTA curve of the sample in synthetic air shows two exothermic peaks, at 341.6 and 579.2 °C, attributed to compound decomposition. In the TG curve, the loss of mass can be seen to occur in two steps between 285.5 and 645.3 °C. The DTA curve obtained in a nitrogen atmosphere shows an exothermic peak, with decomposition of sparfloxacin at 340.0 °C; from the corresponding TG plot, the loss of mass starts at 254.4 °C.

Optical properties and energy-transfer frequency upconversion of Yb 3+-sensitized Ho3+- And Tb3+-doped lead-cadmium-germanate glass and glass ceramic

In this report we investigate the optical properties and energy-transfer upconversion luminescence of Ho3+- and Tb3+/Yb 3+-codoped PbGeO3-PbF2-CdF2 glass-ceramic under infrared excitation. In Ho3+/Yb 3+-codoped sample, green(545 nm), red(652 nm), and near-infrared(754 nm) upconversion luminescence corresponding to the 4S 2(5F4) → 5I8, 5F5 → 5I8, and 4S2(5F4) → 5I 7, respectively, was readly observed. Blue(490 nm) signals assigned to the 5F2,3 → 5I8 transition was also detected. In the Tb3+/Yb3+ system, bright UV-visible emission around 384, 415, 438, 473-490, 545, 587, and 623 nm, identified as due to the 5D3(5G6) → 7FJ(J=6,5,4) and 5D4→ 7FJ(J=6,5,4,3) transitions, was measured. The comparison of the upconversion process in glass ceramic and its glassy precursor revealed that the former samples present much higher upconversion efficiencies. The dependence of the upconversion emission upon pump power, and doping contents was also examined. The results indicate that successive energy-transfer between ytterbium and holmium ions and cooperative energy-transfer between ytterbium and terbium ions followed by excited-state absorption are the dominant upconversion excitation mechanisms herein involved. The viability of using the samples for three-dimensional solid-state color displays is also discussed.

Crystal and molecular structure of dinuclear palladium(II) complex containing nitrogen and phosphorus donor ligands, [Pd2(N3)4(PPh3)2(μ-ted)]

The dinuclear azido-palladium(II) complex [Pd2(N3)4(PPh3)2(μ-ted)], where PPh3 = triphenylphosphine and ted = triethylenediamine, was synthesized and characterized by single-crystal X-ray diffraction. The title compound was crystallized in a triclinic system, space group P1 with a = 11.5875(2)Å, b = 13.0817(3)Å, c = 15.2618(3)Å, α = 93.306(2)°, β =110.040(1)°, γ = 98.486(1)°, V = 2134.95(8)Å3, Z = 2. Each Pd(II) center displays a distorted squareplanar coordination environment formed by two N atoms from two trans terminally coordinated azido groups, one P atom from the phosphine and one N atom from the bridging ted ligand. 2008 © The Japan Society for Analytical Chemistry.

Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is associated with decreased NO production in a mercury-exposed population

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a potent vasodilator and plays a prominent role in regulating the cardiovascular system. Decreased basal NO release may predispose to cardiovascular diseases. Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene may regulate eNOS expression. On the other hand, some recent reports strongly suggest an association between methylmercury (MeHg) exposures and altered NO synthesis. In the present study, we investigate the contribution of the 27-pb tandem repeat polymorphism on nitric oxide production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population. Two-hundred-two participants (98 men and 104 women), all chronically exposed to MeHg through fish consumption were examined. Mean blood Hg concentration and nitrite plasma concentration were 50.5 +/- 35.4 mu g/L and 251.4 +/- 106.3 nM, respectively. Mean systolic and diastolic blood pressure were 120.1 +/- 19.4 mm Hg and 72.0 +/- 10.6 mm Hg, respectively. Mean body mass index was 24.5 +/- 4.3 kg/m(2) and the mean heart rate was 69.8 +/- 11.8 bpm. There were no significant differences in age, arterial blood pressure, body mass index or cardiac frequency between genotype groups (all P>0.05). However, we observed different nitrite concentrations in the genotypes groups, with lower nitrite levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4 polymorphism contributed to nitrite reduction as a result of blood Hg concentration. Taken together, our results show that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels. (C) 2011 Elsevier B.V. All rights reserved.

Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src-Dependent Pathways

Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10(-7) mol/L, 0-120 minutes). Testosterone increased ROS generation, assessed by dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence (30 minutes [SHR] and 60 minutes [both strains]). Flutamide (androgen receptor antagonist) and actinomycin D (gene transcription inhibitor) diminished ROS production (60 minutes). Testosterone increased Nox1 and Nox4 mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively. Flutamide, actinomycin D, and cycloheximide (protein synthesis inhibitor) diminished testosterone effects on p47phox. c-Src phosphorylation was observed at 30 minutes (SHR) and 120 minutes (Wistar-Kyoto rat). Testosterone-induced ROS generation was repressed by 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine (c-Src inhibitor) in SHRs and reduced by apocynin (antioxidant/NADPH oxidase inhibitor) in both strains. Testosterone stimulated VSMCs migration, assessed by the wound healing technique, with greater effects in SHRs. Flutamide, apocynin, and 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day] pyrimidin-4-amine blocked testosterone-induced VSMCs migration in both strains. Our study demonstrates that testosterone induces VSMCs migration via NADPH oxidase-derived ROS and c-Src-dependent pathways by genomic and nongenomic mechanisms, which are differentially regulated in VSMCs from Wistar-Kyoto rats and SHRs. (Hypertension. 2012; 59: 1263-1271.). Online Data Supplement

From 3,3,4,4-Tetraethoxybut-1-yne to furan derivatives

The starting material for this project was the highly functionalized compound 3,3,4,4- tetraethoxybut-1-yne (TEB) and it can be prepared from ethyl vinyl ether by a 4-steps synthesis. The third and the fourth step in TEB synthesis were sensitive to reaction conditions, so it was developed a strategy to try to optimize the third step and obtain TEB with higher yields. An approach, which tries to optimize also the fourth step, will be developed in further works. Several γ-hydroxy-α,β-unsaturated acetylenic ketones can be prepared from 3,3,4,4- tetraethoxybut-1-yne. TEB and γ-hydroxy-α,β-unsaturated acetylenic ketones have been previously synthesized in good yields using various reaction routes. In this work will be shown the synthesis of 1,1-diethoxy-5-hydroxyhex-3-yn-2-one, 1,1-diethoxy-5-hydroxyundec-3-yn-2-one and 1,1-diethoxy-5-hydroxydodec-3-yn-2-one, which will react with ethyl acetoacetate to give, respectively, ethyl 4-(3,3-diethoxy-2-oxopropyl)-2,5-dimethylfuran-3-carboxylate, ethyl 4-(3,3-diethoxy-2-oxopropyl)-5-hexyl-2-methylfuran-3-carboxylate and ethyl 4-(3,3-diethoxy-2-oxopropyl)- 5-heptyl-2-methylfuran-3-carboxylate furan derivatives. This thesis project was carried out during the year 2011, at the Department of Chemistry of the University of Bergen.

Previsione del comportamento dinamico e sismico di un edificio a tre piani in scala reale costituito da pareti sandwich in C.A. gettato in opera da provare su tavola vibrante

