Structural aspects of polyanion and hydrophobically modified polycation multilayers on hydrophilic or hydrophobic surfaces

Multilayer films of carboxymethylcellulose (CMC), a polyanion, and bromide salts of poly(4-vinylpyridine) quaternized with linear aliphatic chains of 2 (ethyl) and 5 (pentyl) carbon atoms, coded as QPVP-C2 and QPVP-C5, respectively, were fabricated by layer-by-layer (LbL) self-assembly onto Si/SiO2 wafers (hydrophilic substrate) or polystyrene, PS, films (hydrophobic substrate). The films were characterized by means of ex situ and in situ ellipsometry, atomic force microscopy (AFM), contact angle measurements and sum frequency generation vibrational spectroscopy (SFG). Antimicrobial tests were used to assess the exposure of pyridinium moieties to the aqueous medium. In situ ellipsometry indicated that for Si/SiO2 the chains were more expanded than the PS films and both substrates systems composed of QPVP-C5 were thicker than those with QPVP-C2. For dried layers, the alkyl side group size had a small effect on the thickness evolution, regardless of the substrate. At pH 2 the multilayers showed high resistance, evidencing that the build-up is driven not only by cooperative polymer-polymer ion pairing, but also by hydrophobic interactions between the alkyl side chains. The LbL films became irregular as the number of depositions increased. After the last deposition, the wettability of QPVP-C2 or QPVP-C5 terminated systems on the Si/SiO2 wafers and PS films were similar, except for QPVP-C2 on Si/SiO2 wafers. Unlike the morphology observed for LbL films on Si/SiO2 wafers, PS induced the formation of porous structures. SFG showed that in air the molecular orientation of pyridinium groups in multilayers with QPVP-C5 was stronger than in those containing QPVP-C2. The exposure of pyridinium moieties to the aqueous medium was more pronounced when the LbL were assembled on Si/SiO2 wafers.

Efeito de revestimentos comestíveis na conservação de mamões minimamente processados

Avaliou-se o efeito de revestimentos à base de carboidratos nas características microbiológicas, físicas, físico-químicas e sensoriais de mamão Formosa minimamente processado (MP), armazenado sob refrigeração. Após tratamento com cloreto de cálcio, os frutos descascados e cortados foram imersos em soluções de amido de arroz (AA) 3%; alginato de sódio (AS) 0,5%; carboximetilcelulose (CMC) 0,25%, e armazenados a 5 ºC e 90% de UR. Os produtos foram avaliados nos dias 1, 3, 6, 9, 12 e 15. O uso de revestimentos à base de AA, AS e CMC em mamões MP resultou em menor contagem de coliformes totais que o controle. Mamões revestidos com AA e CMC apresentaram redução e aumento do processo respiratório, respectivamente. Os frutos revestidos apresentaram menores teores de sólidos solúveis e seus valores de pH se tornaram menores após o 9º dia de armazenamento. O uso da CMC como revestimento proporcionou, no 15º dia, maior firmeza da polpa. As variações nos parâmetros de cor (Luminosidade, Hue e Croma) não comprometeram a qualidade sensorial do mamão MP. Os atributos sensoriais dos mamões com revestimentos não diferiram do controle durante os 15 dias de estudo. Como a maioria dos efeitos positivos das coberturas ocorreu aos 12º e 15º dias e, considerando-se o custo da tecnologia e o preço dos revestimentos, a melhor opção, até 9 dias de armazenamento, consiste em apenas sanitizar os frutos, como feito no controle. Se o interesse for preservar a vida útil por um período maior, até 15 dias, os revestimentos utilizados podem ter resultados satisfatórios, desde que respeitadas as condições de estocagem utilizadas no estudo.

