Zinc is an essential metal ion for the activity of multiple enzymes and transcription factors. Among many other transporting proteins human serum albumin (HSA) is the main carrier of Zn(II) in the blood plasma. HSA displays multiple ligand binding sites with extraordinary binding capacity for a wide range of ions and molecules including fatty acids. Hence, HSA controls the availability and distribution of those molecules throughout the body. Previous studies have established that the existence of one zinc site with high affinity (MBS-A) that is modulated by the presence of fatty acids. Therefore, the fatty acid concentration in the blood influences zinc distribution which may result in a significant effect on both normal physiological processes and a range of diseases. Based on the current knowledge of HSA's structure and its coordination chemistry with zinc ion, here, we attempted to investigate zinc interactions and coordination with HSA and the effect of different fatty acids on the protein structure, stability and on Zn(II) binding. By NMR titration, we examine the Zn(II) binding to HSA and the spectra show distinct movements of some resonances showing a conformational change has occurred as a result of Zn(II) binding. Isothermal calorimetry titrations study was performed to evaluate zinc binding affinity to HSA in the absence and presence of fatty acids. Free HSA results indicates the existence of one high affinity site and multiple low affinity sites. Upon the binding of fatty acids to HSA, three distinct behaviors of Zn(II) affinity was observed ranging from no effect to moderate to significant depending on the FAs. By the use of circular dichroism, we investigate secondary and tertiary structure of HSA in the presence and absence of FAs and Zn(II). We found albumin is predominately α-helical and the overall conformation of the protein remains unchanged even after interacting with FAs and Zn(II) with some exception. The structural stability of HSA was evaluated by obtaining the denaturation temperature in the presence and absence of fatty acid and we found the thermal denaturation of HSA increases with the increase of amount of fatty acids.

Le modèle standard des interactions entre particules élémentaires est la réalisation exceptionnelle des quarante dernières années d'activité expérimentale et théorique en physique des particules. Depuis la découverte du boson de Higgs en 2012 par les expériences du Large Hadron Collider (LHC), la mesure précise est devenue le défi dans les expériences de physique des hautes énergies.De nombreuses usines de Higgs électron-positon avec une précision améliorée sur les mesures de largeur totale de Higgs ont été proposées, y compris le collisionneur linéaire international (ILC) et le collisionneur à électrons positrons circulaires (CEPC).Le programme de physique de Higgs à réaliser dans les futurs collisionneurs $ e^{+}e^{-} $ a été évalué et son degré de précision de nombreux couplages est estimé à des niveaux de pourcentage ou de sous-pourcentage.Afin d'atteindre cette précision, l'utilisation de l'algorithme de flux de particules (PFA) est devenue le paradigme de la conception de détecteurs pour la frontière à haute énergie. L'idée clé est de reconstruire chaque particule d'état finale dans les sous-détecteurs les plus adaptés, et de reconstruire tous les objets physiques au-dessus des particules d'état finales. Les détecteurs orientés à PFA ont une grande efficacité dans la reconstruction d'objets physiques tels que les leptons, les jets et l'énergie manquante.L'identification du lepton est essentielle pour les programmes de physique, en particulier pour la mesure précise du boson de Higgs.Dans cette thèse, une identification par lepton basée sur PFA (Lepton Identification pour calorimètre à haute granularité) a été développée pour des détecteurs utilisant des calorimètres à haute granularité.Utilisation de la géométrie du détecteur conceptuel pour le CEPC avec granularité calorimétrique typique de 1000 et 400 cellules / dm³ pour les parties électromagnétiques et hadroniques respectivement, et les échantillons