INDICE INTRODUZIONE 1 1. DESCRIZIONE DEL SISTEMA COSTRUTTIVO 5 1.1 I pannelli modulari 5 1.2 Le pareti tozze in cemento armato gettate in opera realizzate con la tecnologia del pannello di supporto in polistirene 5 1.3 La connessione tra le pareti e la fondazione 6 1.4 Le connessioni tra pareti ortogonali 7 1.5 Le connessioni tra pareti e solai 7 1.6 Il sistema strutturale così ottenuto e le sue caratteristiche salienti 8 2. RICERCA BIBLIOGRAFICA 11 2.1 Pareti tozze e pareti snelle 11 2.2 Il comportamento scatolare 13 2.3 I muri sandwich 14 2.4 Il “ferro-cemento” 15 3. DATI DI PARTENZA 19 3.1 Schema geometrico - architettonico definitivo 19 3.2 Abaco delle sezioni e delle armature 21 3.3 Materiali e resistenze 22 3.4 Valutazione del momento di inerzia delle pareti estese debolmente armate 23 3.4.1 Generalità 23 3.4.2 Caratteristiche degli elementi provati 23 3.4.3 Formulazioni analitiche 23 3.4.4 Considerazioni sulla deformabilità dei pannelli debolmente armati 24 3.4.5 Confronto tra rigidezze sperimentali e rigidezze valutate analiticamente 26 3.4.6 Stima di un modulo elastico equivalente 26 4. ANALISI DEI CARICHI 29 4.1 Stima dei carichi di progetto della struttura 29 4.1.1 Stima dei pesi di piano 30 4.1.2 Tabella riassuntiva dei pesi di piano 31 4.2 Analisi dei carichi da applicare in fase di prova 32 4.2.1 Pesi di piano 34 4.2.2 Tabella riassuntiva dei pesi di piano 35 4.3 Pesi della struttura 36 4.3.1 Ripartizione del carico sulle pareti parallele e ortogonali 36 5. DESCRIZIONE DEL MODELLO AGLI ELEMENTI FINITI 37 5.1 Caratteristiche di modellazione 37 5.2 Caratteristiche geometriche del modello 38 5.3 Analisi dei carichi 41 5.4 Modello con shell costituite da un solo layer 43 5.4.1 Modellazione dei solai 43 5.4.2 Modellazione delle pareti 44 5.4.3 Descrizione delle caratteristiche dei materiali 46 5.4.3.1 Comportamento lineare dei materiali 46 6. ANALISI DEL COMPORTAMENTO STATICO DELLA STRUTTURA 49 6.1 Azioni statiche 49 6.2 Analisi statica 49 7. ANALISI DEL COMPORTAMENTO DINAMICO DELLA STRUTTURA 51 7.1 Determinazione del periodo proprio della struttura con il modello FEM 51 7.1.1 Modi di vibrare corrispondenti al modello con solai e pareti costituiti da elementi shell 51 7.1.1.1 Modi di vibrare con modulo pari a E 51 7.1.1.2 Modi di vibrare con modulo pari a 0,5E 51 7.1.1.3 Modi di vibrare con modulo pari a 0,1E 51 7.1.2 Modi di vibrare corrispondenti al modello con solai infinitamente rigidi e pareti costituite da elementi shell 52 7.1.2.1 Modi di vibrare con modulo pari a E 52 7.1.2.2 Modi di vibrare con modulo pari a 0,5E 52 7.1.2.3 Modi di vibrare con modulo pari a 0,1E: 52 7.1.3 Modi di vibrare corrispondenti al modello con solai irrigiditi con bielle e pareti costituite da elementi shell 53 7.1.3.1 Modi di vibrare con modulo pari a E 53 7.1.3.2 Modi di vibrare con modulo pari a 0,5E 53 7.1.3.3 Modi di vibrare con modulo pari a 0,1E 53 7.2 Calcolo del periodo proprio della struttura assimilandola ad un oscillatore semplice 59 7.2.1 Analisi svolta assumendo l’azione del sisma in ingresso in direzione X-X 59 7.2.1.1 Analisi svolta assumendo il modulo elastico E pari a 300000 Kg/cm2 59 7.2.1.1.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 59 7.2.1.1.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 61 7.2.1.1.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 63 7.2.1.1.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 66 7.2.1.2 Analisi svolta assumendo il modulo elastico E pari a 150000 Kg/cm2 69 7.2.1.2.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5E 69 7.2.1.2.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,5E 71 7.2.1.2.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 73 7.2.1.2.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 76 7.2.1.3 Analisi svolta assumendo il modulo elastico E pari a 30000 Kg/cm2 79 7.2.1.3.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1E 79 7.2.1.3.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,1E 81 7.2.1.3.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 83 7.2.1.3.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 86 7.2.2 Analisi svolta assumendo l’azione del sisma in ingresso in direzione Y-Y 89 7.2.2.1 Analisi svolta assumendo il modulo elastico E pari a 300000 Kg/cm2 89 7.2.2.1.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 89 7.2.2.1.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 91 7.2.2.1.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 93 7.2.2.1.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 98 7.2.2.1.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 103 7.2.2.1.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 105 7.2.2.1.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 107 7.2.2.1.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 112 7.2.2.2 Analisi svolta assumendo il modulo elastico E pari a 150000 Kg/cm2 117 7.2.2.2.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5E 117 7.2.2.2.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,5E 119 7.2.2.2.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 121 7.2.2.2.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 126 7.2.2.2.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5 E 131 7.2.2.2.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 133 7.2.2.2.