Studies on the interaction of surfactants and neutral cyclodextrins by capillary electrophoresis. Application to chiral analysis

In the present study, mixed systems composed of SDS in the presence of neutral cyclodextrins were considered. Firstly, the effect of the CDs on the CMC of the surfactant was evaluated by CE experiments. Furthermore, a new CE approach based on electric current measurement was developed for the estimation of the stoichiometry as well as of the binding constants of SDS-CDs complexes. The results of these investigations were compared to those obtained with a different technique, electronic paramagnetic resonance (EPR). The obtained results suggested that methylated CDs, in particular (2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD), strongly affect the micellization of SDS in comparison to the other studied CDs. This effect also paralleled the chiral CD-MEKC performance, as indicated by the enantioresolution of (+/-)-Catechin, which was firstly selected as a model compound representative of important chiral phytomarkers. Then a CD-MEKC system, composed of sodium dodecyl sulfate as surfactant (90 mM) and hydroxypropyl-beta-cyclodextrin (25 mM) as chiral selector, under acidic conditions (25 mM borate – phosphate buffer, pH 2.5) was applied to study the thermal epimerisation of epi-structured catechins, (-)-Epicatechin and (-)-Epigallocatechin, to non epi-structured (-)-Catechin and (-)-Gallocatechin. The latter compounds, being non-native molecules, were for the first time regarded as useful phytomarkers of tea sample degradation. The proposed method was applied to the analysis of more than twenty tea samples of different geographical origins (China, Japan, Ceylon), having undergone different storage conditions and manufacturing processes.

Production, purification, properties and application of the cellulases from a wild type strain of a yeast isolate

Kurzzusammenfassung Produktion, Reinigung, Eigenschaften und Anwendung von Cellulasen eines Wildtyp-Hefeisolates. Die effiziente Verwendung von Cellulose wird in naher Zukonft ein wichtiges Instrument zur Vermeidung einer Nahrungsmittel- und Energieknappheit werden. Deshalb haben wir uns intensiv mit Cellulasen befaßt, die aus Hefestämmen isoliert wurden. Die Fähigkeit der Cellulase-produktion eines Hefe-Stammes der Feuerwanze Pyrrhocoris apterus wurde genauer untersucht. Die systematische Stellung des Hefe-Isolates PAG1 wurde durch Sequenzierung der 18S rDNA bestimmt. Es zeigte eine nahe Verwandtschaft zu einem bereits beschriebenen Stämme der Gattung Trichosporon. Außerdem wurden die Wachstums-bedingungen für eine optimale Cellulase–Produktion bestimmt. Anschließend konnte eine der produzierten Cellulasen mit FPLC aufgereinigt und deren biochemische Eigenschaften (z.B. Substratspezifität, Temperatur optimum, optimaler pH-Wert, Einfluß von Chemikalien) untersucht werden. Eine Analyse der Abbau-Produkte zeigte, daß kristalline Cellulose und CMC zu Cellobiose, Cellulotriose, Cellulotetraose und Cellulopentaose in einem molaren Verhältnis von 32:16:8:1 umgesetezt wurden. Bei Zusatz von ?-Glykosidase aus demselben Hefestamm entstand nur Glucose und Cellobiose in einem molaren Verhältnis von 1:10. Da bisher nur eine Publikation über Cellulase-produzierende Hefe-Stämme erschienen ist, zeigen auch unsere Untersuchungen, daß Wildtyp-Hefestämme Cellulasen mit interessanten Eigenschaften produzieren können.

Isolati aperti. Riqualificazione urbana e housing sociale nella Darsena di Città a Ravenna

La presente tesi si pone in continuità con il Laboratorio di Sintesi Finale in Urbanistica “La città e le case. L’urbanistica e lo spazio dell’abitare”e si propone di applicare e sperimentare una nuova forma urbana quella dell’open block derivante dall’omonima teoria dell’architetto francese Christian de Portzamparc. L’intervento si inserisce all’interno della cosiddetta Darsena di Città di Ravenna, un’ex area industriale di 136 ettari collocata a ridosso del centro storico della città, ma priva di collegamenti diretti con questo da cui si discosta nettamente per caratteristiche e funzioni. Nel corso del laboratorio si sono condotte analisi in maniera approfondita rispetto alle caratteristiche dello stato di fatto e dei bisogni principali del territorio, non solo facendo riferimento agli stessi strumenti urbanistici, ma anche avvalendosi dell’incontro con professionisti, tecnici e docenti. La conoscenza dell’area così raggiunta ci ha permesso di redigere, a conclusione del laboratorio, una serie di linee guida generali da cui nasce il masterplan. Su questo si basa la riqualificazione urbana dell’intera area da cui deriva la peculiarità della nuova Darsena ovvero la coesistenza di due rive dalle caratteristiche opposte e allo stesso tempo complementari. A nord trova spazio la “riva naturale” contraddistinta dalla prevalenza di spazi verdi di diversa natura; questa riva si pone in stretta relazione con il verde agricolo collocato nelle immediate vicinanze della Darsena e fortemente segnato dalla centuriazione romana. La riva sud, la “riva urbana”, è invece caratterizzata dalla prevalenza del costruito che trova un diretto confronto con il tessuto urbano preesistente collocato sia all’interno dell’area sia lungo il limite sud della stessa. Grande importanza per la riqualificazione del Comparto Darsena è stata data al mantenimento degli edifici di archeologia industriale ai quali viene dato ruolo centrale attraverso le nuove funzioni che vengono loro affidate. Altro aspetto fondamentale per la riuscita della riqualificazione della Darsena e allo stesso tempo valoreaggiunto per l’intero territorio comunale, nonché argomento centrale della presente tesi, è il tema dell’housing sociale. A seguito di analisi, studi sulle politiche abitative attualmente vigenti a livello regionale e comunale e indagini sui bisogni radicati nel territorio, si è redatto un masterplan da cui nasce un progetto per un quartiere con housing sociale situato all’interno del comparto CMC. Il progetto nasce dalle riflessioni condotte sull’argomento, mette al centro l’idea della mixité e si fonda sulla forma urbana dell’isolato aperto.