de particules chargées uniques d'énergie supérieure à 2 GeV, LICH identifie les électrons ou les muons avec des rendements supérieurs à 99,5% et contrôle le taux de désinscription du hadron aux muons ou aux électrons 1% ou 0.5 %. Réduisant la granularité du calorimètre de 1 ou 2 ordres de grandeur, la performance d'identification du lepton est stable pour les particules avec E > 2 GeV Appliquée à des événements $eeH$ ou $ mumu H$ simulés à $ sqrt{s} = 250 $ GeV, la performance d'identification du lepton est cohérente avec le cas d'une seule particule: l'efficacité d'identifier tous les leptons de haute énergie dans un événement est de 95,5 $ sim $ 98,5 %. Contrairement aux muons et aux électrons, les $ au $ 's sont des objets de physique extrêmement intrigants car leur couplage de Yukawa au boson de Higgs est relativement important. En raison de leurs riches produits de désintégration, des propriétés telles que les paramètres Higgs CP et EW dans une Z-factory. Les produits $ au $-decay dans les collisionneurs de haute énergie sont étroitement collimatés et ont une faible multiplicité, fournissant d'excellentes signatures à sonder. Dans cette thèse, les canaux H $ightarrow $ $ au au $ sont analysés dans différents modes de désintégration Z avec le contexte SM pris en compte. La précision finale combinée de $ sigma imes Br (Hightarrow au au) $ devrait être de 0.89 %. / The Standard Model of elementary particle interactions is the outstanding achievement of the past forty years of experimental and theoretical activity in particle physics. Since the discovery of the Higgs boson in 2012 by the experiments at the Large Hadron Collider (LHC), the precise measurement has become the issue in high energy physics experiments.Many electron-positron Higgs factories with better accuracy on the Higgs total width measurements have been proposed, including the International Linear Collider (ILC) and the Circular Electron Positron Collider (CEPC).The Higgs physics program to be carried out at the future $e^{+}e^{-}$ colliders have been be evaluated and its extent of the precision of many of couplings are estimated to percent or sub-percent levels.In order to achieve this precision, the Particle Flow Algorithm (PFA) has become the paradigm of detector design for the high energy frontier. The key idea is to reconstruct every final state particle in the most suited sub-detectors, and reconstruct all the physics objects on top of the final state particles. The PFA oriented detectors have high efficiency in reconstructing physics objects such as leptons, jets, and missing energy.The lepton identification is essential for the physics programs, especially for the precise measurement of the Higgs boson.In this thesis, a PFA based lepton identification (Lepton Identification for Calorimeter with High granularity) has been developed for detectors using high granularity calorimeters. Using the conceptual detector geometry for the CEPC and single charged particle samples with energy larger than 2 GeV, LICH identifies electrons/muons with efficiencies higher than 99.5% and controls the mis-identification rate of hadron to muons/electrons to better than 1%/0.5%. Reducing the calorimeter granularity by 1-2 orders of magnitude, the lepton identification performance is stable for particles with E > 2 GeV. Applied to fully simulated eeH/$mumu$ H events, the lepton identification performance is consistent with the single particle case: the efficiency of identifying all the high energy leptons in an event, is 95.5-98.5%.Except for e and $mu$, $tau$s are extremely intriguing physics objects as its Yukawa coupling to the Higgs boson is relatively large. Due to its rich decay products, properties such as the Higgs CP and EW parameters at the Z-factory can be precisely measured. The $tau$ decay in high energy colliders is tightly collimated and low multiplicity, which provide excellent signatures to probe. In this thesis, the H$rightarrow$ $tautau$ channels are analyzed in different Z decay modes with SM background taken into account and the combine final accuracy is expected to be 1.3%.