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 135 7.2.2.2.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 140 7.2.2.3 Analisi svolta assumendo il modulo elastico E pari a 30000 Kg/cm2 145 7.2.2.3.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1E 145 7.2.2.3.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,1E 147 7.2.2.3.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 149 7.2.2.3.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 154 7.2.2.3.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1 E 159 7.2.2.3.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 161 7.2.2.3.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 163 7.2.2.3.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 168 7.3 Calcolo del periodo proprio della struttura approssimato utilizzando espressioni analitiche 174 7.3.1 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente un peso P gravante all’estremo libero 174 7.3.1.1 Riferimenti teorici: sostituzione di masse distribuite con masse concentrate 174 7.3.1.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 177 7.3.1.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 179 7.3.2 Approssimazione della struttura ad una mensola incastrata alla base, di peso Q=ql, avente un peso P gravante all’estremo libero e struttura resistente costituita dai soli “maschi murari”delle pareti parallele all’azione del sisma 181 7.3.2.1 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 181 7.3.2.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 186 7.3.3 Approssimazione della struttura ad un portale avente peso Qp = peso di un piedritto, Qt=peso del traverso e un peso P gravante sul traverso medesimo 191 7.3.3.1 Riferimenti teorici: sostituzione di masse distribuite con masse concentrate 191 7.3.3.2 Applicazione allo specifico caso di studio in esame con modulo ellastico E=300000 kg/cm2 192 7.3.3.3 Applicazione allo specifico caso di studio in esame con modulo ellastico E=30000 kg/cm2 194 7.3.4 Approssimazione della struttura ad un portale di peso Qp = peso di un piedritto, Qt=peso del traverso e avente un peso P gravante sul traverso medesimo e struttura resistente costituita dai soli “maschi murari”delle pareti parallele all’azione del sisma 196 7.3.4.1 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 196 7.3.4.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 201 7.3.5 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente le masse m1,m2....mn concentrate nei punti 1,2….n 206 7.3.5.1 Riferimenti teorici: metodo approssimato 206 7.3.5.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 207 7.3.5.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 209 7.3.6 Approssimazione della struttura ad un telaio deformabile con tavi infinitamente rigide 211 7.3.6.1 Riferimenti teorici: vibrazioni dei telai 211 7.3.6.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 212 7.3.6.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 215 7.3.7 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente masse m1,m2....mn concentrate nei punti 1,2….n e studiata come un sistema continuo 218 7.3.7.1 Riferimenti teorici: metodo energetico; Masse ripartite e concentrate; Formula di Dunkerley 218 7.3.7.1.1 Il metodo energetico 218 7.3.7.1.2 Masse ripartite e concentrate. Formula di Dunkerley 219 7.3.7.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 221 7.3.7.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 226 7.4 Calcolo del periodo della struttura approssimato mediante telaio equivalente 232 7.4.1 Dati geometrici relativi al telaio equivalente e determinazione dei carichi agenti su di esso 232 7.4.1.1 Determinazione del periodo proprio della struttura assumendo diversi valori del modulo elastico E 233 7.5 Conclusioni 234 7.5.1 Comparazione dei risultati relativi alla schematizzazione dell’edificio con una struttura ad un grado di libertà 234 7.5.2 Comparazione dei risultati relativi alla schematizzazione dell’edificio con una struttura a più gradi di libertà e a sistema continuo 236 8. ANALISI DEL COMPORTAMENTO SISMICO DELLA STRUTTURA 239 8.1 Modello con shell costituite da un solo layer 239 8.1.1 Analisi dinamica modale con spettro di risposta avente un valore di PGA pari a 0,1g 239 8.1.1.1 Generalità 239 8.1.1.2 Sollecitazioni e tensioni sulla sezione di base 242 8.1.1.2.1 Combinazione di carico ”Carichi verticali più Spettro di Risposta scalato ad un valore di PGA pari a 0,1g” 242 8.1.1.2.2 Combinazione di carico ”Spettro di Risposta scalato ad un valore di 0,1g di PGA” 245 8.1.1.3 Spostamenti di piano 248 8.1.1.4 Accelerazioni di piano 248 8.1.2 Analisi Time-History lineare con accelerogramma caratterizzato da un valore di PGA pari a 0,1g 249 8.1.2.1 Generalità 249 8.1.2.2 Sollecitazioni e tensioni sulla sezione di base 251 8.1.2.2.1 Combinazione di carico ” Carichi verticali più Accelerogramma agente in direzione Ye avente una PGA pari a 0,1g” 251 8.1.2.2.2 Combinazione di carico ” Accelerogramma agente in direzione Y avente un valore di PGA pari a 0,1g ” 254 8.1.2.3 Spostamenti di piano assoluti 257 8.1.2.4 Spostamenti di piano relativi 260 8.1.2.5 Accelerazioni di piano assolute 262 8.1.3 Analisi dinamica modale con spettro di risposta avente un valore di PGA pari a 0,3g 264 8.1.3.1 Generalità 264 8.1.3.2 Sollecitazioni e tensioni sulla sezione di base 265 8.1.