Enteric coated mucoadhesive micropellets in rotary agglomeration process for wet spheronization

In this work a generally applicable method for the preparation of mucoadhesive micropellets of 250 to 600µm diameter is presented using rotor processing without the use of electrolytes. The mucoadhesive micropellets were developed to combine the advantages of mucoadhesion and microparticles. It was possible to produce mucoadhesive micropellets based on different mucoadhesive polymers Na-CMC, Na-alginate and chitosan. These micropellets are characterized by a lower friability (6 to 17%) when compared to industrial produced cellulose pellets (Cellets®) (41.5%). They show great tapped density and can be manufactured at high yields. The most influencing variables of the process are the water content at the of the end spraying period, determined by the liquid binder amount, the spraying rate, the inlet air temperature, the airflow and the humidity of the inlet air and the addition of the liquid binder, determined by the spraying rate, the rotor speed and the type of rotor disc. In a subsequent step a fluidized bed coating process was developed. It was possible to manifest a stable process in the Hüttlin Mycrolab® in contrast to the Mini-Glatt® apparatus. To reach enteric resistance, a 70% coating for Na-CMC micropellets, an 85% for chitosan micropellets and a 140% for Na-alginate micropellets, based on the amount of the starting micropellets, was necessary. Comparative dissolution experiments of the mucoadhesive micropellets were performed using the paddle apparatus with and without a sieve inlay, the basket apparatus, the reciprocating cylinder and flow-through cell. The paddle apparatus and the modified flow-through cell method turned out to be successful methods for the dissolution of mucoadhesive micropellets. All dissolution profiles showed an initial burst release followed by a slow release due to diffusion control. Depending on the method, the dissolution profiles changed from immediate release to slow release. The dissolution rate in the paddle apparatus was mainly influenced by the agitation rate whereas the flow-through cell pattern was mainly influenced by the particle size. Also, the logP and the HLB values of different emulsifiers were correlated to transfer HLB values of excipients into logP values and logP values of API´s into HLB values. These experiments did not show promising results. Finally, it was shown that manufacture of mucoadhesive micropellets is successful resulting in product being characterized by enteric resistency combined with high yields and convincing morphology.

Three-dimensional joint kinematics of swimming using body-worn inertial and magnetic sensors

Wearable inertial and magnetic measurements units (IMMU) are an important tool for underwater motion analysis because they are swimmer-centric, they require only simple measurement set-up and they provide the performance results very quickly. In order to estimate 3D joint kinematics during motion, protocols were developed to transpose the IMMU orientation estimation to a biomechanical model. The aim of the thesis was to validate a protocol originally propositioned to estimate the joint angles of the upper limbs during one-degree-of-freedom movements in dry settings and herein modified to perform 3D kinematics analysis of shoulders, elbows and wrists during swimming. Eight high-level swimmers were assessed in the laboratory by means of an IMMU while simulating the front crawl and breaststroke movements. A stereo-photogrammetric system (SPS) was used as reference. The joint angles (in degrees) of the shoulders (flexion-extension, abduction-adduction and internal-external rotation), the elbows (flexion-extension and pronation-supination), and the wrists (flexion-extension and radial-ulnar deviation) were estimated with the two systems and compared by means of root mean square errors (RMSE), relative RMSE, Pearson’s product-moment coefficient correlation (R) and coefficient of multiple correlation (CMC). Subsequently, the athletes were assessed during pool swimming trials through the IMMU. Considering both swim styles and all joint degrees of freedom modeled, the comparison between the IMMU and the SPS showed median values of RMSE lower than 8°, representing 10% of overall joint range of motion, high median values of CMC (0.97) and R (0.96). These findings suggest that the protocol accurately estimated the 3D orientation of the shoulders, elbows and wrists joint during swimming with accuracy adequate for the purposes of research. In conclusion, the proposed method to evaluate the 3D joint kinematics through IMMU was revealed to be a useful tool for both sport and clinical contexts.