Title Energy expenditure of slackline walking Objectives The aim of this study was to investigate the energy expenditure of slacklining in intermediate and advanced slackliners. Methods In this observatory study, 19 slackliners (10 intermediate, of which 7 men and 3 women, 9 advanced, of which 7 men and 2 women) completed experimental energy expenditure measurement of slacklining using indirect colorimetry. The MetaMax 3B metabolic analyzer (Cortex Biophysik, Germany) was used to determine respiratory parameters and the heart rate monitor (Polar Electro OY, Finland) was used to determine the heart rate (HR). Comparative statistical tools were used in the data analysis. Results Relative energy expenditure of 0,471 kJ·min-1 ·kg-1 was found in intermediate slackliners and 0,377 kJ·min-1 ·kg-1 in advanced slackliners in walking on a 10 m long slackline at a constant speed of 15 m·min-1 . In the static standing on slackline, the relative energy expenditure was found to be 0.368 kJ·min-1 ·kg-1 in intermediate slackliners and 0.289 kJ·min-1 ·kg-1 in advanced slackliners. The weighted arithmetic mean for HR in men and women walking on the slackline at 15 m·min-1 was at 67.3% of the predicted HRmax (220 - age for men, 226 - age for women). The MET value in the advanced group (n = 10) was set at 5.15, and in...

Rostlinné oleje se používají v mnoha odvětvích chemického průmyslu. V průběhu zpracování konkrétního produktu, ve kterém jsou rostlinné oleje použity, dochází často ke zvyšování teploty. Vyšší teplota urychluje průběh auto-oxidace což negativně ovlivňuje stabilitu olejů nebo výrobků z nich připravených. Mezidruhové mísení olejů je poměrně častým jevem jak při samotné výrobě tak i ve finálním výrobku. Cílem této práce bylo stanovit termo-oxidační stabilitu šesti čistých rostlinných olejů a jejich binárních směsí. První část práce zkoumá oleje a připravené směsi pomocí metody diferenciální kompenzační kalorimetrie. Tato metoda umožnila pochopení vztahů mezi termo-oxidačním chováním olejů a jejich směsmi pomocí stanovení teplot degradace. Přímá souvislost mezi obsahem mastných kyselin a stabilitou byla prokázána pouze zčásti, stejně tak jako původní předpoklad, že přídavek stabilnějšího olej zvýší stabilitu oleje méně stabilního. V několika případech docházelo dokonce ke snížení stability pod teplotu degradace obou čistých olejů. Ve druhé části byl zjišťován mechanismus pro-oxidační fáze vedoucí k degradaci olejů pomocí termogravimetrie, která ukázala přírůstek hmotnosti ve vzorcích oleje způsobeného absorpcí kyslíku a tvorbou peroxidů předcházející degradaci. V tomto případě již bylo možné pozorovat jistou souvislost mezi obsahem mastných kyselin a vzrůstem hmotnosti, pouze však jen pro čisté oleje. Ani v tomto případě nebyla prokázána aditivita vlastností způsobujících stabilitu směsí rostlinných olejů.

Solubility is the amount of solute in the solvent system at phase equilibrium with certain temperature and pressure. Many of the new chemical entities are lipophilic molecules that require techniques to enhance solubility. Solubility enhancement can be achieved by either physical and/or chemical modification of the drug. Various techniques are available for solubility enhancement of poorly soluble drugs include particle size reduction, salt formation, solid dispersions, use of surfactants, prodrug, crystal modification, etc. In this study, the three model drugs belong to BCS class II and IV having low solubility with a certain range of physicochemical properties were studies in solubility enhancement using fusion method, co-precipitation, nano-milling and spray drying techniques. The two different polymers employed for solubility enhancement are PEG 8000 and PVP 40,000. Solubility was determined by Shake Flask method at the temperature of 37±0.1 °C. The objective is to investigate the enhancement of solubility of the three model drugs namely Glipizide, Carvedilol and Furosemide in 1:1, 1:5 and 1:10 drug-polymer ratios and are characterized by Differential Scanning Calorimetry (DSC). The Solubility of Glipizide was enhanced from 11.18 ± 1.78 µg/ml to 35.73 ± 0.04 µg/ml by 219 % increase with nano-milling technique at 1:5 ratio with PEG 8000 as carrier whereas with PVP 40000 as carrier, 286 % increase in solubility to 43.26 ± 7.87 µg/ml was observed at 1:1 ratio by fusion method. The solubility of Carvedilol was enhanced from 5.04 ± 0.55 µg/ml to 17.51 ± 0.94 µg/ml by 246 % at 1:5 ratio by fusion method with PEG8000 as carrier and 2924 % enhancement in solubility to 152.70 ± 9.09 µg/ml at 1:10 ratio by nano-milling with PVP40000 as the carrier. Furosemide showed an increase in solubility from 55.94 ± 2.48 µg/ml to 164.11 ± 9.18 µg/ml by 193 % at 1:10 ratio by nano-milling technique with PEG8000 as carrier whereas with PVP40000 as carrier, 444 % increase was observed at 1:1 ratio by nano-milling technique with solubility of 304.52 ± 23.11 µg/ml. The data showed that the decrease in percentage crystallinity and enthalpy of fusion of the model drugs upon implementing solubility enhancement techniques with the effect of particle size and the carrier used resulted in the increase of aqueous solubility of the model drugs.