Synthese, 11 C- und 18 F-Markierung und Evaluierung von Repaglinid-Derivaten zur Quantifizierung der pankreatischen beta-Zell-Masse in vivo mittels PET

Diabetes mellitus umfasst eine heterogene Gruppe von Stoffwechselfunktionsstörungen, die durch hohe Blut-Glukose-Werte gekennzeichnet sind. Zwei Haupttypen von Diabetes mellitus wurden definiert: Typ 1- und Typ 2-Diabetes. Repaglinid ist ein neuer, schnell wirksamer, bei Typ 2-Diabetikern eingesetzter prandialer Glukose-Regulator mit einer kurzen Plasmahalbwertszeit (<1 Stunde) und der erste Vertreter der Carbamoylmethylbenzoesäure Familie, der in klinischen Studien getestet wurde. Die 18F- und 11C-markierten Repaglinid-Derivate (S)-2-(2-[18F]Fluorethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoesäure ([18F]Fluorethoxy-desethoxy-Repaglinid) und (S)-2-([11C]Methoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carba-moyl]-benzoesäure ([11C]Methoxy-desethoxy-Repaglinid) wurden als potentielle Tracer für die nicht-invasive Quantifizierung des Sulfonylharnstoffrezeptor-Typ1-Status (SUR-1) der Insulin-sezernierenden -Zellen mittels Positronen-Emissions-Tomographie (PET) synthetisiert. [18F]Fluorethoxy-desethoxy-Repaglinide konnte in einer radiochemischen Ausbeute (RCA) von 20% nach 135 Minuten mit einer radiochemischen Reinheit >98% unter Verwendung des sekundären Markierungsvorläufers 2-[18F]Fluorethyltosylat erhalten werden. Die spezifische Aktivität lag im Bereich von 50-60 GBq/µmol. Für die radioaktive Synthese des [11C]Methoxy-desethoxy-Repaglinids wurde der sekundäre Markierungsvorläufer [11C]Methyliodid verwendet. Der 11C-Radiotracer wurde in einer RCA von 35% (bezogen auf [11C]CO2) mit einer spezifischen Aktivität von 40-70 GBq/µmol erhalten. Um die Eigenschaften des fluorierten sowie des methoxylierten Repaglinids zu charakterisieren, wurde die Affinität beider Verbindungen zum humanen SUR-1 evaluiert. [19F]Fluorethoxy-desethoxy-Repaglinid und Methoxy-desethoxy-Repaglinid induzierten Verdrängungskurven mit Hill-Koeffizienten nahe 1 und ergaben Dissotiationskonstanten (KD) von 142 nM beziehungsweise 83 nM - vergleichsweise geringe Verluste relativ zu Original-Repaglinid. Die biologische Aktivität wurde mittels Insulin-Sekretionstests an isolierten Ratten-Inselzellen gezeigt und war ebenfalls mit der des Repaglinids vergleichbar. Schließlich wurde die Biodistribution des [18F]Fluorethoxy-desethoxy-Repaglinids in gesunden Sprague-Dawley-Ratten durch Messung der Konzentration der Verbindung in verschiedenen Organen nach intravenöser Injektion untersucht. Das pankreatische Gewebe zeigte im Zeitintervall zwischen 10 und 30 Minuten nach Injektion eine stabile Akkumulation von etwa 0.12% der injizierten Dosis. 50% dieser Tracer-Akkulmulation konnten durch zusätzliche Injektion von nicht-radioaktiv-markiertem Repaglinid verdrängt werden, was auf eine mögliche Eignung des [18F]Fluorethoxy-desethoxy-Repaglinids für in vivo-Untersuchungen mittels PET schließen lässt. Eine erste humane PET-Studie zeigte zwar ebenfalls eine stabile, allerdings nur geringere Akkumulation von [18F]Fluorethoxy-desethoxy-Repaglinid im Pankreas und eine überproportional hohe Aktivitätsanreicherung in der Leber. Die Radioaktivitäts-akkumulation im Blut fiel nach wenigen Minuten unter die des Pankreas.