Il linguaggio spagnolo del turismo nel web 2.0. tripadvisor: Un caso di studio

Internet e turismo sono due settori che si intersecano profondamente e che da sempre risultano interconnessi. Grazie al progresso delle nuove tecnologie l’ambito turistico ha mutato profondamente i suoi connotati, sia da un punto di vista strutturale sia nella gestione e nella distribuzione delle informazioni. Con l’ingresso nell’era digitale, lo sviluppo delle ICT (Information and Communication Technologies) e l’avvento del web 2.0, la comunicazione turistica si è modificata in modo sostanziale: si è passati da una comunicazione monologica e unidirezionale da esperti a pubblico, a un dialogo tra le varie parti coinvolte, dove la centralità dell’utente/consumatore, che ha acquisito un ruolo proattivo e guadagnato il diritto di parola, si fa sempre più evidente. In particolare la comparsa del web sociale, che si contraddistingue per la sua forte dinamicità e un carattere collaborativo e comunitario, ha permesso lo sviluppo di modelli comunicativi originali, che sono riusciti ad apportare elementi innovativi e peculiari anche nel linguaggio del turismo, varietà linguistica già di per sé piuttosto particolare ed eterogenea. Tramite l’analisi della versione spagnola del portale di viaggi più famoso al mondo (Tripadvisor.es), si è cercato di evidenziare quali caratteristiche mostrate nei testi pubblicati in questo spazio fossero riconducibili all’influenza del linguaggio del turismo dei generi più tradizionali (guide, dépliant, cataloghi) e quali invece fossero gli elementi attribuibili al mezzo computer e quindi appartenessero alla sfera della comunicazione mediata dal computer.

Investigation of different shellac grades and improvement of release from air suspension coated pellets

Shellac is the purified product of the natural polymer Lac. Shellac types, from different origins and with different ages, all purified by the solvent extraction process were compared in this study. Their physicochemical properties acid value, glass transition temperatures, color numbers and molecular sizes were determined. Metoprolol tartrate pellets were coated by air suspension coating with these different grades of shellac. Two coating levels 20% w/w and 25% w/w were applied and then subjected to in vitro dissolution testing. Enteric resistance was achieved for all tested brands for the two coating levels. At pH 6.8, 7.2 and 7.4, significant variations were obvious between the brands. rnMoreover the molecular size of shellac has a pronounced effect in that shellac types with larger molecular size show a higher and faster release than others, while the one with the smaller molecular size show the opposite effect on the release of metoprolol.rnIn this study commercially available ready for use aqueous shellac solutions (SSB AQUAGOLD), which are based on shellac SSB 57 (Dewaxed Orange Shellac, Bysakhi-Ber type refined in a solvent extraction process), with different manufacturing dates were used. rnTo improve the enteric coating properties of films from aqueous shellac solutions, different aqueous polymeric solutions of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), carboyxmethyl cellulose (CMC), gum arabic and polysaccharides (Pullulan®) were used. These water soluble polymers will act as pore formers to enhance drug release from pellets coated with the combination of shellac and these polymers. The influence of these polymers on the gloss of the shellac films, mechanical properties of the films and drug release from metoprolol tartrate pellets were studied.rnThe potential of ethanol to alter the rate of drug release from shellac coated pellets was assessed by using a modified in vitro dose dumping in alcohol (DDA) method and the test concluded that shellac coated dosage forms can be co-administered with alcohol beverages containing ≤ 5% with no effect of alcohol on the shellac coat.rnPellets coated with shellac sodium salts, showed higher release rates than pellets coated with shellac as ammonium salt forms. rn