No description available.

Molecular recognition, particularly as it applies to strong binding interactions between complementary ligand/receptor molecules in solution, is important in such varied areas as molecular biology, pharmacology, synthetic chemistry, and chemical detection. Strong binding is the additive result of a number of specific, weak, non-covalent interactions occurring between complementary molecules. This dissertation reports on the energetics of forming complexes between small molecules and model DNA constructs. Ligands included cationic and metallated cationic porphyrins and polyheterocyclic ruthenium compounds. DNA receptors included double stranded B-DNAs (hairpin and short linear sequences) as well G-quadruplex DNAs. Thermodynamic data were collected using isothermal titration calorimetry, circular dichroism spectropolarimetry, ultraviolet-visible spectroscopy, and mass spectrometry. The measured thermodynamic parameters included the changes in free energy, enthalpy and entropy for ligand/receptor complex formation as well as the stoichiometry of the stable complexes. The first section of this dissertation reports that the binding of cationic porphyrins to model G-quadruplex DNA may proceed through two pathways, end stacking and intercalation. Modulating the number of pyridinium groups on a pyridinium substituted porphyrin yielded differing binding thermodynamics leading to the understanding that a balance of surface area, charge, and geometry affect the ability of a porphyrin to bind to G-quadruplex DNA. Further investigations into the binding of metallated porphyrins developed the understanding that the geometry of the central metal ion affected not only the thermodynamics but could also inhibit the intercalative mode. It was previously shown that the high affinity binding for binuclear polyheterocyclic ruthenium compounds proceeds through an intercalative mode. To further understand the binding process and the structureunction relationship of the ligand components, the binding of smaller mononuclear complexes that were representative of portions of the binuclear complex was examined in this dissertation. While limiting the intercalative ability lowered the binding affinity, the mononuclear complex with the full intercalating bridge was able bind to DNA with a higher affinity than the binuclear complex. These studies have been successful in part in determining the contributions of numerous weak interactions including: charge (Coulombic interactions), H-bonding, hydrophobic interactions, and solvent structure (solvation changes), to the overall energetics of this molecular recognition process. The first section of this dissertation reports that the binding of cationic porphyrins to model G-quadruplex DNA may proceed through two pathways, end stacking and intercalation. Modulating the number of pyridinium groups on a pyridinium substituted porphyrin yielded differing binding thermodynamics leading to the understanding that a balance of surface area, charge, and geometry affect the ability of a porphyrin to bind to G-quadruplex DNA. Further investigations into the binding of metallated porphyrins developed the understanding that the geometry of the central metal ion affected not only the thermodynamics but could also inhibit the intercalative mode. It was previously shown that the high affinity binding for binuclear polyheterocyclic ruthenium compounds proceeds through intercalation. To further understand the binding process and the structureunction relationship of the ligand components, the binding of smaller mononuclear complexes that were representative of portions of the binuclear complex was examined in this dissertation. While limiting the intercalative ability lowered the binding affinity, the mononuclear complex with the full intercalating bridge was able bind to DNA with a higher affinity than the binuclear complex. These studies have been successful in part in determining the contributions of numerous weak interactions including: charge (Coulombic interactions), H-bonding, hydrophobic interactions, and solvent structure (solvation changes), to the overall energetics of this molecular recognition process.