Stereoselektive Synthesen von Stickstoffheterocyclen aus 4-substituierten N-Galactosyl-dehydropiperidinonen

Ziel dieser Arbeit war es, an in 4-Position substituierten N-Galactosyl-dehydropiperidinonen die übrigen Positionen des Heterocycluses selektiv zu funktionalisieren und die erarbeiteten Methoden im Rahmen von Total- und Partialsynthesen biologisch aktiver Verbindungen anzuwenden. Ausgehend von N-Galactosyl-2-pyridon, welches sich in drei Stufen aus D-Galactose im Gramm-Maßstab erhalten lässt, konnten die in Position 4-substituierten Dehydropiperidinone in regio- und diastereoselektiv verlaufenden Additionen von Grignard-Reagenzien und Organocupraten synthetisiert werden. Es gelang die Einführung sowohl unverzweigter als auch sekundärer, tertiärer und cyclischer Alkylreste. Ebenfalls gute Ausbeuten und exzellente Diastereoselektivitäten wurden bei der konjugierten Addition verschieden substituierter Aryl- und Benzyl-Grignard-Reagenzien erhalten. Das Kohlenhydratauxiliar kontrolliert dabei nicht nur die faciale Selektivität, sondern es bestimmt gleichzeitig die Regioselektivität. Die absolute Konfiguration der 4-substituierten 2-Pyridone konnte durch Röntgenstrukturanalysen zweier Produkte zweifelsfrei geklärt werden. Dass die so dargestellten Heterocyclen wertvolle Synthone zur asymmetrischen Synthese mehrfach substituierter Piperidinverbindungen sind, konnte gezeigt werden durch die Ausarbeitung verschiedener Methoden zur weitergehenden Funktionalisierung an den Positionen C-2, C-3, C-5 und C-6 sowie durch die Entwicklung eines Verfahrens zur Freisetzung der stereoselektiv synthetisierten Heterocyclen. Diese systematisch untersuchten Synthesewege konnten in Partial- und Totalsynthesen von pharmakologisch relevanten Verbindungen erfolgreich beschritten werden. So gelang die Synthese des biologisch aktiven (3S)-Piperidinols, sowie die des 3-Hydroxy-4-(4-fluorphenyl)-piperidin-Derivates. Weiterhin gelang die formale Totalsynthese von (+)-Paroxetin, welches einen pharmakologisch interessanten Wirkstoff mit der Struktur eines 3,4-trans-disubstituierten Piperidins darstellt. Ein weiterer Themenschwerpunkt dieser Arbeit war die regio- und stereoselektive Synthese von Benzomorphan-Derivaten. Diese gelang durch intramolekulare Amino-Alkylierung der 4-Benzyl-substituierten Dehydropiperidinone. Durch Anwendung dieser Methodik konnte eine Reihe verschieden substituierter 7,8-Benzomorphan-Derivate synthetisiert werden, die interessante Zwischenstufen in der asymmetrischen Benzomorphansynthese darstellen. In einer exemplarischen Synthese wurde so das 7,8-Benzomorphan hergestellt.