Hydrodynamic Characterization of Bile Salt Host-Guest Complexes by Pulsed Field Gradient NMR Spectroscopy

The work described herein is aimed at understanding primary and secondary aggregation of bile salt micelles and how micelles can perform chiral recognition of binapthyl analytes. Previous work with cholate and deoxycholate using micellar electrokinetic chromatography (MEKC) and nuclear magnetic resonance (NMR) has provided insightinto cholate and deoxycholate micelle formation, especially with respect to the critical micelle concentration (CMC). Chiral separations of the model analyte, 1,1â??-binaphthyl-2,2â??-diyl hydrogen phosphate (BNDHP), via cholate (C) and deoxycholate (DC) mediated MEKC separataions previously have shown the DC CMC to be 7-10 mM andthe cholate CMC at 14 mM at ph 12. A second model analyte,1,1â??-binaphthol (BN), was also previously investigated to probe micellar structure, but the MEKC data for this analyte implied a higher CMC, which may be interpreted as secondary aggregation. Thiswork extends the investigation of bile salts to include pulsed field gradient spin echo (PFGSE) NMR experiments being used to gain information about the size and degree of polydispersity of cholate and deoxycholate micelles. Concentrations of cholate below 10mM show a large variation in effective radius likely due to the existence of transient preliminary aggregates. The onset of the primary micelle shows a dramatic increase in effective radius of the micelle in cholate and deoxycholate. In the region of expectedsecondary aggregation a gradual increase of effective radius was observed with cholate; deoxycholate showed a persistent aggregate size in the secondary micelle region that is modulated by the presence of an analyte molecule. Effective radii of cholate anddeoxycholate (individually) were compared with and without R- and S-BNDHP in order to observe the effective radius difference of micelles with and without analyte present. The presence of S-BNDHP consistently resulted in a larger effective aggregate radius incholate and deoxycholate, confirming previous data of the S-BNDHP interacting more with the micelle than R-BNDHP. In total, various NMR techniques, like diffusion NMR can be used to gain a greater understanding of the bile salt micellization process and chiral resolution.

Studying Electrophoretic Separations Using Cholate Micelles: Effects Of Ph, Temperature, And Composition

Micelle-forming bile salts have previously been shown to be effective pseudo-stationary phases for separating the chiral isomers of binaphthyl compounds with micellar electrokinetic capillary chromatography (MEKC). Here, cholate micelles are systematically investigated via electrophoretic separations and NMR using R, S-1, 1¿- binaphthyl- 2, 2¿-diylhydrogenphosphate (BNDHP) as a model chiral analyte. The pH, temperature, and concentration of BNDHP were systematically varied while monitoring the chiral resolution obtained with MEKC and the chemical shift of various protons in NMR. NMR data for each proton on BNDHP is monitored as a function of cholate concentration: as cholate monomers begin to aggregate and the analyte molecules begin to sample the micelle aggregate we observe changes in the cholate methyl and S-BNDHP proton chemical shifts. From such NMR data, the apparent CMC of cholate at pH 12 is found to be about 13-14 mM, but this value decreases at higher pH, suggesting that more extreme pHs may give rise to more effective separations. In general, CMCs increase with temperature indicating that one may be able to obtain better separations at lower temperatures. S-BNDHP concentrations ranging from 50 ¿M to 400 ¿M (pH 12.8) gave rise to apparent cholate CMC values from 10 mM to 8 mM, respectively, indicating that S-BNDHP, the chiral analyte molecule, may play an active role in stabilizing cholate aggregates. In all, these data show that NMR can be used to systematically investigate a complex multi-variable landscape of potential optimizations of chiral separations.

The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: an intravital microscopy study in mice

BACKGROUND: The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. RESULTS: Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. CONCLUSION: Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases.

Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo

BACKGROUND: As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo. METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy. RESULTS: SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings. CONCLUSION: SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1. The experimental data obtained provide rationale to further develop the strategy of the use of the angiogenesis inhibitor SU6668 in the treatment of chondrosarcomas in addition to established therapies such as surgery.