Calcineurin (CaN) plays an important role in T-cell activation, cardiac system development, and nervous system function. Previous studies have suggested that the regulatory domain (RD) of CaN binds Calmodulin (CaM) towards the N-terminal end of CaN. Calcium-loaded CaM activates the serine/threonine phosphatase activity of CaN by binding to the regulatory domain, although the mechanistic details of this interaction remain unclear. It is thought that CaM binding at the RD displaces the auto inhibitory domain (AID) from the active site of CaN, which activates phosphatase activity. In the absence of calcium-loaded CaM, the RD is at least partially disordered, and binding of CaM induces folding in the RD. Previous studies have shown that an ?-helical structure forms in the N-terminal half of the RD, but organization may occur in the C-terminal region as well. Here, we are presenting a model for the structural transition of the full length RD as it binds to CaM. Using nuclear magnetic resonance (NMR) spectroscopy, we have successfully assigned >85% of the 15N, 13C?, 13C? and HN chemical shifts of the unbound, regulatory domain of CaN. Secondary chemical shifts support a model where the RD is highly disordered. Our study of the CaM and CaN interaction supports the formation of a distal helix in the region between the AID and calmodulin-binding region. Heat capacity changes upon binding predict that 43 residues fold when CaM binds to CaN, consistent with the formation of this distal helix. Paramagnetic relaxation enhancement (PRE) studies of this interaction suggest a potential binding mode where the distal helix binds to CaM near residues I10-A11. Mutagenesis in the distal helix disrupts PREs, further supporting this hypothesis. Together, these data suggest that the interactions between CaM and the distal helix of CaN can be important in regulation of phosphatase activity.

The cuticle is constituted of the biopolymer cutin and intra- and epicuticular waxes. In some cases, it has epicuticular wax crystals, protruding from the epicuticular wax film. One of the most important tasks is protection against desiccation. Many investigations were conducted to find the transport limiting component of the cuticle. It is evidentially confirmed that the waxes form this barrier. These waxes are multifactorial blends made of very-long-chain aliphatic (VLCA) compounds and triterpenoids (TRP). The VLCAs were proposed to constitute the transpiration barrier to water. However, experimental confirmation was lacking so far. The present study focuses on the development of a method to selectively extract TRPs from the cuticle and the impact of the removal on the transpiration barrier. The plants deployed in this study exhibited several features. They had no epicuticular crystals on their surfaces, were astomatous, had a rather durable and possibly isolatable cuticle. A broad range of wax compositions was covered from plants with no TRP content and low wax load like Hedera helix and Zamioculcas zamiifolia to plants with high TRP content and high wax load like Nerium oleander. The selective extraction was conducted using a sequence of solvents. TRPs were extracted almost exhaustively from CMs with the first MeOH extract. Only a minor amount of shorter chained VLCAs was obtained. The remaining waxes, consisting mostly of VLCAs and some remnant TRPs, were removed with the following TCM extract. After the extractions, the water permeance of native cuticular membranes (CM), MeOH extracted (M) and dewaxed cuticular discs (MX) was investigated gravimetrically. Compared to the water permeance of CMs, Ms showed no or only a small increase in water conductance. MXs, however, always showed strongly increased values. The knowledge about the wax compounds constituting the transport-limiting properties is vital for different projects. For various issues, it would be favourable to have a standardized wax mixture as an initial point of research. It