Elaeocarpacae-Alkaloide: flexible Synthese optisch aktiver (-) Elaeokanin C Schlüsselbausteine

Kurzzusammenfassung Elaeocarpacae-Alkaloide: flexible Synthesen optisch aktiver (-) Elaeokanin C Schlüsselbausteine Im Tier- und Pflanzenreich sind Alkaloide weit verbreitet und werden von der Biogenese her als Produkte des Aminosäure-Stoffwechsels angesehen. Die Elaeocarpacae-Alkaloide zählen zu den Indolizidinen, welche durch ein Azabicyclo-[4.3.0]-nonan Grundgerüst charakterisiert sind und erstmals Ende der 60er Jahre des letzten Jahrhunderts aus den Blättern der in Neu Guinea beheimateten Ölbaumgewächse isoliert wurden. Für verschiedene Vertreter dieses Alkaloid-Typs wurden sowohl racemische als auch asymmetrische Totalsynthesen entwickelt. Während für das (+) Elaeokanin C bereits Totalsynthesen existieren, gibt es für das (-) Elaeokanin C bis heute keine asymmetrische Synthese. Als Fernziel der vorliegenden Arbeit wurde die erste Totalsynthese von (-) Elaeokanin C ausgewählt. Der Syntheseplan sieht zunächst den diastereoselektiven Aufbau eines optisch aktiven Schlüsselbausteins mit Naturstoff-Stereotriade im Sinne einer konvergenten ex-chiral-pool Synthese vor. Im Rahmen dieser Arbeit konnte dies durch die Aza-Claisen-Umlagerung realisiert werden. Ausgehend von diesem Schlüsselbaustein wurden verschiedene Synthesewege verfolgt um sowohl das Substitutionsmuster der Seitenkette als auch das des Piperidinsegments vielfältig variieren zu können. Die Einführung der Seitenkette erwies sich durch vielfältige Nachbargruppeneffekte wie die unerwünschte 5-exo-trig Cyclisierung zu einem Pyrrolizidin Derivat als große Hürde. Eine geänderte Synthesestrategie mit einem schrittweisen Aufbau der Kette lieferte schließlich den Baustein, aus dem nun in wenigen Stufen das (-) Elaeokanin C sowie vielfältige Analoga herzustellen sein sollten.

Impact of Lifetime Alcohol Use on Liver Fibrosis in a Population of HIV-Infected Patients With and Without Hepatitis C Coinfection

BACKGROUND: The effect of alcohol on liver disease in HIV infection has not been well characterized. METHODS: We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, "FIB-4," which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index ("APRI"), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). RESULTS: Subjects (n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus (HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm(3) . Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis (FIB-4 <1.45) (adjusted odds ratio [AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis (FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. CONCLUSIONS: In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population.