Self-assembling cannabinomimetics: supramolecular structures of N-alkyl amides

Certain fatty acid N-alkyl amides from the medicinal plant Echinacea activate cannabinoid type-2 (CB2) receptors. In this study we show that the CB2-binding Echinacea constituents dodeca-2E,4E-dienoic acid isobutylamide (1) and dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (2) form micelles in aqueous medium. In contrast, micelle formation is not observed for undeca-2E-ene-8,10-diynoic acid isobutylamide (3), which does not bind to CB2, or structurally related endogenous cannabinoids, such as arachidonoyl ethanolamine (anandamide). The critical micelle concentration (CMC) range of 1 and 2 was determined by fluorescence spectroscopy as 200-300 and 7400-10000 nM, respectively. The size of premicelle aggregates, micelles, and supermicelles was studied by dynamic light scattering. Microscopy images show that compound 1, but not 2, forms globular and rod-like supermicelles with radii of approximately 75 nm. The self-assembling N-alkyl amides partition between themselves and the CB2 receptor, and aggregation of N-alkyl amides thus determines their in vitro pharmacological effects. Molecular mechanics by Monte Carlo simulations of the aggregation process support the experimental data, suggesting that both 1 and 2 can readily aggregate into premicelles, but only 1 spontaneously assembles into larger aggregates. These findings have important implications for biological studies with this class of compounds.

Characterization of a Coal Fly Ash-Cement Slurry by the Absolute Foam Index

This dissertation established a standard foam index: the absolute foam index test. This test characterized a wide range of coal fly ash by the absolute volume of air-entraining admixture (AEA) necessary to produce a 15-second metastable foam in a coal fly ash-cement slurry in a specified time. The absolute foam index test was used to characterize fly ash samples having loss on ignition (LOI) values that ranged from 0.17 to 23.3 %wt. The absolute foam index characterized the fly ash samples by absolute volume of AEA, defined as the amount of undiluted AEA solution added to obtain a 15-minute endpoint signified by 15-second metastable foam. Results were compared from several foam index test time trials that used different initial test concentrations to reach termination at selected times. Based on the coefficient of variation (CV), a 15-minute endpoint, with limits of 12 to 18 minutes was chosen. Various initial test concentrations were used to accomplish consistent contact times and concentration gradients for the 15-minute test endpoint for the fly ash samples. A set of four standard concentrations for the absolute foam index test were defined by regression analyses and a procedure simplifying the test process. The set of standard concentrations for the absolute foam index test was determined by analyzing experimental results of 80 tests on coal fly ashes with loss on ignition (LOI) values ranging from 0.39 to 23.3 wt.%. A regression analysis informed selection of four concentrations (2, 6, 10, and 15 vol.% AEA) that are expected to accommodate fly ashes with 0.39 to 23.3 wt.% LOI, depending on the AEA type. Higher concentrations should be used for high-LOI fly ash when necessary. A procedure developed using these standard concentrations is expected to require only 1-3 trials to meet specified endpoint criteria for most fly ashes. The AEA solution concentration that achieved the metastable foam in the foam index test was compared to the AEA equilibrium concentration obtained from the direct adsorption isotherm test with the same fly ash. The results showed that the AEA concentration that satisfied the absolute foam index test was much less than the equilibrium concentration. This indicated that the absolute foam index test was not at or near equilibrium. Rather, it was a dynamic test where the time of the test played an important role in the results. Even though the absolute foam index was not an equilibrium condition, a correlation was made between the absolute foam index and adsorption isotherms. Equilibrium isotherm equations obtained from direct isotherm tests were used to calculate the equilibrium concentrations and capacities of fly ash from 0.17 to 10.5% LOI. The results showed that the calculated fly ash capacity was much less than capacities obtained from isotherm tests that were conducted with higher initial concentrations. This indicated that the absolute foam index was not equilibrium. Rather, the test is dynamic where the time of the test played an important role in the results. Even though the absolute foam index was not an equilibrium condition, a correlation was made between the absolute foam index and adsorption isotherms for fly ash of 0.17 to 10.5% LOI. Several batches of mortars were mixed for the same fly ash type increasing only the AEA concentration (dosage) in each subsequent batch. Mortar air test results for each batch showed for each increase in AEA concentration, air contents increased until a point where the next increase in AEA concentration resulted in no increase in air content. This was maximum air content that could be achieved by the particular mortar system; the system reached its air capacity at the saturation limit. This concentration of AEA was compared to the critical micelle concentration (CMC) for the AEA and the absolute foam index.