could be used to develop screening procedures to investigate the impact of adjuvants on cuticular waxes or the influence of wax constituents on the properties of cuticular waxes. This work concentrated on the development of an artificial wax mixture, which mimics the physical properties of a plant leaf wax sufficiently. As target wax, the leaf wax of Schefflera elegantissima was chosen. The wax of this plant species consisted almost exclusively of VLCAs, had a rather simple composition regarding compound classes and chain length distribution and CMs could be isolated. Artificial binary, ternary and quaternary waxes corresponding to the conditions within the plant wax were investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD) techniques and Fourier-transform infrared (FTIR) spectroscopy. Phase diagrams were mapped out for a series of binary, ternary and quaternary wax mixtures. FTIR experiments were conducted using, ternary and a quaternary artificial wax blends. The blends were chosen to represent the conditions within the wax of the adaxial CM plant wax. The FTIR experiments exhibited an increasing resemblance of the artificial wax to the plant wax (adaxial CM wax) with an increasing number of compounds in the artificial wax. The same trend was found for DSC thermograms. Thermograms of ternary and quaternary blends exhibited more overlapping peaks and occurred in a temperature range more similar to the range of the whole leaf plant wax. The XRD spectrum at room temperature showed good conformity with the quaternary blend. The current work illustrates a method for selective extraction of TRPs from isolated CMs. It gives direct experimental proof of the association of the water permeance barrier with the VLCA rather than to the TRPs. Furthermore, the possibility to mimic cuticular waxes using commercially available wax compounds is investigated. The results show promising feasibility for its viability, enabling it to perform as a standardized initial point for further research (e.g. to examine the influence of different constituents on waxes), revealing valuable knowledge about the structure and the chemistry-function relationship of cuticular waxes. / Die Kutikula ist eine der vielen Anpassungen, die Pflanzen entwickelten um nach der Besiedelung des Landes mit den Herausforderungen ihrer neuen Umgebung fertig zu werden. Sie überzieht überirdische Pflanzenorgane, wie Blüten oder Blätter und erfüllt verschiedene Aufgaben. Hierzu besteht sie aus dem biopolymer Kutin und intra- sowie epikutikulären Wachs. Studien, die sich mit der Lokalisierung der transporteinschänkenden Barriere beschäftigten, zeigten, dass die Wachse sie bilden. Diese sind vielschichtige Mischungen aus langkettigen aliphatischen Verbindungen (VLCA) und pentazyklischen Verbindung wie Triterpenen (TRP). Es wird davon ausgegangen, dass VLCAs die Barriere aufbauen, ein direkter experimenteller Nachweis dafür wurde jedoch noch nicht erbracht. In dieser Arbeit wurde daher ein Verfahren zur selektiven Extraktion von TRPs aus isolierten kutikulären Membranen (CM) entwickelt und deren Auswirkung auf die Transpirationsbarriere untersucht. Die untersuchten Pflanzen wiesen keine epikutikuläre Kristalle auf, hatten keine Stomata auf der Kutikula der Blattoberseite und es war möglich ihre Kutikula zu isolieren. Die Zusammensetzung der Wachse variierte von wenig Wachs ohne TRPs (z. B. Hedera helix, Zamioculcas zamiifolia) hin zu pflanzen mit großer Wachsmenge und hohem TRP- Anteil (Nerium oleander). Die selektive Extraktion wurde durch die sequenzielle Nutzung zweier Lösemittel erreicht. TRPs wurden fast vollständig mit Methanol (MeOH) entfernt, während VLCAs überwiegend nur mit Chloroform (TCM) extrahiert werden konnten. Die gravimetrische Bestimmung der Wassertranspiration von unbehandelten, mit Methanol extrahierten (M) und entwachsten Membranen (MX) in Transpirationskammern zeigte bei allen untersuchten Pflanzenarten einen einheitlichen