Cardiac c-kit+AT2+ cell population is increased in response to ischemic injury and supports cardiomyocyte performance

The expression pattern of angiotensin AT2 receptors with predominance during fetal life and upregulation under pathological conditions during tissue injury/repair process suggests that AT2 receptors may exert an important action in injury/repair adaptive mechanisms. Less is known about AT2 receptors in acute ischemia-induced cardiac injury. We aimed here to elucidate the role of AT2 receptors after acute myocardial infarction. Double immunofluorescence staining showed that cardiac AT2 receptors were mainly detected in clusters of small c-kit+ cells accumulating in peri-infarct zone and c-kit+AT2+ cells increased in response to acute cardiac injury. Further, we isolated cardiac c-kit+AT2+ cell population by modified magnetic activated cell sorting and fluorescence activated cell sorting. These cardiac c-kit+AT2+ cells, represented approximately 0.19% of total cardiac cells in infarcted heart, were characterized by upregulated transcription factors implicated in cardiogenic differentiation (Gata-4, Notch-2, Nkx-2.5) and genes required for self-renewal (Tbx-3, c-Myc, Akt). When adult cardiomyocytes and cardiac c-kit+AT2+ cells isolated from infarcted rat hearts were cocultured, AT2 receptor stimulation in vitro inhibited apoptosis of these cocultured cardiomyocytes. Moreover, in vivo AT2 receptor stimulation led to an increased c-kit+AT2+ cell population in the infarcted myocardium and reduced apoptosis of cardiomyocytes in rats with acute myocardial infarction. These data suggest that cardiac c-kit+AT2+ cell population exists and increases after acute ischemic injury. AT2 receptor activation supports performance of cardiomyocytes, thus contributing to cardioprotection via cardiac c-kit+AT2+ cell population.

Thermal acclimation to 4 or 10 degrees C imparts minimal benefit on swimming performance in Atlantic cod (Gadus morhua L.).

Thermal acclimation is frequently cited as a means by which ectothermic animals improve their Darwinian fitness, i.e. the beneficial acclimation hypothesis. As the critical swimming speed (U (crit)) test is often used as a proxy measure of fitness, we acclimated Atlantic cod (Gadus morhua) to 4 and 10 degrees C and then assessed their U (crit) swimming performance at their respective acclimation temperatures and during acute temperature reversal. Because phenotypic differences exist between different populations of cod, we undertook these experiments in two different populations, North Sea cod and North East Arctic cod. Acclimation to 4 or 10 degrees C had a minimal effect on swimming performance or U (crit), however test temperature did, with all groups having a 10-17% higher U (crit) at 10 degrees C. The swimming efficiency was significantly lower in all groups at 4 degrees C arguably due to the compression of the muscle fibre recruitment order. This also led to a reduction in the duration of "kick and glide" swimming at 4 degrees C. No significant differences were seen between the two populations in any of the measured parameters, due possibly to the extended acclimation period. Our data indicate that acclimation imparts little benefit on U (crit) swimming test in Atlantic cod. Further efforts need to identify the functional consequences of the long-term thermal acclimation process.

Functional importance of conserved nucleotides at the histone RNA 3' processing site.

Histone pre-mRNA 3' processing is controlled by a hairpin element preceding the processing site that interacts with a hairpin-binding protein (HBP) and a downstream spacer element that serves as anchoring site for the U7 snRNP. In addition, the nucleotides following the hairpin and surrounding the processing site (ACCCA'CA) are conserved among vertebrate histone genes. Single to triple nucleotide mutations of this sequence were tested for their ability to be processed in nuclear extract from animal cells. Changing the first four nucleotides had no qualitative and little if any quantitative effects on histone RNA 3' processing in mouse K21 cell extract, where processing of this gene is virtually independent of the HBP. A gel mobility shift assay revealing HBP interactions and a processing assay in HeLa cell extract (where the contribution of HBP to efficient processing is more important) showed that only one of these mutations, predicted to extend the hairpin by one base pair, affected the interaction with HBP. Mutations in the next three nucleotides affected both the cleavage efficiency and the choice of processing sites. Analysis of these novel sites indicated a preference for the nucleotide 5' of the cleavage site in the order A > C > U > G. Moreover, a guanosine in the 3' position inhibited cleavage. The preference for an A is shared with the cleavage/polyadenylation reaction, but the preference order for the other nucleotides is different [Chen F, MacDonald CC, Wilusz J, 1995, Nucleic Acids Res 23:2614-2620].