Trend auf. Im Vergleich zu CMs erhöhte sich die Transpirationsrate bei Ms nicht oder nur geringfügig, während bei MXs ein starker Anstieg festgestellt werden konnte. Diese Ergebnisse stellen den ersten direkten experimentellen Nachweis der Verbindung von VLCAs zur Transpirationsbarriere kutikulärer Wachse dar. Mit dem Wissen, sich bei der Untersuchung der Permeation durch die Kutikula sich nur auf die VLCA Fraktion beschränken zu müssen können weitere Projekte effizient angegangen werden. Ein leicht erhältliches Standartwachsgemisch könnte Ausgangspunkt für die Untersuchung des Einflusses verschiedener Pflanzenwachskomponenten auf deren physikalische Eigenschaften dienen. Als Zielwachs diente das Blattwachs von Schefflera elegantissima. Es bestand fast ausschließlich aus VLCAs, hatte eine recht einfache Zusammensetzung bezüglich der Stoffklassen und Kettenlängenverteilung und die Kutikula war isolierbar. Mit Hilfe von dynamische Differentialkalorimetrie (DSC), Röntgenbeugung (XRD) und Fouriertransformierter Infrarot (FTIR) Spektroskopie wurden binäre, ternäre und quaternäre Gemische, die Verhältnisse im Pflanzenwachs wiederspiegelten, untersucht und Phasendiagramme erstellt. Phasendiagramme wurden von einer Reihe der binären Gemische, bestehend aus Alkanen oder Alkoholen, ternären Gemischen aus zwei Alkanen und einem Alkohol und quaternären Gemischen aus zwei Alkanen und zwei Alkoholen erstellt. FTIR-spektroskopische Versuche zeigten mit zunehmender Komponentenzahl eine erhöhte Ähnlichkeit der artifiziellen Wachse zum Pflanzenwachs (adaxiale isolierte Kutikula). Ein ähnlicher Trend wurde für die Ähnlichkeit der Thermogramme der artifiziellen Gemische zum Pflanzenwachs (aus dem Extrakt ganzer Blätter) ersichtlich. Das Diffraktogramm des quaternären Waches stimmte auf Raumtemperatur gut mit dem des Pflanzenwachses (adaxiale isolierte Kutikula) ein. Diese Arbeit beschreibt eine Methode zur selektiven Extraktion von TRPs aus isolierten kutikulären Membranen. Sie zeigt einen direkten experimentellen Nachweis für die Assoziation der Transpirationsbarriere zu den VLCAs und nicht zu den TRPs. Zusätzlich wird die Möglichkeit kutikulare Wachse mit Hilfe von kommerziell erhältlichen Wachskomponenten nachzustellen untersucht, was vielversprechende Ergebnisse liefert. Dieses Wachs könnte daher als standardisierter Ausgangspunkt für weitere Experimente (z. B. zur Untersuchung des Einflusses verschiedener Wachskomponenten auf dessen physikalische Eigenschaften) dienen. Dies könnte wertvolle Informationen über die Struktur und die Beziehung zwischen chemischer Zusammensetzung und der Funktion kutikulärer Wachse liefern.

The thermotropic behavior of multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC), or of DPPC in admixture with cardiolipin or cholesterol, in the presence of various N-alkyl derivatives of both adriamycin-14-valerate has been investigated by high sensitivity differential scanning calorimetry. The analogues, particularly the 14-valerate derivatives, which were most lipophilic as judged by their lipid/buffer, and to a lesser extent by their octanol/buffer, partition coefficients, were the most effective in depressing the tm of the investigated lipids; correlations, however, were not absolute. Other factors, such as the distribution of the drugs between the solid and liquid-crystalline phases of the bilayer, were also important to the observed membrane perturbations. With all anthracyclines, however, no major changes in the transition enthalpy were observed. In the case of vesicles prepared from pure DPPC, curve fitting analysis based on ideal solution theory (J.M. Sturtevant (1984) Proc. Natl. Acad. Sci. USA 81, 1398-1400) applied at relatively low drug concentrations where single peak transitions were produced, adequately described the differential scanning calorimetric results. At high drug concentrations, however, the presence of multipeak transitions were indicative of non-ideality.